Correlating multi-functional role of cold shock domain proteins with intrinsically disordered regions

Cold shock proteins (CSPs) are an ancient and conserved family of proteins. They are renowned for their role in response to low-temperature stress in bacteria and nucleic acid binding activities. In prokaryotes, cold and non -cold inducible CSPs are involved in various cellular and metabolic processes such as growth and development, osmotic oxidation, starvation, stress tolerance, and host cell invasion. In prokaryotes, cold shock condition re-duces cell transcription and translation efficiency. Eukaryotic cold shock domain (CSD) proteins are evolved form of prokaryotic CSPs where CSD is flanked by N-and C-terminal domains. Eukaryotic CSPs are multi-functional proteins. CSPs also act as nucleic acid chaperons by preventing the formation of secondary structures in mRNA at low temperatures. In human, CSD proteins play a crucial role in the progression of breast cancer, colon cancer, lung cancer, and Alzheimer's disease. A well-defined three-dimensional structure of intrinsically disordered re-gions of CSPs family members is still undetermined. In this article, intrinsic disorder regions of CSPs have been explored systematically to understand the pleiotropic role of the cold shock family of proteins

Az első 200 transzkatéteres aortabillentyű-implantáció a Gottsegen György Országos Kardiológiai Intézetben | The first 200 transcatheter aortic valve implantations in the Gottsegen György Institute of Cardiology, Hungary

Absztrakt Bevezetés: Napjainkban a súlyos panaszos aortastenosis kezelésében a transzkatéteres billentyűimplantáció a sebészi billentyűcsere elérhető alternatíváját jelenti sebészi kontraindikáció és elfogadhatatlanul magas műtéti kockázat esetén. A szerzők intézetében ez a beavatkozás ma már a mindennapi rutin részének számít. Célkitűzés: A szerzők az első 200, transzkatéteres billentyűimplantációban részesült beteg eredményeit tárgyalják. Módszer: 2016. januárig 200 sikeres implantáció történt. A betegek 55%-a nő, átlagéletkoruk 79,9 év volt, az átlagos EuroSCORE: 19,3%, az átlagos ejekciós frakció: 54%, az aortabillentyűn mérhető csúcsgradiens 81,2 Hgmm, az átlaggradiens: 50,9 Hgmm volt. Eredmények: A beavatkozásokat 99%-os sikeraránnyal végezték, a szövődmények feldolgozása a VARC-2 kritériumrendszer alapján történt. Az egy hónapos mortalitás 5%, az egyéves pedig 17,4% volt, utóbbiból a kardiális mortalitás 13,6% volt. Az egyéves cerebrovascularis történések előfordulása 5% volt. Az egyéves kontroll során a betegek 95%-a NYHA I vagy II funkcionális állapotban volt. Következtetés: Az eredmények nem térnek el lényegesen a nemzetközi vizsgálatok eredményeitől. Orv. Hetil., 2016, 157(45), 1786–1792. | Abstract Introduction: Transcatheter aortic valve implantation is a therapeutic alternative for contraindicated and high surgical risk patients with severe symptomatic aortic stenosis. This intervention is part of daily routine in the Institute of the authors. Aim: In the present work the results of the first 200 patients are discussed. Method: Until January, 2016, 200 patients (female 55%, mean age 79.9 years, average EuroSCORE 19.3%, left ventricular ejection fraction 54%, peak gradient 81.2 mmHg, mean aortic gradient 50.9 mmHg) underwent transcatheter aortic valve implantation. Results: The procedure was performed with 99% success rate. Complications were evaluated according to VARC 2 definitions. Mortality was 5% at one month and 17.4% at one year. Cardiac mortality was 13.6 at one year. Cerebrovascular complications were 5% within one year, and 95% of patients were in NYHA I or II functional classes at one year. Conclusion: These findings are consistent with worldwide results. Orv. Hetil., 2016, 157(45), 1786–1792

