Orai1 inhibitor STIM2?? regulates myogenesis by controlling SOCE dependent transcriptional factors

Store-operated Ca2+ entry (SOCE), the fundamental Ca2+ signaling mechanism in myogenesis, is mediated by stromal interaction molecule (STIM), which senses the depletion of endoplasmic reticulum Ca2+ stores and induces Ca2+ influx by activating Orai channels in the plasma membrane. Recently, STIM2??, an eight-residue-inserted splice variant of STIM2, was found to act as an inhibitor of SOCE. Although a previous study demonstrated an increase in STIM2?? splicing during in vitro differentiation of skeletal muscle, the underlying mechanism and detailed function of STIM2?? in myogenesis remain unclear. In this study, we investigated the function of STIM2?? in myogenesis using the C2C12 cell line with RNA interference-mediated knockdown and CRISPR-Cas-mediated knockout approaches. Deletion of STIM2?? delayed myogenic differentiation through the MEF2C and NFAT4 pathway in C2C12 cells. Further, loss of STIM2?? increased cell proliferation by altering Ca2+ homeostasis and inhibited cell cycle arrest mediated by the cyclin D1-CDK4 degradation pathway. Thus, this study identified a previously unknown function of STIM2?? in myogenesis and improves the understanding of how cells effectively regulate the development process via alternative splicing

A rare case of peritoneo-cutaneous fistula after cesarean section

Peritoneo-cutaneous fistula is usually a rare but known entity. Such a case has not been reported after cesarean sections. A 26-year female presented to our clinic in May 2019 with persistent sero-purulent discharge from sinus over abdominal skin. The patient had previously undergone a cesarean section in April 2018 for premature rupture of membranes and non-progress of labour. The surgery and puerperal period were uneventful. The patient presented with document high-grade fever in June 2018. In August 2018, a localized painful swelling was noted by the patient herself over the abdomen, contrast-enhanced computed tomography, which suggested 6.3×3.9×3 cm collection in the right adnexal region and a fistulous tract communicating with abdominal skin. For the same she underwent surgery, wide local excision of the fistulous tract around elliptical skin incision was done. The development of delayed peritoneo-cutaneous fistula has been seen as a complication of difficult cholecystectomy

Electronic Cigarette Use Prevalence, Associated Factors, and Pattern by Cigarette Smoking Status in the United States From NHANES (National Health and Nutrition Examination Survey) 2013-2014

BACKGROUND: To examine the prevalence and patterns of recent electronic cigarette (e-cigarette) use in a nationally representative sample of US adults and adolescents. METHODS AND RESULTS: Using tobacco information from NHANES (National Health and Nutrition Examination Survey) 2013-2014, 5423 adults and 895 adolescents (aged 13-17 years) were included in this analysis. Demographic, tobacco use, and drug use information were self-reported. Recent e-cigarette use (within the previous 5 days) was stratified by smoking status. Of 125 e-cigarette users, 116 participants were aged ≥18 years, corresponding to 2.6% (95% confidence interval [CI], 2.0-3.1) and 1.21% (95% CI, 0.3-2.1) prevalence of e-cigarette use among US adults and adolescents, respectively. E-cigarette adult users were current smokers (68.1%), former smokers (23.7%), and never smokers (8.2%). The highest prevalence of e-cigarette use was among current smokers (8.2%; 95% CI, 6.3-10.1), followed by former smokers (2.7%; 95% CI, 1.4-4.1), and then never smokers (0.4%; 95% CI, 0.2-0.6). After adjusting for age, sex, and ethnicity, e-cigarette users had higher odds of being exposed to secondhand smoke (odds ratio: 6.3; 95% CI, 3.6-11.1) and drinking alcohol (odds ratio: 4.2; 95% CI, 1.8-10.0) and lower odds of having at least a college education or a higher income, compared with tobacco nonusers. CONCLUSIONS: Between 2013 and 2014, e-cigarette use in the United States was more common among younger people, those with low socioeconomic status, and current and former smokers. These findings will help inform future research as well as public policy and regulatory actions

A prospective observational study to determine the utility of placental laterality for prediction of preeclampsia in pregnancy

Background: Preeclampsia is a multisystem disorder of unknown aetiology and recently its link with placental laterality has been explored. The objective of this study was to find the association of placental laterality with maternal and fetal outcomes in pregnancy. Study also determined the predictive ability of placenta laterality for the development of hypertension in pregnancy.Methods: A prospective observational cohort study was conducted on 200 pregnant women. Routine investigations and doppler analysis were done. Placenta position was categorized into central and lateral. Maternal and fetal outcomes were recorded. The data was entered in MS excel spreadsheet and analysis was done using statistical package for social sciences (SPSS) version 21.0. A p value of 0.05). Even the maternal outcomes like mode of delivery, onset of labor, indication of labor induction and caesarean deliveries were comparable among women with central or lateral placenta (p > 0.05). On applying univariate logistic regression analysis, previous history of hypertension in pregnancy was a significant risk factor for development of preeclampsia with odds ratio of 168.43 (p < 0.05).Conclusions: It can be concluded that the maternal and fetal outcomes are independent of the placenta laterality. The doppler characteristics and placenta laterality did not show any increased risk for hypertension in pregnancy. However future studies are recommended with large sample size including more women with diagnosed hypertension in the pregnancy so that a better association can be derived with placenta laterality and doppler characteristics

