title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Autophagy and amino acid metabolism in the brain: implications for epilepsy. | Autophagy is a catabolic pathway responsible for the maintenance of the tissue and organism homeostasis. Several amino acids regulate autophagic activity in different tissues, such as liver and muscle, but much less is known about this regulation in the brain. The lack of autophagy in neurons leads to a strong neurodegenerative phenotype and epileptic disorders. We summarize the current knowledge about the regulation of autophagy mediated by amino acids and how macroautophagy could serve as source of amino acids. We review the contribution of macroautophagy in the brain physiology and pathology emphasizing the relevancy of the proper control of amino acid levels such as glutamate and GABA in the brain due to its role as neurotransmitters and energy source. Furthermore, we discuss how malfunction in autophagy may result in pathological consequences, because many genetic epileptic disorders are related to signaling or metabolic pathways controlling both macroautophagy and amino acid metabolism in the brain. | 25,145,921 | [
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Selective Embolization of Systemic Collaterals for the Treatment of Recurrent Hemoptysis Secondary to the Unilateral Absence of a Pulmonary Artery in a Child. | The unilateral absence of the pulmonary artery (UAPA) is a rare anomaly. Hemoptysis due to systemic collaterals is one of the most common complications of UAPA. To the best of the authors' knowledge, the utility of selective embolization for the treatment of this condition in children has not been reported previously. This report describes a 6-year-old girl with isolated UAPA (IUAPA) admitted for a 10-month history of recurrent hemoptysis that had worsened during the previous 2 months. Selective embolization of the bronchial systemic collaterals was performed. The patient remained asymptomatic with no recurrence of hemoptysis 8 months after the procedure. | 25,145,922 | [
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Ebstein anomaly: assessment, management, and timing of intervention. | Ebstein anomaly is a developmental abnormality of the tricuspid valve and right ventricle that results in tricuspid regurgitation and right heart enlargement. Because of the variation in clinical severity and associated findings, patients require a detailed, well-tailored evaluation. For these reasons, management of adults with Ebstein anomaly should take place in a center with expertise in adult congenital heart disease. In many patients, the decision regarding if and when to perform surgery remains controversial, largely because of a lack of published data demonstrating improved postoperative symptoms and survival compared to the natural history of the disease. Because standard two-dimensional echocardiography and cardiovascular magnetic resonance imaging planes do not provide the necessary data to preoperatively manage patients, comprehensive echocardiography and cardiovascular magnetic resonance imaging protocols by experts trained in congenital heart disease are essential in the preoperative management of patients with Ebstein anomaly. As patients may be unaware of their exercise limitations, and for prognostic value, serial cardiopulmonary exercise stress testing is very useful in the evaluation of Ebstein anomaly patients. Surgical tricuspid valve repair historically has not been highly successful because of the marked distortion of tricuspid valve leaflets and right ventricular pathology. Over the last several years, reports of newer surgical techniques to repair the valve, with concurrent advances in arrhythmia management of patients hold promise for improved long term outcomes of patients with Ebstein anomaly. However, because Ebstein anomaly is rare and tricuspid valve repair remains technically challenging, the newer valve repair techniques have not yet gained widespread acceptance throughout the adult congenital heart disease community. | 25,145,925 | [
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Surface-confined single-layer covalent organic framework on single-layer graphene grown on copper foil. | The integration of 2D covalent organic frameworks (COFs) with atomic thickness with graphene will lead to intriguing two-dimensional materials. A surface-confined covalently bonded Schiff base network was prepared on single-layer graphene grown on copper foil and the dynamic reaction process was investigated with scanning tunneling microscopy. DFT simulations provide an understanding of the electronic structures and the interactions between the surface COF and graphene. Strong coupling between the surface COF and graphene was confirmed by the dispersive bands of the surface COF after interaction with graphene, and also by the experimental observation of tunneling condition dependent contrast of the surface COF. | 25,145,927 | [
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Long-term outcome after arthroscopic rotator cuff treatment. | Arthroscopic techniques have become the gold standard in the operative management of several pathologic conditions of the shoulder. The purpose of this systematic review was to present the long-term outcomes following arthroscopic treatment of rotator cuff pathology. A comprehensive literature review was performed to identify studies reporting clinical or structural results of arthroscopic rotator cuff repairs (ARCRs) at least 5 years after surgery. Ten articles were selected, which described 483 procedures. Study type, surgical approaches, complications, evidences of structural integrity of the repaired lesions, preoperative and postoperative functional scores are identified, analyzed and discussed. Satisfactory results are presented by all authors, and significant postoperative improvement is reported by all the studies with available preoperative data; 16 of 483 cases were re-operated. Although high-level evidences are lacking, ARCR appears to be an effective and safe option to treat the symptoms of rotator cuff tears and to provide successful clinical results durable with time. Current evidences are insufficient to clearly define the relationship between structural integrity of repaired cuffs and long-term clinical outcome. The available data do not allow to draw conclusions regarding the long-term superiority of double-row versus single-row repairs. Review of level II, III and IV studies, Level IV. | 25,145,945 | [
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Role of laparoscopy in patients with peritoneal metastases considered for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). | We hypothesized that diagnostic laparoscopy (DL) was feasible for the evaluation of patients with peritoneal carcinomatosis (PC) undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC). A retrospective review of PC patients treated from January 2010 to April 2013 was conducted. Data on tumor characteristics, treatment details and survival outcomes were extracted and analyzed. Of the 101 PC patients (mean age 52.9 ± 14.1 years), 73 diagnostic laparoscopies DL (61 concurrent with CRS + HIPEC) were performed in 70 patients whereas 31 patients underwent direct exploratory laparotomy (EL). Complete laparoscopic assessment was possible in 63 cases (86.3%), resulting in 18 exclusions (27.7%) while 10 cases were converted to open due to inadequate laparoscopic visualization. Subsequently, CRS + HIPEC was performed in 85.4% (of 55 selected for HIPEC, DL) versus 74.2% (EL, P value = 0.20). Among those excluded from HIPEC at the initial operation, delayed HIPEC after conversion chemotherapy was achieved in 6 (of 11 with extensive disease, DL). The incidence of grade 3 to 5 complications was 0% DL versus 10% EL (P value = 0.2). There were no port site recurrences at mean follow up of 9.1 ± 8 months. Laparoscopy is a feasible technique for selecting patients with PC for CRS + HIPEC, and can help select patients for conversion chemotherapy in the setting of high peritoneal carcinomatosis index (PCI) score. | 25,145,962 | [
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An ESIPT based fluorescent probe for highly selective and ratiometric detection of periodate. | Periodate is widely used in organic and bioorganic chemistry, and also related to food and environmental safety. To best of our knowledge, there is no efficient tools reported for simultaneously quantifying periodate with high accuracy and discriminating periodate from other forms of iodine. We have synthesized, characterized and applied a first ratiometric fluorescent probe (PDS-2) for simultaneous monitoring of changes of periodate based on the excited-state intramolecular proton transfer mechanism. This PDS-2 based fluorescent technique may enable for a better understanding of periodate related biological and chemical processes. Also, it is an efficient tool for public health, food safety and environmental protection. | 25,145,984 | [
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Osteoblastic cell response to spark plasma-sintered zirconia/titanium cermets. | Ceramic/metal composites, cermets, arise from the idea to combine the dissimilar properties in the pure materials. This work aims to study the biocompatibility of new micro-nanostructured 3 Y-TZP/Ti materials with 25, 50 and 75 vol.% Ti, which have been successfully obtained by spark slasma sintering technology, as well as to correlate their surface properties (roughness, wettability and chemical composition) with the osteoblastic cell response. All samples had isotropic and slightly waved microstructure, with sub-micrometric average roughness. Composites with 75 vol.% Ti had the highest surface hydrophilicity. Surface chemical composition of the cermets correlated well with the relative amounts used for their fabrication. A cell viability rate over 80% dismissed any cytotoxicity risk due to manufacturing. Cell adhesion and early differentiation were significantly enhanced on materials containing the nanostructured 3 Y-TZP phase. Proliferation and differentiation of SaOS-2 were significantly improved in their late-stage on the composite with 75 vol.% Ti that, from the osseointegration standpoint, is presented as an excellent biomaterial for bone replacement. Thus, spark plasma sintering is consolidated as a suitable technology for manufacturing nanostructured biomaterials with enhanced bioactivity. | 25,145,987 | [
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Cell-to-cell transfer of HIV infection: implications for HIV viral persistence. | A major research priority for HIV eradication is the elucidation of the events involved in HIV reservoir establishment and persistence. Cell-to-cell transmission of HIV represents an important area of study as it allows for the infection of cell types which are not easily infected by HIV, leading to the establishment of long-lived viral reservoirs. This phenomenon enables HIV to escape elimination by the immune system. This process may also enable HIV to escape suppressive effects of anti-retroviral drugs. During cell-to-cell transmission of HIV, a dynamic series of events ensues at the virological synapse that promotes viral dissemination. Cell-to-cell transmission involves various types of cells of the immune system and this mode of transmission has been shown to have an important role in sexual and mother-to-child transmission of HIV and spread of HIV within the central nervous system and gut-associated lymphoid tissues. There is also evidence that cell-to-cell transmission of HIV occurs between thymocytes and renal tubular cells. Herein, following a brief review of the processes involved at the virological synapse, evidence supporting the role for cell-to-cell transmission of HIV in the maintenance of the HIV reservoir will be highlighted. Therapeutic considerations and future directions for this area of research will also be discussed. | 25,146,006 | [
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Down-regulation of inflammatory mediator synthesis and infiltration of inflammatory cells by MMP-3 in experimentally induced rat pulpitis. | Matrix metalloproteinase (MMP)-3 is a member of the MMP family that degrades the extracellular matrix. Application of MMP-3 to injured pulp tissue induces angiogenesis and wound healing, but its anti-inflammatory effects are still unclear. Here, we evaluated the anti-inflammatory functions of MMP-3 in vitro and in vivo. Nitric oxide and inflammatory mediator synthesis in macrophages activated by lipopolysaccharide (LPS) was measured in the presence or absence of MMP-3. The mouse Mmp3 (mMmp3) expression vector containing full length cDNA sequence of mMmp3 or cDNA sequence of mMmp3 missing the signal peptide and pro-peptide regions was transfected to RAW264, a mouse macrophage cell line, and NO synthesis and inflammatory mediator expression were evaluated. Pulpal inflammation was histologically and immunohistochemically evaluated in a rat model of incisor pulpitis induced by the application of LPS for 9 hours in the presence or absence of MMP-3. NO and pro-inflammatory mediator synthesis promoted by LPS was significantly down-regulated by MMP-3 in vitro. The full length of mMmp3 down-regulated the LPS-induced NO synthesis and chemical mediator mRNA expression, however the mMmp3 missing the signal peptide failed to block the NO synthesis induced by LPS. The numbers of major histocompatibility complex class II+ and CD68+ cells, which infiltrated into the rat incisor pulp tissues in response to the topical application of LPS, were significantly decreased by the application of MMP-3 in vivo. These results indicate that MMP-3 possesses anti-inflammatory functions, suggesting its potential utility as an anti-inflammatory agent for pulpal inflammation. | 25,146,022 | [
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Correlation of root dentin thickness and length of roots in mesial roots of mandibular molars. | The purpose of this study was to analyze the relation of tooth length and distal wall thickness of mesial roots in mandibular molars at different locations (ie, 2 mm below the furcation and at the junction between the middle and apical third). Forty-five mandibular first molars were taken, and the length of each tooth was measured. Then, specimens were divided into three groups according to their length: group I-long (24.2 mm ± 1.8), group II-medium (21 mm ± 1.5) and group III-short (16.8 mm ± 1.8). mesial root of each marked at two levels - at 2 mm below the furcation as well as at junction of apical and middle third of roots. The minimum thickness of the distal root dentine associated with the buccal and lingual canals of the mesial roots was measured, The distance between the buccal and lingual canals and the depth of concavity in the distal surface of the mesial roots were also measured. Statistical analysis was performed by using analysis of variance and the Student-Newman-Keuls test. The minimum thickness of the distal wall of the mesiobuccal canal was significantly different (P < .001) between groups 1 (long) and 3 (short). Distal wall thickness of the mesiobuccal root and distal concavity of the mesial root of mandibular first molars were found to be thinner in longer teeth compared with shorter teeth. | 25,146,027 | [
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The Making Cases Count intiative. | Given the challenges faced, how can homeopaths communicate the power and scope of the therapeutic system of homeopathy? Homeopaths need to communicate to patients, the public and media, other healthcare professionals, healthcare researchers, and funders of healthcare (healthcare insurers, those who commission healthcare services either in publicly funded healthcare systems such as the NHS or charities). Effective communication with these stakeholders requires information that is: (a) easily understood, (b) credible, and (c) relevant. The patient's voice is the trusted, indisputable and easily understood common ground in homeopathy. Yet, the experiences of patients are rarely heard outside the profession of homeopathy. Homeopaths are in a unique position to make these voices heard by disseminating the results of their routine practice cases incorporating their patients' voices. The 'Making Cases Count' initiative has been created in order to bring about a culture where easily understood, trusted and salient information is regularly made available to all stakeholders in homeopathy. The Making Cases Count initiative supports, guides and incentives homeopaths to collect routine data with the aim of bringing about a culture where a significant proportion of homeopaths collect routine data from their patients in a format which will then be able to be transformed (i.e. anonymised, summarised and counted). This routine data requires numbers and categories to report the behavior and the perspective of patients receiving homeopathic treatment. This can be strengthened through the use of validated outcome measures in hearing patients' voices. When transformed, this routine data will then be able to inform homeopaths and more importantly other key stakeholders. It is now time to make patient cases count. | 25,146,064 | [
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Reduction of surgery rate in endometriosis patients who take Chinese medicine: a population-based retrospective cohort study. | Female patients have frequently utilized Chinese medicine (CM) to treat symptoms that could possibly be related to endometriosis. The objective of this population-based retrospective cohort study was to evaluate the relationship between CM use and subsequent surgery among patients with endometriosis. A total of 8,283 CM users were identified among the 22,488 endometriosis patients found in the National Health Insurance reimbursement database between 2000 and 2010. A control group was identified and consisted of 8,283 matched nonusers with the same disease. A Cox proportional regression analysis was performed in order to assess risk factors for surgery for the CM users and nonusers. When compared to nonusers, CM users were significantly less likely to undergo surgery, with a hazard ratio of 0.47 (95% CI=0.421, 0.534) after adjusting for age, occupation, childbirth status, hypermenorrhea, iron-deficient anemia, dysmenorrhea, and amount of conventional medications. Among patients who had undergone surgery, the follow-up time was longer for CM users than for CM nonusers (p<0.001). Moreover, the most frequently used CM single and formula were Cyperus rotundus and Gui-zhi-fu-ling-wan, respectively. These results suggest that whatever the underlying reason, CM provides an alternative option that reduces the incidence rate of surgery in endometriosis patients. | 25,146,066 | [
