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28759998
|
Pharmacist Participation in Acute Ischemic Stroke Decreases Door-to-Needle Time to Recombinant Tissue Plasminogen Activator.
|
Pharmacists are an important member of the stroke team and aid in obtaining medication and medical history, providing education, managing blood pressure, reviewing exclusion criteria for recombinant tissue plasminogen activator (rtPA), and facilitating reconstitution and administration of rtPA.</AbstractText To determine if pharmacist presence at bedside during acute ischemic stroke resulted in a reduction in door-to-needle (DTN) times.</AbstractText This was a retrospective cohort study between January 1, 2011 and December 31, 2015 of patients who received rtPA for acute ischemic stroke in either the emergency department or hospital.</AbstractText Of the 125 included patients, 45 patients (36%) had a pharmacist present (PharmD group) and 80 patients (64%) did not (no PharmD group). Median DTN time was significantly shorter in the PharmD group: 48 minutes versus 73 minutes in the no PharmD group ( P < 0.01). The goal of DTN ≤60 minutes was met in 71% of patients in the PharmD group compared to 29% ( P < 0.01). Pharmacist at the bedside was the only factor found to be independently associated with reduction DTN time (βcoefficient -23.5 minutes, 95% confidence interval [95% CI] -38.6 to -8.50 minutes).</AbstractText A pharmacist at the bedside of emergency department or in-patient stroke codes reduced DTN time by a median of 23.5 minutes after adjusting for confounding factors and increased the percentage of patients meeting DTN goal time of ≤60 minutes by 49%. These findings support the inclusion of a stroke-competent pharmacist in the bedside response team for acute ischemic stroke patients.</AbstractText
|
[
[
"27110714",
"Correction for Inhibition Leads to an Allosteric Co-Agonist Model for Pentobarbital Modulation and Activation of α1β3γ2L GABAA Receptors.",
"Pentobarbital, like propofol and etomidate, produces important general anesthetic effects through GABAA receptors. Photolabeling also indicates that pentobarbital binds to some of the same sites where propofol and etomidate act. Quantitative allosteric co-agonist models for propofol and etomidate account for modulatory and agonist effects in GABAA receptors and have proven valuable in establishing drug site characteristics and for functional analysis of mutants. We therefore sought to establish an allosteric co-agonist model for pentobarbital activation and modulation of α1β3γ2L receptors, using a novel approach to first correct pentobarbital activation data for inhibitory effects in the same concentration range.</AbstractText Using oocyte-expressed α1β3γ2L GABAA receptors and two-microelectrode voltage-clamp, we quantified modulation of GABA responses by a low pentobarbital concentration and direct effects of high pentobarbital concentrations, the latter displaying mixed agonist and inhibitory effects. We then isolated and quantified pentobarbital inhibition in activated receptors using a novel single-sweep \"notch\" approach, and used these results to correct steady-state direct activation for inhibition.</AbstractText Combining results for GABA modulation and corrected direct activation, we estimated receptor open probability and optimized parameters for a Monod-Wyman-Changeux allosteric co-agonist model. Inhibition by pentobarbital was consistent with two sites with IC50s near 1 mM, while co-agonist model parameters suggest two allosteric pentobarbital agonist sites characterized by KPB ≈ 5 mM and high efficacy. The results also indicate that pentobarbital may be a more efficacious agonist than GABA.</AbstractText Our novel approach to quantifying both inhibitory and co-agonist effects of pentobarbital provides a basis for future structure-function analyses of GABAA receptor mutations in putative pentobarbital binding sites.</AbstractText"
]
] |
[
[
"28285191",
"Polychlorinated biphenyls-153 induces metabolic dysfunction through activation of ROS/NF-κB signaling via downregulation of HNF1b.",
"Polychlorinated biphenyls (PCB) is a major type of persistent organic pollutants (POPs) that act as endocrine-disrupting chemicals. In the current study, we examined the mechanism underlying the effect of PCB-153 on glucose and lipid metabolism in vivo and in vitro. We found that PCB-153 induced per se and worsened high fat diet (HFD)-resulted increase of blood glucose level and glucose and insulin intolerance. In addition, PCB-153 induced per se and worsened HFD-resulted increase of triglyceride content and adipose mass. Moreover, PCB-153 concentration-dependently inhibited insulin-dependent glucose uptake and lipid accumulation in cultured hepatocytes and adipocytes. PCB-153 induced the expression and nuclear translocation of p65 NF-κB and the expression of its downstream inflammatory markers, and worsened HFD-resulted increase of those inflammatory markers. Inhibition of NF-κB significantly suppressed PCB-153-induced inflammation, lipid accumulation and decrease of glucose uptake. PCB-153 induced oxidative stress and decreased hepatocyte nuclear factor 1b (HNF1b) and glutathione peroxidase 1 (GPx1) expression in vivo and in vitro. Overexpression of HNF1b increased GPx1 expression, decreased ROS level, decreased Srebp1, ACC and FAS expression, and inhibited PCB-153-resulted oxidative stress, NF-κB-mediated inflammation, and final glucose/lipid metabolic disorder. Our results suggest that dysregulation of HNF1b/ROS/NF-κB plays an important role in PCB-153-induced glucose/lipid metabolic disorder.</AbstractText"
]
] |
35993408
|
A Novel Dynamin 2 Mutation Causing Dominant Intermediate Charcot-Marie-Tooth Neuropathy: Case Report.
|
Dynamin 2 mutations are associated with Charcot-Marie-Tooth neuropathy. We report two siblings with a novel missense heterozygous point mutation (c.1609 G>A) in the highly conserved pleckstrin homology domain in exon 15 of Dynamin 2 presenting with progressive length-dependent sensorimotor polyneuropathy with mixed demyelinating and axonal features on electrodiagnostic studies. The previously unrecognized missense point mutation, which was inherited from their symptomatic but previously undiagnosed mother, was determined to be likely pathogenic based on a non-conservative amino acid substitution (p.Gly537Ser) that is predicted to damage secondary protein structure or function. This report emphasizes the importance of recognizing inherited neuropathies in clinical practice and evaluating suspected pathogenic gene variants initially classified to be of undetermined clinical significance in family cohorts. These cases add to the spectrum of pathogenic Dynamin 2 mutations associated with dominant-intermediate Charcot-Marie-Tooth neuropathy.</AbstractText
|
[
[
"31069783",
"A novel WARS mutation (p.Asp314Gly) identified in a Chinese distal hereditary motor neuropathy family.",
"Distal hereditary motor neuropathy (dHMN) is a clinically and genetically heterogeneous group of inherited neuropathies characterized by distal limb muscle wasting and weakness with no or minimal sensory abnormalities. To investigate the clinical and genetic features of dHMN caused by WARS mutations in mainland China, we performed Sanger sequencing of the coding and untranslated region (UTR) regions of WARS in 160 unresolved dHMN and Charcot-Marie-Tooth (CMT) index patients. We detected a novel heterozygous variant c.941A>G (p.Asp314Gly) of WARS in an index patient from an autosomal dominant dHMN family including five affected members over three generations. The variant completely co-segregates with the dHMN phenotype in the family, and it was classified as likely pathogenic according to the American College of Medical Genetics and Genomics standards and guidelines. The clinical features included juvenile to adult onset (15-23 years), distal wasting and weakness, minimal sensory disturbance and length-dependent motor axonal degeneration with CMT examination score ranging from 6 to 10. Our report further confirms the role of WARS in dHMN and indicates that the variant c.941A>G (p.Asp314Gly) of WARS is related to a mild to moderate affected and later onset phenotype of dHMN.</AbstractText"
]
] |
[
[
"34686764",
"Altered functional brain dynamics in chromosome 22q11.2 deletion syndrome during facial affect processing.",
"Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a multisystem disorder associated with multiple congenital anomalies, variable medical features, and neurodevelopmental differences resulting in diverse psychiatric phenotypes, including marked deficits in facial memory and social cognition. Neuroimaging in individuals with 22q11.2DS has revealed differences relative to matched controls in BOLD fMRI activation during facial affect processing tasks. However, time-varying interactions between brain areas during facial affect processing have not yet been studied with BOLD fMRI in 22q11.2DS. We applied constrained principal component analysis to identify temporally overlapping brain activation patterns from BOLD fMRI data acquired during an emotion identification task from 58 individuals with 22q11.2DS and 58 age-, race-, and sex-matched healthy controls. Delayed frontal-motor feedback signals were diminished in individuals with 22q11.2DS, as were delayed emotional memory signals engaging amygdala, hippocampus, and entorhinal cortex. Early task-related engagement of motor and visual cortices and salience-related insular activation were relatively preserved in 22q11.2DS. Insular activation was associated with task performance within the 22q11.2DS sample. Differences in cortical surface area, but not cortical thickness, showed spatial alignment with an activation pattern associated with face processing. These findings suggest that relative to matched controls, primary visual processing and insular function are relatively intact in individuals with 22q11.22DS, while motor feedback, face processing, and emotional memory processes are more affected. Such insights may help inform potential interventional targets and enhance the specificity of neuroimaging indices of cognitive dysfunction in 22q11.2DS.</AbstractText"
]
] |
40269690
|
Prediction model and scoring system for the risk of atrial fibrillation recurrence in patients with atrial fibrillation and obstructive sleep apnoea syndrome: a retrospective case-control study.
|
The high prevalence of atrial fibrillation (AF) and obstructive sleep apnea syndrome (OSAS) imposes a substantial disease burden on public healthcare, making it a significant health concern in the current era. However, there is currently a lack of risk assessment tools for AF recurrence in patients with AF and OSAS. Therefore, this study aims to explore the factors influencing AF recurrence in patients with AF and OSAS, and to establish a predictive model and scoring system for AF recurrence rates.</AbstractText The study included a total of 423 patients with AF and OSAS, who were randomly divided into train set (n = 296) and test set (n = 127) in a ratio of 7:3. Afterwards, the train set was split into a recurrence group and a non-recurrence group for further analysis of indicators while in hospital.</AbstractText Following Lasso regression screening, 8 variables were selected from a pool of 62 variables from patients with AF and OSAS. Additionally, the study incorporated the CHA<sub The predictive models and scoring systems developed in this study demonstrate good predictive ability in assessing the recurrence of AF in patients with OSAS, offering invaluable clinical guidance and references.</AbstractText Not applicable.</AbstractText
|
[
[
"20725915",
"Blood oxygenation level-dependent activation in basal ganglia nuclei relates to specific symptoms in de novo Parkinson's disease.",
"To aid the development of symptomatic and disease modifying therapies in Parkinson's disease (PD), there is a strong need to identify noninvasive measures of basal ganglia (BG) function that are sensitive to disease severity. This study examines the relation between blood oxygenation level-dependent (BOLD) activation in every nucleus of the BG and symptom-specific disease severity in early stage de novo PD. BOLD activation measured at 3 T was compared between 20 early stage de novo PD patients and 20 controls during an established precision grip force task. In addition to the BG nuclei, activation in specific thalamic and cortical regions was examined. There were three novel findings. First, there were significant negative correlations between total motor Unified PD Rating Scale and BOLD activation in bilateral caudate, bilateral putamen, contralateral external segment of the globus pallidus, bilateral subthalamic nucleus, contralateral substantia nigra, and thalamus. Second, bradykinesia was the symptom that most consistently predicted BOLD activation in the BG and thalamus. Also, BOLD activation in the contralateral internal globus pallidus was related to tremor. Third, the reduced cortical activity in primary motor cortex and supplementary motor area in de novo PD did not relate to motor symptoms. These findings demonstrate that BOLD activity in nuclei of the BG relates most consistently to bradykinesia and functional magnetic resonance imaging has strong potential to serve as a noninvasive marker for the state of BG function in de novo PD.</AbstractText"
]
] |
[
[
"40515391",
"Gene Swin transformer: new deep learning method for colorectal cancer prognosis using transcriptomic data.",
"Transcriptome sequencing has become essential in clinical tumor research, providing in-depth insights into the biology and functionality of tumor cells. However, the vast amount of data generated and the complex relationships between gene expressions make it challenging to effectively identify clinically relevant information. In this study, we developed a method called Gene Swin Transformer to address these challenges. This approach converts transcriptomic data into Synthetic Image Elements (SIEs). We utilized data from 12 datasets, including GSE17536-GSE103479 datasets (n = 1771) and The Cancer Genome Atlas (n = 459), to generate SIEs. These elements were then classified based on survival time using deep learning algorithms to predict colorectal cancer prognosis and build a reliable prognostic model. We trained and evaluated four deep learning models-BeiT, ResNet, Swin Transformer, and ViT Transformer-and compared their performance. The enhanced Swin-T model outperformed the other models, achieving weighted precision, recall, and F1 scores of 0.708, 0.692, and 0.705, respectively, along with area under the curve values of 80.2%, 72.7%, and 76.9% across three datasets. This model demonstrated the strongest prognostic prediction capabilities among those evaluated. Additionally, the PEX10 gene was identified as a key prognostic marker through both visual attention matrix analysis and bioinformatics methods. Our study demonstrates that the Gene Swin model effectively transforms Ribonucleic Acid (RNA) sequencing data into SIEs, enabling prognosis prediction through attention-based algorithms. This approach supports the development of a data-driven, unified, and automated model, offering a robust tool for classification and prediction tasks using RNA sequencing data. This advancement presents a novel clinical strategy for cancer treatment and prognosis forecasting.</AbstractText"
]
] |
22890939
|
SNR-optimized phase-sensitive dual-acquisition turbo spin echo imaging: a fast alternative to FLAIR.
|
Phase-sensitive dual-acquisition single-slab three-dimensional turbo spin echo imaging was recently introduced, producing high-resolution isotropic cerebrospinal fluid attenuated brain images without long inversion recovery preparation. Despite the advantages, the weighted-averaging-based technique suffers from noise amplification resulting from different levels of cerebrospinal fluid signal modulations over the two acquisitions. The purpose of this work is to develop a signal-to-noise ratio-optimized version of the phase-sensitive dual-acquisition single-slab three-dimensional turbo spin echo. Variable refocusing flip angles in the first acquisition are calculated using a three-step prescribed signal evolution while those in the second acquisition are calculated using a two-step pseudo-steady state signal transition with a high flip-angle pseudo-steady state at a later portion of the echo train, balancing the levels of cerebrospinal fluid signals in both the acquisitions. Low spatial frequency signals are sampled during the high flip-angle pseudo-steady state to further suppress noise. Numerical simulations of the Bloch equations were performed to evaluate signal evolutions of brain tissues along the echo train and optimize imaging parameters. In vivo studies demonstrate that compared with conventional phase-sensitive dual-acquisition single-slab three-dimensional turbo spin echo, the proposed optimization yields 74% increase in apparent signal-to-noise ratio for gray matter and 32% decrease in imaging time. The proposed method can be a potential alternative to conventional fluid-attenuated imaging.</AbstractText
|
[
[
"16155898",
"New insights into the mechanisms of signal formation in RF-spoiled gradient echo sequences.",
"RF spoiling is a well established method to produce T(1)-weighted images with short repetition-time gradient-echo sequences, by eliminating coherent transverse magnetization with appropriate RF phase modulation. This paper presents 2 novel approaches to describe signal formation in such sequences. Both methods rely on the formulation of RF spoiling as a linear increase of the precession angle between RF pulses, which is an alternative to the commonly used quadratic pulse phase scheme. The first technique demonstrates that a steady state signal can be obtained by integrating over all precession angles within the voxel, in spite of the lack of a genuine steady-state for separate isochromats. This clear mathematical framework allows a straightforward incorporation of off-resonance effects and detector phase settings. Moreover, it naturally introduces the need for a large net gradient area per repetition interval. In the second step, a modified partition method including RF spoiling is developed to obtain explicit expressions for all signal components. This provides a physical interpretation of the deviations from ideal spoiling behavior in FLASH and echo-shifted sequences. The results of the partition method in the small flip angle regime are compared with numerical simulations based on a Fourier decomposition of magnetization states. Measurements performed with in vitro solutions were in good agreement with numerical simulations at short relaxation times (T(1)/TR = 32 and T(2)/TR = 4); larger deviations occurred at long relaxation times (T(1)/TR = 114 and T(2)/TR = 82).</AbstractText"
]
] |
[
[
"23992544",
"Evaluation of the insulin releasing and antihyperglycaemic activities of GPR55 lipid agonists using clonal beta-cells, isolated pancreatic islets and mice.",
"G-protein coupled receptor (GPR)55 is a novel lipid sensing receptor activated by both cannabinoid endogenous ligands (endocannabinoids) and other non-cannabinoid lipid transmitters. This study assessed the effects of various GPR55 agonists on glucose homeostasis.</AbstractText Insulin secretion and changes in intracellular Ca(2) (+) and cAMP in response to glucose and a range of GPR55 agonists [endogenous ligands (OEA, PEA), chemically synthetic cannabidiol (CBD) analogues (Abn-CBD, 0-1602), an analogue of rimonabant (AM-251) and antagonist (CBD)] were investigated in clonal BRIN-BD11 cells and mouse pancreatic islets. Cytotoxicity was assessed by LDH release, cellular localization by double-staining immunohistochemistry and in vivo effects assessed in mice.</AbstractText The most potent and selective GPR55 agonist was the synthetic CBD analogue, Abn-CBD (pEC50 10.33), maximum stimulation of 67% at 10(-4)  mol·L(-1) (P < 0.001) in BRIN-BD11 cells. AM-251 (pEC50 7.0), OEA (pEC50 7.0), 0-1602 (pEC50 7.3) and PEA (pEC50 6.0) stimulated insulin secretion. Results were corroborated by islet studies, with no cytotoxic effects. Concentration-dependent insulin secretion by GPR55 agonists was glucose-sensitive and accompanied by elevations of [Ca(2) (+) ]i (P < 0.01-P < 0.001) and cAMP (P < 0.05-P < 0.01). GPR55 agonists exhibited insulinotropic and glucose lowering activity in vivo. GPR55 was expressed on BRIN-BD11 cells and confined to islet beta cells with no distribution on alpha cells.</AbstractText These results demonstrate GPR55 is distributed in pancreatic beta cells and is a strong activator of insulin secretion, with glucose-lowering effects in vivo. Development of agents agonizing the GPR55 receptor may have therapeutic potential in the treatment of type 2 diabetes.</AbstractText"
]
] |
40772448
|
Wishes, conflicts, and support needs of informal caregivers of patients in the palliative phase: A qualitative study.
|
This study explored wishes, conflicts, beneficial, and wished support of informal caregivers (ICGs) providing care to a palliative ill close other. We interviewed five current and 15 bereaved ICGs (25-75 years), and used thematic analyses. ICGs wished to continue life as normal as possible, spend time together and with their family, comfort their close other, and continue own activities. Caregivers experienced conflicts in balancing caregiving and own activities, quality time with each other and social contacts, the level of professional or informal support preferred, and in their shifting role from partner/child to nurse. ICGs experienced practical support, being heard, and good professional support as helpful. An overview of available support options, one contact for administrative issues, and an environment that pays attention to ICGs' wellbeing could make caregiving easier. Formal carers and digital tools can support caregivers in balancing wishes and boundaries with the requests of caregiving to decrease conflicts.</AbstractText
|
[
[
"38845595",
"Staying in control: Characterizing the mechanisms underlying cognitive control in high and low arousal states.",
"Throughout the day, humans show natural fluctuations in arousal that impact cognitive function. To study the behavioural dynamics of cognitive control during high and low arousal states, healthy participants performed an auditory conflict task during high-intensity physical exercise (N = 39) or drowsiness (N = 33). In line with the pre-registered hypotheses, conflict and conflict adaptation effects were preserved during both altered arousal states. Overall task performance was markedly poorer during low arousal, but not for high arousal. Modelling behavioural dynamics with drift diffusion analysis revealed evidence accumulation and non-decision time decelerated, and decisional boundaries became wider during low arousal, whereas high arousal was unexpectedly associated with a decrease in the interference of task-irrelevant information processing. These findings show how arousal differentially modulates cognitive control at both sides of normal alertness, and further validate drowsiness and physical exercise as key experimental models to disentangle the interaction between physiological fluctuations on cognitive dynamics.</AbstractText"
]
] |
[
[
"40132153",
"Neuroimaging in Children With Inherited Metabolic Epilepsies.",
"Inherited metabolic epilepsies (IMEs) represent inherited metabolic disorders in which seizures, various in types and typically intractable, are one of the predominant manifestations and primary determinants of the overall outcome. A metabolic etiology should be suspected in any case of refractory seizures stemming from an undetermined cause. While the occurrence rate of individual IMEs is rare, their cumulative prevalence is high enough to pose a significant clinical challenge. Concurrently with genetic and metabolic tests, neuroimaging is considered part of the first tier of their investigation, attained with an aim to affirm or counter the phenotype. It may be normal or nonspecific; however, as described by this overview, there is an appreciable number of IMEs associated with distinct MRI or magnetic resonance spectroscopy patterns. Apart from narrowing or supporting their diagnoses, these neuroimaging patterns may serve as biomarkers to monitor treatment efficacy and outcome. Other advanced modalities and techniques, such as PET, fMRI, diffusion tensor imaging, MRI g-ratio mapping, and functional near-infrared spectroscopy, broaden our insights relating to their pathophysiology, clinical course, targeted treatment development, and prognosis.</AbstractText"
]
] |
40492610
|
MDMA-assisted psychotherapy for AUD: Bayesian analysis of WHO drinking risk level and exploratory analysis of drinking behavior and psychosocial functioning at 3 months follow-up.
|
Safety and tolerability data from the first open-label feasibility study of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for alcohol use disorder was recently published. This paper presents a Bayesian analysis of the impact of MDMA-assisted psychotherapy on treatment success, defined as 2-level reduction in the World Health Organization (WHO) drinking risk at the 3 months follow-up. We also examined the impact on drinking behavior and psychosocial measures at 3 months compared to baseline.</AbstractText Fourteen participants with a diagnosis of alcohol use disorder who had recently undergone detoxification completed an eight-week course of ten psychotherapy sessions, including two sessions with MDMA. Measures assessing drinking behavior, quality of life, sleep, self-compassion, and empathy were collected. Bayesian analysis using flat and skeptical priors was performed to determine treatment success defined as a 2-level reduction in WHO drinking risk.</AbstractText Bayesian analysis suggested that the probability of a 2-level reduction in WHO drinking risk from baseline to 3 months post-treatment is 55%-63%, based upon either a flat or skeptical prior respectively. We present preliminary findings suggesting reductions in alcohol craving (measured by the Penn Alcohol Craving Scale and Obsessive Compulsive Drinking Scale) and improvements in sleep and aspects of psychosocial functioning at 3 months follow-up compared to baseline.</AbstractText The Bayesian analysis provides a useful harm reduction endpoint interpretation of drinking in terms of a 2-level reduction in WHO drinking risk. Further findings provide preliminary insights into the potential impact of MDMA-assisted psychotherapy on quality of life and well-being in addition to reductions in drinking. ClinicalTrials.gov ID: NCT04158778.</AbstractText
|
[
[
"38619933",
"Suggesting a holistic framework for understanding healthcare services leadership competence - a critical interpretive synthesis.",
"Healthcare providers are under pressure due to increasing and more complex demands for services. Increased pressure on budgets and human resources adds to an ever-growing problem set. Competent leaders are in demand to ensure effective and well-performing healthcare organisations that deliver balanced results and high-quality services. Researchers have made significant efforts to identify and define determining competencies for healthcare leadership. Broad terms such as competence are, however, inherently at risk of becoming too generic to add analytical value. The purpose of this study is to suggest a holistic framework for understanding healthcare leadership competence, that can be crucial for operationalising important healthcare leadership competencies for researchers, decision-makers as well as practitioners.</AbstractText In the present study, a critical interpretive synthesis (CIS) was conducted to analyse competency descriptions for healthcare leaders. The descriptions were retrieved from peer reviewed empirical studies published between 2010 and 2022 that aimed to identify healthcare services leadership competencies. Grounded theory was utilised to code the data and inductively develop new categories of healthcare leadership competencies. The categorisation was then analysed to suggest a holistic framework for healthcare leadership competence.</AbstractText Forty-one papers were included in the review. Coding and analysing the competence descriptions resulted in 12 healthcare leadership competence categories: (1) character, (2) interpersonal relations, (3) leadership, (4) professionalism, (5) soft HRM, (6) management, (7) organisational knowledge, (8) technology, (9) knowledge of the healthcare environment, (10) change and innovation, (11) knowledge transformation and (12) boundary spanning. Based on this result, a holistic framework for understanding and analysing healthcare services leadership competencies was suggested. This framework suggests that the 12 categories of healthcare leadership competencies include a range of knowledge, skills and abilities that can be understood across the dimension personal - and technical, and organisational internal and - external competencies.</AbstractText This literature review was conducted with the results of searching only two electronic databases. Because of this, there is a chance that there exist empirical studies that could have added to the development of the competence categories or could have contradicted some of the descriptions used in this analysis that were assessed as quite harmonised. A CIS also opens for a broader search, including the grey literature, books, policy documents and so on, but this study was limited to peer-reviewed empirical studies. This limitation could also have affected the result, as complex phenomenon such as competence might have been disclosed in greater details in, for example, books.</AbstractText The holistic framework for healthcare leadership competences offers a common understanding of a \"fuzzy\" concept such as competence and can be used to identify specific competency needs in healthcare organisations, to develop strategic competency plans and educational programmes for healthcare leaders.</AbstractText This study reveals a lack of consensus regarding the use and understanding of the concept of competence, and that key competencies addressed in the included papers are described vastly different in terms of what knowledge, skills and abilities they entail. This challenges the operationalisation of healthcare services leadership competencies. The proposed framework for healthcare services leadership competencies offers a common understanding of work-related competencies and a possibility to analyse key leadership competencies based on a holistic framework.</AbstractText"
]
] |
[
[
"39955842",
"Hormones, brain and behavior in birds: The Lehrman legacy.",
"This short essay is based on the presentation I gave at the meeting of the Society of Behavioral Neuroendocrinology held in Tours, France in June 2023 when I received the Lehrman award for career achievement. I conducted my PhD at the Institute of Animal Behavior that was founded by Lehrman at Rutgers University. Although I never met Lehrman I was mentored by several scientists who had worked with him. I therefore decided to organize my essay about the Lehrman award around the enduring legacy of Lehrman's work as it influenced my career. Four aspects of the scientific legacy of Daniel Lehrman are distinguished and I discuss how these insights affected my own research program. A concise summary of the research I conducted in collaboration with PhD students and postdocs that relates to these topics is then presented. This research that involves several avian species includes studies of how behavior can influence the endocrine physiology and behavior of receivers of a particular signal. The cloning of the gonadotropin-releasing hormone (GnRH) gene in songbirds and analysis of the environmental factors influencing its expression demonstrated how the GnRH neuronal system is a key link between the perception of behavior and changes in endocrine physiology. Finally, there is a review of studies of the experimental analysis of the brain sites where testosterone acts to control the motivation to sing and the quality of song in songbirds that follow directly in the Lehrman line of work on how steroids regulate avian reproductive behaviors.</AbstractText"
]
] |
38412004
|
Characteristics of Hepatitis B Virus, Hepatitis C Virus, and Syphilis Coinfection in People With HIV/AIDS Contracted Through Different Sources: Retrospective Study.
|
The burden of hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis coinfections remains disproportionately high among people living with HIV/AIDS. Hubei province is located in central China, where there are distinct regional characteristics of the distribution of people living with HIV/AIDS acquired via diverse transmission routes and the AIDS epidemic itself.</AbstractText We aimed to estimate the magnitude of HBV, HCV, or syphilis coinfections among people living with HIV/AIDS with blood-borne transmission, which includes former paid blood donors, contaminated blood recipients, and intravenous drug users, as well as among people with sex-borne HIV transmission (including heterosexual people and men who have sex with men) and people with mother-to-child HIV transmission.</AbstractText From January 2010 to December 2020, people living with HIV/AIDS were tested for hepatitis B surface antigen (HBsAg), HCV antibodies, and syphilis-specific antibodies. The positive patients were further tested for HBV markers, HBV DNA, and HCV RNA, and received a rapid plasma reagin circle card test. All people living with HIV/AIDS were first divided into transmission groups (blood, sex, and mother-to-child); then, people with blood-borne HIV transmission were divided into former paid blood donors, contaminated blood recipients, and intravenous drug users, while people with sex-borne HIV transmission were divided into heterosexual people and men who have sex with men.</AbstractText Among 6623 people living with HIV/AIDS, rates of chronic HCV infection were 80.3% (590/735) in former paid blood donors, 73.3% (247/337) in intravenous drug users, 57.1% (444/777) in contaminated blood recipients, 19.4% (21/108) in people with mother-to-child HIV transmission, 8.1% (240/2975) in heterosexual people, and 1.2% (21/1691) in men who have sex with men. Chronic HBV infection rates were similar among all people with blood-borne HIV transmission. However, compared to heterosexual people, the chronic HBV infection rate was greater in men who have sex with men (213/1691, 12.6% vs 308/2975, 10.4%; χ<sup In people living with HIV/AIDS, HCV transmission intensity was significantly associated with specific exposure modes of blood or sexual contact. The rate of chronic HBV infection among men who have sex with men was higher than in any other population. Attention should be paid to the high prevalence of neurosyphilis in people living with HIV/AIDS who contract HIV by sexual intercourse.</AbstractText
|
[
[
"37795953",
"Diagnostic value of cerebrospinal fluid chemokine c-x-c motif ligand 13 for neurosyphilis: A systematic review and meta-analysis.",
"The diagnostic value of cerebrospinal fluid chemokine c-x-c motif ligand 13 (CSF CXCL13) for neurosyphilis was assessed by meta-analysis in this study. PubMed, Web of Science and Embase databases were searched to identify relevant articles by using MeSH and free terms of CXCL13 and neurosyphilis. A total of 720 syphilis and 338 neurosyphilis individuals in 6 articles were involved in this meta-analysis. The pooled sensitivity and specificity were 0.82 (95% confidence intervals (CI), 0.77-0.87) and 0.84 (95% CI, 0.79-0.87). The pooled positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and the area under receiver operating characteristic curve were 5.10 (95% CI, 3.90-6.60), 0.21 (95% CI, 0.16-0.28), 24.00 (95% CI, 14.00-39.00) and 0.88 (95% CI, 0.84-0.90), respectively. In subgroup analysis, human immunodeficiency virus infection and diagnostic criteria for neurosyphilis were identified to be associated with heterogeneity. Based on limited evidence, CSF CXCL13 can be helpful in diagnosing neurosyphilis.</AbstractText"
]
] |
[
[
"39391051",
"Deciphering Proteomic Expression in Inflammatory Disorders: A Mass Spectrometry Exploration Comparing Infectious, Noninfectious, and Traumatic Brain Injuries in Human Cerebrospinal Fluid.",
"The central nervous system (CNS) evokes a complex inflammatory response to injury. Inflammatory cascades are present in traumatic, infectious, and noninfectious disorders affecting the brain. It contains a mixture of pro- and anti-inflammatory reactions involving well-known proteins, but also numerous proteins less explored in these processes. The aim of this study was to explore the distinct inflammatory response in traumatic brain injury (TBI) compared with other CNS injuries by utilization of mass-spectrometry. In total, 56 patients had their cerebrospinal fluid (CSF) analyzed with the use of mass-spectrometry. Among these, CSF was collected via an external ventricular drain (EVD) from <i"
]
] |
40102551
|
Hair cortisol as a marker of stress in mild traumatic brain injury: a challenging measure.
|
Cortisol is released through activation of the hypothalamic-pituitary-adrenal axis by physiological and psychological stressors, such as mild traumatic brain injury (mTBI). This hormone is accumulated in hair over longer periods of time, reflecting both acute and chronic forms of stress, allowing for retrospective analyses within certain timeframes. The main objectives of this study were to analyze pre- and post-injury hair cortisol concentrations, and to explore possible associations with personality and recovery after mTBI. Hair samples of 61 mTBI patients were collected at 4-6 weeks post-injury and divided into pre- (1 cm) and post-injury (1 cm) segments. For comparison, hair samples of 24 age, sex and education matched healthy controls (HC) were collected and divided into similar segments. Cortisol was quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). At two weeks post-injury, post-traumatic symptoms (PTS), emotional distress (anxiety/depression), and the personality trait neuroticism were measured. At six months post-injury, PTS and functional recovery (Glasgow Outcome Scale Extended) were determined. A significant increase in hair cortisol concentration from pre- to post-injury was found for both mTBI patients and HC, likely due to washout effects, with similar concentrations in both groups. Neither hair cortisol, nor the interaction with neuroticism, were associated with long-term PTS or functional recovery. Additionally, no differences in hair cortisol were observed between patients with a higher and lower risk of developing persistent PTS based on a modified Post-Concussion Symptoms Rule (PoCS Rule) including demographics, acute symptoms, pre-injury mental health and head CT. Altogether, our findings do not support the current use of hair cortisol as a potential marker of stress in mTBI.</AbstractText
|
[
[
"34054681",
"Traumatic Brain Injury Exposure Lowers Age of Cognitive Decline in AD and Non-AD Conditions.",
"We aimed to detect the possible accelerating role of previous traumatic brain injury (TBI) exposures on the onset of later cognitive decline assessed across different brain diseases. We analyzed data from the National Alzheimer's Coordinating Center (NACC), which provide information on history of TBI and longitudinal data on cognitive and non-cognitive domains for each available subject. At the time of this investigation, a total of 609 NACC subjects resulted to have a documented history of TBI. We compared subjects with and without a history of previous TBI (of any type) at the time of their first cognitive decline assessment, and termed them, respectively, TBI+ and TBI- subjects. Three hundred and sixty-one TBI+ subjects (229 male/132 female) and 248 TBI- subjects (156 male/92 female) were available. The analyses included TBI+ and TBI- subjects with a clinical diagnosis of Mild Cognitive Impairment, Alzheimer's disease, Dementia with Lewy bodies, Progressive supranuclear palsy, Corticobasal degeneration, Frontotemporal dementia, Vascular dementia, non-AD Impairment, and Parkinson's disease. The data showed that the mean age of TBI+ subjects was lower than TBI- subjects at the time of their first cognitive decline assessment (71.6 ± 11.2 vs. 74.8 ± 9.5 year; <i"
]
] |
[
[
"39333695",
"Exploring the structure and dynamics of soft and hard cuticle of Bombyx mori using solid-state NMR techniques.",
"This study conducts a comprehensive analysis and comparison of Bombyx mori cuticles across different developmental stages, ranging from larval to adult, utilizing advanced solid-state NMR techniques. The primary objective is to elucidate the underlying reasons for the contrasting hardness of adult cuticles and softness of larval cuticles. Notably, PXRD analysis reveals a prominent broad peak at 19.34°, indicating the predominantly amorphous nature of both larval and adult cuticles. Analysis of <sup"
]
] |
20883353
|
Identification of red-green colour deficiency: sensitivity of the Ishihara and American Optical Company (Hard, Rand and Rittler) pseudo-isochromatic plates to identify slight anomalous trichromatism.
|
Screening sensitivity, based on a specific number of errors, of the Ishihara plates and of the American Optical Company (Hardy, Rand and Rittler) plates (HRR plates) was determined by reviewing data obtained for 486 male anomalous trichromats identified and classified with the Nagel anomaloscope. Data were obtained for the 16 screening plates, with Transformation and Vanishing numeral designs, of the 38 plate Ishihara test, and for the four red-green screening plates (with six Vanishing designs) of the HRR test. Sensitivity of the Ishihara plates was found to be 97.7% on 4 errors and 98.4% on 3 errors. Only anomalous trichromats with slight deficiency, according to the anomaloscope matching range, made 8 errors or fewer. One screening error, a single missed figure, is normally allowed as a pass on the HRR test and 3 errors is often recommended as the fail criterion to eliminate false positive results. Twenty-three subjects made no error on the HRR screening plates and 12 subjects made a single error (35 anomalous trichromats). Screening sensitivity was therefore 92.8% using 2 errors as the fail criterion. Screening sensitivity was reduced to 87% when 3 errors was the fail criterion, and some deuteranomalous trichromats with moderate deficiency, according to the anomaloscope matching range, were not identified. Individuals who make a maximum of 2 errors on the HRR test, or on the Richmond HRR 4th Edition, should be re-examined with the Ishihara plates to determine their colour vision status. The present review confirms that the Ishihara test is a very sensitive screening test and identifies people with slight anomalous trichromatism. The HRR test is unsatisfactory for screening and should not be chosen solely for this purpose.</AbstractText
|
[
[
"15252758",
"Signatures of selection and gene conversion associated with human color vision variation.",
"Trichromatic color vision in humans results from the combination of red, green, and blue photopigment opsins. Although color vision genes have been the targets of active molecular and psychophysical research on color vision abnormalities, little is known about patterns of normal genetic variation in these genes among global human populations. The current study presents nucleotide sequence analyses and tests of neutrality for a 5.5-kb region of the X-linked long-wave \"red\" opsin gene (OPN1LW) in 236 individuals from ethnically diverse human populations. Our analysis of the recombination landscape across OPN1LW reveals an unusual haplotype structure associated with amino acid replacement variation in exon 3 that is consistent with gene conversion. Compared with the absence of OPN1LW amino acid replacement fixation since divergence from chimpanzee, the human population exhibits a significant excess of high-frequency OPN1LW replacements. Our results suggest that subtle changes in L-cone opsin wavelength absorption may have been adaptive during human evolution.</AbstractText"
]
] |
[
[
"20428887",
"The role of anterior insular cortex in social emotions.",
"Functional neuroimaging investigations in the fields of social neuroscience and neuroeconomics indicate that the anterior insular cortex (AI) is consistently involved in empathy, compassion, and interpersonal phenomena such as fairness and cooperation. These findings suggest that AI plays an important role in social emotions, hereby defined as affective states that arise when we interact with other people and that depend on the social context. After we link the role of AI in social emotions to interoceptive awareness and the representation of current global emotional states, we will present a model suggesting that AI is not only involved in representing current states, but also in predicting emotional states relevant to the self and others. This model also proposes that AI enables us to learn about emotional states as well as about the uncertainty attached to events, and implies that AI plays a dominant role in decision making in complex and uncertain environments. Our review further highlights that dorsal and ventro-central, as well as anterior and posterior subdivisions of AI potentially subserve different functions and guide different aspects of behavioral regulation. We conclude with a section summarizing different routes to understanding other people's actions, feelings and thoughts, emphasizing the notion that the predominant role of AI involves understanding others' feeling and bodily states rather than their action intentions or abstract beliefs.</AbstractText"
]
] |
28774650
|
Rapid anatomical brain imaging using spiral acquisition and an expanded signal model.
|
We report the deployment of spiral acquisition for high-resolution structural imaging at 7T. Long spiral readouts are rendered manageable by an expanded signal model including static off-resonance and B<sub
|
[
[
"11810678",
"Elimination of Nyquist ghosting caused by read-out to phase-encode gradient cross-terms in EPI.",
"Echo-planar imaging (EPI) commonly suffers from ghosting artifacts caused by zero- or first-order phase differences between the odd and even echoes that constitute an EPI dataset. Small-bore imaging systems with shielded gradients may suffer significantly from cross-term eddy currents due to the high degree of manufacturing precision required in such systems compared to larger whole-body coils. A Nyquist ghost caused by cross-term eddy current contributions from the read-out to the phase-encode axis was identified in a small-bore system and characterized using a modified EPI experiment and a computer simulation. The artifact was corrected for using both a postprocessing approach and compensation blips along the phase-encode axis. Correction using compensation blips proved to be a more effective strategy to reduce this artifact than the postprocessing method used.</AbstractText"
]
] |
[
[
"29872302",
"Valium without dependence? Individual GABA(A) receptor subtype contribution toward benzodiazepine addiction, tolerance, and therapeutic effects.",
"Benzodiazepines are one of the most prescribed medications as first-line treatment of anxiety, insomnia, and epilepsy around the world. Over the past two decades, advances in the neuropharmacological understanding of gamma aminobutyric acid (GABA)<sub"
]
] |
24711394
|
Homeostasis of functional maps in active dendrites emerges in the absence of individual channelostasis.
|
The maintenance of ion channel homeostasis, or channelostasis, is a complex puzzle in neurons with extensive dendritic arborization, encompassing a combinatorial diversity of proteins that encode these channels and their auxiliary subunits, their localization profiles, and associated signaling machinery. Despite this, neurons exhibit amazingly stereotypic, topographically continuous maps of several functional properties along their active dendritic arbor. Here, we asked whether the membrane composition of neurons, at the level of individual ion channels, is constrained by this structural requirement of sustaining several functional maps along the same topograph. We performed global sensitivity analysis on morphologically realistic conductance-based models of hippocampal pyramidal neurons that coexpressed six well-characterized functional maps along their trunk. We generated randomized models by varying 32 underlying parameters and constrained these models with quantitative experimental measurements from the soma and dendrites of hippocampal pyramidal neurons. Analyzing valid models that satisfied experimental constraints on all six functional maps, we found topographically analogous functional maps to emerge from disparate model parameters with weak pairwise correlations between parameters. Finally, we derived a methodology to assess the contribution of individual channel conductances to the various functional measurements, using virtual knockout simulations on the valid model population. We found that the virtual knockout of individual channels resulted in variable, measurement- and location-specific impacts across the population. Our results suggest collective channelostasis as a mechanism behind the robust emergence of analogous functional maps and have significant ramifications for the localization and targeting of ion channels and enzymes that regulate neural coding and homeostasis.</AbstractText
|
[
[
"12417672",
"Response of neurons in the lateral intraparietal area during a combined visual discrimination reaction time task.",
"Decisions about the visual world can take time to form, especially when information is unreliable. We studied the neural correlate of gradual decision formation by recording activity from the lateral intraparietal cortex (area LIP) of rhesus monkeys during a combined motion-discrimination reaction-time task. Monkeys reported the direction of random-dot motion by making an eye movement to one of two peripheral choice targets, one of which was within the response field of the neuron. We varied the difficulty of the task and measured both the accuracy of direction discrimination and the time required to reach a decision. Both the accuracy and speed of decisions increased as a function of motion strength. During the period of decision formation, the epoch between onset of visual motion and the initiation of the eye movement response, LIP neurons underwent ramp-like changes in their discharge rate that predicted the monkey's decision. A steeper rise in spike rate was associated with stronger stimulus motion and shorter reaction times. The observations suggest that neurons in LIP integrate time-varying signals that originate in the extrastriate visual cortex, accumulating evidence for or against a specific behavioral response. A threshold level of LIP activity appears to mark the completion of the decision process and to govern the tradeoff between accuracy and speed of perception.</AbstractText"
]
] |
[
[
"23893323",
"An atypical case of SCN9A mutation presenting with global motor delay and a severe pain disorder.",
"Erythromelalgia due to heterozygous gain-of-function SCN9A mutations usually presents as a pure sensory-autonomic disorder characterized by recurrent episodes of burning pain and redness of the extremities.</AbstractText We describe a patient with an unusual phenotypic presentation of gross motor delay, childhood-onset erythromelalgia, extreme visceral pain episodes, hypesthesia, and self-mutilation. The investigation of the patient's motor delay included various biochemical analyses, a comparative genomic hybridization array (CGH), electromyogram (EMG), and muscle biopsy. Once erythromelalgia was suspected clinically, the SCN9A gene was sequenced.</AbstractText The EMG, CGH, and biochemical tests were negative. The biopsy showed an axonal neuropathy and neurogenic atrophy. Sequencing of SCN9A revealed a heterozygous missense mutation in exon 7; p.I234T.</AbstractText This is a case of global motor delay and erythromelalgia associated with SCN9A. The motor delay may be attributed to the extreme pain episodes or to a developmental perturbation of proprioceptive inputs.</AbstractText"
]
] |
40056182
|
Review of 7T MRI imaging of pituitary microadenomas: are we there yet?
|
7T MRI imaging of the pituitary gland is an emerging technique. The purpose of this article is to review the current status of the 7T MRI of the pituitary gland, particularly in the context of pituitary microadenoma pathology. We will discuss technical challenges and parallel transmission opportunities.</AbstractText Follow-up study selection and data extraction were performed following PRISMA guidelines. We focused on diagnostic performance and acquisition protocols. Inclusion criteria were: MRI imaging studies of pituitary adenoma at 7T. Exclusion criteria were: Case reports and reviews; studies which did not report MRI protocols; surgical planning studies; studies focusing exclusively on macroadenomas for which ultra-high magnetic field imaging is less decisive than microadenomas in clinical practice.</AbstractText Six studies were included. 7T MRI outperformed 1.5 or 3T MRI for the detection of microadenomas. Acquisition protocols employed were heterogeneous, with two-dimensional T<sub 7T MRI is a promising tool for overcoming the difficulties encountered by conventional MRI, particularly in the case of Cushing disease. However, there is insufficient data to precisely define an optimal protocol yet.</AbstractText • 7T MRI outperforms conventional MRI in detecting microadenomas. • The increased in artifacts at 7T does not affect the interpretation of the data. • A reference protocol cannot be defined, given the heterogeneity of practices.</AbstractText
|
[
[
"19449383",
"A transmit/receive system for magnetic field monitoring of in vivo MRI.",
"Magnetic field monitoring with NMR probes has recently been introduced as a means of measuring the actual spatiotemporal magnetic field evolution during individual MR scans. Receive-only NMR probes as used thus far for this purpose impose significant practical limitations due to radiofrequency (RF) interference with the actual MR experiment. In this work these limitations are overcome with a transmit/receive (T/R) monitoring system based on RF-shielded NMR probes. The proposed system is largely autonomous and protected against RF contamination. As a consequence the field probes can be positioned freely and permit monitoring imaging procedures of arbitrary geometry and angulation. The T/R approach is also exploited to simplify probe manufacturing and remove constraints on material choices. Probe miniaturization permits monitoring imaging scans with nominal resolutions on the order of 400 microm. The added capabilities of the new probes and system are demonstrated by first in vivo results, obtained with monitored gradient-echo and spin-echo echo-planar imaging (EPI) scans.</AbstractText"
]
] |
[
[
"40503482",
"Magnetic resonance defecography assessment of obstructed defecation syndrome in patients with chronic constipation in a tertiary care hospital.",
"Obstructed defecation syndrome (ODS) is a subtype of constipation that is considered one of the major pelvic floor dysfunctions affecting the aging population, particularly women over 50 seeking medical care. The condition is characterized by the urge to defecate but an impaired ability to expel the fecal bolus. ODS is associated with various anorectal abnormalities, which are not always apparent during a standard physical examination, requiring specialized imaging techniques for proper diagnosis.</AbstractText To study the distribution of causes of ODS in patients with chronic constipation by magnetic resonance defecography (MRD).</AbstractText This observational study evaluated the causes of ODS in 57 patients with chronic constipation who presented to Bangabandhu Sheikh Mujib Medical University between July 2020 and June 2021. After obtaining institutional review board approval and informed consent, patients underwent history taking, physical exams, and relevant investigations. ODS was diagnosed using Rome III criteria, with colonoscopy ruling out organic causes. Standard MRD was performed in different phases, and images were analyzed by expert radiologists and reported in a standardized format.</AbstractText Pelvic floor descent and anorectal junction descent were the most frequent findings, each present in 94.7% of cases. Rectocele was observed in 78.9% of patients, while vaginal or uterine prolapse was seen in 59.4% of females. Less common abnormalities included paradoxical contraction (7%), and there were no cases of sigmoidocele. Functional measurements showed significant differences in pelvic floor dynamics between rest and defecation, particularly in the H-line, M-line, and descent of pelvic organs (<i Pelvic floor descent and anorectal descent were the most common findings in patients suffering from ODS, followed by rectocele. Younger females (< 30 years) were most affected.</AbstractText"
]
] |
40166768
|
Crossing the chasm: engaging Black men survivors of gun violence in mental health services.
|
Despite being high risk for post-traumatic stress disorder, Black men survivors of gun violence, and particularly young men aged 18-24, seldom participate in mental health services after injury. The aim of this study was to identify barriers to participation in mental health services for this population.</AbstractText Over a 2-year period, 1 hour-long focus group was conducted with three counselors of the local hospital-based violence intervention program and 21 individual, semistructured in-depth interviews were held with Black men who were hospitalized for a firearm-related injury. All interviews were recorded and transcribed. Transcripts were coded using open coding and grounded theory methodology and ultimately grouped into themes using MAXQDA V.2022 software.</AbstractText Median age of participants was 34 years (IQR=11). Barriers to participation revolved around competing priorities/stressors, expense, difficulty with trust and openness and the demands of street life. Motivating factors included cultural competence, persistence, availability, reliability and genuineness of the therapy staff. Most participants denied negative social stigma of therapy as a barrier but emphasized that the individual must value therapy to participate. Young, Black men were perceived as struggling with self and peer-imposed views of masculinity that conflicted with therapy participation.</AbstractText Black men who have experienced violent firearm injury face strong social pressures that conflict with participation in mental health services. Programs must be integrated with other social services and be responsive to community conditions to be successful.</AbstractText IV.</AbstractText
|
[
[
"25863813",
"Cerebellar Contribution to Context Processing in Extinction Learning and Recall.",
"Whereas acquisition of new associations is considered largely independent of the context, context dependency is a hallmark of extinction of the learned associations. The hippocampus and the prefrontal cortex are known to be involved in context processing during extinction learning and recall. Although the cerebellum has known functional and anatomic connections to the hippocampus and the prefrontal cortex, cerebellar contributions to context processing of extinction have rarely been studied. In the present study, we reanalyzed functional brain imaging data (fMRI) of previous work investigating context effects during extinction in a cognitive associative learning paradigm in 28 young and healthy subjects (Lissek et al. Neuroimage. 81:131-3, 2013). In that study, event-related fMRI analysis did not include the cerebellum. The 3 T fMRI dataset was reanalyzed using a spatial normalization method optimized for the cerebellum. Data of seven participants had to be excluded because the cerebellum had not been scanned in full. Cerebellar activation related to context change during extinction learning was most prominent in lobule Crus II bilaterally (p < 0.01, t > 2.53; partially corrected by predetermined cluster size). No significant cerebellar activations were observed related to context change during extinction retrieval. The posterolateral cerebellum appears to contribute to context-related processes during extinction learning, but not (or less) during extinction retrieval. The cerebellum may support context learning during extinction via its connections to the hippocampus. Alternatively, the cerebellum may support the shifting of attention to the context via its known connections to the dorsolateral prefrontal cortex. Because the ventromedial prefrontal cortex (vmPFC) is critically involved in context-related processes during extinction retrieval, and there are no known connections between the cerebellum and the vmPFC, the cerebellum may be less important during extinction recall.</AbstractText"
]
] |
[
[
"40412529",
"Surgical Nerve Decompression at Lower Extremity for Diabetic Neuropathy: A Systematic Review and Meta-Analysis of Time-Dependent Pain, Sensory Recovery, Amputation, Ulcer Recurrence, and Balance.",
"This systematic review and meta-analysis evaluated the efficacy of surgical nerve decompression in patients with diabetic peripheral neuropathy, focusing on pain relief over time, comprehensive sensory function, reduction in ulcer recurrence, amputation prevention, and balance improvement.</AbstractText Databases including PubMed, Scopus, and Web of Science were systematically searched up to January 8, 2025. Eighteen studies (4 randomized controlled trials and 14 observational studies; total n = 837) met inclusion criteria. Primary outcomes were pain relief and sensory recovery; secondary outcomes were ulcer recurrence, amputation rates, and balance. Data synthesis employed random-effects or fixed-effects models with heterogeneity and publication bias assessments.</AbstractText Surgical decompression significantly reduced pain at short-term (6 months: standardized mean difference [SMD]: 2.40, P < 0.001), medium-term (12 months: SMD: 2.02, P = 0.014), and long-term (> 12 months: SMD: 3.24, P = 0.009) follow-ups. Meta-regression revealed modest attenuation of pain relief over time (R<sup Surgical nerve decompression demonstrates sustained efficacy in pain management and substantially reduces severe diabetic neuropathy complications. Future high-quality randomized controlled trials are necessary to standardize outcomes and confirm long-term benefits.</AbstractText"
]
] |
39570907
|
Functional near-infrared spectrometry for auditory speech stimuli in cochlear implant users: a systematic literature review.