Study of incidence and severity of menopausal symptoms in women of sub Himalayan region, using the Greene Climacteric Scale

Background: Identifying and measuring menopausal symptoms using Greene Climacteric Scale and calculating the mean age at menopause to find out the frequency of the menopausal symptoms so that can be used for better perimenapausal and menopausal care to females.Methods: A cross-sectional study was conducted in a tertiary care center in northern India. All menopausal women in gynaecology outpatient department were enrolled in study, over six months from May 2019 to October 2019. A total of 206 women fulfilled the inclusion criteria and were interviewed using the 21 points Greene Climateric Scale (GCS) Questionnaire. Analysis was done using SPSS 20 Windows software. Descriptive statistics included computation of percentages, means and standard deviations. Level of significance was set at P≤0.05.Results: The mean age of menopause was 47.9±3.42 years. About 90.3% of the menopausal women studied belonged to the rural population. The most frequently perceived symptoms by females were muscle joint pain (100%), vaginal dryness and pruritus vulvae (84%), lower abdominal pain (79.6%), hot flushes (50.5%).The most frequently reported symptoms as per the GCS were muscle and joint pains, loss of interest in sex, headaches, feeling tired or lacking in energy, difficulty in concentrating, attacks of anxiety, difficulty in sleeping and hot flushes. The mean total score was 17.61.Conclusions: Menopausal symptoms were common in this study group but women seeking help for the same was less. Therefore menopause clinics and care programmes need to be developed and strengthened to promote better health and higher quality of life in menopausal women

A comparative study of efficacy of oral pregabalin and clonidine for attenuation of pressor response to intubation

Background: Endotracheal intubation is associated with hemodynamic stress responses. Various drugs have been used in the past to attenuate the pressor response; however, none has been proved to be ideal. Present study was planned to evaluate the oral pregabalin 150 mg and clonidine 200 µg for attenuation of pressor response to intubation.Methods: The study was conducted on 100 adult patients of either gender scheduled to undergo elective surgeries under general anaesthesia (GA). The patients were randomly allocated into 2 groups. In group A patients received pregabalin 150mg and in group B patients received clonidine 200µg orally. The hemodynamic parameters were recorded until 10 minutes after intubation. The sedation, anxiety and side effects were also assessed.Results: In clonidine group, the mean HR remained below the baseline value at all the time intervals. In pregabalin group, the mean HR remained below the baseline value at most of the time intervals but increased above baseline just after intubation (T0i) and 1 minute after intubation (T1i) where increase was only 1.488±1.20% and 0.45±1.16% respectively from baseline. In both pregabalin and clonidine groups, the mean SBP and MAP remained below the baseline value (Tb) at all the time intervals from T0.5 to T10i. Both clonidine and pregabalin provided adequate anxiolysis and sedation with pregabalin providing more pronounced sedation and anxiolysis than clonidine.Conclusions: Both clonidine and pregabalin are effective oral premedication drugs for attenuation of the pressor response to laryngoscopy and endotracheal intubation.

Alternative splicing converts STIM2 from an activator to an inhibitor of store-operated calcium channels

Store-operated calcium entry (SOCE) regulates a wide variety of essential cellular functions. SOCE is mediated by STIM1 and STIM2, which sense depletion of ER Ca2+ stores and activate Orai channels in the plasma membrane. Although the amplitude and dynamics of SOCE are considered important determinants of Ca2+-dependent responses, the underlying modulatory mechanisms are unclear. In this paper, we identify STIM2??, a highly conserved alternatively spliced isoform of STIM2, which, in contrast to all known STIM isoforms, is a potent inhibitor of SOCE. Although STIM2?? does not by itself strongly bind Orai1, it is recruited to Orai1 channels by forming heterodimers with other STIM isoforms. Analysis of STIM2?? mutants and Orai1-STIM2?? chimeras suggested that it actively inhibits SOCE through a sequence-specific allosteric interaction with Orai1. Our results reveal a previously unrecognized functional flexibility in the STIM protein family by which alternative splicing creates negative and positive regulators of SOCE to shape the amplitude and dynamics of Ca2+ signals.open

Long-Term Outcomes and Trends in Liver Transplantation for Hereditary Hemochromatosis in the United States

