Genistein effect in cultured ovine ovarian granulosa cells.

Genistein, an isoflavone has the potential to mimic, augment, or dysregulate the steroid hormone production pathways. We hypothesized that genistein affects the granulosa cell (GCs) functions through a series of biochemical, molecular, and genomic cascades. The present study was conducted to evaluate the impact of genistein exposure on GCs viability, apoptosis, and steroidogenesis. The present study involved 3/5 days of exposure to genistein on GCs collected from abattoir-derived ovine ovaries at doses of 0, 1, 10, 25, 50, and 100 µM. The harvested GCs were used for growth, cytotoxicity, and gene expression studies related to apoptosis, growth, and steroidogenesis. We observed that genistein had both stimulatory at 10 and 25 µM levels as well as inhibitory effects at 50 and 100 µM levels on the growth and proliferation of GCs. Genistein significantly decreased the levels of 17ß-estradiol at higher exposure (50 and 100 µM), whereas the progesterone level increased significantly as the genistein exposure increased. Additionally, genistein could also alter the mRNA expression of the steroidogenic receptor, enzymes, proteins, and growth-related genes suggesting that genistein could potentially alter the steroidogenic pathways. We conclude that genistein can interfere with cell survival and steroidogenesis by exhibiting a dose-dependent biphasic response on the viability, growth-related parameters, and the synthesis of 17ß-estradiol in the cultured GCs.

Health Emergency Risk Management in World Health Organization - South-East Asia Region during 2014-2023: synthesis of experiences.

Health Emergency Risk Management (ERM) has become increasingly critical on the global stage, prompted by the escalating frequency and severity of natural disasters and disease outbreaks. This paper offers a comprehensive synthesis of the World Health Organization's (WHO) experiences in the South-East Asia Region during the period 2014-2023, shedding light on its efforts to manage health emergencies and enhance resilience. The South-East Asia Region's unique environmental and economic diversity exposes it to significant health risks, including emerging infectious diseases and their implications for development, particularly in low-income countries. Here we document the transition from reactive emergency responses to proactive preparedness, catalyzed by prioritizing ERM as one of the regional flagship priorities in 2014. Key components of this initiative included capacity-building, the establishment of the South-East Asia Regional Health Emergency Fund (SEARHEF), and the implementation of the International Health Regulations (IHR 2005). This synthesis highlights the region's achievements in event reporting, development of national actions plan, successful Early Warning, Alert, and Response System (EWARS) implementation, and improvements in core capacities under IHR (2005). It also underscores the challenges associated with cross-border data sharing and regional collaboration that could strengthen ERM and enhance readiness for effective synergistic response.

Global DNA methylation, DNA methyltransferase and stress-related gene expression in ovine oocytes and embryos after exposure to metabolic stressors.

DNA methylation, considered the most prominent epigenetic mark was important for the gene regulation in embryonic development. The present study aimed at evaluating the effects of metabolic stressors [Non-esterified fatty acid (NEFA), ß-hydroxy-butyric acid (BHB), ammonia and urea] exposure during the in vitro ovine oocyte maturation, global DNA methylation, DNA methyltransferase and stress-related gene expression. Colorimetric analysis of global DNA methylation and the expression of the DNA methyltransferase genes (DNMT1, DNMT3A, and DNMT3B) were assessed in the matured oocytes, 2-cell embryos and blastocysts produced in vitro from oocytes exposed with the metabolic stressors during 24 h of the in vitro maturation (IVM). Further, the mRNA expression of the stress-related genes (SOD1, SOD2) in the matured oocytes, 2-cell embryos and blastocysts produced was assessed. Significant difference in global DNA methylation levels between all the treatments tested was observed when compared with control in oocytes, two-cell embryos and blastocysts. Elevated concentration of metabolic stressors resulted in increased expressions of several stress-related genes, i.e., SOD1, SOD2 and in mRNA expression of DNA methyltransferase genes. The present study is the first to report that the DNA methylation was sensitive to the effects of the metabolic stressors in ovine oocytes/embryos. The aberrant expressions of genes during oocyte development targeted in the present study can provide evidence for the early embryo developmental arrest and blastocysts quality. These results highlighted the sensitivity of the early embryogenesis and more precisely of the reprogramming period to metabolites challenges, in a realistic situation of elevated concentration of metabolic stressors.

Does malaria epidemiology project Cameroon as 'Africa in miniature'?

