The Facile Synthesis of N-Aryl Isoxazolones as DNA Intercalators Under Solvent-free Conditions Using Microwave Irradiation

The reaction of chloroheterocycles with some isoxazolones under microwave irradiation and under solvent-free conditions to give the corresponding mono isoxazolinyl derivatives is reported. The main advantages of this method are: (i) elimination of the nitrogen gas (N2), (ii) solvent-free conditions, (iii) microwave irradiation, (iv) avoiding the use of silica gel for purification of the products, and (v) higher and shorter reaction times. These compounds have potential applications as DNA intercalators.Keywords: Isoxazolones, N-aryl isoxazolones, solvent-free, 2-chlorobenzoxazole, 2-chlorobenzothiazol

Traditional values of virginity and sexual behaviour in rural Ethiopian youth: results from a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Delaying sexual initiation has been promoted as one of the methods of decreasing risks of HIV among young people. In traditional countries, such as Ethiopia, retaining virginity until marriage is the norm. However, no one has examined the impact of this traditional norm on sexual behaviour and risk of HIV in marriage. This study examined the effect of virginity norm on having sex before marriage and sexual behaviour after marriage among rural Ethiopian youth.</p> <p>Methods</p> <p>We did a cross-sectional survey in 9 rural and 1 urban area using a probabilistic sample of 3,743 youth, 15–24 years of age. Univariate analysis was used to assess associations between virginity norm and gender stratified by area, and between sexual behaviour and marital status. We applied Kaplan-Meier and Cox regression analysis to estimate age at sexual debut and assessed the predictors of premarital sex among the never-married using SPSS.</p> <p>Results</p> <p>We found that maintaining virginity is still a way of securing marriage for girls, especially in rural areas; the odds of belief and intention to marry a virgin among boys was 3–4 times higher among rural young males. As age increased, the likelihood of remaining a virgin decreased. There was no significant difference between married and unmarried young people in terms of number of partners and visiting commercial sex workers. Married men were twice more likely to have multiple sexual partners than their female counterparts. A Cox regression show that those who did not believe in traditional values of preserving virginity (adjusted hazard ratio [AHR] = 2.91 [1.92–4.40]), alcohol drinkers (AHR = 2.91 [1.97–4.29]), Khat chewers (AHR = 2.36 [1.45–3.85]), literates (AHR = 18.01 [4.34–74.42]), and the older age group (AHR = 1.85 [1.19–2.91]) were more likely to have premarital sex than their counterparts.</p> <p>Conclusion</p> <p>Although virginity norms help delay age at sexual debut among rural Ethiopian youth, and thus reduces vulnerability to sexually transmitted infections and HIV infection, vulnerability among females may increase after marriage due to unprotected multiple risky sexual behaviours by spouses. The use of preventive services, such as VCT before marriage and condom use in marriage should be part of the HIV/AIDS prevention and control strategies.</p

National mortality burden due to communicable, non-communicable, and other diseases in Ethiopia, 1990–2015: findings from the Global Burden of Disease Study 2015

