title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Empathy and compassion. | As humans we are a highly social species: in order to coordinate our joint actions and assure successful communication, we use language skills to explicitly convey information to each other, and social abilities such as empathy or perspective taking to infer another person's emotions and mental state. The human cognitive capacity to draw inferences about other peoples' beliefs, intentions and thoughts has been termed mentalizing, theory of mind or cognitive perspective taking. This capacity makes it possible, for instance, to understand that people may have views that differ from our own. Conversely, the capacity to share the feelings of others is called empathy. Empathy makes it possible to resonate with others' positive and negative feelings alike--we can thus feel happy when we vicariously share the joy of others and we can share the experience of suffering when we empathize with someone in pain. Importantly, in empathy one feels with someone, but one does not confuse oneself with the other; that is, one still knows that the emotion one resonates with is the emotion of another. If this self-other distinction is not present, we speak of emotion contagion, a precursor of empathy that is already present in babies. | 25,247,366 | [
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Robotics and neuroscience. | In the attempt to build adaptive and intelligent machines, roboticists have looked at neuroscience for more than half a century as a source of inspiration for perception and control. More recently, neuroscientists have resorted to robots for testing hypotheses and validating models of biological nervous systems. Here, we give an overview of the work at the intersection of robotics and neuroscience and highlight the most promising approaches and areas where interactions between the two fields have generated significant new insights. We articulate the work in three sections, invertebrate, vertebrate and primate neuroscience. We argue that robots generate valuable insight into the function of nervous systems, which is intimately linked to behaviour and embodiment, and that brain-inspired algorithms and devices give robots life-like capabilities. | 25,247,370 | [
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Synthesis of fluorescent 2,3,5,6-tetraalkynylpyridines by site-selective Sonogashira-reactions of 2,3,5,6-tetrachloropyridines. | 4-Substituted 2,3,5,6-tetraalkynylpyridines were prepared by tetra-fold Sonogashira reactions of the corresponding 2,3,5,6-tetrachloropyridines. 2,6-Dialkynyl-3,5-dichloropyridines were prepared by site-selective Sonogashira reactions from various 4-unsubstituted and 4-substituted tetrachloropyridines. Subsequent two-fold Sonogashira reactions of the products allowed for the synthesis of various 2,3,5,6-tetraalkynylpyridines containing different alkynyl groups. The products exhibit interesting UV/Vis and fluorescence properties. The position of absorption and emission bands can be tuned by systematic variation of the type of alkynyl substituent and by the type of substituent located at position 4 of the pyridine moiety. The presence of electron withdrawing substituents or of an alkynyl group at position 4 as well as the presence of donor substituted alkynyl groups at positions 2, 3, 5 and 6 resulted in high fluorescence quantum yields of up to 0.6, presumably due to the push-pull substitution pattern of the molecules. | 25,247,374 | [
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Oxytetracycline, tetracycline, chlortetracycline and doxycycline in pasteurised cow's milk commercialised in Brazil. | The aim of this study was to investigate the presence of tetracycline residues in pasteurised cow's milk using high-performance liquid chromatography coupled with UV/VIS detection to determine the exposure of Brazilian's population to antibiotic residues. One hundred samples collected from the State of Paraná, Brazil, were analysed. Three of these samples were contaminated at the following concentrations: 121.8 µg·kg(-1) for oxytetracycline, 93.5 µg·kg(-1) for tetracycline and 134.6 µg·kg(-1) for chlortetracycline (61.6 µg·kg(-1)) and doxycycline (73.0 µg·kg(-1)). The median tetracycline residue concentration found in the samples was 42.3 µg·kg(-1), and the estimated daily intake (EDI) was 0.05 µg Kg(-1) bw day(-1) in Brazil. These results demonstrate that the occurrence of tetracycline in Brazilian milk was low (3%) and only for 2% above the maximum residue limit, so the risk to the population from the presence of these residues in milk was low (<1% of the acceptable daily intake). | 25,247,384 | [
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Multidetector CT measurement of myocardial extracellular volume in acute patchy and contiguous infarction: validation with microscopic measurement. | To provide proof of concept that expansion of myocardial extracellular volume (MECV), measured at contrast material-enhanced multidetector computed tomography (CT), can be used as a (a) marker for viability based on histologic confirmation and (b) predictor of severity of myocardial injury. Animals cared for in compliance with Institutional Animal Care and Use Committee served as controls (group 1, n = 6) or were subjected to microinfarction by using 16-mm(3) (60 000 count) microemboli (group 2) and 32-mm(3) (120 000 count) microemboli (group 3), contiguous infarct with left anterior descending artery (LAD) occlusion followed by reperfusion (group 4), or the combination of LAD occlusion and 32-mm(3) microemboli followed by reperfusion (group 5) (n = 7 per group). MECV calculations were based on regional measurements of signal attenuation at contrast-enhanced multidetector CT and counterstaining of infarct at microscopy. Two-way analysis of variance and Student t tests were used to determine significant differences (P < .05). Data were presented as means ± standard deviations. Mean signal attenuation at equilibrium state of contrast media distribution (10 minutes) was significantly different among blood (137 HU ± 10), myocardial muscle (77 HU ± 12, P < .05), and skeletal muscle (35 HU ± 12, P < .05). Patchy microinfarct, contiguous infarct, and microinfarct with preexisting contiguous infarct can be differentiated on the basis of mean MECV (24% ± 3 [group 1] vs 36% ± 3 [group 2], P < .01, and 55% ± 5 [group 4], 56% ± 4 [group 5] vs 41% ± 3 [group 3], P < .05). Microscopy measurements confirmed multidetector CT quantitative measurements and differences in patterns of infarct caused by obstruction of major and minor coronary arteries. Regression analysis revealed excellent correlation between regional MECV using multidetector CT and microscopy (r(2) = 0.92). Contrast-enhanced multidetector CT is a suitable noninvasive imaging technique for assessing MECV in acute patchy and contiguous infarct caused by obstruction of major and minor coronary vessels. | 25,247,406 | [
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New players driving inflammation in monogenic autoinflammatory diseases. | Systemic autoinflammatory diseases are caused by abnormal activation of the cells that mediate innate immunity. In the past two decades, single-gene defects in different pathways, driving clinically distinct autoinflammatory syndromes, have been identified. Studies of these aberrant pathways have substantially advanced understanding of the cellular mechanisms that contribute to mounting effective and balanced innate immune responses. For example, mutations affecting the function of cytosolic immune sensors known as inflammasomes and the IL-1 signalling pathway can trigger excessive inflammation. A surge in discovery of new genes associated with autoinflammation has pointed to other mechanisms of disease linking innate immune responses to a number of basic cellular pathways, such as maintenance of protein homeostasis (proteostasis), protein misfolding and clearance, endoplasmic reticulum stress and mitochondrial stress, metabolic stress, autophagy and abnormalities in differentiation and development of myeloid cells. Although the spectrum of autoinflammatory diseases has been steadily expanding, a substantial number of patients remain undiagnosed. Next-generation sequencing technologies will be instrumental in finding disease-causing mutations in as yet uncharacterized diseases. As more patients are reported to have clinical features of autoinflammation and immunodeficiency or autoimmunity, the complex interactions between the innate and adaptive immune systems are unveiled. | 25,247,411 | [
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HIV disease progression in seroconvertors from the CAPRISA 004 tenofovir gel pre-exposure prophylaxis trial. | Although antiretroviral pre-exposure prophylaxis prevents HIV acquisition, it is not known if it alters HIV disease progression. This study assesses whether tenofovir gel impacted on disease progression among CAPRISA 004 microbicide trial seroconvertors. Eighty-three seroconvertors from the tenofovir and placebo gel arms of the CAPRISA 004 trial were monitored prospectively for a minimum of 2 years by CD4 count and viral load (VL). Linear mixed models were fitted to HIV VL, and log rank test was used to compare time to reach CD4 counts of <350 cells per microliter. Median 2-week postinfection VL was 4.74 and 4.45 log copies per milliliter in women assigned to tenofovir gel (n = 32) and placebo gel (n = 51) (P = 0.189). Corresponding 12-month postinfection VLs were 4.24 and 3.70 log copies per milliliter (P = 0.016). After adjusting for clinical and behavioral characteristics and protective HLA alleles, mean VLs within the first 2 years were 4.51 and 4.02 log copies per milliliter in women from the tenofovir and placebo arms (P = 0.013). Among women with vaginal tenofovir measurements, mean VLs were 4.53 and 4.60 log copies per milliliter in those with detectable versus undetectable levels (P = 0.840). Overall mean CD4 counts were 463 and 514 cells per microliter in women assigned to tenofovir and placebo (P = 0.290). Thirty-two women (38.6%) reached CD4 counts of <350 cells per microliter at median 9.4 months postinfection, 13 (40.6%) from the tenofovir and 19 (37.3%) from the placebo arms (P = 0.786). Tenofovir gel had no impact on postinfection CD4 counts or the rate of CD4 decline. Although seroconvertors from the tenofovir arm experienced higher VLs, this did not result in a need for earlier antiretroviral therapy. | 25,247,433 | [
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Disordered eating in obese individuals. | This article provides an overview of current thinking about the association between disordered eating and obesity, emphasizing binge eating, binge eating disorder and food addiction as useful conceptual models. Binge eating, recurrent and persistent episodes of overeating coupled with a lack of control over eating, and binge eating disorder, the Diagnostic and Statistical Manual-5 mental disorder, have been a major focus of work to clarify the relationship between disordered eating and obesity. A second focus has been the addiction model of aberrant eating, which posits that recurrent overeating of palatable food is similar to addictive behavior and characterized by dysregulation of the dopaminergic reward system. We describe efforts to integrate these models by focusing on binge eating phenotypes as the subgroup of obese individuals characterized by disordered eating. Examples of empirical work based on these models are provided, as well as selected studies that reflect the burgeoning literature focusing on addictive and feeding behaviors across multiple domains and levels of analysis. Research evidence to explain similarities and differences across levels of BMI and varying aspects of feeding behavior may promote the identification of novel interventions that address weight and eating problems. | 25,247,456 | [
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Short and efficient synthesis of fluorinated δ-lactams. | The diastereoselective synthesis of fluorinated δ-lactams has been achieved through an efficient five step process. The route can tolerate a range of functionalities, and provides a quick route for the generation of new fluorinated medicinal building blocks. | 25,247,464 | [
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Kinetic and computational studies on Pd(I) dimer-mediated halogen exchange of aryl iodides. | Building on our previous discovery and reactivity explorations of the Pd(I) dimer [(PtBu3)PdBr]2-mediated halogen exchange of aryl iodides [Chem. Sci. 2013, 4, 4434], this report presents kinetic studies of this process, giving first-order kinetic dependence in the Pd(I) dimer and aryl iodide. An activation free energy barrier of ΔG(‡) = 24.9 ± 3.3 kcal/mol was experimentally determined. Extensive computational studies on the likely reaction pathway were subsequently carried out. A variety of DFT methods were assessed, ranging from dispersion-free methods to those that better account for dispersion (M06L, ωB97XD, D3-DFT). While significant discrepancies in the quantitative prediction of activation barriers were observed, all computational methods consistently predicted the analogous qualitative reactivity that is in agreement with all spectroscopic and reactivity data collected. Overall, these data provide compelling additional support of the direct reactivity of Pd(I)-Pd(I) with aryl iodides. | 25,247,472 | [
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herg1b expression as a potential specific marker in pediatric acute myeloid leukemia patients with HERG 897K/K genotype. | Human ether-a-go-go related gene (herg) encoding HERG K(+) channel has been demonstrated in many previous studies with its association to cell cycle progression and growth in tumor cells. The upregulated expression of HERG K+ channels was determined in different tumor types. Furthermore, not only full-length transcript herg1 but also a truncated isoform herg1b was shown to be expressed in cancer cells. In this study, the expression levels of herg1 and herg1b and the impact of K897T mutation on their expressions were investigated in pediatric acute myeloid leukemia (pAML). Expression levels of herg1 and herg1b isoforms were analyzed by quantitative real time polymerase chain reaction (PCR) in pAML patients together with healthy donors, and their expressions were confirmed by western blotting. The 2690 A>C nucleotide variation in KCNH2 gene corresponding to K897T amino acid change was analyzed by PCR followed by restriction enzyme digestion. herg1b overexpression was observed in tumor cells compared to healthy controls (P = .0024). However, herg1 expression was higher in healthy control cells than tumor cells (P = .001). The prevalence of polymorphic allele 897T was 26% in our patient group and 897T carriers showed increased herg1b expression compared to wild-type allele carriers. Our results demonstrate the presence of the increased levels of herg1b expression in pAML. In addition, we report for the first time that, pAML subgroup with HERG 897K/K genotype compared to 897K/T and T/T genotypes express increased levels of herg1b. In conclusion, HERG 897K/K genotype with increased level of herg1b expression might well be a prognostic marker for pAML. | 25,247,487 | [
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Crack cocaine users show differences in genotype frequencies of the 3' UTR variable number of tandem repeats of the dopamine transporter gene (DAT1/SLC6A3). | Due to the mechanism of action of the dopamine transporter (DAT) in drug addiction, the DAT1 gene is a potential candidate for molecular studies. This paper aims to compare the prevalence of allele and genotype frequencies created by the 3' UTR variable number of tandem repeats (VNTR) of this gene between crack cocaine users and controls. A cross-sectional sample of 237 current adult crack cocaine abusers or dependents (DSM-IV TR criteria) from in- and outpatient clinics in southern Brazil and 205 community controls were compared. The subjects were evaluated using the Adult ADHD Self-Report Scale, the Mini-International Neuropsychiatric Interview - short version, and the Wechsler Intelligence Scale. DNA samples were genotyped for the DAT1 3' VNTR. Logistic regression analysis was performed to compare the frequency of the 10.10 genotype (the putative risk genotype) to those of other genotypes. A significant difference (p = 0.04, OR = 1.758, CI = 1.026-3.012) indicating an increased frequency of the 10.10 genotype in the cases (59.9%) compared to the controls (49.3%) was verified using clinical and demographic covariates. This is one of the first genetic association studies on crack cocaine users in the literature. The results suggest an influence of the DAT1 gene, namely the 3' VNTR 10.10 genotype. However, more analyses will confirm and clarify its contribution as a possible risk factor for crack cocaine dependence. | 25,247,548 | [
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Use of insecticide-treated school uniforms for prevention of dengue in schoolchildren: a cost-effectiveness analysis. | Dengue-related illness is a leading cause of hospitalization and death, particularly among children. Practical, acceptable and affordable measures are urgently needed to protect this age group. Schools where children spend most of their day is proposed as an ideal setting to implement preventive strategies against day-biting Aedes mosquitoes. The use of insecticide-treated school uniforms is a promising strategy currently under investigation. Using a decision-analytic model, we evaluated the cost-effectiveness of the use of insecticide-treated school uniforms for prevention of dengue, compared with a "do-nothing" alternative, in schoolchildren from the societal perspective. We explored how the potential economic value of the intervention varied under various scenarios of intervention effectiveness and cost, as well as dengue infection risk in school-aged children, using data specific to Thailand. At an average dengue incidence rate of 5.8% per year in school-aged children, the intervention was cost-effective (ICER≤$16,440) in a variety of scenarios when the intervention cost per child was $5.3 or less and the intervention effectiveness was 50% or higher. In fact, the intervention was cost saving (ICER<0) in all scenarios in which the intervention cost per child was $2.9 or less per year and the intervention effectiveness was 50% or higher. The results suggested that this intervention would be of no interest to Thai policy makers when the intervention cost per child was $10.6 or higher per year regardless of intervention effectiveness (ICER>$16,440). Our results present the potential economic value of the use of insecticide-treated uniforms for prevention of dengue in schoolchildren in a typical dengue endemic setting and highlight the urgent need for additional research on this intervention. | 25,247,556 | [
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Case 210: Primary ovarian lymphoma. | History A 45-year-old woman presented with a 4-day history of abdominal discomfort, nausea, and vomiting and a 1-month history of poor appetite and weight loss. Her white blood cell count was normal. Physical examination revealed a palpable mass in the abdominopelvic region. Her cancer antigen (CA) 125 level was 1366 U/mL. No history of malignancy had been noted previously. The patient underwent abdominopelvic computed tomography (CT) (Fig 1). There was no other mass lesion at any other site in this patient. | 25,247,567 | [
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Metabolism of cryptic peptides derived from neuropeptide FF precursors: the involvement of insulin-degrading enzyme. | The term "cryptome" refers to the subset of cryptic peptides with bioactivities that are often unpredictable and very different from the parent protein. These cryptic peptides are generated by proteolytic cleavage of proteases, whose identification in vivo can be very challenging. In this work, we show that insulin-degrading enzyme (IDE) is able to degrade specific amino acid sequences present in the neuropeptide pro-NPFFA (NPFF precursor), generating some cryptic peptides that are also observed after incubation with rat brain cortex homogenate. The reported experimental findings support the increasingly accredited hypothesis, according to which, due to its wide substrate selectivity, IDE is involved in a wide variety of physiopathological processes. | 25,247,577 | [
