Oxidative Stress Diminishing Perspectives of Green and Black Tea Polyphenols: A Mechanistic Approach

Polyphenols have credentials to tackle the oxidative stress. Oxidative stress is the imbalance between free radicals production and antioxidant enzymes ability to tackle these radicals resulting the onset various metabolic related disorders. Polyphenols based foods have credential as a shield against these glitches mainly owing to their antioxidant potential. In this context, tea polyphenols have gained paramount attention of scientific community as therapeutic agents for the prevention and treatment of various oxidative stress induce maladies owing to their structural diversity, strong antioxidant ability and capacity to modulate various expression involved in the pathogenesis of these maladies. The notable polyphenols are catechins which are mainly present in green tea and further subdivided into various compounds like ECG, EGC, EGCG which has their unique therapeutic potential. The catechins undergo various structural changes and transformed into theaflavins and thearubigins in the process of black tea formation. These are high molecular weight polyphenols and promising candidates in obesity, diabetes and cancer treatment. Mechanistically, these polyphenols ameliorate oxidative stress by trapping the noxious radicals like superoxide and peroxyl, promote the activity of glutathione, suppressing the malondialdehyde (MDA) activity. The current chapter is an attempt to highlight the therapeutic potential of tea polyphenols

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

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

Factors influencing COVID-19 vaccine hesitancy and acceptance among the Pakistani population

This study examined the factors associated with acceptance of the COVID-19 vaccine compared to hesitance in the Pakistani population and specifically focusing on the perceived beliefs, knowledge, concerns, risk, and safety perception relating to the COVID-19 vaccine. A total of 423 subjects were recruited from the Pakistan Institute of Medical Sciences, Islamabad, Pakistan. A 27-item valid and reliable questionnaire was used to assess socio-demographic characteristics, acceptance, and hesitance toward COVID-19 vaccine, perceived beliefs, knowledge, perceived concerns, risk, and safety of COVID-19 vaccines and its source of information. Chi-square tests and logistic regression were used for analysis. About 53% of the participants were planning to get vaccinated and a significantly greater proportion of better educated, higher income, and healthier participants in the vaccine acceptance group (p < .05). The odds of knowing the vaccine they should get, having the confidence in the vaccine to stop the pandemic, and understanding the way vaccines work, were greater in the vaccine acceptance group than the vaccine-hesitant group (OR: 5.4; 3.5, 2.1, 3.1, respectively). Most participants (52.3%) obtained the information regarding the COVID-19 vaccine from the print and live news media (52.3%) followed by social media (23.7%). The lack of knowledge, understanding, and perception of the risk, safety partly explains the low rate of vaccine acceptance in the Pakistani population. Strategies to raise awareness of the benefits of vaccination should target individuals in the lower socioeconomic group and those with chronic disease

Association of ADIPOQ Non-Synonymous SNPs with Type 2 Diabetes-A Bioinformatics Study

Background: To find out association of nsSNPs in adiponectin gene with Type 2 Diabetes.Methods: In this study Bioinformatic analysis was done by using various bioinformatic tools to identify the nsSNPs present in ADIPOQ gene. The nsSNPs were further checked for their deleterious nature through different computational algorithms.Results: This study identified 19 nsSNPs, out of which three most deleterious were selected i.e., rs372597136 (P47L), rs79645624 (G90S) and rs62625753 (R112H). Characterization and 3D models of superimposed structures of wild type and mutated protein showed the change occur due to presence of nsSNP.Conclusion: Identified SNPs should be now checked in Pakistani population for their association with type-II diabetes. This study can provide platform for clinicians to design novel studies to identify association of genetic risk factors for different complex disease

In Vitro Antimicrobial Activity of Garlic (Allium Sativum) Against Clinical Isolates of Vibrio Cholerae

Introduction: To study the in vitro antimicrobialactivity of garlic (Allium Sativum) against clinicalisolates of Vibrio CholeraeMethods: Thirty three clinical isolates of V.cholerae were evaluated for their susceptibility toaqueous extract of Pakistani and Chinese garlic.ATCC strain of P. aeruginosa (ATCC 27853) wasused as the standard control strain. The cloves werepeeled and blended (50 gm) in 90 ml of distilledwater in separate blenders. The extracts weresterilized by gamma radiation. Aqueous extracts ofPakistani and Chinese garlic were tested intriplicate. Quantitative analysis of Pakistani andChinese garlic aqueous extracts was done. As theextracts of both types of Pakistani and Chinese garlicexhibited inhibitory effect against test strain of V.cholerae, aqueous extracts were further evaluated inagar dilution assay to determine MIC against thirtythree clinical isolates of V. cholerae and one ATCCreference strain.Results: The zones of inhibition measured by usingagar well diffusion assay were 28.12 mm and 32.14mm for Pakistani and Chinese garlic aqueousextracts respectively. All the isolates were inhibitedat concentration of 8.66 mg/mL by Chinese garlic andat 10 mg/mL by Pakistani garlic aqueous extract.Conclusion: Natural sources, like garlic extracts ,may be an effective alternative, to resistant strains ofvibrio cholera

