131 research outputs found

    A single gene defect causing claustrophobia

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    Claustrophobia, the well-known fear of being trapped in narrow/closed spaces, is often considered a conditioned response to traumatic experience. Surprisingly, we found that mutations affecting a single gene, encoding a stress-regulated neuronal protein, can cause claustrophobia. Gpm6a-deficient mice develop normally and lack obvious behavioral abnormalities. However, when mildly stressed by single-housing, these mice develop a striking claustrophobia-like phenotype, which is not inducible in wild-type controls, even by severe stress. The human GPM6A gene is located on chromosome 4q32-q34, a region linked to panic disorder. Sequence analysis of 115 claustrophobic and non-claustrophobic subjects identified nine variants in the noncoding region of the gene that are more frequent in affected individuals (P=0.028). One variant in the 3′untranslated region was linked to claustrophobia in two small pedigrees. This mutant mRNA is functional but cannot be silenced by neuronal miR124 derived itself from a stress-regulated transcript. We suggest that loosing dynamic regulation of neuronal GPM6A expression poses a genetic risk for claustrophobia

    Neuropsychiatric manifestations of COVID-19 can be clustered in three distinct symptom categories

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    Several studies have reported clinical manifestations of the new coronavirus disease. However, few studies have systematically evaluated the neuropsychiatric complications of COVID-19. We reviewed the medical records of 201 patients with confirmed COVID-19 (52 outpatients and 149 inpatients) that were treated in a large referral center in Tehran, Iran from March 2019 to May 2020. We used clustering approach to categorize clinical symptoms. One hundred and fifty-one patients showed at least one neuropsychiatric symptom. Limb force reductions, headache followed by anosmia, hypogeusia were among the most common neuropsychiatric symptoms in COVID-19 patients. Hierarchical clustering analysis showed that neuropsychiatric symptoms group together in three distinct groups: anosmia and hypogeusia; dizziness, headache, and limb force reduction; photophobia, mental state change, hallucination, vision and speech problem, seizure, stroke, and balance disturbance. Three non-neuropsychiatric cluster of symptoms included diarrhea and nausea; cough and dyspnea; and fever and weakness. Neuropsychiatric presentations are very prevalent and heterogeneous in patients with coronavirus 2 infection and these heterogeneous presentations may be originating from different underlying mechanisms. Anosmia and hypogeusia seem to be distinct from more general constitutional-like and more specific neuropsychiatric symptoms. Skeletal muscular manifestations might be a constitutional or a neuropsychiatric symptom. © 2020, The Author(s)

    Recurrent flares in active region NOAA 11283

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    Context. Flares and coronal mass ejections (CMEs) are solar phenomena that are not yet fully understood. Several investigations have been performed to single out their related physical parameters that can be used as indices of the magnetic complexity leading to their occurrence. Aims. In order to shed light on the occurrence of recurrent flares and subsequent associated CMEs, we studied the active region NOAA 11283 where recurrent M and X GOES-class flares and CMEs occurred. Methods. We use vector magnetograms taken by HMI/SDO to calculate the horizontal velocity fields of the photospheric magnetic structures, the shear and the dip angles of the magnetic field, the magnetic helicity flux distribution, and the Poynting fluxes across the photosphere due to the emergence and the shearing of the magnetic field. Results. Although we do not observe consistent emerging magnetic flux through the photosphere during the observation time interval, we detected a monotonic increase of the magnetic helicity accumulated in the corona. We found that both the shear and the dip angles have high values along the main polarity inversion line (PIL) before and after all the events. We also note that before the main flare of X2.1 GOES class, the shearing motions seem to inject a more significant energy than the energy injected by the emergence of the magnetic field. Conclusions. We conclude that the very long duration (about 4 days) of the horizontal displacement of the main photospheric magnetic structures along the PIL has a primary role in the energy release during the recurrent flares. This peculiar horizontal velocity field also contributes to the monotonic injection of magnetic helicity into the corona. This process, coupled with the high shear and dip angles along the main PIL, appears to be responsible for the consecutive events of loss of equilibrium leading to the recurrent flares and CMEs

    The effect of resistance training interventions on weight status in youth:a meta-analysis

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    Abstract Background There has been a rise in research into obesity prevention and treatment programmes in youth, including the effectiveness of resistance-based exercise. The purpose of this meta-analysis was to examine the effect of resistance training interventions on weight status in youth. Methods Meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was registered on PROSPERO (registration number CRD42016038365). Eligible studies were from English language peer-reviewed published articles. Searches were conducted in seven databases between May 2016 and June 2017. Studies were included that examined the effect of resistance training on weight status in youth, with participants of school age (5–18 years). Results There were 24 complete sets of data from 18 controlled trials (CTs) which explored 8 outcomes related to weight status. Significant, small effect sizes were identified for body fat% (Hedges’ g = 0.215, 95% CI 0.059 to 0.371, P = 0.007) and skinfolds (Hedges’ g = 0.274, 95% CI 0.066 to 0.483, P = 0.01). Effect sizes were not significant for: body mass (Hedges’ g = 0.043, 95% CI − 0.103 to 0.189, P = 0.564), body mass index (Hedges’ g = 0.024, 95% CI − 0.205 to 0.253, P = 0.838), fat-free mass (Hedges’ g = 0.073, 95% CI − 0.169 to 0.316, P = 0.554), fat mass (Hedges’ g = 0.180, 95% CI − 0.090 to 0.451, P = 0.192), lean mass (Hedges’ g = 0.089, 95% CI − 0.122 to 0.301, P = 0.408) or waist circumference (Hedges’ g = 0.209, 95% CI − 0.075 to 0.494, P = 0.149). Conclusions The results of this meta-analysis suggest that an isolated resistance training intervention may have an effect on weight status in youth. Overall, more quality research should be undertaken to investigate the impact of resistance training in youth as it could have a role to play in the treatment and prevention of obesity

    Mimicry and well known genetic friends: molecular diagnosis in an Iranian cohort of suspected Bartter syndrome and proposition of an algorithm for clinical differential diagnosis.