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Pediatric invasive pneumococcal disease in Taiwan following a national catch-up program with the 13-valent pneumococcal conjugate vaccine. | Seven-valent pneumococcal conjugate vaccine (PCV) has been available in Taiwan since late 2005. A national catch-up program was launched in Taiwan in 2013, providing 1 dose of 13-valent PCV to children aged 2-5 years. Here, we report the epidemiology of invasive pneumococcal disease (IPD) in children aged ≤5 years in this setting. We collected demographic and clinical information for pediatric patients (≤5 years) with IPD between 2008 and 2013. The incidence of IPD was estimated. The logs for PCV import into Taiwan were obtained to evaluate the impact of PCV usage on IPD epidemiology. The overall incidence of IPD in children aged ≤5 years was 15.9 cases per 100,000 person-years. The IPD incidence caused by 7-valent PCV serotypes decreased significantly from 10.0 cases per 100,000 person-years in 2008 to 2.3 cases per 100,000 person-years in 2013. The incidence of IPD caused by serotype 19A increased substantially from 1.7 cases per 100,000 person-years in 2008 to 10.3 cases per 100,000 person-years in 2012, followed by a significant decrease to 5.6 cases per 100,000 person-years in 2013. The significant decrease in the incidence of serotype 19A IPD occurred primarily in children aged 2-5 years. The 13-valent PCV catch-up program was associated with a significant decrease in serotype 19A IPD incidence in 2013, primarily in children eligible for the 13-valent PCV immunization. Continued surveillance is necessary to assess the further impact of the national catch-up program on pediatric IPD epidemiology in Taiwan. | 25,247,584 | [
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Reading performance is enhanced by visual texture discrimination training in Chinese-speaking children with developmental dyslexia. | High order cognitive processing and learning, such as reading, interact with lower-level sensory processing and learning. Previous studies have reported that visual perceptual training enlarges visual span and, consequently, improves reading speed in young and old people with amblyopia. Recently, a visual perceptual training study in Chinese-speaking children with dyslexia found that the visual texture discrimination thresholds of these children in visual perceptual training significantly correlated with their performance in Chinese character recognition, suggesting that deficits in visual perceptual processing/learning might partly underpin the difficulty in reading Chinese. To further clarify whether visual perceptual training improves the measures of reading performance, eighteen children with dyslexia and eighteen typically developed readers that were age- and IQ-matched completed a series of reading measures before and after visual texture discrimination task (TDT) training. Prior to the TDT training, each group of children was split into two equivalent training and non-training groups in terms of all reading measures, IQ, and TDT. The results revealed that the discrimination threshold SOAs of TDT were significantly higher for the children with dyslexia than for the control children before training. Interestingly, training significantly decreased the discrimination threshold SOAs of TDT for both the typically developed readers and the children with dyslexia. More importantly, the training group with dyslexia exhibited significant enhancement in reading fluency, while the non-training group with dyslexia did not show this improvement. Additional follow-up tests showed that the improvement in reading fluency is a long-lasting effect and could be maintained for up to two months in the training group with dyslexia. These results suggest that basic visual perceptual processing/learning and reading ability in Chinese might at least partially rely on overlapping mechanisms. | 25,247,602 | [
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Smart polymer nanoparticles for high-performance water-borne coatings. | Poly(butyl methacrylate) nanoparticles encapsulating a silica precursor, tetraethoxysilane (TEOS), were synthesized by a two-step emulsion polymerization process. We show that TEOS remains mostly unreacted inside the nanoparticles in water but acts both as a plasticizer and cross-linker in films cast from the dispersions. The diffusion-enhancing plasticizing effect is dominant at annealing temperatures closer to the glass-transition temperature of the polymer, and sol-gel cross-linking reactions predominate at higher temperatures. By choosing an appropriate annealing temperature, we were able to balance polymer interdiffusion and silica cross-linking to obtain films with good mechanical properties and excellent chemical resistance. The hybrid cross-linked films produced from these novel "smart" nanoparticles can be used in water-borne environmentally friendly coatings for high-performance applications. | 25,247,636 | [
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Working with adolescents and young adults to support transition. | Transition of medical care is a multifaceted, active process that attends to the medical, psychosocial, educational and vocational needs of adolescents and young adults as they move from child- to adult-centred care. Transition from paediatric to adult services is recognized as an important part of continuous care for young people with disorders of sex development (DSD), just as it is for all young people affected by chronic medical conditions. There is evidence that the medical community is failing to transition young people with DSD safely, the result being that young people are lost to care and not receiving appropriate services into adulthood. To support transition more effectively, healthcare professionals should provide developmentally appropriate care. To accomplish this, healthcare professionals must understand, recognize and address the real-life challenges faced by young people in general, as well as those challenges specific to having DSD. Communication between paediatric and adult services, individual healthcare professionals, young people and their families is necessary for the successful transition of care. | 25,247,650 | [
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Update on multiple sclerosis treatments. | Relapsing-remitting multiple sclerosis (RRMS) management has dramatically changed over the past decade. New drugs have arrived on the market, allowing for more individualised treatment selection. However, this diversity has increased the complexity of RRMS patient follow-up. In this review, we provide summarised information about treatment efficacy, potential side-effects, follow-up recommendations, vaccinations, and pregnancy safety issues for all currently available disease modifying therapies and those awaiting approval. | 25,247,669 | [
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The role of resting state networks in focal neocortical seizures. | The role of resting state functional networks in epilepsy is incompletely understood. While some pathologic diagnoses have been shown to have maintained but altered resting state connectivity, others have implicated resting state connectivity in disease progression. However little is known about how these resting state networks influence the behavior of a focal neocortical seizure. Using data taken from invasively monitored patients with intractable focal neocortical epilepsy, we evaluated network connectivity (as determined by oscillatory covariance of the slow cortical potential (<0.5 Hz)) as it relates to neocortical seizure foci both in the interictal and ictal states. Similar to what has been shown in the past for sleep and anesthesia, electophysiologic resting state networks that are defined by this slow cortical potential covariance maintain their topographic correlation structure throughout an ictal event. Moreover, in the context of focal epilepsy in which the seizure has a specific site of onset, seizure propagation is not chaotic or random. Rather, the seizure (reflected by an elevation of high frequency power) preferentially propagates along the network that contains the seizure onset zone. Taken together, these findings further undergird the fundamental role of resting state networks, provide novel insights into the network-influenced behavior of seizures, and potentially identify additional targets for surgical disconnection including informing the location for the completion of multiple subpial transections (MSPTs). | 25,247,680 | [
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Dual role of endothelial nitric oxide synthase in oxidized LDL-induced, p66Shc-mediated oxidative stress in cultured human endothelial cells. | The aging gene p66Shc, is an important mediator of oxidative stress-induced vascular dysfunction and disease. In cultured human aortic endothelial cells (HAEC), p66Shc deletion increases endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) bioavailability via protein kinase B. However, the putative role of the NO pathway on p66Shc activation remains unclear. This study was designed to elucidate the regulatory role of the eNOS/NO pathway on p66Shc activation. Incubation of HAEC with oxidized low density lipoprotein (oxLDL) led to phosphorylation of p66Shc at Ser-36, resulting in an enhanced production of superoxide anion (O2-). In the absence of oxLDL, inhibition of eNOS by small interfering RNA or L-NAME, induced p66Shc phosphorylation, suggesting that basal NO production inhibits O2- production. oxLDL-induced, p66Shc-mediated O2- was prevented by eNOS inhibition, suggesting that when cells are stimulated with oxLDL eNOS is a source of reactive oxygen species. Endogenous or exogenous NO donors, prevented p66Shc activation and reduced O2- production. Treatment with tetrahydrobiopterin, an eNOS cofactor, restored eNOS uncoupling, prevented p66Shc activation, and reduced O2- generation. However, late treatment with tetrahydropterin did not yield the same result suggesting that eNOS uncoupling is the primary source of reactive oxygen species. The present study reports that in primary cultured HAEC treated with oxLDL, p66Shc-mediated oxidative stress is derived from eNOS uncoupling. This finding contributes novel information on the mechanisms of p66Shc activation and its dual interaction with eNOS underscoring the importance eNOS uncoupling as a putative antioxidant therapeutical target in endothelial dysfunction as observed in cardiovascular disease. | 25,247,687 | [
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Effect of flaxseed on choroid-sclera complex thickness and on LDL oxidation in the sclera, choroid and retina of diet-induced hypercholesterolaemic rabbits. | The aim of the present study was to evaluate the effect of flaxseed on choroid-sclera complex thickness and on LDL oxidation in the sclera, choroid and retina of diet-induced hypercholesterolaemic rabbits. New Zealand male albino rabbits (n 21) were divided into two groups: group 1 (G1; n 11), fed a hypercholesterolaemic diet, and group 2 (G2; n 10), fed a hypercholesterolaemic diet enriched with flaxseed flour. The serum concentrations of total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol, TAG and fasting blood glucose were determined at the start of the experiment and on the day of killing (8th week). Choroid and sclera samples were subjected to haematoxylin-eosin (HE) staining and histomorphometric and immunohistochemical analyses with the anti-oxidised LDL antibody. Sensory retina samples were subjected to an immunohistochemical analysis with the primary monoclonal nitrotyrosine antibody. At the end of the experiment, a significant increase was observed in TC and LDL-C concentrations in G1 rabbits when compared with G2 rabbits (P= 0·008 and P= 0·02, respectively). HE staining revealed a significant increase in choroid-sclera complex thickness in G1 rabbits when compared with G2 rabbits (P< 0·001). Immunohistochemical analysis of choroid and sclera samples with the anti-oxidised LDL marker revealed a significant increase in immunoreactivity in G1 rabbits when compared with G2 rabbits (P< 0·001). Immunohistochemical analysis of sensory retina samples with the anti-nitrotyrosine marker revealed a significant increase in immunoreactivity in G1 rabbits when compared with G2 rabbits (P= 0·002). Flaxseed reduced the choroid-sclera complex thickness of diet-induced hypercholesterolaemic rabbits and the expression of oxidised LDL in the choroid-sclera complex as well as the expression of nitrotyrosine in the sensory retina. | 25,247,699 | [
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3-Dimensional culture systems for anti-cancer compound profiling and high-throughput screening reveal increases in EGFR inhibitor-mediated cytotoxicity compared to monolayer culture systems. | 3-dimensional (3D) culture models have the potential to bridge the gap between monolayer cell culture and in vivo studies. To benefit anti-cancer drug discovery from 3D models, new techniques are needed that enable their use in high-throughput (HT) screening amenable formats. We have established miniaturized 3D culture methods robust enough for automated HT screens. We have applied these methods to evaluate the sensitivity of normal and tumorigenic breast epithelial cell lines against a panel of oncology drugs when cultured as monolayers (2D) and spheroids (3D). We have identified two classes of compounds that exhibit preferential cytotoxicity against cancer cells over normal cells when cultured as 3D spheroids: microtubule-targeting agents and epidermal growth factor receptor (EGFR) inhibitors. Further improving upon our 3D model, superior differentiation of EC50 values in the proof-of-concept screens was obtained by co-culturing the breast cancer cells with normal human fibroblasts and endothelial cells. Further, the selective sensitivity of the cancer cells towards chemotherapeutics was observed in 3D co-culture conditions, rather than as 2D co-culture monolayers, highlighting the importance of 3D cultures. Finally, we examined the putative mechanisms that drive the differing potency displayed by EGFR inhibitors. In summary, our studies establish robust 3D culture models of human cells for HT assessment of tumor cell-selective agents. This methodology is anticipated to provide a useful tool for the study of biological differences within 2D and 3D culture conditions in HT format, and an important platform for novel anti-cancer drug discovery. | 25,247,711 | [
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1,5-Diaminonaphthalene hydrochloride assisted laser desorption/ionization mass spectrometry imaging of small molecules in tissues following focal cerebral ischemia. | A sensitive analytical technique for visualizing small endogenous molecules simultaneously is of great significance for clearly elucidating metabolic mechanisms during pathological progression. In the present study, 1,5-naphthalenediamine (1,5-DAN) hydrochloride was prepared for matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) of small molecules in liver, brain, and kidneys from mice. Furthermore, 1,5-DAN hydrochloride assisted LDI MSI of small molecules in brain tissue of rats subjected to middle cerebral artery occlusion (MCAO) was carried out to investigate the altered metabolic pathways and mechanisms underlying the development of ischemic brain damage. Our results suggested that the newly prepared matrix possessed brilliant features including low cost, strong ultraviolet absorption, high salt tolerance capacity, and fewer background signals especially in the low mass range (typically m/z < 500), which permitted us to visualize the spatial distribution of a broad range of small molecule metabolites including metal ions, amino acids, carboxylic acids, nucleotide derivatives, peptide, and lipids simultaneously. Nineteen endogenous metabolites involved in metabolic networks such as ATP metabolism, tricarboxylic acid (TCA) cycle, glutamate-glutamine cycle, and malate-aspartate shuttle, together with metal ions and phospholipids as well as antioxidants underwent relatively obvious changes after 24 h of MCAO. The results were highly consistent with the data obtained by MRM MS analysis. These findings highlighted the promising potential of the organic salt matrix for application in the field of biomedical research. | 25,247,713 | [
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Assessment of prosthesis alignment after revision total knee arthroplasty using EOS 2D and 3D imaging: a reliability study. | A new low-dose X-ray device, called EOS, has been introduced for determining lower-limb alignment in 2D and 3D. Reliability has not yet been assessed when using EOS on lower limbs containing a knee prosthesis. Therefore purpose of this study was to determine intraobserver and interobserver reliability of EOS 2D and 3D knee prosthesis alignment measurements after revision total knee arthroplasty (rTKA). Forty anteroposterior and lateral images of 37 rTKA patients were included. Two observers independently performed measurements on these images twice. Varus/valgus angles were measured in 2D (VV2D) and 3D (VV3D). Intraclass correlation coefficients and the Bland and Altman method were used to determine reliability. T-tests were used to test potential differences. Intraobserver and interobserver reliability were excellent for VV2D and VV3D. No significant difference or bias between the first and second measurements or the two observers was found. A significant mean and absolute difference of respectively 1.00° and 1.61° existed between 2D and 3D measurements. EOS provides reliable varus/valgus measurements in 2D and 3D for the alignment of the knee joint with a knee prosthesis. However, significant differences exist between varus/valgus measurements in 2D and 3D. | 25,247,714 | [
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The effect of residual calcium hydroxide on the accuracy of a contemporary electronic apex locator. | The aim of this study was to evaluate the effect of residual calcium hydroxide [Ca(OH)2] on the accuracy of an electronic apex locator (EAL). Working lengths (WLs) of 56 extracted maxillary incisors were determined initially by two different methods. The first method used the 'APEX' reading of the EAL as a reference point, 0.5 mm was subtracted and recorded as WL0. The second method used the '0.5' reading and the score was recorded as WL0.5 without subtraction. The roots were prepared to WL0 and divided randomly into three experimental groups (n = 16) (1 mm in group A, 2 mm in group B and 4 mm in group C) and a control (n = 8). Specimens in all experimental groups were filled with Ca(OH)2 paste. Following its removal, WLs were re-determined with the same methods. In group C, pre/post WLs were significantly different (p < 0.05). No significant difference was observed between the other experimental groups and the control group. Accuracy of EAL decreased proportionally with the amount of paste remaining at the ±0.5-mm tolerance level. Ca(OH)2 paste remnants may cause incorrect EAL readings. | 25,247,720 | [