Habitat preference and roosting behaviour of the Red Junglefowl Gallus gallus (Aves: Galliformes: Phasianidae) in Deva Vatala National Park, Azad Jammu & Kashmir, Pakistan

In Pakistan the Red Junglefowl is reported only from Deva Vatala National Park.  The present study investigated the habitat preference and roosting behavior of the Red Junglefowl in three different habitat types which included a wild area, cultivated lands and a human settlement area.  Habitat preference during the summer season comprised 87.50% wild area, 2.5% cultivated area and 10% human settlement area; during the winter season, the preference was 90% wild area and 10% human settlement area.  More numbers of female birds (22) were seen during both the seasons as compared to males (17).  The birds preferred old trees for roosting.  A total of 16 roost sites were explored on five different tree species; including Acacia nilotica (25%), Acacia modesta (12.5%), Olea ferruginea (18.75%), Magnifera indica (25%) and Dalbergia sissoo (18.75%).  The species roosted in groups of 4-8 birds and the duration of the average roosting time was about eight and half hours.  We propose that similar studies on the ecology of Red Junglefowl should be conducted to get a better understanding of the species in the study area which is perquisite for its conservation. </div

Postoperative Complications in Carcinoma Gall Bladder: A Tertiary Care Hospital Experience

Introduction: Gallbladder cancer is more common than any other part of the biliary system. Accounting between 2% and 3% of all cholecystectomies. Aims &Objectives: To analyze different postoperative complications in various stages of operated gall bladder carcinoma. Place and duration of study: Army Liver Transplant Unit (A.L.T.U.) Pak Emirates Military Hospital Rawalpindi (P.E.M.H.), from November 2020 to April 2022. Material & Methods: This cross-sectional descriptive study looked at all patients diagnosed with gallbladder cancer before surgery or who were subsequently found to have benign gallbladder cancer presenting with intra-luminal lesions and localized or diffuse wall thickening amenable to surgical treatment. A sequential sampling method was used to select the patients. A proforma was developed to streamline the data collection process. The patient's gallbladder cancer was staged using the A.J.C.C.'s Eighth Edition staging system, and the degree of complications was classified using the Clavien-Dindo system. Data was entered and analysed using SPSS version 23. Results: A total of 27 patients were included in the study, with male to female ratio of 1:3; and a mean age of 50.1 ± 4.7 years (range 25-70 years). Six patients were in Stage-1 of whom only 1 (3.7%) developed grade – I complication; 9 patients were in Stage-2, out of which 2 (7.4%) developed grade – II complications; 6 patients were in Stage-3, out of which 2 (7.4%) patients developed grade – III and 1 (4.7%) patient developed grade-II postoperative complications. Six (22.2%) were in Stage-4 and underwent curative resection, where no patient developed postoperative complications. Conclusion: Surgery remains a solitary curative option for gall bladder carcinoma, and when patients are selected carefully, postoperative complications after radical surgery are not very high. Moreover, as the stage of the disease increases, so does the complication grade

High morbidity and mortality in children with untreated congenital deficiency of leptin or its receptor.

The long-term clinical outcomes of severe obesity due to leptin signaling deficiency are unknown. We carry out a retrospective cross-sectional investigation of a large cohort of children with leptin (LEP), LEP receptor (LEPR), or melanocortin 4 receptor (MC4R) deficiency (n = 145) to evaluate the progression of the disease. The affected individuals undergo physical, clinical, and metabolic evaluations. We report a very high mortality in children with LEP (26%) or LEPR deficiency (9%), mainly due to severe pulmonary and gastrointestinal infections. In addition, 40% of surviving children with LEP or LEPR deficiency experience life-threatening episodes of lung or gastrointestinal infections. Although precision drugs are currently available for LEP and LEPR deficiencies, as yet, they are not accessible in Pakistan. An appreciation of the severe impact of LEP or LEPR deficiency on morbidity and early mortality, educational attainment, and the attendant stigmatization should spur efforts to deliver the available life-saving drugs to these children as a matter of urgency