In silico bioprospection analysis for identification of herbal compound targeting Clostridium difficile

655-661Clostridium difficile infection (CDI), the occurrence has been increasing in the community as well as hospital-care facilities, resulting in higher morbidity and mortality rate. C. difficile, anaerobic pathogen greatly associated with antibiotic resistance and majorly linked to the irrational antibiotic use, which accelerate the alarming situation causing endemic as well epidemic globally. It is the budding menace and one of the major sources of nosocomial infection, i.e., hospital-acquired infection. The prevailing risk to public health by the antibiotics and their resistance majorly has driven the urge for utilizing the traditional herbal medicine into a sophisticated approach as a Modern/Ayurvedic Medicinal System (AMS). The current study aims to find out the promising herbals to combat the threat caused by C. difficile by applying herbal informatics as a holistic approach. Total 44 plants were elucidated against the virulence factors of the bacterium using the systematic bioprospection approach, out of which 5 plants were optimized that may be futher validated at the preclinical level

In silico bioprospection analysis for identification of herbal compound targetingClostridium difficile

Clostridium difficile infection (CDI), the occurrence has been increasing in the community as well as hospital-care facilities, resulting in higher morbidity and mortality rate. C. difficile, anaerobic pathogen greatly associated with antibiotic resistance and majorly linked to the irrational antibiotic use, which accelerate the alarming situation causing endemic as well epidemic globally. It is the budding menace and one of the major sources of nosocomial infection, i.e., hospital-acquired infection. The prevailing risk to public health by the antibiotics and their resistance majorly has driven the urge for utilizing the traditional herbal medicine into a sophisticated approach as a Modern/Ayurvedic Medicinal System (AMS). The current study aims to find out the promising herbals to combat the threat caused by C. difficile by applying herbal informatics as a holistic approach. Total 44 plants were elucidated against the virulence factors of the bacterium using the systematic bioprospection approach, out of which 5 plants were optimized that may be futher validated at the preclinical leve

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

Transport model calculations of nuclear stopping from Fermi energy to GeVs/nucleon

We performed a detailed investigation on various observables of nuclear stopping viz energy isotropy ratio, momentum isotropy ratio, vartl and, isospin tracer observable for central collisions of various reactions from Ca+Ca to Au+Au as guided by INDRA and FOPI measurements using Isospin-dependent Quantum Molecular Dynamics (IQMD) model calculations. Energy dependence, system size dependence, fragment size dependence, and isospin effects in the degree of equilibration are examined for a soft momentum-dependent equation of state supplemented with free and reduced NN cross-sections. A confrontation of our calculations with experimental measurements of various nuclear-stopping observables reveals that a much simpler form of reduction factor (a scaling of free nucleon-nucleon cross-section) is to be implemented in the present transport approach to predict most of the nuclear-stopping data on energy, system size, and isospin dependence. The lack of a much-sophisticated form of in-medium effects though induces a systematic uncertainty of the order of 0.1 in favored values of reduction (scaling) factor, with an average scaling factor of 0.8 to be incorporated from tens of MeV/nucleon to around 1 GeV/nucleon

Improving human rights in mental health takes more than just changing the law: An audit of medical assessments in regional community patients in Queensland

Objective: To evaluate the medical assessments of involuntary community patients in a regional mental health service, determine the compliance with requirements under Queensland’s Mental Health Act 2016 (the Act) to regularly review orders and assess patients’ mental capacity. Method: We audited 183 patient records on community treatment authorities (CTAs) to determine whether medical assessments undertaken under the Act included consideration of the person’s capacity, and regular reviews by an authorised doctor as required1s205. Results: The audit revealed that 51% of the CTA patients did not comply with legal requirements either to complete a capacity assessment and/or be medically assessed within three months of the last review. Conclusions: Over 50% of medical assessments did not comply with the legislative requirements to record capacity assessments and review involuntary treatment on at least a three-month basis. However, when the treatment criteria were met, it did not appear to be a basis for CTA revocation. Further research may help determine whether the Mental Health Review Tribunal (Tribunal) could play a greater role in overseeing compliance with the new legislative requirements or if other clinical oversight mechanisms would be appropriate to improve the assessment process