Cameroon, a west-central African country with a ~ 20 million population, is commonly regarded as 'Africa in miniature' due to the extensive biological and cultural diversities of whole Africa being present in a single-country setting. This country is inhabited by ancestral human lineages in unique eco-climatic conditions and diverse topography. Over 90 percent Cameroonians are at risk of malaria infection, and ~ 41 percent have at least one episode of malaria each year. Historically, the rate of malaria infection in Cameroon has fluctuated over the years; the number of cases was about 2 million in 2010 and 2011. The Cameroonian malaria control programme faces an uphill task due to high prevalence of multidrug-resistant parasites and insecticide-resistant malaria vectors. Above all, continued human migration from the rural to urban areas as well as population exchange with adjoining countries, high rate of ecological instabilities caused by deforestation, poor housing, lack of proper sanitation and drainage system might have resulted in the recent increase in incidences of malaria and other vector-borne diseases in Cameroon. The available data on eco-environmental variability and intricate malaria epidemiology in Cameroon reflect the situation in the whole of Africa, and warrant the need for in-depth study by using modern surveillance tools for meaningful basic understanding of the malaria triangle (host-parasite-vector-environment).

Climate change and human health: Indian context.

The article reviews the issue of climate change and health in the Indian context. The importance of climate change leading to estimated loss of above 2.5 million DALYs in southeast Asia, mortality due to heat waves, and the importance of air quality related respiratory diseases, disasters due to excessive floods, malnutrition due to reduction in rice, maize and sorghum crops etc. Latest work undertaken in India, vis-a-vis current scenario and need for further work has been discussed. There is felt need of further studies on assessing the impact on dengue and chikungunya as the transmission dynamics of these diseases involve water availability, storage and life style, etc. Uncertainties and knowledge gaps identified in the studies undertaken so far have also been highlighted. As regards to vector borne diseases, there is a need to concentrate in the areas which are presently free from malaria and with use of best available tools of interventions in already disease endemic areas like northeastern states, the risk of climate change impacts can be minimized.

Cancer mortality in India: a nationally representative survey.

BACKGROUND: The age-specific mortality rates and total deaths from specific cancers have not been documented for the various regions and subpopulations of India. We therefore assessed the cause of death in 2001-03 in homes in small areas that were chosen to be representative of all the parts of India. METHODS: At least 130 trained physicians independently assigned causes to 122,429 deaths, which occurred in 1·1 million homes in 6671 small areas that were randomly selected to be representative of all of India, based on a structured non-medical surveyor's field report. FINDINGS: 7137 of 122,429 study deaths were due to cancer, corresponding to 556,400 national cancer deaths in India in 2010. 395,400 (71%) cancer deaths occurred in people aged 30-69 years (200,100 men and 195,300 women). At 30-69 years, the three most common fatal cancers were oral (including lip and pharynx, 45,800 [22·9%]), stomach (25,200 [12·6%]), and lung (including trachea and larynx, 22,900 [11·4%]) in men, and cervical (33,400 [17·1%]), stomach (27,500 [14·1%]), and breast (19,900 [10·2%]) in women. Tobacco-related cancers represented 42·0% (84,000) of male and 18·3% (35,700) of female cancer deaths and there were twice as many deaths from oral cancers as lung cancers. Age-standardised cancer mortality rates per 100,000 were similar in rural (men 95·6 [99% CI 89·6-101·7] and women 96·6 [90·7-102·6]) and urban areas (men 102·4 [92·7-112·1] and women 91·2 [81·9-100·5]), but varied greatly between the states, and were two times higher in the least educated than in the most educated adults (men, illiterate 106·6 [97·4-115·7] vs most educated 45·7 [37·8-53·6]; women, illiterate 106·7 [99·9-113·6] vs most educated 43·4 [30·7-56·1]). Cervical cancer was far less common in Muslim than in Hindu women (study deaths 24, age-standardised mortality ratio 0·68 [0·64-0·71] vs 340, 1·06 [1·05-1·08]). INTERPRETATION: Prevention of tobacco-related and cervical cancers and earlier detection of treatable cancers would reduce cancer deaths in India, particularly in the rural areas that are underserved by cancer services. The substantial variation in cancer rates in India suggests other risk factors or causative agents that remain to be discovered. FUNDING: Bill & Melinda Gates Foundation and US National Institutes of Health.

Smokeless tobacco: a major public health problem in the SEA region: a review.

Smokeless tobacco use is on the upswing in some parts of the world, including parts of SEAR. It is therefore important to monitor this problem and understand the possible consequences on public health. Material for this review was obtained from documents and data of the World Health Organization, co-authors, colleagues, and searches on key words in PubMed and on Google. Smokeless tobacco use in SEAR, as betel quid with tobacco, declined with increased marketing of cigarettes from the early twentieth century. Smokeless tobacco use began to increase in the 1970s in South Asia, with the marketing of new products made from areca nut and tobacco and convenient packaging. As a consequence, oral precancerous conditions and cancer incidence in young adults have increased significantly. Thailand's successful policies in reducing betel quid use through school health education from the 1920s and in preventing imports of smokeless tobacco products from 1992 are worth emulating by many SEAR countries. India, the largest manufacturing country of smokeless tobacco in the Region, is considering ways to regulate its production. Best practices require the simultaneous control of smokeless and smoking forms of tobacco. Governments in SEAR would do well to adopt strong measures now to control this problem.