|
This study aims to identify the acquisition features of functional near-infrared spectroscopy (fNIRS) in cochlear implant users.</AbstractText A systematic literature review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, EMBASE, LILACS, Web of Science, Scopus, PsycINFO, IEEE Xplore, Google Scholar, and ProQuest Dissertations & Theses Global were searched using the PECOS acronym. Inclusion criteria encompassed studies involving fNIRS with speech stimuli in cochlear implant users of any age, with information on acquisition parameters and features. Risk of bias assessment was performed using the Joanna Briggs Institute tool.</AbstractText Nineteen studies were included, with thirteen exhibiting a low risk of bias. Noteworthy uniformity was observed in certain fNIRS acquisition features among cochlear implant users, including the waking state (awake), auditory stimuli of words or phrases presented in a free field, visual stimuli displayed during data collection as a secondary task, recording of responses in the bilateral temporal lobe, and a three-centimeter distance between optodes. Variations in acquisition were attributed to differing study purposes.</AbstractText This review identifies common acquisition characteristics for fNIRS in cochlear implant users. Multicenter research efforts are advocated to further advance the utility of fNIRS in this population.</AbstractText
|
[
[
"25151264",
"Dimensionality reduction for large-scale neural recordings.",
"Most sensory, cognitive and motor functions depend on the interactions of many neurons. In recent years, there has been rapid development and increasing use of technologies for recording from large numbers of neurons, either sequentially or simultaneously. A key question is what scientific insight can be gained by studying a population of recorded neurons beyond studying each neuron individually. Here, we examine three important motivations for population studies: single-trial hypotheses requiring statistical power, hypotheses of population response structure and exploratory analyses of large data sets. Many recent studies have adopted dimensionality reduction to analyze these populations and to find features that are not apparent at the level of individual neurons. We describe the dimensionality reduction methods commonly applied to population activity and offer practical advice about selecting methods and interpreting their outputs. This review is intended for experimental and computational researchers who seek to understand the role dimensionality reduction has had and can have in systems neuroscience, and who seek to apply these methods to their own data.</AbstractText"
]
] |
[
[
"38159612",
"Association Between Quality of Life and Neurogenic Bowel Symptoms by Bowel Management Program in Spina Bifida.",
"To compare differences in bowel-specific quality of life (QOL), overall qQOL, and neurogenic bowel dysfunction (NBD) severity by bowel management program in patients with spina bifida (SB).</AbstractText We performed a retrospective cross-sectional study of patients ≥12 years old at our multidisciplinary SB center who completed both a modified Peristeen NBD questionnaire (assessing bowel symptom severity and bowel-specific QOL) and the Patient-Reported Outcomes Measurement Information System Pediatric Global Health questionnaire (assessing overall QOL). Nested, multivariable models were fit for associations between outcomes and bowel management program (enemas, conservative management, and none).</AbstractText A total of 173 patients, 56.1% female and 64.6% with myelomeningocele, were included in our analysis. Median age was 18.2 years old. Patients reported using enemas (n = 42), conservative management (n = 63), and no bowel program (n = 68). When adjusting for covariates, there was no significant association between bowel-specific QOL nor overall QOL across bowel management programs. However, the use of conservative management compared to enemas was associated with worse bowel symptoms severity (adjusted beta=2.58, 95%CI=[0.09,5.06]). Additionally, greater bowel symptom severity was significantly associated with lower overall QOL (adjusted beta=-0.33, 95%CI=[-0.57,-0.10]).</AbstractText NBD symptom severity in SB is more strongly associated with QOL than the individual bowel program being utilized. Our findings suggest that different degrees of NBD require different invasiveness of bowel programs, but it is the outcome of the bowel management program and not the specific program itself that is most associated with QOL.</AbstractText"
]
] |
40715419
|
Inter- and intra-bacterial strain diversity remains the "elephant in the (living) room".
|
Acinetobacter baumannii is an opportunistic Gram-negative bacterial pathogen responsible for severe nosocomial infections worldwide. Resistance to last-resort antibiotics causes A. baumannii to be ranked as a top priority for the research and development of new antibiotics by the WHO and an urgent threat to public health by the CDC. It is also a member of the ESKAPE group comprising the most problematic antibiotic-resistant nosocomial pathogens. Resistance towards desiccation, disinfectants, reactive oxygen species, and the host immune system helps A. baumannii thrive in hospital settings and infect individuals compromised by lines, tubes, and indwelling devices. A. baumannii displays extensive genomic heterogeneity, yet recent studies show that this level of plasticity is also prevalent in lab strains widely used to study A. baumannii biology. Successive subculturing of widely used strains and spontaneous genetic variations results in significantly altered genotypes and phenotypes, often not recognized by the scientific community. In addition, the current strain designation methods do not allow efficient communication about such differences. Even presumably identical strains from established culture collections have been found to demonstrate genetic heterogeneity. The "elephant in the (living) room" refers to the risk but also the potential of the bi-partite problem concerning the high diversity amongst A. baumannii isolates (inter-strain variability), and the universal issue of microevolution (intra-strain variability). This is generally ignored as it is not referenced adequately in scientific publications. We aim to raise awareness about the current issues and the problematic consequences generated by intra- and inter-strain diversity based on modern examples of A. baumannii isolates. Therefore, this review provides cases of broadly used A. baumannii strains and their genetic and phenotypic differences.</AbstractText
|
[
[
"33495315",
"Inhibition of Hedgehog Signaling Alters Fibroblast Composition in Pancreatic Cancer.",
"Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease characterized by an extensive fibroinflammatory stroma, which includes abundant cancer-associated fibroblast (CAF) populations. PDAC CAFs are heterogeneous, but the nature of this heterogeneity is incompletely understood. The Hedgehog pathway functions in PDAC in a paracrine manner, with ligands secreted by cancer cells signaling to stromal cells in the microenvironment. Previous reports investigating the role of Hedgehog signaling in PDAC have been contradictory, with Hedgehog signaling alternately proposed to promote or restrict tumor growth. In light of the newly discovered CAF heterogeneity, we investigated how Hedgehog pathway inhibition reprograms the PDAC microenvironment.</AbstractText We used a combination of pharmacologic inhibition, gain- and loss-of-function genetic experiments, cytometry by time-of-flight, and single-cell RNA sequencing to study the roles of Hedgehog signaling in PDAC.</AbstractText We found that Hedgehog signaling is uniquely activated in fibroblasts and differentially elevated in myofibroblastic CAFs (myCAF) compared with inflammatory CAFs (iCAF). Sonic Hedgehog overexpression promotes tumor growth, while Hedgehog pathway inhibition with the smoothened antagonist, LDE225, impairs tumor growth. Furthermore, Hedgehog pathway inhibition reduces myCAF numbers and increases iCAF numbers, which correlates with a decrease in cytotoxic T cells and an expansion in regulatory T cells, consistent with increased immunosuppression.</AbstractText Hedgehog pathway inhibition alters fibroblast composition and immune infiltration in the pancreatic cancer microenvironment.</AbstractText"
]
] |
[
[
"40413347",
"Type-1 Diabetes Impacts Brain Microstructure and Anatomical Associations in Young and Well-Controlled Individuals.",
"Type 1 Diabetes Mellitus (T1DM) progression has a direct impact on brain microstructural integrity and typical functional organization from the early stages of neurodevelopment. Diffusion Tensor Imaging (DTI) is a neuroimaging method that has proven sensitive to changes in white matter microstructure. Using diffusion-weighted probabilistic tractography methods, we aim to evaluate the white matter integrity and anatomical relationships within the Default Mode Network (DMN) brain regions, which have been proven to be particularly affected by T1DM in a group of eighteen carefully selected clinically well-controlled young T1DM patients versus eighteen healthy matched controls according to sex, age, and education level. Results showed no relevant differences in the anatomical distribution of DMN between the groups. However, the transitivity graph metric was significantly lower in T1DM patients, who also showed weaker connectivity between the left ventral prefrontal cortex and the left medial temporal gyrus, representing the anatomical trajectory of the arcuate fasciculus. Considering that neural myelination is affected by language input and the critical role of language-related structures on brain development, the current findings denote early ill-driven brain modifications to better adapt to the increasing daily demands.</AbstractText"
]
] |
40461172
|
Medical management of ADHD in adults: part 2.
|
Methylphenidate and lisdexamfetamine are recommended as first-line pharmacological treatment options for adults with attention deficit hyperactivity disorder (ADHD). Formulations of methylphenidate can generally be classified into three groups according to their duration of action: one group lasts 12 hours, another group lasts 8 hours and the immediate-release group lasts 3-4 hours. Patients are usually able to substitute brands with one of the equivalent release profiles without significant problems. Lisdexamfetamine is a prodrug which has a slow onset and long duration (approximately 12 hours), ensuring minimal potential for abuse compared with its active metabolite dexamfetamine. Second-line treatments such as atomoxetine are also available for those who cannot tolerate or do not respond to methylphenidate or lisdexamfetamine. In the UK, ADHD has been previously managed largely in tertiary clinics, but many cases could be managed by appropriately trained clinicians in secondary or primary care (as already happens in some countries), with great benefit for patients and job satisfaction for clinicians.</AbstractText
|
[
[
"39376970",
"Relationships between screen time and childhood attention deficit hyperactivity disorder: a Mendelian randomization study.",
"In previous observational studies and meta-analyses, childhood attention deficit hyperactivity disorder (ADHD) is found to have a significant association with screen time. However, the causal associations between them remain unclear.</AbstractText This study performed a bidirectional two-sample Mendelian randomization (MR) analysis to confirm the causality between screen time and childhood ADHD. Large-scale genome-wide association studies (GWAS) datasets derived from the Psychiatric Genomics Consortium (PGC) and the UK Biobank were used to identify single nucleotide polymorphisms (SNPs) associated with exposure and outcome. Four categories of datasets were selected to represent screen time. The SNPs that are significantly associated with exposure data (P < 5e-08) and have a strong correlation with the exposure in the F-statistic (F > 10) were selected as instrumental variables. This study also used the PhenoScanner V2 database and the LDlink webtool to exclude confounding factors, and the MR-PRESSO method (p < 0.05) was employed to eliminate outliers with bias. Five commonly used methods were employed to assess the interaction and the Inverse Variance Weighted (IVW) method was utilized as the primary basis for determining the MR estimates in this study.</AbstractText The MR analysis revealed that the length of mobile phone use (OR, 1.848; 95% CI, 1.3360-2.5558; p=2.07e-4) and the time spent watching television (OR, 2.104; 95% CI, 1.3958-3.1703; p=3.8e-4) increased the risk of childhood ADHD. Although the causal relationships were exclusively identified through the IVW and weighted median methods, the results retained their statistical significance following correction. In the reverse analysis, no evidence was found to support an effect of childhood ADHD on screen time. The sensitivity analysis conducted on the significant findings revealed no evidence of horizontal pleiotropy or heterogeneity.</AbstractText This study provides some evidence for the causality of screen time and childhood ADHD. Given the limitations of our study, further research is required to comprehensively investigate this relationship.</AbstractText"
]
] |
[
[
"40737393",
"The β(2)-adrenergic receptor (Adrb2) entrains circadian gene oscillation and CD8(+) T cell differentiation in response to virus infection.",
"Adaptive immune cells are regulated by circadian rhythms both under steady state conditions and during responses to infection. Cytolytic CD8<sup"
]
] |
39853319
|
Neural mechanisms of behavioral addiction: An ALE meta-analysis and MACM analysis.
|
Behavioral addictions (BAs) represent complex and multifaceted disorders often associated with maladaptive neural alteration. To deepen our understanding of the essence of BAs, this study focuses on the neural mechanisms underlying its three stages: reward seeking, self-control, and decision-making. The aim of the current meta-analysis is to investigate the brain regions and neural networks involved in BAs.</AbstractText Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched for relevant articles published before September 1, 2024, in the Web of Science and PubMed databases, and supplemented our search with Google Scholar. We conducted analyses using activation likelihood estimation (ALE) meta-analysis and meta-analytic connectivity modeling (MACM) analyses.</AbstractText A total of 50 functional magnetic resonance imaging studies involving 906 participants were included. The findings showed that individuals with BAs exhibited hyperactivation in the right inferior frontal gyrus (IFG), bilateral caudate and left middle frontal gyrus (MFG), and a high degree of connectivity was found between the right caudate, left caudate, and right IFG. These findings indicated that BAs were associated with the fronto-striatal circuits. Individuals with BAs demonstrate specific neural activation patterns in the reward seeking, self-control, and decision-making stages, characterized by differences in activation and functional connectivity of brain regions associated with these stages.</AbstractText This study verifies the pivotal role of the fronto-striatal circuits in BAs and highlights the specific patterns of brain activity in different stages of addictive behavior. These findings expand our understanding of neural mechanisms underlying BAs and supports and provide partial support for the I-PACE model.</AbstractText
|
[
[
"26802508",
"A failure of suppression within the default mode network in depressed adolescents with compulsive internet game play.",
"Individuals who are chronic, compulsive video game players experience an elevated incidence of major depression. Excessive or problematic game play can interact with depression clinically, and may magnify impulsive behavior associated with video gaming.</AbstractText Functional brain imaging was performed during a Wisconsin Card Sorting Test (WCST) task in 42 healthy control and 95 volunteers seeking treatment for compulsive video game playing, including 60 participants without major depression (pure internet gaming disorder, pure IGD) and 35 participants comorbid with major depression (IGD+MDD).</AbstractText In response to the WCST in contrast to fixation, activation was observed in canonical brain attentional networks including bilateral intraparietal sulcus, frontal eye fields, and middle temporal cortical regions as well as dorsolateral prefrontal, inferior parietal and anterior insula, anterior cingulate cortex in all participants. For WCST>Fixation contrasts, the IGD+MDD group exhibited greater relative activation within the left hippocampus, compared to healthy control participants. For WCST>Fixation contrasts, the IGD+MDD group exhibited greater relative activation within the left hippocampus and the right parahippocampal gyrus immediately posterior to the hippocampus, compared to the pure IGD group.</AbstractText In cohorts of individuals with a history of compulsive internet game play, individuals with depression showed failure to suppress default mode network activity during an attentionally demanding task, compared to individuals without depression, including comparison groups with and without a history of compulsive video gaming. This reduced suppression of the brain regions within the default mode network may be a consequence of depressive neurophysiology or represent a predisposition for depression within compulsive game players.</AbstractText"
]
] |
[
[
"39804020",
"Step Width Haptic Feedback for Gait Stability in Spinocerebellar Ataxia: Preliminary Results.",
"Wider step width and lower step-to-step variability are linked to improved gait stability and reduced fall risk. It is unclear if patients with spinocerebellar ataxia (SCA) can learn to adjust these aspects of gait to reduce fall risk.</AbstractText The aims were to examine the possibility of using wearable step width haptic biofeedback to enhance gait stability and reduce fall risk in individuals with SCA.</AbstractText Thirteen people with SCA type 3 performed step width training (single session) using real-time feedback.</AbstractText Step width increased post-training (19.3 cm, interquartile range [IQR] 16.3-20.2 cm) and at retention (16.6 cm, IQR 16.2-21.1 cm), compared to baseline (11.0 cm, IQR 5.2-15.2 cm; P < 0.001). Step width variability decreased during post-training (19.7%, IQR 17.4%-26.2%) and at retention (22.3%, IQR 18.6%-30.2%), compared to baseline (44.5%, IQR 28.5%-71.2%; P < 0.001). Crossover steps, another mark of instability, decreased after training (P < 0.031).</AbstractText These pilot results suggest that patients with SCA can use a novel, wearable biofeedback system to improve their gait stability. © 2025 International Parkinson and Movement Disorder Society.</AbstractText"
]
] |
29471227
|
The impact of acute and short-term methamphetamine abstinence on brain metabolites: A proton magnetic resonance spectroscopy chemical shift imaging study.
|
Abuse of methamphetamine (MA) is a global health concern. Previous <sup Adults with chronic MA dependence (n = 31) and healthy controls (n = 22) were recruited. Two-dimensional chemical shift <sup Acute MAA showed lower n-acetyl-aspartate (NAA) and n-acetyl-aspartate with n-acetyl-aspartyl-glutamate (NAA + NAAG) in left DLPFC, and glycerophosphocholine with phosphocholine (GPC + PCh) in left FWM. Short-term MAA showed lower NAA + NAAG and higher myo-inositol (mI) in right ACC, lower NAA and NAA + NAAG in the left DLPFC, and lower GPC + PCh in left FWM. Over time, MAA showed decreased NAA and NAA + NAAG and increased mI in right ACC, decreased NAA and NAA + NAAG in right FWM, and decreased in mI in left FWM.</AbstractText In acute MAA, there was damage to the integrity of neuronal tissue, which was enhanced with short-term MAA. From acute to short-term MAA, activation of neuroinflammatory processes are suggested. This is the first <sup
|
[
[
"24897622",
"μHigh resolution-magic-angle spinning NMR spectroscopy for metabolic phenotyping of Caenorhabditis elegans.",
"Analysis of model organisms, such as the submillimeter-size Caenorhabditis elegans, plays a central role in understanding biological functions across species and in characterizing phenotypes associated with genetic mutations. In recent years, metabolic phenotyping studies of C. elegans based on (1)H high-resolution magic-angle spinning (HR-MAS) nuclear magnetic resonance (NMR) spectroscopy have relied on the observation of large populations of nematodes, requiring labor-intensive sample preparation that considerably limits high-throughput characterization of C. elegans. In this work, we open new platforms for metabolic phenotyping of C. elegans mutants. We determine rich metabolic profiles (31 metabolites identified) from samples of 12 individuals using a (1)H NMR microprobe featuring high-resolution magic-angle coil spinning (HR-MACS), a simple conversion of a standard HR-MAS probe to μHR-MAS. In addition, we characterize the metabolic variations between two different strains of C. elegans (wild-type vs slcf-1 mutant). We also acquire a NMR spectrum of a single C. elegans worm at 23.5 T. This study represents the first example of a metabolomic investigation carried out on a small number of submillimeter-size organisms, demonstrating the potential of NMR microtechnologies for metabolomics screening of small model organisms.</AbstractText"
]
] |
[
[
"29905724",
"Energy density and energy flux in the focus of an optical vortex: reverse flux of light energy.",
"Using the Richards-Wolf formulas for an arbitrary circularly polarized optical vortex with an integer topological charge m, we obtain explicit expressions for all components of the electric and magnetic field strength vectors near the focus, as well as expressions for the intensity (energy density) and for the energy flux (components of the Poynting vector) in the focal plane of an aplanatic optical system. For m=2, from the obtained expressions it follows that the energy flux near the optical axis propagates in the reversed direction, rotating along a spiral around the optical axis. On the optical axis itself, the reversed flux is maximal and decays rapidly with the distance from the axis. For m=3, in contrast, the reversed energy flux in the focal plane is minimal (zero) on the optical axis and increases (until the first ring of the light intensity) as a squared distance from the axis.</AbstractText"
]
] |
40385881
|
Post-thalamotomy Changes Mimicking Cavernous Malformations on MRI: A Case Report of a Historical Surgical Treatment.
|
The patient was a 65-year-old man with cervical dystonia onset at age six who had been treated at Chiba University Hospital. He was diagnosed and followed up with cavernous malformations and chronic cerebral infarctions based on an MRI. However, during the re-evaluation of MRI, lesions with low signal intensity (SI) cores surrounded by high SI rims were observed in bilateral thalami and left subthalamic nucleus on T2-weighted images, which differed from typical cavernous malformations. In addition, symmetrical scarring changes were noted in the frontal lobes and bilateral parietal bones, potentially corresponding to the thalamic and subthalamic nucleus lesions. Upon reviewing medical history, it was revealed that the patient had undergone thalamotomy in 1963 and 1964. The literature review suggested the use of procaine-oil blocking during thalamotomies of that era. Chemical shift imaging was added, and the presence of fat was confirmed in bilateral thalamic lesions with high SI on in-phase and low SI on out-of-phase images. Imaging findings resulting from obsolete treatments can be unfamiliar and mistaken for pathological conditions. Investigating the history of suspected treatments can lead to definitive diagnoses through imaging studies.</AbstractText
|
[
[
"21666131",
"Abnormal structure-function relationship in spasmodic dysphonia.",
"Spasmodic dysphonia (SD) is a primary focal dystonia characterized by involuntary spasms in the laryngeal muscles during speech production. Although recent studies have found abnormal brain function and white matter organization in SD, the extent of gray matter alterations, their structure-function relationships, and correlations with symptoms remain unknown. We compared gray matter volume (GMV) and cortical thickness (CT) in 40 SD patients and 40 controls using voxel-based morphometry and cortical distance estimates. These measures were examined for relationships with blood oxygen level-dependent signal change during symptomatic syllable production in 15 of the same patients. SD patients had increased GMV, CT, and brain activation in key structures of the speech control system, including the laryngeal sensorimotor cortex, inferior frontal gyrus (IFG), superior/middle temporal and supramarginal gyri, and in a structure commonly abnormal in other primary dystonias, the cerebellum. Among these regions, GMV, CT and activation of the IFG and cerebellum showed positive relationships with SD severity, while CT of the IFG correlated with SD duration. The left anterior insula was the only region with decreased CT, which also correlated with SD symptom severity. These findings provide evidence for coupling between structural and functional abnormalities at different levels within the speech production system in SD.</AbstractText"
]
] |
[
[
"40446445",
"Optimizing mesenchymal stromal cells priming strategies for tailored effects on the secretome.",
"Mesenchymal stromal cells (MSCs) have emerged as a promising tool in regenerative medicine, with recent focus shifting towards their secretome as a cell-free therapeutic approach. This study investigates the impact of various priming strategies on the immunomodulatory, anti-inflammatory, and regenerative potential of adipose-derived MSCs (ASCs) secretomes. We evaluated the effects of hypoxia, pro-inflammatory cytokines, and spheroid culture conditions on ASC secretome composition and functionality. Gene expression analysis, nanoparticle tracking, protein quantification, and functional assays were performed to characterize the secretomes. RNA sequencing revealed significant differences in gene expression profiles across priming conditions, particularly in pathways related to osteogenesis, angiogenesis, inflammation, and neurotrophic factors. Notably, spheroid culture combined with hypoxia and inflammation resulted in a substantial increase in extracellular vesicle production and altered protein content. Functional assays demonstrated enhanced neutrophil inhibition by secretomes from hypoxia-primed ASCs. Our findings indicate that tailored priming strategies can significantly modulate the therapeutic properties of ASC secretomes, potentially enhancing their efficacy in various clinical applications. This study provides valuable insights for optimizing cell-free therapies in regenerative medicine and offers a basis for developing more targeted and effective treatments.</AbstractText"
]
] |
35317746
|
Comparative study of vestibular projection pathway connectivity in cerebellar injury patients and healthy adults.
|
Cerebellar injury can not only cause gait and postural instability, nystagmus, and vertigo but also affect the vestibular system. However, changes in connectivity regarding the vestibular projection pathway after cerebellar injury have not yet been reported. Therefore, in the current study, we investigated differences in the connectivity of the vestibular projection pathway after cerebellar injury using diffusion tensor imaging (DTI) tractography.</AbstractText We recruited four stroke patients with cerebellar injury. Neural connectivity in the vestibular nucleus (VN) of the pons and medulla oblongata in patients with cerebellar injury was measured using DTI. Connectivity was defined as the incidence of connection between the VN on the pons and medulla oblongata and target brain regions such as the cerebellum, thalamus, parieto-insular vestibular cortex (PIVC), and parietal lobe.</AbstractText At thresholds of 10 and 30, there was lower connectivity in the ipsilateral hemisphere between the VN at the medullar level and thalamus in the patients than in healthy adults. At a threshold of 1 and 10, the patient group showed lower VN connectivity with the PIVC than healthy adults. At a threshold of 1, VN connectivity with the parietal lobe in the contralateral hemisphere was lower in the patients than in healthy adults. Additionally, at a threshold of 30, VN connectivity at the pons level with the cerebellum was lower in healthy adults than in the patients.</AbstractText Cerebellar injury seems to be associated with decreased vestibular projection pathway connectivity, especially in the ipsilateral thalamus, PIVC, and contralateral parietal lobe.</AbstractText
|
[
[
"29129392",
"Targeting Obesity and Cachexia: Identification of the GFRAL Receptor-MIC-1/GDF15 Pathway.",
"Macrophage inhibitory cytokine-1/growth differentiation factor 15 (MIC-1/GDF15) is a divergent transforming growth factor (TGFβ) superfamily cytokine implicated in biological and disease processes including metabolism, cancer, and chronic inflammation, but whose receptor has remained elusive. Four laboratories have recently identified GFRAL, an orphan receptor of the glial-derived neurotrophic factor (GDNF) receptor α family, as the receptor for MIC-1/GDF15, signaling though the coreceptor Ret. These data identify a new systemic to central nervous system (CNS) circuit that regulates metabolism in response to stress and which could be targeted to treat both severe obesity and anorexia/cachexia syndrome.</AbstractText"
]
] |
[
[
"34449006",
"Exploring the Concept of Spiritual Sensitivity from the Perspectives of Healthcare Providers in Iran.",
"Spiritual sensitivity (SS) is defined as attention to the available spiritual values in a conflicting situation and awareness of one's roles and responsibilities in that situation. It helps differentiate between the right and the wrong and leads to sound practice. This study explored the concept of SS from the perspectives of healthcare providers in Iran. This qualitative study was carried out in 2017-2019 using conventional content analysis. Twenty-two physicians, faculty members with clinical work experience, and healthcare providers were purposefully recruited. Data were collected using unstructured interviews and were analyzed using conventional content analysis. Participants' experiences of the concept of SS were grouped into three main themes, namely sense of value, spiritual growth and morale boosting, and SS as a motivator for purposeful service delivery. The findings of the present study will help healthcare managers develop programs for improving healthcare providers' spiritual sensitivity and also will help healthcare providers develop spirituality-based holistic care plans.</AbstractText"
]
] |
37437821
|
LPS priming before plaque deposition impedes microglial activation and restrains Aβ pathology in the 5xFAD mouse model of Alzheimer's disease.
|
Microglia have an innate immunity memory (IIM) with divergent functions in different animal models of neurodegenerative diseases, including Alzheimer's disease (AD). AD is characterized by chronic neuroinflammation, neurodegeneration, tau tangles and β-amyloid (Aβ) deposition. Systemic inflammation has been implicated in contributing to the progression of AD. Multiple reports have demonstrated unique microglial signatures in AD mouse models and patients. However, the proteomic profiles of microglia modified by IIM have not been well-documented in an AD model. Therefore, in the present study, we investigate whether lipopolysaccharide (LPS)-induced IIM in the pre-clinical stage of AD alters the microglial responses and shapes the neuropathology. We accomplished this by priming 5xFAD and wild-type (WT) mice with an LPS injection at 6 weeks (before the robust development of plaques). 140 days later, we evaluated microglial morphology, activation, the microglial barrier around Aβ, and Aβ deposition in both 5xFAD primed and unprimed mice. Priming induced decreased soma size of microglia and reduced colocalization of PSD95 and Synaptophysin in the retrosplenial cortex. Priming appeared to increase phagocytosis of Aβ, resulting in fewer Thioflavin S<sup
|
[
[
"27766433",
"Midbrain Synchrony to Envelope Structure Supports Behavioral Sensitivity to Single-Formant Vowel-Like Sounds in Noise.",
"Vowels make a strong contribution to speech perception under natural conditions. Vowels are encoded in the auditory nerve primarily through neural synchrony to temporal fine structure and to envelope fluctuations rather than through average discharge rate. Neural synchrony is thought to contribute less to vowel coding in central auditory nuclei, consistent with more limited synchronization to fine structure and the emergence of average-rate coding of envelope fluctuations. However, this hypothesis is largely unexplored, especially in background noise. The present study examined coding mechanisms at the level of the midbrain that support behavioral sensitivity to simple vowel-like sounds using neurophysiological recordings and matched behavioral experiments in the budgerigar. Stimuli were harmonic tone complexes with energy concentrated at one spectral peak, or formant frequency, presented in quiet and in noise. Behavioral thresholds for formant-frequency discrimination decreased with increasing amplitude of stimulus envelope fluctuations, increased in noise, and were similar between budgerigars and humans. Multiunit recordings in awake birds showed that the midbrain encodes vowel-like sounds both through response synchrony to envelope structure and through average rate. Whereas neural discrimination thresholds based on either coding scheme were sufficient to support behavioral thresholds in quiet, only synchrony-based neural thresholds could account for behavioral thresholds in background noise. These results reveal an incomplete transformation to average-rate coding of vowel-like sounds in the midbrain. Model simulations suggest that this transformation emerges due to modulation tuning, which is shared between birds and mammals. Furthermore, the results underscore the behavioral relevance of envelope synchrony in the midbrain for detection of small differences in vowel formant frequency under real-world listening conditions.</AbstractText"
]
] |
[
[
"36808307",
"Neurobiological correlates and attenuated positive social intention attribution during laughter perception associated with degree of autistic traits.",
"Laughter plays an important role in group formation, signaling social belongingness by indicating a positive or negative social intention towards the receiver. In adults without autism, the intention of laughter can be correctly differentiated without further contextual information. In autism spectrum disorder (ASD), however, differences in the perception and interpretation of social cues represent a key characteristic of the disorder. Studies suggest that these differences are associated with hypoactivation and altered connectivity among key nodes of the social perception network. How laughter, as a multimodal nonverbal social cue, is perceived and processed neurobiologically in association with autistic traits has not been assessed previously. We investigated differences in social intention attribution, neurobiological activation, and connectivity during audiovisual laughter perception in association with the degree of autistic traits in adults [N = 31, M<sub"
]
] |
36770411
|
Towards the Standardization of Photothermal Measurements of Iron Oxide Nanoparticles in Two Biological Windows.
|
A systematic study on laser-induced heating carried out in two biological windows (800 nm and 1053 nm) for Fe<sub
|
[
[
"34411327",
"The Coax Dipole: A fully flexible coaxial cable dipole antenna with flattened current distribution for body imaging at 7 Tesla.",
"The coax dipole antenna, a flexible antenna for body imaging at 7T is presented. Similar to the high impedance coil, this coaxial cable antenna is fed on the central conductor and through gaps in the shield, the current passes to the outside of the antenna to generate B<sub Finite difference time domain (FDTD) simulations are performed to optimize the positions of the gaps in the shield for a flat current profile. Lumped inductors are added to each end to reduce losses. The performance of a single antenna is compared to a fractionated dipole using B<sub An optimal configuration is found with gaps located at 10 cm from the center and inductor values of 28 nH. In comparison to the fractionated dipole antenna, in single antenna phantom measurements the coax dipole achieves similar B<sub The coax dipole is a novel antenna design with a flattened current distribution resulting in beneficial properties. Also, the flexible design of the coax dipoles allows better adaptation to the body curvature and can potentially be used for a wide range of imaging targets.</AbstractText"
]
] |
[
[
"37738741",
"Cell-specific alterations in autophagy-lysosomal activity near the chronically implanted microelectrodes.",
"Intracortical microelectrodes that can record and stimulate brain activity have become a valuable technique for basic science research and clinical applications. However, long-term implantation of these microelectrodes can lead to progressive neurodegeneration in the surrounding microenvironment, characterized by elevation in disease-associated markers. Dysregulation of autophagy-lysosomal degradation, a major intracellular waste removal process, is considered a key factor in the onset and progression of neurodegenerative diseases. It is plausible that similar dysfunctions in autophagy-lysosomal degradation contribute to tissue degeneration following implantation-induced focal brain injury, ultimately impacting recording performance. To understand how the focal, persistent brain injury caused by long-term microelectrode implantation impairs autophagy-lysosomal pathway, we employed two-photon microscopy and immunohistology. This investigation focused on the spatiotemporal characterization of autophagy-lysosomal activity near the chronically implanted microelectrode. We observed an aberrant accumulation of immature autophagy vesicles near the microelectrode over the chronic implantation period. Additionally, we found deficits in autophagy-lysosomal clearance proximal to the chronic implant, which was associated with an accumulation of autophagy cargo and a reduction in lysosomal protease level during the chronic period. Furthermore, our evidence demonstrates reactive astrocytes have myelin-containing lysosomes near the microelectrode, suggesting its role of myelin engulfment during acute implantation period. Together, this study sheds light on the process of brain tissue degeneration caused by long-term microelectrode implantation, with a specific focus on impaired intracellular waste degradation.</AbstractText"
]
] |
37954642
|
Case series: Intraoperative neuromonitoring and angiography in the surgical treatment of vascular malformations.
|
In the surgical treatment of cerebral vascular malformations, e.g., aneurysms and arteriovenous malformations, the risk of ischemic complications is 6.7%, and a residual aneurysm is possible in 5.2% of these cases. Ischemic lesions can result in permanent neurological deficits, and a residual aneurysm can lead to the recurrence of the aneurysm in 2% of cases. In this article, we present five cases (two cases of ruptured aneurysms, two cases of non-ruptured aneurysms, and a case of arteriovenous malformation) in which we reduced the aforementioned risks with the use of intraoperative neuromonitoring and angiography. Intraoperative neuromonitoring (IONM) is used to measure motor and sensory-evoked potentials to detect brain hypoperfusion. Intraoperative angiography with the dye indocyanine green (ICG-A), which fluoresces in a vessel under a microscope after intravenous administration, helps to identify residual aneurysm sacs and distal blood flow. With the use of IONM and ICG-A, we identified abnormalities and adjusted our interventions and treatments. IONM and ICG-A can lead to a better outcome after surgical treatment of cerebral vascular abnormalities.</AbstractText
|
[
[
"25624933",
"Scalp arteriovenous malformations in young.",
"Scalp arteriovenous malformations are an exceptional group of vascular lesions with curious presentations and an elusive natural history. Their detection in the pediatric population is a rarer occurrence. We discuss our experience with five children suffering from this pathology and their surgical management carried at our institution from 2007 to 2013. The genesis in pediatric patients is, usually, spontaneous in contrast with the history of trauma seen in adults. Clinical symptoms, usually, range from an asymptomatic lesion, local discomfort, headaches to necrosis and massive hemorrhage. Selective angiography remains the cornerstone for investigation. Complete surgical excision, embolization or an approach combining the modalities is curative.</AbstractText"
]
] |
[
[
"36427671",
"The functional connectivity between left insula and left medial superior frontal gyrus underlying the relationship between rumination and procrastination.",
"Procrastination is regarded as a prevalent problematic behavior that impairs people's physical and mental health. Although previous studies have indicated that trait rumination is robustly positively correlated with procrastination, it remains unknown about the neural substrates underlying the relationship between trait rumination and procrastination. To address this issue, we used voxel-based morphometry (VBM) and resting-state functional connectivity (RSFC) approaches to explore the neural basis of the relationship between trait rumination and procrastination. Our behavior results found that trait rumination was significantly positively correlated to procrastination, while the VBM analysis showed that trait rumination was negatively correlated with gray matter volume of the insula. Furthermore, the RSFC results revealed a negative association of the left insula-lmSFG (left medial superior frontal gyrus) functional connectivity with trait rumination. More importantly, the mediation analysis showed that trait rumination could completely mediate the relationship between left insula-lmSFG functional connectivity and procrastination. These results suggest that the left insula-lmSFG functional connectivity involved in emotion regulation modulates the association between trait rumination and procrastination, which provides neural evidence for the relationship between trait rumination and procrastination.</AbstractText"
]
] |
40396767
|
Case series of CT-fusion and real-time US-guidance in percutaneous RF thermocoagulation for trigeminal rhizotomy.
|
This case series evaluates the feasibility, safety, and efficacy of real-time computed tomography fusion with ultrasound guidance (CTF-USG) in percutaneous radiofrequency thermocoagulation (RFT) for trigeminal rhizotomy. Traditional imaging modalities such as CT and fluoroscopy lack real-time visualization, increasing the risk of vascular injury and reducing procedural precision. The CTF-USG technique integrates CT imaging with real-time ultrasound via electromagnetic tracking, enabling accurate needle navigation and anatomical confirmation. Six patients with refractory trigeminal neuralgia affecting the V2 or V3 divisions underwent RFT guided by CTF-USG. All procedures achieved first-attempt needle placement success with no immediate complications. Postoperative assessments demonstrated significant reductions in pain scores at one and three months. The real-time imaging capability facilitated avoidance of critical structures, enhanced procedural safety. In conclusion, CTF-USG offers real-time imaging superior to C-arm fluoroscopy or standard CT, reducing complications and improving procedural accuracy. Primary technique efficacy was 100%. These advantages support its adoption in treating refractory trigeminal neuralgia.</AbstractText <b
|
[
[
"17274022",
"Dissociation of response inhibition and performance monitoring in the stop signal task using event-related fMRI.",
"We examined the neural substrate of motor response inhibition and performance monitoring in the stop signal task (SST) using event-related functional magnetic resonance imaging (fMRI). The SST involves a go task and the occasional requirement to stop the go response. We posit that both the go and the stop phases of the SST involve components of inhibition and performance monitoring. The goal of this study was to determine whether inhibition and performance monitoring during go and stop phases of the task activated different networks. We isolated go-phase activities underlying response withholding, monitoring, and sensorimotor processing and contrasted these with successful inhibition to identify the substrate of response inhibition. Error detection activity was isolated using trials in which a stop signal appeared but the response was executed. These trials were modeled as a hand-specific go trial followed by error processing. Cognitive go-phase processes included response withholding and monitoring and activated right prefrontal and midline networks. Response withdrawal additionally activated right inferior frontal gyrus and basal ganglia (caudate). Error detection invoked by failed inhibition activated dorsal anterior cingulate cortex (dACC) and right middle frontal Brodmann's area 9. Our results confirm that there are distinct aspects of inhibition and performance monitoring functions which come into play at various phases within a given trial of the SST, and that these are separable using fMRI.</AbstractText"
]
] |
[
[
"39810626",
"Recommendations for the Safe Application of Temporal Interference Stimulation in the Human Brain Part II: Biophysics, Dosimetry, and Safety Recommendations.",
"Temporal interference stimulation (TIS) is a new form of transcranial electrical stimulation (tES) that has been proposed as a method for targeted, noninvasive stimulation of deep brain structures. While TIS holds promise for a variety of clinical and nonclinical applications, little data is yet available regarding its effects in humans and its mechanisms of action. To inform the design and safe conduct of experiments involving TIS, researchers require quantitative guidance regarding safe exposure limits and other safety considerations. To this end, we undertook a two-part effort to determine frequency-dependent thresholds for applied currents below which TIS is unlikely to pose risk to humans in terms of heating or unwanted stimulation. In Part II of this effort, described here, we draw on a previously compiled list (see Part I) of adverse effects (AEs) reported for transcranial direct/alternating current stimulation (tDCS/ACS), deep brain stimulation (DBS), and TIS to determine biophysics-informed exposure metrics for assessing safety. Using an in silico approach, we conduct multiphysics simulations of various tACS, DBS, and TIS exposure scenarios in an anatomically detailed head and brain model. By matching the stimulation in terms of the identified exposure metrics, we infer frequency-dependent TIS parameters that produce exposure conditions equivalent to those known to be safe for tACS and DBS. Based on the results of our simulations and existing knowledge regarding tES and DBS safety, we propose frequency-dependent thresholds below which TIS voltages and currents are unlikely to pose a risk to humans. Safety-related data from ongoing and future human studies are required to verify and refine the thresholds proposed here.</AbstractText"
]
] |
38152804
|
Evaluation of 'Normal' Cognitive Functions and Correlation With MRI Volumetry: Towards a Definition of Vascular Cognitive Impairment.
|
Introduction It is important to establish criteria to define vascular cognitive impairment (VCI) in India as VCI is an image-based diagnosis and magnetic resonance imaging (MRI) changes resulting from age with prevalent vascular risk factors may confound MRI interpretation. The objective of this study was to establish normative community data for MRI volumetry including white matter hyperintensity volume (WMHV), correlated with age-stratified cognitive scores and vascular risk factors (VRFs), in adults aged 40 years and above.  Methods We screened 2651 individuals without known neurological morbidity, living in Mumbai and nearby rural areas, using validated Marathi translations of Kolkata Cognitive Battery (KCB) and geriatric depression score (GDS). We stratified 1961 persons with GDS ≤9 by age and cognitive score, and randomly selected 10% from each subgroup for MRI brain volumetry. Crude volumes were standardized to reflect percentage of intracranial volume.  Results MRI volumetry studies were done in 199 individuals (F/M = 90/109; 73 with body mass index (BMI) ≥25; 44 hypertensives; 29 diabetics; mean cognitive score 76.3). Both grey and white matter volumes decreased with increasing age. WMHV increased with age and hypertension. Grey matter volume (GMV) decreased with increasing WMHV. Positive predictors of cognition included standardized hippocampal volume (HCV), urban living, education, and BMI, while WMHV and age were negative predictors. Urban dwellers had higher cognitive scores than rural, and, paradoxically, smaller HCV.  Conclusion In this study of MRI volumetry correlated with age, cognitive scores and VRFs, increasing age and WMHV predicted lower cognitive scores, whereas urban living and hippocampal volume predicted higher scores. Age and WMHV also correlated with decreasing GMV. Further study is warranted into sociodemographic and biological factors that mutually influence cognition and brain volumes, including nutritional and endocrine factors, especially at lower cognitive score bands. In this study, at the lower KCB score bins, the lack of laboratory data pertaining to nutritional and endocrine deficiencies is a drawback that reflects the logistical limitations of screening large populations at the community level. Our volumetric data which is age and cognition stratified, and takes into account the vascular risk factors associated, nevertheless constitutes important baseline data for the Indian population. Our findings could possibly contribute to the formulation of baseline criteria for defining VCI in India and could help in early diagnosis and control of cognitive decline and its key risk factors.</AbstractText
|
[
[
"30962628",
"Working memory revived in older adults by synchronizing rhythmic brain circuits.",
"Understanding normal brain aging and developing methods to maintain or improve cognition in older adults are major goals of fundamental and translational neuroscience. Here we show a core feature of cognitive decline-working-memory deficits-emerges from disconnected local and long-range circuits instantiated by theta-gamma phase-amplitude coupling in temporal cortex and theta phase synchronization across frontotemporal cortex. We developed a noninvasive stimulation procedure for modulating long-range theta interactions in adults aged 60-76 years. After 25 min of stimulation, frequency-tuned to individual brain network dynamics, we observed a preferential increase in neural synchronization patterns and the return of sender-receiver relationships of information flow within and between frontotemporal regions. The end result was rapid improvement in working-memory performance that outlasted a 50 min post-stimulation period. The results provide insight into the physiological foundations of age-related cognitive impairment and contribute to groundwork for future non-pharmacological interventions targeting aspects of cognitive decline.</AbstractText"
]
] |
[
[
"36748121",
"Detecting and treating the protean manifestations of diabetic autonomic neuropathy.",
"The manifestations of diabetic autonomic neuropathy (DAN) are protean and clinically involve multiple systems, including the cardiovascular system, the gastrointestinal system, the genitourinary system as well as the sweat glands (sudomotor dysfunction) and the gallbladder. In addition, cardiac autonomic neuropathy (CAN) is associated with a correctible inability to appreciate and correct hypoglycaemia. While not a clinical problem, pupillary involvement should be the clue and the catalyst to investigate for other manifestations of DAN. This review outlines a practical approach to detecting and investigating the manifestations of DAN. Of particular importance is early detection of cardiovascular involvement where prompt therapy through glycaemic control can decrease the severity of CAN and decelerate the frequency and severity of retinopathy and nephropathy in addition to decreasing cardiovascular events and mortality. CAN also plays a role in accelerating other diabetic complications such as acute ischaemic stroke, heart failure, medial artery calcinosis, foot ulcers, peripheral artery disease and Charcot joints. Many therapies of DAN are available, which should not only decrease morbidity and mortality from DAN, but also improve the patient's quality of life. However, the therapies available are largely symptomatic.</AbstractText"
]
] |
40776133
|
Stroke Cohort Construction Using an Automated Clinical Data Collection System: An Experience of a Single Cerebrovascular Specialty Hospital in South Korea.
|
The growing volume of clinical data necessitates efficient management of Electronic Health Records (EHR) data. Traditional labor-intensive EHR management methods have led to significant risks, including high error rates and data omissions. This study modified and developed EHR templates focusing on key cohort-specific variables and developed a C#-based automated system for extracting and managing data from patients with acute stroke. The system reduced data entry time per patient from 35 minutes to 19 seconds. The data error rate decreased from 2.32% to 0.15%. This system enhances data management efficiency and is expected to support the construction of various cohorts through further expansion.</AbstractText
|
[
[
"24345399",
"Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study.",
"The global burden of atrial fibrillation (AF) is unknown.</AbstractText We systematically reviewed population-based studies of AF published from 1980 to 2010 from the 21 Global Burden of Disease regions to estimate global/regional prevalence, incidence, and morbidity and mortality related to AF (DisModMR software). Of 377 potential studies identified, 184 met prespecified eligibility criteria. The estimated number of individuals with AF globally in 2010 was 33.5 million (20.9 million men [95% uncertainty interval (UI), 19.5-22.2 million] and 12.6 million women [95% UI, 12.0-13.7 million]). Burden associated with AF, measured as disability-adjusted life-years, increased by 18.8% (95% UI, 15.8-19.3) in men and 18.9% (95% UI, 15.8-23.5) in women from 1990 to 2010. In 1990, the estimated age-adjusted prevalence rates of AF (per 100 000 population) were 569.5 in men (95% UI, 532.8-612.7) and 359.9 in women (95% UI, 334.7-392.6); the estimated age-adjusted incidence rates were 60.7 per 100 000 person-years in men (95% UI, 49.2-78.5) and 43.8 in women (95% UI, 35.9-55.0). In 2010, the prevalence rates increased to 596.2 (95% UI, 558.4-636.7) in men and 373.1 (95% UI, 347.9-402.2) in women; the incidence rates increased to 77.5 (95% UI, 65.2-95.4) in men and 59.5 (95% UI, 49.9-74.9) in women. Mortality associated with AF was higher in women and increased by 2-fold (95% UI, 2.0-2.2) and 1.9-fold (95% UI, 1.8-2.0) in men and women, respectively, from 1990 to 2010. There was evidence of significant regional heterogeneity in AF estimations and availability of population-based data.</AbstractText These findings provide evidence of progressive increases in overall burden, incidence, prevalence, and AF-associated mortality between 1990 and 2010, with significant public health implications. Systematic, regional surveillance of AF is required to better direct prevention and treatment strategies.</AbstractText"
]
] |
[
[
"39481376",
"Combinatorial transcription factor binding encodes cis-regulatory wiring of mouse forebrain GABAergic neurogenesis.",
"Transcription factors (TFs) bind combinatorially to cis-regulatory elements, orchestrating transcriptional programs. Although studies of chromatin state and chromosomal interactions have demonstrated dynamic neurodevelopmental cis-regulatory landscapes, parallel understanding of TF interactions lags. To elucidate combinatorial TF binding driving mouse basal ganglia development, we integrated chromatin immunoprecipitation sequencing (ChIP-seq) for twelve TFs, H3K4me3-associated enhancer-promoter interactions, chromatin and gene expression data, and functional enhancer assays. We identified sets of putative regulatory elements with shared TF binding (TF-pRE modules) that orchestrate distinct processes of GABAergic neurogenesis and suppress other cell fates. The majority of pREs were bound by one or two TFs; however, a small proportion were extensively bound. These sequences had exceptional evolutionary conservation and motif density, complex chromosomal interactions, and activity as in vivo enhancers. Our results provide insights into the combinatorial TF-pRE interactions that activate and repress expression programs during telencephalon neurogenesis and demonstrate the value of TF binding toward modeling developmental transcriptional wiring.</AbstractText"
]
] |
40783178
|
Live-attenuated Toxoplasma gondii PruΔpp2a-c mutant elicits protective immunity against toxoplasmosis in mice and cats.