There have been conflicting data regarding liver transplantation (LT) outcomes for hereditary hemochromatosis (HH), with no recent data on LT outcomes in patients with HH in the past decade. Using the United Network for Organ Sharing registry, we evaluated waitlist and post-LT survival in all adult patients listed for HH without concomitant liver disease from 2003 to 2019. Post-LT survival for HH was compared with a propensity-matched (recipient and donor factors) cohort of recipients with chronic liver disease (CLD). From 2003 to 2019, 862 patients with HH were listed for LT, of which 55.6% ( n = 479) patients underwent LT. The 1- and 5-year post-LT survival rates in patients with HH were 88.7% (95% confidence interval [CI], 85.4%-91.4%) and 77.5% (95% CI, 72.8%-81.4%), respectively, and were comparable with those in the propensity-matched CLD cohort ( p value = 0.96). Post-LT survival for HH was lower than for Wilson\u27s disease, another hereditary metabolic liver disease with similar LT volume ( n = 365). Predictors for long-term (5-year) post-LT mortality included presence of portal vein thrombosis (hazard ratio [HR], 1.96; 95% CI, 1.07-3.58), obesity measurements greater than Class II (HR, 1.98; 95% CI, 1.16-3.39), and Karnofsky performance status (HR, 0.98; 95% CI, 0.97-0.99) at the time of LT. The leading cause of post-LT death ( n = 145) was malignancy (25.5%), whereas cardiac disease was the cause in less than 10% of recipients. In conclusion, short- and long-term survival rates for HH are excellent and comparable with those of other LT recipients. Improving extrahepatic metabolic factors and functional status in patients with HH prior to LT may improve outcomes

Long-term outcomes and trends in liver transplantation for hereditary hemochromatosis in the United States.

There have been conflicting data regarding liver transplantation (LT) outcomes for hereditary hemochromatosis (HH), with no recent data on LT outcomes in patients with HH in the past decade. Using the United Network for Organ Sharing registry, we evaluated waitlist and post-LT survival in all adult patients listed for HH without concomitant liver disease from 2003 to 2019. Post-LT survival for HH was compared with a propensity-matched (recipient and donor factors) cohort of recipients with chronic liver disease (CLD). From 2003 to 2019, 862 patients with HH were listed for LT, of which 55.6% ( n = 479) patients underwent LT. The 1- and 5-year post-LT survival rates in patients with HH were 88.7% (95% confidence interval [CI], 85.4%-91.4%) and 77.5% (95% CI, 72.8%-81.4%), respectively, and were comparable with those in the propensity-matched CLD cohort ( p value = 0.96). Post-LT survival for HH was lower than for Wilson's disease, another hereditary metabolic liver disease with similar LT volume ( n = 365). Predictors for long-term (5-year) post-LT mortality included presence of portal vein thrombosis (hazard ratio [HR], 1.96; 95% CI, 1.07-3.58), obesity measurements greater than Class II (HR, 1.98; 95% CI, 1.16-3.39), and Karnofsky performance status (HR, 0.98; 95% CI, 0.97-0.99) at the time of LT. The leading cause of post-LT death ( n = 145) was malignancy (25.5%), whereas cardiac disease was the cause in less than 10% of recipients. In conclusion, short- and long-term survival rates for HH are excellent and comparable with those of other LT recipients. Improving extrahepatic metabolic factors and functional status in patients with HH prior to LT may improve outcomes.AMN/AN/

Genome-Wide Distribution and Organization of Microsatellites in Plants: An Insight into Marker Development in Brachypodium

Plant genomes are complex and contain large amounts of repetitive DNA including microsatellites that are distributed across entire genomes. Whole genome sequences of several monocot and dicot plants that are available in the public domain provide an opportunity to study the origin, distribution and evolution of microsatellites, and also facilitate the development of new molecular markers. In the present investigation, a genome-wide analysis of microsatellite distribution in monocots (Brachypodium, sorghum and rice) and dicots (Arabidopsis, Medicago and Populus) was performed. A total of 797,863 simple sequence repeats (SSRs) were identified in the whole genome sequences of six plant species. Characterization of these SSRs revealed that mono-nucleotide repeats were the most abundant repeats, and that the frequency of repeats decreased with increase in motif length both in monocots and dicots. However, the frequency of SSRs was higher in dicots than in monocots both for nuclear and chloroplast genomes. Interestingly, GC-rich repeats were the dominant repeats only in monocots, with the majority of them being present in the coding region. These coding GC-rich repeats were found to be involved in different biological processes, predominantly binding activities. In addition, a set of 22,879 SSR markers that were validated by e-PCR were developed and mapped on different chromosomes in Brachypodium for the first time, with a frequency of 101 SSR markers per Mb. Experimental validation of 55 markers showed successful amplification of 80% SSR markers in 16 Brachypodium accessions. An online database ‘BraMi’ (Brachypodium microsatellite markers) of these genome-wide SSR markers was developed and made available in the public domain. The observed differential patterns of SSR marker distribution would be useful for studying microsatellite evolution in a monocot–dicot system. SSR markers developed in this study would be helpful for genomic studies in Brachypodium and related grass species, especially for the map based cloning of the candidate gene(s)