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    BACKGROUND: Bartter Syndrome is a rare, genetically heterogeneous, mainly autosomal recessively inherited condition characterized by hypochloremic hypokalemic metabolic alkalosis. Mutations in several genes encoding for ion channels localizing to the renal tubules including SLC12A1, KCNJ1, BSND, CLCNKA, CLCNKB, MAGED2 and CASR have been identified as underlying molecular cause. No genetically defined cases have been described in the Iranian population to date. Like for other rare genetic disorders, implementation of Next Generation Sequencing (NGS) technologies has greatly facilitated genetic diagnostics and counseling over the last years. In this study, we describe the clinical, biochemical and genetic characteristics of patients from 15 Iranian families with a clinical diagnosis of Bartter Syndrome. RESULTS: Age range of patients included in this study was 3 months to 6 years and all patients showed hypokalemic metabolic alkalosis. 3 patients additionally displayed hypercalciuria, with evidence of nephrocalcinosis in one case. Screening by Whole Exome Sequencing (WES) and long range PCR revealed that 12/17 patients (70%) had a deletion of the entire CLCNKB gene that was previously identified as the most common cause of Bartter Syndrome in other populations. 4/17 individuals (approximately 25% of cases) were found to suffer in fact from pseudo-Bartter syndrome resulting from congenital chloride diarrhea due to a novel homozygous mutation in the SLC26A3 gene, Pendred syndrome due to a known homozygous mutation in SLC26A4, Cystic Fibrosis (CF) due to a novel mutation in CFTR and apparent mineralocorticoid excess syndrome due to a novel homozygous loss of function mutation in HSD11B2 gene. 1 case (5%) remained unsolved. CONCLUSIONS: Our findings demonstrate deletion of CLCNKB is the most common cause of Bartter syndrome in Iranian patients and we show that age of onset of clinical symptoms as well as clinical features amongst those patients are variable. Further, using WES we were able to prove that nearly 1/4 patients in fact suffered from Pseudo-Bartter Syndrome, reversing the initial clinical diagnosis with important impact on the subsequent treatment and clinical follow up pathway. Finally, we propose an algorithm for clinical differential diagnosis of Bartter Syndrome

    Role of DNA methylation in head and neck cancer

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    Head and neck cancer (HNC) is a heterogenous and complex entity including diverse anatomical sites and a variety of tumor types displaying unique characteristics and different etilogies. Both environmental and genetic factors play a role in the development of the disease, but the underlying mechanism is still far from clear. Previous studies suggest that alterations in the genes acting in cellular signal pathways may contribute to head and neck carcinogenesis. In cancer, DNA methylation patterns display specific aberrations even in the early and precancerous stages and may confer susceptibility to further genetic or epigenetic changes. Silencing of the genes by hypermethylation or induction of oncogenes by promoter hypomethylation are frequent mechanisms in different types of cancer and achieve increasing diagnostic and therapeutic importance since the changes are reversible. Therefore, methylation analysis may provide promising clinical applications, including the development of new biomarkers and prediction of the therapeutic response or prognosis. In this review, we aimed to analyze the available information indicating a role for the epigenetic changes in HNC

    Physiological and anthropometric determinants of critical power, W ′ and the reconstitution of W ′ in trained and untrained male cyclists

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    From Springer Nature via Jisc Publications RouterHistory: received 2020-01-17, accepted 2020-07-31, registration 2020-08-01, pub-electronic 2020-08-09, online 2020-08-09, pub-print 2020-11Publication status: PublishedAbstract: Purpose: This study examined the relationship of physiological and anthropometric characteristics with parameters of the critical power (CP) model, and in particular the reconstitution of W′ following successive bouts of maximal exercise, amongst trained and untrained cyclists. Methods: Twenty male adults (trained nine; untrained 11; age 39 ± 15 year; mass 74.7 ± 8.7 kg; V̇O2max 58.0 ± 8.7 mL kg−1 min−1) completed three incremental ramps (20 W min−1) to exhaustion interspersed with 2-min recoveries. Pearson’s correlation coefficients were used to assess relationships for W′ reconstitution after the first recovery (W′rec1), the delta in W′ reconstituted between recoveries (∆W′rec), CP and W′. Results: CP was strongly related to V̇O2max for both trained (r = 0.82) and untrained participants (r = 0.71), whereas W′ was related to V̇O2max when both groups were considered together (r = 0.54). W′rec1 was strongly related to V̇O2max for the trained (r = 0.81) but not untrained (r = 0.18); similarly, ∆W′rec was strongly related to V̇O2max (r = − 0.85) and CP (r = − 0.71) in the trained group only. Conclusions: Notable physiological relationships between parameters of aerobic fitness and the measurements of W′ reconstitution were observed, which differed among groups. The amount of W′ reconstitution and the maintenance of W′ reconstitution that occurred with repeated bouts of maximal exercise were found to be related to key measures of aerobic fitness such as CP and V̇O2max. This data demonstrates that trained cyclists wishing to improve their rate of W′ reconstitution following repeated efforts should focus training on improving key aspects of aerobic fitness such as V̇O2max and CP
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