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Flow-induced central bond remodeling mediated by local cytoskeletal tensions as well as reorganization.
72 (0.62 to 0.84, trend p less then 0.001) for total CVD; 0.65 (0.45 to 0.94, trend p=0.065) for CHD; 0.74 (0.62 to 0.87, trend p=0.005) for total stroke; 0.77 (0.62 to 0.97, trend p=0.467) for cerebral infarction; and 0.54 (0.40 to 0.73, trend p less then 0.001) for intracerebral haemorrhage. No associations were observed between tub bathing frequency and risk of sudden cardiac death or subarachnoid haemorrhage. CONCLUSION The frequency of tub bathing was inversely associated with the risk of CVD among middle-aged Japanese. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.Magnocellular neurosecretory cells are intrinsically osmosensitive and can be activated by increases in blood osmolality, triggering the release of antidiuretic hormone vasopressin (VP) to promote water retention. Hence, the activity of magnocellular VP neurons is one of the key elements contributing to the regulation of body fluid homeostasis in healthy organisms. Chronic exposure to high dietary salt leads to excessive activation of VP neurons, thereby elevating levels of circulating VP, which can cause increases in blood pressure contributing to salt-dependent hypertension. However, the molecular basis underlying high salt diet-induced hyperactivation of magnocellular VP neurons remains not fully understood. Previous studies suggest that magnocellular neurosecretory neurons contain a subcortical layer of actin filaments and pharmacological stabilization of this actin network potentiates osmotically-induced activation of magnocellular neurons. Using super-resolution imaging in situ, we investigated the orgasin secretion is a key factor controlling body fluid homeostasis, and excessive vasopressin secretion contributes to fluid balance disorders such as salt-sensitive hypertension. DFOM molecular weight Using super-resolution analysis of different areas of the rat brain, we show that vasopressin neurons feature a unique actin cytoskeleton comprising a subcortical actin layer and an array of cytoplasmic comet-like structures, which are not present in any other neuronal cell type. Moreover, the density of these unique actin structures is increased in a rodent model of salt-sensitive hypertension, and our findings suggest that this modification may contribute to excessive activation of vasopressin neurons in a model salt-sensitive hypertension. Copyright © 2020 Barad et al.OBJECTIVES Introduced in the UK in 2010, the fit note was designed to address the problem of long-term sickness absence. We explored (1) associations between demographic variables and fit note receipt, 'maybe fit' use and long-term conditions, (2) whether individuals with long-term conditions receive more fit notes and are more likely to have the 'maybe fit' option selected and (3) whether long-term conditions explained associations between demographic variables and fit note receipt. METHODS Data were extracted from Lambeth DataNet, a database containing electronic medical records of all 45 general practitioner (GP) practices within the borough of Lambeth. Individual-level anonymised data on GP consultations, prescriptions, Quality and Outcomes Framework diagnostic data and demographic information were analysed using survival analysis. RESULTS In a sample of 326 415 people, 41 502 (12.7%) received a fit note. We found substantial differences in fit note receipt by gender, age, ethnicity and area-level deprivation. Chronic pain (HR 3.7 (95% CI 3.3 to 4.0)) and depression (HR 3.4 (95% CI 3.3 to 3.6)) had the highest rates for first fit note receipt. 'Maybe fit' recommendations were used least often in patients with epilepsy and serious mental illness. The presence of long-term conditions did not explain associations between demographic variables and fit note use. CONCLUSIONS For the first time, we show the relationships between fit note use and long-term conditions using individual-level primary care data from south London. Further research is required in order to evaluate this relatively new policy and to understand the needs of the population it was designed to support. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.Giving birth triggers a wide repertoire of physiological and behavioural changes in the mother to enable her to feed and care for her offspring. These changes require coordination and are often orchestrated from the central nervous system, through as of yet poorly understood mechanisms. A neuronal population with a central role in puerperal changes is the tuberoinfundibular dopamine (TIDA) neurons that control release of the pituitary hormone, prolactin, which triggers key maternal adaptations, including lactation and maternal care. Here, we used Ca2+ imaging on mice from both sexes and whole-cell recordings on female mouse TIDA neurons in vitro to examine if they adapt their cellular and network activity according to reproductive state. In the high-prolactin state of lactation, TIDA neurons shift to faster membrane potential oscillations, a reconfiguration that reverses upon weaning. During the estrous cycle, however, which includes a brief, but pronounced, prolactin peak, oscillation frequency remains stablpecific conductance - Ih - contributes to the altered network rhythm. These findings identify a new facet of maternal brain plasticity at the level of membrane properties and consequent ensemble activity. Copyright © 2020 Pérez et al.For visually guided navigation, the use of environmental cues is essential. Particularly, detecting local boundaries that impose limits to locomotion and estimating their location is crucial. link2 In a series of three fMRI experiments, we