Nitrofurantoin: Furious against bacteria? An in vitro study to test nitrofurantoin as an intracanal medicament against Enterococcus Faecalis

In vitro evaluation of nitrofurantoin as an intracanal medicament against Enterococcus Faecalis. Materials and Methods: 150 single-rooted premolar teeth were chosen and instrumented using a Protaper gold rotary file system; the root canals of these teeth were inoculated for 21 days with an Enterococcus faecalis bacterial solution. The canals were inoculated with Nitrofurantoin, Calcium hydroxide, and MTAP after 21 days and left for 7 days. On the eighth day, the samples were examined to determine the degree of infection. The study's findings revealed that both Nitrofurantoin and MTAP were very successful, with no Colony Forming Units (CFU) production in their respective groups. The current investigation indicated that nitrofurantoin is effective in eradicating E. faecalis cells in pure culture as well as root canals

Efficacy comparison of various oxygen lnhibition layer (OIL) minimizing agents on composite resin by analysis of two different physical properties: An in vitro study

Introduction: Composite resins are the most common restorative materials that are used these days and have been radically improving over the past few years. Their polymerisation reaction can be inhibited during light-curing due to the oxygen presence in atmosphere. Aim/objective: The aim of this study is to evaluate effect of different air inhibition coating strategies on composite resin material in terms of hardness and discolouration. Material and Methodology: Composite discs of 6.5 X 2mm were prepared for samples which were cured under a) 0.5mm thick mylar strip b) thin layer of glycerine c) layer of KY jelly (commercial lubricant) d) air cure. These samples were dipped in cola, turmeric milk, coffee and distilled water for 14 days. Spectrophotometric analysis was done to assess the colour change and Vicker’s hardness test for assessment of the hardness. Statistical analysis was done and the results were concluded. Results: The results were analyzed with ANOVA one-way test followed by Student Newman-Keul test. Moreover, multiple comparisons of means were performed using the Student t-test (p<0.05). Conclusion: Presence of Oxygen inhibition layer(OIL) on surface layer of composite affected the specimens adversely by reducing the microhardness and increasing instability of colour

Nitrofurantoin: Furious Against Bacteria? an in Vitro Study to Test Nitrofurantoin as an Intracanal Medicament Against Enterococcus Faecalis

In vitro evaluation of nitrofurantoin as an intracanal medicament against Enterococcus Faecalis. Materials and Methods: 150 single-rooted premolar teeth were chosen and instrumented using a Protaper gold rotary file system; the root canals of these teeth were inoculated for 21 days with an Enterococcus faecalis bacterial solution. The canals were inoculated with Nitrofurantoin, Calcium hydroxide, and MTAP after 21 days and left for 7 days. On the eighth day, the samples were examined to determine the degree of infection. The study's findings revealed that both Nitrofurantoin and MTAP were very successful, with no Colony Forming Units (CFU) production in their respective groups. The current investigation indicated that nitrofurantoin is effective in eradicating E. faecalis cells in pure culture as well as root canals

Efficacy Comparison of Various Oxygen Lnhibition Layer (OIL) Minimizing Agents on Composite Resin by Analysis of Two Different Physical Properties: an in Vitro Study

Introduction: Composite resins are the most common restorative materials that are used these days and have been radically improving over the past few years. Their polymerisation reaction can be inhibited during light-curing due to the oxygen presence in atmosphere. Aim/objective: The aim of this study is to evaluate effect of different air inhibition coating strategies on composite resin material in terms of hardness and discolouration. Material and Methodology: Composite discs of 6.5 X 2mm were prepared for samples which were cured under a) 0.5mm thick mylar strip b) thin layer of glycerine c) layer of KY jelly (commercial lubricant) d) air cure. These samples were dipped in cola, turmeric milk, coffee and distilled water for 14 days. Spectrophotometric analysis was done to assess the colour change and Vicker's hardness test for assessment of the hardness. Statistical analysis was done and the results were concluded. Results: The results were analyzed with ANOVA one-way test followed by Student Newman-Keul test. Moreover, multiple comparisons of means were performed using the Student t-test (p<0.05). Conclusion: Presence of Oxygen inhibition layer(OIL) on surface layer of composite affected the specimens adversely by reducing the microhardness and increasing instability of colour

Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021

Background: Diabetes is one of the leading causes of death and disability worldwide, and affects people regardless of country, age group, or sex. Using the most recent evidentiary and analytical framework from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), we produced location-specific, age-specific, and sex-specific estimates of diabetes prevalence and burden from 1990 to 2021, the proportion of type 1 and type 2 diabetes in 2021, the proportion of the type 2 diabetes burden attributable to selected risk factors, and projections of diabetes prevalence through 2050. Methods: Estimates of diabetes prevalence and burden were computed in 204 countries and territories, across 25 age groups, for males and females separately and combined; these estimates comprised lost years of healthy life, measured in disability-adjusted life-years (DALYs; defined as the sum of years of life lost [YLLs] and years lived with disability [YLDs]). We used the Cause of Death Ensemble model (CODEm) approach to estimate deaths due to diabetes, incorporating 25 666 location-years of data from vital registration and verbal autopsy reports in separate total (including both type 1 and type 2 diabetes) and type-specific models. Other forms of diabetes, including gestational and monogenic diabetes, were not explicitly modelled. Total and type 1 diabetes prevalence was estimated by use of a Bayesian meta-regression modelling tool, DisMod-MR 2.1, to analyse 1527 location-years of data from the scientific literature, survey microdata, and insurance claims; type 2 diabetes estimates were computed by subtracting type 1 diabetes from total estimates. Mortality and prevalence estimates, along with standard life expectancy and disability weights, were used to calculate YLLs, YLDs, and DALYs. When appropriate, we extrapolated estimates to a hypothetical population with a standardised age structure to allow comparison in populations with different age structures. We used the comparative risk assessment framework to estimate the risk-attributable type 2 diabetes burden for 16 risk factors falling under risk categories including environmental and occupational factors, tobacco use, high alcohol use, high body-mass index (BMI), dietary factors, and low physical activity. Using a regression framework, we forecast type 1 and type 2 diabetes prevalence through 2050 with Socio-demographic Index (SDI) and high BMI as predictors, respectively. Findings: In 2021, there were 529 million (95% uncertainty interval [UI] 500-564) people living with diabetes worldwide, and the global age-standardised total diabetes prevalence was 6·1% (5·8-6·5). At the super-region level, the highest age-standardised rates were observed in north Africa and the Middle East (9·3% [8·7-9·9]) and, at the regional level, in Oceania (12·3% [11·5-13·0]). Nationally, Qatar had the world's highest age-specific prevalence of diabetes, at 76·1% (73·1-79·5) in individuals aged 75-79 years. Total diabetes prevalence-especially among older adults-primarily reflects type 2 diabetes, which in 2021 accounted for 96·0% (95·1-96·8) of diabetes cases and 95·4% (94·9-95·9) of diabetes DALYs worldwide. In 2021, 52·2% (25·5-71·8) of global type 2 diabetes DALYs were attributable to high BMI. The contribution of high BMI to type 2 diabetes DALYs rose by 24·3% (18·5-30·4) worldwide between 1990 and 2021. By 2050, more than 1·31 billion (1·22-1·39) people are projected to have diabetes, with expected age-standardised total diabetes prevalence rates greater than 10% in two super-regions: 16·8% (16·1-17·6) in north Africa and the Middle East and 11·3% (10·8-11·9) in Latin America and Caribbean. By 2050, 89 (43·6%) of 204 countries and territories will have an age-standardised rate greater than 10%. Interpretation: Diabetes remains a substantial public health issue. Type 2 diabetes, which makes up the bulk of diabetes cases, is largely preventable and, in some cases, potentially reversible if identified and managed early in the disease course. However, all evidence indicates that diabetes prevalence is increasing worldwide, primarily due to a rise in obesity caused by multiple factors. Preventing and controlling type 2 diabetes remains an ongoing challenge. It is essential to better understand disparities in risk factor profiles and diabetes burden across populations, to inform strategies to successfully control diabetes risk factors within the context of multiple and complex drivers. Funding: Bill & Melinda Gates Foundation