|
Toxoplasma gondii is a zoonotic protozoan pathogen capable of infecting humans and nearly all warm-blooded animals, and causing substantial economic losses to the livestock industry. Developing an effective vaccine against T. gondii remains an urgent priority for controlling the spread of this zoonotic parasite. In this study, we evaluated the protective efficacy of a live-attenuated T. gondii PruΔpp2a-c mutant in both mice and cats. Immunization with PruΔpp2a-c elicited strong cellular (IL-2, IL-4, IL-10, IL-12, and IFN-γ) and humoral (IgG, IgG1, and IgG2a) immune responses in mice, conferring protection against lethal challenge with various T. gondii strains, including highly virulent Type I (RH), mildly virulent ToxoDB#9 (PYS), and less virulent Type II (Pru) strains. While partial protection was observed against virulent strains, almost complete immune protection was achieved against both acute and chronic infections by the less virulent Pru strain, along with a significant reduction in brain cyst burden (P < 0.01). Notably, vaccination of cats with PruΔpp2a-c induced high antibody titers and led to a 94.5% reduction in fecal oocyst shedding (P < 0.001) following homologous challenge, thereby significantly decreasing the potential for environmental transmission. These findings demonstrate that PruΔpp2a-c provides strong cross-protection against various T. gondii strains and substantially limits oocyst shedding. The dual efficacy observed in both intermediate and definitive hosts highlights PruΔpp2a-c as a promising live-attenuated vaccine candidate for preventing transmission of T. gondii by cats.</AbstractText
|
[
[
"27432990",
"Dynamic neural activity during stress signals resilient coping.",
"Active coping underlies a healthy stress response, but neural processes supporting such resilient coping are not well-known. Using a brief, sustained exposure paradigm contrasting highly stressful, threatening, and violent stimuli versus nonaversive neutral visual stimuli in a functional magnetic resonance imaging (fMRI) study, we show significant subjective, physiologic, and endocrine increases and temporally related dynamically distinct patterns of neural activation in brain circuits underlying the stress response. First, stress-specific sustained increases in the amygdala, striatum, hypothalamus, midbrain, right insula, and right dorsolateral prefrontal cortex (DLPFC) regions supported the stress processing and reactivity circuit. Second, dynamic neural activation during stress versus neutral runs, showing early increases followed by later reduced activation in the ventrolateral prefrontal cortex (VLPFC), dorsal anterior cingulate cortex (dACC), left DLPFC, hippocampus, and left insula, suggested a stress adaptation response network. Finally, dynamic stress-specific mobilization of the ventromedial prefrontal cortex (VmPFC), marked by initial hypoactivity followed by increased VmPFC activation, pointed to the VmPFC as a key locus of the emotional and behavioral control network. Consistent with this finding, greater neural flexibility signals in the VmPFC during stress correlated with active coping ratings whereas lower dynamic activity in the VmPFC also predicted a higher level of maladaptive coping behaviors in real life, including binge alcohol intake, emotional eating, and frequency of arguments and fights. These findings demonstrate acute functional neuroplasticity during stress, with distinct and separable brain networks that underlie critical components of the stress response, and a specific role for VmPFC neuroflexibility in stress-resilient coping.</AbstractText"
]
] |
[
[
"40037512",
"A novel ferroptosis inhibitor phenothiazine derivative reduces cell death and alleviates neurological impairments after cerebral hemorrhage.",
"The precise etiology of brain injury induced by intracerebral hemorrhage (ICH) remains unclear. Currently, there are no effective therapeutic options available to slow down or prevent the progression of the disease. An increasing body of evidence suggests that ferroptosis plays a significant role in the development of injury related to ICH. Furthermore, pharmacological inhibition of ferroptosis has been identified as a promising therapeutic target for ICH injury. The compound 2-(1-(4-(4-methylpiperazin-1-yl)phenyl)ethyl)-10H-phenothiazine (compound-51), a derivative of promethazine, has been demonstrated to exhibit anti-ferroptosis and antioxidant properties. The aim of this study is to investigate the role and mechanism of action of compound-51 in a rat model of ICH. The in vivo experiments demonstrated that compound-51 significantly alleviated neurological impairments, reduced brain edema, and decreased hematoma volume. At the cellular level, compound-51 was observed to significantly enhance cellular survival and inhibit ferroptosis. Furthermore, compound-51 demonstrated a more pronounced therapeutic effect than Fer-1, without causing any injury to the heart, kidney, or liver. In vitro experiments demonstrated that compound-51 significantly increased cell viability and intracellular GPX4 levels, while reducing lipid peroxidation and oxidized glutathione levels. Collectively, these findings indicate that compound-51 exhibits a pronounced anti-ferroptosis function and alleviates neurological impairments in an ICH model, suggesting its potential as a new therapeutic agent for the treatment of ICH.</AbstractText"
]
] |
38195249
|
Treatment outcomes for ARUBA-eligible brain arteriovenous malformations: a comparison of real-world data from the NVQI-QOD AVM registry with the ARUBA trial.
|
Significant controversy exists about the management of unruptured cerebral arteriovenous malformations (AVMs). Results from A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) suggested that intervention increases the risk of stroke/death compared with medical management. However, numerous study limitations raised concerns about the trial's generalizability.</AbstractText To assess the rate of stroke/death and functional outcomes in ARUBA-eligible patients from a multicenter database, the Neurovascular Quality Initiative-Quality Outcomes Database (NVQI-QOD).</AbstractText We performed a retrospective analysis of prospectively collected data of ARUBA-eligible patients who underwent intervention at 18 participating centers. The primary endpoint was stroke/death from any cause. Secondary endpoints included neurologic, systemic, radiographic, and functional outcomes.</AbstractText 173 ARUBA-eligible patients underwent intervention with median follow-up of 269 (25-722.5) days. Seventy-five patients received microsurgery±embolization, 37 received radiosurgery, and 61 received embolization. Baseline demographics, risk factors, and general AVM characteristics were similar between groups. A total of 15 (8.7%) patients experienced stroke/death with no significant difference in primary outcome between treatment modalities. Microsurgery±embolization was more likely to achieve AVM obliteration (P<0.001). Kaplan-Meier survival curves demonstrated no difference in overall death/stroke outcomes between the different treatment modalities' 5-year period (P=0.087). Additionally, when compared with the ARUBA interventional arm, our patients were significantly less likely to experience death/stroke (8.7% vs 30.7%; P<0.001) and functional impairment (mRS score ≥2 25.4% vs 46.2%; P<0.01).</AbstractText Our results suggest that intervention for unruptured brain AVMs at comprehensive stroke centers across the United States is safe.</AbstractText
|
[
[
"26156615",
"Management of a solitary pulmonary arteriovenous malformation by video-assisted thoracoscopic surgery and anatomic lingula resection: video and review.",
"Pulmonary arteriovenous malformations are abnormal communications between the pulmonary arterial and venous vasculature leading to a right-to-left blood shunt. Based on possible complications, including hypoxemia, hemorrhage, infection and paradoxical embolism, deactivation of the malformation from the circulation is the treatment option of choice, either by interventional embolization or by surgery. Embolization is less invasive and has widely replaced surgery, but bears the risk of revascularization, recanalization and downstream migration of the device with paradoxical embolism.</AbstractText We report on the case of a 76-year-old male patient suffering from a complex, plexiform pulmonary arteriovenous malformation in the lingula, which was treated by video-assisted thoracoscopic surgery and anatomic lingula resection. Patient's medical history, clinical examination and imaging studies did not reveal any evidence of hereditary hemorrhagic telangiectasia.</AbstractText Left-sided anterior three-port video-assisted thoracoscopic surgery (VATS) approach was used. Instead of only wedge resecting the very peripherally located pulmonary arteriovenous malformation, the lingular vessels were controlled centrally and an anatomic lingula resection was performed in order to prevent a more central re-malformation. To prevent rupture of the aneurysm sac through pressure overload, the feeding arteries were controlled before the draining vein. Duration of the total procedure was 151 min, the single chest tube was removed on the postoperative day 3, and the patient was discharged on the postoperative day 6.</AbstractText Although interventional embolism of the feeding artery of a pulmonary arteriovenous malformation is the current therapeutic gold standard, minimally invasive anatomic lung resection by video-assisted thoracoscopic surgery can be considered, especially for the treatment of solitary large arteriovenous malformations. By anatomic lung resection, the risk of recanalization, collateralization and peri-interventional paradoxical embolism may be reduced.</AbstractText"
]
] |
[
[
"39595016",
"The Impact of Virtual Reality as a Rehabilitation Method Using TRAVEE System on Functional Outcomes and Disability in Stroke Patients: A Pilot Study.",
"Stroke is the third leading cause of disability. Virtual reality (VR) has shown promising results in post-stroke rehabilitation. The VR TRAVEE system was designed for the neuromotor rehabilitation of the upper limb after a stroke and offers the ability to track limb movements by providing auditory feedback and visual augmentation. The World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0), aligned with the International Classification of Functioning, Disability, and Health (ICF) principles, is a valid tool for measuring disability regardless of its cause. This study aimed to investigate the feasibility of the VR TRAVEE system in upper limb rehabilitation for stroke patients.</AbstractText A total of 14 stroke patients with residual hemiparesis were enrolled in the study. They underwent a 10-day program combining conventional therapy (CnvT) with VR rehabilitation. At baseline (T0), the upper limb was assessed using the Modified Ashworth Scale (MAS), active range of motion (AROM), and the Numeric Rating Scale (NRS) for pain. These assessments were repeated after the 10-day rehabilitation program (T1). Additionally, disability was measured using WHODAS 2.0 at T0 and again 30 days after completing the program.</AbstractText Significant improvements were observed in AROM and MAS scores for the shoulder, elbow, wrist, and metacarpophalangeal joints, as well as in the reduction in shoulder pain (<i Combining CnvT with VR as a rehabilitation approach enhances motor function in the upper limb. This method has the potential to reduce disability scores and promote neuroplasticity.</AbstractText"
]
] |
40371132
|
Neural mechanisms of CALM intervention to improve CRCI in breast cancer survivors: an fMRI-based study.
|
Managing Cancer and Living Meaningfully (CALM) intervention's impact on chemotherapy-related cognitive impairment (CRCI) in breast cancer survivors (BCs) was investigated through resting-state functional magnetic resonance imaging (rs-fMRI) to elucidate the underlying neural mechanisms involved.</AbstractText 68 BCs were randomly assigned to either the CALM group (33 patients) or the care-as-usual (CAU) group (35 patients). Cognitive function was assessed before and after the intervention in both groups using the Mini Mental State Examination (MMSE) scale. Pre- and post-intervention rs-fMRI data were also collected for regional homogeneity (ReHo) and functional connectivity (FC) analyses in the CALM group. A total of 68 BCs were randomly assigned to either the CALM group (n = 33) or the care-as-usual (CAU) group (n = 35). Cognitive function was evaluated pre- and post-intervention using the Mini-Mental State Examination (MMSE). In the CALM group, rs-fMRI data were acquired before and after the intervention to assess alterations in regional homogeneity (ReHo) and functional connectivity (FC).</AbstractText CALM intervention demonstrated a greater enhancement in cognitive function compared to CAU (<i CALM intervention mitigates CRCI in BCs, with the middle frontal gyrus may play a critical.</AbstractText
|
[
[
"33308061",
"Why do imagery and perception look and feel so different?",
"Despite the past few decades of research providing convincing evidence of the similarities in function and neural mechanisms between imagery and perception, for most of us, the experience of the two are undeniably different, why? Here, we review and discuss the differences between imagery and perception and the possible underlying causes of these differences, from function to neural mechanisms. Specifically, we discuss the directional flow of information (top-down versus bottom-up), the differences in targeted cortical layers in primary visual cortex and possible different neural mechanisms of modulation versus excitation. For the first time in history, neuroscience is beginning to shed light on this long-held mystery of why imagery and perception look and feel so different. This article is part of the theme issue 'Offline perception: voluntary and spontaneous perceptual experiences without matching external stimulation'.</AbstractText"
]
] |
[
[
"39707024",
"Mechanical signaling through membrane tension induces somal translocation during neuronal migration.",
"Neurons migrate in a saltatory manner by repeating two distinct steps: extension of the leading process and translocation of the cell body. The former step is critical for determining the migratory route in response to extracellular guidance cues. In the latter step, neurons must generate robust forces that translocate the bulky soma against mechanical barriers of the surrounding three-dimensional environment. However, the link between the leading process extension and subsequent somal translocation remains unknown. By using the membrane tension sensor Flipper-TR and scanning ion conductance microscopy, we show that leading process extension increases plasma membrane tension. The tension elevation activated the mechanosensitive ion channel Tmem63b and triggered Ca<sup"
]
] |
37160674
|
Antitrust as a Guardrail for Socially Responsible Neurotechnology Design.
|
The neurotechnology sector is likely to develop under pressure towards commercialized, nonmedical products and may also undergo market consolidation. This possibility raises ethical, social, and policy concerns about the future responsibility of neurotechnology innovators and companies for high-consequence design decisions. Present-day internet technology firms furnish an instructive example of the problems that arise when providers of communicative technologies become too big for accountability. As a guardrail against the emergence of similar problems, concerned neurotechnologists may wish to draw inspiration from antitrust law and direct efforts, where appropriate, against undue consolidation in the commercial neurotechnology market.</AbstractText
|
[
[
"24904404",
"Decoding spectrotemporal features of overt and covert speech from the human cortex.",
"Auditory perception and auditory imagery have been shown to activate overlapping brain regions. We hypothesized that these phenomena also share a common underlying neural representation. To assess this, we used electrocorticography intracranial recordings from epileptic patients performing an out loud or a silent reading task. In these tasks, short stories scrolled across a video screen in two conditions: subjects read the same stories both aloud (overt) and silently (covert). In a control condition the subject remained in a resting state. We first built a high gamma (70-150 Hz) neural decoding model to reconstruct spectrotemporal auditory features of self-generated overt speech. We then evaluated whether this same model could reconstruct auditory speech features in the covert speech condition. Two speech models were tested: a spectrogram and a modulation-based feature space. For the overt condition, reconstruction accuracy was evaluated as the correlation between original and predicted speech features, and was significant in each subject (p < 10(-5); paired two-sample t-test). For the covert speech condition, dynamic time warping was first used to realign the covert speech reconstruction with the corresponding original speech from the overt condition. Reconstruction accuracy was then evaluated as the correlation between original and reconstructed speech features. Covert reconstruction accuracy was compared to the accuracy obtained from reconstructions in the baseline control condition. Reconstruction accuracy for the covert condition was significantly better than for the control condition (p < 0.005; paired two-sample t-test). The superior temporal gyrus, pre- and post-central gyrus provided the highest reconstruction information. The relationship between overt and covert speech reconstruction depended on anatomy. These results provide evidence that auditory representations of covert speech can be reconstructed from models that are built from an overt speech data set, supporting a partially shared neural substrate.</AbstractText"
]
] |
[
[
"36889873",
"Predicting Malignant Ventricular Arrhythmias Using Real-Time Remote Monitoring.",
"Although implantable cardioverter-defibrillator (ICD) therapies are associated with increased morbidity and mortality, the prediction of malignant ventricular arrhythmias has remained elusive.</AbstractText The purpose of this study was to evaluate whether daily remote-monitoring data may predict appropriate ICD therapies for ventricular tachycardia or ventricular fibrillation.</AbstractText This was a post hoc analysis of IMPACT (Randomized trial of atrial arrhythmia monitoring to guide anticoagulation in patients with implanted defibrillator and cardiac resynchronization devices), a multicenter, randomized, controlled trial of 2,718 patients evaluating atrial tachyarrhythmias and anticoagulation for patients with heart failure and ICD or cardiac resynchronization therapy with defibrillator devices. All device therapies were adjudicated as either appropriate (to treat ventricular tachycardia or ventricular fibrillation) or inappropriate (all others). Remote monitoring data in the 30 days before device therapy were utilized to develop separate multivariable logistic regression and neural network models to predict appropriate device therapies.</AbstractText A total of 59,807 device transmissions were available for 2,413 patients (age 64 ± 11 years, 26% women, 64% ICD). Appropriate device therapies (141 shocks, 10 antitachycardia pacing) were delivered to 151 patients. Logistic regression identified shock lead impedance and ventricular ectopy as significantly associated with increased risk of appropriate device therapy (sensitivity 39%, specificity 91%, AUC: 0.72). Neural network modeling yielded significantly better (P < 0.01 for comparison) predictive performance (sensitivity 54%, specificity 96%, AUC: 0.90), and also identified patterns of change in atrial lead impedance, mean heart rate, and patient activity as predictors of appropriate therapies.</AbstractText Daily remote monitoring data may be utilized to predict malignant ventricular arrhythmias in the 30 days before device therapies. Neural networks complement and enhance conventional approaches to risk stratification.</AbstractText"
]
] |
37756592
|
Attention-based generative adversarial networks improve prognostic outcome prediction of cancer from multimodal data.
|
The prediction of prognostic outcome is critical for the development of efficient cancer therapeutics and potential personalized medicine. However, due to the heterogeneity and diversity of multimodal data of cancer, data integration and feature selection remain a challenge for prognostic outcome prediction. We proposed a deep learning method with generative adversarial network based on sequential channel-spatial attention modules (CSAM-GAN), a multimodal data integration and feature selection approach, for accomplishing prognostic stratification tasks in cancer. Sequential channel-spatial attention modules equipped with an encoder-decoder are applied for the input features of multimodal data to accurately refine selected features. A discriminator network was proposed to make the generator and discriminator learning in an adversarial way to accurately describe the complex heterogeneous information of multiple modal data. We conducted extensive experiments with various feature selection and classification methods and confirmed that the CSAM-GAN via the multilayer deep neural network (DNN) classifier outperformed these baseline methods on two different multimodal data sets with miRNA expression, mRNA expression and histopathological image data: lower-grade glioma and kidney renal clear cell carcinoma. The CSAM-GAN via the multilayer DNN classifier bridges the gap between heterogenous multimodal data and prognostic outcome prediction.</AbstractText
|
[
[
"32300047",
"Categorical Signaling of the Strongest Stimulus by an Inhibitory Midbrain Nucleus.",
"The nucleus isthmi pars magnocellularis (Imc), a group of inhibitory neurons in the midbrain tegmentum, is a critical component of the spatial selection network in the vertebrate midbrain. It delivers long-range inhibition among different portions of the space map in the optic tectum (OT), thereby mediating stimulus competition in the OT. Here, we investigate the properties of relative strength-dependent competitive interactions within the Imc, in barn owls of both sexes. We find that when Imc neurons are presented simultaneously with one stimulus inside the receptive field and a second, competing stimulus outside, they exhibit gradual or switch-like response profiles as a function of relative stimulus strength. They do so both when the two stimuli are of the same sensory modality (both visual) or of different sensory modalities (visual and auditory). Moreover, Imc neurons signal the strongest stimulus in a dynamically flexible manner, indicating that Imc responses reflect an online comparison between the strengths of the competing stimuli. Notably, Imc neurons signal the strongest stimulus more categorically, and earlier than the OT. Paired recordings at spatially aligned sites in the Imc and OT reveal that although some properties of stimulus competition, such as the bias of competitive response profiles, are correlated, others such as the steepness of response profiles, are set independently. Our results demonstrate that the Imc is itself an active site of competition, and may be the first site in the midbrain selection network at which stimulus competition is resolved.<b"
]
] |
[
[
"37043357",
"Connexin 43-mediated neurovascular interactions regulate neurogenesis in the adult brain subventricular zone.",
"The subventricular zone (SVZ) is the largest neural stem cell (NSC) niche in the adult brain; herein, the blood-brain barrier is leaky, allowing direct interactions between NSCs and endothelial cells (ECs). Mechanisms by which direct NSC-EC interactions in the adult SVZ control NSC behavior are unclear. We found that Cx43 is highly expressed by SVZ NSCs and ECs, and its deletion in either leads to increased NSC proliferation and neuroblast generation, suggesting that Cx43-mediated NSC-EC interactions maintain NSC quiescence. This is further supported by single-cell RNA sequencing and in vitro studies showing that ECs control NSC proliferation by regulating expression of genes associated with NSC quiescence and/or activation in a Cx43-dependent manner. Cx43 mediates these effects in a channel-independent manner involving its cytoplasmic tail and ERK activation. Such insights inform adult NSC regulation and maintenance aimed at stem cell therapies for neurodegenerative disorders.</AbstractText"
]
] |
39387957
|
Advanced imaging reveals enhanced malignancy in glioblastomas involving the subventricular zone: evidence of increased infiltrative growth and perfusion.
|
Glioblastoma's infiltrative growth and heterogeneity are influenced by neural, molecular, genetic, and immunological factors, with the precise origin of these tumors remaining elusive. Neurogenic zones might serve as the tumor stem cells' nest, with tumors in contact with these zones exhibiting worse outcomes and more aggressive growth patterns. This study aimed to determine if these characteristics are reflected in advanced imaging, specifically diffusion and perfusion data.</AbstractText In this monocentric retrospective study, 137 glioblastoma therapy-naive patients (IDH-wildtype, grade 4) with advanced preoperative MRI, including perfusion and diffusion imaging, were analyzed. Tumors and neurogenic zones were automatically segmented. Advanced imaging metrics, including cerebral blood volume (CBV) from perfusion imaging, tissue volume mask (TVM), and free water corrected fractional anisotropy (FA-FWE) from diffusion imaging, were extracted.</AbstractText SVZ infiltration positively correlated with CBV, indicating higher perfusion in tumors. Significant CBV differences were noted between high and low SVZ infiltration cases at specific percentiles. Negative correlation was observed with TVM and positive correlation with FA-FWE, suggesting more infiltrative tumor growth. Significant differences in TVM and FA-FWE values were found between high and low SVZ infiltration cases.</AbstractText Glioblastomas with SVZ infiltration exhibit distinct imaging characteristics, including higher perfusion and lower cell density per voxel, indicating a more infiltrative growth and higher vascularization. Stem cell-like characteristics in SVZ-infiltrating cells could explain the increased infiltration and aggressive behavior. Understanding these imaging and biological correlations could enhance the understanding of glioblastoma evolution.</AbstractText
|
[
[
"26798224",
"Pre-Operative Perfusion Skewness and Kurtosis Are Potential Predictors of Progression-Free Survival after Partial Resection of Newly Diagnosed Glioblastoma.",
"To determine whether pre-operative perfusion skewness and kurtosis derived from normalized cerebral blood volume (nCBV) histograms are associated with progression-free survival (PFS) of patients after partial resection of newly diagnosed glioblastoma.</AbstractText A total of 135 glioblastoma patients who had undergone partial resection of tumor (resection of < 50% of pre-operative tumor volume or surgical biopsy) confirmed with immediate postsurgical MRI and examined with both conventional MRI and dynamic susceptibility contrast (DSC) perfusion MRI before the surgery were retrospectively reviewed in this study. They had been followed up post-surgical chemoradiotherapy for tumor progression. Using histogram analyses of nCBV derived from pre-operative DSC perfusion MRI, patients were sub-classified into the following four groups: positive skewness and leptokurtosis (group 1); positive skewness and platykurtosis (group 2); negative skewness and leptokurtosis (group 3); negative skewness and platykurtosis (group 4). Kaplan-Meier analysis and multivariable Cox proportional hazards regression analysis were performed to determine whether clinical and imaging covariates were associated with PFS or overall survival (OS) of these patients.</AbstractText According to the Kaplan-Meier method, median PFS of group 1, 2, 3, and 4 was 62, 51, 39, and 41 weeks, respectively, with median OS of 82, 77, 77, and 72 weeks, respectively. In multivariable analyses with Cox proportional hazards regression, pre-operative skewness/kurtosis pattern (hazard ratio: 2.98 to 4.64; p < 0.001), Karnofsky performance scale score (hazard ratio: 1.04; p = 0.003), and post-operative tumor volume (hazard ratio: 1.04; p = 0.02) were independently associated with PFS but not with OS.</AbstractText Higher skewness and kurtosis of nCBV histogram before surgery were associated with longer PFS in patients with newly diagnosed glioblastoma after partial tumor resection.</AbstractText"
]
] |
[
[
"40726664",
"A retrospective observational study of clinical and electrophysiological types of Guillain-Barre syndrome from Delhi.",
"To understand the demographic characteristics (age, sex and comorbidities), distribution of electrodiagnostic subtypes, and severity and prognosis of Guillain-Barre syndrome (GBS) variants.</AbstractText This 5-year retrospective study was conducted between January 2018 and December 2023. The patients (<i The patient group showed male predominance with an increased incidence with age. Antecedent infections were observed in 52 (38%) patients. Motor weakness, areflexia, and cranial nerve involvement (VII,IX,X,XI) were the most common clinical manifestations. The electrodiagnostic profiling included 96 (70%) patients with acute demyelinating polyradiculoneuropathy (AIDP), 25 (18.24%) patients of axonal forms and 16 (11%) patients of Bickerstaff Brainstem Encephalitis, Miller Fisher syndrome and paraparetic variants. Albumin cytological dissociation was documented in 61 (70%) patients out of 86 patients, which was more marked in AIDP than in other variants. The severity of GBS, using the Hughes disability score, was higher in patients with underlying diabetes mellitus. Recurrent GBS was observed in three (2%) and mortality rate was 2.91%.</AbstractText Our study showed a higher incidence of demyelination than that of axonal variants. There was more variation in albumin cytological dissociation in demyelinating subtypes than in the other variants. GBS severity was significantly higher in the patients with diabetes mellitus.</AbstractText"
]
] |
39163384
|
Childhood family socioeconomic status is linked to adult brain electrophysiology.
|
A large body of research has linked childhood family socioeconomic status (SES) to neurodevelopment in childhood and adolescence. However, it remains unclear to what extent childhood family SES relates to brain functioning in adulthood. To address this gap, the present study investigated the associations between retrospective accounts of objective and subjective childhood family SES and two well-established electrophysiological indices of brain functioning in adulthood-the MMN and P3b event-related potentials (ERP) components, as neural correlates of automatic change detection and cognitive control respectively. Higher objective childhood family SES, as proxied by parent educational attainment in childhood, was associated with larger (more positive) P3b amplitudes in adulthood. In contrast, there was no association between childhood parent educational attainment and the magnitude of MMN. Adult reports of subjective family SES during childhood were not related to the magnitude of MMN or P3b. These findings suggest that the links between childhood parent educational attainment and brain functioning may extend into adulthood, especially for brain functions supporting cognitive control. These results also imply that, when using retrospective accounts of childhood family SES, objective and subjective reports likely proxy different childhood experiences that have distinct links with specific neurodevelopmental outcomes, and that some of these links may not persist into adulthood. Our findings lay the groundwork for future investigations on how and why childhood family SES relates to brain functioning in adulthood.</AbstractText
|
[
[
"15131523",
"The role of GABA in the pathophysiology and treatment of anxiety disorders.",
"Mechanisms underlying the pathological characteristics of the various anxiety disorders have yet to be fully elucidated. One of the most widely accepted mediators known to play a central role in the pathophysiology of anxiety disorders is the g-aminobutyric acid (GABA) system. Evidence supporting the role of a dysfunctional GABA system has resulted from clinical experience with the benzodiazepines, as well as subsequent determination of mechanism of action, genetic engineering, and neuroimaging studies of the GABA receptor. The concatenation of results suggests a relative deficiency in GABA neurotransmission, which can be augmented by agents acting on different components of the GABA system. Agents such as the benzodiazepines, neuroactive steroids, and barbiturates act as allosteric modulators of the GABAA receptor; b-carboline and the barbiturates function as direct GABA agonists. Valproate, gabapentin, pregabalin, and vigabatrin increase brain GABA levels or neurotransmission at least in part by targeting the metabolic pathways of GABA. Tiagabine selectively increases synaptic GABA availability by blocking the reuptake of GABA via transporter inhibition. Evidence exists, to a greater or lesser extent, that all of these agents possess anxiolytic properties, as would be expected by their mechanisms of action. This article reviews the findings implicating the GABA system in the pathophysiology of anxiety disorders and describes the potential role of agents that modulate GABA neurotransmission in the treatment of these disorders.</AbstractText"
]
] |
[
[
"38472551",
"Ocrelizumab use in multiple sclerosis: a real-world experience in a changing therapeutic scenario.",
"CD20-depleting therapies are a real milestone in the treatment of multiple sclerosis (MS). This study examined the ocrelizumab (OCR) use in patients with primary progressive (PP) and relapsing remitting (RR) MS, also evaluating the predictors of treatment response.</AbstractText Patients with MS treated with OCR between 2017 and 2022 were included, and OCR use trends examined. The patients' characteristics were assessed at baseline and after 24 months of OCR to assess the NEDA-3 status.</AbstractText This study included 421 patients: 33 (7.9%) with PP and 388 (92.1%) with RR MS. Among these, 67 (17.3%) were naïve, while switchers from first- and second-line disease-modifying therapies (DMTs) were 199 (51.3%) and 122 (31.4%), respectively. An increasing trend in OCR use was reported. For six patients treated with rituximab, OCR was chosen to improve tolerability; for 390 switcher patients, the choice was due to ineffectiveness; and for 25, as an exit strategy from natalizumab due to JC virus positivity. NEDA-3 status was calculated for subjects exposed to 24 months of OCR and was achieved by 163/192 (84.9%) RR patients and 9/16 (56%) PP patients, with younger age (p = 0.048) and annualized relapse rate in the year previous to OCR (p = 0.005) emerging as determinants. For the 25 patients who switched to OCR after natalizumab, no clinical or MRI activity after 12 months was reported.</AbstractText OCR has been confirmed to be a highly efficacious option for patients with PP and RR MS, even proving to be a valid exit strategy for natalizumab.</AbstractText"
]
] |
40011296
|
Pyrrolidine Dithiocarbamate Ameliorates Sepsis-Associated Encephalopathy by Inhibiting Autophagy and Inflammation in the Brain.
|
Sepsis-associated encephalopathy (SAE) is common and has poor clinical outcome. Sepsis increases autophagy in the brain. This study was designed to determine the role of autophagy on SAE including the brain structures related to learning and memory and the effects of pyrrolidine dithiocarbamate (PDTC), an anti-inflammatory agent, on autophagy and SAE. Six- to eight-week old CD-1 male mice were subjected to cecal ligation and puncture (CLP). Some mice received intracerebroventricular injection of the autophagy suppressor 3-methyladenine (3-MA) or intraperitoneal injection of PDTC immediately at the completion of the CLP. ELISA was used to measure interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor α. Autophagy-related protein expression in the cerebral cortex and hippocampus was analyzed by Western blotting. The cognitive functions of mice were analyzed by Barnes maze and fear conditioning tests. CLP increased microtubuleassociated protein light chain 3 II (LC3II) and Beclin 1 and decreased p62 in the brain. CLP also increased proinflammatory cytokines and impaired learning and memory. These effects were inhibited by 3-MA and PDTC. Spine proliferation and maturation were impaired by CLP, which was attenuated by PDTC and 3MA. Abundant autophagic vacuoles were observed by transmission electron microscopy in CLP group. LC3II immunostaining was co-localized with that of ionized calcium-binding adapter molecule 1 and microtubule-associated protein-2. The co-staining was attenuated by 3-MA and PDTC. Our results suggest that sepsis increases autophagy in the microglia and neurons. Inhibiting autophagy improves SAE and brain structures related to learning and memory in mice. Autophagy and inflammation in the brain may regulate each other during sepsis.</AbstractText
|
[
[
"37331262",
"Treatment outcomes of Veteran men in a comprehensive dialectical behavior therapy program: Characterizing sex differences in symptom trajectories.",
"Dialectical Behavior Therapy (DBT) is one of the primary psychosocial treatments for reducing suicidal behaviors and improving psychosocial outcomes among patients with borderline personality disorder (BPD) and has been shown to reduce BPD symptoms when delivered in a Veteran Affairs medical center setting. Despite evidence of similar rates of BPD in both men and women, the vast majority of treatment outcome research in BPD has focused on women. We sought to characterize sex differences in symptom trajectories among Veterans participating in a comprehensive DBT program. We found that Veteran men and women who entered the DBT program were diagnostically and demographically similar. Participants exhibited reductions in BPD symptoms and improvements in emotion regulation over the course of treatment. Moreover, Veteran men reported BPD symptom reductions that were not statistically inferior to those of Veteran women and exhibited a sharper reduction in these symptoms. This research provides support for the use of DBT as a psychosocial treatment for Veteran men with BPD symptoms.</AbstractText"
]
] |
[
[
"40543407",
"Exploring gastrocnemius medialis behavior during gait in children with cerebral palsy across different gait patterns.",
"Children with spastic cerebral palsy show varied gait patterns and muscle morphological alterations. We explored gastrocnemius medialis behavior during gait in typically developing children and children with cerebral palsy across different gait patterns.</AbstractText Eighteen children with spasticity of the leg muscles (female: 8, age: 11.1 ± 3.3 y) with a diagnosis of cerebral palsy (n = 17) or hereditary spastic paraplegia (n = 1) and 16 typically developing children (female: 11, age: 11.2 ± 3.2 y) walked on an instrumented treadmill. Three distinct gait patterns were determined in children with cerebral palsy. Muscle-tendon unit, fascicle, belly, and tendon behavior were assessed with dynamic ultrasound imaging. Unpaired statistical non-parametric mapping (SnPM) t-tests and Mann-Whitney U tests assessed differences between children with cerebral palsy and typically developing children. One-way ANOVA SnPM tests and Kruskall-Wallis tests assessed differences across gait patterns.</AbstractText Tendon lengthening in the first half of stance was higher in children with cerebral palsy compared to typically developing children (Δ6.6 mm), yet total tendon lengthening in stance (Δ5.3 mm) and fascicle shortening during push-off were decreased (Δ6.2 mm). Children with cerebral palsy displaying a mildly affected kinematic gait pattern showed pathological muscle belly lengthening in stance (Δ5.7 mm), while children with equinus (Δ6.4 mm) or crouch gait (Δ6.0 mm) showed reduced tendon lengthening.</AbstractText Efficient gastrocnemius medialis behavior is compromised in children with spastic cerebral palsy. Children with mildly affected gait show the most deviation in muscular components involved in active force generation, while those with equinus and crouch gait also show deviations in tendinous components. Interventions aimed at improving gait should consider this aberrant behavior.</AbstractText"
]
] |
35065321
|
Selenium ameliorates mercuric chloride-induced brain damage through activating BDNF/TrKB/PI3K/AKT and inhibiting NF-κB signaling pathways.
|
Mercuric chloride (HgCl<sub
|
[
[
"3025747",
"A new mechanism for induced vitamin D deficiency in calcium deprivation.",
"Synthesis of vitamin D in the skin in response to ultraviolet light is the main determinant of vitamin D status in man and it is therefore surprising that rickets and osteomalacia, clinical signs of vitamin D deficiency, remain common in tropical and subtropical countries. Skin pigmentation can reduce vitamin D formation but this is a negligible limitation in people exposed to abundant ultraviolet light. Earlier studies in animals and man suggested that another environmental factor, the low calcium/high cereal diet typical of susceptible populations, might affect the efficiency of vitamin D utilization. We show here in rats that the rate of inactivation of vitamin D in the liver is increased by calcium deprivation. The effect is mediated by 1,25-dihydroxyvitamin D, produced in response to secondary hyperparathyroidism, which promotes hepatic conversion of vitamin D to polar inactivation products that are excreted in bile. This finding has widespread implications both for understanding the pathogenesis of endemic rickets and in that it provides a unifying mechanism for the development of vitamin D deficiency in many clinical disorders.</AbstractText"
]
] |
[
[
"36685218",
"Sources of residual autocorrelation in multiband task fMRI and strategies for effective mitigation.",
"Analysis of task fMRI studies is typically based on using ordinary least squares within a voxel- or vertex-wise linear regression framework known as the general linear model. This use produces estimates and standard errors of the regression coefficients representing amplitudes of task-induced activations. To produce valid statistical inferences, several key statistical assumptions must be met, including that of independent residuals. Since task fMRI residuals often exhibit temporal autocorrelation, it is common practice to perform \"prewhitening\" to mitigate that dependence. Prewhitening involves estimating the residual correlation structure and then applying a filter to induce residual temporal independence. While theoretically straightforward, a major challenge in prewhitening for fMRI data is accurately estimating the residual autocorrelation at each voxel or vertex of the brain. Assuming a global model for autocorrelation, which is the default in several standard fMRI software tools, may under- or over-whiten in certain areas and produce differential false positive control across the brain. The increasing popularity of multiband acquisitions with faster temporal resolution increases the challenge of effective prewhitening because more complex models are required to accurately capture the strength and structure of autocorrelation. These issues are becoming more critical now because of a trend toward subject-level analysis and inference. In group-average or group-difference analyses, the within-subject residual correlation structure is accounted for implicitly, so inadequate prewhitening is of little real consequence. For individual subject inference, however, accurate prewhitening is crucial to avoid inflated or spatially variable false positive rates.</AbstractText In this paper, we first thoroughly examine the patterns, sources and strength of residual autocorrelation in multiband task fMRI data. Second, we evaluate the ability of different autoregressive (AR) model-based prewhitening strategies to effectively mitigate autocorrelation and control false positives. We consider two main factors: the choice of AR model order and the level of spatial regularization of AR model coefficients, ranging from local smoothing to global averaging. We also consider determining the AR model order optimally at every vertex, but we do not observe an additional benefit of this over the use of higher-order AR models (e.g. (AR(6)). To overcome the computational challenge associated with spatially variable prewhitening, we developed a computationally efficient R implementation using parallelization and fast C++ backend code. This implementation is included in the open source R package BayesfMRI.</AbstractText We find that residual autocorrelation exhibits marked spatial variance across the cortex and is influenced by many factors including the task being performed, the specific acquisition protocol, mis-modeling of the hemodynamic response function, unmodeled noise due to subject head motion, and systematic individual differences. We also find that local regularization is much more effective than global averaging at mitigating autocorrelation. While increasing the AR model order is also helpful, it has a lesser effect than allowing AR coefficients to vary spatially. We find that prewhitening with an AR(6) model with local regularization is effective at reducing or even eliminating autocorrelation and controlling false positives.</AbstractText Our analysis revealed dramatic spatial differences in autocorrelation across the cortex. This spatial topology is unique to each session, being influenced by the task being performed, the acquisition technique, various modeling choices, and individual differences. If not accounted for, these differences will result in differential false positive control and power across the cortex and across subjects.</AbstractText"
]
] |
34324976
|
Improvement of sensitivity and specificity for laminar BOLD fMRI with double spin-echo EPI in humans at 7 T.
|
Mapping mesoscopic cortical functional units such as columns or laminae is increasingly pursued by ultra-high field (UHF) functional magnetic resonance imaging (fMRI). The most popular approach for high-resolution fMRI is currently gradient-echo (GE) blood oxygenation level-dependent (BOLD) fMRI. However, its spatial accuracy is reduced due to its sensitivity to draining vessels, including pial veins, whereas spin-echo (SE) BOLD signal is expected to have higher spatial accuracy, albeit with lower sensitivity than the GE-BOLD signal. Here, we introduce a new double spin-echo (dSE) echo-planar imaging (EPI) method to improve the sensitivity of SE-BOLD contrast by averaging two spin-echoes using three radiofrequency pulses. Human fMRI experiments were performed with slices perpendicular to the central sulcus between motor and sensory cortices at 7 T during fist-clenching with touching. First, we evaluated the feasibility of single-shot dSE-EPI for BOLD fMRI with 1.5 mm isotropic resolution and found that dSE-BOLD fMRI has higher signal-to-noise ratio (SNR), temporal SNR (tSNR), and higher functional sensitivity than conventional SE-BOLD fMRI. Second, to investigate the laminar specificity of dSE-BOLD fMRI, we implemented a multi-shot approach to achieve 0.8-mm isotropic resolution with sliding-window reconstruction. Unlike GE-BOLD fMRI, the cortical profile of dSE-BOLD fMRI peaked at ~ 1.0 mm from the surface of the primary motor and sensory cortices, demonstrating an improvement of laminar specificity in humans over GE-BOLD fMRI. The proposed multi-shot dSE-EPI method is viable for high spatial resolution UHF-fMRI studies in the pursuit of resolving mesoscopic functional units.</AbstractText
|
[
[
"32936488",
"Segmented K-space blipped-controlled aliasing in parallel imaging for high spatiotemporal resolution EPI.",
"A segmented k-space blipped-controlled aliasing in parallel imaging (skipped-CAIPI) sampling strategy for EPI is proposed, which allows for a flexible choice of EPI factor and phase encode bandwidth independent of the controlled aliasing in parallel imaging (CAIPI) sampling pattern.</AbstractText With previously proposed approaches, exactly two EPI trajectories were possible given a specific CAIPI pattern, either with slice gradient blips (blipped-CAIPI) or following a shot-selective CAIPI approach (higher resolution). Recently, interleaved multi-shot segmentation along shot-selective CAIPI trajectories has been applied for high-resolution anatomical imaging. For more flexibility and a broader range of applications, we propose segmentation along any blipped-CAIPI trajectory. Thus, all EPI factors and phase encode bandwidths available with traditional segmented EPI can be combined with controlled aliasing.</AbstractText Temporal SNR maps of moderate-to-high-resolution time series acquisitions at varying undersampling factors demonstrate beneficial sampling alternatives to blipped-CAIPI or shot-selective CAIPI. Rapid high-resolution scans furthermore demonstrate SNR-efficient and motion-robust structural imaging with almost arbitrary EPI factor and minimal noise penalty.</AbstractText Skipped-CAIPI sampling increases protocol flexibility for high spatiotemporal resolution EPI. In terms of SNR and efficiency, high-resolution functional or structural scans benefit vastly from a free choice of the CAIPI pattern. Even at moderate resolutions, the independence of sampling pattern, TE, and image matrix size is valuable for optimized functional protocol design. Although demonstrated with 3D-EPI, skipped-CAIPI is also applicable with simultaneous multislice EPI.</AbstractText"
]
] |
[
[
"23103517",
"Towards a neural circuit model of verbal humor processing: an fMRI study of the neural substrates of incongruity detection and resolution.",
"The present study builds on our previous study within the framework of Wyer and Collin's comprehension-elaboration theory of humor processing. In this study, an attempt is made to segregate the neural substrates of incongruity detection and incongruity resolution during the comprehension of verbal jokes. Although a number of fMRI studies have investigated the incongruity-resolution process, the differential neurological substrates of comprehension are still not fully understood. The present study utilized an event-related fMRI design incorporating three conditions (unfunny, nonsensical and funny) to examine distinct brain regions associated with the detection and resolution of incongruities. Stimuli in the unfunny condition contained no incongruities; stimuli in the nonsensical condition contained irresolvable incongruities; and stimuli in the funny condition contained resolvable incongruities. The results showed that the detection of incongruities was associated with greater activation in the right middle temporal gyrus and right medial frontal gyrus, and the resolution of incongruities with greater activation in the left superior frontal gyrus and left inferior parietal lobule. Further analysis based on participants' rating scores provided converging results. Our findings suggest a three-stage neural circuit model of verbal humor processing: incongruity detection and incongruity resolution during humor comprehension and inducement of the feeling of amusement during humor elaboration.</AbstractText"
]
] |
30605083
|
Adaptive Matching Transmitter With Dual-Band Antenna for Intraoral Tongue Drive System.
|
The intraoral Tongue Drive System (iTDS) is a wireless assistive technology that detects users' voluntary tongue gestures, and converts them to user-defined commands, enabling them to access computers and navigate powered wheelchairs. In this paper, we presented a transmitter (Tx) with adaptive matching and three bands (27, 433, and 915 MHz) to create a robust wireless link between iTDS and an external receiver (Rx) by addressing the effects of external RF interference and impedance variations of the Tx antenna in the dynamic mouth environment. The upper two Tx bands share a dual-band antenna, while the lower band drives a coil. The Tx antenna is simulated in a simplified human mouth model in HFSS as well as a real human head model. The adaptive triple-band Tx chip was fabricated in a 0.35-μm 4P2M standard CMOS process. The Tx chip and antenna have been characterized in a human subject as part of an iTDS prototype under open-and closed-mouth scenarios, which present the peak gain of -24.4 and -15.63 dBi at 433 and 915 MHz, respectively. Two adaptive matching networks for these bands compensate variations of the Tx antenna impedance via a feedback mechanism. The measured S<sub
|
[
[
"23556919",
"A prototype MR insertable brain PET using tileable GAPD arrays.",
"The aim of this study was to develop a prototype magnetic resonance (MR)-compatible positron emission tomography (PET) that can be inserted into a MR imager and that allows simultaneous PET and MR imaging of the human brain. This paper reports the initial results of the authors' prototype brain PET system operating within a 3-T magnetic resonance imaging (MRI) system using newly developed Geiger-mode avalanche photodiode (GAPD)-based PET detectors, long flexible flat cables, position decoder circuit with high multiplexing ratio, and digital signal processing with field programmable gate array-based analog to digital converter boards.</AbstractText A brain PET with 72 detector modules arranged in a ring was constructed and mounted in a 3-T MRI. Each PET module was composed of cerium-doped lutetium yttrium orthosilicate (LYSO) crystals coupled to a tileable GAPD. The GAPD output charge signals were transferred to preamplifiers using 3 m long flat cables. The LYSO and GAPD were located inside the MR bore and all electronics were positioned outside the MR bore. The PET detector performance was investigated both outside and inside the MRI, and MR image quality was evaluated with and without the PET system.</AbstractText The performance of the PET detector when operated inside the MRI during MR image acquisition showed no significant change in energy resolution and count rates, except for a slight degradation in timing resolution with an increase from 4.2 to 4.6 ns. Simultaneous PET/MR images of a hot-rod and Hoffman brain phantom were acquired in a 3-T MRI. Rods down to a diameter of 3.5 mm were resolved in the hot-rod PET image. The activity distribution patterns between the white and gray matter in the Hoffman brain phantom were well imaged. The hot-rod and Hoffman brain phantoms on the simultaneously acquired MR images obtained with standard sequences were observed without any noticeable artifacts, although MR image quality requires some improvement.</AbstractText These results demonstrate that the simultaneous acquisition of PET and MR images is feasible using the MR insertable PET developed in this study.</AbstractText"
]
] |
[
[
"29446125",
"Feasibility of high spatiotemporal resolution for an abbreviated 3D radial breast MRI protocol.",
"To develop a volumetric imaging technique with 0.8-mm isotropic resolution and 10-s/volume rate to detect and analyze breast lesions in a bilateral, dynamic, contrast-enhanced MRI exam.</AbstractText A local low-rank temporal reconstruction approach that also uses parallel imaging and spatial compressed sensing was designed to create rapid volumetric frame rates during a contrast-enhanced breast exam (vastly undersampled isotropic projection [VIPR] spatial compressed sensing with temporal local low-rank [STELLR]). The dynamic-enhanced data are subtracted in k-space from static mask data to increase sparsity for the local low-rank approach to maximize temporal resolution. A T<sub The STELLR temporal performance of subtracted data matched the expected temporal perfusion enhancement pattern in small and large vascular structures. Differential enhancement within heterogeneous lesions is demonstrated with corroboration from a basic reconstruction using a strict 10-second temporal footprint. Rapid acquisition, reliable fat suppression, and high spatiotemporal resolution are presented, despite significant data undersampling.</AbstractText The STELLR reconstruction approach of 3D radial sampling with mask subtraction provides a high-performance imaging technique for characterizing enhancing structures within the breast. It is capable of maintaining temporal fidelity, while visualizing breast lesions with high detail over a large FOV to include both breasts.</AbstractText"
]
] |
39730017
|
Forsythoside B ameliorates neuroinflammation via inhibiting NLRP3 inflammasome of glial cells in experimental autoimmune encephalomyelitis mice.
|
Neuroinflammation mediated by glial cells plays a crucial role in demyelination in experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis (MS) model. Forsythoside B (FTS·B), a natural phenylethanoid glycoside isolated from the dried fruits and leaves of Forsythia suspensa (Thunb.) Vahl, has been found to have antioxidant, anti-apoptotic, and anti-inflammatory properties. However, there is currently no report or research on the effectiveness of FTS·B treatment for EAE. The aim of this study was to investigate the neuroprotective properties of (FTS·B) on EAE and reveal its potential mechanisms. Myelin oligodendrocyte glycoprotein-induced EAE mice were randomly categorized into the control, EAE model, and FTS·B treatment groups. Behavioral testing, pathology, immunohistochemistry, immunofluorescence staining, and western blot analysis of spinal cord tissue were used to determine the effects and mechanisms of FTS·B on EAE in mice. We found that FTS·B treatment could significantly alleviate and reduce the clinical symptoms and morbidity of EAE, respectively. In addition, FTS·B administration reduced inflammatory response and demyelination by inhibiting glial cell activation in the spinal cord of EAE mice. Further experiments confirmed that FTS·B inhibited the formation of NLRP3 inflammasome in microglia and astrocytes, thereby suppressing neuroinflammation and GSDMD-mediated pyroptosis. Altogether, these results suggest that FTS·B treatment attenuates central neuroinflammation and pyroptosis by inhibiting NLRP3 inflammasome of glial cells in EAE mice.</AbstractText
|
[
[
"31740269",
"Mitochondrial impairment activates the Wallerian pathway through depletion of NMNAT2 leading to SARM1-dependent axon degeneration.",
"Wallerian degeneration of physically injured axons involves a well-defined molecular pathway linking loss of axonal survival factor NMNAT2 to activation of pro-degenerative protein SARM1. Manipulating the pathway through these proteins led to the identification of non-axotomy insults causing axon degeneration by a Wallerian-like mechanism, including several involving mitochondrial impairment. Mitochondrial dysfunction is heavily implicated in Parkinson's disease, Charcot-Marie-Tooth disease, hereditary spastic paraplegia and other axonal disorders. However, whether and how mitochondrial impairment activates Wallerian degeneration has remained unclear. Here, we show that disruption of mitochondrial membrane potential leads to axonal NMNAT2 depletion in mouse sympathetic neurons, increasing the substrate-to-product ratio (NMN/NAD) of this NAD-synthesising enzyme, a metabolic fingerprint of Wallerian degeneration. The mechanism appears to involve both impaired NMNAT2 synthesis and reduced axonal transport. Expression of WLD<sup"
]
] |
[
[
"39934999",
"MacaqueNet: Advancing comparative behavioural research through large-scale collaboration.",
"There is a vast and ever-accumulating amount of behavioural data on individually recognised animals, an incredible resource to shed light on the ecological and evolutionary drivers of variation in animal behaviour. Yet, the full potential of such data lies in comparative research across taxa with distinct life histories and ecologies. Substantial challenges impede systematic comparisons, one of which is the lack of persistent, accessible and standardised databases. Big-team approaches to building standardised databases offer a solution to facilitating reliable cross-species comparisons. By sharing both data and expertise among researchers, these approaches ensure that valuable data, which might otherwise go unused, become easier to discover, repurpose and synthesise. Additionally, such large-scale collaborations promote a culture of sharing within the research community, incentivising researchers to contribute their data by ensuring their interests are considered through clear sharing guidelines. Active communication with the data contributors during the standardisation process also helps avoid misinterpretation of the data, ultimately improving the reliability of comparative databases. Here, we introduce MacaqueNet, a global collaboration of over 100 researchers (https://macaquenet.github.io/) aimed at unlocking the wealth of cross-species data for research on macaque social behaviour. The MacaqueNet database encompasses data from 1981 to the present on 61 populations across 14 species and is the first publicly searchable and standardised database on affiliative and agonistic animal social behaviour. We describe the establishment of MacaqueNet, from the steps we took to start a large-scale collective, to the creation of a cross-species collaborative database and the implementation of data entry and retrieval protocols. We share MacaqueNet's component resources: an R package for data standardisation, website code, the relational database structure, a glossary and data sharing terms of use. With all these components openly accessible, MacaqueNet can act as a fully replicable template for future endeavours establishing large-scale collaborative comparative databases.</AbstractText"
]
] |
16196033
|
Constitutive neuronal expression of CCR2 chemokine receptor and its colocalization with neurotransmitters in normal rat brain: functional effect of MCP-1/CCL2 on calcium mobilization in primary cultured neurons.
