Src Dependent Pancreatic Acinar Injury Can Be Initiated Independent of an Increase in Cytosolic Calcium

Several deleterious intra-acinar phenomena are simultaneously triggered on initiating acute pancreatitis. These culminate in acinar injury or inflammatory mediator generation in vitro and parenchymal damage in vivo. Supraphysiologic caerulein is one such initiator which simultaneously activates numerous signaling pathways including non-receptor tyrosine kinases such as of the Src family. It also causes a sustained increase in cytosolic calcium- a player thought to be crucial in regulating deleterious phenomena. We have shown Src to be involved in caerulein induced actin remodeling, and caerulein induced changes in the Golgi and post-Golgi trafficking to be involved in trypsinogen activation, which initiates acinar cell injury. However, it remains unclear whether an increase in cytosolic calcium is necessary to initiate acinar injury or if injury can be initiated at basal cytosolic calcium levels by an alternate pathway. To study the interplay between tyrosine kinase signaling and calcium, we treated mouse pancreatic acinar cells with the tyrosine phosphatase inhibitor pervanadate. We studied the effect of the clinically used Src inhibitor Dasatinib (BMS-354825) on pervanadate or caerulein induced changes in Src activation, trypsinogen activation, cell injury, upstream cytosolic calcium, actin and Golgi morphology. Pervanadate, like supraphysiologic caerulein, induced Src activation, redistribution of the F-actin from its normal location in the sub-apical area to the basolateral areas, and caused antegrade fragmentation of the Golgi. These changes, like those induced by supraphysiologic caerulein, were associated with trypsinogen activation and acinar injury, all of which were prevented by Dasatinib. Interestingly, however, pervanadate did not cause an increase in cytosolic calcium, and the caerulein induced increase in cytosolic calcium was not affected by Dasatinib. These findings suggest that intra-acinar deleterious phenomena may be initiated independent of an increase in cytosolic calcium. Other players resulting in acinar injury along with the Src family of tyrosine kinases remain to be explored. © 2013 Mishra et al

Technology Pipeline for Large Scale Cross-Lingual Dubbing of Lecture Videos into Multiple Indian Languages

Cross-lingual dubbing of lecture videos requires the transcription of the original audio, correction and removal of disfluencies, domain term discovery, text-to-text translation into the target language, chunking of text using target language rhythm, text-to-speech synthesis followed by isochronous lipsyncing to the original video. This task becomes challenging when the source and target languages belong to different language families, resulting in differences in generated audio duration. This is further compounded by the original speaker's rhythm, especially for extempore speech. This paper describes the challenges in regenerating English lecture videos in Indian languages semi-automatically. A prototype is developed for dubbing lectures into 9 Indian languages. A mean-opinion-score (MOS) is obtained for two languages, Hindi and Tamil, on two different courses. The output video is compared with the original video in terms of MOS (1-5) and lip synchronisation with scores of 4.09 and 3.74, respectively. The human effort also reduces by 75%

Mutations in sphingosine-1-phosphate lyase cause nephrosis with ichthyosis and adrenal insufficiency

Steroid-resistant nephrotic syndrome (SRNS) causes 15% of chronic kidney disease cases. A mutation in 1 of over 40 monogenic genes can be detected in approximately 30% of individuals with SRNS whose symptoms manifest before 25 years of age. However, in many patients, the genetic etiology remains unknown. Here, we have performed whole exome sequencing to identify recessive causes of SRNS. In 7 families with SRNS and facultative ichthyosis, adrenal insufficiency, immunodeficiency, and neurological defects, we identified 9 different recessive mutations in SGPL1, which encodes sphingosine-1-phosphate (S1P) lyase. All mutations resulted in reduced or absent SGPL1 protein and/or enzyme activity. Overexpression of cDNA representing SGPL1 mutations resulted in subcellular mislocalization of SGPL1. Furthermore, expression of WT human SGPL1 rescued growth of SGPL1-deficient dpl1. yeast strains, whereas expression of disease-associated variants did not. Immunofluorescence revealed SGPL1 expression in mouse podocytes and mesangial cells. Knockdown of Sgpl1 in rat mesangial cells inhibited cell migration, which was partially rescued by VPC23109, an S1P receptor antagonist. In Drosophila, Sply mutants, which lack SGPL1, displayed a phenotype reminiscent of nephrotic syndrome in nephrocytes. WT Sply, but not the disease-associated variants, rescued this phenotype. Together, these results indicate that SGPL1 mutations cause a syndromic form of SRNS

Training during the COVID-19 lockdown : knowledge, beliefs, and practices of 12,526 athletes from 142 countries and six continents