Background: Ethiopia lacks a complete vital registration system that would assist in measuring disease burden and risk factors. We used the Global Burden of Diseases, Injuries, and Risk factors 2015 (GBD 2015) estimates to describe the mortality burden from communicable, non-communicable, and other diseases in Ethiopia over the last 25 years. Methods: GBD 2015 mainly used cause of death ensemble modeling to measure causes of death by age, sex, and year for 195 countries. We report numbers of deaths and rates of years of life lost (YLL) for communicable, maternal, neonatal, and nutritional (CMNN) disorders, non-communicable diseases (NCDs), and injuries with 95% uncertainty intervals (UI) for Ethiopia from 1990 to 2015. Results: CMNN causes of death have declined by 65% in the last two-and-a-half decades. Injury-related causes of death have also decreased by 70%. Deaths due to NCDs declined by 37% during the same period. Ethiopia showed a faster decline in the burden of four out of the five leading causes of age-standardized premature mortality rates when compared to the overall sub-Saharan African region and the Eastern sub-Saharan African region: lower respiratory infections, tuberculosis, HIV/AIDS, and diarrheal diseases; however, the same could not be said for ischemic heart disease and other NCDs. Non-communicable diseases, together, were the leading causes of age-standardized mortality rates, whereas CMNN diseases were leading causes of premature mortality in 2015. Although lower respiratory infections, tuberculosis, and diarrheal disease were the leading causes of age-standardized death rates, they showed major declines from 1990 to 2015. Neonatal encephalopathy, iron-deficiency anemia, protein-energy malnutrition, and preterm birth complications also showed more than a 50% reduction in burden. HIV/AIDS-related deaths have also decreased by 70% since 2005. Ischemic heart disease, hemorrhagic stroke, and ischemic stroke were among the top causes of premature mortality and age-standardized death rates in Ethiopia in 2015. Conclusions: Ethiopia has been successful in reducing deaths related to communicable, maternal, neonatal, and nutritional deficiency diseases and injuries by 65%, despite unacceptably high maternal and neonatal mortality rates. However, the country’s performance regarding non-communicable diseases, including cardiovascular disease, diabetes, cancer, and chronic respiratory disease, was minimal, causing these diseases to join the leading causes of premature mortality and death rates in 2015. While the country is progressing toward universal health coverage, prevention and control strategies in Ethiopia should consider the double burden of common infectious diseases and non-communicable diseases: lower respiratory infections, diarrhea, tuberculosis, HIV/AIDS, cardiovascular disease, cancer, and diabetes. Prevention and control strategies should also pay special attention to the leading causes of premature mortality and death rates caused by non-communicable diseases: cardiovascular disease, cancer, and diabetes. Measuring further progress requires a data revolution in generating, managing, analyzing, and using data for decision-making and the creation of a full vital registration system in the country

Burden of disease attributable to suboptimal diet, metabolic risks, and low physical activity in Ethiopia and comparison with Eastern sub-Saharan African countries, 1990-2015: findings from the Global Burden of Disease Study 2015

Background: Twelve of the 17 Sustainable Development Goals (SDGs) are related to malnutrition (both under- and overnutrition), other behavioral, and metabolic risk factors. However, comparative evidence on the impact of behavioral and metabolic risk factors on disease burden is limited in sub-Saharan Africa (SSA), including Ethiopia. Using data from the Global Burden of Disease (GBD) Study, we assessed mortality and disability-adjusted life years (DALYs) attributable to child and maternal undernutrition (CMU), dietary risks, metabolic risks and low physical activity for Ethiopia. The results were compared with 14 other Eastern SSA countries. Methods: Databases from GBD 2015, that consist of data from 1990 to 2015, were used. A comparative risk assessment approach was utilized to estimate the burden of disease attributable to CMU, dietary risks, metabolic risks and low physical activity. Exposure levels of the risk factors were estimated using spatiotemporal Gaussian process regression (ST-GPR) and Bayesian meta-regression models. Results: In 2015, there were 58,783 [95% uncertainty interval (UI): 43,653-76,020] or 8.9% [95% UI: 6.1-12.5] estimated all-cause deaths attributable to CMU, 66,269 [95% UI: 39,367-106,512] or 9.7% [95% UI: 7.4-12.3] to dietary risks, 105,057 [95% UI: 66,167-157,071] or 15.4% [95% UI: 12.8-17.6] to metabolic risks and 5808 [95% UI: 3449-9359] or 0.9% [95% UI: 0.6-1.1]to low physical activity in Ethiopia. While the age-adjusted proportion of all-cause mortality attributable to CMU decreased significantly between 1990 and 2015, it increased from 10.8% [95% UI: 8.8-13.3] to 14.5% [95% UI: 11.7-18.0] for dietary risks and from 17.0% [95% UI: 15.4-18.7] to 24.2% [95% UI: 22.2-26.1] for metabolic risks. In 2015, Ethiopia ranked among the top four countries (of 15 Eastern SSA countries) in terms of mortality and DALYs based on the age-standardized proportion of disease attributable to dietary risks and metabolic risks. Conclusions: In Ethiopia, while there was a decline in mortality and DALYs attributable to CMU over the last two and half decades, the burden attributable to dietary and metabolic risks have increased during the same period. Lifestyle and metabolic risks of NCDs require more attention by the primary health care system of in the country

Reactive Oxygen Species Play a Role in the Infection of the Necrotrophic Fungi, Rhizoctonia solani in Wheat