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Measuring body constitution: validation of the Body Constitution Questionnaire (BCQ) in Hong Kong. | The Body Constitution Questionnaire (BCQ) was developed in Taiwan to classify people into body constitution (BC) types based on Traditional Chinese Medicine (TCM) theories. Since the culture of Hong Kong is different from Taiwan, the BCQ must be validated before a wider application can be preceded. To adapt and validate the Hong Kong version of BCQ in Hong Kong Chinese population. The content validity of BCQ was investigated by the cognitive debriefing with 10 patients and 10 Chinese Medicine Practitioners (CMP). A cross-sectional study of 1084 Chinese patients recruited from TCM and Western Medicine (WM) outpatient clinics to confirm the construct validity, reliability, sensitivity and responsiveness of BCQ. 225 of the patients were assessed after 2 weeks for the test-retest reliability. 404 subjects were followed up to evaluate the responsiveness after 3-6 months. Cognitive debriefing confirmed the content validity of the BCQ (HK version) with content validity index of all items ranged from 70 to 100%. 1084 out of 2128 patients (51%) completed the cross-sectional study. The construct validity was confirmed with scaling success rates that ranged from 87.5 to 89.5%, moderate correlations between with SF-12v2 scores, and 3-factors structure with confirmatory factor analysis. The reliability was confirmed by the Cronbach's alphas >0.8 and test-retest reliability (intra-class correlation coefficients >0.8). BCQ was adapted and validated on Hong Kong Chinese population. Patients with imbalanced BC types had lower health-related quality of life (HRQOL) than those with balanced BC types, which supported the validity and importance of the body constitution under the concept of TCM. | 25,146,072 | [
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Detection of CoHV-1 by loop-mediated amplification (LAMP). Application of LAMP for CoHV-1 incidence monitoring in domestic pigeons. | The occurrence of Columbid herpesvirus-1 (CoHV-1) in domestic pigeons presents a potential threat for their husbandry and trade. CoHV-1 causes Smadel disease among pigeons but may not be manifested by any clinical signs and complicates secondary infections. The material for our study originated from 42 domestic pigeons sent to private veterinary practice in Lublin, Poland, between 2011 and 2013. Some of birds showed clinical signs similar to Smadel disease. The cytological examination also indicated on CoHV-1 infection. The incidence of CoHV-1 was tested in DNA extracted from liver of birds by loop-mediated isothermal amplification (LAMP). LAMP was used for the monitoring of CoHV-1 presence among pigeons in Poland. Our study showed that LAMP was capable of detecting CoHV-1 presence in 8 (19%) of 42 examined birds without the use of any advanced laboratory equipment. The results were confirmed by real-time PCR and virus isolation in chicken embryo fibroblasts. This is the first report on LAMP application for successful detection of CoHV-1 in domestic pigeons. The incidence of Columbid herpesvirus-1 (CoHV-1) in pigeons was examined for the first time by loop-mediated isothermal amplification (LAMP). The study showed the presence of CoHV-1 in 8 of 42 examined domestic pigeons. LAMP technique developed within this study may be used by not well-equipped veterinary laboratories. | 25,146,091 | [
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Drug conjugation to cyclic peptide-polymer self-assembling nanotubes. | We show for the first time how polymeric nanotubes (NTs) based on self-assembled conjugates of polymers and cyclic peptides can be used as an efficient drug carrier. RAPTA-C, a ruthenium-based anticancer drug, was conjugated to a statistical co-polymer based on poly(2-hydroxyethyl acrylate) (pHEA) and poly(2-chloroethyl methacrylate) (pCEMA), which formed the shell of the NTs. Self-assembly into nanotubes (length 200-500 nm) led to structures exhibiting high activity against cancer cells. | 25,146,103 | [
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Diffusion weighted magnetic resonance imaging demonstrates tumor response following palliative embolization of a recurrent shoulder plasmacytoma. | We report the palliative embolization and functional imaging follow-up of a recurrent shoulder plasmacytoma. The multiple myeloma patient complained of severe pain and discomfort, while he could not tolerate further chemotherapy. The left shoulder lesion had earlier received a high dose of irradiation. Thus, the well-vascularized lesion was embolized via feeding arteries branching off from the left subclavian artery in two sessions. The patient's symptoms rapidly improved post-embolization and the serum free light chain ratio stabilized at a lower level. The follow-up magnetic resonance image showed increased diffusivity in previously restricted tumor foci. This has negatively correlated with the decreased fludeoxyglucose uptake on PET, suggesting post-embolization necrosis. | 25,146,111 | [
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Frequency matters: beta-band subthalamic nucleus deep-brain stimulation induces Parkinsonian-like blink abnormalities in normal rats. | The synchronized beta-band oscillations in the basal ganglia-cortical networks in Parkinson's disease (PD) may be responsible for PD motor symptoms or an epiphenomenon of dopamine loss. We investigated the causal role of beta-band activity in PD motor symptoms by testing the effects of beta-frequency subthalamic nucleus deep-brain stimulation (STN DBS) on the blink reflex excitability, amplitude, and plasticity in normal rats. Delivering 16 Hz STN DBS produced the same increase in blink reflex excitability and impairment in blink reflex plasticity in normal rats as occurs in rats with 6-hydroxydopamine lesions and patients with PD. These deficits were not an artifact of STN DBS because, when these normal rats received 130 Hz STN DBS, their blink characteristics were the same as without STN DBS. To demonstrate that the blink reflex disturbances with 16 Hz STN DBS were frequency specific, we tested the same rats with 7 Hz STN DBS, a theta-band frequency typical of dystonia. In contrast to beta stimulation, 7 Hz STN DBS exaggerated the blink reflex plasticity as occurs in focal dystonia. Thus, without destroying dopamine neurons or blocking dopamine receptors, frequency-specific STN DBS can be used to create PD-like or dystonic-like symptoms in a normal rat. | 25,146,113 | [
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Pollutant toxicity and detoxification by humic substances: mechanisms and quantitative assessment via luminescent biomonitoring. | The paper considers mechanisms of detoxification of pollutant solutions by water-soluble humic substances (HSs), natural detoxifying agents. The problems and perspectives of bioassay application for toxicity monitoring of complex solutions are discussed from ecological point of view. Bioluminescence assays based on marine bacteria and their enzymes are of special attention here; they were shown to be convenient tools to study the detoxifying effects on cellular and biochemical levels. The advantages of bioluminescent enzymatic assay for monitoring both integral and oxidative toxicities in complex solutions of model pollutants and HS were demonstrated. The efficiencies of detoxification of the solutions of organic oxidizers and salts of metals (including radioactive ones) by HS were analyzed. The dependencies of detoxification efficiency on time of exposure to HS and HS concentrations were demonstrated. Antioxidant properties of HS were considered in detail. The detoxifying effects of HS were shown to be complex and regarded as 'external' (binding and redox processes in solutions outside the organisms) and/or 'internal' organismal processes. The paper demonstrates that the HS can stimulate a protective response of bacterial cells as a result of (1) changes of rates of biochemical reactions and (2) stabilization of mucous layers outside the cell walls. Acceleration of auto-oxidation of NADH, endogenous reducer, by HS was suggested as a reason for toxicity increase in the presence of HS due to abatement of reduction ability of intracellular media. | 25,146,119 | [
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Evolution of dissolved organic matter during abiotic oxidation of coal tar--comparison with contaminated soils under natural attenuation. | In former coal transformation plants (coking and gas ones), the major organic contamination of soils is coal tar, mainly composed of polycyclic aromatic compounds (PACs). Air oxidation of a fresh coal tar was chosen to simulate the abiotic natural attenuation impact on PAC-contaminated soils. Water-leaching experiments were subsequently performed on fresh and oxidized coal tars to study the influence of oxidation on dissolved organic matter (DOM) quality and quantity. The characterization of the DOM was performed using a combination of molecular and spectroscopic techniques (high-performance liquid chromatography-size-exclusion chromatography (HPLC-SEC), 3D fluorescence, and gas chromatography coupled with mass spectrometry (GC-MS)) and compared with the DOM from contaminated soils sampled on the field exposed to natural attenuation for several decades. An increase in the oxygenated polycyclic aromatic compound concentrations was observed with abiotic oxidation both in the coal tar and the associated DOM. Polycyclic aromatic hydrocarbon concentrations in the leachates exceeded pure water solubility limits, suggesting that co-solvation with other soluble organic compounds occurred. Furthermore, emission excitation matrix analysis combined with synchronous fluorescence spectra interpretation and size-exclusion chromatography suggests that oxidation induced condensation reactions which were responsible for the formation of higher-molecular weight compounds and potentially mobilized by water. Thus, the current composition of the DOM in aged soils may at least partly result from (1) a depletion in lower-molecular weight compounds of the initial contamination stock and (2) an oxidative condensation leading to the formation of a higher-molecular weight fraction. Abiotic oxidation and water leaching may therefore be a significant combination contributing to the evolution of coal tar-contaminated soils under natural attenuation. | 25,146,121 | [
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Dimeric tetrathiafulvalene linked to pseudo-ortho-[2.2]paracyclophane: chiral electrochromic properties and use as a chiral dopant. | A dimeric tetrathiafulvalene installed into a chiral pseudo-ortho-[2.2]paracyclophane framework was synthesized as a novel chiral electrochromic material. This compound exhibited pronounced chiroptical properties in the UV-Vis-NIR range depending on its redox states without racemization. Each enantiomer was examined as a chiral dopant for nematic liquid crystals (LCs), and the induced helicity of the LC solvent was in accord with that of the tetrathiafulvalene compound. | 25,146,126 | [
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Water activation by small free ruthenium oxide clusters. | The reactions of ruthenium clusters, Rux(+) (x = 2-5), and ruthenium oxide clusters, RuxOy(+) (x = 2-5, y = 1-2), with water molecules have been investigated by gas phase ion trap mass spectrometry and first principle density functional calculations. The joint experimental and theoretical study reveals that the reactions of the ruthenium oxide clusters with water are considerably more efficient. This is assigned theoretically to the stronger binding of the water molecules to RuxOy(+) and, more importantly, to water activation leading to an efficient hydrogen transfer reaction from the water molecules to the oxygen atoms of the ruthenium oxide clusters. The theoretically predicted hydrogen shift reaction has been confirmed experimentally through (16)O/(18)O isotope exchange experiments. Calculated energy profiles for the reactions of selected oxide clusters with water illustrate that the oxygen isotope exchange relies on the facile transfer of hydrogen atoms via [1,3] shift reactions between the oxygen atoms of the complexes due to the relatively low barriers involved. These findings might open perspectives for the future realization of water oxidation driven by ruthenium oxide clusters. | 25,146,165 | [
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[Prevalence of anal-vaginal colonization of Streptococcus agalactiae in third trimester of pregnancy and susceptibility to macrolides and lincosamides, in pregnant women controlled at Clínica Alemana Temuco, Southern Chile]. | Streptococcus agalactiae (GBS) is the most common agent in early neonatal sepsis. Strategies incorporating universal screening for maternal colonization show the lowest rates of perinatal infection. A significant increase in resistance to erythromycin and clindamycin by GBS has been reported around the world. There are no published data regarding prevalence and antimicrobial resistance in southern regions of Chile. Surveillance of antimicrobial resistance is essential to define the drugs of choice and alternatives, in an institution that applies prevention protocols, as Clinica Alemana Temuco (CAT) does. to determine the prevalence of carriage of GBS in vaginal-anal areas at end of pregnancy, in CAT, Araucanía Region, Chile. To determine the susceptibility to erythromycin and clindamycin of GBS strains isolated. 1,181 pregnant women were included; 167 were positive for GBS (14.4% of colonization). Sixteen were resistant to erythromycin (9.5%); 15 of these strains were also clindamycin resistant. Twenty-three of 167 were resistant to clindamycin (13.7%). The prevalence rate of GBS colonization was lower than previously reported in other regions of Chile. Due to the high rates of resistance to clindamycin and erythromycin it is necessary to widen the study of susceptibility to other antimicrobials to have alternatives in allergy to penicillin (primarily cefazolin and vancomycin). | 25,146,205 | [
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Nanoscale nickel oxide/nickel heterostructures for active hydrogen evolution electrocatalysis. | Active, stable and cost-effective electrocatalysts are a key to water splitting for hydrogen production through electrolysis or photoelectrochemistry. Here we report nanoscale nickel oxide/nickel heterostructures formed on carbon nanotube sidewalls as highly effective electrocatalysts for hydrogen evolution reaction with activity similar to platinum. Partially reduced nickel interfaced with nickel oxide results from thermal decomposition of nickel hydroxide precursors bonded to carbon nanotube sidewalls. The metal ion-carbon nanotube interactions impede complete reduction and Ostwald ripening of nickel species into the less hydrogen evolution reaction active pure nickel phase. A water electrolyzer that achieves ~20 mA cm(-2) at a voltage of 1.5 V, and which may be operated by a single-cell alkaline battery, is fabricated using cheap, non-precious metal-based electrocatalysts. | 25,146,255 | [
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Political science. Reverse-engineering censorship in China: randomized experimentation and participant observation. | Existing research on the extensive Chinese censorship organization uses observational methods with well-known limitations. We conducted the first large-scale experimental study of censorship by creating accounts on numerous social media sites, randomly submitting different texts, and observing from a worldwide network of computers which texts were censored and which were not. We also supplemented interviews with confidential sources by creating our own social media site, contracting with Chinese firms to install the same censoring technologies as existing sites, and--with their software, documentation, and even customer support--reverse-engineering how it all works. Our results offer rigorous support for the recent hypothesis that criticisms of the state, its leaders, and their policies are published, whereas posts about real-world events with collective action potential are censored. | 25,146,296 | [
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Effect of temperature and pressure on characteristics and reactivity of biomass-derived chars. | This study evaluates the influence of pyrolysis temperature (350-450°C) and pressure (0.1-2.0MPa) on product yields and char properties. Spruce chars were produced under slow pyrolysis conditions in a fixed bed reactor. Special attention was devoted to the study of the oxidation reactivity of the produced chars, and its relationship with the evaluated char properties. The obtained results showed that the effect of the pyrolysis condition on char production and in particular on the mechanism of secondary char formation strongly influenced the char reactivity. Additionally it has been observed that the interval of temperature between 350 and 450°C may be key in the mechanism of tar repolymerization. The information provided in this study is of great interest for the determination of optimal operation conditions and the design of new gasification concepts or the development of bioenergy carriers via pyrolysis technologies. | 25,146,312 | [
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Triple valve surgery in the modern era: short- and long-term results from a single centre. | Triple valve surgery (TVS) is still a challenge for surgeons because of prolonged cardiopulmonary bypass (CPB) and myocardial ischaemic times. The reported operative mortality rate for TVS ranges between 2.5 and 25%; long-term survival is also diminished, with reported survival rates at 5 and 10 years of 75-82 and 61-75%, respectively. The objective of our study is to define early and late clinical outcomes, reporting the initial experience in the treatment of triple valve disease through a minimally invasive approach. A retrospective, observational, cohort study was undertaken of prospectively collected data on 106 patients who underwent TVS at our institution between October 2001 and June 2013. A total of 101 procedures were done through the standard median sternotomy; however, in 5 patients, the surgical procedure was carried out through a right minithoracotomy. Univariate analysis was performed to identify predictors of early and late survival. The in-hospital mortality rate was 5.6% (6 of 107 patients). Predictors of early mortality were: previous cardiac surgery [odds ratio (OR) 4, 95% confidence interval (CI) 1.08-5.2, P = 0.04], preoperative left ventricular ejection fraction (LVEF) (OR 0.9, 95% CI 0.8-1.1, P = 0.003), prolonged CPB time (OR 1.02, 95% CI 1.01-1.04, P = 0.01) and postoperative pulmonary complications (OR 8, 95% CI 5.8-41, P = 0.0001). Five- and 10-year survival rates were 85 ± 3 and 65 ± 9%, respectively. In univariate analysis, diabetes [hazard ratio (HR) 2.5, 95% CI 1-6.2, P = 0.045], preoperative dialysis (HR 3, 95% CI 2-4.7, P = 0.001), unstable angina (HR 4.8, 95% CI 1-18, P = 0.03), preoperative LVEF (HR 0.9, 95% CI 0.8-1.1, P = 0.02), concomitant coronary artery bypass grafting (CABG) (HR 2.5, 95% CI 1.5-5.7, P = 0.006), prolonged CPB time (HR 1.02, 95% CI 1.01-1.13, P = 0.006), postoperative pacemaker (PMK) implantation (HR 6.2, 95% CI 1.3-18, P = 0.01) and postoperative pulmonary complications (HR 3.3, 95% CI 2.1-7.3, P = 0.002) were found to be significant predictors of late mortality following TVS. The freedom rates from valve-related complications and reoperation at 10 years were 95 ± 2 and 97 ± 2%, respectively. The 10-year freedom rates from thromboembolism and anticoagulation-related haemorrhage were 88 ± 5 and 88 ± 4%, respectively. TVS offers encouraging short-term and long-term patient survival; these good results after TVS in patients with advanced valvular heart disease justify aggressive surgical therapy in these patients. TVS with a minimally invasive approach is feasible and could be another treatment option. | 25,146,323 | [
