Coding Genome Sequence and Protein Sequence Analysis of Dengue Strains: In Silico Correlation

Background: DENV-1, DENV-2, DENV-3, and DENV-4 are the four serotypes of dengue viruses (DENV) that are transferred from person to person through the bite of Aedes mosquitoes. Dengue fever has surged 30-fold in occurrence over the last 50 years, making it one of the world's most serious arboviral diseases. The aim of this study is to bioinformatically correlate the coding sequences of four DENV strains to check their genetic & functional diversity on the basis of the similarity of the sequences.Methods: The coding sequences (CDs) and protein sequences of newly reported dengue strains (DENV 1, DENV 2, DENV 3, and DENV 4) were obtained from the National center for Biotechnology Information (NCBI) nucleotide and protein databases. We compare the genetic and functional compatibility of selected gene sequences from four dengue strains by using various bioinformatics tools and software such as BLAST, MEGA 11.0, ProtParam, GOR4 and SWISS Model.Results: The total number of amino acids in dengue strains DENV1, 2, 3, and 4 is 3392, 3391, 3390, and 3387, according to physiochemical analysis. The phylogenetic analysis reveals that DENV-1 and DENV-2 have more genetic similarity than DENV-2 and DENV-3, with bootstrap values greater than 90%. While different percentages of alpha helices were predicted in secondary structure, such as 33.23 %, 36.51 %, 31.21%, and 32.27% of DENV1, 2, 3, and 4 show little variation. The non-structural proteins NS1 and NS5 of all four DENV strains show more than 65 percent similarity index in 3D structure analysis.Conclusion: This study first presented a bioinformatics comparison of all four DENV strains. The 3D and 2D structures of DENV strains (1-4) show some similarity and dissimilarity index, however the four DENV strains differ in their 2D structure's alpha helix (H), random coil, and number of amino acids.Keywords: Bioinformatics; Dengue strains; Non-structural protein; Coding sequence; viral pathogenesis   

Association of Beta-2 Adrenoreceptor Single Nucleotide Polymorphism with Risk of Type II Diabetes Mellitus

Objective: To determine the genotype of Arg16Gly & Gln27Glu polymorphism in type-2 diabetes mellitus and to find possible association of ADRβ2with type-2 diabetes mellitus. Methodology: A case control study was designed and a total of 192 subjects (98 in each group) were included. After formal approval, subjects were recruited from North West General Hospital (NWGH) Peshawar. After taking consent blood samples were collected from the participants and DNA analysis was done using commercially available kits by salting out protocols, while other biochemical parameters were analyzed using normal laboratory protocols for respective tests. Results: The comparative analysis of SNP rs1042713 indicates that allele G/A was 42(49.4%) in diabetic and 43(50.6%) in non-diabetic subjects. While GG was more frequent 22(59.5%) in diabetic as compare to non-diabetic 15(40.5%). Among AA allele, 19 (65.5%) were non-diabetic while 10(34.5%) were diabetic. However the difference was not statistically significant (p=0.22). In case of “rs1042714” gene the commonest allele was C/C 80 (41.7%) out of which, 47(58.8%) was found in diabetic and 33(41.2%) were non-diabetic. Similarly CG was second common allele out of which diabetics were 27(44.3%) while non-diabetics were 34(55.7%). Allele G/G was found only among 11 subjects (p=0.085). Conclusion: Based on the result of the present study, it is concluded that polymorphism in ADRB2 genes rs1042713 (Arg16Gly) and rs1042714 (Gln27Glu) is associated with susceptibility of T2DM through alteration in BMI & HbA1c

Association of High Prevalence of Vancomycin Resistant Enterococci With Unsafe Waste Disposal Practices in Poultry Shops