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Maternally administered interventions for preterm infants in the NICU: effects on maternal psychological distress and mother-infant relationship. | Although studies have examined the effects of interventions focused on preterm infants, few studies have examined the effects on maternal distress (anxiety, depressive symptoms, post-traumatic stress symptoms, parenting stress) or parenting. This study examined the effects of the auditory-tactile-visual-vestibular (ATVV) intervention and kangaroo care (KC) on maternal distress and the mother-infant relationship compared to an attention control group. 240 mothers from four hospitals were randomly assigned to the three groups. Maternal characteristics in the three groups were similar: 64.1% of ATVV mothers, 64.2% of KC mothers, and 76.5% of control mothers were African American; maternal age averaged 26.3 years for ATVV mothers, 28.1 for KC mothers, and 26.6 for control mothers; and years of education averaged 13.6 for ATVV and KC mothers, and 13.1 for control mothers. Mothers only differed on parity: 68.4% of ATVV and 54.7% of KC mothers were first-time mothers as compared to 43.6% of control mothers. Their infants had a similar mean gestational ages (27.0 weeks for ATVV, 27.2 for KC, and 27.4 for control) and mean birthweights (993 g for ATVV, 1022 for KC, and 1023 for control). Mothers completed questionnaires during hospitalization, and at 2, 6 and 12 months corrected age on demographic characteristics, depressive symptoms, state anxiety, post-traumatic stress symptoms, parenting stress, worry about child health, and child vulnerability (only at 12 months). At 2 and 6 months, 45-min videotapes of mother-infant interactions were made, and the HOME Inventory was scored. Behaviors coded from the videotapes and a HOME subscale were combined into five interactive dimensions: maternal positive involvement and developmental stimulation and child social behaviors, developmental maturity, and irritability. Intervention effects were examined using general linear mixed models controlling for parity and recruitment site. The groups did not differ on any maternal distress variable. Kangaroo care mothers showed a more rapid decline in worry than the other mothers. The only interactive dimensions that differed between the groups were child social behaviors and developmental maturity, which were both higher for kangaroo care infants. Change over time in several individual infant behaviors was affected by the interventions. When mothers reported on the interventions they performed, regardless of group assignment, massage (any form including ATVV) was associated with a more rapid decline in depressive symptoms and higher HOME scores. Performing either intervention was associated with lower parenting stress. These findings suggest that as short-term interventions, KC and ATVV have important effects on mothers and their preterm infants, especially in the first half of the first year. | 25,247,740 | [
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[Cost of Illness of HIV Patients under Anteretroviral Therapy in Germany - Results of the 48-Week Interim Analysis of the Prospective Multicentre Observational Study 'CORSAR']. | With the introduction of highly active combined antiretroviral therapy (c-ART) mortality and morbidity of HIV patients declined substantially. Earlier studies reported that c-ART was able to save health-care costs due to a reduction of other direct medical costs, particularly for inpatient treatments and concomitant medication. To date, analyses of costs and health-related quality of life (HRQOL) of patients under c-ART are lacking in Germany. Hence, this study aims to estimate the current cost of illness and HRQOL of HIV-patients under c-ART in different treatment lines. A multicenter, prospective observational study was carried out in 12 specialised German centres for infectious diseases: 8 private practices/outpatient centres and 4 specialised hospitals offering both inpatient and outpatient services. Demographic, clinical and medication data were derived from patient records. Resource utilisation, information on productivity, out of pocket costs and HRQOL (EQ-5D) were collected every 12 weeks via a patient questionnaire. All costs were calculated based on price information from publicly accessible databases. N=1,154 patients were included in the analysis. Mean direct disease-related costs of -patients under c-ART amounted to 22,563 Euro/year. Patients beyond the 3(rd) line of treatment -incurred considerably higher costs 24,654 Euro/year. In the 1(st) treatment line, c-ART accounted for 83.2% of the total direct costs, in the 2(nd)/3(rd) line for 80.8% and in >3(rd) line for 83.4%, respectively. Indirect costs due to impaired productivity were higher in the 2(nd)/3(rd) treatment line (2,843 Euro) compared to the 1(st) (1,604 Euro) and >3(rd) (1,752 Euro) treatment lines, respectively. The average HRQOL (EQ-5D) varied between 0.77 (self-assessment via visual analogue scale) and 0.91 (utility score based on the German time trade-off tariff). Over the last decade, cost of illness of HIV patients under c-ART decreased slightly with average costs per year still being substantial. Main cost driver of overall costs is c-ART. There have been, however, noticeable shifts between different cost domains. | 25,247,761 | [
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Gingival crevicular fluid interleukin-36β (-1F8), interleukin-36γ (-1F9) and interleukin-33 (-1F11) levels in different periodontal disease. | Periodontal inflammation is driven by the coordinated action of a number of factors, including the IL-1 family. Our study aimed to examine the levels of interleukin (IL)-36β, IL-36γ and IL-33 levels in gingival crevicular fluid (GCF) from patients with different periodontal diseases. A total of 80 subjects, 20 patients with generalized aggressive periodontitis (G-AgP), 20 patients with chronic periodontitis (CP), 20 with gingivitis and 20 periodontally healthy subjects were included. Periodontal status was evaluated by measuring probing depth, clinical attachment loss, papillary bleeding index and plaque index. GCF cytokine levels were analysed by ELISA. CP, gingivitis and healthy groups had similar GCF IL-36β total amount (p>0.008). G-AgP group had elevated IL-36β total amount compared to CP group (p<0.008). G-AgP group had similar GCF IL-36β total amount to gingivitis and healthy groups (p>0.008). GCF IL-36γ and IL-33 total amounts of the study groups were similar (p>0.05). The present study demonstrated for the first time the presence of IL-36β, IL-36γ and IL-33 GCF levels with different periodontal diseases. High levels of IL-36-β in the AgP group in comparison to CP group might suggest that periodontitis in the aggressive form could be related to the increase in GCF IL-36β. | 25,247,780 | [
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Modelling the influence of photospheric turbulence on solar flare statistics. | Solar flares stem from the reconnection of twisted magnetic field lines in the solar photosphere. The energy and waiting time distributions of these events follow complex patterns that have been carefully considered in the past and that bear some resemblance with earthquakes and stockmarkets. Here we explore in detail the tangling motion of interacting flux tubes anchored in the plasma and the energy ejections resulting when they recombine. The mechanism for energy accumulation and release in the flow is reminiscent of self-organized criticality. From this model, we suggest the origin for two important and widely studied properties of solar flare statistics, including the time-energy correlations. We first propose that the scale-free energy distribution of solar flares is largely due to the twist exerted by the vorticity of the turbulent photosphere. Second, the long-range temporal and time-energy correlations appear to arise from the tube-tube interactions. The agreement with satellite measurements is encouraging. | 25,247,788 | [
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A robust and accurate method for feature selection and prioritization from multi-class OMICs data. | Selecting relevant features is a common task in most OMICs data analysis, where the aim is to identify a small set of key features to be used as biomarkers. To this end, two alternative but equally valid methods are mainly available, namely the univariate (filter) or the multivariate (wrapper) approach. The stability of the selected lists of features is an often neglected but very important requirement. If the same features are selected in multiple independent iterations, they more likely are reliable biomarkers. In this study, we developed and evaluated the performance of a novel method for feature selection and prioritization, aiming at generating robust and stable sets of features with high predictive power. The proposed method uses the fuzzy logic for a first unbiased feature selection and a Random Forest built from conditional inference trees to prioritize the candidate discriminant features. Analyzing several multi-class gene expression microarray data sets, we demonstrate that our technique provides equal or better classification performance and a greater stability as compared to other Random Forest-based feature selection methods. | 25,247,789 | [
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A nutritional evaluation of dietary behaviour in various professional sports. | The types of physical exertion undertaken by weightlifters and race walkers markedly differ. This difference should also be reflected in their respective diets. The aim of the study was to investigate and assess the diets of professional weightlifters and race walkers, along with a comparison to the diets of those students studying physical education (PE). Materials and Methods. Subjects were respectively 12 weightlifters, 12 race walkers and 12 physical education students whose body composition and nutrition were determined by weighing the foods that were both eaten and drunk. The study groups showed body differences, which may have arisen through dietary differences. Higher calorie diets were observed for race walkers according to body mass whilst weightlifters showed no difference with the other groups. Dietary intakes of protein, fat, and carbohydrates were however inappropriate for all groups. Vitamin and mineral intakes in weightlifters and students were within tolerable limits, but the rather aggressive taking of supplements by race walkers resulted in standard/recommended consumption levels being greatly exceeded in some cases. The diets of the study groups of weightlifters and race walkers need to be corrected. nutrition in sport, weightlifting, race walking, food supplementation. | 25,247,803 | [
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Identification of amino acid determinants in CYP4B1 for optimal catalytic processing of 4-ipomeanol. | Mammalian CYP4B1 enzymes are cytochrome P450 mono-oxygenases that are responsible for the bioactivation of several exogenous pro-toxins including 4-ipomeanol (4-IPO). In contrast with the orthologous rabbit enzyme, we show here that native human CYP4B1 with a serine residue at position 427 is unable to bioactivate 4-IPO and does not cause cytotoxicity in HepG2 cells and primary human T-cells that overexpress these enzymes. We also demonstrate that a proline residue in the meander region at position 427 in human CYP4B1 and 422 in rabbit CYP4B1 is important for protein stability and rescues the 4-IPO bioactivation of the human enzyme, but is not essential for the catalytic activity of the rabbit CYP4B1 protein. Systematic substitution of native and p.S427P human CYP4B1 with peptide regions from the highly active rabbit enzyme reveals that 18 amino acids in the wild-type rabbit CYP4B1 protein are key for conferring high 4-IPO metabolizing activity. Introduction of 12 of the 18 amino acids that are also present at corresponding positions in other human CYP4 family members into the p.S427P human CYP4B1 protein results in a mutant human enzyme (P+12) that is as stable and as active as the rabbit wild-type CYP4B1 protein. These 12 mutations cluster in the predicted B-C loop through F-helix regions and reveal new amino acid regions important to P450 enzyme stability. Finally, by minimally re-engineering the human CYP4B1 enzyme for efficient activation of 4-IPO, we have developed a novel human suicide gene system that is a candidate for adoptive cellular therapies in humans. | 25,247,810 | [
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Retrospective review of lung cancers diagnosed in annual rounds of CT screening. | The purpose of this study was to review the records of patients with diagnoses of lung cancer in annual repeat rounds of CT screening in the International Early Lung Cancer Action Program to determine whether the cancer could have been identified in the previous round of screening. Three radiologists reviewed the scans of 104 lung cancer patients and assigned the findings to one of three categories: 1, cancer was not visible at previous CT screening; 2, cancer was visible at previous CT screening but not identified; 3, abnormality was identified at previous CT screening but not classified as malignant. Nodule size, nodule consistency, cell type, and stage at the previous screening and when identified for further workup for each of the three categories were tabulated. Twenty-four (23%) patients had category 1 findings; 56 (54%) category 2; and 24 (23%) category 3. When diagnosed, seven (29%) category 1, 10 (18%) category 2, and four (17%) category three cancers had progressed beyond stage I. All cancers seen in retrospect were in clinical stage I at the previous screening. Category 1 cancers, compared with categories 2 and 3, had faster growth rates, were less frequently adenocarcinomas (29% vs 54% and 67%, p = 0.01), and were more often small cell carcinomas (29% vs 14% and 12%, p = 0.12). Lung cancers found on annual repeat screenings were frequently identified in the previous round of screening, suggesting that review of the varied appearance and incorporation of advanced image display may be useful for earlier detection. | 25,247,825 | [
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Inflammation and endometrial bleeding. | Most of the key physiological processes in the human reproductive tract involve a significant inflammatory component. These processes include follicle development, ovulation, implantation, pregnancy, labor, postpartum, remodeling and menstruation. In this context, the term 'inflammation' usually means an influx of leukocytes ('immune cells'), often of different types, into a reproductive tract tissue. These examples of inflammation are not overtly associated with any infective process. There may also be evidence that these invading leukocytes have altered their functions to take on specific and relevant local regulatory roles. Specific sequential changes in different leukocytes can be demonstrated within human endometrium during the different phases of the normal menstrual cycle. Leukocytes are fairly sparse in numbers through the proliferative phase, but increase substantially into and through the secretory phase, so much so that around 40% of all stromal cells in the premenstrual phase are leukocytes, mainly uterine natural killer cells, a large granulated lymphocyte. Other leukocytes which play key roles in menstruation appear to be macrophages, mast cells, dendritic cells, neutrophils, eosinophils and regulatory T cells. Premenstrual withdrawal of progesterone increases the endometrial expression of inflammatory mediators, including IL-8 and MCP-1, which are believed to drive endometrial leukocyte recruitment at this time. Macrophages and neutrophils are rich sources of defensins and whey acid protein motif proteins, which play important roles in ensuring microbial protection while the epithelial barrier is disrupted. Mast cells are increasingly activated as the menstrual phase approaches, and leukocyte proteases trigger a cascade of matrix metalloproteinases and degradation of extracellular matrix. Dendritic cells and other antigen-presenting cells (e.g. macrophages) almost certainly facilitate clearance of cellular debris from the uterine cavity, and reduce the amount of viable cellular material transiting the Fallopian tubes. All of these processes are influenced or controlled by regulatory T cells. Many of these leukocytes also have the potential to release regulatory molecules which stimulate endometrial repair mechanisms. Increasing recent evidence also implicates disturbances of immune cells and their cytokine mediators in contributing to symptoms of abnormal uterine bleeding and pelvic pain. These recent findings all point towards the importance of the 'inflammatory process' in both normal and abnormal endometrial bleeding. | 25,247,830 | [
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High-resolution ultrasonic spectroscopy study of interactions between hyaluronan and cationic surfactants. | Interactions in a cationic surfactant-hyaluronan system in water and in sodium chloride solution were investigated by high-resolution ultrasonic spectroscopy at 25 °C. Two alkyltrimethylammonium bromide surfactants of different chain lengths (tetradecyl and hexadecyl) were used; hyaluronan molecular weight ranged from 10 to 1750 kDa. Two main parameters-ultrasonic velocity and attenuation-were measured in the titration regime. Up to six different regions could be identified in the velocity titration profiles in water in a narrow interval of surfactant concentration. These regions differed primarily in the compressibility of structures formed in the system. The number of detected transitions was higher for the tetradecyl surfactant; therefore, the increased length of the hydrophobic chain simplified the details of the structure-forming behavior. The measurement of attenuation was much less sensitive and detected only the formation of microheterogeneous structures or visible phase separates. The richness of the titration profiles was depressed in salt solution, where essentially only two principal regions were observed. On the other hand, the effect of hyaluronan molecular weight on the positions of boundaries between regions was more significant in the presence of salt. Besides electrostatic interactions, hydrophobic interactions are also relevant for determining the behavior of hyaluronan-surfactant systems and the properties of formed complexes (aggregates). | 25,247,835 | [
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Synthesis and anti-inflammatory and pro-resolving activities of 22-OH-PD1, a monohydroxylated metabolite of protectin D1. | Protectin D1 (PD1 (3)), a C22-dihydroxylated polyunsaturated fatty acid biosynthesized from all-Z-docosahexaenoic acid, belongs to the new family of endogenous mediators referred to as specialized pro-resolving lipid mediators. PD1 (3) is a natural product that displays potent anti-inflammatory properties together with pro-resolving actions including inhibition of polymorphonuclear leukocyte (PMN) infiltration and promotion of macrophage phagocytosis and efferocytosis. Given its potent endogenous actions, this compound has entered several clinical development programs. Little has been reported on the metabolism of PD1 (3). The synthesis and biological evaluations of the ω-22 monohydroxylated metabolite of PD1 (3), named herein 22-OH-PD1 (6), are presented. LC-MS/MS data of the free acid 6, obtained from hydrolysis of the synthetic methyl ester 7, matched data for the endogenously produced 22-OH-PD1 (6). Compound 6 exhibited potent pro-resolving actions by inhibiting PMN chemotaxis in vivo and in vitro comparable to its precursor PD1 (3) and decreased pro-inflammatory mediator levels in inflammatory exudates. The results reported herein provide new knowledge of the metabolism of the protectin class of specialized pro-resolving mediators. | 25,247,845 | [
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Does long time spending on the electronic devices affect the reading abilities? A cross-sectional study among Chinese school-aged children. | Home literacy environment (HLE) is one of most important modifiable risk factors to dyslexia. With the development in technology, we include the electronic devices usage at home, such as computers and televisions, to the definition of HLE and investigate its impact on dyslexia based on the on-going project of Tongji's Reading Environment and Dyslexia Study. The data include 5063 children, primary school students (grade 3-grade 6), from a middle-sized city in China. We apply the principal component analysis (PCA) to reduce the large dimension of variables in HLE, and find the first three components, denoted as PC1, PC2 and PC3, can explain 95.45% of HLE information. PC1 and PC2 demonstrate strong positive association with 'total time spending on electronic devices' and 'literacy-related activity', respectively. PC3 demonstrates strong negative association with 'restrictions on using electronic devices'. From the generalized linear model, we find that PC1 significantly increases the risk of dyslexia (OR = 1.043, 95% CI: 1.018-1.070), while PC2 significantly decreases the risk of dyslexia (OR = 0.839, 95% CI: 0.795-0.886). Therefore, reducing the total time spending on electronic devices and increasing the literacy-related activity would be the potential protective factors for dyslexic children in China. | 25,247,847 | [