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Developmental markers of ganglion cells in the enteric nervous system and their application for evaluation of Hirschsprung disease. | Hirschsprung disease (HSCR) is a congenital disease resulting from failure of neural crest-derived ganglion cells to colonize the colon. Conventional diagnostic methods are insufficient for evaluating the 'functional' prognosis of HSCR. In order to elucidate the maturation of ganglion cells, 17 immunohistochemical markers were examined. We examined the digestive tracts of 2 human early delivery patients, 2 miniature swine fetuses, 4 little infants, 3 infants, 3 children, 6 adults, and 3 aged individuals. With increasing age, the labeling index (LI) for both calretinin and tyrosine hydroxylase (TH) increased, whereas that for SOX10 decreased. We then examined the 'transitional zone' of HSCR in 21 affected patients and 18 controls for these three markers. The LI of calretinin and TH were significantly lower than in the controls (median: 3.7 in HSCR and 8.2 in controls, P < 0.001, median: 27.9 in HSCR and 44.4 in controls, P < 0.001, respectively). In contrast, the LI for SOX10 showed no significant difference (median: 33.7 in HSCR and 29.2 in controls, P = 0.666) however, hierarchical cluster analysis was able to divide HSCR patients into two groups. These results suggest that immature ganglion cells are present in the transitional zone of HSCR, and that HSCR may have two different pathophysiological processes. | 25,146,344 | [
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Inferring human mobility using communication patterns. | Understanding the patterns of mobility of individuals is crucial for a number of reasons, from city planning to disaster management. There are two common ways of quantifying the amount of travel between locations: by direct observations that often involve privacy issues, e.g., tracking mobile phone locations, or by estimations from models. Typically, such models build on accurate knowledge of the population size at each location. However, when this information is not readily available, their applicability is rather limited. As mobile phones are ubiquitous, our aim is to investigate if mobility patterns can be inferred from aggregated mobile phone call data alone. Using data released by Orange for Ivory Coast, we show that human mobility is well predicted by a simple model based on the frequency of mobile phone calls between two locations and their geographical distance. We argue that the strength of the model comes from directly incorporating the social dimension of mobility. Furthermore, as only aggregated call data is required, the model helps to avoid potential privacy problems. | 25,146,347 | [
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On copper diffusion in silicon measured by glow discharge mass spectrometry. | Copper contamination occurs frequently in silicon for photovoltaic applications due to its very fast diffusion coupled with a low solid solubility, especially at room temperature. The combination of these properties exerts a challenge on the direct analysis of Cu bulk concentration in Si by sputtering techniques like glow discharge mass spectrometry (GDMS). This work aims at addressing the challenges in quantitative analysis of fast diffusing elements in Si matrix by GDMS. N-type, monocrystalline (Czochralski) silicon samples were intentionally contaminated with Cu after solidification and consequently annealed at 900 °C to ensure a homogeneous distribution of Cu in the bulk. The samples were quenched after annealing to control the extent of the diffusion to the surface prior to the GDMS analyses, which were carried out at different time intervals from within few minutes after cooling onward. The Cu profiles were measured by high-resolution GDMS operating in a continuous direct current mode, where the integration step length was set to ∼0.5 μm over a total sputtered depth of 8-30 μm. The temperature of the samples during the GDMS analyses was also measured in order to evaluate the diffusion. The Cu contamination of n-type Si samples was observed to be highly material dependent. The practical impact of Cu out-diffusion on the calculation of the relative sensitivity factor (RSF) of Cu in Si is discussed. | 25,146,357 | [
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Wheat allergy in children - new tools for diagnostics. | The detection of wheat-specific IgE in children often leads to a suspicion of wheat allergy, but little information is available on the most reliable wheat allergens for predicting clinical reactivity. To evaluate the role of allergenic components of wheat in wheat allergy diagnostics. One hundred and eight children (median age 1.5 years; range 0.6-17.3 years) with suspected wheat allergy underwent open or double-blinded, placebo-controlled oral wheat challenges. Responsiveness to different allergenic components of wheat was studied by skin prick tests and by determination of serum IgE antibodies using a semi-quantitative microarray assay. Thirty (28%) children reacted with immediate symptoms, and 27 (25%) with delayed symptoms to ingested wheat, whereas 51 (47%) children exhibited no reactions in oral wheat challenges. Positive IgE responses to any of the 12 allergenic components of wheat was seen in 93%, 41%, and 43% of those with immediate, delayed or no reactions to ingested wheat, respectively (P < 0.001 to P < 0.05 in every comparisons between those with immediate reactions and those with no reactions). Positive IgE responses to ≥5 different allergenic components improved significantly the diagnostic accuracy (with a positive likelihood ratio (LR+) of 5.10). Alpha-amylase inhibitors (AAI), in particular dimeric AAI 0.19 (LR+ 6.12), alpha-, beta-, and gamma-gliadins (LR+ from 3.57 to 4.53), and high-molecular-weight (HMW) glutenin subunits (LR+ 4.37) were the single allergenic components of wheat differentiating most effectively those with immediate symptoms from those who did not exhibit any reactions. Wheat allergy diagnostics is difficult, even using sophisticated component methods. Our results confirm earlier findings about gliadins and identify the dimeric AAI 0.19, as a relevant allergen in clinically reactive patients when compared to non-reactive subjects. The accuracy of wheat allergy diagnosis may be improved by measuring IgE responses to several components of wheat. | 25,146,380 | [
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Liquid chromatography with mass spectrometry method based two-step precursor ion scanning for the structural elucidation of flavonoids. | Plant flavonoids are very important secondary metabolites for insect and virus control of their host plant and are potent nutrients for humans. To be able to understand the bioavailability and functions of plant flavonoids, it is necessary to reveal their exact chemical structures. Liquid chromatography with tandem mass spectrometry is a powerful approach for structural elucidation of metabolites. In this report, a two-step precursor ion scanning based liquid chromatography with tandem mass spectrometry method was developed for the structural elucidation of plant flavonoids. The established method consists of the two-step precursor ions scanning for possible flavonoids extraction, MS(2) fragment spectra acquisition and comparison with an online database, liquid chromatography retention rules correction, and commercial standards verification. The developed method was used for the structure elucidation of flavonoids in flowers and leaves of tobacco (Nicotiana tabacum), and 17 flavonoids were identified in the tobacco variety Yunyan 97. Nine of the 17 identified flavonoids were considered to be found in tobacco flowers or/and leaves for the first time based on the available references. This method was proved to be very effective and can be used for the identification of flavonoids in other plants. | 25,146,381 | [
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Twist1 induces endothelial differentiation of tumour cells through the Jagged1-KLF4 axis. | The mechanisms controlling tumour-induced angiogenesis are presently not clear. In principle, angiogenesis can be achieved through the activation of endothelial cells in existing vessels or by transdifferentiation of tumour cells into endothelial cells. However, whether tumour cells can go through a prior epithelial-mesenchymal transition and further differentiate into endothelial cells remains unknown. Here we show that overexpression of Twist1, a transcriptional regulator that induces and promotes cancer metastasis, leads to endothelial differentiation in head and neck cancer (HNC) cells. Induction of Jagged1 expression by Twist1 is essential for Twist1-induced endothelial differentiation. The Jagged1/Notch signalling subsequently activates KLF4, inducing stem-like properties in HNC cells and conferring them with drug resistance. Our results indicate that the Twist1-Jagged1/KLF4 axis is essential both for transdifferentiation of tumour cells into endothelial cells and for chemoresistance acquisition. | 25,146,389 | [
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Measurement of greenhouse gas flux from agricultural soils using static chambers. | Measurement of greenhouse gas (GHG) fluxes between the soil and the atmosphere, in both managed and unmanaged ecosystems, is critical to understanding the biogeochemical drivers of climate change and to the development and evaluation of GHG mitigation strategies based on modulation of landscape management practices. The static chamber-based method described here is based on trapping gases emitted from the soil surface within a chamber and collecting samples from the chamber headspace at regular intervals for analysis by gas chromatography. Change in gas concentration over time is used to calculate flux. This method can be utilized to measure landscape-based flux of carbon dioxide, nitrous oxide, and methane, and to estimate differences between treatments or explore system dynamics over seasons or years. Infrastructure requirements are modest, but a comprehensive experimental design is essential. This method is easily deployed in the field, conforms to established guidelines, and produces data suitable to large-scale GHG emissions studies. | 25,146,426 | [
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Glucocorticoid-induced leucine zipper (GILZ) controls inflammation and tissue damage after spinal cord injury. | Spinal cord injury (SCI) occurs following damage to the spinal column. Following trauma, tissue damage is further exacerbated by a secondary damage due to a SCI-activated inflammatory process. Control of leukocytes activity is essential to therapeutic inhibition of the spinal cord damage to ameliorate the patient's conditions. The mechanisms that regulate neuroinflammation following SCI, including T-cell infiltration, have not been completely clarified. Glucocorticoids (GC) are antiinflammatory drugs widely used in therapy, including treatment of SCI. GC efficacy may be linked to many molecular mechanisms that are involved in regulation of leukocytes migration, activation, and differentiation. We have previously shown that the antiinflammatory activity of GC is in part mediated by glucocorticoid-induced leucine zipper (GILZ). Here, we investigated the role of GILZ in inflammation and spinal cord tissue damage following a spinal trauma. We address the role of GILZ in SCI-induced inflammation and tissue damage using a model of SCI in gilz knockout (gilz KO) and wild-type (WT) mice. We found that GILZ deficiency is associated with a strong reduction of SCI-induced inflammation and a significantly reduced lesion area following SCI. These results demonstrate that GILZ is involved in induction of neuroinflammation and functional outcomes of spinal cord trauma. | 25,146,427 | [
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Dose heterogeneity correction for low-energy brachytherapy sources using dual-energy CT images. | Permanent seed implant brachytherapy is currently used for adjuvant radiotherapy of early stage prostate and breast cancer patients. The current standard for calculation of dose around brachytherapy sources is based on the AAPM TG-43 formalism, which generates the dose in a homogeneous water medium. Recently, AAPM TG-186 emphasized the importance of accounting for tissue heterogeneities. We have previously reported on a methodology where the absorbed dose in tissue can be obtained by multiplying the dose, calculated by the TG-43 formalism, by an inhomogeneity correction factor (ICF). In this work we make use of dual energy CT (DECT) images to extract ICF parameters. The advantage of DECT over conventional CT is that it eliminates the need for tissue segmentation as well as assignment of population based atomic compositions. DECT images of a heterogeneous phantom were acquired and the dose was calculated using both TG-43 and TG-43 [Formula: see text] formalisms. The results were compared to experimental measurements using Gafchromic films in the mid-plane of the phantom. For a seed implant configuration of 8 seeds spaced 1.5 cm apart in a cubic structure, the gamma passing score for 2%/2 mm criteria improved from 40.8% to 90.5% when ICF was applied to TG-43 dose distributions. | 25,146,446 | [
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Altered cerebrovascular reactivity velocity in mild cognitive impairment and Alzheimer's disease. | Interindividual variation in neurovascular reserve and its relationship with cognitive performance is not well understood in imaging in neurodegeneration. We assessed the neurovascular reserve in amnestic mild cognitive impairment (aMCI) and Alzheimer's dementia (AD). Twenty-eight healthy controls (HC), 15 aMCI, and 20 AD patients underwent blood oxygen level-dependent imaging for 9 minutes, breathing alternatively air and 7% carbon dioxide mixture. The data were parcellated into 88 anatomic regions, and carbon dioxide regressors accounting for different washin and washout velocities were fitted to regional average blood oxygen level-dependent signals. Velocity of cerebrovascular reactivity (CVR) was analyzed and correlated with cognitive scores. aMCI and AD patients had significantly slower response than HC (mean time to reach 90% of peak: HC 33 seconds, aMCI and AD 59 seconds). CVR velocity correlated with Mini Mental State Examination in 35 of 88 brain regions (p = 0.019, corrected for multiple comparisons), including 10 regions of the default-mode network, an effect modulated by age. This easily applicable protocol yielded a practical assessment of CVR in cognitive decline. | 25,146,454 | [
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Oxygenated monoterpenes citral and carvacrol cause oxidative damage in Escherichia coli without the involvement of tricarboxylic acid cycle and Fenton reaction. | Oxygenated monoterpenes citral and carvacrol are common constituents of many essential oils (EOs) that have been extensively studied as antimicrobial agents but whose mechanisms of microbial inactivation have not been totally elucidated. A recent study described a mechanism of Escherichia coli death for (+)-limonene, a hydrocarbon monoterpene also frequently present in EOs, similar to the common mechanism proposed for bactericidal antibiotics. This mechanism involves the formation of Fenton-mediated hydroxyl radical, a reactive oxygen species (ROS), via tricarboxylic acid (TCA) cycle, which would ultimately inactivate cells. Our objective was to determine whether E. coli MG1655 inactivation by citral and carvacrol follows a similar mechanism of cell death. Challenging experiments with 300μL/L citral and 100μL/L carvacrol inactivated at least 2.5log10cycles of exponentially growing cells in 3h under aerobic conditions. The presence of thiourea (an ROS scavenger) reduced cell inactivation in 2log10cycles, demonstrating the role of ROS in cell death. Decreased resistance of a ΔrecA mutant (deficient in an enzyme involved in SOS response to DNA damage) indicated that citral and carvacrol caused oxidative damage to DNA. Although the mechanism of E. coli inactivation by carvacrol and citral was similarly mediated by ROS, their formation did not follow the same pathways described for (+)-limonene and bactericidal drugs because neither Fenton reaction nor NADH production via the TCA cycle was involved in cell death. Moreover, further experiments demonstrated antimicrobial activity of citral and carvacrol in anaerobic environments without the involvement of ROS. As a consequence, cell death by carvacrol and citral in anaerobiosis follows a different mechanism than that observed under aerobic conditions. These results demonstrated a different mechanism of inactivation by citral and carvacrol with regard to (+)-limonene and bactericidal antibiotics, indicating the complexity of the mechanisms of bacterial inactivation among EO constituents. Advancements in the description of these mechanisms will help in extending and improving the use of these compounds as natural antimicrobials. | 25,146,464 | [
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Engineering the donor selectivity of D-fructose-6-phosphate aldolase for biocatalytic asymmetric cross-aldol additions of glycolaldehyde. | D-Fructose-6-phosphate aldolase (FSA) is a unique catalyst for asymmetric cross-aldol additions of glycolaldehyde. A combination of a structure-guided approach of saturation mutagenesis, site-directed mutagenesis, and computational modeling was applied to construct a set of FSA variants that improved the catalytic efficiency towards glycolaldehyde dimerization up to 1800-fold. A combination of mutations in positions L107, A129, and A165 provided a toolbox of FSA variants that expand the synthetic possibilities towards the preparation of aldose-like carbohydrate compounds. The new FSA variants were applied as highly efficient catalysts for cross-aldol additions of glycolaldehyde to N-carbobenzyloxyaminoaldehydes to furnish between 80-98 % aldol adduct under optimized reaction conditions. Donor competition experiments showed high selectivity for glycolaldehyde relative to dihydroxyacetone or hydroxyacetone. These results demonstrate the exceptional malleability of the active site in FSA, which can be remodeled to accept a wide spectrum of donor and acceptor substrates with high efficiency and selectivity. | 25,146,467 | [
