Hypotensive Activity of Moringa oleifera Lam (Moringaceae) Root Extracts and its Volatile Constituents

Purpose: To explore the hypotensive activity and chemical composition of Moringa oleifera Lam (Moringaceae) roots.Methods: The fresh roots of M. oleifera was cut into small pieces and successively extracted with petroleum ether (PE) and dichloromethane (DC). PE extract was  further divided into MRP and MRP -1. DC extract showed a thick mass during evaporation which was separated as MRDC - IN. The mother liquor left was divided into MRDC and MRDC -1. All residues were analyzed by gas chromatographymass spectroscopy (GC-MS) using ZB-5 column. Identification of each extract and fraction was based on comparison of their retention indices (RI), by co-injecting authentic compounds, as well as by comparing literature data available in NIST Standard Reference Database. Hypotensive activity was determined on urethane-anesthetized normotensive Sprague Dawly rats.Results: Petroleum ether (MRP) and dichloromethane (MRDC) extracts of M. oleifera roots showed 50.06 ± 3.48 and 48.16 ± 1.79 % fall in mean arterial blood  pressure (MABP), respectively, at a dose of 30 mg/kg (p < 0.01 and p < 0.05, respectively) compared with control. GC-MS analysis of MRP and MRDC extracts and fractions resulted in the identification of seventy four (74) compounds. Methyl hexadecanoate (7, 20.3 %) , stigmastan - 3, 5, diene (24, 19.32 %), methyl  14-hydroxy-5-tetradecenoate (9, 19.22 %), 1 , 11 diphenyl undecane (47, 18.78 %) and cyclopentanyl hexadecane (39, 14.44 %) were the major constituents  among the various hydrocarbons, fatty acids, esters, alcohols, aldehydes, isothiocyanate, aromatics, steroids, terphenyl and sulphur-containing compounds. Conclusion: The findings reveal the hypotensive potential of M. oleifera roots and the presence of specific hydrocarbons, fatty acid esters, thioureides, steroids and isothiocyanates in active fractions. Further study is required to determine the suitability of the plant as an antihypertensive remedy.Keywords: Moringa oleifera, Methyl hexadecanoate, Methyl 14-hydroxy-5-tetradecenoate, Petroleum ether, Stigmastan - 3, 5, diene, Cyclopentanyl hexadecan

Risk Factors of Diarrhoea in Malnourished Children Under Age of 5 Years

Background: Acute infectious enteritis remains one of the commonest causes of death among infants and children in developing countries. Acute enteritis is defined as a loss of stool consistency with pasty or liquid stools, and/or an increase in stool frequency to more than three stools in 24 hours with or without fever or vomiting. Human survival depends on the secretion and reabsorption of fluid and electrolytes in the intestinal tract. The objective of the study is to evaluate the risk factors of diarrhoea in children under age of 5 years. Methodology: It was an observational study. Study was completed in about six months. Non-probability purposive sampling technique was used. In this study, 270 samples were taken from Diarrheal ward of The Children Hospital Lahore, Pakistan. Results: In this study, out of 270 patients, 58.52% were males and 41.48% were females. 90.37% patients were vaccinated. 54.81% had weaning history. 91.85% patients had feeding history. 29.26% had blood in stool. 96.67% patients were dehydrated. 95.56% patients had loose watery diarrhoea. 62.96% patients used boiled water. 58.52% patients consumed less than half litre of water, 30.00% patients consumed 1 litre of water and 11.48% patients consumed > 1 litre of water. 49.18% patients had proper hygiene. 38.15% mothers of patients were well educated. 40.37% patients had model household condition. 57.41% patients lived in rural area and 42.59% patients lived in urban area. Conclusion: The variation in the level of diarrheal morbidity was well explained by maternal education, income, personal hygiene, refuse disposal system and the effect of health extension programme