Identification of Close Relatives in the HUGO Pan-Asian SNP Database

The HUGO Pan-Asian SNP Consortium has recently released a genome-wide dataset, which consists of 1,719 DNA samples collected from 71 Asian populations. For studies of human population genetics such as genetic structure and migration history, this provided the most comprehensive large-scale survey of genetic variation to date in East and Southeast Asia. However, although considered in the analysis, close relatives were not clearly reported in the original paper. Here we performed a systematic analysis of genetic relationships among individuals from the Pan-Asian SNP (PASNP) database and identified 3 pairs of monozygotic twins or duplicate samples, 100 pairs of first-degree and 161 second-degree of relationships. Three standardized subsets with different levels of unrelated individuals were suggested here for future applications of the samples in most types of population-genetics studies (denoted by PASNP1716, PASNP1640 and PASNP1583 respectively) based on the relationships inferred in this study. In addition, we provided gender information for PASNP samples, which were not included in the original dataset, based on analysis of X chromosome data

Population Genetic Structure of Peninsular Malaysia Malay Sub-Ethnic Groups

Patterns of modern human population structure are helpful in understanding the history of human migration and admixture. We conducted a study on genetic structure of the Malay population in Malaysia, using 54,794 genome-wide single nucleotide polymorphism genotype data generated in four Malay sub-ethnic groups in peninsular Malaysia (Melayu Kelantan, Melayu Minang, Melayu Jawa and Melayu Bugis). To the best of our knowledge this is the first study conducted on these four Malay sub-ethnic groups and the analysis of genotype data of these four groups were compiled together with 11 other populations' genotype data from Indonesia, China, India, Africa and indigenous populations in Peninsular Malaysia obtained from the Pan-Asian SNP database. The phylogeny of populations showed that all of the four Malay sub-ethnic groups are separated into at least three different clusters. The Melayu Jawa, Melayu Bugis and Melayu Minang have a very close genetic relationship with Indonesian populations indicating a common ancestral history, while the Melayu Kelantan formed a distinct group on the tree indicating that they are genetically different from the other Malay sub-ethnic groups. We have detected genetic structuring among the Malay populations and this could possibly be accounted for by their different historical origins. Our results provide information of the genetic differentiation between these populations and a valuable insight into the origins of the Malay sub-ethnic groups in Peninsular Malaysia

The global burden of adolescent and young adult cancer in 2019 : a systematic analysis for the Global Burden of Disease Study 2019

Background In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults. Findings There were 1.19 million (95% UI 1.11-1.28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59.6 [54.5-65.7] per 100 000 person-years) and high-middle SDI countries (53.2 [48.8-57.9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14.2 [12.9-15.6] per 100 000 person-years) and middle SDI (13.6 [12.6-14.8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23.5 million (21.9-25.2) DALYs to the global burden of disease, of which 2.7% (1.9-3.6) came from YLDs and 97.3% (96.4-98.1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Clinical Profile of Patients Hospitalized with Heart Failure inBharatpur, Nepal

Introduction: Heart failure (HF) is a common cardiovascular condition whose incidence and prevalence are increasing. Being a common reason for urgent hospital admission, it is a major cause of morbidity and mortality for the patients. In the developed countries coronary artery disease remains the leading cause of HF, whereas, in the underdeveloped countries, rheumatic heart disease leading to valvular lesion still remains the commonest causes of HF admission. The current study was designed to evaluate the clinical profile and medications prescribed reflecting the extent to which evidence based medicine is being practiced at our community. Methods: Clinical profile and prescribed medications of patients with diagnosis of HF who were admitted in the cardiology department of College of Medical Sciences & Teaching Hospital (CMS-TH), Bharatpur, Nepal, April 2010 to May 2012, were analyzed. A total of 255 patients presented with HF during the studied period were included. Results: Coronary artery disease, rheumatic heart disease, dilated cardiomyopathy, hypertensive heart failure, cor-pulmonale, and congenital heart disease leading to HF were found in 93 (36.5%), 65 (25.5%), 37 (14.5%), 22 (8.6%), 31 (12.2%),and 7 (2.7%) patients respectively. The commonest presenting symptom was shortness of breath (81%) and the commonest sign was bilateral basal crepitations (68%). From all patients, 89%, 64%, 51%, 16%, 48%, and 32% received loop diuretics, angiotensin-converting enzyme inhibitor, digoxin, angiotensin receptor blocker, spironolactone, and beta-blocking agents respectively. Conclusion: Coronary artery disease leading to HF was the commonest cause of HF admission in our centre. Despite current guidelines suggesting the use of beta-blocking agent in patients with HF, only 32% of our patients received this class of medications. Thus, many patients were not being managed fully in accordance with the evidence-based guidelines