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Effect of different breath alcohol concentrations on driving performance in horizontal curves. | Driving under the influence of alcohol on curved roadway segments has a higher risk than driving on straight segments. To explore the effect of different breath alcohol concentration (BrAC) levels on driving performance in roadway curves, a driving simulation experiment was designed to collect 25 participants' driving performance parameters (i.e., speed and lane position) under the influence of 4 BrAC levels (0.00%, 0.03%, 0.06% and 0.09%) on 6 types of roadway curves (3 radii×2 turning directions). Driving performance data for 22 participants were collected successfully. Then the average and standard deviation of the two parameters were analyzed, considering the entire curve and different sections of the curve, respectively. The results show that the speed throughout curves is higher when drinking and driving than during sober driving. The significant interaction between alcohol and radius exists in the middle and tangent segments after a curve exit, indicating that a small radius can reduce speed at high BrAC levels. The significant impairment of alcohol on the stability of speed occurs mainly in the curve section between the point of curve (PC) and point of tangent (PT), with no impairment noted in tangent sections. The stability of speed is significantly worsened at higher BrAC levels. Alcohol and radius have interactive effects on the standard deviation of speed in the entry segment of curves, indicating that the small radius amplifies the instability of speed at high BrAC levels. For lateral movement, drivers tend to travel on the right side of the lane when drinking and driving, mainly in the approach and middle segments of curves. Higher BrAC levels worsen the stability of lateral movement in every segment of the curve, regardless of its radius and turning direction. The results are expected to provide reference for detecting the drinking and driving state. | 25,146,494 | [
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The selective noradrenergic reuptake inhibitor reboxetine restores spatial learning deficits, biochemical changes, and hippocampal synaptic plasticity in an animal model of depression. | Depression is a major psychiatric illness that is associated with cognitive dysfunctions. The underlying mechanism of depression-associated memory impairment is unclear. Previously, we showed altered hippocampal synaptic plasticity in an animal model of depression. Although several antidepressants are beneficial in the treatment of depression, very little is known about the effects of these drugs on depression-associated learning and memory deficits. Prolonged antidepressant treatment might contribute to neuroplastic changes required for clinical outcomes. Accordingly, we evaluated the effect of chronic reboxetine (a selective noradrenergic reuptake inhibitor) treatment on depression-induced reduced hippocampal synaptic plasticity, neurotransmitter levels, and spatial learning and memory impairments. Depression was induced in male Wistar rats by the administration of clomipramine from postnatal days 8 to 21, and these rats were treated with reboxetine in adulthood. The neonatal clomipramine administration resulted in impaired hippocampal long-term potentiation (LTP), decreased hippocampal cholinergic activity and monoamine levels, and poor performance in a partially baited eight-arm radial maze task. Chronic reboxetine treatment restored the hippocampal LTP, acetylcholinesterase activity, and levels of biogenic amines and ameliorated spatial learning and memory deficits in the depressed state. Thus, restoration of hippocampal synaptic plasticity might be a cellular mechanism underlying the beneficial effect of reboxetine in depression-associated cognitive deficits. This study furthers the existing understanding of the effects of antidepressants on learning, memory, and synaptic plasticity and could ultimately assist in the development of better therapeutic strategies to treat depression and associated cognitive impairments. | 25,146,499 | [
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[Results of surgical treatment of cholelithiasis by laparotomic and minimally invasive accesses]. | The article presents the results of surgical treatment of 1038 patients with cholelithiasis, acute and chronic calculous cholecystitis and complicated forms of the disease. Operations were performed with traditional laparotomic and minimally invasive approaches. Indications for choosing access, as well as the advantages and disadvantages of various options of surgery in patients with cholelithiasis are discussed. | 25,146,538 | [
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[The impact of thromboprophylaxis with enoxaparin on bleeding rate in rejuvenating facelift procedures]. | A retrospective study on safety of prophylactic use of Enoxaparin in rejuvenating face lift procedures. The prophylactic use of Enoxaparin was not found to be associated with increased perioperative bleeding or higher incidence of postoperative hematomas requiring reoperation. | 25,146,545 | [
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The control of insulin secretion by adipokines: current evidence for adipocyte-beta cell endocrine signalling in metabolic homeostasis. | Metabolic homeostasis is maintained by the coordinated action of multiple organ systems. Insulin secretion is often enhanced during obesity or insulin resistance to maintain glucose and lipid homeostasis, whereas a loss of insulin secretion is associated with type 2 diabetes. Adipocytes secrete hormones known as adipokines which act on multiple cell types to regulate metabolism. Many adipokines have been shown to influence beta cell function by enhancing or inhibiting insulin release or by influencing beta cell survival. Insulin, in turn, regulates lipolysis and promotes glucose uptake and lipid storage in adipocytes. As adipokine secretion and action is strongly influenced by obesity, this provides a potential route by which beta cell function is coordinated with adiposity, independently of alterations in blood glucose or lipid levels. In this review, I assess the evidence for the direct regulation of beta cell function by the adipokines leptin, adiponectin, extracellular nicotinamide phosphoribosyltransferase, apelin, resistin, retinol binding protein 4, fibroblast growth factor 21, nesfatin-1 and fatty acid binding protein 4. I summarise in vitro and in vivo data and discuss the influence of obesity and diabetes on circulating adipokine concentrations, along with the potential for influencing beta cell function in human physiology. Finally, I highlight future research questions that are likely to yield new insights into the exciting field of insulinotropic adipokines. | 25,146,550 | [
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Sonochemistry: what potential for conversion of lignocellulosic biomass into platform chemicals? | This Review focuses on the use of ultrasound to produce chemicals from lignocellulosic biomass. However, the question about the potential of sonochemistry for valorization/conversion of lignocellulosic biomass into added-value chemicals is rather conceptual. Until now, this technology has been mainly used for the production of low-value chemicals such as biodiesel or as simple method for pretreatment or extraction. According to preliminary studies reported in literature, access to added-value chemicals can be easily and sometimes solely obtained by the use of ultrasound. The design of sonochemical parameters offers many opportunities to develop new eco-friendly and efficient processes. The goal of this Review is to understand why the use of ultrasound is focused rather on pretreatment or extraction of lignocellulosic biomass rather than on the production of chemicals and to understand, through the reported examples, which directions need to be followed to favor strategies based on ultrasound-assisted production of chemicals from lignocellulosic biomass. We believe that ultrasound-assisted processes represent an innovative approach and will create a growing interest in academia but also in the industry in the near future. Based on the examples reported in the literature, we critically discuss how sonochemistry could offer new strategies and give rise to new results in lignocellulosic biomass valorization. | 25,146,583 | [
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Prevalence of osteoporosis and vertebral fractures and related factors in patients with ankylosing spondylitis. | Osteoporosis and vertebral factures are well recognized features in patients with ankylosing spondylitis (AS). The aim of this study was to investigate the prevalence and risk factors of osteoporosis and vertebral fractures in patients with AS. Fifty-nine AS patients and 40 healthy controls were enrolled. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DEXA) at posterior-anterior (PA) lumbar, lateral lumbar and hip regions. Thoracic and lumbar X-rays were obtained for morphometric measurements. Clinical, biological and radiological statuses were evaluated with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Radiology Index-total (BASRI-t), erythrocyte sedimentation rate (ESR) and the C-reactive protein levels. Osteoporosis was present in 32% of patients and 5% of controls according to lateral vertebral BMD measurements. Fracture was present in 31% of patients. The effect of some clinical and laboratory parameters on BMD status and vertebral fractures was analyzed in the patient group. Osteoporosis in lateral lumbar DEXA was associated with higher BASMI, BASFI, BASRI-t scores and ESR level. Low hip BMD was associated with low BMI and high BASFI and BASRI-t scores. Vertebral fractures were associated with advanced age, longer disease duration, longer duration since diagnosis, higher BASMI and BASRI-t scores, higher ESR level, reduced femoral and lateral lumbar BMD. Logistic regression analysis revealed that only BASRI-t score was significantly associated with low lateral spinal BMD and BMI and BASFI score were independently associated with low hip BMD. The presence of compression fractures was independently associated with BASRI-t score and low lateral lumbar BMD. Osteoporosis and vertebral fractures in AS seem to be related to the extent of radiological involvement. A low lateral lumbar BMD is an important risk factor for vertebral fractures. | 25,146,606 | [
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Pathogenic analysis in different types of orthopedic implant infections. | Diversity of orthopedic infections with various local environments affects the pattern and prevalence of pathogens. It is not well-characterized whether different pathogens have different propensity to cause different types of orthopedic infections. We aimed to investigate the frequency of different pathogens derived from orthopedic infections, and determine the relationship between the prevalence of clinical isolates and the type of orthopedic implants, especially focusing on staphylococci. From January 2006 to December 2011, orthopedic infections were identified retrospectively from clinical microbiology laboratory and orthopedic medical records. The sources of orthopedic infections were divided into two main groups: those associated with implants and those not associated with implants. Implants-associated infections were further subdivided into five subgroups: arthroplasty, internal fixation, external fixation, internal and external fixation, and others. We analyzed microbiological spectrum in different groups and subgroups. Antibiotic susceptibility of staphylococci was analyzed. Only coagulase-negative staphylococci (CoNS) was significantly more likely to be associated with implants-associated infections (P = 0.029). The overall pathogens prevalence of arthroplasty was significantly different from other subgroups (P < 0.05). 65% isolates from external fixation was Gram-negative bacteria. Some percentage (55%) of S. aureus and (83%) CoNS were resistant to methicillin. No resistance to glycopeptide was seen in all of staphylococci. Staphylococcus aureus was the most frequent isolates in orthopedic infections but was not associated with the presence or absence of implants. Only CoNS was implants-associated, especially for arthroplasty infection. Cefazolin alone is not enough for orthopedic surgery prophylaxis in settings with a high prevalence of methicillin-resistant staphylococci. | 25,146,607 | [
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The evolution of the four subunits of voltage-gated calcium channels: ancient roots, increasing complexity, and multiple losses. | The alpha subunits of voltage-gated calcium channels (Ca(v)s) are large transmembrane proteins responsible for crucial physiological processes in excitable cells. They are assisted by three auxiliary subunits that can modulate their electrical behavior. Little is known about the evolution and roles of the various subunits of Ca(v)s in nonbilaterian animals and in nonanimal lineages. For this reason, we mapped the phyletic distribution of the four channel subunits and reconstructed their phylogeny. Although alpha subunits have deep evolutionary roots as ancient as the split between plants and opistokonths, beta subunits appeared in the last common ancestor of animals and their close-relatives choanoflagellates, gamma subunits are a bilaterian novelty and alpha2/delta subunits appeared in the lineage of Placozoa, Cnidaria, and Bilateria. We note that gene losses were extremely common in the evolution of Ca(v)s, with noticeable losses in multiple clades of subfamilies and also of whole Ca(v) families. As in vertebrates, but not protostomes, Ca(v) channel genes duplicated in Cnidaria. We characterized by in situ hybridization the tissue distribution of alpha subunits in the sea anemone Nematostella vectensis, a nonbilaterian animal possessing all three Ca(v) subfamilies common to Bilateria. We find that some of the alpha subunit subtypes exhibit distinct spatiotemporal expression patterns. Further, all six sea anemone alpha subunit subtypes are conserved in stony corals, which separated from anemones 500 MA. This unexpected conservation together with the expression patterns strongly supports the notion that these subtypes carry unique functional roles. | 25,146,647 | [
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[Connexin-43 antibodies in intraoperative diagnosis of experimental poorly differentiated gliomas]. | Fluorescent diagnosis was first proposed in the early XX century and has been used in neurosurgery for about 15 years. The method relies on selective accumulation of strongly fluorescent protoporphyrin IX in tumor cells. Over the past years, the method of intraoperative fluorescence diagnosis has occupied its niche in many neurosurgical clinics around the world and is now used for fast intraoperative diagnosis in brain tumor surgery. However, the efficiency of fluorescent intraoperative diagnosis using 5-aminolevulinic acid is 80-90% and 58.8% for surgery of Grade III-IV and I-II gliomas, respectively. One of the methods to improve the efficiency of fluorescent diagnosis is to use vector systems for delivering fluorescent drugs into the tumor. This paper reports the results of an experimental study of systems for delivering fluorescent agents (protoporphyrin IX, Alexa 488, Alexa 660) using connexin-43 antibodies in rats with transplanted C6 glioma. | 25,146,651 | [
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Feline cutaneous lymphocytosis: case report and summary of the literature. | Feline cutaneous lymphocytosis is a rare disease characterized by proliferation of T and/or B lymphocytes in the dermis. Although some of the clinical and histopathologic findings of this condition can overlap with cutaneous lymphoma, it is important to distinguish these entities since their treatment and clinical outcomes vary greatly. This report presents a summary of the literature on feline cutaneous lymphocytosis and describes a case of this condition which showed some unique clinical features and was successfully controlled with oral glucocorticoids. | 25,146,663 | [
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Cell cycle-dependent O-GlcNAc modification of tobacco histones and their interaction with the tobacco lectin. | The Nicotiana tabacum agglutinin or Nictaba is a nucleocytoplasmic lectin that is expressed in tobacco after the plants have been exposed to jasmonate treatment or insect herbivory. Nictaba specifically recognizes GlcNAc residues. Recently, it was shown that Nictaba is interacting in vitro with the core histone proteins from calf thymus. Assuming that plant histones - similar to their animal counterparts - undergo O-GlcNAcylation, this interaction presumably occurs through binding of the lectin to the O-GlcNAc modification present on the histones. Hereupon, the question was raised whether this modification also occurs in plants and if it is cell cycle dependent. To this end, histones were purified from tobacco BY-2 suspension cells and the presence of O-GlcNAc modifications was checked. Concomitantly, O-GlcNAcylation of histone proteins was studied. Our data show that similar to animal histones plant histones are modified by O-GlcNAc in a cell cycle-dependent fashion. In addition, the interaction between Nictaba and tobacco histones was confirmed using lectin chromatography and far Western blot analysis. Collectively these findings suggest that Nictaba can act as a modulator of gene transcription through its interaction with core histones. | 25,146,688 | [
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Effective light absorption and absolute electron transport rates in the coral Pocillopora damicornis. | Pulse Amplitude Modulation (PAM) fluorometry has been widely used to estimate the relative photosynthetic efficiency of corals. However, both the optical properties of intact corals as well as past technical constrains to PAM fluorometers have prevented calculations of the electron turnover rate of PSII. We used a new Multi-colour PAM (MC-PAM) in parallel with light microsensors to determine for the first time the wavelength-specific effective absorption cross-section of PSII photochemistry, σII(λ), and thus PAM-based absolute electron transport rates of the coral photosymbiont Symbiodinium both in culture and in hospite in the coral Pocillopora damicornis. In both cases, σII of Symbiodinium was highest in the blue spectral region and showed a progressive decrease towards red wavelengths. Absolute values for σII at 440 nm were up to 1.5-times higher in culture than in hospite. Scalar irradiance within the living coral tissue was reduced by 20% in the blue when compared to the incident downwelling irradiance. Absolute electron transport rates of P. damicornis at 440 nm revealed a maximum PSII turnover rate of ca. 250 electrons PSII(-1) s(-1), consistent with one PSII turnover for every 4 photons absorbed by PSII; this likely reflects the limiting steps in electron transfer between PSII and PSI. Our results show that optical properties of the coral host strongly affect light use efficiency of Symbiodinium. Therefore, relative electron transport rates do not reflect the productivity rates (or indeed how the photosynthesis-light response is parameterised). Here we provide a non-invasive approach to estimate absolute electron transport rates in corals. | 25,146,689 | [