Prescription of medicines by medical students of Karachi, Pakistan: A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Prescription of medicines by non-doctors is an issue with serious global implications. To our knowledge prescription of drugs by medical and non-medical students has not been studied before. We aimed to determine the practice and attitudes of drug prescription by medical students and: a) how non-medical students respond to this practice, b) How this compares with the attitudes and practices of non-medical students.</p> <p>Methods</p> <p>A cross-sectional study was conducted on a sample of 600 students randomly selected from 2 medical and 2 non-medical universities. Ethical requirements were ensured and data was collected using self administered questionnaires. The Chi square tests and logistic univariate regression analyses were performed using SPSS v 14 to identify associations and differences.</p> <p>Results</p> <p>A total of 572 forms were completed and the sample consisted of 295 medical students and 277 non-medical students with no significant difference in their demographic profile. Of the 295 medical students 163 (55.3%) had prescribed a medicine independently and most (48.5%) said that they did this 2–3 times a year. The commonest reasons for this were 'previous experience' (68.7%), 'problem too trivial' (34.4%) and 'we knew everything about the condition' (31.3%). One-third (33.6%) of the undergraduate medical students thought that it was alright to independently diagnose an illness while a vast majority (78.3%) thought that it was alright for them to prescribe medicines to others. Common prescriptions were pain-killers, antipyretics, antiallergics and antibiotics. Medical students who prescribed medicines were of lesser age (CI = 1.366–1.887) and more likely to belong to the 1^st(CI = 3.588–21.731), 2^nd(CI = 2.059– 10.869) or 3^rd(CI = 4.331–26.374) year of medical college. One-third (33.9%) of the non-medical students reported that a medical student had prescribed medicines to them and 21.3% said that they trusted medical students and would follow their advice blindly. Many students thought it alright for medical students to diagnose and treat illnesses. A similar proportion of non-medical students (58.5%) reported prescribing medicines to others.</p> <p>Conclusion</p> <p>Prescription of medicines by non-doctors is rampant and urgent corrective measures are warranted. We have highlighted areas for future research and intervention and have given a few recommendations.</p

Tackling antimicrobial resistance in primary care facilities across Pakistan : current challenges and implications for the future

Antibiotics are gradually becoming less effective against bacteria worldwide, and this issue is of particular concern in economically-developing nations like Pakistan. We undertook a scoping review in order to review the literature on antimicrobial use, prescribing, dispensing and the challenges associated with antimicrobial resistance in primary care (PC) settings in Pakistan. Furthermore, this review aims to identify potential solutions to promote appropriate use of antimicrobials in Pakistan. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) checklist, a comprehensive scoping review was conducted to review the literature of antimicrobials used, prescribed and dispensed in PC settings in Pakistan. Google Scholar and Pub-Med were searched for the period 2000–2023. Papers were analyzed on the basis of eligibility i.e., included antimicrobial use, prescribing and dispensing practices by general population at homes, by prescribers in outpatient departments of hospitals and by pharmacists/dispensers in community pharmacies, respectively. Two researchers analyzed the articles thoroughly and disagreements were resolved through discussion with a third reviewer. Both quantitative and qualitative research studies were eligible for inclusion. Additionally, the selected papers were grouped into different themes. We identified 4070 papers out of which 46 studies satisfied our eligibility criteria. The findings revealed limited understanding of antimicrobial resistance (AMR) by physicians and community pharmacists along with inappropriate practices in prescribing and dispensing antibiotics. Moreover, a notable prevalence of self-medication with antibiotics was observed among the general population, underscoring a lack of awareness and knowledge concerning proper antibiotic usage. Given the clinical and public health implications of AMR, Pakistan must prioritize its policies in PC settings. Healthcare professionals (HCPs) need to reduce inappropriate antibiotic prescribing and dispensing, improve their understanding of the AWaRe (access, watch and reserve antibiotics) classification and guidance, monitor current usage and resistance trends, as well as implement antimicrobial stewardship (ASP) activities starting in targeted locations

Envelope 2 protein phosphorylation sites S75 & 277 of hepatitis C virus genotype 1a and interferon resistance: A sequence alignment approach

<p>Abstract</p> <p>Background</p> <p>Hepatitis C is a major health problem affecting more than 200 million individuals in world including Pakistan. Current treatment regimen consisting of interferon alpha and ribavirin does not always succeed to eliminate virus completely from the patient's body.</p> <p>Results</p> <p>Interferon induced antiviral protein kinase R (PKR) has a role in the hepatitis C virus (HCV) treatment as dsRNA activated PKR has the capacity to phosphorylate the serine and threonine of E2 protein and dimerization viral RNA. E2 gene of hepatitis C virus (HCV) genotype 1 has an active role in IFN resistance. E2 protein inhibits and terminates the kinase activity of PKR by blocking it in protein synthesis and cell growth. This brings forward a possible relation of E2 and PKR through a mechanism via which HCV evades the antiviral effect of IFN.</p> <p>Conclusion</p> <p>A hybrid in-silico and wet laboratory approach of motif prediction, evolutionary and structural anlysis has pointed out serine 75 and 277 of the HCV E2 gene as a promising candidate for the serine phosphorylation. It is proposed that serine phosphorylation of HCV E2 gene has a significant role in interferon resistance.</p