|
Chemokines and their receptors are well described in the immune system, where they promote cell migration and activation. In the central nervous system, chemokine has been implicated in neuroinflammatory processes. However, an increasing number of evidence suggests that they have regulatory functions in the normal nervous system, where they could participate in cell communication. In this work, using a semiquantitative immunohistochemistry approach, we provide the first neuroanatomical mapping of constitutive neuronal CCR2 localization. Neuronal expression of CCR2 was observed in the anterior olfactory nucleus, cerebral cortex, hippocampal formation, caudate putamen, globus pallidus, supraoptic and paraventricular hypothalamic nuclei, amygdala, substantia nigra, ventral tegmental area, and in the brainstem and cerebellum. These data are largely in accordance with results obtained using quantitative autoradiography with [(125)I]MCP-1/CCL2 and RT-PCR CCR2 mRNA analysis. Furthermore, using dual fluorescent immunohistochemistry we studied the chemical phenotype of labeled neurons and demonstrated the coexistence of CCR2 with classical neurotransmitters. Indeed, localization of CCR2 immunostaining is observed in dopaminergic neurons in the substantia nigra pars compacta and in the ventral tegmental area as well as in cholinergic neurons in the substantia innominata and caudate putamen. Finally, we show that the preferential CCR2 ligand, MCP-1/CCL2, elicits Ca(2+) transients in primary cultured neurons from various rat brain regions including the cortex, hippocampus, hypothalamus, and mesencephalon. In conclusion, the constitutive neuronal CCR2 expression in selective brain structures suggests that this receptor could be involved in neuronal communication and possibly associated with cholinergic and dopaminergic neurotransmission and related disorders.</AbstractText
|
[
[
"36857176",
"Positive and negative allosteric modulation of GluK2 kainate receptors by BPAM344 and antiepileptic perampanel.",
"Kainate receptors (KARs) are a subtype of ionotropic glutamate receptors that control synaptic transmission in the central nervous system and are implicated in neurological, psychiatric, and neurodevelopmental disorders. Understanding the regulation of KAR function by small molecules is essential for exploring these receptors as drug targets. Here, we present cryoelectron microscopy (cryo-EM) structures of KAR GluK2 in complex with the positive allosteric modulator BPAM344, competitive antagonist DNQX, and negative allosteric modulator, antiepileptic drug perampanel. Our structures show that two BPAM344 molecules bind per ligand-binding domain dimer interface. In the absence of an agonist or in the presence of DNQX, BPAM344 stabilizes GluK2 in the closed state. The closed state is also stabilized by perampanel, which binds to the ion channel extracellular collar sites located in two out of four GluK2 subunits. The molecular mechanisms of positive and negative allosteric modulation of KAR provide a guide for developing new therapeutic strategies.</AbstractText"
]
] |
[
[
"38010204",
"Associations between white matter integrity of the cingulum bundle, surrounding gray matter regions, and cognition across the dementia continuum.",
"Previous Alzheimer's disease and related dementias (AD/ADRD) research studies have illustrated the significance of studying alterations in white matter (WM). Fewer studies have examined how WM integrity, measured with diffusion tensor imaging (DTI), is associated with volume of gray matter (GM) regions and measures of cognitive function in aged participants spanning the dementia continuum.</AbstractText Magnetic resonance imaging and cognitive data were collected from 241 Boston University Alzheimer's Disease Research Center participants who spanned from cognitively normal controls to amnestic mild cognitive impairment to having dementia. Primary DTI tracts of interest were the cingulum ventral (CV) and cingulum dorsal (CD) pathways. GM regions of interest (ROIs) were in the medial temporal lobe (MTL), prefrontal cortex, and retrosplenial cortex. Analyses of covariance models were used to assess differences in WM integrity across groups (control, amnestic mild cognitive impairment, and dementia). Multiple linear regression models were used to assess associations between WM integrity and GM volume, and with measures of memory and executive function.</AbstractText Differences in WM integrity were shown in both cingulum pathways in participants across the dementia continuum. Associations between WM integrity of both cingulum pathways and volume of selected GM ROIs were widespread. Functionally significant associations were found between WM of the CV pathway and memory, independent of MTL GM volume.</AbstractText Differences in WM integrity of the cingulum bundle and surrounding GM ROI are likely related to the progression of AD/ADRD. Such differences should continue to be studied, particularly in association with memory performance.</AbstractText"
]
] |
34132175
|
Creutzfeldt-Jakob disease in pregnancy: the use of modified RT-QuIC to determine infectivity in placental tissues.
|
Sporadic Creutzfeldt-Jakob Disease (sCJD) rarely affects women of childbearing age. There is currently no evidence of vertical transmission. Given the biosafety implications of performing Caesarean sections (C-section) in these patients, we used sensitive real-time quaking-induced conversion (RT-QuIC) assays to test for the infectious prion protein (PrP<sup
|
[
[
"29186501",
"The Amygdala as a Locus of Pathologic Misfolding in Neurodegenerative Diseases.",
"Over the course of most common neurodegenerative diseases the amygdala accumulates pathologically misfolded proteins. Misfolding of 1 protein in aged brains often is accompanied by the misfolding of other proteins, suggesting synergistic mechanisms. The multiplicity of pathogenic processes in human amygdalae has potentially important implications for the pathogenesis of Alzheimer disease, Lewy body diseases, chronic traumatic encephalopathy, primary age-related tauopathy, and hippocampal sclerosis, and for the biomarkers used to diagnose those diseases. Converging data indicate that the amygdala may represent a preferential locus for a pivotal transition from a relatively benign clinical condition to a more aggressive disease wherein multiple protein species are misfolded. Thus, understanding of amygdalar pathobiology may yield insights relevant to diagnoses and therapies; it is, however, a complex and imperfectly defined brain region. Here, we review aspects of amygdalar anatomy, connectivity, vasculature, and pathologic involvement in neurodegenerative diseases with supporting data from the University of Kentucky Alzheimer's Disease Center autopsy cohort. Immunohistochemical staining of amygdalae for Aβ, Tau, α-synuclein, and TDP-43 highlight the often-coexisting pathologies. We suggest that the amygdala may represent an \"incubator\" for misfolded proteins and that it is possible that misfolded amygdalar protein species are yet to be discovered.</AbstractText"
]
] |
[
[
"33143627",
"Diabetes and Its Complications: Therapies Available, Anticipated and Aspired.",
"Worldwide, diabetes ranks among the ten leading causes of mortality. Prevalence of diabetes is growing rapidly in low and middle income countries. It is a progressive disease leading to serious co-morbidities, which results in increased cost of treatment and over-all health system of the country. Pathophysiological alterations in Type 2 Diabetes (T2D) progressed from a simple disturbance in the functioning of the pancreas to triumvirate to ominous octet to egregious eleven to dirty dozen model. Due to complex interplay of multiple hormones in T2D, there may be multifaceted approach in its management. The 'long-term secondary complications' in uncontrolled diabetes may affect almost every organ of the body, and finally may lead to multi-organ dysfunction. Available therapies are inconsistent in maintaining long term glycemic control and their long term use may be associated with adverse effects. There is need for newer drugs, not only for glycemic control but also for prevention or mitigation of secondary microvascular and macrovascular complications. Increased knowledge of the pathophysiology of diabetes has contributed to the development of novel treatments. Several new agents like Glucagon Like Peptide - 1 (GLP-1) agonists, Dipeptidyl Peptidase IV (DPP-4) inhibitors, amylin analogues, Sodium-Glucose transport -2 (SGLT- 2) inhibitors and dual Peroxisome Proliferator-Activated Receptor (PPAR) agonists are available or will be available soon, thus extending the range of therapy for T2D, thereby preventing its long term complications. The article discusses the pathophysiology of diabetes along with its comorbidities, with a focus on existing and novel upcoming antidiabetic drugs which are under investigation. It also dives deep to deliberate upon the novel therapies that are in various stages of development. Adding new options with new mechanisms of action to the treatment armamentarium of diabetes may eventually help improve outcomes and reduce its economic burden.</AbstractText"
]
] |
40717422
|
Empowering learners through student-led integration of environmental health into small group discussions.
|
With ongoing climate change and other major human-induced changes to the biosphere, there is a greater need to improve future healthcare providers' environmental health (EH) literacy. As of 2022, 45% of U.S. MD programs lacked a required EH curriculum. A self-assembled group of four medical students conceptualized and planned this pilot study to characterize matriculating medical students' EH knowledge and attitudes. This group also developed EH content for integration into a preexisting 18-month Case-Based Learning (CBL) curriculum to enhance small-group discussion and learning. Matriculating medical students were invited to participate in an anonymous cross-sectional survey assessing EH literacy and the need for an EH-specific curriculum in August 2023. Concurrently, the student group analyzed 44 cases in the current CBL curriculum and searched PubMed and the PEHSU Climate Resources for Health Education for pertinent topics from the case review. The group then formulated learning objectives and discussion questions for the facilitator guide for 30 cases, with expert review by curriculum faculty members. 70 of 200 students (35%) fully completed a survey about EH literacy. Eighty percent of students reported no previous coursework pertinent to EH, with most students demonstrating a basic understanding of the concept. Students reported low confidence in counseling patients regarding pertinent EH matters and a limited understanding of social determinants of health pertinent to the local area. In 30 identified medical conditions across 10 disciplines, 57 new objectives were developed to address environmental exposures, infectious diseases, climate change, and local implications. Increasing EH literacy among medical students represents a high-impact educational need. This pilot study, conceived and led by medical students, successfully characterized the EH knowledge gap among medical students and integrated novel discipline-specific learning objectives and discussion points into a pre-existing CBL curriculum. This model may easily be adapted to other institutions' curricula.</AbstractText
|
[
[
"40282146",
"Exploring the Complexity of Children's Math and Vocabulary Learning: The Role of Cognitive, Dispositional, and Parental Factors.",
"Early mathematical and vocabulary skills serve as critical foundations for academic success, yet the mechanisms underlying their development remain complex. This study examines the role of parents' education, children's attentional control, and learning approaches as predictors of kindergarteners' mathematics and vocabulary performance. Using a sample of 149 children aged 60-72 months in Shanghai, China, we conducted a path analysis to explore direct and indirect relationships among these factors. Findings indicate that parental education indirectly predicts math ability through children's learning approaches and attentional control, emphasizing the role of both cognitive and behavioral pathways. Conversely, vocabulary development is directly influenced by parental education and learning approaches, suggesting distinct developmental trajectories for math and language acquisition. These results highlight the interconnected nature of cognitive, behavioral, and environmental influences on early academic performance. Implications for early childhood education emphasize the need for targeted interventions that not only engage parents in fostering language-rich and cognitively stimulating environments but also support children's motivation, persistence, and attentional capacities.</AbstractText"
]
] |
[
[
"40423643",
"Comorbidities and anthropometric parameters in obstructive sleep apnea syndrome: a phenotype-based study.",
"Obstructive Sleep Apnea Syndrome (OSAS) is a heterogeneous syndrome and shows different phenotypic, clinical and physiopathological features. The aim of this study was to examine the relationships between OSAS phenotypes and comorbidities and anthropometric measurements and to identify OSAS phenotypes that should be referred for early diagnosis and treatment.</AbstractText We retrospectively reviewed 600 patients who underwent polysomnography (PSG) in our sleep center. Seven phenotypes were defined as Simple Snoring (SS)-Control, Mild, Moderate and Severe OSAS, Rem Dependent OSAS (RDO), Position Dependent OSAS (PDO) and Rem+Position dependent OSAS (R+PDO). Demographic data, anthropometric measurements and comorbid diseases of the patients were obtained retrospectively from their files. OSAS phenotypes were compared with comorbidities and anthropometric measurements.</AbstractText Severe OSAS was the most common phenotype. Oxygen desaturation index (ODI) and anthropometric measurements showed significant differences between phenotypes (<i This study revealed that OSAS phenotypes exhibit different clinical and anthropometric characteristics and differ in comorbidity risks. HT was found to be higher in severe OSAS, moderate OSAS and R+PDO, and CHD was higher in severe OSAS and RDO. Our study emphasized the importance of phenotypic characteristics as well as AHI in the management of comorbidities in OSAS.</AbstractText"
]
] |
38013916
|
A Deep Learning Based Anti-aliasing Self Super-resolution Algorithm for MRI.
|
High resolution magnetic resonance (MR) images are desired in many clinical applications, yet acquiring such data with an adequate signal-to-noise ratio requires a long time, making them costly and susceptible to motion artifacts. A common way to partly achieve this goal is to acquire MR images with good in-plane resolution and poor through-plane resolution (i.e., large slice thickness). For such 2D imaging protocols, aliasing is also introduced in the through-plane direction, and these high-frequency artifacts cannot be removed by conventional interpolation. Super-resolution (SR) algorithms which can reduce aliasing artifacts and improve spatial resolution have previously been reported. State-of-the-art SR methods are mostly learning-based and require external training data consisting of paired low resolution (LR) and high resolution (HR) MR images. However, due to scanner limitations, such training data are often unavailable. This paper presents an anti-aliasing (AA) and self super-resolution (SSR) algorithm that needs no external training data. It takes advantage of the fact that the in-plane slices of those MR images contain high frequency information. Our algorithm consists of three steps: 1) We build a self AA (SAA) deep network followed by 2) an SSR deep network, both of which can be applied along different orientations within the original images, and 3) recombine the multiple orientations output from Steps 1 and 2 using Fourier burst accumulation. We perform our SAA+SSR algorithm on a diverse collection of MR data without modification or preprocessing other than N4 inhomogeneity correction, and demonstrate significant improvement compared to competing SSR methods.</AbstractText
|
[
[
"28074530",
"Slice profile and B(1) corrections in 2D magnetic resonance fingerprinting.",
"The goal of this study is to characterize and improve the accuracy of 2D magnetic resonance fingerprinting (MRF) scans in the presence of slice profile (SP) and B<sub The SP and B<sub The SP and B<sub This study demonstrates that MRF is sensitive to both SP and B<sub"
]
] |
[
[
"29938010",
"The Parent Trauma Response Questionnaire (PTRQ): development and preliminary validation.",
"<b <b 背景：在儿童遭受创伤之后，父母的反应在促进或阻碍儿童的心理调整方面发挥着重要作用。 然而，由于缺乏有效和可靠的测量方法，要考察创伤后期父母反应的作用不免受到阻碍。目标：本研究的目的是设计并初步验证《父母创伤反应问卷（PTRQ）》，这是一项用于在儿童创伤后，父母自我报告对儿童应对状况的评估和支持的测量工具。方法：我们对365名被试施测了一套有78题目的初始问卷，被试都是经历过创伤性事件的2-19岁的儿童的父母。 我们进行了主轴因子分析，然后通过与父母过度保护的标准化问卷对比评估减少题目后的问卷效度，以及与儿童创伤后心理健康的关联。结果：因子分析产生了三个队父母适应不良评估的测量因素：（i）永久变化/损害，（ii）集中于儿童的脆弱性，以及（iii）自责。 另外，识别五个因素来评估父母对儿童应对的支持：（i）行为逃避，（ii）认知回避，（iii）过度保护，（iv）保持创伤前日常，以及（v）趋近应对。 父母过度保护和儿童创伤后应激症状的测量验证了问卷具有良好的效度。 该问卷还显示出了的良好重测信度。结论：PTRQ是在儿童创伤后的父母认知和应对的有效可靠的自评测量工具。.</AbstractText"
]
] |
39989429
|
Novel plasma biomarkers of amyloid plaque pathology and cortical thickness: Evaluation of the NULISA targeted proteomic platform in an ethnically diverse cohort.
|
Proteomic evaluation of plasma samples could accelerate the identification of novel Alzheimer's disease (AD) biomarkers. We evaluated the novel NUcleic acid Linked Immuno-Sandwich Assay (NULISA) proteomic method in an ethnically diverse cohort.</AbstractText Plasma biomarkers were measured with NULISA in the Human Connectome Project, a predominantly preclinical biracial community cohort in southwestern Pennsylvania. Selected biomarkers were additionally measured using Simoa and Quest immunoassays and compared.</AbstractText On NULISA, phosphorylated tau (p-tau217, p-tau231, and p-tau181), glial fibrillary acidic protein (GFAP), and microtubule-associated protein tau (MAPT-tau) showed the top significant association with amyloid beta (Aβ) positron emission tomography (PET) status, followed by the neuroinflammation markers C-C motif ligand 2 (CCL2), chitotriosidase 1 (CHIT1) and interleukin-8 (CXCL8), and the synaptic marker neurogranin (NRGN). Biomarkers associated with cortical thickness included astrocytic protein chitinase-3-like protein 1 (CHI3L1), cytokine CD40 ligand (CD40LG), brain-derived neurotrophic factor (BDNF), the Aβ-associated metalloprotein TIMP3 (tissue inhibitor of metalloprotein 3), and ficolin 2 (FCN2). Furthermore, moderate to strong between-platform correlations were observed for various assays.</AbstractText NULISA multiplexing advantage allowed concurrent assessment of established and novel plasma biomarkers of Aβ pathology and neurodegeneration.</AbstractText Classical Alzheimer's disease (AD) biomarkers measured using the NUcleic acid Linked Immuno-Sandwich Assay (NULISA) with next-generation sequencing readout (NULISAseq) CNS panel showed strong concordance with those measured using established immunoassay methods from Quanterix and Quest, with glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) exhibiting the strongest correlation. NULISAseq proteomic analysis identified several plasma biomarkers strongly associated with AD pathology in a biracial community cohort of older adults. Notably, phosphorylated tau-217 (p-tau217), GFAP, and p-tau231 displayed the strongest association with amyloid beta (Aβ) pathology, whereas brain-derived neurotrophic factor (BDNF) was strongly associated with neurodegeneration. We demonstrate that plasma biomarker levels could be influenced by age, sex, apolipoprotein E (APOE) genotype, and self-identified race. Specifically, GFAP, NfL, and surfactant protein D (SFTPD) showed a strong association with age; CD63 and S100 calcium-binding protein B (S100B) with self-identified race; synaptosomal-associated protein 25 (SNAP25) with APOE genotype; and serum amyloid A1 (SAA1) and superoxide dismutase 1 (SOD1) with significant sex differences.</AbstractText
|
[
[
"38020757",
"The key role of depression and supramarginal gyrus in frailty: a cross-sectional study.",
"The age-related decrease in reserve and resistance to stressors is recognized as frailty, one of the most significant challenges identified in recent years. Despite a well-acknowledged association of frailty with cognitive impairment, depression, and gray matter morphology, no clear data are available regarding the nature of this relationship. This cross-sectional study aims to disentangle the role of the behavioral, neuropsychological, and neural components as predictors or moderators of frailty.</AbstractText Ninety-six older adults (mean age = 75.49 ± 6.62) were consecutively enrolled and underwent a clinical and MRI (3 T) evaluation to assess frailty, physical activity, global cognitive level, depression, wellbeing, autonomy in daily living, cortical thickness, and subcortical volumes.</AbstractText Results showed a full mediation of depression on the link between cortical thickness and frailty, while the cognitive level showed no significant mediating role. In particular, left supramarginal thickness had a predicting role on depression, that in turn impacted frailty occurrence. Finally, handgrip weakness was an early key indicator of frailty in this study's cohort.</AbstractText These data substantiate the role of depression in mediating the link between neural integrity of the supramarginal gyrus and frailty. In the complexity of frailty, handgrip weakness seems to be an early key indicator. These results are relevant for the design of rehabilitation interventions aimed at reversing the frail condition.</AbstractText"
]
] |
[
[
"40746470",
"Could the sealer thickness affect the filling ability of bioceramic endodontic materials? Evaluation in a simulated physiological condition.",
"Bioceramic sealers must provide filling and dimensional stability over time.</AbstractText To evaluate by micro-computed tomography (micro-CT), the effect of sealer thickness on the physical properties of Bio-C Sealer (BCS) and BioRoot RCS (BR) after immersion in phosphate-buffered saline (PBS) for 7 and 30 days.</AbstractText Extracted bovine teeth were prepared with ProDesign Logic 40/0.05, and the last 4-mm apical of the roots was sectioned. Then, the specimens were filled using the single-cone technique with BCS or BR (<i ANOVA/Tukey, paired, and unpaired t-tests were performed (α =0.05).</AbstractText Sealer thickness did not influence the filling capacity in all conditions tested. After 7 days, BR had a higher volume loss than BCS, with no influence of the sealer thickness. The volumetric loss and percentage of interface gaps were higher for both sealers with GT from 7 to 30 days of immersion. BR with GT showed a higher presence of interface gaps compared to the other groups in all the experimental periods.</AbstractText GT negatively influences the volumetric change and presence of gaps in the material/dentin interface, especially for BR. Both materials demonstrate adequate filling ability regardless of the sealer thickness used.</AbstractText"
]
] |
29434794
|
Biomechanical analysis of brachial plexus injury: Availability of three-dimensional finite element model of the brachial plexus.
|
Adult brachial plexus injuries frequently lead to significant and permanent physical disabilities. Investigating the mechanism of the injury using biomechanical approaches may lead to further knowledge with regard to preventing brachial plexus injuries. However, there are no reports of biomechanical studies of brachial plexus injuries till date. Therefore, the present study used a complex three-dimensional finite element model (3D-FEM) of the brachial plexus to analyze the mechanism of brachial plexus injury and to assess the validity of the model. A complex 3D-FEM of the spinal column, dura mater, spinal nerve root, brachial plexus, rib bone and cartilage, clavicle, scapula, and humerus were conducted. Stress was applied to the model based on the mechanisms of clinically reported brachial plexus injuries: Retroflexion of the cervical, lateroflexion of the cervical, rotation of the cervical, and abduction of the upper limb. The present study analyzed the distribution and strength of strain applied to the brachial plexus during each motion. When the cervical was retroflexed or lateroflexed, the strain was focused on the C5 nerve root and the upper trunk of the brachial plexus. When the upper limb was abducted, strain was focused on the C7 and C8 nerve roots and the lower trunk of the brachial plexus. The results of brachial plexus injury mechanism corresponded with clinical findings that demonstrated the validity of this model. The results of the present study hypothesized that the model has a future potential for analyzing pathological conditions of brachial plexus injuries and other injuries or diseases, including that of spine and spinal nerve root.</AbstractText
|
[
[
"28624567",
"Results of Operative Treatment of Brachial Plexus Injury Resulting from Shoulder Dislocation: A Study with A Long-Term Follow-Up.",
"Injury to the infraclavicular brachial plexus is an uncommon but serious complication of shoulder dislocation. This work aims to determine the effectiveness of operative treatment in patients with this type of injury.</AbstractText Thirty-three patients (26 men and 7 women; mean age, 45 years and 3 months) treated operatively for brachial plexus injury resulting from shoulder dislocation between the years 2000 and 2013 were included in this retrospective case series. Motor function of affected limbs was assessed pre- and postoperatively with the use of the British Medical Research Council (BMRC) scale. Sensory function in the areas innervated by ulnar and median nerves was evaluated with the BMRC scale modified by Omer and Dellon and in the remaining areas with the Highet classification. Follow-up lasted 2-10 years (mean, 5.1 years).</AbstractText Good postoperative recovery of nerve function was observed in 100% of musculocutaneous, 93.3% of radial, 66.7% of median, 64% of axillary, and 50% of ulnar nerve injuries. No recovery was observed in 5.6% of median, 6.7% of radial, 10% of ulnar, and 20% of axillary nerve injuries. Injury to a single nerve was associated with worse treatment outcome than multiple nerve injury.</AbstractText Obtaining improvement in peripheral nerve function after injury resulting from shoulder dislocation may require operative intervention. The type of surgical procedure depends on intraoperative findings: sural nerve grafting in cases of neural elements' disruption, internal neurolysis when intraneural fibrosis is observed, and external neurolysis in the remaining cases. The outcomes of surgical treatment are good, and the risk of intra- and postoperative complications is low.</AbstractText"
]
] |
[
[
"28525629",
"The Association of Perceived Memory Loss with Osteoarthritis and Related Joint Pain in a Large Appalachian Population.",
"Previous studies have documented memory impairment in several chronic pain syndromes. However, the potential link between memory loss and osteoarthritis (OA), the second most common cause of chronic pain, remains little explored. In this cross-sectional study, we examine the association of perceived memory loss to OA and assess the potential mediating influence of sleep and mood disturbance in a large Appalachian population.</AbstractText Cross-sectional.</AbstractText US Ohio Valley.</AbstractText A total of 21,982 Appalachian adults age 40 years or older drawn from the C8 Health Project (N = 19,004 adults without and 2,478 adults with OA). All participants completed a comprehensive health survey between 2005 and 2006. Medical history, including physician diagnosis of OA, lifestyle factors, short- and long-term memory loss, sleep quality, and mood were assessed via self-report.</AbstractText After adjustment for demographic, lifestyle, health-related, and other factors, participants with OA were almost three times as likely to report frequent memory loss (adjusted odds ratios [ORs] for short- and long-term memory loss, respectively = 2.7, 95% confidence interval [CI] = 2.2-3.3, and 2.6, 95% CI = 2.0-3.3). The magnitude of these associations increased significantly with rising frequency of reported joint pain (adjusted OR for OA with frequent joint pain vs no OA = 3.3, 95% CI = 2.6-4.1, Ptrend < 0.00001). Including measures of mood and sleep impairment attenuated but did not eliminate these associations (ORs for any memory loss = 2.0, 95% CI = 1.6-2.4, and 2.1, 95% CI = 1.7-2.8, adjusted for sleep and mood impairment, respectively; OR = 1.8, 95% CI = 1.4-2.2, adjusted for both factors).</AbstractText In this large cross-sectional study, OA and related joint pain were strongly associated with perceived memory loss; these associations may be partially mediated by sleep and mood disturbance.</AbstractText"
]
] |
15528098
|
Semantic processing of Chinese in left inferior prefrontal cortex studied with reversible words.
|
This study utilized fast event-related fMRI with reversible words to examine the role of left inferior prefrontal cortex (PFC) in semantic processing of Chinese. As a special linguistic phenomenon in Chinese, a reversible word is a two-character word (AB) that, when read from right to left (BA), opposite to the normal left to right reading direction, is also a real word. The two words, AB and BA, can have very different meanings. Fourteen native Chinese saw a reversible word (BA) and were asked to read it backward silently to obtain the meaning of AB, defined as the target meaning. They then saw two test words and decided which of the two was semantically related to the target meaning. Activity in a subregion of BA47 was found to be modulated by the extent to which irrelevant semantic activation of the distractor word BA interfered with semantic retrieval of the target word AB. This finding demonstrated the involvement of the left inferior PFC in the control processes of semantic retrieval in Chinese. In addition, comparing conditions using reversible with that using nonreversible words, we found evidence suggesting a semantic/phonological functional subdivision in left inferior PFC, consistent with that in English.</AbstractText
|
[
[
"33540359",
"The only-child effect in the neural and behavioral signatures of trust revealed by fNIRS hyperscanning.",
"In daily life, trust is important in interpersonal interactions. However, little is known about interpersonal brain synchronization with respect to trust; in particular, the differences between individuals with and without siblings are not clear. Therefore, this study applied functional near-infrared spectroscopy hyperscanning in a sequential reciprocal-trust task. We divided pairs of participants (strangers) into two groups according to their only-child status. The two strangers interacted with one another in an online trust game while their brain activities in the medial prefrontal cortex (mPFC) and the right temporoparietal junction (rTPJ) were measured. The behavioral results revealed that compared with the non-only-child group, the only-child group exhibited lower repayment, less reciprocation, and less cooperative decisions during the process. In addition, the brain imaging results showed that the interpersonal synchronization of the mPFC in the only-child group was significantly weaker than that in the non-only-child group. Our findings demonstrate neurobehavioral support for the only-child effect in terms of the trust by revealing that an only child shows less trust than does a non-only-child, resulting in lower inter-brain coherence.</AbstractText"
]
] |
[
[
"40216214",
"Brain-based gene expression and corresponding behavioural relevance of risk genes for broad antisocial behaviour.",
"Antisocial behaviour (ASB) involves persistent irresponsible, delinquent activities violating rights and safety of others. A meta-analysis of genome-wide association studies revealed significant genetic associations with ASB, yet their brain expression patterns and behavioural relevance remain unclear. Our investigation of fifteen genes associated with ASB examined their biological role and distribution across tissues, integrating post-mortem brain sample data from the Allen-Human-Brain Atlas and the Genotype-Tissue Expression project. We found that these genes were differentially expressed in the brain, particularly in regions like the cerebellum, putamen, and caudate, and were notably downregulated in the pancreas. Single cell type expression analysis revealed that ASB-associated genes had strong correlations with ductal and endothelial cells in the pancreas, indicating a possible metabolic influence on ASB. Certain genes like NTN1, SMAD5, NCAM2, and CDC42EP3 displayed specificity for cognitive terms including chronic pain, heart rate, and aphasia. These expression patterns aligned with neurocognitive domains related to thinking, and learning, distress, motor skills, as determined by fMRI analysis. This study connects specific brain gene expression with potential genetic and metabolic factors in ASB, offering novel insights into its biological basis and possible interdisciplinary approaches to understanding and addressing aggressive behaviours.</AbstractText"
]
] |
40088962
|
Dual targeting of the mitochondrial Lon peptidase 1 and the chymotrypsin-like proteasome activity as a potential therapeutic strategy in malignant astrocytoma models.
|
Malignant astrocytomas are aggressive primary brain tumors characterized by extensive hypoxia-induced, mitochondria-dependent changes such as altered respiration, increased chymotrypsin-like (CT-L) proteasome activity, decreased apoptosis, drug resistance, stemness, and increased invasiveness. Mitochondrial Lon Peptidase 1 (LonP1) overexpression and increased CT-L proteasome activity are biomarkers of an aggressive high-grade phenotype and found to be associated with recurrence and poor patient survival. In preclinical models, small molecule agents targeting either LonP1 or the proteasome CT-L activity have anti-astrocytoma activity. Here, we present evidence that the dual inhibition of LonP1 and CT-L proteasome activity effectively induces ROS production, leading to apoptosis in malignant astrocytoma established cell lines and patient-derived glioma stem cell-like cultures. We also evaluated a novel small molecule, BT317, derived from the coumarinic compound 4 (CC4) using structure-activity modeling, which we found to inhibit both LonP1 and CT-L proteasome activity. Using gain- and loss-of-function genetic models, we discovered that LonP1 is both necessary and sufficient to drive BT317 drug sensitivity in established and patient-derived glioma stem-like cells by generating ROS and inducing apoptosis. In vitro, BT317 had activity as a single agent but, more importantly, enhanced synergy with the standard of care commonly used chemotherapeutic temozolomide (TMZ). In an orthotopic xenograft astrocytoma model, BT317 crossed the blood-brain barrier, showed selective activity at the tumor site, and demonstrated therapeutic efficacy as a single agent and combined with TMZ. BT317 defines an emerging class of LonP1 and CT-L inhibitors that exhibited promising anti-tumor activity and could be a potential candidate for malignant astrocytoma therapeutics. SIMPLE SUMMARY: Malignant astrocytoma patients have poor clinical outcomes, and novel treatments are needed to limit tumor recurrence and improve their overall survival. These tumors have a malignant phenotype mediated by altered mitochondrial metabolism, abnormal protein processing, and adaptation to hypoxia. We have previously published that astrocytomas are especially vulnerable to proteasome inhibitors as well as to inhibitors of the mitochondrial Lon Peptidase 1 (LonP1), but the effect of combining the two strategies has not been reported. Here, we present evidence that the dual inhibition of LonP1 and Chymotrypsin-like (CT-L) proteasome activity effectively induces cellular reactive oxygen species (ROS) production, leading to apoptosis in malignant astrocytoma established cell lines and patient-derived glioma stem cell-like cultures. We developed BT317, a small molecule dual inhibitor, which crosses the blood-brain barrier and shows strong synergy with the standard of care, temozolomide (TMZ), in the astrocytoma cell lines independent of their isocitrate dehydrogenase (IDH) profile and in an orthotopic glioma murine model. This preclinical study demonstrated the potential of dual LonP1 and CT-L proteasome inhibition as a novel therapeutic strategy for malignant astrocytoma and provides insight for future clinical translational studies alone or in combination with other chemotherapies.</AbstractText
|
[
[
"33204688",
"Hemangiopericytoma: Incidence, Treatment, and Prognosis Analysis Based on SEER Database.",
"Hemangiopericytomas are rare tumors derived from pericytes surrounding the blood vessels. The clinicopathological characteristics and prognosis of hemangiopericytoma patients remain mostly unknown. In this retrospective cohort study, we assessed the clinicopathological characteristics of hemangiopericytoma patients, as well as the clinical usefulness of different treatment modalities. <i Data from 1474 patients were analyzed in our study cohort (hemangiopericytoma: <i Our findings suggested that hemangiopericytoma had a similar prognosis with hemangioendothelioma. Surgery was the only effective treatment that provided survival benefits in hemangiopericytoma patients, while the clinical usefulness of adjuvant chemotherapy or radiotherapy was limited.</AbstractText"
]
] |
[
[
"40753796",
"Acupressure as a non-pharmacological treatment for depression: Neurophysiological, biochemical, and psychological mechanisms.",
"Depression is a common and serious psychological disorder with high prevalence and recurrence rates. Still, there are treatment-resistant depression in the clinic, so exploring other treatments is necessary. Acupressure is a non-invasive therapeutic method based on the principles of traditional Chinese medicine, which promotes health and relieves symptoms by applying pressure to specific acupoints on the body. Modern medical research on acupressure has gradually deepened, explaining and validating it through multiple perspectives, e.g., physiology, neurology, and biochemistry. However, the mechanisms underlying the treatment of depression with acupressure, the adoption of a multidisciplinary model of collaboration in treatment, and the improvement of the quality of related research have not yet been thoroughly described. Therefore, the present review summarized the mechanisms, including the neurophysiological, biochemical, and psychological mechanisms behind the treatment of depression with acupressure, its strengths (e.g., no side effects, easy operation, and good patient compliance), and limitations (e.g., individual differences in effects and lack of large-scale systematic studies) in treatment of depression and researches, and its potential for collaboration with other therapies (e.g., acupressure with medication, psychotherapy, and other Chinese medicine), and multidisciplinary approaches.</AbstractText"
]
] |
26041961
|
Magnetic resonance imaging and spectroscopy in hepatic encephalopathy.
|
Hepatic encephalopathy is a brain alteration associated to liver failure that produces cognitive impairments at long term. Neuroimaging are non-invasive methods for the study of the brain by means of spectroscopy and imaging techniques. These technologies give huge information about cerebral metabolism and water distribution to explore brain pathways involved in the pathogenesis of hepatic encephalopathy. Furthermore, new magnetic resonance implementations such as voxel-based morphometry or resting-state functional magnetic resonance imaging allow studying brain atrophy and neuronal connectivity of the cerebral network involved in the neurocognitive impairments observed in the patients. The development of magnetic resonance technology will generate handy tools for the brain study of liver failure to elucidate the time-course of the pathology and thus to obtain an early diagnosis of cerebral complications.</AbstractText
|
[
[
"18321730",
"Myelin water imaging of multiple sclerosis at 7 T: correlations with histopathology.",
"Myelin water imaging (MWI) promises to be invaluable in understanding neurological diseases like MS. However, a limitation of MWI is signal to noise ratio. Recently, a number of investigators have performed MWI at field strengths higher than 1.5 T. Our goal was to determine if myelin water imaging at increased SNR, arising from the use of a small bore 7 T MR system with optimized coil geometry, enables the production of superior myelin water maps with increased spatial detail and enables better correlations with histology. Ten formalin-fixed MS brain samples underwent a 32-echo T(2) relaxation experiment which measured myelin water fraction (MWF) on a 7-T animal MRI scanner. MWF correlated strongly qualitatively and quantitatively with luxol fast blue staining for myelin [mean (range): R(2)=0.78 (0.56-0.95), p<0.0001]. The quality and detail of 7 T myelin water maps were far superior to that previously seen at 1.5 T, allowing for visualization of fine structures such as the normal prominent myelination of the deeper cortical layers, the alveus of the hippocampus and rings of preserved myelin in a concentric Balo's lesion. 7 T imaging will allow detailed assessment of myelin pathology to a degree not possible with lower field strengths.</AbstractText"
]
] |
[
[
"25860885",
"Serum albumin is associated with peripheral nerve function in patients with type 2 diabetes.",
"The aim of this study is to investigate the association between serum albumin concentrations and nerve conduction (NC) parameters in Chinese patients with type 2 diabetes (T2DM). A total of 409 T2DM patients were enrolled between October 2010 and April 2014. All participants underwent nerve conduction studies. The composite Z scores for NC parameters including conduction velocity (CV), amplitude, and latency were calculated as well. Serum albumin was measured by Bromcresol Green dye-binding method. The composite Z scores of CV and amplitude increased with the increasing albumin tertiles (test for trend, both P < 0.001), while the composite Z score of latency decreased with increasing albumin tertiles (test for trend, P < 0.001). After adjusting for age, sex, duration, and HbA1c, higher serum albumin concentrations were associated with higher composite Z scores of CV (β = 0.314, P < 0.001), amplitude (β = 0.279, P < 0.001), and lower composite Z score of latency (β = -0.279, P < 0.001). When participants were stratified into albuminuria and normoalbuminuria group, we found the associations of serum albumin with composite Z scores of NC parameters remained significant only in the albuminuria group (CV Z score: β = 0.253, P = 0.002; amplitude Z score: β = 0.233, P = 0.006; latency Z score: β = -0.217 P = 0.013) after further adjustment for urinary albumin to creatinine ratio. The optimal cutoff point of serum albumin to indicate abnormal peripheral nerve function was 36.75 g/L in T2DM patients with albuminuria, with a sensitivity of 65.6 % and a specificity of 78.0 %. Serum albumin was independently associated with peripheral nerve function in T2DM patients, especially in those with albuminuria. Serum albumin could be a potential biomarker for diabetic peripheral neuropathy.</AbstractText"
]
] |
35467010
|
Different characteristics of cortical spreading depression in the sleep and wake states.
|
The objective of this study is to characterize the effects of the sleep-wake cycle on neurovascular and behavioral characteristics of cortical spreading depression (CSD).</AbstractText There is an important bi-directional relationship between migraine and the sleep-wake cycle, but the basic mechanisms of this relationship are poorly understood.</AbstractText We have developed a minimally invasive microchip system to continuously monitor cerebral blood volume (CBV) with optical intrinsic signal (OIS), head movement, and multiple other physiological and behavioral parameters in freely behaving mice over weeks. Behavior is also monitored with simultaneous video recording. This system can also be used to intermittently trigger and record CSD and accompanying neurovascular and behavioral responses. CSD was triggered optically in different stages of the sleep-wake cycle.</AbstractText The optical stimulus threshold to trigger CSD was significantly higher in the wake state compared to sleep (stimulation duration = 16.4 ± 9.7 s vs. 10.8 ± 5.8 s, p = 0.037, n = 6 mice). CSD evoked in the wake versus sleep state produced changes in CBV that were smaller (largest relative change -4.5 ± 5.0% ∆OIS vs. -14.3 ± 8.5% ∆OIS, p = 0.001) and shorter in duration (33:22 ± 6:37 vs. 49:42 ± 8:05 min:s, p = 0.012, n = 6 mice). The threshold for CSD and kinetics of associated CBV changes were correlated with the time since falling asleep or awakening (n = 47 CSDs in 6 mice). CSD triggered in the wake state was associated with a transient freezing behavior. CSD triggered during sleep typically caused a transient awakening and behavioral response. This was followed by a return to sleep until recovery from the sustained phase of decreased CBV that occurred 30-60 min later, at which time there was consistent awakening with behaviors similar to those that occurred at CSD onset. CSD triggered in the wake state evoked a transient decrease in heart rate (from 11.9 ± 0.8 to 9.6 ± 0.8 Hz, p = 0.002, n = 5), whereas when triggered in the sleep state there was a transient increase in HR (from 7.5 ± 0.4 Hz to 9.3 ± 1.1 Hz, p = 0.016, n = 5).</AbstractText The sleep-wake cycle has significant effects on CSD that may have relevance to the clinical presentations of migraine and brain injury.</AbstractText
|
[
[
"32677977",
"Compressed-sensing accelerated 4D flow MRI of cerebrospinal fluid dynamics.",
"4D flow magnetic resonance imaging (MRI) of CSF can make an important contribution to the understanding of hydrodynamic changes in various neurological diseases but remains limited in clinical application due to long acquisition times. The aim of this study was to evaluate the accuracy of compressed SENSE accelerated MRI measurements of the spinal CSF flow.</AbstractText In 20 healthy subjects 4D flow MRI of the CSF in the cervical spine was acquired using compressed sensitivity encoding [CSE, a combination of compressed sensing and parallel imaging (SENSE) provided by the manufacturer] with acceleration factors between 4 and 10. A conventional scan using SENSE was used as reference. Extracted parameters were peak velocity, absolute net flow, forward flow and backward flow. Bland-Altman analysis was performed to determine the scan-rescan reproducibility and the agreement between SENSE and compressed SENSE. Additionally, a time accumulated flow error was calculated. In one additional subject flow of the spinal canal at the level of the entire spinal cord was assessed.</AbstractText Averaged acquisition times were 10:21 min (SENSE), 9:31 min (CSE4), 6:25 min (CSE6), 4:53 min (CSE8) and 3:51 min (CSE10). Acquisition of the CSF flow surrounding the entire spinal cord took 14:40 min. Bland-Altman analysis showed good agreement for peak velocity, but slight overestimations for absolute net flow, forward flow and backward flow (< 1 ml/min) in CSE4-8. Results of the accumulated flow error were similar for CSE4 to CSE8.</AbstractText A quantitative analysis of acceleration factors CSE4-10 showed that CSE with an acceleration factor up to 6 is feasible. This allows a scan time reduction of 40% and enables the acquisition and analysis of the CSF flow dynamics surrounding the entire spinal cord within a clinically acceptable scan time.</AbstractText"
]
] |
[
[
"36573133",
"Weakly-supervised learning method for the recognition of potato leaf diseases.",
"As a crucial food crop, potatoes are highly consumed worldwide, while they are also susceptible to being infected by diverse diseases. Early detection and diagnosis can prevent the epidemic of plant diseases and raise crop yields. To this end, this study proposed a weakly-supervised learning approach for the identification of potato plant diseases. The foundation network was applied with the lightweight MobileNet V2, and to enhance the learning ability for minute lesion features, we modified the existing MobileNet-V2 architecture using the fine-tuning approach conducted by transfer learning. Then, the atrous convolution along with the SPP module was embedded into the pre-trained networks, which was followed by a hybrid attention mechanism containing channel attention and spatial attention submodules to efficiently extract high-dimensional features of plant disease images. The proposed approach outperformed other compared methods and achieved a superior performance gain. It realized an average recall rate of 91.99% for recognizing potato disease types on the publicly accessible dataset. In practical field scenarios, the proposed approach separately attained an average accuracy and specificity of 97.33% and 98.39% on the locally collected image dataset. Experimental results present a competitive performance and demonstrate the validity and feasibility of the proposed approach.</AbstractText"
]
] |
38295508
|
Comparison of quantitative REM without atonia parameters in isolated REM sleep behavior disorder and early untreated Parkinson's disease.
|
To analyze REM sleep without atonia (RWA) metrics in patients with isolated REM sleep behavior disorder (iRBD), Parkinson's disease (PD) and healthy subjects and compare them in terms of degree of presumed brainstem damage.</AbstractText Forty-nine iRBD patients, 62 PD patients and 38 healthy controls were included into the analysis. Detailed polysomnographic and clinical data including motor, olfactory, autonomic, and cognitive assessment were obtained in all participants and subsequently compared within groups without RBD (i.e., healthy controls, PD-RBD-) and with RBD (i.e., iRBD, PD-RBD+). SINBAR criteria were used to score RWA.</AbstractText Twenty-one PD patients (33.8 %) had RBD. When comparing PD-RBD-patients and controls, RWA tonic (p = 0.001) and RWA mixed (p = 0.03) were higher in PD-RBD-group. PD-RBD-patients had worse olfactory function than controls (p < 0.001); no significant difference in autonomic or cognitive function was registered. There were no significant differences in RWA parameters when comparing iRBD and PD-RBD + groups. iRBD patients had better olfactory function than PD-RBD+ (p = 0.006); no significant difference in autonomic or cognitive function was registered. PD-RBD + had worse autonomic (p = 0.006) and olfactory (p = 0.001) but not motor and cognitive function compared to PD-RBD-.</AbstractText Untreated de-novo PD patients without RBD have increased RWA metrics compared to healthy subjects indicating subclinical degeneration of brainstem nuclei responsible for RWA. iRBD patients do not differ in RWA metrics from untreated de-novo PD patients with premotor RBD suggesting a similar level of brainstem degeneration caudal to substantia nigra in both groups. Groups with RBD are associated with autonomic dysfunction.</AbstractText
|
[
[
"38701162",
"Oscillation-Specific Nodal Differences in Parkinson's Disease Patients with Anxiety.",
"Parkinson's disease (PD) is a common neurodegenerative disorder that is predominantly known for its motor symptoms but is also accompanied by non-motor symptoms, including anxiety.</AbstractText The underlying neurobiological substrates and brain network changes associated with comorbid anxiety in PD require further exploration.</AbstractText An analysis of oscillation-specific nodal properties in patients with and without anxiety was conducted using resting-state functional magnetic resonance imaging (rs-fMRI) and graph theory. We used a band-pass filtering approach to differentiate oscillatory frequency bands for subsequent functional connectivity (FC) and graph analyses.</AbstractText The study included 68 non-anxiety PD (naPD) patients, 62 anxiety PD (aPD) patients, and 64 healthy controls (NC). Analyses of nodal betweenness centrality (BC), degree centrality (DC), and efficiency were conducted across multiple frequency bands. The findings indicated no significant differences in BC among naPD, aPD, and NC within the 0.01-0.08 Hz frequency range. However, we observed a specific reduction in BC at narrower frequency ranges in aPD patients, as well as differing patterns of change in DC and efficiency, which are believed to reflect the neurophysiological bases of anxiety symptoms in PD.</AbstractText Differential oscillation-specific nodal characteristics have been identified in PD patients with anxiety, suggesting potential dysregulations in brain network dynamics. These findings emphasize the complexity of brain network alterations in anxiety-associated PD and identify oscillatory frequencies as potential biomarkers. The study highlights the importance of considering oscillatory frequency bands in the analysis of brain network changes.</AbstractText"
]
] |
[
[
"39160029",
"Haemodynamic effects of non-Newtonian fluid blood on the abdominal aorta before and after double tear rupture.",
"Intimal tears caused by aortic dissection can weaken the arterial wall and lead to aortic aneurysms. However, the effect of different tear states on the blood flow behaviour remains complex. This study uses a novel approach that combines numerical haemodynamic simulation with in vitro experiments to elucidate the effect of arterial dissection rupture on the complex blood flow state within the abdominal aneurysm and the endogenous causes of end-organ malperfusion.</AbstractText Based on the CT imaging data and clinical physiological parameters, the overall arterial models including aortic dissection and aneurysm with single tear and double tear were established, and the turbulence behaviours and haemodynamic characteristics of arterial dissection and aneurysm under different blood pressures were simulated by using non-Newtonian flow fluids with the pulsatile blood flow rate of the clinical patients as a cycle, and the results of the numerical simulation were verified by in vitro simulation experiments.</AbstractText Hemodynamic simulations revealed that the aneurysm and single-tear false lumen generated a maximum pressure of 320.591 mmHg, 267 % over the 120 mmHg criterion. The pressure differential generates reflux, leading to a WSS of 2247.9 Pa at the TL inlet and blood flow velocities of up to 6.41 m/s inducing extend of the inlet. DTD Medium FL instantaneous WP above 120 mmHg Standard 151 % Additionally, there was 82.5 % higher flow in the right iliac aorta than in the left iliac aorta, which triggered malperfusion. Thrombus was accumulated distal to the tear and turbulence. These results are consistent with the findings of the in vitro experiments.</AbstractText This study reveals the haemodynamic mechanisms by which aortic dissection induces aortic aneurysms to produce different risk states. This will contribute to in vitro simulation studies as a new fulcrum in the process of moving from numerical simulation to clinical trials.</AbstractText"
]
] |
28546311
|
Evidence for Functional Networks within the Human Brain's White Matter.
|
Investigation of the functional macro-scale organization of the human cortex is fundamental in modern neuroscience. Although numerous studies have identified networks of interacting functional modules in the gray-matter, limited research was directed to the functional organization of the white-matter. Recent studies have demonstrated that the white-matter exhibits blood oxygen level-dependent signal fluctuations similar to those of the gray-matter. Here we used these signal fluctuations to investigate whether the white-matter is organized as functional networks by applying a clustering analysis on resting-state functional MRI (RSfMRI) data from white-matter voxels, in 176 subjects (of both sexes). This analysis indicated the existence of 12 symmetrical white-matter functional networks, corresponding to combinations of white-matter tracts identified by diffusion tensor imaging. Six of the networks included interhemispheric commissural bridges traversing the corpus callosum. Signals in white-matter networks correlated with signals from functional gray-matter networks, providing missing knowledge on how these distributed networks communicate across large distances. These findings were replicated in an independent subject group and were corroborated by seed-based analysis in small groups and individual subjects. The identified white-matter functional atlases and analysis codes are available at http://mind.huji.ac.il/white-matter.aspx Our results demonstrate that the white-matter manifests an intrinsic functional organization as interacting networks of functional modules, similarly to the gray-matter, which can be investigated using RSfMRI. The discovery of functional networks within the white-matter may open new avenues of research in cognitive neuroscience and clinical neuropsychiatry.<b
|
[
[
"30911222",
"Strength and Temporal Variance of the Default Mode Network to Investigate Chronic Mild Traumatic Brain Injury in Service Members with Psychological Trauma.",
"There is a significant number of military personnel with a history of mild traumatic brain injury (mTBI) who suffer from comorbid posttraumatic stress symptoms (PTS). Although there is evidence of disruptions of the default mode network (DMN) associated with PTS and mTBI, previous studies have only studied static connectivity while ignoring temporal variability of connectivity.</AbstractText To assess DMN disrupted or dysregulated neurocircuitry, cognitive functioning, and psychological health of active-duty military with mTBI and PTS.</AbstractText U.S. Army soldiers with PTS (n = 14), mTBI + PTS (n = 25), and healthy controls (n = 21) voluntarily completed a cognitive and symptom battery. In addition, participants had magnetic resonance imaging (MRI) to assess both static functional connectivity (SFC) and variance of dynamic functional connectivity (vDFC) of the DMN.</AbstractText Both the PTS and mTBI + PTS groups had significant symptoms, but only the comorbid group had significant decrements in cognitive functioning. Both groups showed less stable and disrupted neural signatures of the DMN, mainly constituting the cingulate-frontal-temporal-parietal attention network. Specifically, the PTS group showed a combination of both <i Findings suggest that individuals with PTS and mTBI + PTS have a propensity for accentuated generation of thoughts, feelings, sensations, and/or images while in a resting state. Compared with controls, only the PTS group was associated with accentuated variability of the <i"
]
] |
[
[
"12574424",
"Formation of complement membrane attack complex in mammalian cerebral cortex evokes seizures and neurodegeneration.",
"The complement system consists of >30 proteins that interact in a carefully regulated manner to destroy invading bacteria and prevent the deposition of immune complexes in normal tissue. This complex system can be activated by diverse mechanisms proceeding through distinct pathways, yet all converge on a final common pathway in which five proteins assemble into a multimolecular complex, the membrane attack complex (MAC). The MAC inserts into cell membranes to form a functional pore, resulting in ion flux and ultimately osmotic lysis. Immunohistochemical evidence of the MAC decorating neurons in cortical gray matter has been identified in multiple CNS diseases, yet the deleterious consequences, if any, of MAC deposition in the cortex of mammalian brain in vivo are unknown. Here we demonstrate that the sequential infusion of individual proteins of the membrane attack pathway (C5b6, C7, C8, and C9) into the hippocampus of awake, freely moving rats induced both behavioral and electrographic seizures as well as cytotoxicity. The onset of seizures occurred during or shortly after the infusion of C8/C9. Neither seizures nor cytotoxicity resulted from the simultaneous infusion of all five proteins premixed in vitro. The requirement for the sequential infusion of all five proteins together with the temporal relationship of seizure onset to infusions of C8/C9 implies that the MAC was formed in vivo and triggered both seizures and cytotoxicity. Deposition of the complement MAC in cortical gray matter may contribute to epileptic seizures and cell death in diverse diseases of the human brain.</AbstractText"
]
] |
39111111
|
Post-treatment alterations in white matter integrity in PTSD: Effects on symptoms and functional connectivity a secondary analysis of an RCT.