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Preoperative low-dose steroid can prevent respiratory insufficiency after thymectomy in generalized myasthenia gravis. | Postoperative respiratory insufficiency (PRI) in myasthenia gravis (MG) often occurs within several days after thymectomy and remains problematic. In limited studies reporting that preoperative steroids prevented PRI in patients with MG, high doses of steroids were used and detailed information on the use of steroids is limited. Because high-dose steroids significantly increase the risk of adverse effects, we studied 37 patients with generalized MG to investigate whether low-dose steroids might prevent PRI. The low-dose steroids were started orally, and the dose was gradually increased to the maximum level (30 mg/day). Immediately before thymectomy, patients received the maximum dose of oral steroids daily. PRI was defined as the development of restrictive dysfunction requiring mechanical ventilation within 3 days after thymectomy and total postoperative mechanical ventilation support time of >24 h. The rate of PRI in the low-dose steroid use group was significantly lower than that in the no-steroid use group. The postoperative stay in the intensive care unit was shorter in the steroid use group. Extended thymectomy is a well-accepted surgical treatment for selected patients with MG. However, PRI remains problematic. Our results suggest that not only preoperative high-dose steroid treatment, but also low-dose steroid treatment can prevent PRI. | 25,247,848 | [
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Redox-responsive magnetic nanoparticle for targeted convection-enhanced delivery of O6-benzylguanine to brain tumors. | Resistance to temozolomide (TMZ) based chemotherapy in glioblastoma multiforme (GBM) has been attributed to the upregulation of the DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT). Inhibition of MGMT using O(6)-benzylguanine (BG) has shown promise in these patients, but its clinical use is hindered by poor pharmacokinetics that leads to unacceptable toxicity. To improve BG biodistribution and efficacy, we developed superparamagnetic iron oxide nanoparticles (NP) for targeted convection-enhanced delivery (CED) of BG to GBM. The nanoparticles (NPCP-BG-CTX) consist of a magnetic core coated with a redox-responsive, cross-linked, biocompatible chitosan-PEG copolymer surface coating (NPCP). NPCP was modified through covalent attachment of BG and tumor targeting peptide chlorotoxin (CTX). Controlled, localized BG release was achieved under reductive intracellular conditions and NPCP-BG-CTX demonstrated proper trafficking of BG in human GBM cells in vitro. NPCP-BG-CTX treated cells showed a significant reduction in MGMT activity and the potentiation of TMZ toxicity. In vivo, CED of NPCP-BG-CTX produced an excellent volume of distribution (Vd) within the brain of mice bearing orthotopic human primary GBM xenografts. Significantly, concurrent treatment with NPCP-BG-CTX and TMZ showed a 3-fold increase in median overall survival in comparison to NPCP-CTX/TMZ treated and untreated animals. Furthermore, NPCP-BG-CTX mitigated the myelosuppression observed with free BG in wild-type mice when administered concurrently with TMZ. The combination of favorable physicochemical properties, tumor cell specific BG delivery, controlled BG release, and improved in vivo efficacy demonstrates the great potential of these NPs as a treatment option that could lead to improved clinical outcomes. | 25,247,850 | [
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Comparing i-Tree modeled ozone deposition with field measurements in a periurban Mediterranean forest. | Ozone flux estimates from the i-Tree model were compared with ozone flux measurements using the Eddy Covariance technique in a periurban Mediterranean forest near Rome (Castelporziano). For the first time i-Tree model outputs were compared with field measurements in relation to dry deposition estimates. Results showed generally a good agreement between predicted and measured ozone fluxes (least sum square=5.6 e(-4)) especially when cumulative values over the whole measurement campaign are considered. However at daily and hourly time-step some overestimations were observed in estimated values especially in hot dry periods. The use of different m values in the Ball-Berry formula in the different periods, produced the best fit between predicted and measured ozone fluxes. This suggests that a variable value for the coefficient m accounting for water availability may be appropriate to improve model estimates for Mediterranean and drought prone regions. | 25,247,877 | [
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Termination chemistry-driven dislocation structure at SrTiO3/MgO heterointerfaces. | Exploiting the promise of nanocomposite oxides necessitates a detailed understanding of the dislocation structure at the interfaces, which governs diverse and technologically relevant properties. Here we report atomistic simulations demonstrating a strong dependence of the dislocation structure on the termination chemistry at the SrTiO3/MgO heterointerface. The SrO- and TiO2-terminated interfaces exhibit distinct nearest neighbour arrangements between cations and anions, leading to variations in local electrostatic interactions across the interface that ultimately dictate the dislocation structure. Networks of dislocations with different Burgers vectors and dislocation spacing characterize the two interfaces. These networks in turn influence the overall stability of and the behaviour of oxygen vacancies at the heterointerface, which will dictate vital properties such as mass transport at the interface. To date, the observed correlation between the dislocation structure and the termination chemistry at the interface has not been recognized, and offers novel avenues for fine-tuning oxide nanocomposites with enhanced functionalities. | 25,247,885 | [
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The neurosurgical treatment of Alzheimer's disease: a review. | Alzheimer's disease (AD) is a debilitating neurological illness of increasing prevalence. Because many patients are affected and current treatments have limited effectiveness, other therapeutic strategies are urgently needed. Here we provide a review of the neurosurgical approaches that have been attempted or are currently being investigated for the treatment of AD. Computerized database searches identified all of the published studies in the English-language literature examining the surgical treatment of AD since 1950. The following 5 categories of neurosurgical treatment were identified: cerebrospinal fluid shunting, intraventricular infusions, tissue grafting, gene therapy, and electrical neural stimulation. While none of the neurosurgical approaches applied to the treatment of AD have proven effective to date, recent trials involving gene therapy and electrical neural stimulation are showing promising early results. Larger trials investigating these treatments have been proposed or are currently under way. | 25,247,891 | [
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Prevalence of low back pain in Latin America: a systematic literature review. | Chronic low back pain is considered as a high-impact condition that affects the working population of Latin America, with long reaching social and economic repercussions. Its true frequency is unknown due to the absence of well-designed clinical trials that use standardized definitions and criteria. To evaluate the prevalence of chronic non-specific low back pain among the Latin American population. A systematic review of chronic non-specific low back pain in Latin America. Meeting of Change Pain Latin America, Mexico. Data sources included relevant literature identified through searches of published studies between August 30, 2002, and August 30, 2012, in 7 electronic databases: Cochrane BVS, Pubmed, Medline, Lilacs, Scielo, Hinari, and MedCarib. Publications dealing with low back pain of a post-traumatic, infectious, or malignant origin were excluded. Two reviewers selected in an independent manner all eligible studies using the MOOSE checklist and extracted data on both prevalence and risk factors associated with low back pain. A narrative synthesis of the results was drafted, which was later validated by a panel of clinical experts on pain. Twenty-eight studies were included in the review, comprising a total of 20,559 subjects from 7 countries in the region. Four of these studies, with significant methodological differences between them, measured the frequency of chronic low back pain with results that varied from 4.2% to 10.1%. Four studies are part of the Community Oriented Program for Control of Rheumatic Diseases (COPCORD) program reports, and were pooled and analyzed separately because of their particular design. Their prevalence estimations varied between 1.8% and 11.3%. The remaining 20 studies evaluated a total population of 6,992 subjects, and found a prevalence of low back pain of 31.3%. Based on an epidemiological model constructed on both times to resolution and low back pain recurrence rates, the prevalence of chronic low back pain in Latin America was estimated to be around 10.5%. Some risk factors reported by the authors are long working hours with the worker in the sitting position, obesity and overweight, pregnancy, smoking, advanced age, lifting and carrying heavy loads, domestic work, sedentary lifestyles, and duration of current employment. A subgroup analysis of the population under study yielded an estimated prevalence of low back pain of 16.7% for the population exposed to a lower number of risk factors and 65% for the higher risk subgroup. In this review, we made an exhaustive search of studies evaluating the epidemiology of chronic low back pain in the Latin America region. The large topographic and chronologic variability in definitions of low back pain, interviewer bias, and subject selection bias. Despite the sparse information and the methodological heterogeneity of the studies, pooled results allowed for an indirect estimation of the prevalence of low back pain in the region that was pretty consistent with the published results obtained from other settings. New studies need to be carried out to supplement and overcome the methodological weaknesses of those previously conducted. | 25,247,896 | [
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Catheter-based treatments for hepatic metastases from neuroendocrine tumors. | The purpose of this article is to present our experience in treating patients with hepatic metastases from a neuroendocrine primary malignancy. The tumor and patient characteristics, vascular access, and features of treatment all play a role in the long-term management of patients with metatastic neuroendocrine tumors. Routine prophylactic measures are recommended to reduce the frequency and severity of crisis events related to hormone release in patients with neuroendocrine tumors. | 25,247,935 | [
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Metal artifact reduction software used with abdominopelvic dual-energy CT of patients with metal hip prostheses: assessment of image quality and clinical feasibility. | The objective of our study was to determine the feasibility of using Metal Artifact Reduction (MAR) software for abdominopelvic dual-energy CT in patients with metal hip prostheses. This retrospective study included 33 patients (male-female ratio, 19:14; mean age, 63.7 years) who received total hip replacements and 20 patients who did not have metal prostheses as the control group. All of the patients underwent dual-energy CT. The quality of the images reconstructed using the MAR algorithm and of those reconstructed using the standard reconstruction was evaluated in terms of the visibility of the bladder wall, pelvic sidewall, rectal shelf, and bone-prosthesis interface and the overall diagnostic image quality with a 4-point scale. The mean and SD attenuation values in Hounsfield units were measured in the bladder, pelvic sidewall, and rectal shelf. For validation of the MAR interpolation algorithm, pelvis phantoms with small bladder "lesions" and metal hip prostheses were made, and images of the phantoms both with and without MAR reconstruction were evaluated. Image quality was significantly better with MAR reconstruction than without at all sites except the rectal shelf, where the image quality either had not changed or had worsened after MAR reconstruction. The mean attenuation value was changed after MAR reconstruction to its original expected value at the pelvic sidewall (p < 0.001) and inside the bladder (p < 0.001). The SD attenuation value was significantly decreased after MAR reconstruction at the pelvic sidewall (p = 0.019) but did not show significant differences at the bladder (p = 0.173) or rectal shelf (p = 0.478). In the phantom study, all lesions obscured by metal artifacts on the standard reconstruction images were visualized after MAR reconstruction; however, new artifacts had developed in other parts of the MAR reconstruction images. The use of MAR software with dual-energy CT decreases metal artifacts and increases diagnostic confidence in the assessment of the pelvic cavity but also introduces new artifacts that can obscure pelvic structures. | 25,247,944 | [
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Transverse sinus stenosis in adult patients with Chiari malformation type I. | Transverse sinus stenosis is an imaging finding very highly associated with elevated intracranial pressure (ICP). Patients with the Chiari I malformation may potentially have elevated ICP due to impairment of CSF flow at the foramen magnum. This study evaluated whether patients with Chiari I malformation have transverse sinus stenosis and other imaging findings indicative of elevated ICP. Thirty patients with Chiari I malformation treated surgically and 76 control subjects were identified retrospectively. All control subjects and all patients with Chiari I malformation (preoperatively) underwent standardized contrast-enhanced brain MRI including a contrast-enhanced 3D T1-weighted sequence from which curved reformats of the transverse sinuses were generated. Two different readers blinded to the diagnosis then independently evaluated these curved reformats for severity of transverse sinus stenosis. Orbital and skull-base findings previously described in association with elevated ICP were also evaluated. Frequency of MRI findings between the two groups was compared. Patients with Chiari I malformation had significantly greater frequency of unilateral or bilateral transverse sinus stenosis than did control subjects (p < 0.001). There was complete interreader agreement on presence or absence of transverse sinus stenosis by patient (κ = 1.0 [95% CI, 0.89-1.0]). Logistic regression analysis controlling for age, sex, and body mass index found that transverse sinus stenosis significantly predicted Chiari I malformation versus control status (odds ratio, 11.2 [95% CI, 2.1-59.0]; p = 0.004) but that no other features were significantly associated with the Chiari I malformation. Patients with Chiari I malformation who had transverse sinus stenosis had significantly greater pituitary flattening than did those without transverse sinus stenosis (p = 0.02). Patients with Chiari I malformation have higher likelihood of transverse sinus stenosis, which may reflect associated elevated ICP. | 25,247,957 | [
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Prognostic value of FDG PET metabolic tumor volume in human papillomavirus-positive stage III and IV oropharyngeal squamous cell carcinoma. | The purpose of this study was to establish the prognostic utility in human papillomavirus (HPV)-positive stage III and IV oropharyngeal squamous cell carcinoma (SCC) of the (18)F-FDG parameters maximal, mean, and peak standardized uptake value (SUVmax, SUVmean, and SUVpeak, respectively); metabolic tumor volume (MTV); and total lesion glycolysis (TLG). We included 70 patients in the present study who had a biopsy-proven HPV-positive (by in situ hybridization) stage III and IV oropharyngeal SCC and had a baseline PET/CT examination at our institution. Outcome endpoint was event-free survival (EFS), which included recurrence-free and overall survival. Cox proportional hazards multivariate regression analyses were performed. Survival analysis was performed using Kaplan-Meier survival curves. In Cox regression proportional hazard univariate analysis, total MTV (hazard ratio [HR], 1.02; p = 0.008), primary-tumor MTV (HR, 1.02; p = 0.024), neck nodal MTV (HR, 1.03; p = 0.006), neck nodal TLG (HR, 1.01; p = 0.006), and neck node status (HR, 4.45; p = 0.03) showed a statistically significant association with EFS. There was no statistically significant association of EFS with SUVmax, SUVmean, SUVpeak, and primary-tumor or overall TLG. In Cox regression proportional hazard multivariate model I, total MTV remained an independent prognostic marker for EFS when adjusted for every other variable individually in the model; in model II, primary-tumor MTV, neck node status, and SUVpeak are independent prognostic markers for EFS. The Kaplan-Meier survival curves using optimum cut point of 41 mL of total MTV were not significant (p = 0.09). Total MTV and primary-tumor MTV are associated with survival outcomes in patients with HPV-positive stage III and IV oropharyngeal SCC. | 25,247,958 | [
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Lymphoid nodular hyperplasia of the terminal ileum can mimic active crohn disease on MR enterography. | The purpose of this article is to describe the MRI findings associated with lymphoid nodular hyperplasia at MR enterography and test the ability of radiologists to differentiate healthy control subjects from patients with Crohn disease (CD). Ethical approval was granted for this retrospective study. Thirty-five subjects (nine with lymphoid nodular hyperplasia, 13 with CD, and 13 control subjects) who had undergone MR enterography and ileocolonoscopy were identified from the hospital database. Two abdominal radiologists, working in consensus and blinded to diagnosis, scored enteric MR images for T2 signal, contrast enhancement, mural thickness, and diffusion-weighted imaging (DWI) signal and measured the apparent diffusion coefficient (ADC) in all three groups. Scores were compared using the Kruskal-Wallis test. T2 signal and contrast enhancement were judged subjectively to be greater in patients with lymphoid nodular hyperplasia and CD than control subjects (p < 0.001). Mural thickness was greater for patients with lymphoid nodular hyperplasia (median, 6.0 mm) and CD (median, 7.3 mm) than control subjects (median, 2.3 mm) (p < 0.001). Lymphoid nodular hyperplasia and CD increased subjective DWI signal and reduced ADC in comparison with normal control subjects; median ADC was 1.34 × 10(-3) mm(2)/s for lymphoid nodular hyperplasia, 1.36 × 10(-3) mm(2)/s for CD, and 1.86 × 10(-3) mm(2)/s for control subjects (p < 0.001). None of T2 signal, contrast enhancement, wall thickness, DWI signal, or ADC value significantly differed between lymphoid nodular hyperplasia and CD. Lymphoid nodular hyperplasia was erroneously diagnosed as CD in blinded assessment in four of nine cases (44%), whereas all cases of CD and healthy control subjects were correctly classified. Lymphoid nodular hyperplasia alters both subjective and quantitative MRI parameters, including T2 signal, contrast enhancement, mural thickness, and ADC. In a subset of patients, lymphoid nodular hyperplasia may be indistinguishable from CD on MR enterography. | 25,247,969 | [
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In-phase signal intensity loss in solid renal masses on dual-echo gradient-echo MRI: association with malignancy and pathologic classification. | The purposes of this study were to determine the prevalence of in-phase signal intensity loss on dual-echo gradient-echo MRI in solid renal masses using visual and quantitative techniques and to test for any association between in-phase signal intensity loss and pathologic classification. The renal MRI studies of 177 patients (192 solid masses consisting of 166 renal cell carcinomas [RCCs], four malignant non-RCCs, and 22 benign tumors) were qualitatively reviewed by two blinded readers for visual evidence of relative in-phase signal intensity loss. For lesions without visual evidence, whole-lesion ROIs were used to attempt quantification of subtle signal intensity loss between opposed- and in-phase images (signal intensity loss index). Visual in-phase signal intensity loss was noted in 18% of clear cell RCC, 42% of papillary RCC, and no benign lesions. There was significant correlation between malignancy and visual signal intensity loss (Fisher exact test, p = 0.0092). Visual signal intensity loss was predictive of papillary RCC over clear cell RCC (odds ratio, 5.79; p = 0.0002) in logistic regression analysis of all RCCs, controlling for size. Quantitative assessment of remaining lesions provided no additional diagnostic benefit. Visible in-phase signal intensity loss is relatively common within solid renal masses and was associated with RCC and particularly papillary RCC (among all RCCs) in our population. Quantitative analysis in lesions without visible signal intensity loss was not predictive of RCC. Further work should be performed to validate the usefulness of this additional imaging parameter to help characterize renal masses and to determine the impact of this finding on imaging techniques potentially sensitive to susceptibility effects. | 25,247,971 | [
