Assessment of threatened status, phytochemical composition and biological properties of three Aconitum species from Kashmir Himalaya - India

Genus Aconitum (Ranunculaceae) is represented by 6–8 species from Kashmir Himalaya.  Traditionally Aconitum species are used to treat a wide array of diseases, but their ethnopharmacological validation and phytochemistry are hitherto unreported from Kashmir Himalaya. The present study was undertaken to bring insights into the traditional use and distribution pattern of three Aconitum species from the region. An ethnobotany-directed approach was employed to study the conservation status of three Aconitum species. Their phytochemical profiles and biological properties were screened under in vitro conditions. Folin–ciocalteu and Aluminium chloride assays were employed to measure their total phenolic and total flavonoid contents, respectively. Plant extracts were evaluated for antioxidant, antimicrobial and anti-inflammatory activities. Three Aconitum species, viz. Aconitum heterophyllum Wall. ex Royle, Aconitum violaceum Jacquem. ex Stapf and Aconitum chasmanthum Stapf. ex Holmes showed dwindling conservation status in Kashmir Himalaya. Aconitum extracts showed significant variations in total phenolic and flavonoid contents. Antioxidant activity of Aconitum chasmanthum methanolic extract was studied to be comparatively higher (80.115%). Aconitum chasmanthum DCM & methanolic extracts showed a good MIC value of 0.125 mg/ml against Candida albicans and Streptococus pyogenes, respectively. The percent inhibition of NLRP inflammasome was found significant in Aconitum violaceum ethyl acetate extract (74.61%). The present study revealed that Aconitum species are constantly declining at least in investigated habitats of Kashmir Himalaya and hence need strategic conservation planning. The results also emphasized the utility of Aconitum species as an antioxidant, antimicrobial and anti-inflammatory agent that could be used to manage various health problems

Evaluating the in vitro antituberculosis, antibacterial and antioxidant potential of fungal endophytes isolated from Glycyrrhiza glabra L

Abstract Endophytes, especially from medicinal plants and those from biodiversity rich ecoregions synthesize important bioactive molecules. The aim of the present study was to isolate and characterize the bioactive fungal endophytes from Glycyrrhiza glabra L. of Kashmir Himalayas-a biodiversity rich ecoregion in India. Plant material was collected from different location of Kashmir region for isolation of fungal endophytes. A total of thirty-three strains were isolated and their broth was screened for their antimicrobial activity by well diffusion assay. Potent endophytes were selected and identified by ribosomal gene sequence technique. The extracts of selected endophytes were evaluated for antibacterial as well as antimycobacterial and antioxidant activities by broth microdilution technique and DPPH assay, respectively. Thirteen isolates (40%) displayed antimicrobial activity against at least one pathogen. The extract of isolates identified as Fusarium solanistrain (KT16646), Fusarium oxysporum strain (KT166447), Colletotrichum gleosporoides strain (KT166445) and Alternaria alternate strain (KT166448) displayed strong antimicrobial activity with MIC ranging from <2.34 to 125 µg/ml against various tested bacterial pathogens. F. solani and C. gleosporoides showed good activity against Mycobacterium tuberculosis (M. tb) strain H37Rv with MIC of 18.5 and 75 µg/ml, respectively. F. oxysporum exhibited good antioxidant activity with IC 50 value of <100 µg/ml. To the best of our knowledge, this is the first study that reports antimycobacterial activity of any fungal endophyte isolated from G. glabra against the virulent strain of M tb. Thus, this study sets background towards the exploration of potential bioactive molecules that may have antituberculosis, antibacterial and antioxidant activity from the fungal endophytes of G. glabra

Association of respiratory symptoms and lung function with occupation in the multinational Burden of Obstructive Lung Disease (BOLD) study

Background Chronic obstructive pulmonary disease has been associated with exposures in the workplace. We aimed to assess the association of respiratory symptoms and lung function with occupation in the Burden of Obstructive Lung Disease study. Methods We analysed cross-sectional data from 28 823 adults (≥40 years) in 34 countries. We considered 11 occupations and grouped them by likelihood of exposure to organic dusts, inorganic dusts and fumes. The association of chronic cough, chronic phlegm, wheeze, dyspnoea, forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1)/FVC with occupation was assessed, per study site, using multivariable regression. These estimates were then meta-analysed. Sensitivity analyses explored differences between sexes and gross national income. Results Overall, working in settings with potentially high exposure to dusts or fumes was associated with respiratory symptoms but not lung function differences. The most common occupation was farming. Compared to people not working in any of the 11 considered occupations, those who were farmers for ≥20 years were more likely to have chronic cough (OR 1.52, 95% CI 1.19–1.94), wheeze (OR 1.37, 95% CI 1.16–1.63) and dyspnoea (OR 1.83, 95% CI 1.53–2.20), but not lower FVC (β=0.02 L, 95% CI −0.02–0.06 L) or lower FEV1/FVC (β=0.04%, 95% CI −0.49–0.58%). Some findings differed by sex and gross national income. Conclusion At a population level, the occupational exposures considered in this study do not appear to be major determinants of differences in lung function, although they are associated with more respiratory symptoms. Because not all work settings were included in this study, respiratory surveillance should still be encouraged among high-risk dusty and fume job workers, especially in low- and middle-income countries.publishedVersio

