Impaired lipid levels and inflammatory response in rats exposed to cadmium

To investigate the subchronic effect of cadmium intoxication on lipid metabolism and the inflammatory responses accompanying it, rats were administered 50 and 100 ppm cadmium through their drinking water for 7 weeks. At both concentrations, cadmium exposure resulted in significant elevation (p < 0.05) of total cholesterol and gave rise to hypertriglyceridemia in the plasma of the animals. The proinflammatory cytokines, IL-2, IL-6 and TNF-α, were highly expressed in the animals. At the 50 ppm dose level, plasma IL-2, IL-6 and TNF-α levels were increased by 20 %, 87 % and 336 % respectively, while the 100 ppm dose yielded 32 %, 57 % and 470 % increases, respectively. A drastic build-up of MDA in the liver elicited by the metal led to an 85 % increase in lipid peroxidation at high dose. A 3-fold increase of lipid hydroperoxidation (LOOH) products was obtained on exposure to cadmium at 100 ppm. Cadmium caused more than a 2-fold increase in oxLDL levels at both doses tested. Paraoxonase activity was also significantly repressed, culminating in a 43 % reduction in activity at 100 ppm dose. Disruption of lipid metabolism, increased lipid peroxidation as well as imbalance in proinflammatory cytokine levels may thus, be means by which cadmium induces its toxicity

In vitro induction of rat liver mitochondrial membrane permeability transition pore opening by solvent extracts of Momordica charantia leaves

Alteration of mitochondrial functions such as permeability transition (PT), a process associated with the uncoupling of oxidative phosphorylation, has been found to play a vital role in the apoptotic process induced by certain anti-cancer agents. When triggered, PT facilitates the release of mitochondrial apoptogenic proteins which in turn activate the caspase cascade of apoptosis. Thus, this study investigated the in vitro effects of varying concentrations (0.2, 0.4, 0.6, 0.8 and 1.0 mg/ml) of different leaf extracts [Crude Water-Soluble Extract (CWSE), Decoction (DE) and Methanol Extract (ME)] of Momordica charantia (M. charantia), a purported anti-cancer plant of the family Cucurbitaceae on normal rat liver mitochondria. Opening of mitochondrial membrane permeability transition pore (MMPTP) was spectrophotometrically assayed under succinate-energized condition. Results obtained showed concentration-dependent and significant (P&lt;0.05) increases in the extents to which MMPTP opening was induced by the three extract types when compared with the control group. Inductions caused by CWSE and DE increased with increasing concentrations while those caused by ME decreased with increasing concentrations, giving the maximum induction at 1.0 mg/ml (8.1-fold increase) of CWSE and the least induction at 1.0 mg/ml (4.3-fold increase) of ME, respectively. Spermine, a reference inhibitor of MMPTP opening, reversed all observed openings. These results indicate that the tested leaf extracts of M. charantia are potent (CWSE being the most potent) MMPTP opening inducers and the pathway by which M. charantia causes apoptosis in cancer cells is probably mitochondrial-mediated (intrinsic)

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

Chitosan-thymolsulfonephthalein-cobalt nanocomposites for colorimetric detection of sulfide anions in aqueous solution

Background: Water pollution by sulfide ions, arising from the exploration and exploitation of sulfide mineral ore, can cause many chronic and acute health challenges. However, owing to the cost of sophisticated equipment and technical expertise required to detect anionic sulfides in water has inspired the preparation of easy-to-use naked-eye colorimetric devices. Methods: In this study, the functionalization of chitosan solution with thymolsulfonephthalein solution (CFTS) at moderate conditions was utilized for the chemical synthesis of cobalt nanocomposites (CFTS-CoNCs) based chemosensors. Results: The prepared material's scanning electron micrograph shows the high Co dispersion on the surface of CFTS with a thorn-shaped morphology in uniform spheres. In contrast, the transmission electron micrograph shows good dispersibility of the tiny rod-like particles distributed on a dendrite-like surface. The interaction of the orange-colored CFTS-CoNCs chemosensor solution with the colorless S2− ions was accompanied by an instant and stable black color change. Furthermore, the selective and sensitive chemosensor could detect ≥ 15 ppm aqueous S2− ions solution at lower pH. The mechanism of detection could be due to a nucleophilic attack of S2− on the cobalt-induced hydroxylmethylpropyl benzoxathiole amine cation giving rise to the strong UV–Vis absorption at 592 nm. Conclusion: The highly selective and sensitive CFTS-CoNCs chemosensor can be applied for real-time and quick on-site analysis. In addition, the colorimetric device will serve as a lifesaver in terms of reducing both time and cost, user-friendly, and hands-on tools for the rapid/accurate detection of sulfide ions in water