|
Post-traumatic stress disorder (PTSD) has been linked to altered communication within the limbic system, including reduced structural connectivity in the uncinate fasciculus (UNC; i.e., decreased fractional anisotropy; FA) and reduced resting-state functional connectivity (RSFC) between the hippocampus and ventromedial prefrontal cortex (vmPFC). Previous research has demonstrated attenuation of PTSD symptoms and alterations in RSFC following exposure-based psychotherapy. However, the relationship between changes in structural and functional connectivity patterns and PTSD symptoms following treatment remains unclear. To investigate this, we conducted a secondary analysis of data from a randomized clinical trial of intensive exposure therapy, evaluating alterations in UNC FA, hippocampus-vmPFC RSFC, and PTSD symptoms before (pre-treatment), 7 days after (post-treatment), and 30 days after (follow-up) the completion of therapy. Our results showed that post-treatment changes in RSFC were positively correlated with post-treatment and follow-up changes in UNC FA and that post-treatment changes in UNC FA were positively correlated with post-treatment and follow-up changes in PTSD symptoms. These findings suggest that early changes in functional connectivity are associated with sustained changes in anatomical connectivity, which in turn are linked to reduced PTSD symptom severity.</AbstractText
|
[
[
"37185137",
"Photochemically induced thalamus infarction impairs cognition in a mouse model.",
"Small subcortical infarcts account for up to 25% of ischaemic strokes. Thalamus is one of the subcortical structures that commonly manifest with lacunar infarcts on MRI of the brain. Studies have shown that thalamus infarction is associated with cognitive decline. However, due to the lack of proper animal models, little is known about the mechanism. We aimed to establish a focal thalamus infarction model, characterise the infarct lesion and assess functional effects.</AbstractText Male C57BL/6J mice were anaesthetised, and Rose Bengal dye was injected through the tail vein. The right thalamus was illuminated with green laser light by stereotactic implantation of optic fibre. Characteristics of the infarct and lesion evolution were evaluated by histological analysis and 7T MRI at various times. The cognitive and neurological functions were assessed by behavioural tests. Retrograde tracing was performed to analyse neural connections.</AbstractText An ischaemic lesion with small vessel occlusion was observed in the thalamus. It became a small circumscribed infarct with reactive astrocytes accumulated in the infarct periphery on day 21. The mice with thalamic infarction demonstrated impaired learning and memory without significant neurological deficits. Retrogradely labelled neurons in the retrosplenial granular cortex were reduced.</AbstractText This study established a mouse model of thalamic lacunar infarction that exhibits cognitive impairment. Neural connection dysfunctions may play a potential role in post-stroke cognitive impairment. This model helps to clarify the pathophysiology of post-stroke cognitive impairment and to develop potential therapies.</AbstractText"
]
] |
[
[
"39203743",
"Possible Extracellular Signals to Ameliorate Sarcopenia in Response to Medium-Chain Triglycerides (8:0 and 10:0) in Frail Older Adults.",
"In frail older adults (mean age 85 years old), a 3-month supplementation with a low dose (6 g/day) of medium-chain triglycerides (MCTs; C8:0 and C10:0) given at a meal increased muscle mass and function, relative to supplementation with long-chain triglycerides (LCTs), but it decreased fat mass. The reduction in fat mass was partly due to increased postprandial energy expenditure by stimulation of the sympathetic nervous system (SNS). However, the extracellular signals to ameliorate sarcopenia are unclear. The following three potential extracellular signals to increase muscle mass and function after MCT supplementation are discussed: (1) Activating SNS-the hypothesis for this is based on evidence that a beta2-adrenergic receptor agonist acutely (1-24 h) markedly upregulates isoforms of peroxisomal proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) mRNAs, promotes mitochondrial biogenesis, and chronically (~1 month) induces muscle hypertrophy. (2) An increased concentration of plasma acyl-ghrelin stimulates growth hormone secretion. (3) A nitrogen-sparing effect of ketone bodies, which fuel skeletal muscle, may promote muscle protein synthesis and prevent muscle protein breakdown. This review will help guide clinical trials of using MCTs to treat primary (age-related) sarcopenia.</AbstractText"
]
] |
37838358
|
Management of Cholinergic Rebound After Abrupt Withdrawal of Clozapine: A Case Report and Systematic Literature Review.
|
Cholinergic discontinuation symptoms, also known as "cholinergic rebound," from abrupt clozapine discontinuation are characterized by a range of somatic and psychiatric symptoms.</AbstractText The objective of this study was to describe the clinical features and management options for clozapine withdrawal-associated cholinergic rebound syndrome (henceforth referred to as CWCRS) and present an illustrative case report.</AbstractText Based on a literature search of the databases PubMed, OVID Medline, and Embase as well as reviewing reference lists of relevant past reviews, we carried out a systematic review of case reports on the management of CWCRS from 1946 to 2023.</AbstractText We identified 10 previously published articles on the clinical management of CWCRS, with a total of 18 patients (6 female, 12 male) with an average age of 43 years (standard deviation 14). Half of the patients had a history of tardive dyskinesia. The mean dose of clozapine before discontinuation was 351 mg/day, with duration of clozapine treatment ranging from 3 weeks to 9 years. Clozapine was the most effective treatment, followed by benztropine.</AbstractText Given the small number of cases and the nonexperimental nature of the available studies, this review could not provide reliable data to guide management of CWCRS. The findings, however, suggest that clozapine may be more effective than other commonly used treatment options. With the high rates of discontinuation among patients on clozapine, there is a pressing need for further research into the epidemiology, natural history, and management of clozapine withdrawal syndromes.</AbstractText
|
[
[
"36449471",
"Impact-Tardive Dyskinesia (Impact-TD) Scale: A Clinical Tool to Assess the Impact of Tardive Dyskinesia.",
"<b"
]
] |
[
[
"39554587",
"Plasma levels of progranulin, a tumorigenic protein, are persistently elevated during the first month after minimally invasive colorectal cancer resection.",
"Progranulin (PGRN), also identified as Precursor cell-derived growth factor (PCDGF), is a glycoprotein that is expressed and released ubiquitously. PGRN is plays a crucial role in regulating cell proliferation, differentiation, and pathological pathways. PGRN overexpression has been noted in many cancers and plays an important role in wound healing. Surgery's impact on PGRN levels is unknown. The aim of this study was to assess the levels of plasma PGRN before during the first month after minimally invasive colorectal resection (MICR) for colorectal cancer (CRC) resection.</AbstractText CRC patients who were enrolled in a data/plasma bank approved by an Institutional Review Board and underwent MICR for whom adequate plasma samples were available were studied. Blood samples were obtained before surgery and at different time intervals after the operation and late samples were grouped into 7-day blocks and considered as single time points. PGRN levels (pg/mL) were determined in duplicate via ELISA and reported as median and 95% confidence interval (95% CI) values. The paired <i Preoperative and 1 or more late postoperative plasma sample were available for 93 MICR CRC patients. The distribution of cancer stages in the final analysis was: stage I accounted for 37% of cases, stage II for 27%, stage III for 32%, and stage IV for 4%. The median preoperative PGRN level was 50.69 pg/mL, 95% CI: 47.71-56.30, n=93. When compared to preoperative levels, significantly elevated (P<0.001) median levels (pg/mL) were noted on postoperative day (POD) 1 (64.78, 95% CI: 60.86-68.83, n=92), POD 3 (69.15, 95% CI: 66.43-74.32, n=85), POD 7-13 (63.93, 95% CI: 59.62-68.35, n=68), and POD 14-20 (68.19, 95% CI: 60.12-73.37, n=26), POD 21-27 (67.38, 95% CI: 60.30-76.65, n=20) and on POD 28-41 (75.13, 95% CI: 54.02-83.16, n=22; P<0.01).</AbstractText Following surgery for CRC, plasma PGRN levels showed a significant increase compared to baseline levels, persisting for a duration of one month. This initial surge post-operation could potentially be attributed to the transient acute inflammatory response. The elevation observed in weeks 2 and 4 could potentially be attributed to the process of wound healing, as PGRN has been shown to enhance the accumulation of fibroblasts and facilitate angiogenesis within wounds. Additional investigation is warranted.</AbstractText"
]
] |
39402611
|
Cognitive flexibility predicts attitudes towards vaccination: evidence from a New Zealand sample.
|
Vaccine hesitancy (the reluctance or refusal to vaccinate) poses a significant threat to public health worldwide, with declining vaccination coverage resulting in the resurgence of vaccine-preventable diseases (e.g., measles) in recent years. Despite efforts to combat vaccine hesitancy through information-based campaigns and other interventions, vaccine-hesitant attitudes persist. Given that such interventions likely expose individuals to information that conflicts with their own viewpoints about vaccination, cognitive flexibility - the ability to adapt one's thoughts, attitudes, beliefs, or behavior in response to changing information or environmental demands - may play a role in vaccine hesitancy.</AbstractText The current study investigated the relationship between cognitive flexibility and attitudes towards vaccination in a sample of New Zealand residents (N = 601). Cognitive flexibility was measured using perseverative responses in the Wisconsin Card-Sorting Task, and vaccination attitudes were measured using an adapted version of the Multidimensional Vaccine Hesitancy Scale (MVHS). Linear regression was used with MVHS scores as the dependent variable and cognitive flexibility and sociodemographic variables (age, gender, ethnicity, education level, religion) as predictors.</AbstractText Cognitive flexibility predicted personal barriers to vaccination (e.g.," vaccines go against my personal beliefs"), with participants with lower levels of cognitive flexibility reporting greater personal barriers. In contrast, there was no significant relationship between cognitive flexibility and external barriers to vaccination (e.g., "vaccines cost too much"). Additionally, religious participants reported overall higher levels of vaccine hesitancy than non-religious participants.</AbstractText These findings join others demonstrating that individual differences in cognitive style are associated with attitudes towards vaccination, and tentatively suggest that interventions aiming to reduce vaccine hesitancy may be more effective if combined with techniques to increase cognitive flexibility. To be sure, future work is needed to test the causal relationship between cognitive flexibility and attitudes towards vaccination.</AbstractText
|
[
[
"29287743",
"A novel ex vivo method for measuring whole brain metabolism in model systems.",
"Many neuronal and glial diseases have been associated with changes in metabolism. Therefore, metabolic reprogramming has become an important area of research to better understand disease at the cellular level, as well as to identify targets for treatment. Model systems are ideal for interrogating metabolic questions in a tissue dependent context. However, while new tools have been developed to study metabolism in cultured cells there has been less progress towards studies in vivo and ex vivo.</AbstractText We have developed a method using newly designed tissue restraints to adapt the Agilent XFe96 metabolic analyzer for whole brain analysis. These restraints create a chamber for Drosophila brains and other small model system tissues to reside undisrupted, while still remaining in the zone for measurements by sensor probes.</AbstractText This method generates reproducible oxygen consumption and extracellular acidification rate data for Drosophila larval and adult brains. Single brains are effectively treated with inhibitors and expected metabolic readings are observed. Measuring metabolic changes, such as glycolytic rate, in transgenic larval brains demonstrates the potential for studying how genotype affects metabolism.</AbstractText Current methodology either utilizes whole animal chambers to measure respiration, not allowing for targeted tissue analysis, or uses technically challenging MRI technology for in vivo analysis that is not suitable for smaller model systems. This new method allows for novel metabolic investigation of intact brains and other tissues ex vivo in a quick, and simplistic way with the potential for large-scale studies.</AbstractText"
]
] |
[
[
"38392440",
"Effectiveness of Different Neurocognitive Intervention Approaches on Functionality in Healthy Older Adults: A Systematic Review.",
"Subtle loss of functionality in healthy older adults is considered one of the most important predictors of cognitive decline. Neurocognitive interventions are increasingly being used, from a preventive maintenance approach to functional capacity. This study evaluates the effectiveness of different neurocognitive approaches on the functionality of healthy older adults. In this systematic review (CRD42023473944), an extensive search was conducted for articles published in the last 10 years (2013-2023) in the following databases: Medline, Scopus, and Web of Science. A total of 809 trials were identified, of which 18 were considered to be eligible for inclusion in the review. The data revealed heterogeneity in sample size, measures of functional assessment, neurocognitive interventions used, number of sessions, session duration, and time. Traditional cognitive stimulation is shown to have no significant functional benefit, while other less commonly used neurocognitive interventions, such as those based on everyday cognition, are associated with more significant benefits. Moreover, it is demonstrated that although the Instrumental Activities of Daily Living scale (IADL) is the most used test in similar studies, it is not sensitive enough to detect changes in functionality in healthy elderly individuals, with other tests such as the Timed Instrumental Activities of Daily Living (TIADL) being more advantageous. Therefore, a new guideline is proposed for its use in clinical practice and research, using homogeneous study protocols and neurocognitive interventions that allow for the transfer and generalization of results in daily life.</AbstractText"
]
] |
39456253
|
The Ambivalence of Post COVID-19 Vaccination Responses in Humans.
|
The Coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has prompted a massive global vaccination campaign, leading to the rapid development and deployment of several vaccines. Various COVID-19 vaccines are under different phases of clinical trials and include the whole virus or its parts like DNA, mRNA, or protein subunits administered directly or through vectors. Beginning in 2020, a few mRNA (Pfizer-BioNTech BNT162b2 and Moderna mRNA-1273) and adenovirus-based (AstraZeneca ChAdOx1-S and the Janssen Ad26.COV2.S) vaccines were recommended by WHO for emergency use before the completion of the phase 3 and 4 trials. These vaccines were mostly administered in two or three doses at a defined frequency between the two doses. While these vaccines, mainly based on viral nucleic acids or protein conferred protection against the progression of SARS-CoV-2 infection into severe COVID-19, and prevented death due to the disease, their use has also been accompanied by a plethora of side effects. Common side effects include localized reactions such as pain at the injection site, as well as systemic reactions like fever, fatigue, and headache. These symptoms are generally mild to moderate and resolve within a few days. However, rare but more serious side effects have been reported, including allergic reactions such as anaphylaxis and, in some cases, myocarditis or pericarditis, particularly in younger males. Ongoing surveillance and research efforts continue to refine the understanding of these adverse effects, providing critical insights into the risk-benefit profile of COVID-19 vaccines. Nonetheless, the overall safety profile supports the continued use of these vaccines in combating the pandemic, with regulatory agencies and health organizations emphasizing the importance of vaccination in preventing COVID-19's severe outcomes. In this review, we describe different types of COVID-19 vaccines and summarize various adverse effects due to autoimmune and inflammatory response(s) manifesting predominantly as cardiac, hematological, neurological, and psychological dysfunctions. The incidence, clinical presentation, risk factors, diagnosis, and management of different adverse effects and possible mechanisms contributing to these effects are discussed. The review highlights the potential ambivalence of human response post-COVID-19 vaccination and necessitates the need to mitigate the adverse side effects.</AbstractText
|
[
[
"28500804",
"A Large Outbreak of Thiamine Deficiency Among Illegal Gold Miners in French Guiana.",
"From September 2013 to July 2014, several gold miners working in the tropical forest consulted the Maripasoula Health Center in French Guiana for edema and findings consistent with right-sided cardiac failure. Of the 42 cases of beriberi that were diagnosed, one patient died. The laboratory and clinical investigation demonstrated vitamin B1 deficiency in most of the patients tested. Furthermore, 30 of 42 patients responded favorably to 500 mg of intravenous or intramuscular thiamine supplementation. In addition, dietary investigation showed insufficient thiamine intake in these patients. We concluded that patients had acquired beriberi because of diet restrictions, hard labor, and infectious diseases, notably malaria. In 2016, cases were still being reported. We recommend screening for compatible symptoms in gold miners, thiamine supplementation, and nutritional intervention.</AbstractText"
]
] |
[
[
"39053336",
"Two-year mortality and seizure recurrence following status epilepticus in Auckland, New Zealand: A prospective cohort study.",
"To document the 2-year mortality and seizure recurrence rate of a prospective cohort of patients identified with status epilepticus (SE).</AbstractText Patients presenting to any hospital in the Auckland region between April 6 2015, and April 5 2016, with a seizure lasting 10 min or longer were identified. Follow up was at 2 years post index SE episode via telephone calls and detailed review of clinical notes.</AbstractText We identified 367 patients with SE over the course of one year. 335/367 (91.3 %) were successfully followed up at the 2-year mark. Two-year all-cause mortality was 50/335 (14.9 %), and 49/267 (18.4 %) when febrile SE was excluded. Two-year seizure recurrence was 197/335 (58.8 %). On univariate analyses, children (preschoolers 2 to < 5 years and children 5 to < 15 years), Asian ethnicity, SE duration <30 mins and acute (febrile) aetiology were associated with lower mortality, while older age >60 and progressive causes were associated with higher mortality on both univariate and multivariate analyses. Age < 2 years and acute aetiology were associated with lower seizure recurrence, while non convulsive status epilepticus (NCSE) with coma and a history of epilepsy were associated with higher seizure recurrence. On multivariate analyses, a history of epilepsy, as well as having both acute and remote causes were associated with higher seizure recurrence.</AbstractText All-cause mortality in both the paediatric and adult populations at 2 years was lower than most previous reports. Older age, SE duration ≥30 mins and progressive aetiologies were associated with the highest 2-year mortality, while febrile SE had the lowest mortality. A history of epilepsy, NCSE with coma, and having both acute and remote causes were associated with higher seizure recurrence at 2 years. Future studies should focus on functional measures of outcome and long-term quality of life.</AbstractText"
]
] |
39428042
|
Optineurin regulates motor and learning behaviors by affecting dopaminergic neuron survival in mice.
|
Optineurin (OPTN) is an autophagy receptor that participates in the degradation of damaged mitochondria, protein aggregates, and invading pathogens. OPTN is closely related to various types of neurodegenerative diseases. However, the role of OPTN in the central nervous system is unclear. Here, we found that OPTN dysregulation in the compact part of substantia nigra (SNc) led to motor and learning deficits in animal models. Knockdown of OPTN increased total and phosphorylated α-synuclein levels which induced microglial activation and dopaminergic neuronal loss in the SNc. Overexpression of OPTN can't reverse the motor and learning phenotypes. Mechanistic analysis revealed that upregulation of OPTN increased α-synuclein phosphorylation independent of its autophagy receptor activity, which further resulted in microglial activation and dopaminergic neuronal loss similar to OPTN downregulation. Our study uncovers the crucial role of OPTN in maintaining dopaminergic neuron survival and motor and learning functions which are disrupted in PD patients.</AbstractText
|
[
[
"28554413",
"The Nonmotor Features of Parkinson's Disease.",
"Nonmotor symptoms (NMS) of Parkinson's disease (PD) were recognized by the great James Parkinson himself who mentioned symptoms such as sleep dysfunction, delirium, dementia, and dysautonomia, in his seminal 1817 essay, \"An Essay on the Shaking Palsy\" (Parkinson, 1817). In spite of the key impact of PD NMS on quality of life, there was little holistic research and awareness till the validation and use of comprehensive tools such as the NMS questionnaire, scale, and the revised version of the unified PD rating scale. Research studies using these tools highlighted the key impact of the burden of NMS on quality of life of PD patients and the need for NMS to be routinely assessed in clinic. We now define PD as a motor and nonmotor disorder, and the natural history includes a long prodromal phase of PD dominated by a range of NMS. The prodromal phase is the subject of much research particularly in relation to neuroprotection and identifying subjects at risk. Use of NMS tools has also validated burden grading of NMS with cutoff values, which can be used as outcome measure in clinical trials. Finally, the complex multineurotransmitter dysfunction that is seen in PD has been shown to manifest clinically as nonmotor subtypes. Recognition of such subtypes is likely to lead to the emergence of personalized and precision medicine in PD.</AbstractText"
]
] |
[
[
"38315591",
"SARF: Aliasing Relation-Assisted Self-Supervised Learning for Few-Shot Relation Reasoning.",
"Few-shot relation reasoning on knowledge graphs (FS-KGR) is an important and practical problem that aims to infer long-tail relations and has drawn increasing attention these years. Among all the proposed methods, self-supervised learning (SSL) methods, which effectively extract the hidden essential inductive patterns relying only on the support sets, have achieved promising performance. However, the existing SSL methods simply cut down connections between high-frequency and long-tail relations, which ignores the fact, i.e., the two kinds of information could be highly related to each other. Specifically, we observe that relations with similar contextual meanings, called aliasing relations (ARs), may have similar attributes. In other words, the ARs of the target long-tail relation could be in high-frequency, and leveraging such attributes can largely improve the reasoning performance. Based on the interesting observation above, we proposed a novel Self-supervised learning model by leveraging Aliasing Relations to assist FS-KGR, termed SARF. Specifically, we propose a graph neural network (GNN)-based AR-assist module to encode the ARs. Besides, we further provide two fusion strategies, i.e., simple summation and learnable fusion, to fuse the generated representations, which contain extra abundant information underlying the ARs, into the self-supervised reasoning backbone for performance enhancement. Extensive experiments on three few-shot benchmarks demonstrate that SARF achieves state-of-the-art (SOTA) performance compared with other methods in most cases.</AbstractText"
]
] |
40286791
|
B cell-derived acetylcholine promotes liver regeneration by regulating Kupffer cell and hepatic CD8(+) T cell function.
|
Liver regeneration (LR) is essential for recovery from acute trauma, cancer surgery, or transplantation. Neurotransmitters such as acetylcholine (ACh) play a role in LR by stimulating immune cells and augmenting hepatocyte proliferation, but the source of this ACh remains unclear. Here, we demonstrated that B cells expressing choline acetyltransferase (ChAT), which synthesizes ACh, were required for LR. Mice lacking ChAT<sup
|
[
[
"21746786",
"SIRT-1 and vascular endothelial dysfunction with ageing in mice and humans.",
"We tested the hypothesis that reductions in the cellular deacetylase, sirtuin-1 (SIRT-1), contribute to vascular endothelial dysfunction with ageing via modulation of endothelial nitric oxide synthase (eNOS) acetylation/activation-associated nitric oxide (NO) production. In older (30 months, n = 14) vs. young (5-7 months, n = 16) B6D2F1 mice, aortic protein expression of SIRT-1 and eNOS phosphorylated at serine 1177 were lower (both P < 0.05), and acetylated eNOS was 6-fold higher (P < 0.05), whereas total eNOS did not differ (P = 0.65). Acetylcholine (ACh)-induced peak endothelium-dependent dilatation (EDD) was lower in isolated femoral arteries with ageing (P < 0.001). Incubation with sirtinol, a SIRT-1 inhibitor, reduced EDD in both young and older mice, abolishing age-related differences, whereas co-administration with l-NAME, an eNOS inhibitor, further reduced EDD similarly in both groups. Endothelium-independent dilatation to sodium nitroprusside (EID), was not altered by age or sirtinol treatment. In older (64 ± 1 years, n = 22) vs. young (25 ± 1 years, n = 16) healthy humans, ACh-induced forearm EDD was impaired (P = 0.01) and SIRT-1 protein expression was 37% lower in endothelial cells obtained from the brachial artery (P < 0.05), whereas EID did not differ. In the overall group, EDD was positively related to endothelial cell SIRT-1 protein expression (r = 0.44, P < 0.01). Reductions in SIRT-1 may play an important role in vascular endothelial dysfunction with ageing. SIRT-1 may be a key therapeutic target to treat arterial ageing.</AbstractText"
]
] |
[
[
"40725047",
"Exploring the Interplay Between Gut Microbiota and the Melatonergic Pathway in Hormone Receptor-Positive Breast Cancer.",
"Emerging evidence suggests a bidirectional relationship between gut microbiota, melatonin synthesis, and breast cancer (BC) development in hormone receptor-positive patients (HR+HER2+ and HR+HER2-). This study investigated alterations in gut microbiota composition, the serum serotonin-N-acetylserotonin (NAS)-melatonin axis, fecal short-chain fatty acids (SCFAs) and beta-glucuronidase (βGD) activity, and serum zonulin in HR+ BC patients compared to healthy controls. Blood and fecal samples were analyzed using mass spectrometry for serotonin, NAS, melatonin, and SCFAs; ELISA for AANAT, ASMT, 14-3-3 protein, and zonulin; fluorometric assay for βGD activity; and 16S rRNA sequencing for gut microbiota composition. HR+ BC patients exhibited gut dysbiosis with reduced <i"
]
] |
37818027
|
18F-fluoro-2-deoxy-2-d-glucose PET-CT (FDG PET-CT) in staging of high-risk renal and urothelial bladder cancers (COPPER-T) trial protocol.
|
Role of <sup There will be two subgroups of patients: RCC and urinary bladder carcinoma. In each of these, the patients will be randomized to either Arm A or Arm B. In each of the arms, each patient will be subjected to diagnostic imaging by FDG PET-CT. The CT scan will be a contrast-enhanced scan like that in conventional staging. A radiologist and nuclear medicine specialist will report the scan independently. The radiologist will not have access to the PET scan sequences and will only review the contrast-enhanced computed tomography (CECT) images. In Arm A, the report of the conventional imaging modality, that is, CECT and bone scan if done, will be reviewed first by the clinician, and based on this report, a management plan will be made. Then, the PET-CT report will be reviewed, and change in the management plan will be noted. New findings or equivocal findings if any in the PET-CT report would be noted. In Arm B, the report of the PET-CT report will be reviewed first by the clinicians, and a management plan will be made. Then, the CECT and/or bone scan reports will be reviewed, and any change in the management plan will be noted.</AbstractText Final analysis of the data after completion of the trial will help in clarifying the role of FDG PET-CT in high risk RCC and transitional cell carcinoma (TCC) of the bladder, its diagnostic accuracy compared with conventional imaging and the impact of using it on patient management.</AbstractText
|
[
[
"32906630",
"Orbital and Eyelid B-Cell Lymphoma: A Multicenter Retrospective Study.",
"The aim of this study was to analyze patients diagnosed, staged and treated for orbital and eyelid B-cell lymphoma (OEL).</AbstractText One hundred and forty-one cases of OEL were included in this study. Primary endpoints were to analyze the histopathologic findings, the main risk factors and the type of treatment and to correlate them with recurrence of OEL. The secondary endpoint was to determine the progression-free survival (PFS) time.</AbstractText Extranodal marginal zone B-cell lymphoma was the most frequent subtype (66%), followed by small lymphocytic lymphoma (12.7%), diffuse large B-cell lymphoma (DLBCL) (9.2%), follicular lymphoma (6.6%), mantle cell lymphoma (4.3%) and Burkitt lymphoma (1.2%). The probability of relapse was influenced by the histopathologic subtype DLBCL (OR = 7.7, 95% CI 1.8-32.3) and treatment with chemotherapy (OR = 14.9, 95% CI 2.6-83.7). Multivariate analysis showed that the histopathologic subtype DLBCL and chemotherapy treatment retained statistical significance for a poorer PFS, with hazard ratios of 8.581 (<i Five lymphoma subtypes were found in patients with OEL. The histopathologic subtype and the type of treatment were found to be the main factors influencing treatment outcome.</AbstractText"
]
] |
[
[
"37645082",
"Validity and Reliability of the Pictures of Facial Affect (POFA) in Healthy People and Patients with Essential Tremor in the Turkish Population.",
"This study aimed to conduct the validity and reliability of the (Pictures of Facial Affect) POFA test for the Turkish population and contribute to increasing the number of tests that are still insufficient in our country.</AbstractText This descriptive, randomized controlled study was conducted in two steps, namely Step 1 (Pilot Study and Validity Studies) and Step 2 (Reliability Study Step). The number of participants was planned regarding the original study by which the POFA test was developed. The EYES test was also used for comparison. In the pilot study, the most widely identified emotions from 47 of 110 photos in the POFA test were chosen as the new POFA picture set to be used in the reliability and validity study under the name \"POFA Test Short Form\". A total of 100 participants, including 82 healthy volunteers and 18 essential tremor (ET) patients, were enrolled in the first step of the study. Another cohort of 22 healthy volunteers was enrolled in the second step of the study for test-retest reliability analysis.</AbstractText A significant positive correlation was found between the total POFA Test Short Form and EYES Test scores in the healthy volunteer group in terms of criterion-related validity (r=0.44, p<0.01). There were statistically significant differences between healthy volunteers and ET groups regarding EYES Total, POFA Total, POFA Sadness, POFA Anger, and POFA Neutral scores. It was observed that the 47-item POFA Test Short Form total score showed skewness and kurtosis, which demonstrated suitability for clinical use.</AbstractText The POFA Test Short Form was found to be a valid and reliable assessment tool in the Turkish population to be used in studies on emotion recognition and was shown to be beneficial for the discrimination of healthy individuals and ET patients.</AbstractText"
]
] |
35403392
|
[Modulation of transcutaneous auricular vagus nerve stimulation on default mode network in patients with primary insomnia].
|
To explore the modulation of transcutaneous auricular vagus nerve stimulation (taVNS) on default mode network (DMN) in patients with primary insomnia (PI).</AbstractText A total of 22 PI patients (one patient dropped off and two patients were excluded) were included and treated with taVNS. The bilateral auricular points of Xin (CO<sub After treatment, the total score of PSQI in PI patients was lower than that before treatment (<i taVNS can modulate the FC between anterior and posterior DMN, and between DMN and cognitive control network of PI patients, which may be one of the brain effect mechanisms of taVNS in the treatment of PI patients.</AbstractText <b
|
[
[
"17599700",
"Recent advances in magnetic resonance neurospectroscopy.",
"Over the past two decades, proton magnetic resonance spectroscopy (proton MRS) of the brain has made the transition from research tool to a clinically useful modality. In this review, we first describe the localization methods currently used in MRS studies of the brain and discuss the technical and practical factors that determine the applicability of the methods to particular clinical studies. We also describe each of the resonances detected by localized solvent-suppressed proton MRS of the brain and discuss the metabolic and biochemical information that can be derived from an analysis of their concentrations. We discuss spectral quantitation and summarize the reproducibility of both single-voxel and multivoxel methods at 1.5 and 3-4 T. We have selected three clinical neurologic applications in which there has been a consensus as to the diagnostic value of MRS and summarize the information relevant to clinical applications. Finally, we speculate about some of the potential technical developments, either in progress or in the future, that may lead to improvements in the performance of proton MRS.</AbstractText"
]
] |
[
[
"35218310",
"GSH-Responsive Metal-Organic Framework for Intratumoral Release of NO and IDO Inhibitor to Enhance Antitumor Immunotherapy.",
"Immunotherapy brings great benefits for tumor therapy in clinical treatments but encounters the severe challenge of low response rate mainly because of the immunosuppressive tumor microenvironment. Multifunctional nanoplatforms integrating effective drug delivery and medical imaging offer tremendous potential for cancer treatment, which may play a critical role in combinational immunotherapy to overcome the immunosuppressive microenvironment for efficient tumor therapy. Here, a nanodrug (BMS-SNAP-MOF) is prepared using glutathione (GSH)-sensitive metal-organic framework (MOF) to encapsulate an immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO) inhibitor BMS-986205, and the nitric oxide (NO) donor s-nitrosothiol groups. The high T1 relaxivity allows magnetic resonance imaging to monitor nanodrug distribution in vivo. After the nanodrug accumulation in tumor tissue via the EPR effect and subsequent internalization into tumor cells, the enriched GSH therein triggers cascade reactions with MOF, which disassembles the nanodrug to rapidly release the IDO-inhibitory BMS-986205 and produces abundant NO. Consequently, the IDO inhibitor and NO synergistically modulate the immunosuppressive tumor microenvironment with increase CD8<sup"
]
] |
39735539
|
Circulating extracellular vesicles and neutrophil extracellular traps contribute to endothelial dysfunction in preeclampsia.
|
Preeclampsia (PE) is a pregnancy complication characterized by hypertension, proteinuria, endothelial dysfunction, and complement dysregulation. Placenta-derived extracellular vesicles (EVs), necessary in maternal-fetal communication, might contribute to PE pathogenesis. Moreover, neutrophil extracellular traps (NETs) play a pathogenic role in other complement-mediated pathologies, and their contribution in PE remains unexplored.</AbstractText EVs were isolated from PE (peEVs) and normotensive pregnant women sera. NETs were obtained incubating donor-pre-activated neutrophils with PE or control sera. Microvascular (HMEC) endothelial cells (ECs) were incubated with PE or control sera with or without (depleted sera) EVs or NETs, to assess changes in VCAM-1, ICAM-1, VE-cadherin, eNOS, VWF, ROS, and C5b-9 deposits. Results were expressed as fold increase vs. control.</AbstractText VWF, VCAM-1, and ROS expression was significantly higher in cells exposed to PE sera vs. control (12.3 ± 8.1, 3.6 ± 2.3, and 1.8 ± 0.2, respectively, <i Both circulating EVs and NETs from PE pregnant women exhibit a deleterious effect on ECs. Whereas EVs trigger a pro-oxidant and proinflammatory state, NETs potentiate the activation of the complement system, as already described in PE.</AbstractText
|
[
[
"37766893",
"Advantages of photo-curable collagen-based cell-laden bioinks compared to methacrylated gelatin (GelMA) in digital light processing (DLP) and extrusion bioprinting.",
"The development of cell-laden bioinks that possess high biocompatibility and printability is crucial in the field of bioprinting for the creation of cell-embedded tissue engineering scaffolds. As widely known, methacrylated gelatin (GelMA) is one of the most commonly used photo-crosslinkable bioink for cell-laden bioprinting with different printing methods, but GelMA is the derivative of gelatin, so it loses the unique triple-helix molecular structure of collagen and may not be able to successfully activate the cellular pathways or facilitate cell-matrix interaction as effectively as collagen. Recently, methacrylated collagen (CMA) was developed to be an alternative photocrosslinkable bioink with a good bioactivity, but its low printability and biocompatibility limited that application in tissue engineering. In this study, the synthetic process for CMA was improved by synthesizing under 4 °C and using acidic aqueous solution as solvent. Our CMA bioinks were demonstrated a similar printability as GelMA in extrusion bioprinting, while a better formability in digital light processing (DLP). To further analyze the bioactive properties, CMA bioinks were encapsulated with Schwann cells (SCs) and bone mesenchymal stem cells (BMSCs) for printing. SCs-laden CMA bioinks had a significantly higher proliferation rate and expression of neural stem cell-associated genes than GelMA in DLP bioprinting. While, BMSCs-laden CMA bioinks demonstrated >95% cellular viability, better cell spreading and higher expression of osteogenesis-related genes than that of GelMA. Overall, we speculate that the CMA-based bioink developed in this study could be potential bioinks for 3D cell-laden bioprinting in the future.</AbstractText"
]
] |
[
[
"38342980",
"Improving quantitative MRI using self-supervised deep learning with model reinforcement: Demonstration for rapid T1 mapping.",
"This paper proposes a novel self-supervised learning framework that uses model reinforcement, REference-free LAtent map eXtraction with MOdel REinforcement (RELAX-MORE), for accelerated quantitative MRI (qMRI) reconstruction. The proposed method uses an optimization algorithm to unroll an iterative model-based qMRI reconstruction into a deep learning framework, enabling accelerated MR parameter maps that are highly accurate and robust.</AbstractText Unlike conventional deep learning methods which require large amounts of training data, RELAX-MORE is a subject-specific method that can be trained on single-subject data through self-supervised learning, making it accessible and practically applicable to many qMRI studies. Using quantitative <mml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" The proposed method generates high-quality MR parameter maps that correct for image artifacts, removes noise, and recovers image features in regions of imperfect image conditions. Compared with other state-of-the-art conventional and deep learning methods, RELAX-MORE significantly improves efficiency, accuracy, robustness, and generalizability for rapid MR parameter mapping.</AbstractText This work demonstrates the feasibility of a new self-supervised learning method for rapid MR parameter mapping, that is readily adaptable to the clinical translation of qMRI.</AbstractText"
]
] |
40714509
|
The function and application potential of L-theanine: From biotechnological production, biosynthesis, bioactivity to food industry.
|
L-theanine (γ-glutamylethylamide), a unique amino acid predominantly biosynthesized in tea plants (Camellia sinensis), exhibits multifaceted roles in human health and food innovation. This review elucidates its biosynthesis regulated by nitrogen availability and epigenetic mechanisms, alongside sustainable biotechnological production strategies, including extraction technologies to biotransformation. Mechanistically, L-theanine modulates glutamate receptors to enhance neuroprotection (BDNF upregulation, cortisol reduction), activates AMPK for anti-obesity effects (lipid oxidation, adiponectin secretion), and activates of γδ T cells to bolster immunomodulation. Emerging food applications include cognitive-enhancing beverages, plant-based preservatives (metal chelation), and low-sodium umami enhancers. By integrating molecular insights with scalable production and functional food design, this work positions L-theanine as a pivotal nutraceutical bridging metabolic health, sustainable biotechnological innovations, and consumer-driven dietary trends.</AbstractText
|
[
[
"32621777",
"Association between tear and blood glucose concentrations: Random intercept model adjusted with confounders in tear samples negative for occult blood.",
"To prevent diabetic complications, strict glucose control and frequent monitoring of blood glucose levels with invasive methods are necessary. We considered the monitoring of tear glucose levels might be a possible method for non-invasive glucose monitoring. To develop tear glucose monitoring for clinical application, we investigated the precise correlation between the blood and tear glucose concentrations.</AbstractText A total of 10 participants and 20 participants with diabetes were admitted, and blood and tear samples were collected. Before statistical analysis, we eliminated tear samples contaminated with blood. We observed the daily blood and tear glucose dynamics, and carried out a random intercept model analysis to examine the association between the blood and tear glucose concentrations.</AbstractText Tear occult blood tests showed that the tear glucose concentrations and their variation increased in both participants with and without diabetes as contamination of blood increased. In both participants with and without diabetes, fluctuations of the plasma glucose concentrations were observed depending on the timing of collection of the samples, and the dynamics of the tear glucose concentrations paralleled those of the plasma glucose concentrations. The random intercept model analysis showed a significant association between the plasma and tear glucose concentrations in participants with diabetes (P < 0.001). This association still existed even after adjusting for the glycated hemoglobin levels and the prandial state (P < 0.001).</AbstractText It is important to eliminate the tear samples contaminated with blood. Tear glucose monitoring might be a reliable and non-invasive substitute method for monitoring the blood glucose concentrations for diabetes patients, irrespective of glycated hemoglobin levels and timing of sample collection.</AbstractText"
]
] |
[
[
"40744504",
"Effects of N-Acetylcysteine and l-Carnitine on Wound Healing of Palatal Mucosa in a Rat Model.",
"Surgical procedures in oral and maxillofacial surgery inevitably cause wound formation, making the patient vulnerable to infections as well as discomfort. As antioxidant agents exert great potential to accelerate wound healing, we investigated the effects of N-acetylcysteine (NAC) and l-carnitine (LC) on palatal wound healing.</AbstractText Sixty-four Wistar rats were randomly divided into four groups. 5 mm diameter wounds were created in the hard palates of the rats. 150 mg/kg/day NAC, 100 mg/kg/day LC, or both were injected intraperitoneally to the treatment groups until sacrification on Day 5 or 10. Hematoxylin and eosin, Masson's Trichrome staining, and immunohistochemistry (α-SMA, FGF-2) were performed on wound tissues.</AbstractText On Days 5 and 10, reepithelialization was incomplete and inflammation was observed in all groups. Collagen density tended to increase in the LC and NAC + LC groups on Day 5, and significantly differed between the LC and NAC groups on day 10. A slight elevation in α-SMA expression was observed in the NAC group on Day 5, while NAC + LC treatment significantly reduced α-SMA levels compared to NAC alone. FGF-2 expression showed an increasing trend in the NAC + LC group on Day 5 and in the NAC and LC groups on Day 10. A significant increase in FGF-2 was observed in the NAC + LC group versus the NAC group on Day 5, and within the NAC group between Days 5 and 10.</AbstractText Our findings have shown that LC in the late stage and NAC + LC combination in the early stage may positively affect palatal wound healing.</AbstractText"
]
] |
40689283
|
Evaluating Children's Drawings as a Means of Expression in Children with Chronic Diseases.
|
Children's drawings are considered an important tool for detecting emotions and experiences that a child may be unable or unwilling to express verbally.</AbstractText This study aimed to assess the emotional state, psychological development, and adjustment mechanisms of children with chronic diseases using projective drawing tests, and to compare their responses with those of healthy children.</AbstractText A cross-sectional design was implemented in one region of Greece, involving 100 children aged 6-12 years. The sample included 50 children with chronic diseases (25 with type 1 diabetes and 25 with cystic fibrosis) and 50 healthy children serving as a control group, selected from pediatric clinics and schools. Data collection took place between January and June 2023. Participants completed three projective tests: the Kinetic Family Drawing Test (KFD), Tree Drawing Test, and House Drawing Test, which assessed emotional expression and psychological functioning.</AbstractText Children with chronic diseases expressed emotions differently compared to healthy peers. In the KFD, they depicted fewer smiling faces, indicating higher emotional distress and a more negative perception of their family environment. In the tree drawings, symbolic elements such as birds-representing freedom or hope - were more common among children with chronic diseases, while healthy children more often drew roots, suggesting emotional stability. The House Drawing Test revealed no significant differences between the two groups.</AbstractText Projective tests such as the KFD and Tree Drawing Test appear to be effective in identifying emotional issues in children with chronic illnesses, unlike the House Drawing Test. These findings support the integration of such tools into psychological assessments and therapeutic interventions for pediatric chronic disease populations.</AbstractText
|
[
[
"37966840",
"Ascertainment of Minimal Clinically Important Differences in the Diabetes Distress Scale-17: A Secondary Analysis of a Randomized Clinical Trial.",
"The Diabetes Distress Scale-17 (DDS-17) is a common measure of diabetes distress. Despite its popularity, there are no agreed-on minimal clinically important difference (MCID) values for the DDS-17.</AbstractText To establish a distribution-based metric for MCID in the DDS-17 and its 4 subscale scores (interpersonal distress, physician distress, regimen distress, and emotional distress).</AbstractText This secondary analysis of a randomized clinical trial used baseline and postintervention data from a hybrid (implementation-effectiveness) trial evaluating Empowering Patients in Chronic Care (EPICC) vs an enhanced form of usual care (EUC). Participants included adults with uncontrolled type 2 diabetes (glycated hemoglobin A1c [HbA1c] level >8.0%) who received primary care during the prior year in participating Department of Veterans Affairs clinics across Illinois, Indiana, and Texas. Data collection was completed in November 2018, and data analysis was completed in June 2023.</AbstractText Participants in EPICC attended 6 group sessions led by health care professionals based on collaborative goal-setting theory. EUC included diabetes education.</AbstractText The main outcome was distribution-based MCID values for the total DDS-17 and 4 DDS-17 subscales, calculated using the standard error of measurement. Baseline to postintervention changes in DDS-17 and its 4 subscale scores were grouped into 3 categories: improved, no change, and worsened. Multilevel logistic and linear regression models examined associations between treatment group and MCID change categories and whether improvement in HbA1c varied in association with MCID category.</AbstractText A total of 248 individuals with complete DDS-17 data were included (mean [SD] age, 67.4 [8.3] years; 235 [94.76%] men), with 123 participants in the EPICC group and 125 participants in the EUC group. The MCID value for DDS-17 was 0.25 and MCID values for the 4 distress subscales were 0.38 for emotional and interpersonal distress and 0.39 for physician and regimen distress. Compared with EUC, more EPICC participants were in the MCID improvement category on DDS-17 (63 participants [51.22%] vs 40 participants [32.00%]; P = .003) and fewer EPICC participants were in the worsened category (20 participants [16.26%] vs 39 participants [31.20%]; P = .008). There was no direct association of DDS-17 MCID improvement (β = -0.25; 95% CI, -0.59 to 0.10; P = .17) or worsening (β = 0.18; 95% CI, -0.22 to 0.59; P = .38) with HbA1c levels among all participants.</AbstractText In this secondary analysis of data from a randomized clinical trial, an MCID improvement or worsening of more than 0.25 on the DDS-17 was quantitatively significant and patients in the EPICC group were more likely to experience improvement than those in the EUC group.</AbstractText ClinicalTrials.gov Identifier: NCT01876485.</AbstractText"
]
] |
[
[
"39988194",
"The intrinsic functional connectivity patterns of the phonological and semantic networks in word reading.",
"Previous studies have revealed that phonological and semantic processing recruit separate brain networks. However, the intrinsic functional connectivity patterns of the phonological and semantic networks remain unclear. To address this issue, the present study explored the static and dynamic functional connectivity patterns of phonological and semantic networks during the resting state. The static functional connectivity pattern of the two networks was examined by adopting a voxel-based global brain connectivity (GBC) method. In this analysis, we estimated the within-network connectivity (WNC), between-network connectivity between phonological and semantic networks (BNC_PS), and between-network connectivity of the two language networks (i.e., phonological and semantic networks) with the non-language network (BNC_N). The results showed that both phonological and semantic networks exhibited stronger intra-network connectivity (i.e., WNC) than inter-network connectivity (i.e., BNC_PS and BNC_N), indicating that both networks are relatively encapsulated. For dynamic functional connectivity, three distinct dynamic functional states were identified. Specifically, State 1 showed an overall positive connectivity pattern. State 2 exhibited an overall weak connectivity pattern. State 3 showed positive intra-network connectivity and negative inter-network connectivity. These results suggested that phonological and semantic networks exhibited a flexible integration and segregation pattern over time. Taken together, our results revealed that the phonological and semantic networks showed an intra-network integration and inter-network segregation pattern. These findings deepen our understanding of the intrinsic functional connectivity patterns of language networks.</AbstractText"
]
] |
37019439
|
Passive Recording of Bioelectrical Signals from Non-Excitable Cells by Fluorescent Mirroring.
|
Bioelectrical variations trigger different cell responses, including migration, mitosis, and mutation. At the tissue level, these actions result in phenomena such as wound healing, proliferation, and pathogenesis. Monitoring these mechanisms dynamically is highly desirable in diagnostics and drug testing. However, existing technologies are invasive: either they require physical access to the intracellular compartments, or they imply direct contact with the cellular medium. Here, we present a novel approach for the passive recording of electrical signals from non-excitable cells adhering to 3D microelectrodes, based on optical mirroring. Preliminary results yielded a fluorescence intensity output increase of the 5,8% in the presence of a HEK-293 cell on the electrode compared to bare microelectrodes. At present, this technology may be employed to evaluate cell-substrate adhesion and monitor cell proliferation. Further refinements could allow extrapolating quantitative data on surface charges and resting potential to investigate the electrical phenomena involved in cell migration and cancer progression.</AbstractText
|
[
[
"12813152",
"Loss of force induced by high extracellular [K+] in rat muscle: effect of temperature, lactic acid and beta2-agonist.",
"Loss of K+ from active muscles, leading to increased [K+]o, has been proposed to cause muscle fatigue by reducing excitability. Since exercise increases muscle temperature, we investigated the influence of temperature on muscle [K+]o sensitivity. Intact rat soleus or extensor digitorum longus (EDL) muscles were mounted on force transducers and stimulated electrically to evoke short isometric tetani at regular intervals. In each experiment, control force at 4 mM K+ was initially determined at every temperature used. In soleus muscles at 20 degrees C, 9 mM K+ reduced force to 33 +/- 5 % of control force. Increasing the temperature to 30 degrees C restored force to 89 +/- 5 % of control force. Likewise, at 30 degrees C 11 mM K+ reduced force to 16 +/- 4 % and increasing the temperature to 35 degrees C restored force to 35 +/- 5 %. Similar results were obtained using EDL. The force recovery induced by elevating temperature, reflecting reduced [K+]o sensitivity, was associated with improved excitability assessed from compound action potentials. Force recovery induced by a temperature elevation from 20 to 30 degrees C was associated with hyperpolarization (5 mV), reduced [Na+]i and a 93 % increase in Na+-K+ pump activity. The force recovery was blocked by ouabain. Since intensive exercise leads to lactic acidosis and increased plasma catecholamines, the effect of these two factors was also investigated. At 11 mM K+, force was completely restored by combining temperature elevation (30 to 35 degrees C), L-lactic acid (10 mM) and the beta2-agonist salbutamol (10-5 M). We suggest an exercise scenario where the depressing action of exercise-induced hyperkalaemia is counteracted by elevated muscle temperature, lactic acidosis and catecholamines.</AbstractText"
]
] |
[
[
"36398570",
"[Metacognitions and interoceptive sensibility in the perception of premonitory urges in tic disorders across the lifespan].",
"Metacognitions and interoceptive sensibility in the perception of premonitory urges in tic disorders across the lifespan <b <b"
]
] |
27861208
|
Left Ventricular Myocardial Fibrosis, Atrophy, and Impaired Contractility in Patients With Pulmonary Arterial Hypertension and a Preserved Left Ventricular Function: A Cardiac Magnetic Resonance Study.