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Impact of Sod on the expression of stress-related genes in Listeria monocytogenes 4b G with/without paraquat treatment. | Listeria monocytogenes is a foodborne pathogen that causes listeriosis. Paraquat can generate reactive oxygen species (ROS) in cells, which results in oxidative stress. It was first shown that 1 mM of paraquat inhibited the growth rate of a superoxide dismutase (sod)-deletion mutant (∆sod) generated from L. monocytogenes 4b G but not in the wild-type, and induced the expression of other resistance genes (kat, fri, perR, sigB, and recA) as well as sod in the wild type. Interestingly, without paraquat treatment the expression of all the 5 genes were repressed in ∆sod compared to the wild type, while the expression of recA triggering SOS response, a global response to DNA damage, was increased in ∆sod in the presence of 1 mM paraquat. Taken together, these results suggest that SOD plays a central role in oxidant defense of L. monocytogenes 4b G, and SOS probably significantly impacts ∆sod survival under oxidative stress. | 25,146,690 | [
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Implantable defibrillators for secondary prevention of sudden cardiac death in cardiac surgery patients with perioperative ventricular arrhythmias. | Randomized studies of implantable cardioverter defibrillators (ICD) have excluded sudden cardiac death survivors who had revascularization before or after an arrhythmic event. To evaluate the role of ICD and the effects of clinical variables including degree of revascularization, we studied cardiac surgery patients who had an ICD implanted for sustained perioperative ventricular arrhythmias. The electronic database for Southern California Kaiser Foundation hospitals was searched for patients who had cardiac surgery between 1999 and 2005 and an ICD implanted within 3 months of surgery. One hundred sixty-four patients were identified; 93/164 had an ICD for sustained pre- or postoperative ventricular tachycardia or fibrillation requiring resuscitation. Records were reviewed for the following: presenting arrhythmia, ejection fraction, and degree of revascularization. The primary end point was total mortality (TM) and/or appropriate ICD therapy (ICD-T), and secondary end points are TM and ICD-T. During the mean follow up of 49 months, the primary endpoint of TM+ICD-T and individual end points of TM and ICD-T were observed in 52 (56%), 35 (38%), and 28 (30%) patients, respectively, with 55% of TM, and 23% of ICD-T occurring within 2 years of implant. In multivariate risk analysis, none of the following was associated with any of the end points: incomplete revascularization, presenting ventricular arrhythmia, and timing of arrhythmias. Our data supports the recent guidelines for ICD in this cohort of patients, as the presence of irreversible substrate and triggers of ventricular arrhythmias, cannot be reliably excluded even with complete revascularization. Further studies are needed to understand this complex group of patients. | 25,146,702 | [
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Addition of bortezomib to standard dose chop chemotherapy improves response and survival in relapsed mantle cell lymphoma. | The proteasome inhibitor, bortezomib, potentially increases cell sensitivity to chemotherapy. This study was performed to determine the overall response rate (ORR), overall survival (OS), progression-free survival (PFS) and toxicity of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) compared to CHOP + bortezomib chemotherapy in mantle cell lymphoma (MCL) patients at first relapse. Forty-six patients were randomly assigned to standard dose CHOP ± bortezomib 1·6 mg/m(2) given on a 21-d cycle for up to eight cycles of treatment. Median age was 71 years (CHOP arm) and 69 years (CHOP-bortezomib arm). Median Eastern Cooperative Oncology Group performance status was 1 (CHOP) and 0 (CHOP-bortezomib) with 65% and 52%, respectively, having a disease stage of IV. ORR was 47·8% (CHOP) and 82·6% (CHOP-bortezomib). Complete response rate was 21·7% (CHOP) vs. 34·8% (CHOP-bortezomib); partial response rate was 26·1% (CHOP) vs. 47·8% (CHOP-bortezomib). Median OS was 11·8 months (CHOP) and 35·6 months (CHOP-bortezomib) (P = 0·01, Hazard ratio [HR] 0·37 [95% confidence interval (CI) 0·16-0·83)] and there was a non-significant improvement in PFS: 8·1 months (CHOP) and 16·5 months (CHOP-bortezomib) [P = 0·12, HR 0·60 (95% CI 0·31-1·15)]. Severe (≥grade 3) sensory neuropathy was similar in both arms (4·3% CHOP vs. 6·5% CHOP-bortezomib). We conclude that the addition of bortezomib to CHOP chemotherapy for relapsed MCL significantly improves outcome with a manageable increase in toxicity. | 25,146,720 | [
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A mouse polyomavirus-encoded microRNA targets the cellular apoptosis pathway through Smad2 inhibition. | Some viruses and most eukaryotic cells have microRNAs that regulate the expression of many genes. Although many viral miRNAs have been identified, only a few have been included in in vivo functional studies. Here we show that a Py-encoded miRNA downregulates the expression of the pro-apoptotic factor Smad2, resulting in the suppression of the apoptosis pathway. To study the Py miRNA in an in vivo context, a miRNA-deficient mutant virus was created on the background of the LID virus strain which establishes a rapid and lethal infection in newborn mice. Apoptosis analysis on kidney tissues indicates that the pro-apoptotic pathway is targeted in the infected host as well. Suppression of apoptosis through targeting of Smad2 by the Py miRNA is expected to synergize with anti-apoptotic effects previously attributed to the polyoma tumor antigens in support of virus replication in the natural host. | 25,146,733 | [
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[Effects of postconditioning on autophagy of lung ischemic reperfusion injury in rats]. | To explore the effects of postconditioning on autophagy of lung injury in situ during lung ischemic reperfusion. Twenty-four male Sprague-Dawley rats were randomly divided into 3 groups of sham-operated (S), ischemic-reperfusion (I/R) and ischemic postconditioning (IpostC) (n = 8 each). All underwent left thoracotomy after anesthesia. In the S group, a line was only placed around left hilum but not fastened. In the I/R group, a line was fastened to block the blood flow of left lung for 30 min and then loosened for reperfusion for 120 min. In the IpostC group, after blocking the blood flow of left lung for 30 min, left hilum was fastened for 30 sec and loosened for 30 sec. Lung tissues were measured by Western blot. Histopathological changes of lung tissues were observed, lung injury scores calculated and autophagic vacuoles determined by electron microscope. The relative expression levels of mammalian target of rapamycin (mTOR) and phosphorylated mTOR (p-mTOR) in group I/R (0.40 ± 0.03, 0.33 ± 0.10) were not different with those of group S (0.37 ± 0.07, 0.31 ± 0.10) (both P > 0.05). However, both significantly increased in group IpostC (0.46 ± 0.09, 0.55 ± 0.07) (both P < 0.05). As compared with group S, the relative expression level of LC3-IIand lung injury score significantly increased in groups I/R and IpostC (0.53 ± 0.08, 0.38 ± 0.03 vs 0.25 ± 0.06; 15.79 ± 1.33, 11.67 ± 1.55 vs 5.58 ± 0.39) while obviously declined in group IpostC versus group I/R (all P < 0.05). In group I/R, neutrophil infiltration, interstitial edema, atelectasis and hyaline membrane formation were observed microscopically in lung tissues and the formation of autophagic vacuoles was evident under electron microscope. The changes of group IpostC were milder than those of group I/R. Ischemic postconditioning has protective effects on lung ischemic reperfusion injury by attenuating autophagy. It may be related with strengthening mTOR. | 25,146,749 | [
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Chemical composition and phytotoxic effects of essential oils obtained from Ailanthus altissima (Mill.) swingle cultivated in Tunisia. | Ailanthus altissima Mill. Swingle (Simaroubaceae), also known as tree of heaven, is used in the Chinese traditional medicine as a bitter aromatic drug for the treatment of colds and gastric diseases. In Tunisia, Ailanthus altissima is an exotic tree, which was introduced many years ago and used particularly as a street ornamental tree. Here, the essential oils of different plant parts of this tree, viz., roots, stems, leaves, flowers, and samaras (ripe fruits), were obtained by hydrodistillation. In total, 69 compounds, representing 91.0-97.2% of the whole oil composition, were identified in these oils by GC-FID and GC/MS analyses. The root essential oil was clearly distinguishable for its high content in aldehydes (hexadecanal (1); 22.6%), while those obtained from flowers and leaves were dominated by oxygenated sesquiterpenes (74.8 and 42.1%, resp.), with caryophyllene oxide (4) as the major component (42.5 and 22.7%, resp.). The samara oil was rich in the apocarotenoid derivative hexahydrofarnesyl acetone (6; 58.0%), and the oil obtained from stems was characterized by sesquiterpene hydrocarbons (54.1%), mainly β-caryophyllene (18.9%). Principal component and hierarchical cluster analyses separated the five essential oils into four groups, each characterized by the major oil constituents. Contact tests showed that the germination of lettuce seeds was totally inhibited by all the essential oils except of the samara oil at a dose of 1 mg/ml. The flower oil also showed a significant phytotoxic effect against lettuce germination at 0.04 and 0.4 mg/ml (-55.0 ± 3.5 and -85.0 ± 0.7%, resp.). Moreover, the root and shoot elongation was even more affected by the oils than germination. The inhibitory effect of the shoot and root elongation varied from -9.8 to -100% and from -38.6 to -100%, respectively. Total inhibition of the elongation (-100%) at 1 mg/ml was detected for all the oils, with the exception of the samara oil (-74.7 and -75.1% for roots and shoots, resp.). | 25,146,765 | [
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[Preoperative tests recommendations in adult patients for ambulatory surgery]. | Anesthetic assessment traditionally included a series of laboratory tests intended to detect undiagnosed diseases, and to ensure that the patient undergoes surgery following safety criteria. These tests, without a specific clinical indication, are expensive, of questionable diagnostic value and often useless. In the context of outpatient surgery, recent evidence suggests that patients of any age without significant comorbidity, ASA physical status gradei and grade ii, do not need additional preoperative tests routinely. The aim of the present recommendations is to determine the general indications in which these tests should be performed in ASA gradei and grade ii patients undergoing ambulatory surgery. | 25,146,773 | [
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Influence of post-transplant immunosuppressive therapy on gastrointestinal transit using biomagnetic method: a pilot study. | Immunosuppressive therapy after kidney transplant is necessary to prevent allograft rejection and it is the cause of several gastrointestinal (GI) disorders that have been scantily studied. This study was aimed at investigating the influence of triple immunosuppressive therapy on GI transit in renal transplant patients by employing a biomagnetic technique. Twenty-one renal transplant patients underwent triple therapy, which included either tacrolimus (TAC) or cyclosporin A (CsA) associated with prednisone and azathioprine. They were all evaluated, and fifteen other healthy individuals formed the control group. After a standardized meal, GI transit of magnetic markers was assessed using Alternating Current Biosusceptometry (ACB). Patients taking TAC had significantly accelerated gastric emptying and colonic arrival (p ≤ 0.001) when compared with those taking CsA and those in the control group. However, no differences were observed in small bowel transit among the groups studied. Overall, the inter-subject coefficients of variation for gastrointestinal transit parameters were higher for the TAC group and similar for the CsA and control groups. This study demonstrated that ACB is a suitable methodology when evaluating the influence of different immunosuppressive therapies on gastrointestinal transit after renal transplantation. Pronounced inter-individual variation was found in patients treated with tacrolimus, thus showing the prokinetic effect of this drug on GI motility. Studies of motility patterns in this population could be useful as complementary information toward determining the mechanisms and the relationship between motility and therapeutic doses. | 25,146,844 | [
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Decreased expression of HLA-DQ and HLA-DR on cells of the monocytic lineage in cystic fibrosis. | We studied HLA class II molecules on blood monocyte subsets, blood dendritic cells, sputum macrophages, and monocyte-derived macrophages at the protein (flow cytometry) and mRNA level (RT-PCR) in adult patients with cystic fibrosis (CF) and healthy control subjects as putative contributors to the CF phenotype. In healthy donors, we found a high average HLA-DQ expression of 4.35 mean specific fluorescence intensity units (ΔMnI) on classical blood monocytes. In F508del homozygous CF patients, the average ΔMnI was low (1.80). Patients were divided into two groups, in which 14 of these patients had HLA-DQ expression above 2 ΔMnI (average 3.25 ΔMnI, CF-DQ(group1)) and 36 below (average 1.24 ΔMnI, CF-DQ(group2)). Also, the CD16-positive monocyte subset and blood dendritic cells showed much lower levels of HLA-DQ for the CF-DQ(group2) patients compared with healthy controls. In macrophages from sputum and derived from monocytes, in vitro HLA-DQ expression was dramatically decreased to background levels in CF-DQ(group2). MHC class II transcripts were reduced in CF with a sevenfold decrease in HLA-DQβ1 for CF-DQ(group2) patients. Higher levels of the inflammation marker CRP were associated with low HLA-DQ protein expression, and in vitro treatment with the inflammatory molecule lipopolysaccharide reduced HLA-DQ expression. Interferon γ (IFNγ) could overcome this effect in healthy donor cells while, in CF, the IFNγ-induced activation was impaired. Our data demonstrate a pronounced reduction of HLA-DQ expression in CF, which is associated with inflammation and a reduced response to IFNγ. • CF patients show a reduced expression of MHCII molecules in monocytes and macrophages. • HLA-DQ and HLA-DR transcript levels are also reduced in CF patients. • CF patient C-reactive protein levels correlate with low HLA-DQ expression. • Reduced expression of MHC class II molecules appears to be linked to inflammation. • CF patients exhibit an impaired response to IFNgamma. | 25,146,850 | [
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Healthy Spaces in Meaningful Places: The Rural Church and Women's Health Promotion. | The influence of place on health is beginning to be addressed in health research. Current understanding of rural places, however, remains in a state of disequilibrium, balancing between geographic and sociocultural positions. This article illuminates the significance of place for rural women's experiences of health promotion in the rural church. This study used a novel approach to interpretive phenomenological methodology by including the photovoice method to elicit both individual and shared experiential meanings. Twenty-two participants took pictures, wrote in logbooks, and participated in individual and group interviews to share their experiences of health promotion in the rural church. The church as a place was realized through three broad discourses: (a) an intersection of physical and geographic environments, (b) a gateway to experiential attachment and personal meaning, and (c) a connection to shared culture and beliefs. It is also suggested that place may best be interpreted with an experiential lens as it exhibits lived and felt spaces. Data analysis suggests that place consists of both physical and experiential realities, in addition to being a resource of culture and meaning. Implications for rural women's health promotion include fostering a deeper recognition of place-shaped experiences of health. | 25,146,851 | [
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Comparison of cancer stem cell antigen expression by tumor cell lines and by tumor biopsies from dogs with melanoma and osteosarcoma. | Cancer stem cells (CSCs) represent a small subpopulation of tumor cells that play a critical role in initiating and sustaining tumor growth. However, we currently have an incomplete understanding of the expression patterns of CSC antigens in tumors of dogs, nor do we understand how expression of these antigens vary between tumor cell lines and tumor biopsy specimens. Therefore, we used flow cytometry and commonly reported CSC surface and intracellular markers to evaluate the phenotype and overall frequency of CSC subpopulations in tumor cell lines and primary tumor biopsy samples from dogs with melanoma and osteosarcoma. We found that cells expressing common CSC antigens were rare in tumor cell lines, with the exception of tumor cells expressing CD44 and CD90. In contrast, tumor cells expressing conventional CSC antigens such as CD133, CD34, CD44, CD24 and Oct3/4 were much more common in tumor biopsy samples. Notably, the frequency and types of putative CSC subpopulations were very similar in biopsy samples from dogs with either melanoma or osteosarcoma. Our results suggest that the tumor microenvironment significantly influences CSC subpopulations within tumors and that tumor cell lines may not accurately reflect the actual frequency or types of CSC subpopulations present in tumor tissues in vivo. | 25,146,881 | [