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Population specific impact of genetic variants in KCNJ11 gene to type 2 diabetes: a case-control and meta-analysis study. | Potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene have a key role in insulin secretion and is of substantial interest as a candidate gene for type 2 diabetes (T2D). The current work was performed to delineate the genetic influence of KCNJ11 polymorphisms on risk of T2D in South Indian population through case-control association study along with systematic review and meta-analysis. A case-control study of 400 T2D cases and controls of South Indian origin were performed to analyze the association of KCNJ11 polymorphisms (rs5219, rs5215, rs41282930, rs1800467) and copy number variations (CNV) on the risk of T2D. In addition a systematic review and meta-analysis for KCNJ11 rs5219 was conducted in 3,831 cases and 3,543 controls from 5 published reports from South-Asian population by searching various databases. Odds ratio with 95% confidence interval (CI) was used to assess the association strength. Cochran's Q, I2 statistics were used to study heterogeneity between the eligible studies. KCNJ11 rs5215, C-G-C-C haplotype and two loci analysis (rs5219 vs rs1800467) showed a significant association with T2D but CNV analysis did not show significant variation between T2D cases and control subjects. Lower age of disease onset (P = 0.04) and higher body mass index (BMI) (P = 0.04) were associated with rs5219 TT genotype in T2D patients. The meta-analysis of KCNJ11 rs5219 on South Asian population showed no association on susceptibility to T2D with an overall pooled OR = 0.98, 95% CI = 0.83-1.16. Stratification analysis showed East Asian population and global population were associated with T2D when compared to South Asians. KCNJ11 rs5219 is not independently associated with T2D in South-Indian population and our meta-analysis suggests that KCNJ11 polymorphism (rs5219) is associated with risk of T2D in East Asian population and global population but this outcome could not be replicated in South Asian sub groups. | 25,247,988 | [
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Species richness and evidence of random patterns in assemblages of South American Titanosauria during the Late Cretaceous (Campanian-Maastrichtian). | The Titanosauria were much diversified during the Late Cretaceous, but paleobiological information concerning these sauropods continues to be scarce and no studies have been conducted utilizing modern methods of community analysis to infer possible structural patterns of extinct assemblages. The present study sought to estimate species richness and to investigate the existence of structures in assemblages of the South American Titanosauria during the Late Cretaceous. Estimates of species richness were made utilizing a nonparametric estimator and null models of species co-occurrences and overlapping body sizes were applied to determine the occurrence of structuring in this assemblages. The high estimate of species richness (n = 57) may have been influenced by ecological processes associated with extinction events of sauropod groups and with the structures of the habitats that provided abundant support to the maintenance of large numbers of species. The pseudocommunity analysis did not differ from that expected by chance, indicating the lack of structure in these assemblages. It is possible that these processes originated from phylogenetic inertia, associated with the occurrence of stabilized selection. Additionally, stochastic extinction events and historical factors may also have influenced the formation of the titanosaurian assemblages, in detriment to ecological factors during the Late Cretaceous. However, diagenetic and biostratinomic processes, influenced by the nature of the sedimentary paleoenvironment, could have rendered a random arrangement that would make assemblage structure undetectable. | 25,247,998 | [
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RGDechi-hCit: αvβ3 selective pro-apoptotic peptide as potential carrier for drug delivery into melanoma metastatic cells. | αvβ3 integrin is an important tumor marker widely expressed on the surface of cancer cells. Recently, we reported some biological features of RGDechi-hCit, an αvβ3 selective peptide antagonist. In the present work, we mainly investigated the pro-apoptotic activity of the molecule and its ability to penetrate the membrane of WM266 cells, human malignant melanoma cells expressing high levels of αvβ3 integrin. For the first time we demonstrated the pro-apoptotic effect and the ability of RGDechi-hCit to enter into cell overexpressing αvβ3 integrin mainly by clathrin- and caveolin-mediated endocytosis. Furthermore, we deepened and confirmed the selectivity, anti-adhesion, and anti-proliferative features of the peptide. Altogether these experiments give insight into the biological behavior of RGDechi-hCit and have important implications for the employment of the peptide as a new selective carrier to deliver drugs into the cell and as a therapeutic and diagnostic tool for metastatic melanoma. Moreover, since the peptide shows a pro-apoptotic effect, a great perspective could be the development of a new class of selective systems containing RGDechi-hCit and pro-apoptotic molecules or other therapeutic agents to attain a synergic action. | 25,248,000 | [
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Comprehensive intestinal T helper cell profiling reveals specific accumulation of IFN-γ+IL-17+coproducing CD4+ T cells in active inflammatory bowel disease. | Skewed T helper (TH) cell responses and specific functions of TH1, TH2, TH17, and Treg cells have been implicated in the pathogenesis of inflammatory bowel disease (IBD) that led to the establishment of the pathogenic TH1/TH2 and TH17/Treg cell imbalance paradigms. However, the relevant TH cell population driving mucosal inflammation is still unknown. We performed a comprehensive TH cell profiling of circulating and intestinal lymphocytes isolated from patients with Crohn's disease (CD; n = 69) and ulcerative colitis (UC; n = 41) undergoing endoscopy or surgical resection and compared them with healthy controls (n = 45). Mucosal inflammation was assessed endoscopically and histologically. TH cells were analyzed by flow cytometric evaluation of cytokine production and differentiation marker expression. Specialized TH cell populations were enriched in the intestinal mucosa compared with peripheral blood. Specifically, we observed a concomitant upregulation of TH17 cells and Tregs in active inflammatory lesions in patients with both CD and UC compared with quiescent/mildly inflamed lesions and healthy tissue. Of note, interferon γ+ interleukin (IL)-17+coproducing CD4+ T cells with high expression of T-bet, CD26, and IL-22 resembling recently described pathogenic TH17 cells were specifically enriched in the inflamed mucosal tissue. Our results argue against the controversial TH1/TH2 or TH17/Treg paradigms. In contrast, they suggest that a subpopulation of TH17 cells sharing a TH1 signature may be specifically involved in intestinal inflammation in CD and UC. These findings provide a better understanding of IBD pathogenesis and may help explain the efficacy of anti-IL-12p40/IL-23 and failure of anti-IL-17A therapies despite the enrichment of TH17 cells. | 25,248,005 | [
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Poor Validity of the DSM-IV Schizoid Personality Disorder Construct as a Diagnostic Category. | This study sought to evaluate the construct validity of schizoid personality disorder (SZPD) by investigating a sample of 2,619 patients from the Norwegian Network of Personality-Focused Treatment Programs by a variety of statistical techniques. Nineteen patients (0.7%) reached the diagnostic threshold of SZPD. Results from the factor analyses indicated that SZPD consists of three factors: social detachment, withdrawal, and restricted affectivity/ anhedonia. Overall, internal consistency and diagnostic efficiency were poor and best for the criteria that belong to the social detachment factor. These findings pose serious questions about the clinical utility of SZPD as a diagnostic category. On the other hand, the three factors were in concordance with findings from previous studies and with the trait model for personality disorders in DSM-5, supporting the validity of SZPD as a dimensional construct. The authors recommend that SZPD should be deleted as a diagnostic category in future editions of DSM-5. | 25,248,009 | [
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Steroid regulation of T cell function appears unaltered in borderline personality disorder. | Borderline personality disorder (BPD) is characterized by instability of interpersonal relationships and affection, impulsivity, and cognitive disruptions. Increasing evidence suggests hypothalamic-pituitary-adrenal (HPA) axis alterations in BPD. Changed glucocorticoid sensitivity of peripheral blood mononuclear cells is known in mood and posttraumatic stress disorders, representing frequent comorbidities in BPD. However, to the authors' knowledge, in BPD glucocorticoid sensitivity at the receptor level remains unexplored. Sixteen age-matched female BPD patients were compared to sixteen female healthy controls. In vitro steroid sensitivity of T cell proliferation was tested using aldosterone, dexamethasone, and hydrocortisone. Steroid sensitivity of BPD patients and healthy controls appeared comparable. Psychiatric comorbidities such as major depressive disorder or posttraumatic stress disorder and early life stress seemed to have had no influence on steroid sensitivity parameters. The data suggest unaltered GC sensitivity of T cell function in BPD. | 25,248,018 | [
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Engineering 3D bio-artificial heart muscle: the acellular ventricular extracellular matrix model. | Current therapies in left ventricular systolic dysfunction and end-stage heart failure include mechanical assist devices or transplant. The development of a tissue-engineered integrative platform would present a therapeutic option that overcomes the limitations associated with current treatment modalities. This study provides a foundation for the fabrication and preliminary viability of the acellular ventricular extracellular matrix (AVEM) model. Acellular ventricular extracellular matrix was fabricated by culturing 4 million rat neonatal cardiac cells around an excised acellular ventricular segment. Acellular ventricular extracellular matrix generated a maximum spontaneous contractile force of 388.3 μN and demonstrated a Frank-Starling relationship at varying pretensions. Histologic assessment displayed cell cohesion and adhesion within the AVEM as a result of passive cell seeding. | 25,248,038 | [
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Particle embolization for the treatment of life-threatening epistaxis in a left ventricular assist device patient. | While epistaxis is self-limiting in most cases, patients who are anticoagulated are at increased risk for life-threatening hemorrhage. The management of epistaxis in patients with a left ventricular assist device is further complicated by an increased risk for hemodynamic instability. Here, we detail the successful treatment of massive epistaxis in a left ventricular assist device patient by endovascular particle embolization. We hope to increase awareness in the cardiovascular community of this minimally invasive, potentially life-saving procedure. | 25,248,039 | [
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Default network connectivity is linked to memory status in multiple sclerosis. | Memory impairment affects 50% of multiple sclerosis (MS) patients. Altered resting-state functional connectivity (FC) has been observed in the default network (DN) of MS patients. No study to date has examined the association of DN FC to its behavioral concomitant, memory. The approach of the present study represents a methodological shift allowing straightforward interpretation of FC alterations in MS, as it presupposes specificity of a network to its paired cognitive function. We examined FC from fMRI collected during rest in the DN of 43 MS patients with and without memory-impairment. Memory-intact patients showed increased DN FC relative to memory-impaired patients. There were no regions of higher FC in memory-impaired patients. DN FC was positively correlated with memory function, such that higher FC was associated with better memory performance. Results were unchanged after controlling for cognitive efficiency, supporting specificity of the DN to memory and not cognitive status more generally. These findings support DN FC as a marker of memory function in MS patients that can be targeted by future treatment interventions. Pairing a functional network with its behavioral concomitant represents a straightforward method for interpreting FC alterations in patients with MS. | 25,248,054 | [
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Urinary tract infection in elderly trauma patients: review of the Trauma Quality Improvement Program identifies the population at risk. | Elderly trauma patients are at high risk for urinary tract infection (UTI). Despite this, UTI has been deemed a potentially preventable problem and therefore not reimbursable by the Centers for Medicare and Medicaid Services. Early identification of UTI in these patients should lead to prompt treatment, improved outcomes, and cost savings. Risk factors for UTI development in this population must be elucidated to realize these goals. The Trauma Quality Improvement Program (TQIP) database was used to analyze elderly patients (≥65 years) admitted as a result of injury during 2011. Patients with genitourinary injuries or undergoing dialysis before admission were excluded. Multivariable logistic regression analysis was conducted to identify UTI risk factors. Mean cost of UTI was calculated based on the assumption of $862 to $1,007 per UTI. In total, 33,257 patients were identified; 1,492 developed UTI (4.5%). Multiple significant risk factors were identified, including age greater than 75 years, female sex, ascites, moderate head injury, impaired sensorium, congestive heart failure, and duration of hospital stay (all p < 0.05). Assuming that UTIs diagnosed on hospital Day 1 were preexisting, the cost of UTI to TQIP hospitals ranged from $1,280,959 to $1,496,434 per year. Duration of stay has a profound impact on the development of UTIs in elderly trauma patients, but overall severity of injury does not. In addition, multiple nonmodifiable risk factors were identified, prompting the possibility for increased screening of occult UTIs. Reimbursement for care of UTI in this complicated patient population should be revisited. The TQIP database must improve urinary catheter data. Epidemiologic study, level III. | 25,248,065 | [
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Integrating diffusion tensor imaging-based tractography into deep brain stimulation surgery: a review of the literature. | It has been generally accepted that deep brain stimulation (DBS) not only acts in the nucleus where it is being applied, as initially thought, but that chronic stimulation activates axons located in its scope, and that this activation can exert its effects in distant areas. Considering this, DBS target identification should be made based on techniques that identify white matter tracts, such as tractography, rather than only by identifying specific nuclei on conventional magnetic resonance imaging. In this study, we performed a review of the literature on the use of tractography in DBS surgery and provide an overview of the main results. Tractography has been used in the field of DBS to help clarify relevant aspects in the selection of targets and in evaluating its therapeutic effects in movement disorders, psychiatric diseases and pain. Studies are scarce so far, but they have provided data that, if confirmed, may optimize DBS surgery. Tractography might become a routine tool for DBS surgery in the near future. | 25,248,076 | [
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Evaluation of BACTEC MGIT 960 system for testing susceptibility of Mycobacterium tuberculosis to first-line drugs in China. | The purpose of this study was to evaluate the performance of the BACTEC MGIT 960 (M960) system compared with the proportion method (PM) on Löwenstein-Jensen (L-J) medium in a peripheral laboratory in China for the testing of Mycobacterium tuberculosis (MTB) susceptibility to streptomycin (SM), isoniazid (INH) rifampicin (RIF) and ethambutol (EMB) a combination known as SIRE. The susceptibility of 205 clinical isolates of MTB to SM, INH, RIF and EMB was performed with the M960 system. The drugs were tested at the following concentrations: 1.0 µg/ml for SM, 0.1 µg/ml for INH, 1.0 µg/ml for RIF, and 5.0 µg/ml for EMB. The results were compared with those obtained by the L-J PM. The L-J PM at an arbiter site was used to resolve any discordant results. The overall consistency was 96.6% and concordance values were 95.6% for SM, 97.6% for INH, 98.0% for RIF and 95.1% for EMB. The overall sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the M960 system for PM (the standard method) was 95.6%, 97.3%, 96.2% and 96.9% respectively, and the sensitivity were 93.3% for SM, 96.9% for INH, 97.4% for RIF and 94.6% for EMB, the specificity were 96.9% for SM, 98.2% for INH, 98.4% for RIF and 95.5% for EMB, the PPV were 94.6% for SM, 97.9% for INH, 97.4% for RIF and 94.6% for EMB, the NPV were 96.2% for SM, 97.3% for INH, 98.4% for RIF and 95.5% for EMB. The turnaround time with the M960 system (median 8.0 days, ranged from 5 to 14 days) was significantly shorter than that with the PM (28 days or 42 days). There was a substantial degree of agreement between the two methods. The M960 system was a reliable and rapid method for SIRE susceptibility testing of tuberculosis in China. | 25,248,118 | [
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Current trends in research and clinical issues in the study of personality and its disorders: a survey of the presentations at the ISSPD anniversary congress. | The International Society for the Study of Personality Disorders (ISSPD) celebrated its 25th anniversary in September 2013 in Copenhagen and commemorated the First International Congress at the same site. The overall theme of the congress was "Bridging Personality and Psychopathology: The Person Behind the Illness." More than 400 abstracts were submitted, and the program included 8 keynote presentations, 18 invited symposia, a debate on current controversial issues in the classification of personality disorders (Fossati, Tyrer, Livesley, and Krueger), an ISSPD award lecture (Silk), a jubilee lecture (Simonsen), a young researchers' symposium (Hopwood, Sharp, and Kaess), and special lectures on the Danish philosopher Soeren Kierkegaard and the poet Hans Christian Andersen. In this article we will survey the presentations and highlight the important issues in order to underline the current trends in research and clinical interests in personality disorders. The keynote video presentations, invited symposia, and slide presentations are freely available at www.isspd2013.com. | 25,248,121 | [