|
Using a cardiac magnetic resonance (CMR) approach we investigated left ventricular (LV) myocardial changes associated with pulmonary arterial hypertension (PAH) by strain analysis and mapping techniques.</AbstractText Seventeen patients with PAH (9 men; mean age, 64.2±13.6 y) and 20 controls (10 men, 63.2±10.5 y) were examined using CMR at 1.5 T. Native LV T1-relaxation times (T1) and extracellular volume fraction (ECV) were assessed using a MOLLI sequence, T2-relaxation times (T2) by means of a gradient spin-echo sequence, and LV longitudinal strain (LVS) and right ventricular (RV) longitudinal strain (RVS) by means of CMR feature tracking. The hematocrit and serum levels of pro-Brain Natriuretic Peptide were determined on the day of the CMR examination. Pulmonary arterial pressure and 6-minute walking distance were assessed as part of the clinical evaluation.</AbstractText T1 and ECV were higher (1048.5±46.6 vs. 968.3±22.9 ms and 32.4%±5.7% vs. 28.4%±3.8%; P<0.05) and LVS was lower in patients with PAH (-18.0±5.6 vs. -23.0±2.9; P<0.01) compared with controls. LV mass and interventricular septal thickness were lower in PAH patients (65.7±18.0 vs. 86.7±26.9 g and 7.6±1.9 vs. 10±2.4 mm; P<0.05); there were no differences in LV ejection fraction (61.2%±6.9% vs. 61.9%±6.7%; P=0.86). T1-derived parameters correlated significantly with RVS, LVS, the 6-minute walking distance, RV ejection fraction, pro-Brain Natriuretic Peptide, and baseline mean pulmonary arterial pressure. There were no significant differences in T2.</AbstractText In patients with PAH, changes in T1 and ECV support the hypothesis of LV myocardial fibrosis and atrophy with a consecutively impaired contractility despite a preserved LV function, possibly due to longstanding PAH-associated LV underfilling.</AbstractText
|
[
[
"23319072",
"Early brain pseudoatrophy while on natalizumab therapy is due to white matter volume changes.",
"Investigation of atrophy data from a pivotal natalizumab trial has demonstrated an increased rate of volume loss, compared to placebo, after the first year of therapy. It was considered to be probably due to a pseudoatrophy effect.</AbstractText To assess grey and white matter volume changes and their relation to global brain volume changes and to baseline inflammation, for patients under natalizumab therapy.</AbstractText We selected 45 patients on natalizumab therapy for at least 24 months, with magnetic resonance imaging (MRI) scans at baseline, 12 and 24 months. We calculated the percentage brain volume change (PBVC) for the first and second year, using SIENA software. Grey and white matter fractions (GMF and WMF, respectively) for the first year were calculated with SPM5, using lesion masks. After quality checks, six patients were excluded. We studied the predictive variables of change in brain volumes.</AbstractText The PBVC decrease was faster during the first year (-1.10% ± 1.43%), as compared to the second (-0.51% ± 0.96%) (p = 0.037). These differences were more marked in patients with baseline gadolinium-enhancing lesions (p = 0.005). Mean GMF and WMF changes during the first year of treatment were +1.15% (n.s.) and -1.72% (p = 0.017), respectively. The presence of active lesions at baseline MRI predicted PBVC (p = 0.022) and WMF change (p = 0.026) during the first year of treatment, after adjusting for age and corticosteroid treatment. No predictors were found for GMF volume changes.</AbstractText Early brain volume loss during natalizumab therapy is mainly due to WMF volume loss and it is related to the inflammatory activity present at the onset of therapy. We found that the pseudoatrophy effect is mostly due to white matter volume changes.</AbstractText"
]
] |
[
[
"28585255",
"Life years lost among patients with a given disease.",
"A number of suggested measures of life years lost among patients with a given disease are reviewed, and some new ones are proposed. The methods are all phrased in the framework of a (Markov or non-Markov) illness-death model in combination with a population life table. The methods are illustrated using data on Danish male patients with bipolar disorder, and some recommendations are given. Copyright © 2017 John Wiley & Sons, Ltd.</AbstractText"
]
] |
37489383
|
Management of Migraine-Associated Vestibulocochlear Disorders.
|
Migraine is a chronic neurological disorder that frequently coexists with different vestibular and cochlear symptoms (sudden hearing loss, tinnitus, otalgia, aural fullness, hyperacusis, dizziness, imbalance, and vertigo) and disorders (recurrent benign positional vertigo, persistent postural perceptual dizziness, mal de debarquement, and Menière's disease). Despite evidence of an epidemiological association and similar pathophysiology between migraine and these vestibulocochlear disorders, patients suffering from migraine-related symptoms are usually underdiagnosed and undertreated. Current migraine treatment options have shown success in treating vestibulocochlear symptoms. Lifestyle and dietary modifications (reducing stress, restful sleep, avoiding migraine dietary triggers, and avoiding starvation and dehydration) and supplements (vitamin B2 and magnesium) offer effective first-line treatments. Treatment with migraine prophylactic medications such as tricyclic antidepressants (e.g., nortriptyline), anticonvulsants (e.g., topiramate), and calcium channel blockers (e.g., verapamil) is implemented when lifestyle and dietary modifications are not sufficient in improving a patient's symptoms. We have included an algorithm that outlines a suggested approach for addressing these symptoms, taking into account our clinical observations. Greater recognition and understanding of migraine and its related vestibular and cochlear symptoms are needed to ensure the appropriate diagnosis and treatment of affected patients.</AbstractText
|
[
[
"34672361",
"Association Between Asthma and Meniere's Disease: A Nested Case-Control Study.",
"This study aimed to investigate the association between Meniere's disease and prior history of asthma.</AbstractText A nested case-control study.</AbstractText Among the patients aged ≥40 years from the Korean National Health Insurance Service-Health Screening Cohort 2002-2015, 7,734 diagnosed with Meniere's disease between 2004 and 2015 were enrolled in this study. From the 505,834 participants without a prior history of Meniere's disease, 30,936 control participants were selected based on age, sex, income, and region of residence. The presence of a prior history of asthma before the diagnosis of Meniere's disease was compared between the Meniere's disease group and control group using conditional logistic regression with odds ratios (ORs) and 95% confidence intervals (95% CIs).</AbstractText Prior history of asthma was associated with 1.30 (1.21-1.39) times higher odds of Meniere's disease (E-value = 1.92 [1.71]). Both allergic asthma and nonallergic asthma patients demonstrated higher odds of Meniere's disease than the control group (adjusted OR = 1.21 [1.08-1.36] and E-value = 1.72 [1.37] for allergic asthma; adjusted OR = 1.26 [1.17-1.36] and E-value = 1.83 [1.60] for nonallergic asthma).</AbstractText This study is the first to demonstrate a positive relationship between Meniere's disease and prior asthma history in adults. The association between prior asthma history and Meniere's disease was noted in both allergic and nonallergic asthma cases. The potential development of Meniere's disease should be considered when managing the asthma patients with dizziness or vertigo.</AbstractText 3 Laryngoscope, 132:864-872, 2022.</AbstractText"
]
] |
[
[
"37393007",
"Mini-review: \"Enteric glia functions in nervous tissue repair: Therapeutic target or tool?\".",
"In the body, nerve tissue is not only present in the central nervous system, but also in the periphery. The enteric nervous system (ENS) is a highly organized intrinsic network of neurons and glial cells grouped to form interconnected ganglia. Glial cells in the ENS are a fascinating cell population: their neurotrophic role is well established, as well as their plasticity in specific circumstances. Gene expression profiling studies indicate that ENS glia retain neurogenic potential. The identification of neurogenic glial subtype(s) and the molecular basis of glia-derived neurogenesis may have profound biological and clinical implications. In this review, we discuss the potential of using gene-editing for ENS glia and cell transplantation as therapies for enteric neuropathies. Glia in the ENS: target or tool for nerve tissue repair?</AbstractText"
]
] |
37336998
|
A sub 1 GHz ultra miniaturized folded dipole patch antenna for biomedical applications.
|
A miniaturized folded dipole patch antenna (FDPA) design for biomedical applications operating at sub 1 GHz (434 MHz) band is presented. Antenna is fabricated on FR-4 substrate material having dimensions of 16.40 mm [Formula: see text] 8.60 mm [Formula: see text] 1.52 mm (0.023[Formula: see text] [Formula: see text] 0.012[Formula: see text] [Formula: see text] 0.002[Formula: see text]). Indirect feed coupling is applied through two parallel strips at bottom layer of the substrate. The antenna size is reduced by 83% through lumped inductor placed at the center path of the radiating FDPA, suitable for biomedical (implantable) applications and hyperthermia. Moreover, Impedance matching is achieved without using any Balun transformer or any other complex matching network. The proposed antenna provides an impedance bandwidth of 6 MHz (431-437 MHz) below - 10 dB and a gain of - 31 dB at 434 MHz. The designed antenna is also placed on a human body model to evaluate its performance for hyperthermia through Specific Absorption Rate (SAR), Effective Field Size (EFS), and penetration depth (PD).</AbstractText
|
[
[
"33730953",
"Challenges and recommendations for magnetic hyperthermia characterization measurements.",
"The localized heating of magnetic nanoparticles (MNPs) <i An interlaboratory study (across <i The data show that although there is very good intralaboratory repeatability, the overall interlaboratory measurement accuracy is poor, with the consolidated <i We conclude that the study reveals a current lack of harmonization in MFH characterization of MNPs, and highlights the growing need for standardized, quantitative characterization techniques for this emerging medical technology.</AbstractText"
]
] |
[
[
"33568700",
"Morphometry of SARS-CoV and SARS-CoV-2 particles in ultrathin plastic sections of infected Vero cell cultures.",
"SARS-CoV-2 is the causative of the COVID-19 disease, which has spread pandemically around the globe within a few months. It is therefore necessary to collect fundamental information about the disease, its epidemiology and treatment, as well as about the virus itself. While the virus has been identified rapidly, detailed ultrastructural analysis of virus cell biology and architecture is still in its infancy. We therefore studied the virus morphology and morphometry of SARS-CoV-2 in comparison to SARS-CoV as it appears in Vero cell cultures by using conventional thin section electron microscopy and electron tomography. Both virus isolates, SARS-CoV Frankfurt 1 and SARS-CoV-2 Italy-INMI1, were virtually identical at the ultrastructural level and revealed a very similar particle size distribution with a median of about 100 nm without spikes. Maximal spike length of both viruses was 23 nm. The number of spikes per virus particle was about 30% higher in the SARS-CoV than in the SARS-CoV-2 isolate. This result complements a previous qualitative finding, which was related to a lower productivity of SARS-CoV-2 in cell culture in comparison to SARS-CoV.</AbstractText"
]
] |
38754255
|
Long-term seizure diary tracking habits in clinical studies: Evidence from the Human Epilepsy Project.
|
To characterize seizure tracking patterns of people with focal epilepsy using electronic seizure diary entries, and to assess for risk factors associated with poor tracking.</AbstractText We analyzed electronic seizure diary data from 410 participants with newly diagnosed focal epilepsy in the Human Epilepsy Project 1 (HEP1). Each participant was expected to record data each day during the study, regardless of seizure occurrence. The primary outcome of this post-hoc analysis was whether each participant properly tracked a seizure diary entry each day during their study participation. Using finite mixture modeling, we grouped patient tracking trajectories into data-driven clusters. Once defined, we used multinomial modeling to test for independent risk factors of tracking group membership.</AbstractText Using over up to three years of daily seizure diary data per subject, we found four distinct seizure tracking groups: consistent, frequent at study onset, occasional, and rare. Participants in the consistent tracking group tracked a median of 92% (interquartile range, IQR: 82%, 99%) of expected days, compared to 47% (IQR:34%, 60%) in the frequent at study onset group, 37% (IQR: 26%, 49%) in the occasional group, and 9% (IQR: 3%, 15%) in the rare group. In multivariable analysis, consistent trackers had lower rates of seizure days per tracked year during their study participation, compared to other groups.</AbstractText Future efforts need to focus on improving seizure diary tracking adherence to improve quality of outcome data, particularly in those with higher seizure burden. In addition, accounting for missing data when using seizure diary data as a primary outcome is important in research trials. If not properly accounted for, total seizure burden may be underestimated and biased, skewing results of clinical trials.</AbstractText
|
[
[
"36941137",
"Association of FAT1 with focal epilepsy and correlation between seizure relapse and gene expression stage.",
"The FAT1 gene encodes FAT atypical cadherin 1, which is essential for foetal development, including brain development. This study aimed to investigate the relationship between FAT1 variants and epilepsy.</AbstractText Trio-based whole-exome sequencing was performed on a cohort of 313 patients with epilepsy. Additional cases with FAT1 variants were collected from the China Epilepsy Gene V.1.0 Matching Platform.</AbstractText Four pairs of compound heterozygous missense FAT1 variants were identified in four unrelated patients with partial (focal) epilepsy and/or febrile seizures, but without intellectual disability/developmental abnormalities. These variants presented no/very low frequencies in the gnomAD database, and the aggregate frequencies in this cohort were significantly higher than those in controls. Two additional compound heterozygous missense variants were identified in two unrelated cases using the gene-matching platform. All patients experienced infrequent (yearly/monthly) complex partial seizures or secondary generalised tonic-clonic seizures. They responded well toantiseizure medication, but seizures relapsed in three cases when antiseizure medication were decreased or withdrawn after being seizure-free for three to six years, which correlated with the expression stage of FAT1. Genotype-phenotype analysis showed that epilepsy-associated FAT1 variants were missense, whereas non-epilepsy-associated variants were mainly truncated. The relationship between FAT1 and epilepsy was evaluated to be \"Strong\" by the Clinical Validity Framework of ClinGen.</AbstractText FAT1 is a potential causative gene of partial epilepsy and febrile seizures. Gene expression stage was suggested to be one of the considerations in determining the duration ofantiseizure medication. Genotype-phenotype correlation helps to explain the mechanisms underlying phenotypic variation.</AbstractText"
]
] |
[
[
"39141740",
"Single neuron responses to perceptual difficulty in the mouse auditory cortex.",
"Perceptual learning leads to improvement in behavioral performance, yet how the brain supports challenging perceptual demands is unknown. We used two photon imaging in the mouse primary auditory cortex during behavior in a Go-NoGo task designed to test perceptual difficulty. Using general linear model analysis, we found a subset of neurons that increased their responses during high perceptual demands. Single neurons increased their responses to both Go and NoGo sounds when mice were engaged in the more difficult perceptual discrimination. This increased responsiveness contributes to enhanced cortical network discriminability for the learned sounds. Under passive listening conditions, the same neurons responded weaker to the more similar sound pairs of the difficult task, and the training protocol by itself induced specific suppression to the learned sounds. Our findings identify how neuronal activity in auditory cortex is modulated during high perceptual demands, which is a fundamental feature associated with perceptual improvement.</AbstractText"
]
] |
39060866
|
Tension hydrothorax complicating syringopleural shunt for post-traumatic syringomyelia.
|
Syringomyelia is a rare phenomenon that is typically associated with Chiari malformations. However, they can occur in the setting of post-traumatic spinal injury. Potential diversion treatments include syringopleural (SPS), syringoperitoneal and syringosubarachnoid shunts. Short-term complications have been reported in the literature, however, long term complications are not well documented. This case report is of a 43-year-old woman found deceased in bed. She had a history of a traumatic spinal injury following a motor vehicle accident 15 years prior to death. This was complicated by a syringomyelia/syrinx requiring a SPS insertion. Post-mortem imaging and autopsy findings demonstrated a large right tension hydrothorax with dense fibrosis of the pleural surfaces, contralateral diffuse alveolar damage lung changes histologically and a patent SPS. Her cause of death was registered as "Right tension hydrothorax and diffuse alveolar damage complicating right syringopleural shunt and thoracic syrinx".</AbstractText
|
[
[
"22186848",
"Trigger factors for rupture of intracranial aneurysms in relation to patient and aneurysm characteristics.",
"Female gender, age above 60 years, and an aneurysm larger than 5 mm or location on the posterior circulation are associated with a higher rupture risk of intracranial aneurysms. We hypothesized that this association is explained by a higher susceptibility to (one of) the eight trigger factors that were recently identified. We included 250 patients with aneurysmal subarachnoid hemorrhage. We calculated relative risks (RR) with 95% confidence intervals (95% CI) of aneurysmal rupture for trigger factors according to sex, age, site, and size of the aneurysms by means of the case-crossover design. None of the triggers except for physical exercise differed according to patient and aneurysm characteristics. In the hour after exposure to physical exercise: (1) patients over the age of 60 have a six-times-higher risk of rupture (RR 13; 95% CI 6.3-26) than those of 60 years of age and under (RR 2.3; 1.3-4.1); (2) aneurysms at the internal carotid artery have a higher risk than those at other locations (RR 17; 7.8-37), but this was only statistically significant when compared to anterior communicating artery aneurysms (RR 3.2; 1.6-6.1); (3) aneurysms 5 mm or smaller had a higher risk of rupture (RR 9.5; 4.6-19) than larger aneurysms (RR 2.4; 1.3-4.3); and (4) women and men had similar risks. A higher susceptibility to exercise might explain part of the higher risk of rupture in older patients. Why women and patients with aneurysms larger than 5 mm or posterior circulation aneurysms have a higher risk of rupture remains to be settled.</AbstractText"
]
] |
[
[
"39705858",
"A minor role for hemispheric specialization in determining pseudoneglect: A pre-registered replication-extension study.",
"Neurologically intact individuals display a mild asymmetry in spatial attention that can be measured during experimental spatial tasks such as line bisection. Although this phenomenon, known as pseudoneglect, is traditionally explained as the consequence of right hemisphere dominance for visuospatial attention, surmounting evidence suggests this is not its sole or even its most important determinant. For instance, a recent fMRI study in left-handers revealed that rare individuals with a reversed, left hemispheric dominance (LHDS, N = 23) also demonstrated left-sided pseudoneglect, although their spatial bias was less marked compared to typically lateralized controls (N = 40). The current study sought to replicate and extend these findings in a broader cohort of right-handers (N = 75) and left-handers (N = 181), while addressing methodological limitations of the original study. Contrary to the predictions of the hemispheric specialization account, pseudoneglect was not reversed in LHDS participants (N = 49). However, the pseudoneglect effect was reduced compared to controls with typical cerebral laterality (N = 207) due to a population-level randomization of pseudoneglect in the LHDS group. These results align with those of the original study, supporting a multifactorial interpretation of pseudoneglect, with hemisphere specialization as one among many determinants rather than being the predominant cause.</AbstractText"
]
] |
39709140
|
Safety and efficacy of GLP-1/FGF21 dual agonist HEC88473 in MASLD and T2DM: A randomized, double-blind, placebo-controlled study.
|
Glucagon-like peptide-1 (GLP-1) and fibroblast growth factor 21 (FGF21) are key regulators of glucose and lipid metabolism. In the present study, we assessed the safety and efficacy of a novel GLP-1/FGF21 dual agonist HEC88473 for the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD) combined with type 2 diabetes mellitus (T2DM).</AbstractText This was a randomized, double-blind, placebo-controlled, multiple-ascending-dose phase Ib/IIa trial. Sixty patients with MASLD and T2DM were randomized (10:2) to receive HEC88473 (5.1, 15.3, 30.6, 45.9, or 68.0 mg) or placebo via weekly subcutaneous injection for 5 weeks.</AbstractText After 5 weeks of treatment with HEC88473, MRI-proton density fat fraction (MRI-PDFF) was reduced in a dose-proportional manner. The largest relative mean change reached -47.21% (p = 0.0143) in the 30.6 mg cohort, compared with -15.05% in the placebo group, with a higher proportion of >30% relative reductions in patients with baseline PDFF >8%. The 5-week treatment with HEC88473 significantly reduced levels of HbA1c (glycated hemoglobin), as well as fasting and postprandial glucose levels. The largest mean change in HbA1c was -1.10% in the 68.0 mg cohort, compared with -0.31% in the placebo group. Improvement was also observed in participants' lipid profiles. Most adverse events were mild to moderate in severity. The most frequently reported adverse events were gastrointestinal disorders (n = 29, 48.3%).</AbstractText Herein, we report the clinical safety and proof-of-concept data for the GLP-1/FGF21 dual agonist HEC88473. A 5-week treatment with HEC88473 was generally safe and well tolerated, with multiple positive effects observed, including reduced liver fat, and improved glycemic control, insulin resistance and lipid metabolism, together indicating comprehensive improvement in metabolic syndrome.</AbstractText In this randomized, double-blind, placebo-controlled phase Ib/IIa study, we assessed clinical safety, pharmacodynamic and pharmacokinetic data of the GLP-1/FGF21 dual agonist HEC88473 in patients with MASLD (metabolic dysfunction-associated steatotic liver disease) and T2DM (type 2 diabetes mellitus). HEC88473 was generally safe and well tolerated. The GLP-1/FGF21 dual agonist significantly reduced the hepatic fat fraction assessed using MRI-proton density fat fraction, and improved glycemic control and lipid profiles with only 5 weeks' treatment, leading to comprehensive improvement in metabolic syndrome. The present results suggest that HEC88473 could be a promising treatment option in this patient population.</AbstractText Chinese Drug Trial Identifier (http://www.chinadrugtrials.org.cn/index.html): CTR20211088.</AbstractText GOV: NCT05943886.</AbstractText
|
[
[
"35842609",
"Utilization of T1-Mapping for the pelvic and thigh muscles in Duchenne Muscular Dystrophy: a quantitative biomarker for disease involvement and correlation with clinical assessments.",
"Little is known about the disease distribution and severity detected by T1-mapping in Duchenne muscular dystrophy (DMD). Furthermore, the correlation between skeletal muscle T1-values and clinical assessments is less studied. Hence, the purposes of our study are to investigate quantitative T1-mapping in detecting the degree of disease involvement by detailed analyzing the hip and thigh muscle, future exploring the predicting value of T1-mapping for the clinical status of DMD.</AbstractText Ninety-two DMD patients were included. Grading fat infiltration and measuring the T1-values of 19 pelvic and thigh muscles (right side) in axial T1-weighted images (T1WI) and T1-maps, respectively, the disease distribution and severity were evaluated and compared. Clinical assessments included age, height, weight, BMI, wheelchair use, timed functional tests, NorthStar ambulatory assessment (NSAA) score, serum creatine kinase (CK) level. Correlation analysis were performed between the muscle T1-value and clinical assessments. Multiple linear regression analysis was conducted for the independent association of T1-value and motor function.</AbstractText The gluteus maximus had the lowest T1-value, and the gracilis had the highest T1-value. T1-value decreased as the grade of fat infiltration increased scored by T1WI (P < 0.001). The decreasing of T1-values was correlated with the increase of age, height, weight, wheelchair use, and timed functional tests (P < 0.05). T1-value correlated with NSAA (r = 0.232-0.721, P < 0.05) and CK (r = 0.208-0.491, P < 0.05) positively. T1-value of gluteus maximus, tensor fascia, vastus lateralis, vastus intermedius, vastus medialis, and adductor magnus was independently associated with the clinical motor function tests (P < 0.05). Interclass correlation coefficient (ICC) analysis and Bland-Altman plots showed excellent inter-rater reliability of T1-value region of interest (ROI) measurements.</AbstractText T1-mapping can be used as a quantitative biomarker for disease involvement, further assessing the disease severity and predicting motor function in DMD.</AbstractText"
]
] |
[
[
"40634289",
"Failure to resolve inflammation contributes to juvenile onset cardiac damage in a mouse model of Duchenne muscular dystrophy.",
"Absence of dystrophin protein causes cardiac dysfunction in patients with Duchenne muscular dystrophy (DMD). Unlike boys with DMD, the common mouse model of DMD (B10-mdx) does not manifest cardiac deficits until late adulthood. This has limited our understanding of the mechanism and therapeutic approaches to target the pediatric onset of cardiac pathology in DMD. Here we show that the mdx mouse model on the DBA/2 J genetic background (D2-mdx) displays juvenile-onset cardiac degeneration. Molecular and histological analysis revealed that cardiac damage in this model is linked to increased leukocyte chemotactic signaling and an inability to resolve inflammation. These deficiencies result in chronic inflammation and fibrotic conversion of the extracellular matrix (ECM) in the juvenile D2-mdx heart. To address these pathologies, we tested the utility of pro-resolution therapy to clear chronic cardiac inflammation. Use of an N-formyl peptide receptor (FPR) agonist helped physiologically resolve inflammation and mitigate the downstream events that lead to fibrotic degeneration of cardiomyocytes, preventing juvenile onset cardiac muscle loss. These results establish the utility of D2-mdx model to study events associated with pediatric-onset cardiac damage and demonstrates pro-resolution therapy as an alternate to anti-inflammatory therapy for treating degenerative cardiac pathology that leads to cardiomyopathy in DMD.</AbstractText Facioscapulohumeral muscular dystrophy (FSHD) typically presents with weakness of the facial muscles, the stabilizers of the scapula, and/or the dorsiflexors of the foot. Severity is highly variable. Weakness can be slowly progressive and approximately 20% of affected individuals eventually require a wheelchair. Life expectancy is not shortened.</AbstractText The diagnosis of FSHD1 is established in a proband with characteristic clinical features and a heterozygous pathogenic contraction of the D4Z4 repeat array in the subtelomeric region of chromosome 4q35 on a permissive chromosome 4 haplotype. The diagnosis of FSHD2 is established in a proband with characteristic clinical features and hypomethylation of the D4Z4 repeat array in the subtelomeric region of chromosome 4q35 on a permissive chromosome 4 haplotype. Hypomethylation of the D4Z4 repeat array can be the result of a heterozygous pathogenic variant in <i <i <i"
]
] |
38958626
|
How to Achieve Highly Professional Care in the Postoperative Ward: The Care of Infants and Toddlers.
|
The purpose of this study was to describe the experiences of critical care nurses (CCNs) and registered nurse anesthetists (RNAs) when monitoring and observing infants and toddlers recovering from anesthesia.</AbstractText A qualitative design with a critical incident approach.</AbstractText Semistructured individual interviews were conducted with a purposeful sample of CCNs and RNAs (n = 17) from postanesthesia care units at two hospitals. The critical incident technique approach was used to guide the interviews, and data were analyzed inductively using thematic analysis.</AbstractText The main finding was the CCNs' and RNAs' description of how they "watch over the children and stay close" to provide emotional and physical safety. CCNs' and RNAs' experiences of observing and managing the children's small, immature airways were reflected in the theme "using situation awareness of the small, immature airways." The theme "understanding emergence agitation" describes the challenge that arises when children are anxious, feel insecure, and have pain, and the theme "having parents nearby" shows the necessity and value of involving parents in their children's care.</AbstractText Findings from this study suggest that caring for infants and toddlers recovering from anesthesia requires experience and both technical and nontechnical skills. These are prerequisites for achieving readiness for planning, setting priorities, and adapting one's behavior if an adverse event occurs. Alertness and the ability to solve acute problems and make quick decisions are essential because of the risks associated with children's small, immature airways, as is the ability to understand and respond to emergence agitation. Having parents nearby is equally important for creating the conditions for compassionate child- and family-centered care.</AbstractText
|
[
[
"32498631",
"Relationships between sleep, exercise timing, and chronotype in young adults.",
"To examine the relationships between exercise timing, chronotype, sleep, and mood, college students (<i"
]
] |
[
[
"40558907",
"Stress Distribution on Endodontically Treated Anterior Teeth Restored via Different Ceramic Materials with Varying Post Lengths Versus Endocrown-A 3D Finite Element Analysis.",
"This study aims to evaluate the stress distribution on endodontically treated anterior teeth restored using different restorative materials and different post lengths versus endocrowns employing finite element analysis (FEA).</AbstractText An extracted human central incisor tooth with a fully formed apex was scanned using high-resolution cone beam computed tomography (CBCT) to generate 3D finite element models. Six models of restorations of badly destructed central incisor were grouped according to the type of ceramic material and post length versus endocrown restorations. Group V-L: Vita Enamic, long post (10 mm intra-radicular), Group C-L: Celtra Duo, long post (10 mm intra-radicular), Group V-Sh: Vita Enamic, short post (3 mm intra-radicular), Group C-Sh: Celtra Duo, short post (3 mm intra-radicular), Group V-E: Vita Enamic endocrown (3 mm intra-radicular), and Group C-E: Celtra Duo endocrown (3 mm intra-radicular). A static load of 200 N was applied to the palatal surface at a 45 degree angle to the tooth's long axis. The maximum equivalent von Mises stress and maximum principal stress were analyzed at four locations: the finish line, coronal third of the root (12 mm from the apex), middle third of the root (8 mm from the apex), and apical third of the root (4 mm from the apex).</AbstractText Group C-L exhibited the highest maximum VM stress and PS at the finish line, in addition to the highest maximum VM stress and PS at the root apical third, while group C-Sh reported the least maximum VM stress at the root apical third among the groups. All Celtra Duo groups reported higher maximum VM stress than the corresponding groups of Vita Enamic at the finish line and root coronal thirds. However, at the root middle and apical thirds, both materials recorded similar stresses.</AbstractText Short posts and Vita Enamic endocrowns showed minimal stress, especially at the finish line, while long posts increased stress and fracture risk. The findings support conservative restorations without posts, although clinical validation is needed to confirm their long-term effectiveness and safety.</AbstractText"
]
] |
40685869
|
Analysis of ALPS-Index: Difference in Type 2 Diabetes Mellitus With or Without Mild Cognitive Impairment and Its Relationship With Hippocampal Microstructure.
|
Type 2 diabetes mellitus (T2DM) with cognitive impairment has a high incidence rate globally, and there is a need to investigate the relationship among the glymphatic system, hippocampus microstructure, and cognition in T2DM. The present study aims to delineate changes in the perivascular space index (ALPS-index) among T2DM patients with different cognitive states and investigate any possible correlation between the ALPS-index and the diffusive indicators of the bilateral hippocampi in T2DM. In addition, we seek to identify specific cognitive domains with substantial correlation with the ALPS-index in the general population.</AbstractText A total of 113 participants were recruited, comprising 37 T2DM patients with normal cognitive function (DMNC), 39 T2DM patients with mild cognitive impairment (DMMCI), and 37 healthy controls (HC). Clinical information, neuropsychological assessments, and experienced multimodal magnetic resonance imaging scans were recorded from all the participants. A noninvasive method was applied to obtain all ALPS-index measures, such as the left, right, and average ALPS-index, along with diffusive indicators of the bilateral hippocampi, comprising fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD).</AbstractText A statistically marginal difference in the average ALPS-index was noted among HC, DMNC, and DMMCI groups. According to binary logistic regression analysis results, the average ALPS-index significantly altered the cognitive function in T2DM. Partial correlation analyses revealed a positive association between the average ALPS-index and FA, as well as a negative association with MD and RD in the bilateral hippocampi of the T2DM groups. In the general population, partial correlation analysis indicated that the average ALPS-index correlated with the auditory verbal learning test (AVLT) immediate recall scores.</AbstractText In summary, our findings demonstrated that glymphatic system function in the brain progressively deteriorates with worsening cognitive impairment among T2DM patients. Moreover, T2DM significantly disrupts the relationship patterns between the glymphatic system and bilateral hippocampal microstructure. Thus, the mean ALPS-index may act as a novel neuroimaging biomarker for assessing cognitive function in T2DM.</AbstractText
|
[
[
"36041852",
"Cortical Ripples during NREM Sleep and Waking in Humans.",
"Hippocampal ripples index the reconstruction of spatiotemporal neuronal firing patterns essential for the consolidation of memories in the cortex during non-rapid eye movement sleep (NREM). Recently, cortical ripples in humans have been shown to enfold the replay of neuron firing patterns during cued recall. Here, using intracranial recordings from 18 patients (12 female), we show that cortical ripples also occur during NREM in humans, with similar density, oscillation frequency (∼90 Hz), duration, and amplitude to waking. Ripples occurred in all cortical regions with similar characteristics, unrelated to putative hippocampal connectivity, and were less dense and robust in higher association areas. Putative pyramidal and interneuron spiking phase-locked to cortical ripples during NREM, with phase delays consistent with ripple generation through pyramidal-interneuron feedback. Cortical ripples were smaller in amplitude than hippocampal ripples but were similar in density, frequency, and duration. Cortical ripples during NREM typically occurred just before the upstate peak, often during spindles. Upstates and spindles have previously been associated with memory consolidation, and we found that cortical ripples grouped cofiring between units within the window of spike timing-dependent plasticity. Thus, human NREM cortical ripples are as follows: ubiquitous and stereotyped with a tightly focused oscillation frequency; similar to hippocampal ripples; associated with upstates and spindles; and associated with unit cofiring. These properties are consistent with cortical ripples possibly contributing to memory consolidation and other functions during NREM in humans.<b"
]
] |
[
[
"40404790",
"Early life stress impairs hippocampal subfield myelination.",
"The hippocampus is an archicortical structure that is highly sensitive to experience and is made up of individual subfields. These subfields, crucial for learning and memory, rapidly develop and are vulnerable to early stress, yet the mechanisms are unknown. Here, we analyse data from 520 neonates born between 23 and 42 weeks' gestation to assess how early extrauterine exposure-related stress influences subfield maturation. Subfields are segmented automatically by training a U-net model on infant data using HippUnfold, a novel tool for subfield segmentation. Results indicate that subfield volumes are resilient to early stress, while myelination shows greater vulnerability and variation, which may contribute to long-term outcomes. Notably, subfields are not uniformly impacted by stress, with CA1 and CA2 showing the largest effects. Developmental context, including time spent in and ex utero, primarily influences hippocampal subfield myelination.</AbstractText"
]
] |
22028681
|
The Relationship between Saccadic Choice and Reaction Times with Manipulations of Target Value.
|
Choosing the option with the highest expected value (EV; reward probability × reward magnitude) maximizes the intake of reward under conditions of uncertainty. However, human economic choices indicate that our value calculation has a subjective component whereby probability and reward magnitude are not linearly weighted. Using a similar economic framework, our goal was to characterize how subjective value influences the generation of simple motor actions. Specifically, we hypothesized that attributes of saccadic eye movements could provide insight into how rhesus monkeys, a well-studied animal model in cognitive neuroscience, subjectively value potential visual targets. In the first experiment, monkeys were free to choose by directing a saccade toward one of two simultaneously displayed targets, each of which had an uncertain outcome. In this task, choices were more likely to be allocated toward the higher valued target. In the second experiment, only one of the two possible targets appeared on each trial. In this task, saccadic reaction times (SRTs) decreased toward the higher valued target. Reward magnitude had a much stronger influence on both choices and SRTs than probability, whose effect was observed only when reward magnitude was similar for both targets. Across EV blocks, a strong relationship was observed between choice preferences and SRTs. However, choices tended to maximize at skewed values whereas SRTs varied more continuously. Lastly, SRTs were unchanged when all reward magnitudes were 1×, 1.5×, and 2× their normal amount, indicating that saccade preparation was influenced by the relative value of the targets rather than the absolute value of any single-target. We conclude that value is not only an important factor( )for deliberative decision making in primates, but also for the selection and preparation of simple motor actions, such as saccadic eye movements. More precisely, our results indicate that, under conditions of uncertainty, saccade choices and reaction times are influenced by the relative expected subjective value of potential movements.</AbstractText
|
[
[
"19321780",
"The neurobiology of reference-dependent value computation.",
"A key focus of current research in neuroeconomics concerns how the human brain computes value. Although, value has generally been viewed as an absolute measure (e.g., expected value, reward magnitude), much evidence suggests that value is more often computed with respect to a changing reference point, rather than in isolation. Here, we present the results of a study aimed to dissociate brain regions involved in reference-independent (i.e., \"absolute\") value computations, from those involved in value computations relative to a reference point. During functional magnetic resonance imaging, subjects acted as buyers and sellers during a market exchange of lottery tickets. At a behavioral level, we demonstrate that subjects systematically accorded a higher value to objects they owned relative to those they did not, an effect that results from a shift in reference point (i.e., status quo bias or endowment effect). Our results show that activity in orbitofrontal cortex and dorsal striatum track parameters such as the expected value of lottery tickets indicating the computation of reference-independent value. In contrast, activity in ventral striatum indexed the degree to which stated prices, at a within-subjects and between-subjects level, were distorted with respect to a reference point. The findings speak to the neurobiological underpinnings of reference dependency during real market value computations.</AbstractText"
]
] |
[
[
"22254584",
"Graphic patterns of cortical functional connectivity of depressed patients on the basis of EEG measurements.",
"Considerable evidences have shown a decrease of neuronal activity in the left frontal lobe of depressed patients, but the underlying cortical network is still unclear. The present study intends to investigate the conscious-state brain network patterns in depressed patients compared with control individuals. Cortical functional connectivity is quantified by the partial directed coherence (PDC) analysis of multichannel EEG signals from 12 depressed patients and 12 healthy volunteers. The corresponding PDC matrices are first converted into unweighted graphs by applying a threshold to obtain the topographic property in-degree (K(in)). A significantly larger K(in) in the left hemisphere is identified in depressed patients, while a symmetric pattern is found in the control group. Another two topographic measures, i.e., clustering coefficients (C) and characteristic path length (L), are obtained from the original weighted PDC digraphs. Compared with control individuals, significantly smaller C and L are revealed in the depression group, indicating a random network-like architecture due to affective disorder. This study thereby provides further support for the presence of a hemispheric asymmetry syndrome in the depressed patients. More importantly, we present evidence that depression is characterized by a loss of optimal small-world network characteristics in conscious state.</AbstractText"
]
] |
22609941
|
Selective loss of AMPA receptors at corticothalamic synapses in the epileptic stargazer mouse.
|
Absence seizures are common in the stargazer mutant mouse. The mutation underlying the epileptic phenotype in stargazers is a defect in the gene encoding the normal expression of the protein stargazin. Stargazin is involved in the membrane trafficking and synaptic targeting of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) at excitatory glutamatergic synapses. Thus, the genetic defect in the stargazer results in a loss of AMPARs and consequently, excitation at glutamatergic synapses. Absence seizures are known to arise in thalamocortical networks. In the present study we show for the first time, using Western blot analysis and quantitative immunogold cytochemistry, that in the epileptic stargazer mouse, there is a global loss of AMPAR protein in nucleus reticularis (RTN) and a selective loss of AMPARs at corticothalamic synapses in inhibitory neurons of the RTN thalamus. In contrast, there is no significant loss of AMPARs at corticothalamic synapses in excitatory relay neurons in the thalamic ventral posterior (VP) region. The findings of this study thus provide cellular and molecular evidence for a selective regional loss of synaptic AMPAR within the RTN that could account for the loss of function at these inhibitory neuron synapses, which has previously been reported from electrophysiological studies. The specific loss of AMPARs at RTN but not relay synapses in the thalamus of the stargazer, could contribute to the absence epilepsy phenotype by altering thalamocortical network oscillations. This is supported by recent evidence that loss of glutamate receptor subunit 4 (GluA4) (the predominant AMPAR-subtype in the thalamus), also leads to a specific reduction in strength in the cortico-RTN pathway and enhanced thalamocortical oscillations, in the Gria4(-/-) model of absence epilepsy. Thus further study of thalamic changes in these models could be important for future development of drugs targeted to absence epilepsy.</AbstractText
|
[
[
"22344687",
"T-type calcium channel blockers that attenuate thalamic burst firing and suppress absence seizures.",
"Absence seizures are a common seizure type in children with genetic generalized epilepsy and are characterized by a temporary loss of awareness, arrest of physical activity, and accompanying spike-and-wave discharges on an electroencephalogram. They arise from abnormal, hypersynchronous neuronal firing in brain thalamocortical circuits. Currently available therapeutic agents are only partially effective and act on multiple molecular targets, including γ-aminobutyric acid (GABA) transaminase, sodium channels, and calcium (Ca(2+)) channels. We sought to develop high-affinity T-type specific Ca(2+) channel antagonists and to assess their efficacy against absence seizures in the Genetic Absence Epilepsy Rats from Strasbourg (GAERS) model. Using a rational drug design strategy that used knowledge from a previous N-type Ca(2+) channel pharmacophore and a high-throughput fluorometric Ca(2+) influx assay, we identified the T-type Ca(2+) channel blockers Z941 and Z944 as candidate agents and showed in thalamic slices that they attenuated burst firing of thalamic reticular nucleus neurons in GAERS. Upon administration to GAERS animals, Z941 and Z944 potently suppressed absence seizures by 85 to 90% via a mechanism distinct from the effects of ethosuximide and valproate, two first-line clinical drugs for absence seizures. The ability of the T-type Ca(2+) channel antagonists to inhibit absence seizures and to reduce the duration and cycle frequency of spike-and-wave discharges suggests that these agents have a unique mechanism of action on pathological thalamocortical oscillatory activity distinct from current drugs used in clinical practice.</AbstractText"
]
] |
[
[
"22447075",
"Genetically determined P2X7 receptor pore formation regulates variability in chronic pain sensitivity.",
"Chronic pain is highly variable between individuals, as is the response to analgesics. Although much of the variability in chronic pain and analgesic response is heritable, an understanding of the genetic determinants underlying this variability is rudimentary. Here we show that variation within the coding sequence of the gene encoding the P2X7 receptor (P2X7R) affects chronic pain sensitivity in both mice and humans. P2X7Rs, which are members of the family of ionotropic ATP-gated receptors, have two distinct modes of function: they can function through their intrinsic cationic channel or by forming nonselective pores that are permeable to molecules with a mass of up to 900 Da. Using genome-wide linkage analyses, we discovered an association between nerve-injury-induced pain behavior (mechanical allodynia) and the P451L mutation of the mouse P2rx7 gene, such that mice in which P2X7Rs have impaired pore formation as a result of this mutation showed less allodynia than mice with the pore-forming P2rx7 allele. Administration of a peptide corresponding to the P2X7R C-terminal domain, which blocked pore formation but not cation channel activity, selectively reduced nerve injury and inflammatory allodynia only in mice with the pore-forming P2rx7 allele. Moreover, in two independent human chronic pain cohorts, a cohort with pain after mastectomy and a cohort with osteoarthritis, we observed a genetic association between lower pain intensity and the hypofunctional His270 (rs7958311) allele of P2RX7. Our findings suggest that selectively targeting P2X7R pore formation may be a new strategy for individualizing the treatment of chronic pain.</AbstractText"
]
] |
23986248
|
Using IQ discrepancy scores to examine the neural correlates of specific cognitive abilities.
|
The underlying neural determinants of general intelligence have been studied intensively, and seem to derive from the anatomical and functional characteristics of a frontoparietal network. Little is known, however, about the underlying neural correlates of domain-specific cognitive abilities, the other factors hypothesized to explain individual performance on intelligence tests. Previous preliminary studies have suggested that spatially distinct neural structures do not support domain-specific cognitive abilities. To test whether differences between abilities that affect performance on verbal and performance tasks derive instead from the morphological features of a single anatomical network, we assessed in two independent samples of healthy human participants (N=83 and N=58; age range, 5-57 years) the correlation of cortical thickness with the magnitude of the verbal intelligence quotient (VIQ)-performance intelligence quotient (PIQ) discrepancy. We operationalized the VIQ-PIQ discrepancy by regressing VIQ onto PIQ (VIQ-regressed-on-PIQ score), and by regressing PIQ onto VIQ (PIQ-regressed-on-VIQ score). In both samples, a progressively thinner cortical mantle in anterior and posterior regions bilaterally was associated with progressively greater (more positive) VIQ-regressed-on-PIQ scores. A progressively thicker cortical mantle in anterior and posterior regions bilaterally was associated with progressively greater (more positive) PIQ-regressed-on-VIQ scores. Variation in cortical thickness in these regions accounted for a large portion of the overall variance in magnitude of the VIQ-PIQ discrepancy. The degree of hemispheric asymmetry in cortical thickness accounted for a much smaller but statistically significant portion of variance in VIQ-PIQ discrepancy.</AbstractText
|
[
[
"17204295",
"Neural correlates of processing facial identity based on features versus their spacing.",
"Adults' expertise in recognizing facial identity involves encoding subtle differences among faces in the shape of individual facial features (featural processing) and in the spacing among features (a type of configural processing called sensitivity to second-order relations). We used fMRI to investigate the neural mechanisms that differentiate these two types of processing. Participants made same/different judgments about pairs of faces that differed only in the shape of the eyes and mouth, with minimal differences in spacing (featural blocks), or pairs of faces that had identical features but differed in the positions of those features (spacing blocks). From a localizer scan with faces, objects, and houses, we identified regions with comparatively more activity for faces, including the fusiform face area (FFA) in the right fusiform gyrus, other extrastriate regions, and prefrontal cortices. Contrasts between the featural and spacing conditions revealed distributed patterns of activity differentiating the two conditions. A region of the right fusiform gyrus (near but not overlapping the localized FFA) showed greater activity during the spacing task, along with multiple areas of right frontal cortex, whereas left prefrontal activity increased for featural processing. These patterns of activity were not related to differences in performance between the two tasks. The results indicate that the processing of facial features is distinct from the processing of second-order relations in faces, and that these functions are mediated by separate and lateralized networks involving the right fusiform gyrus, although the FFA as defined from a localizer scan is not differentially involved.</AbstractText"
]
] |
[
[
"23990221",
"Locomotor activity and anxiety status, but not spatial working memory, are affected in mice after brief exposure to cuprizone.",
"Chronic long-term exposure to cuprizone causes severe brain demyelination in mice, which leads to changes in locomotion, working memory and anxiety. These findings suggest the importance of intact myelin for these behaviors. This study aimed to investigate the possible behavioral changes in mice with mild oligodendrocyte/myelin damage that parallels the white matter changes seen in the brains of patients with psychiatric disporders. We used the cuprizone-treated mouse model to test both tissue changes and behavioral functions (locomotor activity, anxiety status, and spatial working memory). The results showed that mice given cuprizone in their diet for 7 days had no significant myelin breakdown as evaluated by immunohistochemical staining for myelin basic protein, while the number of mature oligodendrocytes was reduced. The number and length of Caspr protein clusters, a structural marker of the node of Ranvier, did not change. The locomotor activity of the cuprizone-treated mice increased whereas their anxiety levels were lower than in normal controls; spatial working memory, however, did not change. These results, for the first time, link emotion-related behavior with mild white matter damage in cuprizone-treated mice.</AbstractText"
]
] |
40620288
|
The correlation between muscle strength, inhibitory function, and cognitive function in older adults with cognitive impairment: evidence from resting-state electroencephalography.
|
This study explored the associations among muscle strength, inhibitory control, and cognitive function in older adults with cognitive impairment, focusing on related EEG changes.</AbstractText Among 247 adults aged 70 and above, 120 with cognitive impairment were included. Assessments included the Montreal Cognitive Assessment (MoCA), Stroop task, grip strength, and resting-state EEG.</AbstractText Inhibitory control was significantly related to cognitive function: accuracy in congruent (r = 0.599, <i Muscle strength may support cognitive and inhibitory function by influencing specific EEG activities. These findings highlight the neurophysiological links among muscle strength, cognition, and brain activity, offering potential biomarkers for early detection and intervention in cognitive decline.</AbstractText
|
[
[
"11834781",
"Placebo and opioid analgesia-- imaging a shared neuronal network.",
"It has been suggested that placebo analgesia involves both higher order cognitive networks and endogenous opioid systems. The rostral anterior cingulate cortex (rACC) and the brainstem are implicated in opioid analgesia, suggesting a similar role for these structures in placebo analgesia. Using positron emission tomography, we confirmed that both opioid and placebo analgesia are associated with increased activity in the rACC. We also observed a covariation between the activity in the rACC and the brainstem during both opioid and placebo analgesia, but not during the pain-only condition. These findings indicate a related neural mechanism in placebo and opioid analgesia.</AbstractText"
]
] |
[
[
"40097941",
"Integrating parent report, observed behavior, and physiological measures to identify biomarkers of sensory over-responsivity in autism.",
"Sensory over-responsivity (SOR) is a heightened reaction to environmental stimuli commonly seen in autism spectrum disorder (ASD) which impacts daily functioning. Parent-reported and observed behavioral assessments are used to study SOR, but show limited associations with each other, possibly because they measure different aspects of SOR or because children inhibit their responses during standardized assessments. Physiological measures provide an objective measure of sensory reactivity, and atypical heart rate (HR) responses to aversive stimuli have been shown to be related to SOR in ASD youth. This study aimed to compare how reported and observed measures of SOR predict HR and to examine if the level of reported behavioral inhibition in ASD youth affects how observed SOR behaviors correlate with physiological reactivity.</AbstractText Participants were 54 typically developing (TD) and 83 ASD youth, ages 8-17, who completed a standardized behavioral assessment of SOR while electrocardiogram recordings were collected. Participants' parents also reported on their child's SOR symptoms and behavioral inhibition.</AbstractText ASD youth showed lower inter-beat-intervals (IBI; higher HR) across all auditory and tactile stimuli. For ASD youth, parent-reported SOR interacted with observed SOR to predict HR changes across the stimulation periods, indicating that ASD participants whose parents reported they had high SOR in their daily life, and showed high observed SOR in the lab assessment, exhibited reduced HR deceleration (orienting) after the onset of the stimulus and subsequent increased HR acceleration. Finally, we found that ASD participants who had lower parent-reported behavioral inhibition had a stronger correlation between observed SOR behavior and atypical HR responses.</AbstractText Results support prior findings that increased HR responses to aversive stimuli is related to both ASD and SOR. Furthermore, observed and parent-reported SOR interacted to predict HR, suggesting that a multi-method approach may best capture the extent of SOR for an individual. However, observed SOR measures may be most accurate for ASD youth who are less likely to inhibit their behavioral responses. This study illustrates the importance of integrating multiple measures of sensory reactivity to identify SOR. HR measures of sensory reactivity have the potential to serve as a biomarker of SOR across a diverse range of individuals.</AbstractText"
]
] |
34900214
|
Role of the Dorsal Posterior Parietal Cortex in the Accurate Perception of Object Magnitude in Peripheral Vision.