The management of the faeces passed by under five children: an exploratory, cross-sectional research in an urban community in Southwest Nigeria

Abstract Background Safe management of faeces (SMoF) and environmental contamination by faecal pathogens have been extensively researched although the SMoF in under-five children has been perennially neglected perhaps due to the misconception that it is harmless. This research, therefore, studied the situation, to determine the magnitude and dimensions of the problem aimed at making policy level stakeholders aware of child faeces management systems and so, inform evidence-based implementation of child and health-related programmes in Nigeria. Methods The study utilized an exploratory cross-sectional design and a multi-stage sampling technique to identify 300 respondents from 12 randomly selected streets from 4 wards in Ife central local government area. The study collected data with a pretested questionnaire which included direct observations of child defecation practices and existing toilet facilities. Cleaned data were analyzed by IBM-SPSS version 20 with child faeces management outcomes as the dependent variable. Results The mean age of respondents’ and monthly income (mode) were 30.8 ± 7.5 years and ₦10,000.00 ($28.60). Most respondents were mothers to the under five children (84.7%), had a secondary education (72.0%) and were semi-skilled (57.0%). The caregivers had access to improved water sources (93.7%), improved toilets (64.3%), with 64% and 53.7% having above average scores in knowledge and attitudes, respectively. In the study, 19.7% and 69.0% of caregivers practiced safe disposal of faeces passed by the under five child during the day and at night respectively, though most caregivers (94.3%) omitted steps in the safe management of child faeces chain. The under five diarrhoea prevalence rate was 13.7% and unsanitary passage of child faeces is associated with four folds likelihood of having diarrhoea (p = 0.001). The caregivers whose under five children practiced safe sanitation were rich (p = 0.009) and knowledge was significantly associated with ownership of household toilet (P = 0.037), night faeces management chain practice (P < 0.001) and disposal of anal cleaning materials (P = 0.002). Handwashing was significantly associated with household toilet (P < 0.001), wealth (P < 0.001), under five child defecation preferences during the day (P < 0.001) and at night (P = 0.008). Conclusion The high knowledge and positive attitudes exhibited by the caregivers were at variance with practice. Where under five children defecate during the day were influenced by the disposal of their anal cleaning materials, distance to the toilet and caregivers’ education. The findings highlight the dangers of unsanitary disposal of child faeces and the need to strengthen the related policies that can increase caregivers awareness and practice at all levels and in all livelihood domains

In vitro induction of rat liver mitochondrial membrane permeability transition pore opening by solvent extracts of Momordica charantia leaves

Alteration of mitochondrial functions such as permeability transition (PT), a process associated with the uncoupling of oxidative phosphorylation, has been found to play a vital role in the apoptotic process induced by certain anti-cancer agents. When triggered, PT facilitates the release of mitochondrial apoptogenic proteins which in turn activate the caspase cascade of apoptosis. Thus, this study investigated the in vitro effects of varying concentrations (0.2, 0.4, 0.6, 0.8 and 1.0 mg/ml) of different leaf extracts [Crude Water-Soluble Extract (CWSE), Decoction (DE) and Methanol Extract (ME)] of Momordica charantia (M. charantia), a purported anti-cancer plant of the family Cucurbitaceae on normal rat liver mitochondria. Opening of mitochondrial membrane permeability transition pore (MMPTP) was spectrophotometrically assayed under succinate-energized condition. Results obtained showed concentration-dependent and significant (P<0.05) increases in the extents to which MMPTP opening was induced by the three extract types when compared with the control group. Inductions caused by CWSE and DE increased with increasing concentrations while those caused by ME decreased with increasing concentrations, giving the maximum induction at 1.0 mg/ml (8.1-fold increase) of CWSE and the least induction at 1.0 mg/ml (4.3-fold increase) of ME, respectively. Spermine, a reference inhibitor of MMPTP opening, reversed all observed openings. These results indicate that the tested leaf extracts of M. charantia are potent (CWSE being the most potent) MMPTP opening inducers and the pathway by which M. charantia causes apoptosis in cancer cells is probably mitochondrial-mediated (intrinsic)