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N-acetylcysteine attenuates hexavalent chromium-induced hypersensitivity through inhibition of cell death, ROS-related signaling and cytokine expression. | Chromium hypersensitivity (chromium-induced allergic contact dermatitis) is an important issue in occupational skin disease. Hexavalent chromium (Cr (VI)) can activate the Akt, Nuclear factor κB (NF-κB), and Mitogen-activated protein kinase (MAPK) pathways and induce cell death, via the effects of reactive oxygen species (ROS). Recently, cell death stimuli have been proposed to regulate the release of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1). However, the exact effects of ROS on the signaling molecules and cytotoxicity involved in Cr(VI)-induced hypersensitivity have not yet been fully demonstrated. N-acetylcysteine (NAC) could increase glutathione levels in the skin and act as an antioxidant. In this study, we investigated the effects of NAC on attenuating the Cr(VI)-triggered ROS signaling in both normal keratinocyte cells (HaCaT cells) and a guinea pig (GP) model. The results showed the induction of apoptosis, autophagy and ROS were observed after different concentrations of Cr(VI) treatment. HaCaT cells pretreated with NAC exhibited a decrease in apoptosis and autophagy, which could affect cell viability. In addition, Cr (VI) activated the Akt, NF-κB and MAPK pathways thereby increasing IL-1α and TNF-α production. However, all of these stimulation phenomena could be inhibited by NAC in both of in vitro and in vivo studies. These novel findings indicate that NAC may prevent the development of chromium hypersensitivity by inhibiting of ROS-induced cell death and cytokine expression. | 25,248,126 | [
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Transgene regulation using the tetracycline-inducible TetR-KRAB system after AAV-mediated gene transfer in rodents and nonhuman primates. | Numerous studies have demonstrated the efficacy of the Adeno-Associated Virus (AAV)-based gene delivery platform in vivo. The control of transgene expression in many protocols is highly desirable for therapeutic applications and/or safety reasons. To date, the tetracycline and the rapamycin dependent regulatory systems have been the most widely evaluated. While the long-term regulation of the transgene has been obtained in rodent models, the translation of these studies to larger animals, especially to nonhuman primates (NHP), has often resulted in an immune response against the recombinant regulator protein involved in transgene expression regulation. These immune responses were dependent on the target tissue and vector delivery route. Here, using AAV vectors, we evaluated a doxycyclin-inducible system in rodents and macaques in which the TetR protein is fused to the human Krüppel associated box (KRAB) protein. We demonstrated long term gene regulation efficiency in rodents after subretinal and intramuscular administration of AAV5 and AAV1 vectors, respectively. However, as previously described for other chimeric transactivators, the TetR-KRAB-based system failed to achieve long term regulation in the macaque after intramuscular vector delivery because of the development of an immune response. Thus, immunity against the chimeric transactivator TetR-KRAB emerged as the primary limitation for the clinical translation of the system when targeting the skeletal muscle, as previously described for other regulatory proteins. New developments in the field of chimeric drug-sensitive transactivators with the potential to not trigger the host immune system are still needed. | 25,248,159 | [
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Automatic deformable MR-ultrasound registration for image-guided neurosurgery. | In this work, we present a novel algorithm for registration of 3-D volumetric ultrasound (US) and MR using Robust PaTch-based cOrrelation Ratio (RaPTOR). RaPTOR computes local correlation ratio (CR) values on small patches and adds the CR values to form a global cost function. It is therefore invariant to large amounts of spatial intensity inhomogeneity. We also propose a novel outlier suppression technique based on the orientations of the RaPTOR gradients. Our deformation is modeled with free-form cubic B-splines. We analytically derive the derivatives of RaPTOR with respect to the transformation, i.e., the displacement of the B-spline nodes, and optimize RaPTOR using a stochastic gradient descent approach. RaPTOR is validated on MR and tracked US images of neurosurgery. Deformable registration of the US and MR images acquired, respectively, preoperation and postresection is of significant clinical significance, but challenging due to, among others, the large amount of missing correspondences between the two images. This work is also novel in that it performs automatic registration of this challenging dataset. To validate the results, we manually locate corresponding anatomical landmarks in the US and MR images of tumor resection in brain surgery. Compared to rigid registration based on the tracking system alone, RaPTOR reduces the mean initial mTRE over 13 patients from 5.9 to 2.9 mm, and the maximum initial TRE from 17.0 to 5.9 mm. Each volumetric registration using RaPTOR takes about 30 sec on a single CPU core. An important challenge in the field of medical image analysis is the shortage of publicly available dataset, which can both facilitate the advancement of new algorithms to clinical settings and provide a benchmark for comparison. To address this problem, we will make our manually located landmarks available online. | 25,248,177 | [
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Optimal transition probability of reversible data hiding for general distortion metrics and its applications. | Recently, a recursive code construction (RCC) approaching the rate-distortion bound of reversible data hiding (RDH) was proposed. However, to estimate the rate-distortion bound or execute RCC, one should first estimate the optimal transition probability matrix (OTPM). By previous methods, OTPM can be effectively estimated only for some specific distortion metrics, such as square error distortion or L1-Norm. In this paper, we proposed a unified framework of estimating the OTPM for general distortion metrics, with which we can calculate the rate-distortion bound of RDH for general cases and extend RCC to improve state-of-the-art RDH schemes based on any distortion metrics. | 25,248,187 | [
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A multiple-feature and multiple-kernel scene segmentation algorithm for humanoid robot. | This technical correspondence presents a multiple-feature and multiple-kernel support vector machine (MFMK-SVM) methodology to achieve a more reliable and robust segmentation performance for humanoid robot. The pixel wise intensity, gradient, and C1 SMF features are extracted via the local homogeneity model and Gabor filter, which would be used as inputs of MFMK-SVM model. It may provide multiple features of the samples for easier implementation and efficient computation of MFMK-SVM model. A new clustering method, which is called feature validity-interval type-2 fuzzy C-means (FV-IT2FCM) clustering algorithm, is proposed by integrating a type-2 fuzzy criterion in the clustering optimization process to improve the robustness and reliability of clustering results by the iterative optimization. Furthermore, the clustering validity is employed to select the training samples for the learning of the MFMK-SVM model. The MFMK-SVM scene segmentation method is able to fully take advantage of the multiple features of scene image and the ability of multiple kernels. Experiments on the BSDS dataset and real natural scene images demonstrate the superior performance of our proposed method. | 25,248,211 | [
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A survey on bimanual haptic interaction. | When interacting with virtual objects through haptic devices, most of the time only one hand is involved. However, the increase of computational power, along with the decrease of device costs, allow more and more the use of dual haptic devices. The field which encompasses all studies of the haptic interaction with either remote or virtual environments using both hands of the same person is referred to as bimanual haptics. It differs from the common unimanual haptic field notably due to specificities of the human bimanual haptic system, e.g., the dominance of the hands, their differences in perception and their interactions at a cognitive level. These specificities call for adapted solutions in terms of hardware and software when applying the use of two hands to computer haptics. This paper reviews the state of the art on bimanual haptics, encompassing the human factors in bimanual haptic interaction, the currently available bimanual haptic devices, the software solutions for two-handed haptic interaction, and the existing interaction techniques. | 25,248,213 | [
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[Antibodies against alfa-enolase as an indication of inflammatory process in patients with celiac disease--preliminary results]. | Celiac disease (CD) is an autoimmunological gluten sensitive enteropathy occuring to genetically predisposed individuals. Active CD is accompanied by presence of multiple antibodies. Anti alpha enolase antibodies were reported in several autoimmunological disorders like rheumatoid arthritis, primary sclerosing cholangitis. Data about its presence and role in CD is avaricious. The aim of this study was to determine presence of anti alpha enolase antibodies in CD, correlation with gluten exposure, presence of anti tranglutaminase antibodies and Marsh scale. Sera from 31 patients with CD (21 females, 10 males) and 6 healthy subjects were collected. Evaluation of CD activity and adherence to gluten free diet were obtained by serology tests (presence of endomyslum antibodies and/or anti transglutamineses in IgA or IgG classes) and histological hallmarks. Anti alpha enolase antibodies were identified in sera using ELISA kit. Titres of anti alpha enolase antibodies were identified among patients with newly diagnosed CD, CD patients non adhering to gluten free diet (GFD), adhering to GFD and among healthy subjects. Mean titre of anti alpha enolase antibodies was higher in CD patients (both treated and non treated) in comparison to control group, respectively 1.1 ng/mL, and 0.795 ngl mL. Among CD patients non adhering to gluten free diet mean titre was 1.4 ng/mL. Higher anti alpha enolase antibodies titres in non treated CD suggest usefulness of its measurement. These antibodies might be a novel marker of chronic inflammation among CD patients non adhering to GFD. | 25,248,239 | [
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[Atypical BCR-ABL transcripts in patients with chronic myeloid leukemia--the scheme for the diagnosis and monitoring of minimal residual disease]. | More than 95% of patients with detected translocation t(9;22), is characterized by the fusion between exons e13 or e14 of BCR gene, which are located in major breakpoint cluster region (M-bcr) and exon a2 of ABL gene. These fusions are described as b2a2 (e13a2) and b3a2 (e14a2). Other fusions of exons e1, e6, e8, e12, e19, e20 of BCR gene with exons a2 or a3 of ABL gene occur very rarely and lead to formation of so called unusual fusion BCR-ABL genes. The aim of this study is to describe long-term observations of the occurrence and routine procedure in the diagnosis of atypical variants of the fusion gene BCR-ABL in a population of patients with chronic myeloid leukemia (CML). It was found that the vast majority of patients with detected BCR-ABL transcripts were b3a2 and b2a2. Other detected variants, which are described as rare were: e1a2, b2a3, b3a3, c3a2, e6a2, e6a3. At the stage of diagnosis as well as during monitoring of the effects of treatment, molecular methods which are based on polymerase chain reaction were used (multiplex RT-PCR, nested RT-PCR, RQ-PCR). Multiplex RT-PCR reaction gave possibility to detect variants of the fusion BCR-ABL gene in one reaction and was crucial in the selection of appropriate test used for further monitoring of the disease and the effectiveness of treatment. This paper proposes a scheme for dealing with the diagnosis and monitoring of minimal residual disease (MRD) in patients with CML treated with tyrosine kinase inhibitors (TKIs) in the presence of rare fusion of the BCR and ABL genes. | 25,248,240 | [
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[Syndrome of inappropriate secretion of antidiuretic hormone]. | Hyponatremia is a commonly encountered electrolyte abnormality in clinical practice and in some groups of patients is associated with significant morbidity and mortality. Although the pathophysiology of this disturbance is complex, its understanding is vital to the disorder's evaluation and treatment. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the commonest form of euvolemic hyponatremia and is the clinical and biochemical manifestation of a wide range of disease processes, mostly associated with malignancy, pulmonary, or neurologic disorders, and of pharmacotherapy. Symptoms vary depending on the severity of hyponatremia and, if occur, can range from weakness, mild headache, muscle cramps, nausea, and vomiting to convulsions, coma, and death. Identifying the underlying disorder remains an integral part of the diagnostic evaluation of patients. The most frequently used treatment options include water restriction, oral intake of salt, hypertonic saline and vaptans, being nonpeptide vasopressin antagonists interfering with the antidiuretic effect of the hormone. The aim of our paper is to present a practical diagnostic approach and management of SIADH, with a particular emphasis on the results of recent studies. | 25,248,244 | [
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[The observation and analysis the function and morphology of the eustachian tube in secretory otitis media and chronic rhinosinusitis in children]. | To observe and analyze the function and morphology of pharyngeal ostium of the eustachian tubes in secretory otitis media and chronic rhinosinusitis in children under direct vision,in order to provide an objective basis for clinical treatments. Fifty cases of secretory otitis media,50 cases of chronic rhinosinusitis and a control group of 50 cases with hoarseness were examined under video laryngoscope to observe the pharyngeal ostium morphological changes of the eustachian tubes, and their functional statuses were tested by using acoustic impedance instrument. All the data were analyzed by statistical methods. (1) In the secretory otitis group, the abnomal rate of the pharyngeal ostium of the eustachian tubes was 94% while the chronic rhinosinusitis group was 80%,and between them there was no significant differences (P > 0.05). But both of them had significant differences with the control group (P < 0.05). (2) In the secretory otitis group, the rate of the eustachian tube dysfunction was 70% while the chronic rhinosinusitis group was 26%, and between them there was significant differences (P < 0.05), and both of them have significant differences when compared with the control group (P < 0.05). There are some abnormal points exist in the function and the morphology of the eustachian tube in secretory otitis media and chronic rhinosinusitis in children. Eustachian tube dysfunction played a dominant role in the pathogenesis of secretory otitis media in children rather than the morphological change did compared to the chronic rhinosinusitis in children. | 25,248,251 | [
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[Expression of IL-35, Epstein-Barr virus-induced gene 3 mRNA and IL-12A mRNA in peripheral blood of patients with allergic rhinitis]. | To explore the expression of IL-35, Epstein-Barr virus-induced gene 3 (EBI3) mRNA and IL-12A mRNA in peripheral blood of patients with allergic rhinitis and its significance. Peripheral blood were collected from patients with allergic rhinitis (46 cases) and healthy human controls(30 cases). The level of IL-35 in serum was measured by enzyme-linked immunosorbent assay. The subunit EB13 and IL-12A of IL-35 mRNA expressions in peripheral blood mononuclear cell(PBMC) were detected by SYBR Green real-time quantitative PCR. IL-35 level in AR group (251.22 +/- 46.27) ng/L was significantly lower compared with that in the normal control group (382.17 +/- 25.41) ng/L, (P < 0.01). The mRNA expression level of EBI3 in the patients with allergic rhinitis was significantly lower than that in the normal control group (P < 0.01), AR group EB13 mRNA level was about half of that in the normal control group. But the mRNA expression level of IL-12A in the patients with allergic rhinitis has not significant difference with that in the normal control group (P > 0. 05). The decrease of IL-35 and EBI3 mRNA in AR,indicated that IL-35 and EBl3 mRNA may play an important role in allergic rhinitis. | 25,248,258 | [
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Diagnostic tools for alzheimer's disease dementia and other dementias: an overview of diagnostic test accuracy (DTA) systematic reviews. | Dementia includes a group of neurodegenerative disorders characterized by progressive loss of cognitive function and a decrease in the ability to perform activities of daily living. Systematic reviews of diagnostic test accuracy (DTA) focus on how well the index test detects patients with the disease in terms of figures such as sensitivity and specificity. Although DTA reviews about dementia are essential, at present there is no information about their quantity and quality. We searched for DTA reviews in MEDLINE (1966-2013), EMBASE (1980-2013), The Cochrane Library (from its inception until December 2013) and the Database of Abstracts of Reviews of Effects (DARE). Two reviewers independently assessed the methodological quality of the reviews using the AMSTAR measurement tool, and the quality of the reporting using the PRISMA checklist. We describe the main characteristics of these reviews, including basic characteristics, type of dementia, and diagnostic test evaluated, and we summarize the AMSTAR and PRISMA scores. We selected 24 DTA systematic reviews. Only 10 reviews (41.6%), assessed the bias of included studies and few (33%) used this information to report the review results or to develop their conclusions Only one review (4%) reported all methodological items suggested by the PRISMA tool. Assessing methodology quality by means of the AMSTAR tool, we found that six DTA reviews (25%) pooled primary data with the aid of methods that are used for intervention reviews, such as Mantel-Haenszel and separate random-effects models (25%), while five reviews (20.8%) assessed publication bias by means of funnel plots and/or Egger's Test. Our assessment of these DTA reviews reveals that their quality, both in terms of methodology and reporting, is far from optimal. Assessing the quality of diagnostic evidence is fundamental to determining the validity of the operating characteristics of the index test and its usefulness in specific settings. The development of high quality DTA systematic reviews about dementia continues to be a challenge. | 25,248,284 | [
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Influence of the tourniquet on tibial cement mantle thickness in primary total knee arthroplasty. | The purpose of the study was whether the use of a tourniquet increases cement mantle thickness in primary total knee arthroplasty and influences the calculated blood loss and postoperative pain. Ninety patients with a primary total knee arthroplasty (TKA) were enroled in this prospective randomised trial and divided into a group with (n = 45) and without tourniquet (n = 45). The radiological tibial cement mantle thickness was evaluated postoperatively in four zones on anteroposterior and two zones on lateral radiographs, and values were cumulated. Additionally, the calculated blood loss and postoperative pain levels were recorded. There was a median cumulative cement mantle thickness of 13 mm (range 8-19 mm) without tourniquet and of 14.2 mm (range 9-18 mm) with tourniquet (p = 0.009). The median calculated blood loss was 0.6 L (range 0.2-2.0 L) without and 0.9 L (range 0.3-1.5 L) (p = 0.02) with tourniquet. Patient-reported postoperative pain levels were significantly higher in the tourniquet group during mobilisation (p = 0.01) and at rest (p = 0.001). The use of a tourniquet in primary TKA increased the tibial cement mantle thickness but also increased the postoperative calculated blood loss and postoperative pain. Surgeons might take this into consideration for decision-making whether to use a tourniquet during TKA. II. | 25,248,311 | [