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Relationship between universal health outcome priorities and willingness to take medication for primary prevention of myocardial infarction. | To determine how well universal health outcome priorities represent individuals' preferences in specific clinical situations. Observational cohort study. Community. Community-dwelling adults aged 65 and older (N = 357). Participants used three tools assessing universal health outcome priorities related to two common trade-offs: quality versus quantity of life and future health versus present inconveniences and burdens of treatment. The tools' ability to identify participants who were unwilling to take a medication that reduced the risk of myocardial infarction but caused dizziness and fatigue was analyzed. There were consistent and significant associations between unwillingness to take the medication and prioritizing quality of life or future health for all three tools in the expected direction (P < .05). Despite these associations, the positive (PPV) and negative predictive values for the tools were generally modest (0.49-0.83). The tool with the most specific statements resembling the medication scenario had the best specificity (0.97) and PPV (0.83). Universal health outcome priorities only modestly identified older persons who would be unwilling to take a medication for primary prevention of myocardial infarction that causes adverse effects. Although tools that are the most general in their assessment of priorities have the benefit of being applicable across the widest range of scenarios, tools with greater specificity may be necessary to inform individual treatment decisions. | 25,146,885 | [
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Characteristics associated with physical activity among independently ambulant children and adolescents with unilateral cerebral palsy. | This study aimed to quantify the contribution of physical, personal and environmental characteristics to physical activity among independently ambulant children with unilateral cerebral palsy (CP). One-hundred and two children with unilateral CP (52 males, 50 females; 52 right hemiplegia; mean age 11y 3mo, range 8-17y [SD 2y 4mo]) classified at Gross Motor Function Classification System (GMFCS) levels I = 44 and II = 58 participated. Physical activity was measured over 4 days using ActiGraph accelerometers recording as activity counts. GMFCS, functional strength, 6-minute walk test (6MWT), mobility limitations (MobQues28), age, sex, Assessment of Life-Habits recreation domain, Participation and Environment Measure for Children and Youth (PEM-CY) and environmental characteristics were considered for selection in a linear regression model. These served as independent variables which were determined using a backwards selection procedure. Younger age, male sex, increased performance on the 6MWT, and increased participation in the home and community measured using the PEM-CY were significantly associated with activity counts (p<0.001). However, the model fit was somewhat weak (R(2) =0.32), indicating that much of the variation was unexplained. Older age and reduced community participation were associated with high inactivity (p<0.001). Physical activity interventions should primarily target adolescents and females. Walking endurance and participation in the home and community may represent modifiable characteristics to increase physical activity. | 25,146,888 | [
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Mannosylated lipoarabinomannan in serum as a biomarker candidate for subclinical bovine tuberculosis. | Early and unambiguous detection of bovine tuberculosis (bTB), a significant disease of cattle worldwide, is necessary to control the spread of infection to other animals and humans. Current testing strategies are laborious, time consuming and heavily reliant on host responses that do not distinguish bTB from other mycobacteria. We report the presence of a pathogen signature, liparabinomannan (LAM), as a potential biomarker for bTB infection. Fifty-five animals (uninfected [n = 33], bTb [n = 10] and exposed cases [n = 12]) from a well characterized bovine serum repository were screened for the presence of LAM using a commercially available ELISA. Analysis showed that LAM had a sensitivity of 100% and a specificity of 91.7% for bTB detection (bTB positive versus bTB exposed animals). LAM detection easily separated bTB infected animals from bTB exposed and negative controls. We propose that pathogen related markers, such as LAM, should be included with current testing strategies as a battery diagnostic for bTB. | 25,146,892 | [
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Platinum-free binary Co-Ni alloy counter electrodes for efficient dye-sensitized solar cells. | Dye-sensitized solar cells (DSSCs) have attracted growing interest because of their application in renewable energy technologies in developing modern low-carbon economies. However, the commercial application of DSSCs has been hindered by the high expenses of platinum (Pt) counter electrodes (CEs). Here we use Pt-free binary Co-Ni alloys synthesized by a mild hydrothermal strategy as CE materials in efficient DSSCs. As a result of the rapid charge transfer, good electrical conduction, and reasonable electrocatalysis, the power conversion efficiencies of Co-Ni-based DSSCs are higher than those of Pt-only CEs, and the fabrication expense is markedly reduced. The DSSCs based on a CoNi0.25 alloy CE displays an impressive power conversion efficiency of 8.39%, fast start-up, multiple start/stop cycling, and good stability under extended irradiation. | 25,146,894 | [
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Intermittent hypoxia preconditioning-induced epileptic tolerance by upregulation of monocarboxylate transporter 4 expression in rat hippocampal astrocytes. | Noxious stimuli applied at doses close to but below the threshold of cell injury induce adaptive responses that provide a defense against additional stress. Epileptic preconditioning protects neurons against status epilepticus and ischemia; however, it is not known if the converse is true. During hypoxia/ischemia (H/I), lactate released from astrocytes is taken up by neurons and is stored for energy, a process mediated by monocarboxylate transporter 4 (MCT4) in astroglia. The present study investigated whether H/I preconditioning can provide protection to neurons against epilepsy through upregulation of MCT4 expression in astrocytes in vitro and in vivo. An oxygen/glucose deprivation protocol was used in primary astrocyte cultures, while rats were subjected to an intermittent hypoxia preconditioning (IHP) paradigm followed by lithium-pilocarpine-induced epilepsy as well as lactate transportation inhibitor injection, with a subsequent evaluation of protein expression as well as behavior. H/I induced an upregulation of MCT4 expression, while an IHP time course of 5 days provided the greatest protection against epileptic seizures, which was most apparent by 3 days after IHP. However, lactate transport function disturbances can block the protective effect induced by IHP. These findings provide a potential basis for the clinical treatment of epilepsy. | 25,146,899 | [
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Inhibition of microbial adhesion to plastic surface and human buccal epithelial cells by Rhodomyrtus tomentosa leaf extract. | The adherence of oral pathogenic microorganisms to host tissues is the initial step for successful process of oral diseases. This study aimed to determine the effect of the Rhodomyrtus tomentosa leaf extract and rhodomyrtone, an antibacterial compound from R. tomentosa leaf, on adhesion of some oral pathogens to polystyrene plastic surface and human buccal epithelial cells. The minimum inhibitory concentration (MIC) was evaluated using broth microdilution method. The microbial adhesion to the plastic surface and buccal cells was determined using microtiter plate method and microscopy technique. The ethanol extract of leaf demonstrated antibacterial activity against oral microorganisms including Staphylococcus aureus ATCC 25923, Streptococcus mutans (clinical isolate), and Candida albicans ATCC 90028 with the MIC values of 31.25, 15.62, and 1000μg/ml, respectively. Rhodomyrtone displayed activity with the MIC values of 0.78 and 0.39μg/ml against S. aureus ATCC 25923 and S. mutans, respectively. The MIC value of the compound against C. albicans ATCC 90028 was more than 100μg/ml which was the highest test concentration. All pathogenic microorganisms treated with the extract and rhodomyrtone at their subinhibitory concentrations resulted in a decrease in their adherence ability to both plastic surface and buccal cells. It is suggested that R. tomentosa extract and rhodomyrtone may be useful in therapy or as prophylaxis in infections involving oral pathogens. | 25,146,902 | [
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Proton conductive watery channels constructed by Anderson polyanions and lanthanide coordination cations. | A 3D inorganic-organic hybrid proton conductor, [Sm(H2O)5(CO2CH2NH3)2][Al(OH)6Mo6O18]·10H2O (), has been synthesized by using coordination cations, [Sm(H2O)5(gly)2](3+) (gly = (-)CO2CH2NH3(+)), and polyanions, [Al(OH)6Mo6O18](3-) ([AlMo6]). The polyanions ([AlMo6]) and the coordination cations ([Sm(H2O)5(gly)2](3+)) stack to form a 3D supramolecular network structure containing 1D channels along the c axis by electrostatic force and H-bonding. Significantly, the 1D channels are water-filled with a high water content (both Sm coordinated and in lattice). Dynamic adsorption measurements were implemented at 1 atm, and 95% relative humidity (RH). The water adsorption amount (6.51 wt% at 25 °C and 5.68 wt% at 80 °C) consistent with the number of lattice water molecules of suggests that the water chains were retained at elevated temperatures (80 °C) under 95% RH. Alternating-current (AC) impedance measurements of reveal an outstanding conductivity for of 4.53 × 10(-3) S cm(-1) at 80 °C under 95% RH. The activation energy of calculated from the Arrhenius plots of the proton conductivity is 1.09 eV, which indicated that the protons transfer by a vehicle mechanism. | 25,146,912 | [
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Ovarian hyperstimulation syndrome and thrombotic events. | Ovarian hyperstimulation syndrome (OHSS) is one of the most important complications of ovarian stimulation with severe morbidity and is still a threat to every patient undergoing ovulation induction. This manuscript reviews the current evidence regarding the relationship between OHSS and thromboembolism in infertile patients undergoing ovarian stimulation published in the world literature. The PubMed Database was searched for publications on reported cases of OHSS and thromboembolic phenomenon published between 1965 and 2013. One hundred and forty cases of OHSS and thromboembolic phenomena were retrieved. The vascular accident had already occurred in the first cycle of treatment among 119 women (85%), at early stage of OHSS in 43% and late stage in 57% of cases. Venous thrombotic events were recorded mostly in unusual sites, jugular, and subclavian veins, with 69 and 38 thrombotic events, respectively. Coagulation status was found at 86 of the 140 cases (61%). Fifty-three of the pregnant patients (68%) delivered singleton births and 47% had preterm deliveries, and termination of pregnancy was indicated in 11 cases (14%). The most serious complication associated with OHSS is thrombotic phenomena as shown in the present review of 140 cases, world data, on both arterial and venous side. Thromboprophylaxis should be initiated in patients with thrombophilia and who develop moderate-to-severe OHSS. | 25,146,913 | [
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Real-time imaging of endothelial cell-cell junctions during neutrophil transmigration under physiological flow. | During inflammation, leukocytes leave the circulation and cross the endothelium to fight invading pathogens in underlying tissues. This process is known as leukocyte transendothelial migration. Two routes for leukocytes to cross the endothelial monolayer have been described: the paracellular route, i.e., through the cell-cell junctions and the transcellular route, i.e., through the endothelial cell body. However, it has been technically difficult to discriminate between the para- and transcellular route. We developed a simple in vitro assay to study the distribution of endogenous VE-cadherin and PECAM-1 during neutrophil transendothelial migration under physiological flow conditions. Prior to neutrophil perfusion, endothelial cells were briefly treated with fluorescently-labeled antibodies against VE-cadherin and PECAM-1. These antibodies did not interfere with the function of both proteins, as was determined by electrical cell-substrate impedance sensing and FRAP measurements. Using this assay, we were able to follow the distribution of endogenous VE-cadherin and PECAM-1 during transendothelial migration under flow conditions and discriminate between the para- and transcellular migration routes of the leukocytes across the endothelium. | 25,146,919 | [
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HIV-1 Tat C modulates NOX2 and NOX4 expressions through miR-17 in a human microglial cell line. | HIV-1 invades CNS in the early course of infection, which can lead to the cascade of neuroinflammation. NADPH oxidases (NOXs) are the major producers of reactive oxygen species (ROS), which play important roles during pathogenic insults. The molecular mechanism of ROS generation via microRNA-mediated pathway in human microglial cells in response to HIV-1 Tat protein has been demonstrated in this study. Over-expression and knockdown of microRNAs, luciferase reporter assay, and site-directed mutagenesis are main molecular techniques used in this study. A significant reduction in miR-17 levels and increased NOX2, NOX4 expression levels along with ROS production were observed in human microglial cells upon HIV-1 Tat C exposure. The validation of NOX2 and NOX4 as direct targets of miR-17 was done by luciferase reporter assay. The over-expression and knockdown of miR-17 in human microglial cells showed the direct role of miR-17 in regulation of NOX2, NOX4 expression and intracellular ROS generation. We demonstrated the regulatory role of cellular miR-17 in ROS generation through over-expression and knockdown of miR-17 in human microglial cells exposed to HIV-1 Tat C protein. Activated microglial cells mediated neuroinflammatory events are observed in HIV-associated neurological disorders. The reduction in miR-17 levels was observed in microglial cells exposed to HIV-1 Tat C protein. miR-17 regulated the expression of NOX2 and NOX4, which in turn regulated the reactive oxygen species (ROS) production in microglial cells. Increased ROS production led to the activation of microglial cells and increased cytokine production. This study thus demonstrated a novel miR-17-mediated regulatory pathway of ROS production in microglial cells. HMC3 = human microglia clone 3 cell lines. | 25,146,963 | [
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Prevalence and Risk Factors for Overweight and Obesity among HIV-Infected Adults in Dar es Salaam, Tanzania. | Overweight and obesity are increasingly prevalent among HIV-infected populations. We describe their prevalence and associated risk factors among HIV-infected adults in Dar es Salaam, Tanzania. A cross-sectional study was conducted to determine the proportion of patients who were overweight or obese at enrollment to care and treatment centres from 2004 to 2011. Multivariate relative risk regression models were fit to identify risk factors. A total of 53 825 patients were included in the analysis. In all, 16% of women and 8% of men were overweight, while 7% and 2% were obese, respectively. In multivariate analyses, older age, higher CD4 count, higher hemoglobin levels, female sex, and being married were associated with obesity and overweight. World Health Organization HIV disease stage, tuberculosis history, and previous antiretroviral therapy were inversely associated with obesity and overweight. Overweight and obesity were highly prevalent among HIV-infected patients. Screening for overweight and obesity and focused interventions should be integrated into HIV care. | 25,146,972 | [
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Prognostic value of multifocal electroretinography and optical coherence tomography in eyes undergoing panretinal photocoagulation for diabetic retinopathy. | To investigate the prognostic utility on visual acuity of multifocal electroretinography (mfERG) and optical coherence tomography (OCT) in diabetic eyes receiving panretinal photocoagulation (PRP). Patients with severe nonproliferative diabetic retinopathy (NPDR) or early proliferative diabetic retinopathy (PDR) who needed PRP were included in this study. The mfERG and OCT data were recorded before PRP, and the final best-corrected visual acuity (BCVA) was recorded at 6 months after PRP. The correlation between pre-PRP data and post-PRP BCVA was analyzed using Pearson's correlation analysis and multivariate linear regression analysis. Among the 42 eyes included, 31 eyes (73.8%) had improvement or remained stable in visual acuity, and 11 eyes (26.2%) had deterioration in BCVA. The final BCVA was significantly correlated with the amplitude and latency of mfERG in all nine sectors, and the amplitude had a stronger correlation than latency. The foveal ellipsoid zone of the photoreceptors and external limiting membrane (ELM) status, as well as the retinal thickness in most sectors, were also correlated with the final BCVA. In a multivariate linear regression model, age, pre-PRP BCVA, amplitude of mfERG in the central sector, and foveal ellipsoid zone status were significantly correlated with the final BCVA. The retinal thickness was correlated with the amplitude or latency of mfERG in some sectors, and the correlation was tighter in temporal and inferior sectors. A lower amplitude of mfERG and disrupted foveal ellipsoid zone status were significantly correlated with a worse visual prognosis in diabetic eyes after PRP. | 25,146,984 | [
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High-resolution imaging of photoreceptors in macular microholes. | To assess photoreceptor structure in macular microholes by using adaptive optics scanning laser ophthalmoscopy (AO-SLO) and spectral-domain optical coherence tomography (SD-OCT) and compare with visual acuity. Fourteen eyes from 12 patients with macular microholes underwent a full ophthalmologic examination and imaging with a fundus camera, SD-OCT, and an original prototype AO-SLO system at each visit. All eyes had a cone outer segment tip line disruption and a normal retinal pigment epithelium line on SD-OCT images. Adaptive optics scanning laser ophthalmoscopy revealed foveal cone disruption (13 eyes, round or oval; 1 eye, T-shaped) in all eyes. Cone disruption area (mean = 14,805 ± 9120 μm(2); range, 3495-35,901 μm(2)) positively correlated with logMAR visual acuity at the first visit (P = 0.015, rs = 0.679). During the follow-up period, cone disruption area increased in two eyes, was stable in seven eyes, and decreased in five eyes. At the last visit, cone disruption area (mean = 8717 ± 7432 μm(2); range, 0-25,746 μm(2)) also positively correlated with logMAR visual acuity (P = 0.035, rs = 0.610). In one patient with bilateral microholes and no apparent vitreous traction, lesion size gradually increased. Cone disruption area decreased and visual acuity improved following oral prednisone therapy. Cone disruption occurs in eyes with macular microholes and a larger cone disruption area translates into a poorer visual acuity. Macular microholes, which are commonly observed as foveal cone inner and outer segment disruptions, may occur in eyes with or without vitreofoveal traction. | 25,146,990 | [