|
Following superior parietal lobule and intraparietal sulcus (SPL-IPS) damage, optic ataxia patients underestimate the distance of objects in the ataxic visual field such that they produce hypometric pointing errors. The metrics of these pointing errors relative to visual target eccentricity fit the cortical magnification of central vision. The SPL-IPS would therefore implement an active "peripheral magnification" to match the real metrics of the environment for accurate action. We further hypothesized that this active compensation of the central magnification by the SPL-IPS contributes to actual object' size perception in peripheral vision. Three optic ataxia patients and 10 age-matched controls were assessed in comparing the thickness of two rectangles flashed simultaneously, one in central and another in peripheral vision. The bilateral optic ataxia patient exhibited exaggerated underestimation bias and uncertainty compared to the control group in both visual fields. The two unilateral optic ataxia patients exhibited a pathological asymmetry between visual fields: size perception performance was affected in their contralesional peripheral visual field compared to their healthy side. These results demonstrate that the SPL-IPS contributes to accurate size perception in peripheral vision.</AbstractText
|
[
[
"30692225",
"An Essential Role of the Intraparietal Sulcus in Response Inhibition Predicted by Parcellation-Based Network.",
"The posterior parietal cortex (PPC) features close anatomical and functional relationships with the prefrontal cortex. However, the necessity of the PPC in executive functions has been questioned. The present study used the stop-signal task to examine response inhibition, an executive function that inhibits prepotent response tendency. The brain activity and resting-state functional connectivity were measured to analyze a parcellation-based network that was aimed at identifying a candidate PPC region essential for response inhibition in humans. The intraparietal sulcus (IPS) was activated during response inhibition and connected with the inferior frontal cortex and the presupplementary motor area, the two frontal regions known to be necessary for response inhibition. Next, transcranial magnetic stimulation (TMS) was used to test the essential role of the IPS region for response inhibition. TMS over the IPS region prolonged the stop-signal reaction time (SSRT), the standard behavioral index used to evaluate stopping performance, when stimulation was applied 30-0 ms before stopping. On the contrary, stimulation over the temporoparietal junction region, an area activated during response inhibition but lacking connectivity with the two frontal regions, did not show changes in SSRT. These results indicate that the IPS identified using the parcellation-based network plays an essential role in executive functions.<b"
]
] |
[
[
"33995766",
"Use of geographic information systems web mapping application to support active case search to guide public health and social measures in the context of COVID-19 in Zimbabwe: a preliminary report to guide replication of methods in similar resource settings.",
"the new coronavirus (COVID-19) that emerged from Wuhan, Hubei Province of China in December 2019, causing severe acute respiratory syndrome (SARS) has fast spread across the entire globe, with most countries struggling to slow and reduce the spread of the virus through rapid screening, testing, isolation, case management, contact tracing, implementing social distancing and lockdowns. This has been shown to be a major factor in countries that have been successful in containing COVID-19 transmission. Early detection of cases is important, and the use of geospatial technology can support to detect and easily identify potential hotspots that will require timely response. The use of spatial analysis with geographic information systems (GIS) had proved to be effective in providing timely and effective solutions in supporting epidemic response and pandemics over the years. It has developed and evolved rapidly with a complete technological tool for representing data, model construction, visualization and platform construction among others.</AbstractText we conducted a geospatial analysis to develop a web mapping application using ArcMap and ArcGIS online to guide and support active case search of potential COVID-19 cases, within 500m radius of COVID-19 confirmed cases to improve detection and testing of suspected cases.</AbstractText the web mapping application tool guides the active case search teams in the field, with clear boundaries on the houses to be visited within 500-meter radius of confirmed positive cases, to conduct active case search of all cases of severe acute respiratory illnesses (SARI), acute respiratory illnesses (ARI), pneumonia etc, to detect and test for COVID-19 towards containing the pandemic.</AbstractText the use of GIS and spatial statistical tools have become an important and valuable tool in decision-making and, more importantly, guiding health care professional and other stakeholders in the response being carried out in a more coherent and easy manner. It has proven to be effective in supporting the active case search process to rapidly detect, test and isolate cases during the process, towards containing the COVID-19 pandemic.</AbstractText"
]
] |
39280509
|
Anti-recoverin Antibody-Associated Post-acute COVID Vaccination Syndrome After BNT162b2 in HLA-B27-Positive Spondylarthritis: A Case Report.
|
Retinopathy, small fiber neuropathy (SFN), and encephalopathy associated with recoverin antibodies have not been previously reported as side effects of BNT162b2 vaccination in a patient with HLA-B27-associated spondylarthritis. The patient is a 47-year-old male with a 10-year history of HLA-B27-associated spondylarthritis without recurrence, who developed acute and post-acute COVID vaccination syndrome (ACVS/PACVS) after the first dose of the BNT162b2 vaccine. The PACVS manifested as cerebral disease, eye disease, and SFN. Two years after the onset of the adverse effects, recurrent elevated recoverin antibodies were detected. Despite the administration of various treatments, most symptoms persisted for more than three years, and only a few interventions such as glucocorticoids, hyperbaric oxygen therapy, botulinum toxin, inuspheresis, and HELP (heparin-induced extracorporeal LDL precipitation) apheresis showed a transient beneficial effect. In conclusion, this case offers an example of a collection of symptoms following SARS-CoV-2 vaccination (SC2V) in a patient with a specific autoimmune disorder and positivity for anti-recoverin antibodies. These clinical manifestations may be triggered by an exaggerated immune response known as multisystemic inflammatory syndrome in adults to SC2V. Clinicians should report other similar cases to determine if a pattern exists.</AbstractText
|
[
[
"26733600",
"Migraine and its psychiatric comorbidities.",
"Migraine is a highly prevalent and disabling neurological disorder associated with a wide range of psychiatric comorbidities. In this manuscript, we provide an overview of the link between migraine and several comorbid psychiatric disorders, including depression, anxiety and post-traumatic stress disorder. We present data on psychiatric risk factors for migraine chronification. We discuss the evidence, theories and methods, such as brain functional imaging, to explain the pathophysiological links between migraine and psychiatric disorders. Finally, we provide an overview of the treatment considerations for treating migraine with psychiatric comorbidities. In conclusion, a review of the literature demonstrates the wide variety of psychiatric comorbidities with migraine. However, more research is needed to elucidate the neurocircuitry underlying the association between migraine and the comorbid psychiatric conditions and to determine the most effective treatment for migraine with psychiatric comorbidity.</AbstractText"
]
] |
[
[
"38195625",
"Multiple redox switches of the SARS-CoV-2 main protease in vitro provide opportunities for drug design.",
"Besides vaccines, the development of antiviral drugs targeting SARS-CoV-2 is critical for preventing future COVID outbreaks. The SARS-CoV-2 main protease (M<sup"
]
] |
37882887
|
Associations between GRM7 polymorphisms and obesity in patients selected for sleeve gastrectomy.
|
Obesity is a worldwide problem in which genetic factors have a prominent role. We have selected two single nucleotide polymorphisms (SNPs) within glutamate metabotropic receptor 7 (GRM7) gene, namely rs6782011 and rs779867 to weigh their association with obesity in an Iranian cohort. The distribution of rs6782011 alleles was significantly different in the obese patients from normal controls (P < 0.0001; 434 obese patients vs. 297 normal controls). Distribution of alleles was also measured between sex-based groups of obese patients and controls. We detected remarkable differences between female obese cases and female control subjects (P < 0.0001; 374 female obese cases vs. 216 female normal controls); nevertheless, the difference in allele distribution was not significant for male cases compared with corresponding normal controls (p = 0.47; 60 male patients vs. 81 normal males). Contrariwise, distribution of rs779867 alleles was not significantly different between total obese patients compared with normal controls (P = 0.21; 434 obese patients vs. 297 normal BMI controls). There was also no significant difference for female and male obese patients compared with female and male normal BMI controls. Thus, GRM7 can be considered as a risk locus for obesity.</AbstractText
|
[
[
"20143275",
"Differential sensitivity of A2A and especially D2 receptor trafficking to cocaine compared with lipid rafts in cotransfected CHO cell lines. Novel actions of cocaine independent of the DA transporter.",
"The effects of low and high concentrations of cocaine have been studied in vitro on the trafficking of plasma membrane A(2A) and D(2) immunoreactivities in previously characterized A(2A)-D(2) CHO cell lines. Receptor double immunofluorescence staining was performed with D(2) and A(2A) antibodies, planar lipid rafts immunolabeling with biotinylated cholera toxin subunit B and membrane invaginations with an anti-caveolin-1 antibody. A computer-assisted image analysis demonstrated a substantial and highly significant rise of membrane-associated D(2) immunoreactivity (IR) after 8 h of exposure to a low concentration of cocaine (150 nM). At this low concentration of cocaine, there was also an increase of membrane associated A(2A) immunoreactivity but smaller and less significant. However, this increase became considerably larger and highly significant at 150 microM at which concentration the rise of D(2) immunoreactivity had begun to disappear. It may be suggested that an allosteric action of cocaine at 150 nM on the D(2) receptors may primarily increase the insertion of D(2) monomers, homomers and also of a subpopulation of A(2A)-D(2) heteromers from the cytoplasm into the plasma membrane due to the conformational change induced by cocaine in the D(2) receptor. The planar lipid rafts and the caveolae are only affected by the higher concentrations of cocaine. It is proposed that changes in D(2) and A(2A)-D(2) trafficking induced by allosteric actions of cocaine at D(2) receptors may contribute to the alterations of D(2) signaling found in cocaine abusers.</AbstractText"
]
] |
[
[
"36780364",
"Molding Helmet Therapy for Severe Deformational Brachycephaly: Position of Eurion and Therapeutic Effect.",
"Molding helmet therapy is used routinely for moderate to severe deformational plagiocephaly. However, there have been few reports of its use for deformational brachycephaly (DB). The incidence and severity of DB are high in the Asian population, including Japanese people, but there are no reports of treatment for severe cases. The current study showed significant improvement even in severe DB with various deformities. The difference in improvement according to the morphologic classification was investigated.</AbstractText The study included 47 patients treated with helmet therapy for DB with a cephalic index of greater than 100%. Three-dimensional head scans were used for classification and measurement. DB was classified into four types according to the position of the eurion and the presence of deformational plagiocephaly. The therapeutic effect was determined by changes in cephalic index and cranial asymmetry.</AbstractText Patients exhibited a mean change of 8.0% in cephalic index and 6.4 mm in cranial asymmetry. An older age at initiation was associated with less change in both cephalic index and cranial asymmetry. A significant difference in the amount of cephalic index change was observed depending on the position of the eurion when the starting age was 6 months or older ( P < 0.05).</AbstractText Molding helmet therapy for severe DB results in significant morphological improvement. However, depending on the position of the eurion, the effect of treatment may be decreased if it is started too late. It is necessary to understand the difference in improvement depending on the morphology and to ensure early intervention.</AbstractText Risk, II.</AbstractText"
]
] |
31019105
|
Collateral blood flow measurement with intravoxel incoherent motion perfusion imaging in hyperacute brain stroke.
|
To determine if intravoxel incoherent motion (IVIM) magnetic resonance perfusion can measure the quality of the collateral blood flow in the penumbra in hyperacute stroke.</AbstractText A 6 b values IVIM MRI sequence was acquired in stroke patients with large vessel occlusion imaged <16 hours of last seen well. IVIM perfusion measures were evaluated in regions of interest drawn in the infarct core (D < 600 mm<sup A total of 34 patients were included. In the stroke core, IVIM f was significantly lower (4.6 ± 3.3%) compared to the healthy contralateral region (6.3 ± 2.2%, <i IVIM is a promising tool to assess the quality of the collateral blood flow in hyperacute stroke. IVIM penumbra perfusion lesion may be a marker of nonsalvageable tissue despite treatment with thrombectomy, suggesting that the IVIM penumbra perfusion lesion might be counted to the stroke core, together with the DWI lesion.</AbstractText
|
[
[
"35912523",
"Vascular topology and blood flow are acutely impacted by experimental febrile status epilepticus.",
"Febrile status epilepticus (FSE) is an important risk factor for temporal lobe epilepsy and early identification of those at high risk for epilepsy is vital. In a rat model of FSE, we identified an acute (2 hrs) novel MRI signal where reduced T2 relaxation values in the basolateral amygdala (BLA) predicted epilepsy in adulthood; this T2 signal remains incompletely understood and we hypothesized that it may be influenced by vascular topology. Experimental FSE induced in rat pups reduced blood vessel density of the cortical vasculature in a lateralized manner at 2 hrs post FSE. Middle cerebral artery (MCA) exhibited abnormal topology in FSE pups but not in controls. In the BLA, significant vessel junction reductions and decreased vessel diameter were observed, together with a strong trend for reduced vessel length. Perfusion weighted MRI (PWI) was acutely increased cerebral blood flow (CBF) in cortex, amygdala and hippocampus of FSE pups that correlated to decreased T2 relaxation values compared to controls. This is consistent with increased levels of deoxyhemoglobin associated with increased metabolic demand. In summary, FSE acutely modifies vascular topological and CBF in cortex and BLA that may underlie acute MRI signal changes that predict progression to future epilepsy.</AbstractText"
]
] |
[
[
"31790563",
"Association of Longitudinal β-Amyloid Accumulation Determined by Positron Emission Tomography With Clinical and Cognitive Decline in Adults With Probable Lewy Body Dementia.",
"In patients with probable dementia with Lewy bodies (DLB), overlapping Alzheimer disease pathology is frequent and is associated with faster decline and shorter survival. More than half of patients with DLB have elevated β-amyloid levels on carbon-11 labeled Pittsburgh compound B (PiB) positron emission tomography, but the trajectory of longitudinal β-amyloid accumulation and its associations with clinical and cognitive decline in DLB are not known.</AbstractText To determine the trajectory of β-amyloid accumulation in patients with probable DLB and to investigate the associations of β-amyloid accumulation with measures of clinical and cognitive decline over time in DLB.</AbstractText This cohort study included 35 consecutive patients with probable DLB from the Mayo Clinic Alzheimer Disease Research Center and matched them by age, sex, and apolipoprotein e4 status with 140 cognitively unimpaired participants from the population-based Mayo Clinic Study of Aging. Participants were observed from April 2010 to September 2017. Data analysis was conducted from January 2018 to January 2019.</AbstractText Baseline and follow-up PiB positron emission tomography and comprehensive clinical evaluations.</AbstractText Rate of change in PiB standardized uptake value ratios (SUVRs) by PiB SUVR and time in years; the associations between baseline PiB SUVR, change in PiB SUVR, and change in several measures of clinical and cognitive decline.</AbstractText A total of 175 participants were evaluated (35 [20.0%] with probable DLB; mean [SD] age, 69.6 [7.3] years; 16 [45.7%] apolipoprotein e4 carriers; 31 [88.6%] men; and 140 [80.0%] cognitively unimpaired adults; mean [SD] age, 69.7 [7.2] years; 64 [45.7%] apolipoprotein e4 carriers; 124 [88.6%] men). In both groups, the rates of change in PiB SUVR showed an initial acceleration at lower baseline PiB SUVR followed by a deceleration at higher baseline PiB SUVR, thus forming an inverted-U shape. The trajectories of the rates of change in PiB SUVR did not differ between participants with probable DLB and cognitively unimpaired participants in terms of shape (P = .59) or vertical shift (coefficient [SE] 0.007 [0.006]; P = .22). The integral association of cumulative PiB SUVR with time in years showed a sigmoid-shaped functional form in both groups. In participants with probable DLB, higher baseline PiB SUVR and change in PiB SUVR were associated with more rapid clinical decline, as measured by the Clinical Dementia Rating, sum of boxes (baseline PiB SUVR: regression coefficient [SE], 1.90 [0.63]; P = .005; R2 = 0.215; change in PiB SUVR, regression coefficient [SE], 16.17 [7.47]; P = .04; R2 = 0.124) and the Auditory Verbal Learning Test, delayed recall (baseline PiB SUVR, regression coefficient [SE], -2.09 [0.95]; P = .04; R2 = 0.182; change in PiB SUVR, regression coefficient [SE], -25.05 [10.04]; P = .02; R2 = 0.221).</AbstractText In this study, the rate of change in PiB SUVR among participants with probable DLB increased, peaked, and then decreased, which was similar to the trajectory in cognitively unimpaired participants and the Alzheimer disease dementia continuum. Higher baseline PiB SUVR and change in PiB SUVR were associated with more rapid clinical and cognitive decline over time. Measuring the change in PiB SUVR has implications for designing anti-β-amyloid randomized clinical trials for individuals with probable DLB.</AbstractText"
]
] |
38957962
|
Ileus at Altitude.
|
Ebert-Santos, Christine, and Ana Campos. Ileus at altitude. <i
|
[
[
"30578016",
"Il-23/Th17 cell pathway: A promising target to alleviate thymic inflammation maintenance in myasthenia gravis.",
"IL-23/Th17 pathway has been identified to sustain inflammatory condition in several autoimmune diseases and therefore being targeted in various therapeutic and effective approaches. Patients affected with autoimmune myasthenia gravis exhibit a disease effector tissue, the thymus, that harbors ectopic germinal centers that sustain production of auto-antibodies, targeting proteins located in the neuromuscular junction, cause of the organ-specific chronic autoimmune disease. The present study aims to investigate the IL-23/Th17 cell pathway in the thymic inflammatory and pathogenic events. We found that thymuses of MG patients displayed overexpression of Interleukin-17, signature cytokine of activated Th17 cells. This activation was sustained by a higher secretion of Interleukin-23 by TEC, in addition to the increased expression of cytokines involved in Th17 cell development. The overexpression of Interleukin-23 was due to a dysregulation of interferon type I pathway. Besides, Interleukin-17 secreted, and Th17 cells were localized around thymic ectopic germinal centers. These cells expressed podoplanin, a protein involved in B-cell maturation and antibody secretion. Finally, production of Interleukin-23 was also promoted by Interleukin-17 secreted itself by Th17 cells, highlighting a chronic loop of inflammation sustained by thymic cell interaction. Activation of the IL-23/Th17 pathway in the thymus of autoimmune myasthenia gravis patients creates an unstoppable loop of inflammation that may participate in ectopic germinal center maintenance. To alleviate the physio-pathological events in myasthenia gravis patients, this pathway may be considered as a new therapeutic target.</AbstractText"
]
] |
[
[
"37995745",
"Adolescent-Onset Epilepsy: Clinical Features and Predictive Factors for First-Year Seizure Freedom.",
"Teenagers with epilepsy require special attention to ensure a successful treatment journey. Our objective was to delineate the clinical characteristics of adolescent-onset epilepsy (AOE) and investigate the predictive factors influencing first-year seizure freedom.</AbstractText We retrospectively analyzed the medical records of patients whose first seizure occurred between the ages of 10 and 19 years and who received antiseizure medication (ASM) treatment for at least 12 months.</AbstractText A total of 67 patients were included, with an average age of 13.5 ± 2.3 years at the onset of their first seizure. The average follow-up period was 45.2 ± 16.9 months, and comorbid conditions were present in 23 patients (34.3%). The majority of the patient population (83.6%) was affected by generalized epilepsy. The most common epilepsy syndrome was epilepsy with generalized tonic-clonic seizures alone at 70.1% (juvenile myoclonic epilepsy 11.9%, juvenile absence epilepsy 1.5%). Regarding ASM treatment, 31 patients (46.3%) received monotherapy, and 28 (41.8%) received dual therapy. Five patients (7.5%) encountered issues related to medication adherence. First-year seizure freedom was observed in 42 patients (62.7%). In multivariate analysis, a negative family history of epilepsy (odds ratio 12.1, 95% confidence interval 1.27-115.44, <i These findings suggest that AOE typically exhibits effective control of seizures. A negative family history of epilepsy and ASM monotherapy emerges as robust predictor of achieving favorable outcomes within the early stage of treatment.</AbstractText"
]
] |
38580877
|
Exploring variability in cognitive functioning in patients with spinal muscular atrophy: a scoping review.
|
The cognitive functioning of individuals with spinal muscular atrophy (SMA) is not well understood, prompting a call for more research to better grasp cognitive involvement in SMA. This study aims to explore recent findings regarding cognitive outcomes in SMA patients, including correlations between clinical features and cognitive abilities. The investigation seeks to identify commonly used measures for assessing cognitive function in this patient population. A scoping review following the Joanna Briggs Institute methodology examined literature until December 2023. Two databases were searched along with relevant article references using specific terms such as "spinal muscular atrophy," "SMA," "cognitive," "abilities," "functions," "intellective," or "intellectual." Screening focused on titles and abstracts from English language peer-reviewed journals. After the initial research, 1452 articles were identified. Subsequent screening and selection led to the inclusion of 13 articles in the review. Among these studies, four indicated a cognitive trend within the normal range for SMA patients. In four other studies, the majority of patients fell within the normal range. However, smaller proportions were observed to be either above or below the norm compared to the controls. Three studies reported noted cognitive performance below the average, while two showed above-average scores. The scoping review suggests that most SMA patients have cognitive abilities similar to the general population, with types II and III showing even lesser impact. However, certain cognitive domains may be affected in type I patients, highlighting the need for further research to fully understand cognitive involvement in SMA.</AbstractText
|
[
[
"38664795",
"Dysregulation of innate immune signaling in animal models of spinal muscular atrophy.",
"Spinal muscular atrophy (SMA) is a devastating neuromuscular disease caused by hypomorphic loss of function in the survival motor neuron (SMN) protein. SMA presents across a broad spectrum of disease severity. Unfortunately, genetic models of intermediate SMA have been difficult to generate in vertebrates and are thus unable to address key aspects of disease etiology. To address these issues, we developed a Drosophila model system that recapitulates the full range of SMA severity, allowing studies of pre-onset biology as well as late-stage disease processes.</AbstractText Here, we carried out transcriptomic and proteomic profiling of mild and intermediate Drosophila models of SMA to elucidate molecules and pathways that contribute to the disease. Using this approach, we elaborated a role for the SMN complex in the regulation of innate immune signaling. We find that mutation or tissue-specific depletion of SMN induces hyperactivation of the immune deficiency (IMD) and Toll pathways, leading to overexpression of antimicrobial peptides (AMPs) and ectopic formation of melanotic masses in the absence of an external challenge. Furthermore, the knockdown of downstream targets of these signaling pathways reduced melanotic mass formation caused by SMN loss. Importantly, we identify SMN as a negative regulator of a ubiquitylation complex that includes Traf6, Bendless, and Diap2 and plays a pivotal role in several signaling networks.</AbstractText In alignment with recent research on other neurodegenerative diseases, these findings suggest that hyperactivation of innate immunity contributes to SMA pathology. This work not only provides compelling evidence that hyperactive innate immune signaling is a primary effect of SMN depletion, but it also suggests that the SMN complex plays a regulatory role in this process in vivo. In summary, immune dysfunction in SMA is a consequence of reduced SMN levels and is driven by cellular and molecular mechanisms that are conserved between insects and mammals.</AbstractText"
]
] |
[
[
"39289957",
"[Selection of inner ear fenestration strategy and surgical effect of patients with oval window atresia accompanied by facial nerve aberration].",
"<b <b"
]
] |
30203180
|
The association between migraine and physical exercise.
|
There is an unmet need of pharmacological and non-pharmacological treatment options for migraine patients. Exercise can be used in the treatment of several pain conditions, including. However, what exact role exercise plays in migraine prevention is unclear. Here, we review the associations between physical exercise and migraine from an epidemiological, therapeutical and pathophysiological perspective.</AbstractText The review was based on a primary literature search on the PubMed using the search terms "migraine and exercise".</AbstractText Low levels of physical exercise and high frequency of migraine has been reported in several large population-based studies. In experimental studies exercise has been reported as a trigger factor for migraine as well as migraine prophylaxis. Possible mechanisms for how exercise may trigger migraine attacks, include acute release of neuropeptides such as calcitonin gene-related peptide or alternation of hypocretin or lactate metabolism. Mechanisms for migraine prevention by exercise may include increased beta-endorphin, endocannabinoid and brain-derived neurotrophic factor levers in plasma after exercise.</AbstractText In conclusion, it seems that although exercise can trigger migraine attacks, regular exercise may have prophylactic effect on migraine frequency. This is most likely due to an altered migraine triggering threshold in persons who exercise regularly. However, the frequency and intensity of exercise that is required is still an open question, which should be addressed in future studies to delineate an evidence-based exercise program to prevent migraine in sufferers.</AbstractText
|
[
[
"21423403",
"Microbial induction of immunity, inflammation, and cancer.",
"The human microbiota presents a highly active metabolic that influences the state of health of our gastrointestinal tracts as well as our susceptibility to disease. Although much of our initial microbiota is adopted from our mothers, its final composition and diversity is determined by environmental factors. Westernization has significantly altered our microbial function. Extensive experimental and clinical evidence indicates that the westernized diet, rich in animal products and low in complex carbohydrates, plus the overuse of antibiotics and underuse of breastfeeding, leads to a heightened inflammatory potential of the microbiota. Chronic inflammation leads to the expression of certain diseases in genetically predisposed individuals. Antibiotics and a \"clean\" environment, termed the \"hygiene hypothesis,\" has been linked to the rise in allergy and inflammatory bowel disease, due to impaired beneficial bacterial exposure and education of the gut immune system, which comprises the largest immune organ within the body. The elevated risk of colon cancer is associated with the suppression of microbial fermentation and butyrate production, as butyrate provides fuel for the mucosa and is anti-inflammatory and anti-proliferative. This article will summarize the work to date highlighting the complicated and dynamic relationship between the gut microbiota and immunity, inflammation and carcinogenesis.</AbstractText"
]
] |
[
[
"28990857",
"The role of regional heterogeneity in age-related differences in functional hemispheric asymmetry: an fMRI study.",
"Neuroimaging literature has documented age-related hemispheric asymmetry reduction in frontal regions during task performances. As most studies employed working memory paradigms, it is therefore less clear if this pattern of neural reorganization is constrained by working memory processes or it would also emerge in other cognitive domains which are predominantly lateralized. Using blocked functional magnetic resonance imaging (fMRI), the present study used a homophone judgment task and a line judgment task to investigate age-related differences in functional hemispheric asymmetry in language and visuospatial processing respectively. Young and older adults achieved similar task accuracy although older adults required a significantly longer time. Age-related functional hemispheric asymmetry reduction was found only in dorsal inferior frontal gyrus and was associated with better performance when the homophone condition was contrasted against fixation, and not line condition. Our data thus highlights the importance of considering regional heterogeneity of aging effects together with general age-related cognitive processes.</AbstractText"
]
] |
31408691
|
Prion disease and recommended procedures for flexible endoscope reprocessing - a review of policies worldwide and proposal for a simplified approach.
|
Several guidelines recommend specific treatments for endoscopes, procedures of quarantine for endoscopes, or additional treatments for the endoscope washer disinfector (EWD) in suspected or confirmed cases of Creutzfeldt-Jakob disease (CJD) or variant CJD (vCJD) but vary in many details. This study therefore reviewed guidelines on reprocessing flexible endoscopes after use in patients with suspected or confirmed prion disease. In addition, a literature search was performed in Medline on prion, CJD, vCJD, chemical inactivation, transmission healthcare, epidemiology healthcare, concentration tissue human and endoscope. Thus far, no case of CJD or vCJD transmitted by flexible endoscope has been reported. In animals it has been shown that oral uptake of 0.1-5 g of bovine spongiform encephalopathy (BSE)-infected brain homogenate is necessary for transmission. The maximum prion concentration in other tissues (e.g., terminal ileum) is at least 100-fold lower. Automated cleaning of endoscopes alone results in very low total residual protein ≤5.6 mg per duodenoscopes. Recommendations vary between countries, sometimes with additional cleaning, use of alkaline cleaners, no use of cleaners with fixative properties, use of disinfectants without fixative properties or single-use disinfectants. Sodium hydroxide (1 M) and sodium hypochlorite (10,000 and 25,000 mg/L) are very effective in preventing transmission via contaminated wires implanted into animal brains, but their relevance for endoscopes is questionable. Based on circumstantial evidence, it is proposed to consider validated reprocessing as appropriate in the case of delayed suspected prion disease when immediate bedside cleaning, routine use of alkaline cleaners, no fixative agents anywhere prior to disinfection and single use brushes and cleaning solutions can be assured.</AbstractText
|
[
[
"31088163",
"Speech network regional involvement in bulbar ALS: a multimodal structural MRI study.",
"<i"
]
] |
[
[
"32243859",
"Stress Disrupts Human Hippocampal-Prefrontal Function during Prospective Spatial Navigation and Hinders Flexible Behavior.",
"The ability to anticipate and flexibly plan for the future is critical for achieving goal-directed outcomes. Extant data suggest that neural and cognitive stress mechanisms may disrupt memory retrieval and restrict prospective planning, with deleterious impacts on behavior. Here, we examined whether and how acute psychological stress influences goal-directed navigational planning and efficient, flexible behavior. Our methods combined fMRI, neuroendocrinology, and machine learning with a virtual navigation planning task. Human participants were trained to navigate familiar paths in virtual environments and then (concurrent with fMRI) performed a planning and navigation task that could be most efficiently solved by taking novel shortcut paths. Strikingly, relative to non-stressed control participants, participants who performed the planning task under experimentally induced acute psychological stress demonstrated (1) disrupted neural activity critical for mnemonic retrieval and mental simulation and (2) reduced traversal of shortcuts and greater reliance on familiar paths. These neural and behavioral changes under psychological stress were tied to evidence for disrupted neural replay of memory for future locations in the spatial environment, providing mechanistic insight into why and how stress can alter planning and foster inefficient behavior.</AbstractText"
]
] |
22163987
|
An innovations-based noise cancelling technique on inverse kepstrum whitening filter and adaptive FIR filter in beamforming structure.
|
This paper presents an acoustic noise cancelling technique using an inverse kepstrum system as an innovations-based whitening application for an adaptive finite impulse response (FIR) filter in beamforming structure. The inverse kepstrum method uses an innovations-whitened form from one acoustic path transfer function between a reference microphone sensor and a noise source so that the rear-end reference signal will then be a whitened sequence to a cascaded adaptive FIR filter in the beamforming structure. By using an inverse kepstrum filter as a whitening filter with the use of a delay filter, the cascaded adaptive FIR filter estimates only the numerator of the polynomial part from the ratio of overall combined transfer functions. The test results have shown that the adaptive FIR filter is more effective in beamforming structure than an adaptive noise cancelling (ANC) structure in terms of signal distortion in the desired signal and noise reduction in noise with nonminimum phase components. In addition, the inverse kepstrum method shows almost the same convergence level in estimate of noise statistics with the use of a smaller amount of adaptive FIR filter weights than the kepstrum method, hence it could provide better computational simplicity in processing. Furthermore, the rear-end inverse kepstrum method in beamforming structure has shown less signal distortion in the desired signal than the front-end kepstrum method and the front-end inverse kepstrum method in beamforming structure.</AbstractText
|
[
[
"11077208",
"Effects of masker frequency and duration in forward masking: further evidence for the influence of peripheral nonlinearity.",
"Forward masking has often been thought of in terms of neural adaptation, with nonlinearities in the growth and decay of forward masking being accounted for by the nonlinearities inherent in adaptation. In contrast, this study presents further evidence for the hypothesis that forward masking can be described as a linear process, once peripheral, mechanical nonlinearities are taken into account. The first experiment compares the growth of masking for on- and off-frequency maskers. Signal thresholds were measured as a function of masker level for three masker-signal intervals of 0, 10, and 30 ms. The brief 4-kHz sinusoidal signal was masked by a 200-ms sinusoidal forward masker which had a frequency of either 2.4 kHz (off-frequency) or 4 kHz (on-frequency). As in previous studies, for the on-frequency condition, the slope of the function relating signal threshold to masker level became shallower as the delay between the masker and signal was increased. In contrast, the slopes for the off-frequency condition were independent of masker-signal delay and had a value of around unity, indicating linear growth of masking for all masker-signal delays. In the second experiment, a broadband Gaussian noise forward masker was used to mask a brief 6-kHz sinusoidal signal. The spectrum level of the masker was either 0 or 40 dB (re: 20 microPa). The gap between the masker and signal was either 0 or 20 ms. Signal thresholds were measured for masker durations from 5 to 200 ms. The effect of masker duration was found to depend more on signal level than on gap duration or masker level. Overall, the results support the idea that forward masking can be modeled as a linear process, preceded by a static nonlinearity resembling that found on the basilar membrane.</AbstractText"
]
] |
[
[
"20652766",
"Juguloarterial endothelin-1 gradients after severe traumatic brain injury.",
"Endothelin-1 (ET-1) is a potent vasoconstrictor and is thought to be responsible for secondary ischemia and vasogenic edema after traumatic brain injury (TBI). Both CSF and plasma concentrations have been shown to be increased after TBI, but there is little evidence to confirm an intracranial site of production.</AbstractText Using paired arterial and jugular venous bulb sampling, we measured arterial and jugular levels of ET-1 and its precursor, big endothelin (Big ET), and calculated juguloarterial (JA) gradients for the first 5 days post-TBI.</AbstractText Arterial levels of both Big ET and ET-1 were maximal on day 1 post-TBI, and decreased thereafter (P < 0.05). Arterial levels of Big ET and ET-1 showed correlation across all 5 days of the study (r(2) = 0.25, P < 0.001). While there was no significant JA gradient for Big ET, significant gradients were observed for ET-1 on days 1-4 post-TBI (P < 0.05). There was no correlation between JA gradients for Big ET and ET-1 (r(2) < 0.1, P > 0.9). These data suggest parenchymal production of ET-1 by brain tissue with spill over into the blood, rather than local intraluminal cleavage of Big ET in the cerebral vasculature. Systemic ET-1 levels and JA gradients of ET-1 were unrelated to the injury severity, APACHE II score, Marshall Grade, the presence of subarachnoid or subdural hemorrhage, or eventual outcome.</AbstractText These findings confirm the synthesis of Big ET and its cleavage to ET-1 within the brain after TBI. More work is needed to elucidate the pathophysiological role and the outcome impact of ET-1 generation after TBI.</AbstractText"
]
] |
36149680
|
Development of a Manual for Disaster Medical Support Using Korean Medicine for Disaster Survivors.
|
<b
|
[
[
"23895939",
"White matter in aphasia: a historical review of the Dejerines' studies.",
"The Objective was to describe the contributions of Joseph Jules Dejerine and his wife Augusta Dejerine-Klumpke to our understanding of cerebral association fiber tracts and language processing. The Dejerines (and not Constantin von Monakow) were the first to describe the superior longitudinal fasciculus/arcuate fasciculus (SLF/AF) as an association fiber tract uniting Broca's area, Wernicke's area, and a visual image center in the angular gyrus of a left hemispheric language zone. They were also the first to attribute language-related functions to the fasciculi occipito-frontalis (FOF) and the inferior longitudinal fasciculus (ILF) after describing aphasia patients with degeneration of the SLF/AF, ILF, uncinate fasciculus (UF), and FOF. These fasciculi belong to a functional network known as the Dejerines' language zone, which exceeds the borders of the classically defined cortical language centers. The Dejerines provided the first descriptions of the anatomical pillars of present-day language models (such as the SLF/AF). Their anatomical descriptions of fasciculi in aphasia patients provided a foundation for our modern concept of the dorsal and ventral streams in language processing.</AbstractText"
]
] |
[
[
"37833406",
"A cytoskeleton-membrane interaction conserved in fast-spiking neurons controls movement, emotion, and memory.",
"The pathogenesis of schizophrenia is believed to involve combined dysfunctions of many proteins including microtubule-associated protein 6 (MAP6) and Kv3.1 voltage-gated K<sup"
]
] |
40772555
|
Depression Polygenicity and Disease Activity and Disability Worsening in Multiple Sclerosis.
|
A better understanding of factors associated with multiple sclerosis (MS) disease activity and disability is needed. Given the strong link between comorbid depression and MS disease activity and disability, we aimed to determine whether the depression genetic burden, as modelled using its polygenic score, is associated with MS disease activity and disability worsening.</AbstractText In this cohort study, we used samples from neurologist-defined adult people with MS (PwMS) followed in clinical care or during a clinical trial from existing cohorts: Canada, the United States (US), and Sweden with extensive longitudinal phenotypes. We computed the depression polygenic score (PGS) and tested its association with annualized relapse rate and worsening disability. In the US cohort, we additionally explored the time to relapse, number of enhancing lesions, and confirmed Expanded Disability Status Scale (EDSS) worsening during the study period.</AbstractText We included 3,420 relapsing-onset PwMS of European genetic ancestry with a median follow-up of 3 to 5 years. Meta-analyses revealed for each 1-standard deviation increase in the depression PGS, the relapse rate increased (incidence rate ratio: 1.23, 95% confidence interval [CI] = 1.01-1.50). In the US cohort, higher depression PGS was associated with protocol-defined relapses (hazard ratio [HR] = 1.58, 95% CI = 1.03-2.43), and time to confirmed EDSS worsening (HR = 1.51, 95% CI = 1.03-2.22) with this effect largely direct.</AbstractText Meta-analyses showed a higher depression genetic burden was associated with increased MS disease activity. In the US clinical trial cohort only, we found a significant association between higher depression PGS and time to relapse and confirmed EDSS worsening. These findings may provide insights into MS disease activity and disability worsening. ANN NEUROL 2025.</AbstractText
|
[
[
"38383156",
"Incidence and determinants of seizures in multiple sclerosis: a meta-analysis of randomised clinical trials.",
"Seizures are reported to be more prevalent in individuals with multiple sclerosis (MS) compared with the general population. Existing data predominantly originate from population-based studies, which introduce variability in methodologies and are vulnerable to selection and reporting biases.</AbstractText This meta-analysis aims to assess the incidence of seizures in patients participating in randomised clinical trials and to identify potential contributing factors. Data were extracted from 60 articles published from 1993 to 2022. The pooled effect size, representing the incidence rate of seizure events, was estimated using a random-effect model. Metaregression was employed to explore factors influencing the pooled effect size.</AbstractText The meta-analysis included data from 53 535 patients and 120 seizure events in a median follow-up of 2 years. The pooled incidence rate of seizures was 68.0 per 100 000 patient-years, significantly higher than the general population rate of 34.6. Generalised tonic-clonic seizures were the most common type reported, although there was a high risk of misclassification for focal seizures with secondary generalisation. Disease progression, longer disease duration, higher disability levels and lower brain volume were associated with a higher incidence of seizures. Particularly, sphingosine-1-phosphate receptor (S1PR) modulators exhibited a 2.45-fold increased risk of seizures compared with placebo or comparators, with a risk difference of 20.5 events per 100 000 patient-years.</AbstractText Patients with MS face a nearly twofold higher seizure risk compared with the general population. This risk appears to be associated not only with disease burden but also with S1PR modulators. Our findings underscore epilepsy as a significant comorbidity in MS and emphasise the necessity for further research into its triggers, preventive measures and treatment strategies.</AbstractText"
]
] |
[
[
"39946538",
"Hidden complexity of α7 nicotinic acetylcholine receptor desensitization revealed by MD simulations and Markov state modeling.",
"The α7 nicotinic acetylcholine receptor is a pentameric ligand-gated ion channel that plays an important role in neuronal signaling throughout the nervous system. Its implication in neurological disorders and inflammation has spurred the development of numerous compounds that enhance channel activation. However, the therapeutic potential of these compounds has been limited by the characteristically fast desensitization of the α7 receptor. Using recent high-resolution structures from cryo-EM, and all-atom molecular dynamic simulations augmented by Markov state modeling, here we explore the mechanism of α7 receptor desensitization and its implication on allosteric modulation. The results provide a precise characterization of the desensitization gate and illuminate the mechanism of ion-pore opening/closing with an agonist bound. In addition, the simulations reveal the existence of a short-lived, open-channel intermediate between the activated and desensitized states that rationalizes the paradoxical pharmacology of the L247T mutant and may be relevant to type-II allosteric modulation. This analysis provides an interpretation of the signal transduction mechanism and its regulation in α7 receptors.</AbstractText"
]
] |
17901391
|
Evidence against a perihemorrhagic penumbra provided by perfusion computed tomography.
|
Several recent studies analyzing perfusion changes in acute intracerebral hemorrhage fed the debate whether there is secondary ischemic tissue damage in the vicinity of intracerebral hemorrhage. We used perfusion CT to address this question.</AbstractText We examined 36 patients between 2001 and 2002 with acute intracerebral hemorrhage (within 24 hours after symptom onset). A subgroup of 8 patients was examined serially on day 1, between days 2 and 4, and after day 5. Nonenhanced CT images and maps of cerebral blood flow, cerebral blood volume, and time to peak were evaluated by region of interest analysis.</AbstractText In comparison to the contralateral hemisphere, perfusion values were clearly reduced around the hematoma (relative values: cerebral blood flow 0.51, cerebral blood volume 0.62, time to peak 1.7 seconds). There was no difference in size between the area of reduced perfusion and the area of edema (5.17 versus 5.75 cm(2), respectively) surrounding the hematoma. At time point 2, the edema grew significantly.</AbstractText In accordance with previous studies, we found reduced perfusion as well as edema surrounding acute intracerebral hemorrhage. Regarding ischemic tissue damage, we did not detect an initial mismatch between the perfusion deficit and the edema and therefore could not identify any tissue at risk of ischemia. We therefore interpret the reduced perfusion as a secondary phenomenon, ie, reduced oxygen demand of tissue damaged by pressure and clot components, not as the cause of any tissue damage associated with acute intracerebral hemorrhage.</AbstractText
|
[
[
"18055222",
"Accurate prediction of V1 location from cortical folds in a surface coordinate system.",
"Previous studies demonstrated substantial variability of the location of primary visual cortex (V1) in stereotaxic coordinates when linear volume-based registration is used to match volumetric image intensities [Amunts, K., Malikovic, A., Mohlberg, H., Schormann, T., and Zilles, K. (2000). Brodmann's areas 17 and 18 brought into stereotaxic space-where and how variable? Neuroimage, 11(1):66-84]. However, other qualitative reports of V1 location [Smith, G. (1904). The morphology of the occipital region of the cerebral hemisphere in man and the apes. Anatomischer Anzeiger, 24:436-451; Stensaas, S.S., Eddington, D.K., and Dobelle, W.H. (1974). The topography and variability of the primary visual cortex in man. J Neurosurg, 40(6):747-755; Rademacher, J., Caviness, V.S., Steinmetz, H., and Galaburda, A.M. (1993). Topographical variation of the human primary cortices: implications for neuroimaging, brain mapping, and neurobiology. Cereb Cortex, 3(4):313-329] suggested a consistent relationship between V1 and the surrounding cortical folds. Here, the relationship between folds and the location of V1 is quantified using surface-based analysis to generate a probabilistic atlas of human V1. High-resolution (about 200 microm) magnetic resonance imaging (MRI) at 7 T of ex vivo human cerebral hemispheres allowed identification of the full area via the stria of Gennari: a myeloarchitectonic feature specific to V1. Separate, whole-brain scans were acquired using MRI at 1.5 T to allow segmentation and mesh reconstruction of the cortical gray matter. For each individual, V1 was manually identified in the high-resolution volume and projected onto the cortical surface. Surface-based intersubject registration [Fischl, B., Sereno, M.I., Tootell, R.B., and Dale, A.M. (1999b). High-resolution intersubject averaging and a coordinate system for the cortical surface. Hum Brain Mapp, 8(4):272-84] was performed to align the primary cortical folds of individual hemispheres to those of a reference template representing the average folding pattern. An atlas of V1 location was constructed by computing the probability of V1 inclusion for each cortical location in the template space. This probabilistic atlas of V1 exhibits low prediction error compared to previous V1 probabilistic atlases built in volumetric coordinates. The increased predictability observed under surface-based registration suggests that the location of V1 is more accurately predicted by the cortical folds than by the shape of the brain embedded in the volume of the skull. In addition, the high quality of this atlas provides direct evidence that surface-based intersubject registration methods are superior to volume-based methods at superimposing functional areas of cortex and therefore are better suited to support multisubject averaging for functional imaging experiments targeting the cerebral cortex.</AbstractText"
]
] |
[
[
"26382174",
"Influence of Amyloid-β on Cognitive Decline After Stroke/Transient Ischemic Attack: Three-Year Longitudinal Study.",
"We hypothesized that comorbid amyloid-beta (Aβ) deposition played a key role in long-term cognitive decline in subjects with stroke/transient ischemic attack.</AbstractText We recruited 72 subjects with cognitive impairment after stroke/transient ischemic attack to receive Carbon-11-labeled Pittsburgh compound B positron emission tomography. We excluded subjects with known clinical Alzheimer's disease. Those with and without Alzheimer's disease-like Aβ deposition were classified as mixed vascular cognitive impairment (mVCI, n=14) and pure VCI (pVCI, n=58), respectively. We performed Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment to evaluate global cognition and cognitive domains (memory, visuospatial function, language, attention, and executive function) at 3 to 6 months (baseline) and annually for 3 years after the index event. We compared cognitive changes between mVCI and pVCI using linear mixed models and analysis of covariance adjusted for age and education.</AbstractText Over 3 years, there were significant differences between mVCI and pVCI on change of MMSE score over time (group×time interaction, P=0.007). We observed a significant decline on MMSE score (P=0.020) in the mVCI group but not in the pVCI group (P=0.208). The annual rates of decline on MMSE (P=0.023) and Montreal Cognitive Assessment score (P=0.003) were greater in the mVCI group than in the pVCI group. Memory, visuospatial, and executive function domain scores on the Montreal Cognitive Assessment were related to Aβ deposition.</AbstractText Compared with subjects without Alzheimer's disease-like Aβ deposition, those with Aβ deposition experienced a more severe and rapid cognitive decline over 3 years after stroke/transient ischemic attack. Aβ was associated with changes in multiple cognitive domains.</AbstractText"
]
] |
33794840
|
Validation and investigation of cross cultural equivalence of the Fremantle back awareness questionnaire - German version (FreBAQ-G).
|
Disrupted self-perception of the low back might contribute to chronic non-specific low back pain. The Fremantle back awareness questionnaire is a simple questionnaire to assess back specific self-perception. The questionnaire has recently been translated to German (FreBAQ-G). The aim was to further investigate the psychometric properties of the FreBAQ-G, to evaluate its cross cultural validity in patients with chronic non-specific LBP and to explore potential relationships between body perception, pain, disability and back pain beliefs.</AbstractText In this cross-sectional multicentre study, sample data were merged with data from the validation sample of the original English version to examine cross-cultural validity. Item Response Theory was used to explore psychometric properties and differential item function (DIF) to evaluate cross-cultural validity and item invariance. Correlations and multiple linear regression analyses were used to explore the relationship between altered back specific self- perception and back pain parameters.</AbstractText Two hundred seventy-two people with chronic low back pain completed the questionnaires. The FreBAQ-G showed good internal consistency (Cronbach's alpha = 0.84), good overall reliability (r = 0.84) and weak to moderate scalability (Loevinger Hj between 0.34 and 0.48). The questionnaire showed unidimensional properties with factor loadings between 0.57 and 0.80 and at least moderate correlations (r > 0.35) with pain intensity, pain related disability and fear avoidance beliefs (FABQ total - and subscores). Item and test properties of the FreBAQ-G are given. Only item 7 showed uniform DIF indicating acceptable cross-cultural validity.</AbstractText Our results indicate that the FreBAQ-G is a suitable questionnaire to measure back specific self-perception, and has comparable properties to the English-language version.</AbstractText
|
[
[
"32928886",
"Parallel Processing of Facial Expression and Head Orientation in the Macaque Brain.",
"When we move the features of our face, or turn our head, we communicate changes in our internal state to the people around us. How this information is encoded and used by an observer's brain is poorly understood. We investigated this issue using a functional MRI adaptation paradigm in awake male macaques. Among face-selective patches of the superior temporal sulcus (STS), we found a double dissociation of areas processing facial expression and those processing head orientation. The face-selective patches in the STS fundus were most sensitive to facial expression, as was the amygdala, whereas those on the lower, lateral edge of the sulcus were most sensitive to head orientation. The results of this study reveal a new dimension of functional organization, with face-selective patches segregating within the STS. The findings thus force a rethinking of the role of the face-processing system in representing subject-directed actions and supporting social cognition.<b"
]
] |
[
[
"34082217",
"Differential patterns of dynamic functional connectivity variability in major depressive disorder treated with cognitive behavioral therapy.",
"Numerous studies have shown that major depressive disorder (MDD) is characterized by a range of impairments in emotional and cognitive functions that are closely related to abnormalities in brain structure and function. Cognitive behavioral therapy (CBT) can be used as treatment for mild to moderate MDD, which can assist with ameliorating the symptoms. Previous studies have assumed that the internal fluctuations throughout the entire scan are static. However, it has recently been suggested that the brain connectivity is dynamic and relative to continuous rhythmic activity. The effect of dynamic changes in CBT on MDD patients is unknown.</AbstractText Nineteen first-episode, unmedicated MDD patients and twenty-two healthy controls (HC) participated in the study. The patients received early CBT treatment once a week for 6 weeks. Symptom examinations and magnetic resonance imaging (MRI) scans were performed pre and post treatment. Degree centrality (DC) was used to investigate the whole-brain connectivity differences between patients with MDD and healthy controls, and sliding window correlation analysis was applied to investigate the dynamic changes of functional connectivity among MDD patients treated with CBT. The variance of dynamic functional connectivity (dFC) was calculated to evaluate the temporal variability along the time.</AbstractText Patients with MDD showed abnormal DC in dorsolateral prefrontal cortex (dlPFC), insula and postcentral gyrus. Correlation analysis revealed that degree centrality of dlPFC was negatively correlated with the course of disease in patients with MDD. Results of dynamic functional connectivity showed that, compared to HC, MDD patients-remained excessively stable in dlPFC and precuneus connectivity, which is associated with emotional cognitive symptoms. After CBT, patients showed increased dFC variability in dlPFC and precuneus (p < 0.01, GRF corrected).</AbstractText DLPFC plays an important role in pathophysiological mechanism of MDD. CBT helped patients suppress redundant thoughts and negative self-focus. As a connecting node, dlPFC participates in the mechanism of action of CBT.</AbstractText"
]
] |
33194616
|
Impact of Positioning Errors on the Dosimetry of Breath-Hold-Based Volumetric Arc Modulated and Tangential Field-in-Field Left-Sided Breast Treatments.