Rhizoctonia solani is a nectrotrophic fungal pathogen that causes billions of dollars of damage to agriculture worldwide and infects a broad host range including wheat, rice, potato and legumes. In this study we identify wheat genes that are differentially expressed in response to the R. solani isolate, AG8, using microarray technology. A significant number of wheat genes identified in this screen were involved in reactive oxygen species (ROS) production and redox regulation. Levels of ROS species were increased in wheat root tissue following R. solani infection as determined by Nitro Blue Tetrazolium (NBT), 3,3'-diaminobenzidine (DAB) and titanium sulphate measurements. Pathogen/ROS related genes from R. solani were also tested for expression patterns upon wheat infection. TmpL, a R. solani gene homologous to a gene associated with ROS regulation in Alternaria brassicicola, and OAH, a R. solani gene homologous to oxaloacetate acetylhydrolase which has been shown to produce oxalic acid in Sclerotinia sclerotiorum, were highly induced in R. solani when infecting wheat. We speculate that the interplay between the wheat and R. solani ROS generating proteins may be important for determining the outcome of the wheat/R. solani interaction

Glucose- but Not Rice-Based Oral Rehydration Therapy Enhances the Production of Virulence Determinants in the Human Pathogen Vibrio cholerae

Despite major attempts to prevent cholera transmission, millions of people worldwide still must address this devastating disease. Cholera research has so far mainly focused on the causative agent, the bacterium Vibrio cholerae, or on disease treatment, but rarely were results from both fields interconnected. Indeed, the treatment of this severe diarrheal disease is mostly accomplished by oral rehydration therapy (ORT), whereby water and electrolytes are replenished. Commonly distributed oral rehydration salts also contain glucose. Here, we analyzed the effects of glucose and alternative carbon sources on the production of virulence determinants in the causative agent of cholera, the bacterium Vibrio cholerae during in vitro experimentation. We demonstrate that virulence gene expression and the production of cholera toxin are enhanced in the presence of glucose or similarly transported sugars in a ToxR-, TcpP- and ToxT-dependent manner. The virulence genes were significantly less expressed if alternative non-PTS carbon sources, including rice-based starch, were utilized. Notably, even though glucose-based ORT is commonly used, field studies indicated that rice-based ORT performs better. We therefore used a spatially explicit epidemiological model to demonstrate that the better performing rice-based ORT could have a significant impact on epidemic progression based on the recent outbreak of cholera in Haiti. Our results strongly support a change of carbon source for the treatment of cholera, especially in epidemic settings

Population-level risks of alcohol consumption by amount, geography, age, sex, and year: a systematic analysis for the Global Burden of Disease Study 2020

Background The health risks associated with moderate alcohol consumption continue to be debated. Small amounts of alcohol might lower the risk of some health outcomes but increase the risk of others, suggesting that the overall risk depends, in part, on background disease rates, which vary by region, age, sex, and year. Methods For this analysis, we constructed burden-weighted dose–response relative risk curves across 22 health outcomes to estimate the theoretical minimum risk exposure level (TMREL) and non-drinker equivalence (NDE), the consumption level at which the health risk is equivalent to that of a non-drinker, using disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for 21 regions, including 204 countries and territories, by 5-year age group, sex, and year for individuals aged 15–95 years and older from 1990 to 2020. Based on the NDE, we quantified the population consuming harmful amounts of alcohol. Findings The burden-weighted relative risk curves for alcohol use varied by region and age. Among individuals aged 15–39 years in 2020, the TMREL varied between 0 (95% uncertainty interval 0–0) and 0·603 (0·400–1·00) standard drinks per day, and the NDE varied between 0·002 (0–0) and 1·75 (0·698–4·30) standard drinks per day. Among individuals aged 40 years and older, the burden-weighted relative risk curve was J-shaped for all regions, with a 2020 TMREL that ranged from 0·114 (0–0·403) to 1·87 (0·500–3·30) standard drinks per day and an NDE that ranged between 0·193 (0–0·900) and 6·94 (3·40–8·30) standard drinks per day. Among individuals consuming harmful amounts of alcohol in 2020, 59·1% (54·3–65·4) were aged 15–39 years and 76·9% (73·0–81·3) were male. Interpretation There is strong evidence to support recommendations on alcohol consumption varying by age and location. Stronger interventions, particularly those tailored towards younger individuals, are needed to reduce the substantial global health loss attributable to alcohol. Funding Bill & Melinda Gates Foundation