Abstract: The occurrence of antibiotic resistant bacteria in human consumables like poultry is a major concern to be addressed. Fecal samples from broilers were analyzed for the presence of Vancomycin resistant Enterococci. A total of 100 broiler fecal samples obtained from different slaughterhouses of Lahore were spread on Kanamycin Aesculin Azide agar and incubated for overnight at 37ºC. The Vancomycin concentrations used during this study were 16µg/ml and 64µg/ml of the medium for enumeration of Vancomycin resistance and superbugs Enterococci, respectively. Chicken feces samples were contaminated with VRE and superbugs were 79% and 25%, respectively. It was observed that chicken feces collected from Dharampura, Islampura, Shadbagh, Garhi Shahu and Data Nagar had a heavy load of VRE. These congested and highly populated areas where there are inappropriate waste disposal systems and poor management practices contained high number of Vancomycin resistant Enterococci in chicken feces. Chicken feces samples collected from posh areas i.e., Lahore Cantt, Gulberg, Model Town, Samanabad, Walton Cantt and Allama Iqbal Town did not show any prevalence of Vancomycin resistant Enterococcus because of best hygienic practices. The prevalence of Vancomycin resistant Enterococci was high in all localities of northern division of Lahore as compared to other divisions. Results have confirmed that areas with unhygienic conditions and poor waste disposal practices promote the prevalence of Vancomycin resistant Enterococci. So, it is recommended to manage safe waste disposal practices in poultry shops to reduce the risk of food borne diseases

Comparison of Post-Operative Analgesic Efficacy of Caudal Epidural Block versus Penile Block in Children Undergoing Hypospadias

Objective: To compare the post-operative analgesic efficacy of penile block vs caudal block following hypospadias repair. Study Design: Quasi-experimental study. Place and Duration of Study: Pediatric and Plastic Surgery Departments, Combined Military Hospital, Multan Pakistan, from Jul 2019 to Jul 2021. Methodology: The total of 34 patients undergoing hypospadias operation was booked for this study after approval of the ethical committee. All patients were operated on under General anaesthesia. The booked patients were randomly divided into Groups 1 and 2. For post-operative analgesia, the first group got penile block while the latter was given caudal epidural block. Results: The mean age of the patients was 3.99±2.68 years. These patients were split into two groups. Group-1 (n=17)underwent a Penile block, and Group-2 (n=17) underwent a Caudal block. There were no serious complications after a penile block or caudal block. A substantial decline in pain scores was noted, more in the penile block group. Conclusion: For patients being treated for Hypospadias, the penile block is a more effective and simple method of pain control post-operatively. This can be performed by the surgeon

Prospecting Secondary Raw Materials in the Urban Mine and mining wastes (ProSUM) - Final Report

Batteries, electrical and electronic equipment, vehicles and mining waste contain both significant amounts and a large variety of raw materials, ranging from base metals to plastics, as well as precious metals and critical raw materials (CRMs). The EU is reliant on imports for many of these raw materials and aims to a Circular Economy. Securing responsible sourcing of those materials as well as increasing recycling rates is a complex societal challenge, partly because of the lack of structured data on the quantities, concentrations, trends and final whereabouts in different waste flows of these secondary raw materials in the Urban Mine in Europe. Currently, data on primary and secondary raw materials are available in Europe, but scattered amongst a variety of institutions including government agencies, universities, NGOs and industry. The aim of the ProSUM project was to provide a state of the art knowledge base, using best available data in a harmonised and updateable format, which allows the recycling industry and policymakers to make more informed investment and policy decisions to increase the supply and recycling of secondary raw materials

Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

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

Critical metals for electromobility : global demand scenarios for passenger vehicles, 2015–2050

Electrification of future transport sector is important to reduce direct greenhouse gas emissions and the burden on fossil fuels. The modern clean energy technologies, such as electric vehicles (EVs), contain a number of hi-tech electronics and other components that depend on a wide range of metals for their functioning. A transition to large-scale deployment of such technologies might be constrained by the limited availability of these metals in future. This study is aimed at resource criticality assessment for passenger EVs, where three main scenarios are modelled considering future demand of EVs in five geographic regions by 2050. The focus metals are aluminium (Al), cobalt (Co), copper (Cu), iron (Fe), lithium (Li), manganese (Mn), nickel (Ni), and the two rare earth elements (REEs): neodymium (Nd) and dysprosium (Dy). The scenario results show an increase in total number of EVs from 1.13 billion in 2011 to 2.6 billion in the baseline scenario, 2.55 billion in the moderate scenario, and 2.25 billion in the stringent scenario by 2050. The geological reserves of cobalt, lithium and nickel seem to face higher pressure resulting from increasing demand of these metals by EVs’ batteries. Whereas, the geopolitical supply risk factor becomes important in case of REEs due to existing market concentration. Recycling and technology substitution at various levels seem to reduce the vulnerability of EVs to increasing geological and geopolitical supply risk of metals