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

Monilethrix

Monilethrix is a rare heritable disorder characterized by a structural defect of the hair with increased fragility. We here by report a case of monilethrix in a nine year old male child in view of the rarity of this condition

Antimicrobials: Shift from Conventional to Extreme Sources

Antimicrobials- the chemical substances that inhibit the growth of microorganisms and stop their multiplication are immensely useful in the context of pathogenic microorganisms where these substances either contain their growth by inhibiting them from growing (bacteriostatic) or killing them permanently (bacteriocidal). They may broadly be either antibiotics, antifungals, antivirals and antiparasitics. A major class of antimicrobials are antibiotics and almost half of the total percent of antibiotics driven from microbials are sourced from different taxonomic levels of actinomycetota (formerly actinobacteria), significantly from the genus Streptomyces. Adaptability and mechanisms to resist drug effects has outpushed the evolution of drug resisitant pathogenic microorganisms and outnumbered their growth vis a vis the discovery of new antimicrobials. Gone is the golden age of antibiotics: the tussle between antimicrobials to resist the growth of pathogens and the latter to contain the inhibitory effects of former has largely weighed on the pathogenic side- thanks to the inefficient and excessive use of antibiotics and their misapplication. Growth of drug (multi-drug) resistant pathogens coupled with inadequate antibiotics has set a dire need to explore new habitats-aquatic, terrestrial and microbiomes associated as endophytes in other plants and animals. The shift in habitat selection from conventional to extreme locations is met with convincingly successful outcomes. Researchers successfully explore the actinomycetota drug discovery potential of deep sea oceans, extreme high altitude Himalayas that remain capped with snow and glaciers round the year. The abyssopelagic and glaciated peaks both share similarity in that they are constrained by different pressure parameters. The environmental pressures associated with deep pelagic oceans are partial to complete exclusion of light, lack of phothosynthesis and associated vegetation, limited nutrition and hydrostatic pressure by thounsands of pounds per square inch. Mountain peaks are glaciated, ice cold with limited nutrition and oligotrophic in nature. These temperature constraints in both the aquatic and terrestrial environments have activated the drug expression secondary metabolite machinary of actinomycetota to kill or inhibit other microorganisms and spare the already limited resources for their own growth. This antibiotic secretion paradigm also applies to actinomycetota living as endophytes in an interactive dynamic environments with insects and other organisms. The antibiotic potential hidden in these extreme selected sites is worthy of killing the microbial bugs and conatining the ever growing resistant pathogen load. Successful exploitation strategies should be hastened to garner the antimicrobial potential of these extreme sources

Serum Lipid Profile In Leprosy Patients In Kashmir Valley

Serum lipid profile was evaluated in twenty leprosy patients (paucibacillary and multibacillary cases) and twenty age and sex matched healthy controls. The serum lipid profile of the two groups showed no statistically significant difference

Dexamethasone pulse therapy in patients of systemic sclerosis: Is it a viable proposition? A study from kashmir

Background: Systemic sclerosis is a multisystemic autoimmune disorder. Intravenous dexamethasone pulse therapy has been used since 1998. Aim: The aim was to report the beneficial effects of dexamethasone pulse in patients of systemic sclerosis vis-á-vis the side effects. Materials and Methods: Forty-seven patients of systemic sclerosis were included. After looking at the history and physical examination, the patients were submitted to various relevant investigations. Clinical scoring of the patient was done at baseline and 6-month interval according to Furst′s organ indices score. Results: A total of 47 patients of systemic sclerosis were included (45 females, 2 males). In majority, acrosclerosis was seen. Severe sclerosis and contractures were seen in two patients. Moderate proteinuria, restrictive lung disease, dysphagia, and valvular heart involvement were seen. A total of 13 patients on dexamethasone pulse therapy developed tuberculosis. Improvement in skin scoring and decreased severity of Raynaud′s phenomenon was seen. No improvement in dysphagia, severe vascular symptoms, or restrictive lung disease was seen. Conclusion: Thus, beneficial effects of dexamethasone pulse therapy seem to be merely cosmetic

Evaluation of anticancer and antimicrobial activities of selected medicinal plants of Kashmir Himalayas, India

141-145Medicinal plants are known for their multifarious use in folk medicine of Kashmir Himalayas, India. The present study was designed to evaluate the anticancer and antimicrobial activities of extracts of some medicinal plants. Three different types of extracts were prepared by cold maceration technique using methanol, hexane and water. Anticancer activity of extracts was determined by using Sulpharhodamine B assay on four human cancer cell lines. Antimicrobial activity was done by using microdilution method. The methanol extract of Euonymus hamiltonianus exhibited broad spectrum anticancer activity with IC50 value of 20, 14, 27 and 55µg/ml against Lung A-549, Colon HCT-116, Pancreatic MiaPaca and Breast MCF-7 cell lines, respectively. The lowest IC50 value of 14µg/ml was observed against Colon HCT-116 cancer cell line. Colorectal cancer is the second leading cause of cancer deaths worldwide. The methanol and aqueous extracts of Euphorbia wallichii specifically inhibited the growth of Staphylococcus aureus which is one of the foremost pathogens in the list of antibiotic resistant strains. The MIC values were found to be 128-256µg/ml. Euonymus hamiltonianus and Euphorbia wallichii with promising activities could act as important source of biologically active compounds