OBJECTIVE Our objective was to explore the training-related knowledge, beliefs, and practices of athletes and the influence of lockdowns in response to the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS Athletes (n = 12,526, comprising 13% world class, 21% international, 36% national, 24% state, and 6% recreational) completed an online survey that was available from 17 May to 5 July 2020 and explored their training behaviors (training knowledge, beliefs/attitudes, and practices), including specific questions on their training intensity, frequency, and session duration before and during lockdown (March–June 2020). RESULTS Overall, 85% of athletes wanted to “maintain training,” and 79% disagreed with the statement that it is “okay to not train during lockdown,” with a greater prevalence for both in higher-level athletes. In total, 60% of athletes considered “coaching by correspondence (remote coaching)” to be sufficient (highest amongst world-class athletes). During lockdown, < 40% were able to maintain sport-specific training (e.g., long endurance [39%], interval training [35%], weightlifting [33%], most (83%) training for “general fitness and health maintenance” during lockdown. Athletes trained alone (80%) and focused on bodyweight (65%) and cardiovascular (59%) exercise/training during lockdown. Compared with before lockdown, most athletes reported reduced training frequency (from between five and seven sessions per week to four or fewer), shorter training sessions (from ≥ 60 to < 60 min), and lower sport-specific intensity (~ 38% reduction), irrespective of athlete classification. CONCLUSIONS COVID-19-related lockdowns saw marked reductions in athletic training specificity, intensity, frequency, and duration, with notable within-sample differences (by athlete classification). Higher classification athletes had the strongest desire to “maintain” training and the greatest opposition to “not training” during lockdowns. These higher classification athletes retained training specificity to a greater degree than others, probably because of preferential access to limited training resources. More higher classification athletes considered “coaching by correspondence” as sufficient than did lower classification athletes. These lockdown-mediated changes in training were not conducive to maintenance or progression of athletes’ physical capacities and were also likely detrimental to athletes’ mental health. These data can be used by policy makers, athletes, and their multidisciplinary teams to modulate their practice, with a degree of individualization, in the current and continued pandemic-related scenario. Furthermore, the data may drive training-related educational resources for athletes and their multidisciplinary teams. Such upskilling would provide athletes with evidence to inform their training modifications in response to germane situations (e.g., COVID related, injury, and illness).A specific funding was provided by the National Sports Institute of Malaysia for this study.The National Sports Institute of Malaysia.https://www.springer.com/journal/40279am2023Sports Medicin

COVID-19 lockdown : a global study investigating athletes’ sport classification and sex on training practices

PURPOSE : To investigate differences in athletes’ knowledge, beliefs, and training practices during COVID-19 lockdowns with reference to sport classification and sex. This work extends an initial descriptive evaluation focusing on athlete classification. METHODS : Athletes (12,526; 66% male; 142 countries) completed an online survey (May–July 2020) assessing knowledge, beliefs, and practices toward training. Sports were classified as team sports (45%), endurance (20%), power/technical (10%), combat (9%), aquatic (6%), recreational (4%), racquet (3%), precision (2%), parasports (1%), and others (1%). Further analysis by sex was performed. RESULTS : During lockdown, athletes practiced body-weight-based exercises routinely (67% females and 64% males), ranging from 50% (precision) to 78% (parasports). More sport-specific technical skills were performed in combat, parasports, and precision (∼50%) than other sports (∼35%). Most athletes (range: 50% [parasports] to 75% [endurance]) performed cardiorespiratory training (trivial sex differences). Compared to prelockdown, perceived training intensity was reduced by 29% to 41%, depending on sport (largest decline: ∼38% in team sports, unaffected by sex). Some athletes (range: 7%–49%) maintained their training intensity for strength, endurance, speed, plyometric, change-of-direction, and technical training. Athletes who previously trained ≥5 sessions per week reduced their volume (range: 18%–28%) during lockdown. The proportion of athletes (81%) training ≥60 min/session reduced by 31% to 43% during lockdown. Males and females had comparable moderate levels of training knowledge (56% vs 58%) and beliefs/attitudes (54% vs 56%). CONCLUSIONS : Changes in athletes’ training practices were sport-specific, with few or no sex differences. Team-based sports were generally more susceptible to changes than individual sports. Policy makers should provide athletes with specific training arrangements and educational resources to facilitate remote and/or home-based training during lockdown-type events.https://journals.humankinetics.com/view/journals/ijspp/ijspp-overview.xmlhj2023Sports Medicin

A cross-sectional study of persisting symptoms following 2 months post-COVID-19 and risk factors for delayed return to pre-COVID-19 health among patients attending a teaching hospital in Kerala

Background: A large number of people are being discharged from the hospital following COVID-19 without assessment of recovery. Systematic follow-up identifies the physical and physiological burden which could be used to inform the need for rehabilitation and/or further investigations. Methodology: A cross-sectional observational study of sample size 103 who were tested positive by TruNAAT in the month of August to September 2020 was conducted, whose data were collected from the medical records. Phone call interviews were conducted 2 months post-COVID-19, after ethical and institutional permission, and they were asked for any persisting symptoms at this point and the risk factors were noted. Data were analysed using various statistical methods. Result: The most common symptoms at onset were fever (49.5%), cough (28.2%), sore throat (18.4%) and loss of smell (17.5%). The most common comorbidities noted were diabetes mellitus (30.1%), hypertension (14.6%) and heart disease (7.8%). The cases with more than 14 days for COVID-19 to be negative are almost the same in cases with comorbidities (11.1%) and no comorbidities (16.3%). Around 43.7% had post-COVID-19 symptoms. The most common post-COVID-19 symptoms noted were fatigue (28.2%), breathing difficulty (12.6%) and body pain (4.9%). The post_COVID_19 symptoms are significantly higher in cases who took treatment from hospital(moderate to severe cases) (54.4%) compared to the cases who took treatment at home (35.7%). Persisting breathing difficulty is significantly higher in cases with pre-COVID-19 asthma/COPD compared to the cases with no pre-COVID-19 asthma/COPD, which makes COPD and asthma patients to be considered high risk for post-COVID-19 sequelae. Conclusion: Follow-up of COVID-19 patients should become an essential part of family physician's clinical practice