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Uptake of the antisecretory factor peptide AF-16 in rat blood and cerebrospinal fluid and effects on elevated intracranial pressure. | AF-16 is a 16-amino-acid-long peptide derived from the amino-terminal part of the endogenous protein, antisecretory factor (AF). AF-16 in vivo has been shown to regulate dysfunctions in the water and ion transport system under various pathological conditions and also to counteract experimentally increased tissue pressure. Rats were subjected to a cryogenic brain injury in order to increase the intracranial pressure (ICP). The distribution of AF-16 in blood and CSF after intravenous or intranasal administration was determined in injured and control rats. ICP was monitored in freely moving, awake rats, by means of an epidural pressure transducer catheter connected to a wireless device placed subcutaneously on the skull. The continuous ICP registrations were achieved by means of telemetry. Intranasal administration of AF-16 resulted in a significantly higher CSF concentrations of AF-16 in injured than in control rats, 1.3 versus 0.6 ng/ml, whereas no difference between injured and control rats was seen when AF-16 was given intravenously. Rats subjected to cryogenic brain injury developed gradually increasing ICP levels. Intranasal administration of AF-16 suppressed the increased ICP to normal values within 30 min. Optimal AF-16 concentrations in CSF are achieved after intranasal administration in rats subjected to a cryogenic brain injury. The ability of AF-16 to suppress an increased ICP was manifested. | 25,248,325 | [
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Measuring and optimizing results in multipolar RFA: Techniques and early findings in an experimental setting. | Radiofrequency ablation (RFA) has shown to be a reasonable alternative for the treatment of hepatic tumors and metastases although multiple limitations remain. Cooling effects due to larger vessels can prevent complete coverage and may lead to early tumor relapse. This preliminary in vivo pig study combines the use of multipolar RFA with three applicators (six electrodes) and interrupted liver perfusion using Pringle's maneuver to overcome the most serious limitations. Furthermore, immediate detection of incomplete RFA is important to revise ablation. We used contrast enhanced computed tomography (CECT) to evaluate post ablation results in comparison to macroscopic images in healthy pig liver. We found significantly (p = 0.001) larger ablation zones and no affection by larger vessels with interrupted liver perfusion. This allows effective RFA for larger tumors. Immediate postinterventional CECT provided comparable results (r = 0.985) to macroscopic evaluation. | 25,248,350 | [
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In a class of their own: the Danish public considers obesity less deserving of treatment compared with smoking-related diseases. | This study examined public support for publicly funded treatment of obesity (weight-loss surgery and medical treatment) and two pulmonary diseases (chronic obstructive pulmonary disease (COPD) and lung cancer) in Denmark. It also investigated whether beliefs about the causes of lifestyle-related diseases (external environment, genetic disposition and lack of willpower) and agreement that 'people lack responsibility for their life and welfare' influenced support. This was a questionnaire study in which a sample of 1003 Danes (age 18-65 years) drawn from an Internet database were surveyed. Approximately one in three supported publicly funded weight-loss surgery (30%) and medical treatment of obesity (34.4%). A large majority supported treatment for lung cancer (86.1%), and a clear majority also supported treatment for COPD, whether it was framed as 'smoker's lung' (61.9%) or COPD (71.2%). The belief that lifestyle-related diseases are caused by the external environment or genetic disposition did not systematically influence support. Agreement that 'people lack responsibility for their life and welfare' reduced support significantly for all treatment types. However, in contrast with pulmonary diseases, support for publicly funded obesity treatments decreased considerably when beliefs about individual failure (that is that people lack 'willpower' and 'individual responsibility') were detected. Support for publicly funded COPD and lung cancer treatment is considerably higher than that for obesity treatment. This could encourage institutional discrimination through policies that involve charging patients for the treatment of obesity but not for the treatment of other lifestyle-related diseases. | 25,248,357 | [
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Screening travellers to high-endemic countries for infection with Mycobacterium tuberculosis using interferon gamma release assay; a prospective study. | International travel from low-incidence to high-incidence countries for tuberculosis (TB) is regarded as a risk factor for acquiring TB infection. In this prospective study among long-term travellers we examined the incidence of TB infection using Interferon gamma release assay (IGRA) test and compared these data with results from a visit to the TB department to which all long-term travellers were routinely referred. Immunocompetent adults, travelling for 13-52 weeks to TB-endemic countries, donated blood pre- and post-travel for IGRA. The pre-travel IGRA was only tested in case of a positive IGRA post-travel. Results from their visit(s) to the TB department for TST pre- and post-travel were collected and compared with study results. We found two IGRA conversions in a group of 516 travellers, resulting in an attack rate (AR) of 0.4% (95% CI: 0.5 - 13.9) and an incidence rate (IR) of 0.85 per 1000 person-months (95% CI: 0.1-3.1).We found 5 tuberculin skin test (TST) conversions, resulting in AR of 1.9% (5/261; 95% CI: 0.6 - 4.4) and an IR of 4.26 per 1000 person-months (95% CI: 1.38- 9.94). In our study these converters all had a negative IGRA. One traveller however, who was retested later at the TB department due to a positive TST, then appeared to have seroconverted. The risk of long-term travellers among our study population acquiring TB infection is low. We conclude that post-travel IGRA alone could be used for screening for TB infection among long-term travellers to high-endemic TB countries, but preferably not earlier than 8 weeks after return. One might even argue that IGRA testing should be limited to only those travellers who are going to work in a medical setting. A person with a positive IGRA should be referred to a TB physician for further evaluation. | 25,248,372 | [
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Abrogation of CC chemokine receptor 9 ameliorates collagen-induced arthritis of mice. | Biological drugs are effective in patients with rheumatoid arthritis (RA), but increase severe infections. The CC chemokine receptor (CCR) 9 antagonist was effective for Crohn's disease without critical adverse effects including infections in clinical trials. The present study was carried out to explore the pathogenic roles of chemokine (C-C motif) ligand (CCL) 25 and its receptor, CCR9, in autoimmune arthritis and to study if the CCR9 antagonist could be a new treatment for RA. CCL25 and CCR9 expression was examined with immunohistochemistry and Western blotting. Concentration of interleukin (IL)-6, matrix metalloproteinase (MMP)-3 and tumor necrosis factor (TNF)-α was measured with enzyme-linked immunosorbent assays. Effects of abrogating CCR9 on collagen-induced arthritis (CIA) was evaluated using CCR9-deficient mice or the CCR9 antagonist, CCX8037. Fluorescence labeled-CD11b+ splenocytes from CIA mice were transferred to recipient CIA mice and those infiltrating into the synovial tissues of the recipient mice were counted. CCL25 and CCR9 proteins were found in the RA synovial tissues. CCR9 was expressed on macrophages, fibroblast-like synoviocytes (FLS) and dendritic cells in the synovial tissues. Stimulation with CCL25 increased IL-6 and MMP-3 production from RA FLS, and IL-6 and TNF-α production from peripheral blood monocytes. CIA was suppressed in CCR9-deficient mice. CCX8037 also inhibited CIA and the migration of transferred CD11b+ splenocytes into the synovial tissues. The interaction between CCL25 and CCR9 may play important roles in cell infiltration into the RA synovial tissues and inflammatory mediator production. Blocking CCL25 or CCR9 may represent a novel safe therapy for RA. | 25,248,373 | [
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Fibroblast Growth Factor-2 alone as an efficient inducer for differentiation of human bone marrow mesenchymal stem cells into dopaminergic neurons. | The reported efficiency of differentiation of human bone marrow derived Mesenchymal Stem Cells (hBM MSC) into dopaminergic neurons with different inducers is found to vary. Thus, in the current study we have investigated the response of hBM MSC to some of the neuronal inducers and their combinations. Neuronal differentiation inducing agents Fibroblastic Growth Factor 2 (FGF2), Sonic Hedge Hog (Shh), Fibroblastic Growth Factor 8 (FGF8) & All Trans Retinoic Acid (ATRA) were used either singly or in varied combinations. The differentiated and undifferentiated hBM MSC were characterized in terms of morphology, expression of cell markers at transcriptional and translational levels, amount of dopamine secreted by the cells in the media and changes in cell membrane potential by calcium ions imaging. Induced hBM MSC revealed neuron like morphology and expressed cellular markers suggesting neuronal differentiation with all the inducing agents. However, upon quantitative analysis through qPCR, cells induced with FGF2 were found to show maximum expression of tyrosine hydroxylase (TH) by 47.5 folds. Immunofluorescence analysis of differentiated and undifferentiated cells also revealed expression of nestin, neurofilament, microtubule associated protein- 2, beta tubulin III and TH in differentiated cells, at translational level. This data was supported by immunoblotting analysis. Further, ELISA study also supported the release of dopamine by cultures induced with FGF2. When the cells were depolarised with KCl solution, those induced with Shh & FGF8 showed maximum calcium ion trafficking, followed by the cells induced with FGF2 only. We conclude that hBM MSC can be coaxed to differentiate efficiently into dopaminergic neurons in the presence of a very simple media cocktail containing only one main inducer like FGF2 and thus contribute towards cellular therapy in Parkinson's and other related disorders. These dopaminergic neurons are also functionally active, as shown by calcium ion trafficking. | 25,248,378 | [
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Phase I trial of bortezomib (PS-341; NSC 681239) and "nonhybrid" (bolus) infusion schedule of alvocidib (flavopiridol; NSC 649890) in patients with recurrent or refractory indolent B-cell neoplasms. | This phase I study was conducted to determine the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) for the combination of bortezomib and alvocidib in patients with B-cell malignancies (multiple myeloma, indolent lymphoma, Waldenstrom macroglobulinemia, and mantle cell lymphoma). Patients received bortezomib (intravenous push), followed by alvocidib (1-hour infusion), on days 1, 4, 8, and 11 of a 21-day treatment cycle. Patients experiencing responses or stable disease continued on treatment at the investigator's discretion. A standard 3+3 dose-escalation design was used to identify the MTD based on DLTs, and pharmacokinetic and pharmacodynamic studies were conducted. A total of 44 patients were enrolled, with 39 patients assessed for response. The MTD was established as 1.3 mg/m(2) for bortezomib and 40 mg/m(2) for alvocidib. The most common hematologic toxicities included leukopenia, lymphopenia, neutropenia, and thrombocytopenia. The most common nonhematologic toxicities included diarrhea, fatigue, and sensory neuropathy. Three complete remissions (8%) and 10 partial remissions (26%) were observed for a total response rate of 33%. Pharmacokinetic findings with the current dosing regimen were consistent with the comparable literature and the hybrid dosing regimen. Pharmacodynamic study results did not correlate with clinical responses. The combination of bortezomib and alvocidib is tolerable, and an MTD has been established for this schedule. The regimen appears to be efficacious in patients with relapsed/refractory multiple myeloma or indolent non-Hodgkin lymphoma. As the nonhybrid regimen is less cumbersome than the previous hybrid dosing schedule regimen, the current schedule is recommended for successor studies. | 25,248,382 | [
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Simulation and comparison of progression-free survival among patients with non-squamous non-small-cell lung cancer receiving sequential therapy. | In recent years, the treatment landscape in advanced non-squamous non-small-cell lung cancer (nsNSCLC) has changed. New therapies (e.g., bevacizumab indicated in first line) have become available and other therapies (e.g., pemetrexed in first line and second line) moved into earlier lines in the treatment paradigm. While there has been an expansion of the available treatment options, it is still a key research question which therapy sequence results in the best survival outcomes for patients with nsNSCLC. A therapy-sequencing disease model that approximates treatment outcomes in up to five lines of treatment was developed for patients with nsNSCLC. The primary source of data for progression-free survival (PFS) and time to death was published pivotal trial data. All patients were treatment-naïve and in the PFS state, received first-line treatment with either bevacizumab-based therapy or doublet chemotherapy (including the option of pemetrexed + cisplatin). Patients would then progress to a subsequent line of therapy, remain in PFS or die. In case of progression, it was assumed that each survivor would receive a subsequent line of therapy, based on EMA licensed therapies. Weibull distribution curves were fitted to the data. All bevacizumab-based first-line therapy sequences analyzed achieved total PFS of around 15 months. Bevacizumab + carboplatin + paclitaxel (first line) → pemetrexed (second line) → erlotinib (third line) → docetaxel (fourth line) resulted in total mean PFS time of 15.7 months, for instance. Sequences with pemetrexed in combination with cisplatin in first line achieved total PFS times between 12.6 and 12.8 months with a slightly higher total PFS time achieved when assuming pemetrexed continuation therapy in maintenance after pemetrexed + cisplatin in first-line induction. Overall survival results followed the same trend as PFS. The model suggests that treatment-sequencing strategies starting with a bevacizumab-based combination in first line yield better survival outcomes than those starting with pemetrexed-based combinations, a result that is attributable to the possibility of one further line of treatment with first-line bevacizumab-based treatment sequences. | 25,248,391 | [
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International Charter of principles for sharing bio-specimens and data. | There is a growing international agreement on the need to provide greater access to research data and bio-specimen collections to optimize their long-term value and exploit their potential for health discovery and validation. This is especially evident for rare disease research. Currently, the rising value of data and bio-specimen collections does not correspond with an equal increase in data/sample-sharing and data/sample access. Contradictory legal and ethical frameworks across national borders are obstacles to effective sharing: more specifically, the absence of an integrated model proves to be a major logistical obstruction. The Charter intends to amend the obstacle by providing both the ethical foundations on which data sharing should be based, as well as a general Material and Data Transfer Agreement (MTA/DTA). This Charter is the result of a careful negotiation of different stakeholders' interest and is built on earlier consensus documents and position statements, which provided the general international legal framework. Further to this, the Charter provides tools that may help accelerate sharing. The Charter has been formulated to serve as an enabling tool for effective and transparent data and bio-specimen sharing and the general MTA/DTA constitutes a mechanism to ensure uniformity of access across projects and countries, and may be regarded as a consistent basic agreement for addressing data and material sharing globally. The Charter is forward looking in terms of emerging issues from the perspective of a multi-stakeholder group, and where possible, provides strategies that may address these issues. | 25,248,399 | [
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International precipitants to psychiatric patient assaults in community settings: review of published findings, 2000-2012. | In studying psychiatric patient assaults, assessing the person × event × environment interaction is important in enhancing safety and ensuring quality care. Precipitants to patient assaults have traditionally received less attention than the characteristics of such assaults. A recent review of inpatient precipitants noted acute psychosis, denial of services, and substance abuse as common precipitants in these settings. Even though health care systems are moving toward community-based services, no community studies were included in this inpatient review. The present study reviewed the precipitants reported in community studies internationally from 2000-2012. A variety of community precipitants, including acute psychosis and substance abuse, were obtained. How these community precipitants differ from the inpatient preciptiants and a detailed methodological inquiry are presented. | 25,248,419 | [
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Classification of Physiological 18F-fluorodeoxyglucose Uptake in the Large Intestine: a Preliminary Study. | Varying degrees of physiological uptake of 18F-fluorodeoxyglucose (FDG) are often noted in the large intestine and can be problematic when interpreting positron emission tomography (PET) images. In relation to colorectal tumor detection with FDG PET, we tentatively classified physiological FDG uptake in the large intestine according to its patterns and intensity. Subjects were 144 asymptomatic individuals (109 men, 35 women; mean age 57.5 ± 10.1 years) in our cancer screening program who underwent total colonoscopy within 24 days of FDG PET study and showed no evidence of colonic lesions on colonoscopy. Distinct FDG uptake on FDG PET images was classified into four types: focal, defined as distinctly nodular and visible on at least 4 axial; localized, 2 to 8 cm with SUVmean ≥ 4; diffuse, > 8 cm with SUVmean ≥ 4; and mixed, of more than one type. SUVmeans were examined by placing multiple circular regions of interest of 1 cm in diameter on the axial images. We found 21 distinct FDG uptakes matching our criteria in 20 of 144 subjects (13.9%): focal (n = 4), localized (n = 1), diffuse (n = 14), and mixed (n = 1; focal and diffuse). With regard to colorectal tumor detection, 6 subjects (4.2%) with focal or localized type of uptake were considered at risk of false-positive tumor identification, and 15 subjects (10.4%) with diffuse type of uptake were considered at risk of their tumors being missed at the site of FDG uptake. To confirm the feasibility of our criteria, this classification should be tested with a larger number of subjects. | 25,248,430 | [
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The phenomenon of micronutrient deficiency among children in China: a systematic review of the literature. | The present study aimed to review the literature on micronutrient deficiency and other factors influencing a deficiency status among children living in China. A systematic review was performed to analyse the literature. Studies were identified through a search of PubMed and secondary references. Children living in China aged less than 18 years. Sixty-one articles were included. The prevalence of vitamin A deficiency decreased to approximately 10 % in 1995-2009. It increased with age but no significant difference was found between genders. The prevalence of thiamin and vitamin B12 deficiency was 10·5 % in Yunnan and 4·5 % in Chongqing provinces, respectively. Higher vitamin D deficiency rates were seen in spring and winter. The incidence of bleeding due to vitamin K deficiency was 3·3 % in 1998-2001 and more prevalent in rural areas. Both iodine deficiency and excess iodine intake were observed. Goitre rates were reported in Tibet, Jiangxi, Gansu and Hong Kong (3·5-46 %). Anaemia rates ranged from 20 % to 40 % in 2007-2011. High Se deficiency rates were found in Tibet, Shaanxi and Jiangsu. High Zn deficiency rates were also found (50-70 %) in 1995-2006. Few studies reported Ca deficiency rates (19·6-34·3 %). The degrees of deficiency for vitamin A, vitamin B12, Fe and Zn were more substantial in rural areas compared with urban areas. The prevalence of micronutrient deficiency rates varied. Socio-economic status, environmental factors and the Chinese diet may influence micronutrient deficiency. Public health policies should consider implementing programmes of supplementation, food fortification and nutrition education to address these deficiencies among Chinese children. | 25,248,458 | [