investigated whether there is a neural coding of navigational distance in the human visual cortex (both female and male). We used a Virtual Reality software to systematically manipulate the distance from a viewer perspective to different types of a boundary. Using a multivoxel pattern classification employing a linear support vector machine, we found that the occipital place area (OPA) is sensitive to the navigational distance restricted by the transparent glass wall. Further, the OPA was sensitive to a non-crossable boundary only, suggesting an importance of the functional constraint of a boundary. Taken together, we propose the OPA as a perceptual source of external environmental features relevant for navigation.Significance Statement One of major goals in cognitive neuroscience has been to understand the nature of visual scene representation in human ventral visual cortex. An aspect of scene perception that has been overlooked despite its ecological importance is the analysis of space for navigation. One of critical computation necessary for navigation is coding of distance to environmental boundaries that impose limit on navigator's movements. This paper reports the first empirical evidence for coding of navigational distance in the human visual cortex and its striking sensitivity to functional constraint of environmental boundaries. Such finding links the paper to previous neurological and behavioral works that emphasized the distance to boundaries as a crucial geometric property for reorientation behavior of children and other animal species. Copyright © 2020 Park and Park.OBJECTIVE Direct comparison of the clinical outcomes between nucleos(t)ide analogue (NA) discontinuation versus NA continuation has not been performed in patients with chronic hepatitis B who achieved HBsAg-seroclearance. Whether NA discontinuation was as safe as NA continuation after NA-induced surface antigen of HBV (HBsAg) seroclearance was investigated in the present study. DESIGNS This multicentre study included 276 patients from 16 hospitals in Korea who achieved NA-induced HBsAg seroclearance 131 (47.5%) discontinued NA treatment within 6 months after HBsAg seroclearance (NA discontinuation group) and 145 (52.5%) continued NA treatment (NA continuation group). Primary endpoint was HBsAg reversion and secondary endpoints included serum HBV DNA redetection and development of hepatocellular carcinoma (HCC). RESULTS During follow-up (median=26.9 months, IQR=12.2-49.2 months), 10 patients (3.6%) experienced HBsAg reversion, 6 (2.2%) showed HBV DNA redetection and 8 (2.9%) developed HCC. Compared with NA continuation, NA discontinuation was not associated with HBsAg reversion in both univariable (HR=0.45, 95% CI=0.12 to 1.76, log-rank p=0.24) and multivariable analyses (adjusted HR=0.65, 95% CI=0.16 to 2.59, p=0.54). The cumulative probabilities of HBsAg reversion at 1, 3 and 5 years were 0.8%, 2.3% and 5.0% in the NA discontinuation group, and 1.5%, 6.3% and 8.4% in the NA continuation group, respectively. NA discontinuation was not associated with higher risk of either HBV redetection (HR=0.83, 95% CI=0.16 to 4.16, log-rank p=0.82) or HCC development (HR=0.53, 95% CI=0.12 to 2.23, log-rank p=0.38). CONCLUSION The discontinuation of NA was not associated with a higher risk of either HBsAg reversion, serum HBV DNA redetection or HCC development compared with NA continuation among patients who achieved HBsAg seroclearance with NA. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVE Endocuff Vision (ECV) is the second generation of a device designed to improve polyp detection. link3 The aim of this study was to evaluate its impact on adenoma detection rate (ADR) in routine colonoscopy. DESIGN This cluster-randomised crossover trial compared Endocuff-assisted (ECV+) with standard (ECV-) colonoscopy. Two teams of 11 endoscopists each with prior ECV experience, balanced in terms of basal ADR, gender and case volume were compared. In randomised fashion, the teams started with ECV+ or ECV- and switched group after inclusion of half of the cases. The main outcome criterion was ADR difference between ECV+ and ECV-. Subgroup analysis was done for physicians with low and high ADR ( less then or ≥ 25%). RESULTS During two periods of 20 and 21 weeks, respectively, the 22 endoscopists included 2058 patients (1032 ECV- vs 1026 ECV+, both groups being comparable). Overall ADR for both groups taken together was higher with ECV (39.2%) than without (29.4%; p less then 0.001) irrespective of the sequence of use (ECV+ or ECV- first), but mostly in adenomas less then 1 cm. In the physician subgroup analysis, only high detectors showed a significant ADR increase (from 31% to 41%, p less then 0.001), while the increase in the low detectors was not significant (from 24% to 30%, p=0.11). ECV had a positive impact in all colonic locations, except for the rectum. No ECV- related complication was reported. CONCLUSION We observed a significant ADR difference of approximately 10% by the use of ECV. By subgroup analysis, this increase was significant only in physicians classified as high detectors. TRIAL REGISTRATION NUMBER ClinicalTrials.gov (NCT03344055). © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular and microenvironmental features determine the propensity of RCD to drive adaptive immunity. Here, we provide an updated operational definition of immunogenic cell death (ICD), discuss the key factors that dictate the ability of dying cells to drive an adaptive immune response, summarize experimental assays that are currently available for the assessment of ICD in vitro and in vivo, and formulate guidelines for their interpretation. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.
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