|
Heart diseases and cardiovascular events are well-known side effects in left-sided breast irradiation. Deep inspiration breath hold (BH) combined with fast delivery techniques such as volumetric modulated arc therapy (VMAT) or tangential field-in-field (TFiF) can serve as a valuable solution to reduce the dose to the heart. This study aims to compare the impact of positioning errors in VMAT and TFiF plans for BH left-sided breast treatments. Fifteen left-sided breast patients treated in BH with TFiF technique were included in this retrospective study. For each patient, a second plan with VMAT technique was optimized. Eighteen setup variations were introduced in each of these VMAT and TFiF reference plans, shifting the isocenter along six different directions by 3, 5, and 10 mm. A total of 540 perturbed plans, 270 for each technique, were recalculated and analyzed. The dose distributions on the target and organs at risk obtained in the different perturbed scenarios were compared with the reference scenarios, using as dosimetric endpoints the dose-volume histograms (DVH). The results were compared using the Wilcoxon test. Comparable plan quality was obtained for the reference VMAT and TFiF plans, except for low doses to organs at risk for which higher values (p < 0.05) were obtained for VMAT plans. For TFiF plans, perturbations of the isocenter position of 3, 5, or 10 mm produced mean deviations of the target DVH dosimetric parameters up to -0.5, -1.0, and -5.2%, respectively; VMAT plans were more sensitive to positioning errors resulting in mean deviations up to -0.5, -4.9, and -13.9%, respectively, for the same magnitude of the above mentioned perturbations. For organs at risk, only perturbations along the left, posterior, and inferior directions resulted in dose increase with a maximum deviation of +2% in the DVH dosimetric parameters. A notable exception were low doses to the left lung and heart for 10 mm isocenter shifts for which the mean differences ranged between +2.7 and +4.1%. Objective information on how external stresses affect the dosimetry of the treatment is the first step towards personalized radiotherapy.</AbstractText
|
[
[
"26795695",
"Characterization of 3D geometric distortion of magnetic resonance imaging scanners commissioned for radiation therapy planning.",
"To develop a method for the assessment and characterization of 3D geometric distortion as part of routine quality assurance for MRI scanners commissioned for Radiation Therapy planning.</AbstractText In this study, the in-plane and through-plane geometric distortions on a 1.5T GE MRI-SIM unit are characterized and the 2D and 3D correction algorithms provided by the vendor are evaluated. We used a phantom developed by GE Healthcare that covers a large field of view of 500mm, and consists of layers of foam embedded with a matrix of ellipsoidal markers. An in-house Java-based software module was developed to automatically assess the geometric distortion by calculating the center of each marker using the center of mass method, correcting of gross rotation errors and comparing the corrected positions with a CT gold standard data set. Spatial accuracy of typical pulse sequences used in RT planning was assessed (2D T1/T2 FSE, 3D CUBE, T1 SPGR) using the software. The accuracy of vendor specific geometric distortion correction (GDC) algorithms was quantified by measuring distortions before and after the application of the 2D and 3D correction algorithms.</AbstractText Our algorithm was able to accurately calculate geometric distortion with sub-pixel precision. For all typical MR sequences used in Radiotherapy, the vendor's GDC was able to substantially reduce the distortions. Our results showed also that the impact of the acquisition produced a maximum variation of 0.2mm over a radial distance of 200mm. It has been shown that while the 2D correction algorithm remarkably reduces the in-plane geometric distortion, 3D geometric distortion further reduced the geometric distortion by correcting both in-plane and through-plane distortions in all acquisitions.</AbstractText The presented methods represent a valuable tool for routine quality assurance of MR applications that require stringent spatial accuracy assessment such as radiotherapy. The phantom used in this study provides three dimensional arrays of control points. These tools and the detailed results can be also used for developing new geometric distortion correction algorithms or improving the existing ones.</AbstractText"
]
] |
[
[
"31713622",
"New developments on the Encyclopedia of DNA Elements (ENCODE) data portal.",
"The Encyclopedia of DNA Elements (ENCODE) is an ongoing collaborative research project aimed at identifying all the functional elements in the human and mouse genomes. Data generated by the ENCODE consortium are freely accessible at the ENCODE portal (https://www.encodeproject.org/), which is developed and maintained by the ENCODE Data Coordinating Center (DCC). Since the initial portal release in 2013, the ENCODE DCC has updated the portal to make ENCODE data more findable, accessible, interoperable and reusable. Here, we report on recent updates, including new ENCODE data and assays, ENCODE uniform data processing pipelines, new visualization tools, a dataset cart feature, unrestricted public access to ENCODE data on the cloud (Amazon Web Services open data registry, https://registry.opendata.aws/encode-project/) and more comprehensive tutorials and documentation.</AbstractText"
]
] |
39790816
|
GFR Estimation and Correlation for Oncology Patients by Two Methods, Gates Method and Dual Time Point Plasma Sampling Method.
|
With the increasing number of oncology cases and a parallel surge in chemotherapeutic drugs for treatment, the treating physicians conducts nephrotoxicity evaluation to provide a personalized dosing strategy. Of the various tests available, glomerular filtration rate (GFR) under gamma camera with help of Gates method has gained importance, being a good index of overall kidney functions. In addition to this, there has been an alternate and old method for GFR estimation: plasma sampling. We at our Institution conducted both the methods for better evaluation of GFR in cancer patient management.</AbstractText Comparison of Gates' camera based GFR based on kidney depth correction using Tonessen's method and CT based manual depth calculation with dual time point plasma sampling in cancer patients.</AbstractText A retrospective study wherein patients' database were evaluated over a period of four months after approval from our Institutional Review Board. Thirty patients were included in the study. GFR was evaluated by two methods: Gates camera based and dual time plasma sampling method. Statistical analysis was done to help evaluate a correlation coefficient between the methods (Gates' method with and without CT based manual depth correction and dual time point plasma sampling).</AbstractText Our study showed moderate correlation between Gates' camera based GFR and dual time plasma sampling method.</AbstractText One need to understand the limitation of each method and see if the renal depth corrections can be done with the help of CT or lateral images of NM for near accurate GFR and in case of selecting dual plasma sampling, errors to be minimized in pipetting and sample counting. Hence, it will be better to use both the methods for coming to a conclusion.</AbstractText
|
[
[
"34928300",
"Association of Antenatal Diet and Physical Activity-Based Interventions With Gestational Weight Gain and Pregnancy Outcomes: A Systematic Review and Meta-analysis.",
"Excessive gestational weight gain (GWG) is common and associated with adverse pregnancy outcomes. Antenatal lifestyle interventions limit GWG; yet benefits of different intervention types and specific maternal and neonatal outcomes are unclear.</AbstractText To evaluate the association of different types of diet and physical activity-based antenatal lifestyle interventions with GWG and maternal and neonatal outcomes.</AbstractText A 2-stage systematic literature search of MEDLINE, Embase, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, and Health Technology Assessment Database was conducted from February 1, 2017, to May 31, 2020. Search results from the present study were integrated with those from a previous systematic review from 1990 to February 2017.</AbstractText Randomized trials reporting GWG and maternal and neonatal outcomes.</AbstractText Data were extracted for random-effects meta-analyses to calculate the summary effect estimates and 95% CIs.</AbstractText Outcomes were clinically prioritized, with mean GWG as the primary outcome. Secondary outcomes included gestational diabetes, hypertensive disorders of pregnancy, cesarean section, preterm delivery, large or small for gestational age neonates, neonatal intensive care unit admission, or fetal death.</AbstractText A total of 117 randomized clinical trials of antenatal lifestyle interventions (involving 34 546 women) were included. Overall lifestyle intervention was associated with reduced GWG (-1.15 kg; 95% CI, -1.40 to -0.91), risk of gestational diabetes (odds ratio [OR], 0.79; 95% CI, 0.70-0.89), and total adverse maternal outcomes (OR, 0.89; 95% CI, 0.84-0.94) vs routine care. Compared with routine care, diet was associated with less GWG (-2.63 kg; 95% CI, -3.87 to -1.40) than physical activity (-1.04 kg; 95% CI, -1.33 to -0.74) or mixed interventions (eg, unstructured lifestyle support, written information with weight monitoring, or behavioral support alone) (-0.74 kg; 95% CI, -1.06 to -0.43). Diet was associated with reduced risk of gestational diabetes (OR, 0.61; 95% CI, 0.45-0.82), preterm delivery (OR, 0.43; 95% CI, 0.22-0.84), large for gestational age neonate (OR, 0.19; 95% CI, 0.08-0.47), neonatal intensive care admission (OR, 0.68; 95% CI, 0.48-0.95), and total adverse maternal (OR, 0.75; 95% CI, 0.61-0.92) and neonatal outcomes (OR, 0.44; 95% CI, 0.26-0.72). Physical activity was associated with reduced GWG and reduced risk of gestational diabetes (OR, 0.60; 95% CI, 0.47-0.75), hypertensive disorders (OR, 0.66; 95% CI, 0.48-0.90), cesarean section (OR, 0.85; 95% CI, 0.75-0.95), and total adverse maternal outcomes (OR, 0.78; 95% CI, 0.71-0.86). Diet with physical activity was associated with reduced GWG (-1.35 kg; 95% CI, -1.95 to -0.75) and reduced risk of gestational diabetes (OR, 0.72; 95% CI, 0.54-0.96) and total adverse maternal outcomes (OR, 0.81; 95% CI, 0.69-0.95). Mixed interventions were associated with reduced GWG only.</AbstractText This systematic review and meta-analysis found level 1 evidence that antenatal structured diet and physical activity-based lifestyle interventions were associated with reduced GWG and lower risk of adverse maternal and neonatal outcomes. The findings support the implementation of such interventions in routine antenatal care and policy around the world.</AbstractText"
]
] |
[
[
"38844342",
"Cerebral Gray Matter May Not Explain Sleep Slow-Wave Characteristics after Severe Brain Injury.",
"Sleep slow waves are the hallmark of deeper non-rapid eye movement sleep. It is generally assumed that gray matter properties predict slow-wave density, morphology, and spectral power in healthy adults. Here, we tested the association between gray matter volume (GMV) and slow-wave characteristics in 27 patients with moderate-to-severe traumatic brain injury (TBI, 32.0 ± 12.2 years old, eight women) and compared that with 32 healthy controls (29.2 ± 11.5 years old, nine women). Participants underwent overnight polysomnography and cerebral MRI with a 3 Tesla scanner. A whole-brain voxel-wise analysis was performed to compare GMV between groups. Slow-wave density, morphology, and spectral power (0.4-6 Hz) were computed, and GMV was extracted from the thalamus, cingulate, insula, precuneus, and orbitofrontal cortex to test the relationship between slow waves and gray matter in regions implicated in the generation and/or propagation of slow waves. Compared with controls, TBI patients had significantly lower frontal and temporal GMV and exhibited a subtle decrease in slow-wave frequency. Moreover, higher GMV in the orbitofrontal cortex, insula, cingulate cortex, and precuneus was associated with higher slow-wave frequency and slope, but only in healthy controls. Higher orbitofrontal GMV was also associated with higher slow-wave density in healthy participants. While we observed the expected associations between GMV and slow-wave characteristics in healthy controls, no such associations were observed in the TBI group despite lower GMV. This finding challenges the presumed role of GMV in slow-wave generation and morphology.</AbstractText"
]
] |
25536499
|
(S)-citalopram influences amygdala modulation in healthy subjects: a randomized placebo-controlled double-blind fMRI study using dynamic causal modeling.
|
Citalopram and Escitalopram are gold standard pharmaceutical treatment options for affective, anxiety, and other psychiatric disorders. However, their neurophysiologic function on cortico-limbic circuits is incompletely characterized. Here we studied the neuropharmacological influence of Citalopram and Escitalopram on cortico-limbic regulatory processes by assessing the effective connectivity between orbitofrontal cortex (OFC) and amygdala using dynamic causal modeling (DCM) applied to functional MRI data. We investigated a cohort of 15 healthy subjects in a randomized, crossover, double-blind design after 10days of Escitalopram (10mg/d (S)-citalopram), Citalopram (10mg/d (S)-citalopram and 10mg/d (R)-citalopram), or placebo. Subjects performed an emotional face discrimination task, while undergoing functional magnetic resonance imaging (fMRI) scanning at 3 Tesla. As hypothesized, the OFC, in the context of the emotional face discrimination task, exhibited a down-regulatory effect on amygdala activation. This modulatory effect was significantly increased by (S)-citalopram, but not (R)-citalopram. For the first time, this study shows that (1) the differential effects of the two enantiomers (S)- and (R)-citalopram on cortico-limbic connections can be demonstrated by modeling effective connectivity methods, and (2) one of their mechanisms can be linked to an increased inhibition of amygdala activation by the orbitofrontal cortex.</AbstractText
|
[
[
"16680688",
"BOLD contrast sensitivity enhancement and artifact reduction with multiecho EPI: parallel-acquired inhomogeneity-desensitized fMRI.",
"Functional MRI (fMRI) generally employs gradient-echo echo-planar imaging (GE-EPI) to measure blood oxygen level-dependent (BOLD) signal changes that result from changes in tissue relaxation time T(*) (2) between activation and rest. Since T(*) (2) strongly varies across the brain and BOLD contrast is maximal only where the echo time (TE) equals the local T(*) (2), imaging at a single TE is a compromise in terms of overall sensitivity. Furthermore, the long echo train makes EPI very sensitive to main field inhomogeneities, causing strong image distortion. A method is presented that uses accelerated parallel imaging to reduce image artifacts and acquire images at multiple TEs following a single excitation, with no need to increase TR. Sensitivity gains from the broadened T(*) (2) coverage are optimized by pixelwise weighted echo summation based on local T(*) (2) or contrast-to-noise ratio (CNR) measurements. The method was evaluated using an approach that allows differential BOLD CNR to be calculated without stimulation, as well as with a Stroop experiment. Results obtained at 3 T showed that BOLD sensitivity improved by 11% or more in all brain regions, with larger gains in areas typically affected by strong susceptibility artifacts. The use of parallel imaging markedly reduces image distortion, and hence the method should find widespread application in functional brain imaging.</AbstractText"
]
] |
[
[
"26286206",
"Use of perampanel in one case of super-refractory hypoxic myoclonic status: Case report.",
"Proper treatment of hypoxic myoclonic status is not clearly determined. Induced hypothermia is improving prognosis and a more aggressive treatment might be beneficial in some patients. Among the new options of antiepileptic drugs, perampanel (PER) is a drug with a novel mechanism, and it might be a promising drug for myoclonic status or as an antimyoclonic drug. We describe the use of PER in one patient with hypoxic super-refractory myoclonic status.</AbstractText A 51-year-old patient presented after an out-of-hospital cardiac arrest due to an acute myocardial infarction. The patient was diagnosed with clinical and electrical (EEG) myoclonic status at the rewarming phase. Several treatments were used, starting with clonazepam, valproate, sedation (midazolam, propofol), and subsequently barbiturate-induced coma with persistent myoclonic status. Finally, we decided to try PER (dose: 6-8 mg) through a nasogastric tube, resulting in a marked improvement of EEG activity and myoclonus decrease. The patient had a progressive clinical improvement, with a CPC (Cerebral Performance Category) scale score of 1.</AbstractText This case shows the potential utility of PER as a therapeutic option in super-refractory hypoxic status and even its potential use before other aggressive alternatives considering their greater morbidity.</AbstractText"
]
] |
24834409
|
Tools for cardiovascular magnetic resonance imaging.
|
In less than fifteen years, as a non-invasive imaging option, cardiovascular MR has grown from a being a mere curiosity to becoming a widely used clinical tool for evaluating cardiovascular disease. Cardiovascular magnetic resonance imaging (CMRI) is now routinely used to study myocardial structure, cardiac function, macro vascular blood flow, myocardial perfusion, and myocardial viability. For someone entering the field of cardiac MR, this rapid pace of development in the field of CMRI might make it difficult to identify a cohesive starting point. In this brief review, we have attempted to summarize the key cardiovascular imaging techniques that have found widespread clinical acceptance. In particular, we describe the essential cardiac and respiratory gating techniques that form the backbone of all cardiovascular imaging methods. It is followed by four sections that discuss: (I) the gradient echo techniques that are used to assess ventricular function; (II) black-blood turbo spin echo (SE) methods used for morphologic assessment of the heart; (III) phase-contrast based techniques for the assessment of blood flow; and (IV) CMR methods for the assessment of myocardial ischemia and viability. In each section, we briefly summarize technical considerations relevant to the clinical use of these techniques, followed by practical information for its clinical implementation. In each of those four areas, CMRI is considered either as the benchmark imaging modality against which the diagnostic performance of other imaging modalities are compared against, or provides a complementary capability to existing imaging techniques. We have deliberately avoided including cutting-edge CMR imaging techniques practiced at few academic centers, and restricted our discussion to methods that are widely used and are likely to be available in a clinical setting. Our hope is that this review would propel an interested reader toward more comprehensive reviews in the literature.</AbstractText
|
[
[
"1523332",
"Minimum scan speeds for suppression of motion artifacts in CT.",
"Cardiac and ventilatory motions cause artifacts at chest computed tomography (CT). To determine how short the scan times on third-generation units must be to avoid such artifacts, motion was measured with fast and ultrafast CT scans. Minimum detectable motion was then determined. The longest scan time that avoided a barely perceptible artifact was calculated by dividing the minimum detectable motion by the peak physiologic velocity. The posterior left ventricular wall moved at a maximum velocity of 52.5 mm/sec, necessitating a scan time of 19.1 msec or less to avoid artifact. Lung vessels near the heart moved at 40.5 mm/sec for a scan time of 24.7 msec or less. During quiet breathing, pulmonary vessels moved at 10.7 mm/sec for a scan time of 93.5 msec or less. The authors conclude that the shortest scan time on third-generation units (0.6 second) cannot prevent all artifacts arising from motion in the chest. Even ultrafast scan times (50 msec) are not short enough to eliminate artifacts on these units. Thus, reduction of motion artifacts will require techniques other than fast scanning.</AbstractText"
]
] |
[
[
"24741031",
"Seeing scenes: topographic visual hallucinations evoked by direct electrical stimulation of the parahippocampal place area.",
"In recent years, functional neuroimaging has disclosed a network of cortical areas in the basal temporal lobe that selectively respond to visual scenes, including the parahippocampal place area (PPA). Beyond the observation that lesions involving the PPA cause topographic disorientation, there is little causal evidence linking neural activity in that area to the perception of places. Here, we combined functional magnetic resonance imaging (fMRI) and intracranial EEG (iEEG) recordings to delineate place-selective cortex in a patient implanted with stereo-EEG electrodes for presurgical evaluation of drug-resistant epilepsy. Bipolar direct electrical stimulation of a cortical area in the collateral sulcus and medial fusiform gyrus, which was place-selective according to both fMRI and iEEG, induced a topographic visual hallucination: the patient described seeing indoor and outdoor scenes that included views of the neighborhood he lives in. By contrast, stimulating the more lateral aspect of the basal temporal lobe caused distortion of the patient's perception of faces, as recently reported (Parvizi et al., 2012). Our results support the causal role of the PPA in the perception of visual scenes, demonstrate that electrical stimulation of higher order visual areas can induce complex hallucinations, and also reaffirm direct electrical brain stimulation as a tool to assess the function of the human cerebral cortex.</AbstractText"
]
] |
38165551
|
Reducing pediatric total-body PET/CT imaging scan time with multimodal artificial intelligence technology.
|
This study aims to decrease the scan time and enhance image quality in pediatric total-body PET imaging by utilizing multimodal artificial intelligence techniques.</AbstractText A total of 270 pediatric patients who underwent total-body PET/CT scans with a uEXPLORER at the Sun Yat-sen University Cancer Center were retrospectively enrolled. <sup Multimodal artificial intelligence techniques can significantly improve PET image quality. When fused with prior CT information, the anatomical information of the images was enhanced, and 60 s of scan data produced images of quality comparable to that of the full-time data.</AbstractText Multimodal artificial intelligence techniques can effectively improve the quality of pediatric total-body PET/CT images acquired using ultrashort scan times. This has the potential to decrease the use of sedation, enhance guardian confidence, and reduce the probability of motion artifacts.</AbstractText
|
[
[
"33545580",
"Optical brain imaging and its application to neurofeedback.",
"Besides passive recording of brain electric or magnetic activity, also non-ionizing electromagnetic or optical radiation can be used for real-time brain imaging. Here, changes in the radiation's absorption or scattering allow for continuous in vivo assessment of regional neurometabolic and neurovascular activity. Besides magnetic resonance imaging (MRI), over the last years, also functional near-infrared spectroscopy (fNIRS) was successfully established in real-time metabolic brain imaging. In contrast to MRI, fNIRS is portable and can be applied at bedside or in everyday life environments, e.g., to restore communication and movement. Here we provide a comprehensive overview of the history and state-of-the-art of real-time optical brain imaging with a special emphasis on its clinical use towards neurofeedback and brain-computer interface (BCI) applications. Besides pointing to the most critical challenges in clinical use, also novel approaches that combine real-time optical neuroimaging with other recording modalities (e.g. electro- or magnetoencephalography) are described, and their use in the context of neuroergonomics, neuroenhancement or neuroadaptive systems discussed.</AbstractText"
]
] |
[
[
"39061402",
"Creatine Kinase and Respiratory Decline in Amyotrophic Lateral Sclerosis.",
"Respiratory dysfunction is an important hallmark of amyotrophic lateral sclerosis (ALS). Elevation of creatine kinase (CK) has been reported in 23-75% of ALS patients, but the underlying mechanisms remain unknown. This work aims to enlighten the role of CK as a prognostic factor of respiratory dysfunction in ALS. A retrospective analysis of demographic and clinical variables, CK, functional decline per month (ΔFS), forced vital capacity (%FVC), and mean amplitude of the phrenic nerve compound motor action potential (pCMAP) in 319 ALS patients was conducted. These measurements were evaluated at study entry, and patients were followed from the moment of first observation until death or last follow-up visit. High CK values were defined as above the 90th percentile (CK ≥ P90) adjusted to sex. We analyzed survival and time to non-invasive ventilation (NIV) as proxies for respiratory impairment. Linear regression analysis revealed that high CK was associated with male sex (<i"
]
] |
40016658
|
Effects of multisystem exercises on balance, postural stability, mobility, walking speed, and pain in patients with diabetic peripheral neuropathy: a randomized controlled trial.
|
Diabetic peripheral neuropathy (DPN), a common complication of diabetes mellitus, is associated with peripheral nerve damage, leading to balance impairments, postural instability, and reduced mobility. Addressing these challenges requires comprehensive interventions that target multiple deficits simultaneously. Evidence suggests that exercise programs combining balance, proprioception, strength, and reaction time training can improve postural stability, enhance mobility, and alleviate pain in individuals with DPN.</AbstractText The objective of this study was to compare the effects of multisystem exercises and conventional exercises on balance, postural stability, mobility, and walking speed and to reduce pain in patients with diabetic peripheral neuropathy.</AbstractText This double-blinded, two-arm parallel design randomized controlled trial was conducted at DHQ Hospital, Pakpattan, Pakistan. A total of 50 participants who met the inclusion criteria were recruited using the nonprobability convenience sampling technique. They were randomly assigned to either a multisystem physical exercise (MPE) group (n = 26) and a conventional exercise group (n = 24). The MPE program included balance, proprioception, strength, and reaction time training, while the control group received conventional exercises, consisted of strength, balance, stretching, and range of motion exercises. Both groups underwent 30 min intervention sessions, 3 times per week, for 8 weeks. The outcome measures used for assessing the balance, postural stability, mobility, and pain included the Berg balance scale (BBS), functional reach test (FRT), time up and go test (TUG), 10 min walk test (10-MWT), and numeric pain rating scale (NPRS). The data was analyzed using SPSS version 26.</AbstractText Significant group and time interactions were observed for all outcome measures including BBS, FRT, TUG, 10-MWT, and NPRS (p < 0.001). The between-group analysis also revealed significant differences between the multisystem physical exercise group and the conventional exercise group at both the 4th week and 8th week for BBS, FRT, TUG, 10-MWT, and NPRS (p < 0.05).</AbstractText The study concluded that multisystem exercises resulted in significant improvement in balance, postural stability, mobility, and walking speed, along with reduction in pain, compared to conventional exercises in patients with diabetic peripheral neuropathy.</AbstractText This randomized controlled study was registered prospectively on November 11th, 2023 with the ClinicalTrials.gov (NCT06130917).</AbstractText
|
[
[
"29430561",
"The CGRP receptor antagonist BIBN4096 inhibits prolonged meningeal afferent activation evoked by brief local K(+) stimulation but not cortical spreading depression-induced afferent sensitization.",
"Cortical spreading depression (CSD) is believed to promote migraine headache by enhancing the activity and mechanosensitivity of trigeminal intracranial meningeal afferents. One putative mechanism underlying this afferent response involves an acute excitation of meningeal afferents by cortical efflux of K<sup We sought to investigate whether (1) a brief meningeal K<sup Extracellular single-unit recording were used to record the activity of meningeal afferents in anesthetized male rats. Stimulations included a brief meningeal application of K<sup Meningeal K<sup While CGRP-mediated activation of meningeal afferents evoked by cortical efflux of K<sup"
]
] |
[
[
"40618797",
"Preparation, characterization, and functional properties of zein/gallic acid/sodium alginate ternary composite nanoparticles for enhancing stability and bioaccessibility of phytosterols.",
"Phytosterols, a class of phytochemicals exhibiting limited aqueous solubility and low oil solubility, possess diverse physiological functions that have attracted considerable research interest. However, their poor aqueous solubility significantly restricts practical applications in functional food systems. To address these limitations, we developed a novel core-shell nanoparticle system. This system features zein as the hydrophobic core, which encapsulates phytosterols through hydrophobic interactions and hydrogen bonding, while sodium alginate forms the hydrophilic outer protective layer via electrostatic interactions. Gallic acid, functioning as both a cross-linker and antioxidant, was adsorbed at the zein/sodium alginate interface via hydrogen bonding and electrostatic interactions. The phytosterol-loaded zein/gallic acid/sodium alginate (ZGSP) nanoparticles were synthesized using an anti-solvent precipitation technique and systematically characterized using dynamic light scattering (DLS), fluorescence spectroscopy, Fourier transform infrared spectroscopy (FTIR), circular dichroism (CD), differential scanning calorimetry (DSC), scanning electron microscope (SEM), and transmission electron microscopy (TEM). The resulting ZGSP nanoparticles exhibited greater structural compactness, higher encapsulation efficiency (81.1 ± 0.03 %), improved oxidative stability, and superior physicochemical stability compared to controls. Furthermore, the nanoparticles demonstrated excellent colloidal stability under diverse conditions, including a broad pH range (3.0-8.0), high ionic strength (50-500 mM NaCl), and simulated gastrointestinal environments. Notably, the ZGSP nanoparticles significantly enhanced phytosterol bioaccessibility compared to free phytosterol controls (P < 0.05). These findings demonstrate that the ZGSP nanoparticles provide an effective platform for phytosterol encapsulation, protection, and delivery; thereby expanding the potential applications of phytosterols in functional foods and nutraceuticals.</AbstractText"
]
] |
40720222
|
How Solvation Structures Define the Cryoprotection Efficiency of Ethylene Glycol.
|
Understanding the molecular mechanisms of cryopreservation is crucial for optimizing antifreeze formulations. In this study, we investigate the hydrogen bond (HB) configurations of aqueous ethylene glycol (EG) solutions using a combined approach of Fourier transform infrared (FTIR) spectroscopy and molecular dynamics (MD) simulations. Our results reveal that EG progressively integrates into the HB network, modifying the structural organization of water across different concentrations. At low EG content, water maintains its percolating HB-network, while at intermediate concentrations (X<sub
|
[
[
"38482933",
"Varying the degree of oxidation of graphite: effect of oxidation time and oxidant mass.",
"In this work, we employ a fast and less toxic modified Hummers' method to develop graphene oxide (GO) with varying degrees of oxidation and investigate the effect of the latter on the structure and the thermal properties of the synthesized materials. Two different key parameters, the time of the oxidation reaction and the mass of the oxidation agent, were systematically altered in order to fine tune the oxidation degree. All graphene oxides were characterized by a plethora of experimental techniques, like X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) as well as infrared spectroscopy (IR) and X-ray photoelectron spectroscopy (XPS) for their structural, thermal and chemical identification. The results revealed that for a certain amount of oxidant, the time does not affect the final degree of oxidation of the materials, at least for the examined reaction times, because very similar structural patterns and thermal properties were obtained. At the same time, the oxygen-containing functional groups were found very similar. On the other hand, the degree of oxidation was found highly dependent on the mass of the oxidizing agent. XRD analysis showed a systematic increase of the interlayer distance of the synthesized GOs with the increase of the oxidant mass, whereas both the enthalpy of reduction and the % weight loss were increased. Moreover, XPS measurements provided a quantitative evaluation of the amount of carbon and oxygen in the materials; the increase of the oxidant mass led to a decrease of the total carbon content with the concurrent increase of the total oxygen amount.</AbstractText"
]
] |
[
[
"40655172",
"Addiction Education in the Undergraduate Space: A Novel Course Connecting Neurobiology of Addiction and Compassion for Individuals with Substance Use Disorder.",
"Substance use disorder (SUD) is a chronic, relapsing disease with medical, psychological, and social complications. Sufficient knowledge of addiction mechanisms and compassion for individuals with SUD are essential for combatting the prevailing stigma associated with substance use and generating efforts for effective treatments. This article describes a unique undergraduate course on addiction where efforts to enhance understanding of the neurobiology of addiction are coordinated with an emphasis on the human element of SUD. Reinforcing the neurobiological details of addiction and their relation to SUD behaviors can humanize addiction and further motivate students to invest in learning these complex details. College students have increased exposure to and opportunities for drug use and face an increased risk of developing a SUD. Substance use among college students can contribute to physical, mental, academic, and social issues. A thorough education on the neurobiological mechanisms of addiction with emphasis on the human element can help students gain a better understanding of what happens in the brain and an appreciation for the disease nature of addiction. Ultimately, this knowledge can benefit students dealing directly or indirectly with SUD and can encourage and equip them to champion for more effective and empathetic approaches for tackling addiction. The impact of this course on student learning and motivation was measured by before and after course surveys. The results demonstrate that students developed a better understanding of addiction as a disease, gained a more compassionate view of individuals with SUD, and were inspired to learn more about how addiction affects the brain.</AbstractText"
]
] |
20633659
|
Cognitive levels of performance account for hemispheric lateralisation effects in dyslexic and normally reading children.
|
Recent theories of developmental dyslexia explain reading deficits in terms of deficient phonological awareness, attention, visual and auditory processing, or automaticity. Since dyslexia has a neurobiological basis, the question arises how the reader's proficiency in these cognitive variables affects the brain regions involved in visual word recognition. This question was addressed in two fMRI experiments with 19 normally reading children (Experiment 1) and 19 children with dyslexia (Experiment 2). First, reading-specific brain activation was assessed by contrasting the BOLD signal for reading aloud words vs. overtly naming pictures of real objects. Next, ANCOVAs with brain activation during reading the individuals' scores for all five cognitive variables assessed outside the scanner as covariates were performed. Whereas the normal readers' brain activation during reading showed co-variation effects predominantly in the right hemisphere, the reverse pattern was observed for the dyslexics. In particular, middle frontal gyrus, inferior parietal cortex, and precuneus showed contralateral effects for controls as compared to dyslexics. In line with earlier findings in the literature, these data hint at a global change in hemispheric asymmetry during cognitive processing in dyslexic readers, which, in turn, might affect reading proficiency.</AbstractText
|
[
[
"11163606",
"Unilateral vibrotactile stimulation induces emotional biases in cognition and performance.",
"We administered 24 min of unilateral vibrotactile stimulation to the left or right ventral forearm of experimental participants. A separate control group did not receive stimulation but completed all experimental tasks. Participants who received right-side stimulation persisted more in attempting to solve insoluble puzzles and also made more positive judgments about an emotionally neutral film compared to participants who received left-side stimulation. The performance of the control group was intermediate to that of the stimulation groups, but was significantly different only from the right stimulation group. The absence of a significant left-side stimulation effect is not readily interpretable because floor effects may have limited the attenuating effects of left-side stimulation on persistence in problem solving. Emotional biases in cognition and performance resulting from unilateral vibrotactile stimulation can be explained with reference to activation of structures involved in the processing of emotion within the contralateral cerebral hemisphere, and by the laterality of emotion specified in the Valence Hypothesis. These results support the contention that similar biases elicited by unilateral muscle contractions result from their sensory consequences.</AbstractText"
]
] |
[
[
"27751941",
"Sources and implications of whole-brain fMRI signals in humans.",
"Whole-brain fMRI signals are a subject of intense interest: variance in the global fMRI signal (the spatial mean of all signals in the brain) indexes subject arousal, and psychiatric conditions such as schizophrenia and autism have been characterized by differences in the global fMRI signal. Further, vigorous debates exist on whether global signals ought to be removed from fMRI data. However, surprisingly little research has focused on the empirical properties of whole-brain fMRI signals. Here we map the spatial and temporal properties of the global signal, individually, in 1000+ fMRI scans. Variance in the global fMRI signal is strongly linked to head motion, to hardware artifacts, and to respiratory patterns and their attendant physiologic changes. Many techniques used to prepare fMRI data for analysis fail to remove these uninteresting kinds of global signal fluctuations. Thus, many studies include, at the time of analysis, prominent global effects of yawns, breathing changes, and head motion, among other signals. Such artifacts will mimic dynamic neural activity and will spuriously alter signal covariance throughout the brain. Methods capable of isolating and removing global artifactual variance while preserving putative \"neural\" variance are needed; this paper adopts no position on the topic of global signal regression.</AbstractText"
]
] |
38415151
|
Myelin water quantification in multiple sclerosis using short repetition time adiabatic inversion recovery prepared-fast spin echo (STAIR-FSE) imaging.
|
Myelin water imaging (MWI) is a myelin-specific technique, which has great potential for the assessment of demyelination and remyelination. This study develops a new MWI method, which employs a short repetition time adiabatic inversion recovery (STAIR) technique in combination with a commonly used fast spin echo (FSE) sequence and provides quantification of myelin water (MW) fractions.</AbstractText Whole-brain MWI was performed using the short repetition time adiabatic inversion recovery prepared-fast spin echo (STAIR-FSE) technique on eight healthy volunteers (mean age: 38±14 years, four-males) and seven patients with multiple sclerosis (MS) (mean age: 53.7±8.7 years, two-males) on a 3T clinical magnetic resonance imaging scanner. To facilitate the quantification of apparent myelin water fraction (aMWF), a proton density-weighted FSE was also used during the scans to allow total water imaging. The aMWF measurements of MS lesions and normal-appearing white matter (NAWM) regions in MS patients were compared with those measured in normal white matter (NWM) regions in healthy volunteers. Both the analysis of variance (ANOVA) test and paired comparison were performed for the comparison.</AbstractText The MW in the whole-brain was selectively imaged and quantified using the STAIR-FSE technique in all participants. MS lesions showed much lower signal intensities than NAWM in the STAIR-FSE images. ANOVA analysis revealed a significant difference in the aMWF measurements between the three groups. Moreover, the aMWF measurements in MS lesions were significantly lower than those in both NWM of healthy volunteers and NAWM of MS patients. Lower aMWF measurements in NAWM were also found in comparison with those in NWM.</AbstractText The STAIR-FSE technique is capable of measuring aMWF values for the indirect detection of myelin loss in MS, thus facilitating clinical translation of whole brain MWI and quantification, which show great potential for the detection and evaluation of changes in myelin in the brain of patients with MS for future larger cohort studies.</AbstractText
|
[
[
"29908362",
"Magnetic Resonance vs Transient Elastography Analysis of Patients With Nonalcoholic Fatty Liver Disease: A Systematic Review and Pooled Analysis of Individual Participants.",
"Magnetic resonance elastography (MRE) and transient elastography (TE) are noninvasive techniques for detection of liver fibrosis. Single-center studies have compared the diagnostic performance of MRE vs TE in patients with nonalcoholic fatty liver disease (NAFLD). We conducted a pooled analysis of individual participant data from published studies to compare the diagnostic performance of MRE vs TE for staging of liver fibrosis in patients with NAFLD, using liver biopsy as reference.</AbstractText We performed a systematic search of publication databases, from 2005 through 2017. We identified 3 studies of adults with NAFLD who were assessed by MRE, TE, and liver biopsy. In a pooled analysis, we calculated the cluster-adjusted area under the curve (AUROC) of MRE and TE for the detection of each stage of fibrosis. AUROC comparisons between MRE and TE were performed using the Delong test.</AbstractText Our pooled analysis included 230 participants with biopsy-proven NAFLD with mean age of 52.2±13.9 years and a body mass index of 31.9±7.5 kg/m2. The proportions of patients with fibrosis of stages 0, 1, 2, 3, and 4 were: 31.7%, 27.8%, 15.7%, 13.9%, and 10.9%, respectively. The AUROC of TE vs MRE for detection of fibrosis stages ≥1 was 0.82 (95% CI, 0.76-0.88) vs 0.87 (95% CI, 0.82-0.91) (P=.04); for stage≥ 2 was 0.87 (95% CI, 0.82-0.91) vs 0.92 (95% CI, 0.88-0.96) (P=.03); for stage ≥3 was 0.84 (95% CI, 0.78-0.90) vs 0.93 (95% CI, 0.89-0.96) (P=.001); for stage ≥ 4 was 0.84 (95% CI, 0.73-0.94) vs 0.94 (95% CI, 0.89-0.99) (P=.005).</AbstractText In a pooled analysis of data from individual participants with biopsy-proven NAFLD, we found MRE to have a statistically significantly higher diagnostic accuracy than TE in detection of each stage of fibrosis. MRE and TE each have roles in detection of fibrosis in patients with NAFLD, depending upon the level of accuracy desired.</AbstractText"
]
] |
[
[
"37918767",
"A powerful metric for expressive language lateralization in MEG.",
"Magnetoencephalography (MEG) has proven valuable for presurgical language lateralization. Investigators have established that low-beta (13-23 Hz) event-related desynchrony (ERD), a neuromagnetic signature for increased neuronal firing, maps to critical language centers for expressive language tasks in MEG. The distribution of low-beta ERD is relatively bilateral in early childhood, transitioning to left lateralized by adolescence or early adulthood. Recently, we showed that a complementary signal, low-beta event-related synchrony, thought to reflect neuronal inhibition, becomes increasingly right lateralized across development. Here, we introduce a hybrid laterality index for language derived from both low-beta ERD and ERS. We present findings from a large cohort of children performing verb generation in MEG, and show that inclusion of low-beta ERS provides relatively powerful estimation of language lateralization.</AbstractText"
]
] |
38819648
|
Haptic and visuo-haptic impairments for object recognition in children with autism spectrum disorder: focus on the sensory and multisensory processing dysfunctions.
|
Dysfunctions in sensory processing are widely described in individuals with autism spectrum disorder (ASD), although little is known about the developmental course and the impact of these difficulties on the learning processes during the preschool and school ages of ASD children. Specifically, as regards the interplay between visual and haptic information in ASD during developmental age, knowledge is very scarce and controversial. In this study, we investigated unimodal (visual and haptic) and cross-modal (visuo-haptic) processing skills aimed at object recognition through a behavioural paradigm already used in children with typical development (TD), with cerebral palsy and with peripheral visual impairments. Thirty-five children with ASD (age range: 5-11 years) and thirty-five age-matched and gender-matched typically developing peers were recruited. The procedure required participants to perform an object-recognition task relying on only the visual modality (black-and-white photographs), only the haptic modality (manipulation of real objects) and visuo-haptic transfer of these two types of information. Results are consistent with the idea that visuo-haptic transfer may be significantly worse in ASD children than in TD peers, leading to significant impairment in multisensory interactions for object recognition facilitation. Furthermore, ASD children tended to show a specific deficit in haptic information processing, while a similar trend of maturation of visual modality between the two groups is reported. This study adds to the current literature by suggesting that ASD differences in multisensory processes also regard visuo-haptic abilities necessary to identify and recognise objects of daily life.</AbstractText
|
[
[
"16768363",
"Electrophysiological evidence of the capture of visual attention.",
"We investigated the ability of salient yet task-irrelevant stimuli to capture attention in two visual search experiments. Participants were presented with circular search arrays that contained a highly salient distractor singleton defined by color and a less salient target singleton defined by form. A component of the event-related potential called the N2pc was used to track the allocation of attention to lateralized positions in the arrays. In Experiment 1, a lateralized distractor elicited an N2pc when a concurrent target was presented on the vertical meridian and thus could not elicit lateralized components such as the N2pc. A similar distractor-elicited N2pc was found in Experiment 2, which was conducted to rule out certain voluntary search strategies. Additionally, in Experiment 2 both the distractor and the target elicited the N2pc component when the two stimuli were presented on opposite sides of the search array. Critically, the distractor-elicited N2pc preceded the target-elicited N2pc on these trials. These results demonstrate that participants shifted attention to the target only after shifting attention to the more salient but task-irrelevant distractor. This pattern of results is in line with theories of attention in which stimulus-driven control plays an integral role.</AbstractText"
]
] |
[
[
"38386744",
"The macroevolutionary singularity of snakes.",
"Snakes and lizards (Squamata) represent a third of terrestrial vertebrates and exhibit spectacular innovations in locomotion, feeding, and sensory processing. However, the evolutionary drivers of this radiation remain poorly known. We infer potential causes and ultimate consequences of squamate macroevolution by combining individual-based natural history observations (>60,000 animals) with a comprehensive time-calibrated phylogeny that we anchored with genomic data (5400 loci) from 1018 species. Due to shifts in the dynamics of speciation and phenotypic evolution, snakes have transformed the trophic structure of animal communities through the recurrent origin and diversification of specialized predatory strategies. Squamate biodiversity reflects a legacy of singular events that occurred during the early history of snakes and reveals the impact of historical contingency on vertebrate biodiversity.</AbstractText"
]
] |
27608601
|
Elucidating the neural correlates of related false memories using a systematic measure of perceptual relatedness.
|
Previous memory research has exploited the perceptual similarities between lures and targets in order to evoke false memories. Nevertheless, while some studies have attempted to use lures that are objectively more similar than others, no study has systematically controlled for perceptual overlap between target and lure items and its role in accounting for false alarm rates or the neural processes underlying such perceptual false memories. The current study looked to fill this gap in the literature by using a face-morphing program to systematically control for the amount of perceptual overlap between lures and targets. Our results converge with previous studies in finding a pattern of differences between true and false memories. Most importantly, expanding upon this work, parametric analyses showed false memory activity increases with respect to the similarity between lures and targets within bilateral middle temporal gyri and right medial prefrontal cortex (mPFC). Moreover, this pattern of activation was unique to false memories and could not be accounted for by relatedness alone. Connectivity analyses further find that activity in the mPFC and left middle temporal gyrus co-vary, suggestive of gist-based monitoring within the context of false memories. Interestingly, neither the MTL nor the fusiform face area exhibited modulation as a function of target-lure relatedness. Overall, these results provide insight into the processes underlying false memories and further enhance our understanding of the role perceptual similarity plays in supporting false memories.</AbstractText
|
[
[
"15772354",
"The roles of the caudate nucleus in human classification learning.",
"The caudate nucleus is commonly active when learning relationships between stimuli and responses or categories. Previous research has not differentiated between the contributions to learning in the caudate and its contributions to executive functions such as feedback processing. We used event-related functional magnetic resonance imaging while participants learned to categorize visual stimuli as predicting \"rain\" or \"sun.\" In each trial, participants viewed a stimulus, indicated their prediction via a button press, and then received feedback. Conditions were defined on the bases of stimulus-outcome contingency (deterministic, probabilistic, and random) and feedback (negative and positive). A region of interest analysis was used to examine activity in the head of the caudate, body/tail of the caudate, and putamen. Activity associated with successful learning was localized in the body and tail of the caudate and putamen; this activity increased as the stimulus-outcome contingencies were learned. In contrast, activity in the head of the caudate and ventral striatum was associated most strongly with processing feedback and decreased across trials. The left superior frontal gyrus was more active for deterministic than probabilistic stimuli; conversely, extrastriate visual areas were more active for probabilistic than deterministic stimuli. Overall, hippocampal activity was associated with receiving positive feedback but not with correct classification. Successful learning correlated positively with activity in the body and tail of the caudate nucleus and negatively with activity in the hippocampus.</AbstractText"
]
] |
[
[
"28147273",
"miR-182 Regulates Slit2-Mediated Axon Guidance by Modulating the Local Translation of a Specific mRNA.",
"During brain wiring, cue-induced axon behaviors such as directional steering and branching are aided by localized mRNA translation. Different guidance cues elicit translation of subsets of mRNAs that differentially regulate the cytoskeleton, yet little is understood about how specific mRNAs are selected for translation. MicroRNAs (miRNAs) are critical translational regulators that act through a sequence-specific mechanism. Here, we investigate the local role of miRNAs in mRNA-specific translation during pathfinding of Xenopus laevis retinal ganglion cell (RGC) axons. Among a rich repertoire of axonal miRNAs, miR-182 is identified as the most abundant. Loss of miR-182 causes RGC axon targeting defects in vivo and impairs Slit2-induced growth cone (GC) repulsion. We find that miR-182 targets cofilin-1 mRNA, silencing its translation, and Slit2 rapidly relieves the repression without causing miR-182 degradation. Our data support a model whereby miR-182 reversibly gates the selection of transcripts for fast translation depending on the extrinsic cue.</AbstractText"
]
] |
40086873
|
Feedback scales the spatial tuning of cortical responses during both visual working memory and long-term memory.
|
Perception, working memory, and long-term memory each evoke neural responses in visual cortex. While previous neuroimaging research on the role of visual cortex in memory has largely emphasized similarities between perception and memory, we hypothesized that responses in visual cortex would differ depending on the origins of the inputs. Using fMRI, we quantified spatial tuning in visual cortex while participants (both sexes) viewed, maintained in working memory, or retrieved from long-term memory a peripheral target. In each condition, BOLD responses were spatially tuned and aligned with the target's polar angle in all measured visual field maps including V1. As expected given the increasing sizes of receptive fields, polar angle tuning during perception increased in width up the visual hierarchy from V1 to V2, V3, hV4, and beyond. In stark contrast, the tuned responses were broad across the visual hierarchy during long-term memory (replicating a prior result) and during working memory. This pattern is consistent with the idea that mnemonic responses in V1 stem from top-down sources, even when the stimulus was recently viewed and is held in working memory. Moreover, in long-term memory, trial-to-trial biases in these tuned responses (clockwise or counterclockwise of target), predicted matched biases in memory, suggesting that the reinstated cortical responses influence memory guided behavior. We conclude that feedback widens spatial tuning in visual cortex during memory, where earlier visual maps inherit broader tuning from later maps thereby impacting the precision of memory.<b
|
[
[
"16672292",
"Plasticity in the human central nervous system.",
"Long-term potentiation (LTP) is a well-characterized form of synaptic plasticity that fulfils many of the criteria for a neural correlate of memory. LTP has been studied in a variety of animal models and, in rodents in particular, there is now a strong body of evidence demonstrating common underlying molecular mechanisms in LTP and memory. Results are beginning to emerge from studies of neural plasticity in humans. This review will summarize findings demonstrating that synaptic LTP can be induced in human CNS tissue and that rodent and human LTP probably share similar molecular mechanisms. We will also discuss the application of non-invasive stimulation techniques to awake human subjects to induce LTP-like long-lasting changes in localized neural activity. These techniques have potential therapeutic application in manipulating neural plasticity to treat a variety of conditions, including depression, Parkinson's disease, epilepsy and neuropathic pain.</AbstractText"
]
] |
[
[
"39716006",
"Isolating Synaptic Vesicles from Neurospheres for Proteomics.",
"This chapter presents an optimized method for isolating synaptic vesicles (SVs) from neurospheres derived from human induced pluripotent stem cells (hiPSCs). The protocol begins with neurosphere cultivation to achieve mature neurons, which is essential for the functional studies of neuronal activity. Following this, neurosphere-derived synaptosomes are isolated, and SVs are enriched through differential centrifugation. The method culminates in the proteomic analysis of SVs using nano-liquid chromatography coupled with high-resolution tandem mass spectrometry (nanoLC-MS/MS), providing a detailed proteome profile of the isolated vesicles. This protocol can contribute to the understanding of SV molecular heterogeneity and the mechanisms of neurotransmitter uptake and release and be applied to the field of research in neurological and neuropsychiatric disorders.</AbstractText"
]
] |
15556023
|
Conflict monitoring and anterior cingulate cortex: an update.
|
One hypothesis concerning the human dorsal anterior cingulate cortex (ACC) is that it functions, in part, to signal the occurrence of conflicts in information processing, thereby triggering compensatory adjustments in cognitive control. Since this idea was first proposed, a great deal of relevant empirical evidence has accrued. This evidence has largely corroborated the conflict-monitoring hypothesis, and some very recent work has provided striking new support for the theory. At the same time, other findings have posed specific challenges, especially concerning the way the theory addresses the processing of errors. Recent research has also begun to shed light on the larger function of the ACC, suggesting some new possibilities concerning how conflict monitoring might fit into the cingulate's overall role in cognition and action.</AbstractText
|
[
[
"16635578",
"Divide and conquer: a defense of functional localizers.",
"Numerous functionally distinct regions of cortex (e.g., V1, MT, the fusiform face area) can be easily identified in any normal human subject in just a few minutes of fMRI scanning. However, the locations of these regions vary across subjects. Investigations of these regions have therefore often used a functional region of interest (fROI) approach in which the region is first identified functionally in each subject individually, before subsequent scans in the same subjects test specific hypotheses concerning that region. This fROI method, which resembled long-established practice in visual neurophysiology, has methodological, statistical, and theoretical advantages over standard alternatives (such as whole-brain analyses of group data): (i) because functional properties are more consistently and robustly associated with fROIs than with locations in stereotaxic space, functional hypotheses concerning fROIs are often the most straightforward to frame, motivate, and test, (ii) because hypotheses are tested in only a handful of fROIs (instead of in tens of thousands of voxels), advance specification of fROIs provides a massive increase in statistical power over whole-brain analyses, and (iii) some fROIs may serve as candidate distinct components of the mind/brain worth investigation as such. Of course fROIs can be productively used in conjunction with other complementary methods. Here, we explain the motivation for and advantages of the fROI approach, and we rebut the criticism of this method offered by Friston et al. (Friston, K., Rotshtein, P., Geng, J., Sterzer, P., Henson, R., in press. A critique of functional localizers. NeuroImage).</AbstractText"
]
] |
[
[
"15082137",
"Ethosuximide reverses paclitaxel- and vincristine-induced painful peripheral neuropathy.",
"Paclitaxel (Taxol) is one of the most effective and frequently used chemotherapeutics for the treatment of solid tumours. However, paclitaxel produces peripheral neurotoxicity with patients reporting sensory abnormalities and neuropathic pain during and often persisting after paclitaxel therapy. The mechanisms underlying this dose-limiting side effect are currently unknown and there are no validated drugs for its prevention or control. Male Sprague-Dawley rats received four intraperitoneal (i.p.) injections on alternate days of 2 mg/kg paclitaxel. Behavioural assessment using von Frey filaments and acetone showed that such paclitaxel treatment induced a pronounced mechanical and cold allodynia/hyperalgesia. Thus these studies aim to test potential analgesics on established paclitaxel-induced pain. Paclitaxel-induced pain appears to be relatively resistant to opioid therapy i.p. 4 mg/kg morphine was ineffective and i.p. 8 mg/kg morphine only elicited up to a 50% reversal of mechanical allodynia/hyperalgesia. Interestingly, a maximally tolerated dose (i.p. 0.2 mg/kg) of the potent NMDA receptor antagonist MK-801 produced no significant reversal of the mechanical allodynia/hyperalgesia suggesting that NMDA receptors have little role in paclitaxel-induced pain. Ethosuximide (i.p. 450 mg/kg) an anti-epileptic and relatively selective T-type calcium channel blocker elicited a near complete reversal of mechanical allodynia/hyperalgesia. Repetitive dosing with ethosuximide (i.p. 100 or 300 mg/kg daily for 3 days) showed a dose-related consistent reversal of mechanical allodynia/hyperalgesia with no evidence of tolerance. Ethosuximide (i.p. 300 mg/kg) also reversed paclitaxel-induced cold allodynia and vincristine-induced mechanical allodynia/hyperalgesia. These data suggest that T-type calcium channels may play a role in chemotherapy-induced neuropathy and moreover identify ethosuximide as a new potential treatment for chemotherapy-induced pain.</AbstractText"
]
] |
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