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Trimodality bladder-sparing approach without neoadjuvant chemotherapy for node-negative localized muscle-invasive urinary bladder cancer resulted in comparable cystectomy-free survival. | To retrospectively review the efficacy and organ preservation experience for muscle-invasive bladder cancer by trimodality therapy at our institution. Between July 2004 and February 2012, seventy patients (M/F = 55/15; median age = 69 years) of lymph node negative localized muscle-invasive bladder cancer were treated primarily with trimodality approach including transurethral resection of bladder tumor (TURBT) prior to combined chemotherapy and radiotherapy (CCRT). Radiotherapy consisted of initial large field size irradiation with 3D conformal technique (3D-CRT), followed by cone-down tumor bed boost with intensity modulated radiotherapy (IMRT) technique. The median total doses delivered to bladder tumor bed and whole bladder were 59.4Gy and 40.0Gy, respectively. No patient received neoadjuvant chemotherapy (NAC). Weekly cisplatin was administered during radiotherapy. Toxicity was scored according to the RTOG criteria. Tumor response was evaluated both cystoscopically and radiographically 3 months after treatment. The numbers of patients with T2, T3 and T4 lesions were 41, 16 and 13, respectively. Overall survival (OS) and progression-free survival (PFS) at 2 and 5 year were 65.7%, 51.9% and 50.8%, 39.9%, respectively, after a median follow-up time of 24 months. Local-regional control and distant metastasis free survival at 2 year were 69.8% and 73.5%, respectively. Complete response (CR) rate assessed three month after CCRT was 78.1%. Ten patients (20%) had local recurrence after initial CR (n = 50), 3 of them were superficial recurrence. One patient underwent radical cystectomy after recurrence. The overall 5-year bladder intact survival was 49.0% (95% CI, 35.5% to 62.5%). Acute toxicities were limited to grade 1-2. One patient developed late grade 3 GU toxicity. Our result suggested that trimodality bladder-sparing approach without NAC or dose-intensification could be well-tolerated with a high CR rate and bladder preserving rate for muscle-invasive bladder cancer. | 25,248,470 | [
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Usefulness of endoluminal catheter colonization surveillance cultures to reduce catheter-related bloodstream infections in hemodialysis. | To evaluate the use of surveillance cultures (SCs) to prevent catheter-related bloodstream infections (CRBSIs) in asymptomatic hemodialysis (HD) patients. In 2011-2012, we conducted a prospective study of HD patients with tunneled cuffed central venous catheters (TCCs). Colonization of the catheter lumen was assessed every 15 days by inoculating ~5 mL endoluminal blood into aerobic culture bottles. Individual patients were triaged based on SC results: group 1 (negative); group 2 (coagulase-negative Staphylococcus [CoNS] with time-to-positivity (TTP) >14 hours); group 3 (CoNS with TTP ≤14 hours); and group 4 (any microorganism other than CoNS and any TTP). We studied 104 patients (129 TCCs). Median follow-up was 262.5 days (interquartile range [IR], 135.0-365.0). A total of 1,734 SCs were collected (median, 18 per patient; IR, 10.0-24.0), of which 1,634 (94.2%) were negative (group 1) and 100 (5.8%) were positive (group 2: 79; group 3: 12, group 4: 9). In groups 2 and 3, 19 TCCs required antibiotic lock therapy (ALT). In group 4, all patients received intravenous therapy and ALT. Under this protocol, there were 0.27 episodes of CRBSI per 1,000 catheter days compared with 1.65 (P < .001) prior to its implementation. SCs based on easily accessible samples proved useful in triaging HD patients at a high risk of infection. | 25,248,485 | [
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Disentangling quality and safety indicator data: a longitudinal, comparative study of hand hygiene compliance and accreditation outcomes in 96 Australian hospitals. | The study aims are twofold. First, to investigate the suitability of hand hygiene as an indicator of accreditation outcomes and, second, to test the hypothesis that hospitals with better accreditation outcomes achieve higher hand hygiene compliance rates. A retrospective, longitudinal, multisite comparative survey. Acute public hospitals in New South Wales, Australia. 96 acute hospitals with accreditation survey results from two surveys during 2009-2012 and submitted data for more than four hand hygiene audits between 2010 and 2013. Our primary outcome comprised observational hand hygiene compliance data from eight audits during 2010-2013. The explanatory variables in our multilevel regression model included: accreditation outcomes and scores for the infection control standard; timing of the surveys; and hospital size and activity. Average hand hygiene compliance rates increased from 67.7% to 80.3% during the study period (2010-2013), with 46.7% of hospitals achieving target compliance rates of 70% in audit 1, versus 92.3% in audit 8. Average hand hygiene rates at small hospitals were 7.8 percentage points (pp) higher than those at the largest hospitals (p<0.05). The association between hand hygiene rates, accreditation outcomes and infection control scores is less clear. Our results indicate that accreditation outcomes and hand hygiene audit data are measuring different parts of the quality and safety spectrum. Understanding what is being measured when selecting indicators to assess the impact of accreditation is critical as focusing on accreditation results would discount successful hand hygiene implementation by smaller hospitals. Conversely, relying on hand hygiene results would discount the infection control related research and leadership investment by larger hospitals. Our hypothesis appears to be confounded by an accreditation programme that makes it more difficult for smaller hospitals to achieve high infection control scores. | 25,248,496 | [
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Employment outcomes one year after bariatric surgery: the role of patient and psychosocial factors. | Patients undergoing bariatric surgery generally report improved work performance after this procedure; however, previous research has been limited by a lack of standardized employment measures and a failure to account for the impact of psychiatric illness on employment outcomes. To address these limitations, this study aims to assess changes in patients' employment impairment and productivity 12 months post-surgery and to identify psychosocial predictors of change in employment outcomes. A total of 164 patients underwent bariatric surgery between February 2010 and November 2012 in this prospective cohort study. The primary outcome was a change in employment impairment (EI) as measured by total Lam Employment Absence and Productivity Scale (LEAPS) scores and changes in participants' job status category. Multiple linear regression models assessed whether baseline demographic or clinical factors, including a history of psychiatric illness and changes in depressive, anxiety and quality of life (QOL) symptoms, were associated with a change in LEAPS scores. Participants reported a significant reduction in EI post-surgery (p < 0.0001) and improvement in work productivity (p < 0.0001) 12 months after surgery. Only changes in depression (confidence interval (CI) 0.46, 0.76, p < 0.0001), anxiety (CI 0.49, 0.85, p < 0.0001) and mental QOL (CI -0.30, -0.17, p < 0.0001) were significant predictors of change in EI total scores. Logistic regression analysis did not identify significant predictors of change in participant job status. Patients with pre-bariatric surgery psychiatric distress are more likely to report greater employment impairment and worse employment productivity pre-surgery. These patients also experience the greatest improvements in post-surgery employment functioning. | 25,248,509 | [
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Prevalence, causes and consequences of compassion satisfaction and compassion fatigue in emergency care: a mixed-methods study of UK NHS Consultants. | To estimate prevalence and explore potential causes and consequences of compassion satisfaction and compassion fatigue in UK emergency medicine consultants. A sequential mixed-methods design. Cross-sectional e-survey to all UK NHS emergency medicine consultants (n=1317) including Professional Quality of Life (ProQOL) (compassion satisfaction/fatigue), followed by interviews with consultants scoring above (n=6) and below (n=6) predefined ProQOL thresholds. 681 (52%) consultants responded. Most (98%) reported at least 'average' compassion satisfaction. Higher scores were associated with type of workplace (designated trauma centres faring better) and number of years worked as a consultant (gradually worsen over time, except 20 years onwards when it improves). Consultants with lower (worse) compassion satisfaction scores were more likely to report being irritable with patients or colleagues and reducing their standards of care (a third reported these behaviours at least monthly) and were more likely to intend to retire early (59% had such plans). Key features distinguishing 'satisfied' from 'fatigued' interviewed consultants included having strategies to deal with the high work intensities associated with their role and having positive views of the team within which they worked. The degree of variety in their roles and the ability to maintain empathy for their patients were also distinguishing features between these groups. Findings support an urgent review of workforce and resources in emergency medicine and suggest that a multifactorial approach to identification, prevention and treatment of occupational stress in the workforce is required that considers individual, job and organisational factors, particularly those that impact on perceived control and support at work. | 25,248,545 | [
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Bone quality is affected by food restriction and by nutrition-induced catch-up growth. | Growth stunting constitutes the most common effect of malnutrition. When the primary cause of malnutrition is resolved, catch-up (CU) growth usually occurs. In this study, we have explored the effect of food restriction (RES) and refeeding on bone structure and mechanical properties. Sprague-Dawley male rats aged 24 days were subjected to 10 days of 40% RES, followed by refeeding for 1 (CU) or 26 days long-term CU (LTCU). The rats fed ad libitum served as controls. The growth plates were measured, osteoclasts were identified using tartrate-resistant acid phosphatase staining, and micro-computed tomography (CT) scanning and mechanical testing were used to study structure and mechanical properties. Micro-CT analysis showed that RES led to a significant reduction in trabecular BV/TV and trabecular number (Tb.N), concomitant with an increase in trabecular separation (Tb.Sp). Trabecular BV/TV and Tb.N were significantly greater in the CU group than in the RES in both short- and long-term experiments. Mechanical testing showed that RES led to weaker and less compliant bones; interestingly, bones of the CU group were also more fragile after 1 day of CU. Longer term of refeeding enabled correction of the bone parameters; however, LTCU did not achieve full recovery. These results suggest that RES in young rats attenuated growth and reduced trabecular bone parameters. While nutrition-induced CU growth led to an immediate increase in epiphyseal growth plate height and active bone modeling, it was also associated with a transient reduction in bone quality. This should be taken into consideration when treating children undergoing CU growth. | 25,248,555 | [
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Elucidating dimensions of posttraumatic stress symptoms and their functional correlates in disaster-exposed adolescents. | The aim of this study was to elucidate the dimensional structure of posttraumatic stress disorder (PTSD) and potential moderators and functional correlates of this structure in disaster-affected adolescents. A population-based sample of 2000 adolescents aged 12-17 years (M = 14.5 years; 51% female) completed interviews on post-tornado PTSD symptoms, substance use, and parent-adolescent conflict between 4 and 13 months (M = 8.8, SD = 2.6) after tornado exposure. Confirmatory factor analyses revealed that all models fit well but a 5-factor dysphoric arousal model provided a statistically significantly better representation of adolescent PTSD symptoms compared to 4-factor dysphoria and emotional numbing models. There was evidence of measurement invariance of the dysphoric arousal model across gender and age, although girls and older adolescents aged 15-17 years had higher mean scores than boys and younger adolescents aged 12-14 years, respectively, on some PTSD dimensions. Differential magnitudes of association between PTSD symptom dimensions and functional correlates were observed, with emotional numbing symptoms most strongly positively associated with problematic substance use since the tornado, and dysphoric arousal symptoms most strongly positively associated with parent-adolescent conflict; both correlations were significantly larger than the corresponding correlations with anxious arousal. Taken together, these results suggest that the dimensional structure of tornado-related PTSD symptomatology in adolescents is optimally characterized by five separate clusters of re-experiencing, avoidance, numbing, dysphoric arousal, and anxious arousal symptoms, which showed unique associations with functional correlates. Findings emphasize that PTSD in disaster-exposed adolescents is not best conceptualized as a homogenous construct and highlight potential differential targets for post-disaster assessment and intervention. | 25,248,557 | [
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One-step isolation of sappanol and brazilin from Caesalpinia sappan and their effects on oxidative stress-induced retinal death. | Caesalpinia sappan is a well-distributed plant that is cultivated in Southeast Asia, Africa, and the Americas. C. sappan has been used in Asian folk medicine and its extract has been shown to have pharmacological effects. Two homoisoflavonoids, sappanol and brazilin, were isolated from C. sappan by using centrifugal partition chromatography (CPC), and tested for protective effects against retinal cell death. The isolated homoisoflavonoids produced approximately 20-fold inhibition of N-retinylidene-N-retinyl-ethanolamine (A2E) photooxidation in a dose-dependent manner. Of the 2 compounds, brazilin showed better inhibition (197.93 ± 1.59 μM of IC50). Cell viability tests and PI/Hoechst 33342 double staining method indicated that compared to the negative control, sappanol significantly attenuated H2O2-induced retinal death. The compounds significantly blunted the up-regulation of intracellular reactive oxygen species (ROS), and sappanol inhibited lipid peroxidation in a concentration-dependent manner. Thus, both compounds represent potential antioxidant treatments for retinal diseases. | 25,248,564 | [
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Genetic aspects of hypothalamic and pituitary gland development. | Hypothalamo-pituitary development during embryogenesis is a highly complex process involving the interaction of a network of spatiotemporally regulated signaling molecules and transcription factors. Mutations in any of the genes encoding these components can lead to congenital hypopituitarism, which is often associated with a wide spectrum of defects affecting craniofacial/midline development. In turn, these defects can be incompatible with life, or lead to disorders encompassing holoprosencephaly (HPE) and cleft palate, and septo-optic dysplasia (SOD). In recent years, there has been increasing evidence of an overlapping genotype between this spectrum of disorders and Kallmann syndrome (KS), defined as the association of hypogonadotropic hypogonadism (HH) and anosmia. This is consistent with the known phenotypic overlap between these disorders and opens a new avenue of identifying novel genetic causes of the hypopituitarism spectrum. This chapter reviews the genetic and molecular events leading to the successful development of the hypothalamo-pituitary axis during embryogenesis, and focuses on genes in which variations/mutations occur, leading to congenital hypopituitarism and associated defects. | 25,248,576 | [
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Craniopharyngioma. | Craniopharyngiomas are partly cystic embryogenic malformations of the sellar and parasellar region. With an overall incidence of 0.5-2.0 new cases per million population per year, approximately 30-50% of all cases represent childhood craniopharyngioma. Typical manifestations at diagnosis are some combination of headache, visual impairment, polyuria/polydypsia, growth retardation, and significant weight gain. Therapy of choice in patients with favorable tumor localization is complete resection with specific focus on maintaining functions of the optic nerve and hypothalamic-pituitary axes. In patients whose unfavorable tumor localization makes maintaining hypothalamic functionality surgically challenging, a limited resection followed by local irradiation is recommended. The overall survival rates are high (92%) but occurrences of reduced quality of life are also high. Recurrences after complete resection and progressions of residual tumor after incomplete resection are frequent postsurgical events. Because irradiation is efficient in preventing tumor progression, appropriate timing of postsurgical irradiation is currently under investigation in the randomized multinational trial KRANIOPHARYNGEOM 2007 that analyzes quality of life as primary endpoint. Childhood craniopharyngioma should be recognized as a chronic disease requiring constant monitoring of the clinical and quality of life consequences in order to provide optimal care of surviving patients. | 25,248,591 | [
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A decisional account of subjective inflation of visual perception at the periphery. | Human peripheral vision appears vivid compared to foveal vision; the subjectively perceived level of detail does not seem to drop abruptly with eccentricity. This compelling impression contrasts with the fact that spatial resolution is substantially lower at the periphery. A similar phenomenon occurs in visual attention, in which subjects usually overestimate their perceptual capacity in the unattended periphery. We have previously shown that at identical eccentricity, low spatial attention is associated with liberal detection biases, which we argue may reflect inflated subjective perceptual qualities. Our computational model suggests that this subjective inflation occurs because under the lack of attention, the trial-by-trial variability of the internal neural response is increased, resulting in more frequent surpassing of a detection criterion. In the current work, we hypothesized that the same mechanism may be at work in peripheral vision. We investigated this possibility in psychophysical experiments in which participants performed a simultaneous detection task at the center and at the periphery. Confirming our hypothesis, we found that participants adopted a conservative criterion at the center and liberal criterion at the periphery. Furthermore, an extension of our model predicts that detection bias will be similar at the center and at the periphery if the periphery stimuli are magnified. A second experiment successfully confirmed this prediction. These results suggest that, although other factors contribute to subjective inflation of visual perception in the periphery, such as top-down filling-in of information, the decision mechanism may be relevant too. | 25,248,620 | [
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-... |
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