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Identifying functional co-activation patterns in neuroimaging studies via poisson graphical models. | Studying the interactions between different brain regions is essential to achieve a more complete understanding of brain function. In this article, we focus on identifying functional co-activation patterns and undirected functional networks in neuroimaging studies. We build a functional brain network, using a sparse covariance matrix, with elements representing associations between region-level peak activations. We adopt a penalized likelihood approach to impose sparsity on the covariance matrix based on an extended multivariate Poisson model. We obtain penalized maximum likelihood estimates via the expectation-maximization (EM) algorithm and optimize an associated tuning parameter by maximizing the predictive log-likelihood. Permutation tests on the brain co-activation patterns provide region pair and network-level inference. Simulations suggest that the proposed approach has minimal biases and provides a coverage rate close to 95% of covariance estimations. Conducting a meta-analysis of 162 functional neuroimaging studies on emotions, our model identifies a functional network that consists of connected regions within the basal ganglia, limbic system, and other emotion-related brain regions. We characterize this network through statistical inference on region-pair connections as well as by graph measures. | 25,147,001 | [
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Transplantation of tail skin to study allogeneic CD4 T cell responses in mice. | The study of T cell responses and their consequences during allo-antigen recognition requires a model that enables one to distinguish between donor and host T cells, to easily monitor the graft, and to adapt the system in order to answer different immunological questions. Medawar and colleagues established allogeneic tail-skin transplantation in mice in 1955. Since then, the skin transplantation model has been continuously modified and adapted to answer specific questions. The use of tail-skin renders this model easy to score for graft rejection, requires neither extensive preparation nor deep anesthesia, is applicable to animals of all genetic background, discourages ischemic necrosis, and permits chemical and biological intervention. In general, both CD4(+) and CD8(+) allogeneic T cells are responsible for the rejection of allografts since they recognize mismatched major histocompatibility antigens from different mouse strains. Several models have been described for activating allogeneic T cells in skin-transplanted mice. The identification of major histocompatibility complex (MHC) class I and II molecules in different mouse strains including C57BL/6 mice was an important step toward understanding and studying T cell-mediated alloresponses. In the tail-skin transplantation model described here, a three-point mutation (I-A(bm12)) in the antigen-presenting groove of the MHC-class II (I-A(b)) molecule is sufficient to induce strong allogeneic CD4(+) T cell activation in C57BL/6 mice. Skin grafts from I-A(bm12) mice on C57BL/6 mice are rejected within 12-15 days, while syngeneic grafts are accepted for up to 100 days. The absence of T cells (CD3(-/-) and Rag2(-/-) mice) allows skin graft acceptance up to 100 days, which can be overcome by transferring 2 x 10(4) wild type or transgenic T cells. Adoptively transferred T cells proliferate and produce IFN-γ in I-A(bm12)-transplanted Rag2(-/-) mice. | 25,147,005 | [
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Balneohydrotherapy in the treatment of chronic venous insufficiency. | Physical therapy has not been evaluated much for the treatment of chronic venous insufficiency before. The question is whether balneohydrotherapy and usual care combined is superior to usual care alone. In a randomized trial comparing spa therapy versus waiting list patients were treated on an out-patient basis in a private spa center. Patients had to be between 18 and 80 years old, with chronic venous insufficiency (stage 3 or 4 according to the CEAP classification). The balneohydrotherapy group received 18 days of treatment in Aix-Les-Bains spa center continuing their usual care. The control group continued their usual care as well during the study. The balneohydrotherapy program consisted of Kneipp therapy (10 minutes), walking 10 minutes in a special mineral water pool with underwater jets at 23 °C, massage and bathing in a mineral water tub at 34 °C. The main outcome criterion was the number of patients with 20 % self assessed improvement on the Chronic Venous Insufficiency Questionnaire at three months after therapy. 192 patients were assessed for eligibility, 99 were randomized 5 retired drew back their consent and were not included in the intention to treat analysis. None were lost to follow up. After three months 32 (66 %) patients improved in the balneohydrotherapy group and 13 (28 %) in the control group. The difference between groups was significant (odd ratio 5.08 [1.94 - 13.55], relative risk reduction 2.33 [1.42 - 3.84]).There were no serious side effects. Balneohydrotherapy seems to improve quality of life of patients with chronic venous insufficiency. | 25,147,013 | [
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Lack of body positional effects on paresthesias when stimulating the dorsal root ganglion (DRG) in the treatment of chronic pain. | One prominent side effect from neurostimulation techniques, and in particular spinal cord stimulation (SCS), is the change in intensity of stimulation when moving from an upright (vertical) to a recumbent or supine (horizontal) position and vice versa. It is well understood that the effects of gravity combined with highly conductive cerebrospinal fluid provide the mechanism by which changes in body position can alter the intensity of stimulation-induced paresthesias. While these effects are well established for leads that are placed within the more medial aspects of the spinal canal, little is known about these potential effects in leads placed in the lateral epidural space and in particular within the neural foramina near the dorsal root ganglion (DRG). We prospectively validated a newly developed paresthesia intensity rating scale and compared perceived paresthesia intensities when subjects assumed upright vs. supine bodily positions during neuromodulation of the DRG. On average, the correlation coefficient between stimulation intensity (pulse amplitude) and perceived paresthesia intensity was 0.83, demonstrating a strong linear relationship. No significant differences in paresthesia intensities were reported within subjects when moving from an upright (4.5 ± 0.14) to supine position 4.5 (± 0.12) (p > 0.05). This effect persisted through 12 months following implant. Neuromodulation of the DRG produces paresthesias that remain consistent across body positions, suggesting that this paradigm may be less susceptible to positional effects than dorsal column stimulation. | 25,147,020 | [
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Basic helix-loop-helix transcription factor BcbHLHpol functions as a positive regulator of pollen development in non-heading Chinese cabbage. | Cytoplasmic male sterility (CMS) is a common trait in higher plants, and several transcription factors regulate pollen development. Previously, we obtained a basic helix-loop-helix transcription factor, BcbHLHpol, via suppression subtractive hybridization in non-heading Chinese cabbage. However, the regulatory function of BcbHLHpol during anther and pollen development remains unclear. In this study, BcbHLHpol was cloned, and its tissue-specific expression profile was analyzed. The results of real-time polymerase chain reaction showed that BcbHLHpol was highly expressed in maintainer buds and that the transcripts of BcbHLHpol significantly decreased in the buds of pol CMS. A virus-induced gene silencing vector that targets BcbHLHpol was constructed and transformed into Brassica campestris plants to further explore the function of BcbHLHpol. Male sterility and short stature were observed in BcbHLHpol-silenced plants. The degradation of tapetal cells was inhibited in BcbHLHpol-silenced plants, and nutrients were insufficiently supplied to the microspore. These phenomena resulted in pollen abortion. This result indicates that BcbHLHpol functions as a positive regulator in pollen development. Yeast two-hybrid and bimolecular fluorescence complementation assays revealed that BcbHLHpol interacted with BcSKP1 in the nucleus. This finding suggests that BcbHLHpol and BcSKP1 are positive coordinating regulators of pollen development. Quantitative real-time PCR indicated that BcbHLHpol and BcSKP1 can be induced at low temperatures. Thus, we propose that BcbHLHpol is necessary for meiosis. This study provides insights into the regulatory functions of the BcbHLHpol network during anther development. | 25,147,023 | [
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Quantum non-Markovianity: characterization, quantification and detection. | We present a comprehensive and up-to-date review of the concept of quantum non-Markovianity, a central theme in the theory of open quantum systems. We introduce the concept of a quantum Markovian process as a generalization of the classical definition of Markovianity via the so-called divisibility property and relate this notion to the intuitive idea that links non-Markovianity with the persistence of memory effects. A detailed comparison with other definitions presented in the literature is provided. We then discuss several existing proposals to quantify the degree of non-Markovianity of quantum dynamics and to witness non-Markovian behavior, the latter providing sufficient conditions to detect deviations from strict Markovianity. Finally, we conclude by enumerating some timely open problems in the field and provide an outlook on possible research directions. | 25,147,025 | [
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The oral microbiome diversity and its relation to human diseases. | As one of the most clinically relevant human habitats, the human mouth is colonized by a set of microorganisms, including bacteria, archaea, fungi, and viruses. Increasing evidence has supported that these microbiota contribute to the two commonest oral diseases of man (dental caries and periodontal diseases), presenting significant risk factors to human health conditions, such as tumor, diabetes mellitus, cardiovascular diseases, bacteremia, preterm birth, and low birth weight in infants. It is widely accepted that oral microorganisms cause diseases mainly by a synergistic or cooperative way, and the interspecies interactions within the oral community play a crucial role in determining whether oral microbiota elicit diseases or not. Since a comprehensive understanding of the complex interspecies interactions within a community needs the knowledge of its endogenous residents, a plenty of research have been carried out to explore the oral microbial diversity. In this review, we focus on the recent progress in this field, including the oral microbiome composition and its association with human diseases. | 25,147,055 | [
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Structure-activity relationship, biological, and pharmacological characterization of the proline sulfonamide ACT-462206: a potent, brain-penetrant dual orexin 1/orexin 2 receptor antagonist. | The orexin system consists of two G-protein-coupled receptors, the orexin 1 and orexin 2 receptors, widely expressed in diverse regions of the brain, and two peptide agonists, orexin A and orexin B, which are produced in a small assembly of neurons in the lateral hypothalamus. The orexin system plays an important role in the maintenance of wakefulness. Several compounds (almorexant, SB-649868, suvorexant) have been in advanced clinical trials for treating primary insomnia. ACT-462206 is a new, potent, and selective dual orexin receptor antagonist (DORA) that inhibits the stimulating effects of the orexin peptides at both the orexin 1 and 2 receptors. It decreases wakefulness and increases non-rapid eye movement (non-REM) and REM sleep while maintaining natural sleep architectures in rat and dog electroencephalography/electromyography (EEG/EMG) experiments. ACT-462206 shows anxiolytic-like properties in rats without affecting cognition and motor function. It is therefore a potential candidate for the treatment of insomnia. | 25,147,058 | [
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Omega-3 fatty acid therapy dose-dependently and significantly decreased triglycerides and improved flow-mediated dilation, however, did not significantly improve insulin sensitivity in patients with hypertriglyceridemia. | Experimental studies demonstrate that higher intake of omega-3 fatty acids (n-3 FA) improves insulin sensitivity, however, we reported that n-3 FA 2g therapy, most commonly used dosage did not significantly improve insulin sensitivity despite reducing triglycerides by 21% in patients. Therefore, we investigated the effects of different dosages of n-3 FA in patients with hypertriglyceridemia. This was a randomized, single-blind, placebo-controlled, parallel study. Age, sex, and body mass index were matched among groups. All patients were recommended to maintain a low fat diet. Forty-four patients (about 18 had metabolic syndrome/type 2 diabetes mellitus) in each group were given placebo, n-3 FA 1 (O1), 2 (O2), or 4 g (O4), respectively daily for 2 months. n-3 FA therapy dose-dependently and significantly decreased triglycerides and triglycerides/HDL cholesterol and improved flow-mediated dilation, compared with placebo (by ANOVA). However, each n-3 FA therapy did not significantly decrease high-sensitivity C-reactive protein and fibrinogen, compared with placebo. O1 significantly increased insulin levels and decreased insulin sensitivity (determined by QUICKI) and O2 significantly decreased plasma adiponectin levels relative to baseline measurements. Of note, when compared with placebo, each n-3 FA therapy did not significantly change insulin, glucose, adiponectin, glycated hemoglobin levels and insulin sensitivity (by ANOVA). We observed similar results in a subgroup of patients with the metabolic syndrome. n-3 FA therapy dose-dependently and significantly decreased triglycerides and improved flow-mediated dilation. Nonetheless, n-3 FA therapy did not significantly improve acute-phase reactants and insulin sensitivity in patients with hypertriglyceridemia, regardless of dosages. | 25,147,070 | [
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Challenge of representing entropy at different levels of resolution in molecular simulation. | The role of entropic contributions in processes involving biomolecules is illustrated using the process of vaporization or condensation of the solvents water and methanol and the process of polypeptide folding in solution using molecular models at different levels of resolution: subatomic, atomic, supra-atomic, and supramolecular. For the folding process, a β-hexapeptide that adopts, as inferred from NMR experiments, both a right-handed 2.710/12-helical fold and a left-handed 314-helical fold in methanol, is used to illustrate the challenge of modeling thermodynamically driven processes at different levels of resolution. | 25,147,102 | [
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A theta-band EEG based index for early diagnosis of Alzheimer's disease. | Despite recent advances, early diagnosis of Alzheimer's disease (AD) from electroencephalography (EEG) remains a difficult task. In this paper, we offer an added measure through which such early diagnoses can potentially be improved. One feature that has been used for discriminative classification is changes in EEG synchrony. So far, only the decrease of synchrony in the higher frequencies has been deeply analyzed. In this paper, we investigate the increase of synchrony found in narrow frequency ranges within the θ band. This particular increase of synchrony is used with the well-known decrease of synchrony in the α band to enhance detectable differences between AD patients and healthy subjects. We propose a new synchrony ratio that maximizes the differences between two populations. The ratio is tested using two different data sets, one of them containing mild cognitive impairment patients and healthy subjects, and another one, containing mild AD patients and healthy subjects. The results presented in this paper show that classification rate is improved, and the statistical difference between AD patients and healthy subjects is increased using the proposed ratio. | 25,147,104 | [
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The pathophysiology of axonal transport in Alzheimer's disease. | Neurons communicate in the nervous system by carrying out information along the length of their axons to finally transmit it at the synapse. Proper function of axons and axon terminals relies on the transport of proteins, organelles, vesicles, and other elements from the site of synthesis in the cell body. Conversely, neurotrophins secreted from axonal targets and other components at nerve terminals need to travel toward the cell body for clearance. Molecular motors, namely kinesins and dyneins, are responsible for the movement of these elements along cytoskeletal tracks. Given the challenging structure of neurons, axonal transport machinery plays a crucial role in maintaining neuronal viability and function, allowing the proper neurotransmitter release at the presynaptic ending. On this basis, failure of axonal transport has been proposed as a key player in the development and/or progression of neurodegenerative disorders such as Alzheimer's disease (AD). Increasing evidence suggests that amyloid-β peptide, a hallmark of AD, may disrupt axonal transport and in so doing, contribute to AD pathophysiology. Here we discuss the molecular mechanisms of axonal transport with specific emphasis on the possible relationship between defective axonal transport and AD. | 25,147,115 | [