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

Biodiversity of Gut Microbiota: Impact of Various Host and Environmental Factors

Human bodies encompass very important symbiotic and mutualistic relationships with tiny creatures known as microbiota. Trillions of these tiny creatures including protozoa, viruses, bacteria, and fungi are present in and on our bodies. They play important roles in various physiological mechanisms of our bodies. In return, our bodies provide them with the habitat and food necessary for their survival. In this review, we comprehend the gut microbial species present in various regions of the gut. We can get benefits from microbiota only if they are present in appropriate concentrations, as if their concentration is altered, it will lead to dysbiosis of microbiota which further contributes to various health ailments. The composition, diversity, and functionality of gut microbiota do not remain static throughout life as they keep on changing over time. In this review, we also reviewed the various biotic and abiotic factors influencing the quantity and quality of these microbiota. These factors serve a significant role in shaping the gut microbiota population

Synchronized electrochemical detection of hydroquinone and catechol in real water samples using a Co@SnO2-polyaniline composite

The conductive composite Co@SnO2-PANI was successfully synthesized using hydrothermal/oxidative synthesis. Using differential pulse voltammetry, a glassy carbon electrode modified with a CoSnO2-PANI (polyaniline)-based electrochemical biosensor has been created for the quick detection of two phenolics, hydroquinone (Hq) and catechol (Cat). Differential pulse voltammetry (DPV) measurements revealed two well-resolved, strong peaks for GCE@Co-SnO2-PANI, which corresponded to the oxidation of Hq and Cat at 275.87 mV and +373.76 mV, respectively. The oxidation peaks of Hq and Cat mixtures were defined and separated at a pH of 8.5. High conductivity and remarkable selectivity reproducibility was tested by electrochemical impedance spectroscopy, chronoamperometry, and cyclic voltammetry techniques in standard solution and real water samples. The proposed biosensor displayed a low detection limit of 4.94 nM (Hq) and 1.5786 nM (Cat), as well as a large linear range stretching from 2 × 10−2 M to 2 × 10−1 M. The real-sample testing showed a good recovery for the immediate detection of Hq (96.4% recovery) and Cat (98.8% recovery) using the investigated sensing apparatus. The synthesized biosensor was characterized by XRD, FTIR, energy dispersive spectroscopy and scanning electron microscopy

The causes of stillbirths in south Asia: Results from a prospective study in India and Pakistan (PURPOSe)

Background: South Asia contributes more than a third of all global stillbirths, yet the causes remain largely unstudied in this region. New investigations, including novel assessments of placental and fetal tissues, facilitate more precise determination of the underlying causes of stillbirth. We sought to assess underlying and contributing causes of stillbirth from settings in India and Pakistan.Methods: In this prospective cohort study (PURPOSe), we report the cause of death in stillbirths in hospitals in central India and south Pakistan (Davangere, India [three public and private hospitals] and Karachi, Pakistan [one public maternity and one children\u27s hospital]). Women aged 15 years or older and with a known stillbirth (defined as a pregnancy at 20 or more weeks of gestation with the in-utero death of a fetus) weighing 1000 g or more were included in the study. Maternal clinical factors, placental evaluation, fetal tissue evaluation (from minimally invasive tissue sampling), and PCR for microbial pathogens were used to identify the causes of death. An expert panel reviewed available data for all stillbirths to identify the primary and contributing maternal, placental, and fetal causes of stillbirth.Findings: Between Sept 1, 2018, and Feb 12, 2020, 981 stillborns were included and, of those, 611 were reviewed by the expert panel. The primary maternal causes of stillbirth were hypertensive disease in 221 (36%) of 611 stillbirths, followed by severe anaemia in 66 (11%) stillbirths. The primary placental causes were maternal and fetal vascular malperfusion, in 289 (47%) stillbirths. The primary fetal cause of stillbirth was intrauterine hypoxia, in 437 (72%) stillbirths. We assessed the overlap of main causes and 116 (19%) stillbirths had intrauterine hypoxia, placental malperfusion, and eclampsia or pre-eclampsia indicated as primary causes of death. Infection (including of the placenta, its membranes, and in the fetus) and congenital anomalies also were causative of stillbirth.Interpretation: In south Asia, fetal asphyxia is the major cause of stillbirth. Several placental lesions, especially those associated with maternal and fetal vascular malperfusion and placental abruption, have an important role in asphyxia and fetal death. Maternal hypertension, and especially pre-eclampsia, is often the primary maternal condition associated with this pathway.Funding: Bill & Melinda Gates Foundation