Prospective randomized trial to evaluate the efficacy of single low dose ATG induction in renal transplant recipient with spousal kidney

Objective: To see the efficacy and safety of single low dose ATG induction on graft survival, rejection, infection and development of malignancy in spousal renal trans-plant recipient. Materials and Methods: A prospective randomized trial was conducted between July 1996-January 2000. Single dose (3.5-5 mg/kg) ATG induction was used in 30 patients while 30 patients were taken as control. Standard triple drug immunosuppression was given to both the groups, while study received additional single shot of rabbit ATG (Fresenius, Germany: 200 mg in 200 ml of saline). The patients were followed up for a mean of 30.4 months (range 19-46 months) in both groups. Graft function, rejections, episodes, anti-rejection therapy, infections and develop-ment of malignancy was analyzed at the last follow-up. Result: There were 24 males and 6 females in control group with a mean age of′44.26 years and 26 males and 4 females in control group with a mean age of 41.26 years. Patients′ characteristics in both the groups were compa-rable. A total of 26 (86.3%) patients in induction and 24(80%) patients in control group were evaluated at last follow-up (mean 30.4 vs. 30.2 months). Stable graft func-tion was present in 83.3% patients in induction versus 70% in control group. Impaired graft, function (serum creati-nine> 2 mg%) was present only in 10% of control group and none of the patients in the study group at last follow-up. The total number of rejections were 23.3 and 43.3% in induction and control group respectively. 2 patients in each group who developed multiple episodes of rejection progressed to chronic rejection. Steroid resistant rejec-tions were less with induction therapy than with control group (14.4 vs. 30.7%). Apart from increased urinary tract infections in study group (46.7 vs. 23.3%), infection at other sites were comparable in both the groups. 2 patients in study group and 4 patients in control group died with, functioning graft due to medical problems. 2 patients were lost to follow-up in both the groups. I patient required graft nephrectomy in induction group, due to severe graft dysfunction with significant proteinuria. Conclusion: Single shot low dose ATG induction therapy reduces the rejection episodes (p=0.05), but it has not shown any improvement in graft survival at 2′/z years. It is associated with higher urinary infection rates. How-ever, long-term, follow-up is needed to see any benefit of less rejection on long-term graft survival

Design and Analysis of Welding Electrode Coating die and set up for coating of flux on SS308 core wire

This project deals with designing and developing of welding electrode coating set up for coating of flux on SS308 core wire. The composition and constituents of flux material like rutile, dolomite, etc. are used for coating of core wire. These compositions can be varied well on hit and trial basis to attain the desired results and observe reduction of welding defects. A small set up for preparing the flux cored welding wires specially for welding austenitic stainless steel of SS 308 is designed using manual feeding and collecting system. Basic process parameters like die cross section, required pressure, wire feed rate in die and volume of flux material required for proper coating of single electrode are calculated with the help of data obtained by industry survey. Analysis of the die used in setup has been presented in this paper. With the help of the calculated values an appropriate die of AISI 304 is designed

Cardiac Rhabdomyoma In Familial Tuberous Sclerosis

Cardiac rhabdomyomas are often associated with tuberous sclerosis in infants. We report a 5 month old child presented with a tumor in the right ventricle and echocardiography features of rhabdomyoma. Both the child and her father had cutaneous features of tuberous sclerosis. In the absence of features of congestive heart failure, surgery is rarely required