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Acetylcholinesterase biosensor based on multi-walled carbon nanotubes-SnO₂-chitosan nanocomposite. | A sensitive amperometric acetylcholinesterase (AChE) biosensor was developed based on the nanocomposite of multi-walled carbon nanotubes (MWCNTs), tin oxide (SnO2) nanoparticles and chitosan (CHIT). Acetylcholinesterase (AChE) and Nafion were immobilized onto the nanocomposite film to prepare AChE biosensor for pesticide residues detection. The morphologies and electrochemistry properties of the surface modification were investigated using cyclic voltammetry, differential pulse voltammetry, and scanning electron microscopy, respectively. Compared with individual MWCNTs-CHIT, SnO2-CHIT and bare gold electrode, this nanocomposite showed the most obvious electrochemical signal in the presence of [Fe(CN)6](3-/4-) as a redox couple. Incorporating MWCNTs and SnO2 into 0.2% CHIT solution can promote electron transfer, enhance the electrochemical response, and improve the microarchitecture of the electrode surface. All variables involved in the preparation process and analytical performance of the biosensor were optimized. Under optimized conditions, the AChE biosensor exhibited a wide linear range from 0.05 to 1.0 × 10(5 )μg/L and with a detection limit for chlorpyrifos was 0.05 μg/L. Based on the inhibition of pesticides on the AChE activity, using chlorpyrifos as model pesticide, the proposed biosensor exhibited a wide range, low detection limit, good reproducibility, and high stability. Using cabbages, lettuces, leeks, and pakchois as model samples, acceptable recovery of 98.7-105.2% was obtained. The proposed method was proven to be a feasible quantitative method for chlorpyrifos analysis, which may open a new door ultrasensitive detection of chlorpyrifos residues in vegetables and fruits. | 25,147,124 | [
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Water with food intake does not influence caloric intake after gastric bypass (GBP): a cross-over trial. | Bariatric patients seeking information meet very different recommendations on postoperative diet and eating behaviour. A reason for variability may be lack of hard evidence. A national survey on current dietary advice was conducted to serve as background for the present study on how drinking during a meal influenced caloric consumption. A standardised questionnaire was sent to all units in the Scandinavian Obesity surgery registry (SOReg) in order to obtain information regarding current diet advice after gastric bypass. Twenty-eight patients, 14 in each group, were studied either 2 months or 1 year after a standard gastric bypass (GBP). A standardised lunch was served on two separate days with or without water in randomised order. Meal and water weights were measured before and after. Hunger/satiety scores were obtained using visual analogue scales. Response rate for surgeons was low, for dieticians 75 %. No clear consensus for liquid intake during meals was found; few surgeons advised patients whether or not to drink with meals. All patients ate to full satiety. Two months post-GBP, 7/14 patients consumed more solid food when allowed drinking water; the increase in caloric consumption was not significant. One year post-GBP, 5/14 patients consumed more solid food when allowed drinking water, the difference not reaching statistical significance. Our study does not indicate that patients should refrain from drinking during meals the first year after a GBP, at least not from a caloric intake point of view. | 25,147,125 | [
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Anonymization of DICOM electronic medical records for radiation therapy. | Electronic medical records (EMR) and treatment plans are used in research on patient outcomes and radiation effects. In many situations researchers must remove protected health information (PHI) from EMRs. The literature contains several studies describing the anonymization of generic Digital Imaging and Communication in Medicine (DICOM) files and DICOM image sets but no publications were found that discuss the anonymization of DICOM radiation therapy plans, a key component of an EMR in a cancer clinic. In addition to this we were unable to find a commercial software tool that met the minimum requirements for anonymization and preservation of data integrity for radiation therapy research. The purpose of this study was to develop a prototype software code to meet the requirements for the anonymization of radiation therapy treatment plans and to develop a way to validate that code and demonstrate that it properly anonymized treatment plans and preserved data integrity. We extended an open-source code to process all relevant PHI and to allow for the automatic anonymization of multiple EMRs. The prototype code successfully anonymized multiple treatment plans in less than 1min/patient. We also tested commercial optical character recognition (OCR) algorithms for the detection of burned-in text on the images, but they were unable to reliably recognize text. In addition, we developed and tested an image filtering algorithm that allowed us to isolate and redact alpha-numeric text from a test radiograph. Validation tests verified that PHI was anonymized and data integrity, such as the relationship between DICOM unique identifiers (UID) was preserved. | 25,147,130 | [
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An in silico case study of idiopathic dilated cardiomyopathy via a multi-scale model of the cardiovascular system. | Mathematical modelling has been used to comprehend the pathology and the assessment of different treatment techniques such as heart failure and left ventricular assist device therapy in the cardiovascular field. In this study, an in-silico model of the heart is developed to understand the effects of idiopathic dilated cardiomyopathy (IDC) as a pathological scenario, with mechanisms described at the cellular, protein and organ levels. This model includes the right and left atria and ventricles, as well as the systemic and pulmonary arteries and veins. First, a multi-scale model of the whole heart is simulated for healthy conditions. Subsequently, the model is modified at its microscopic and macroscopic spatial scale to obtain the characteristics of IDC. The extracellular calcium concentration, the binding affinity of calcium binding proteins and the maximum and minimum elastances have been identified as key parameters across all relevant scales. The modified parameters cause a change in (a) intracellular calcium concentration characterising cellular properties, such as calcium channel currents or the action potential, (b) the proteins being involved in the sliding filament mechanism and the proportion of the attached crossbridges at the protein level, as well as (c) the pressure and volume values at the organ level. This model allows to obtain insight and understanding of the effects of the treatment techniques, from a physiological and biological point of view. | 25,147,131 | [
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Synthesis and anticancer activity of (E)-2-benzothiazole hydrazones. | Benzothiazole hydrazones have been synthesized and evaluated for their in vitro antiproliferative activity against three human cancer cell lines: HL-60 (leukemia), MDAMB-435 (breast) and HCT-8 (colon). The good cytotoxicity for the three cancer cell lines and theoretical profile of compounds 3o and 3p pointed them as promising lead molecules for anticancer drug design. | 25,147,145 | [
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Sulfamates of methyl triterpenoates are effective and competitive inhibitors of carbonic anhydrase II. | Carbonic anhydrase II, belonging to one of the most important enzyme groups of the human body, is a well-studied isozyme from the family of the carbonic anhydrases. Since it is involved in several physiological processes, it has been a pharmaceutical target for many years. In this study we synthesized a number of sulfamates derived from pentacyclic methyl triterpenoates, and we demonstrate their potential as carbonic anhydrase II inhibitors using the well-established photometric 4-nitrophenyl acetate assay. Inhibition constants, as an indicator of their inhibition strength, were in the micromolar range; one compound (10, methyl (3β) 3-(aminosulfonyloxy)-oleanoate) showed a Ki value as low as 0.3 μM. This Ki value is comparable to that of acetazolamide which is a potent carbonic anhydrase inhibitor and a drug for the treatment of glaucoma. | 25,147,151 | [
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Kaempferol, a potential cytostatic and cure for inflammatory disorders. | Kaempferol (3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) is a flavonoid found in many edible plants (e.g., tea, broccoli, cabbage, kale, beans, endive, leek, tomato, strawberries, and grapes) and in plants or botanical products commonly used in traditional medicine (e.g., Ginkgo biloba, Tilia spp, Equisetum spp, Moringa oleifera, Sophora japonica and propolis). Its anti-oxidant/anti-inflammatory effects have been demonstrated in various disease models, including those for encephalomyelitis, diabetes, asthma, and carcinogenesis. Moreover, kaempferol act as a scavenger of free radicals and superoxide radicals as well as preserve the activity of various anti-oxidant enzymes such as catalase, glutathione peroxidase, and glutathione-S-transferase. The anticancer effect of this flavonoid is mediated through different modes of action, including anti-proliferation, apoptosis induction, cell-cycle arrest, generation of reactive oxygen species (ROS), and anti-metastasis/anti-angiogenesis activities. In addition, kaempferol was found to exhibit its anticancer activity through the modulation of multiple molecular targets including p53 and STAT3, through the activation of caspases, and through the generation of ROS. The anti-tumor effects of kaempferol have also been investigated in tumor-bearing mice. The combination of kaempferol and conventional chemotherapeutic drugs produces a greater therapeutic effect than the latter, as well as reduces the toxicity of the latter. In this review, we summarize the anti-oxidant/anti-inflammatory and anticancer effects of kaempferol with a focus on its molecular targets and the possible use of this flavonoid for the treatment of inflammatory diseases and cancer. | 25,147,152 | [
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Off-label uses of alvimopan and methylnaltrexone. | Off-label uses of the peripheral μ-opioid receptor antagonists alvimopan and methylnaltrexone are reviewed. Alvimopan is approved by the Food and Drug Administration (FDA) for postoperative ileus after surgeries that include partial bowel resection with primary anastomosis, while methylnaltrexone is approved for the treatment of opioid-induced constipation (OIC) in patients with advanced illness who are receiving palliative care. Literature describing the off-label use of alvimopan in the treatment of OIC and of methylnaltrexone in postoperative ileus was reviewed and included retrospective studies and prospective Phase II-IV trials. Randomized controlled trials did not demonstrate consistent benefit of alvimopan in OIC nor of methylnaltrexone in postoperative ileus. A greater proportion of patients receiving alvimopan for OIC experienced severe adverse cardiovascular events, leading to a risk evaluation and mitigation strategy and discontinuation of its study in this condition. Data are limited and unreplicated for the off-label use of alvimopan for postoperative ileus in patients undergoing abdominal hysterectomy. Individual studies suggest benefit with methylnaltrexone for OIC in unlabeled populations, including patients with non-cancer-related pain, opioid dependence, opioid sedation, and opioid use after orthopedic surgery; however, confirmatory evaluations have not been performed. Trials of alvimopan in the FDA-approved use of methylnaltrexone (OIC) indicate potentially serious cardiovascular safety concerns and conflicting findings of efficacy. Similarly, trials of methylnaltrexone in the FDA-approved use of alvimopan (postoperative ileus) consistently showed no benefit. Evaluations of both drugs in their labeled conditions in populations not endorsed in their product labeling have been limited and largely unreplicated. | 25,147,168 | [
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Stability of ertapenem 100 mg/mL in polypropylene syringes stored at 25, 4, and -20 °C. | The stability of ertapenem solution in syringes at room, refrigerator, and freezer temperatures was determined to establish options for extended storage. Six replicate solutions of ertapenem (100 mg/mL) in 0.9% sodium chloride injection were prepared in 20-mL polypropylene syringes and stored at 25, 4, or -20 °C. Syringe samples were collected immediately after preparation and at preselected time points and assayed by a validated high-performance liquid chromatography (HPLC) method. The ertapenem solution was considered stable if at least 90% of the mean initial concentration remained at the time of HPLC analysis. The mean±S.D. baseline ertapenem concentration across all stability studies was 109.9±9.2 mg/mL. One hour after preparation, the mean±S.D. ertapenem concentration of samples kept at room temperature was 87.8±4.6% of the initial concentration. After 24 and 48 hours of refrigeration, mean±S.D. drug concentrations had declined to 93.6±5.9% and 86.2±4.3% of the respective baseline concentrations. Frozen syringes required 1 hour to thaw at room temperature; after 14 and 28 days of frozen storage, the mean±S.D. ertapenem concentrations of these samples 4 hours after thawing were 93.4±3.5% and 86.4±2.6% of the respective baseline values. Ertapenem 100 mg/mL prepared in 20-mL polypropylene syringes was stable at room temperature for approximately 30 minutes. Room-temperature stability was extended to 4 hours after 24 hours of refrigeration. After being frozen for 14 or 28 days, ertapenem was stable for 3-5 hours after removal from the freezer. | 25,147,172 | [
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Implementation of standardized pediatric i.v. medication concentrations. | The development and implementation of a comprehensive and standardized list of pediatric i.v. medication concentrations across a large healthcare system are described. In accordance with National Patient Safety Goals, facilities affiliated with the Hospital Corporation of America system had independently standardized and limited the number of drug concentrations in use. This resulted in variation among facilities, which prevented the systemwide standardization of drug dictionaries within the computerized pharmacy and prescriber-order-entry systems, complicated the movement of providers among facilities, and contributed to inconsistency in medication prescribing. A team of experts collaborated to create a comprehensive standard list that included 119 medications and 372 concentrations for pediatric i.v. medications. Implementation of this standard list was driven through a financial incentive from the malpractice insurance provider; facilities that completed the required activities for this optional program could apply for a credit of a portion of their malpractice insurance cost. For the standardization of pediatric i.v. medications, required activities included approval of the standard medication list, incorporation of this list into facility pharmacy dictionaries, and update of all smart pump software to include only the new standard medications and concentrations. Of the 145 facilities that were eligible for the implementation of standard pediatric i.v. medication concentrations, 141 (97%) completed all requirements and received the 2% malpractice insurance cost credit. The use of a financial incentive strategy, in the form of a malpractice insurance credit, successfully motivated the implementation of standardized pediatric medication concentrations across a large healthcare system. | 25,147,175 | [
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The sexual cascade and the rise of pre-ejaculatory (Darwinian) sexual selection, sex roles, and sexual conflict. | After brief historic overviews of sexual selection and sexual conflict, I argue that pre-ejaculatory sexual selection (the form of sexual selection discussed by Darwin) arose at a late stage in an inevitable succession of transitions flowing from the early evolution of syngamy to the evolution of copulation and sex roles. If certain conditions were met, this "sexual cascade" progressed inevitably, if not, sexual strategy remained fixed at a given stage. Prolonged evolutionary history of intense sperm competition/selection under external fertilization preceded the rise of advanced mobility, which generated pre-ejaculatory sexual selection, followed on land by internal fertilization and reduced sperm competition in the form of postcopulatory sexual selection. I develop a prospective model of the early evolution of mobility, which, as Darwin realized, was the catalyst for pre-ejaculatory sexual selection. Stages in the cascade should be regarded as consequential rather than separate phenomena and, as such, invalidate much current opposition to Darwin-Bateman sex roles. Potential for sexual conflict occurs throughout, greatly increasing later in the cascade, reaching its peak under precopulatory sexual selection when sex roles become highly differentiated. | 25,147,177 | [
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Dual tasking with the timed "up & go" test improves detection of risk of falls in people with Parkinson disease. | Falls are a common and disabling feature of Parkinson disease (PD). Early identification of patients at greatest risk of falling is a key goal of physical therapy assessment. The Timed "Up & Go" Test (TUG), a frequently used mobility assessment tool, has moderate sensitivity and specificity for identifying fall risk. The study objective was to investigate whether adding a task (cognitive or manual) to the TUG (TUG-cognitive or TUG-manual, respectively) increases the utility of the test for identifying fall risk in people with PD. This was a retrospective cohort study of people with PD (N=36). Participants were compared on the basis of self-reported fall exposure in the preceding 6 months (those who had experienced falls ["fallers"] versus those who had not ["nonfallers"]). The time taken to complete the TUG, TUG-cognitive, and TUG-manual was measured for both groups. Between-group differences were calculated with the Mann-Whitney U test. The discriminative performance of the test at various cutoff values was examined, and estimates of sensitivity and specificity were based on receiver operating characteristic curve plots. Fallers took significantly longer than nonfallers (n=19) to complete the TUG under all 3 conditions. The TUG-cognitive showed optimal discriminative performance (receiver operating characteristic area under the curve=0.82; 95% confidence interval [CI]=0.64, 0.92) at a cutoff of 14.7 seconds. The TUG-cognitive was more likely to correctly classify participants with a low risk of falling (positive likelihood ratio=2.9) (<14.7 seconds) and had higher estimates of sensitivity (0.76; 95% CI=0.52, 0.90) than of specificity (0.73; 95% CI=0.51, 0.88) at this threshold (negative likelihood ratio=0.32). Retrospective classification of fallers and nonfallers was used. The addition of a cognitive task to the TUG enhanced the identification of fall risk in people with PD. The TUG-cognitive should be considered a component of a multifaceted fall risk assessment in people with PD. | 25,147,186 | [
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