Necrotrophism Is a Quorum-Sensing-Regulated Lifestyle in Bacillus thuringiensis

How pathogenic bacteria infect and kill their host is currently widely investigated. In comparison, the fate of pathogens after the death of their host receives less attention. We studied Bacillus thuringiensis (Bt) infection of an insect host, and show that NprR, a quorum sensor, is active after death of the insect and allows Bt to survive in the cadavers as vegetative cells. Transcriptomic analysis revealed that NprR regulates at least 41 genes, including many encoding degradative enzymes or proteins involved in the synthesis of a nonribosomal peptide named kurstakin. These degradative enzymes are essential in vitro to degrade several substrates and are specifically expressed after host death suggesting that Bt has an active necrotrophic lifestyle in the cadaver. We show that kurstakin is essential for Bt survival during necrotrophic development. It is required for swarming mobility and biofilm formation, presumably through a pore forming activity. A nprR deficient mutant does not develop necrotrophically and does not sporulate efficiently in the cadaver. We report that necrotrophism is a highly regulated mechanism essential for the Bt infectious cycle, contributing to spore spreading

Setting research priorities to improve global newborn health and prevent stillbirths by 2025.

BACKGROUND: In 2013, an estimated 2.8 million newborns died and 2.7 million were stillborn. A much greater number suffer from long term impairment associated with preterm birth, intrauterine growth restriction, congenital anomalies, and perinatal or infectious causes. With the approaching deadline for the achievement of the Millennium Development Goals (MDGs) in 2015, there was a need to set the new research priorities on newborns and stillbirth with a focus not only on survival but also on health, growth and development. We therefore carried out a systematic exercise to set newborn health research priorities for 2013-2025. METHODS: We used adapted Child Health and Nutrition Research Initiative (CHNRI) methods for this prioritization exercise. We identified and approached the 200 most productive researchers and 400 program experts, and 132 of them submitted research questions online. These were collated into a set of 205 research questions, sent for scoring to the 600 identified experts, and were assessed and scored by 91 experts. RESULTS: Nine out of top ten identified priorities were in the domain of research on improving delivery of known interventions, with simplified neonatal resuscitation program and clinical algorithms and improved skills of community health workers leading the list. The top 10 priorities in the domain of development were led by ideas on improved Kangaroo Mother Care at community level, how to improve the accuracy of diagnosis by community health workers, and perinatal audits. The 10 leading priorities for discovery research focused on stable surfactant with novel modes of administration for preterm babies, ability to diagnose fetal distress and novel tocolytic agents to delay or stop preterm labour. CONCLUSION: These findings will assist both donors and researchers in supporting and conducting research to close the knowledge gaps for reducing neonatal mortality, morbidity and long term impairment. WHO, SNL and other partners will work to generate interest among key national stakeholders, governments, NGOs, and research institutes in these priorities, while encouraging research funders to support them. We will track research funding, relevant requests for proposals and trial registers to monitor if the priorities identified by this exercise are being addressed

Setting research priorities to improve global newborn health and prevent stillbirths by 2025

Background In 2013, an estimated 2.8 million newborns died and 2.7 million were stillborn. A much greater number suffer from long term impairment associated with preterm birth, intrauterine growth restriction, congenital anomalies, and perinatal or infectious causes. With the approaching deadline for the achievement of the Millennium Development Goals (MDGs) in 2015, there was a need to set the new research priorities on newborns and stillbirth with a focus not only on survival but also on health, growth and development. We therefore carried out a systematic exercise to set newborn health research priorities for 2013-2025. Methods We used adapted Child Health and Nutrition Research Initiative (CHNRI) methods for this prioritization exercise. We identified and approached the 200 most productive researchers and 400 program experts, and 132 of them submitted research questions online. These were collated into a set of 205 research questions, sent for scoring to the 600 identified experts, and were assessed and scored by 91 experts. Results Nine out of top ten identified priorities were in the domain of research on improving delivery of known interventions, with simplified neonatal resuscitation program and clinical algorithms and improved skills of community health workers leading the list. The top 10 priorities in the domain of development were led by ideas on improved Kangaroo Mother Care at community level, how to improve the accuracy of diagnosis by community health workers, and perinatal audits. The 10 leading priorities for discovery research focused on stable surfactant with novel modes of administration for preterm babies, ability to diagnose fetal distress and novel tocolytic agents to delay or stop preterm labour. Conclusion These findings will assist both donors and researchers in supporting and conducting research to close the knowledge gaps for reducing neonatal mortality, morbidity and long term impairment. WHO, SNL and other partners will work to generate interest among key national stakeholders, governments, NGOs, and research institutes in these priorities, while encouraging research funders to support them. We will track research funding, relevant requests for proposals and trial registers to monitor if the priorities identified by this exercise are being addressed

Spatial, temporal, and demographic patterns in prevalence of chewing tobacco use in 204 countries and territories, 1990-2019 : a systematic analysis from the Global Burden of Disease Study 2019

Interpretation Chewing tobacco remains a substantial public health problem in several regions of the world, and predominantly in south Asia. We found little change in the prevalence of chewing tobacco use between 1990 and 2019, and that control efforts have had much larger effects on the prevalence of smoking tobacco use than on chewing tobacco use in some countries. Mitigating the health effects of chewing tobacco requires stronger regulations and policies that specifically target use of chewing tobacco, especially in countries with high prevalence. Findings In 2019, 273 center dot 9 million (95% uncertainty interval 258 center dot 5 to 290 center dot 9) people aged 15 years and older used chewing tobacco, and the global age-standardised prevalence of chewing tobacco use was 4 center dot 72% (4 center dot 46 to 5 center dot 01). 228 center dot 2 million (213 center dot 6 to 244 center dot 7; 83 center dot 29% [82 center dot 15 to 84 center dot 42]) chewing tobacco users lived in the south Asia region. Prevalence among young people aged 15-19 years was over 10% in seven locations in 2019. Although global agestandardised prevalence of smoking tobacco use decreased significantly between 1990 and 2019 (annualised rate of change: -1 center dot 21% [-1 center dot 26 to -1 center dot 16]), similar progress was not observed for chewing tobacco (0 center dot 46% [0 center dot 13 to 0 center dot 79]). Among the 12 highest prevalence countries (Bangladesh, Bhutan, Cambodia, India, Madagascar, Marshall Islands, Myanmar, Nepal, Pakistan, Palau, Sri Lanka, and Yemen), only Yemen had a significant decrease in the prevalence of chewing tobacco use, which was among males between 1990 and 2019 (-0 center dot 94% [-1 center dot 72 to -0 center dot 14]), compared with nine of 12 countries that had significant decreases in the prevalence of smoking tobacco. Among females, none of these 12 countries had significant decreases in prevalence of chewing tobacco use, whereas seven of 12 countries had a significant decrease in the prevalence of tobacco smoking use for the period. Summary Background Chewing tobacco and other types of smokeless tobacco use have had less attention from the global health community than smoked tobacco use. However, the practice is popular in many parts of the world and has been linked to several adverse health outcomes. Understanding trends in prevalence with age, over time, and by location and sex is important for policy setting and in relation to monitoring and assessing commitment to the WHO Framework Convention on Tobacco Control. Methods We estimated prevalence of chewing tobacco use as part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 using a modelling strategy that used information on multiple types of smokeless tobacco products. We generated a time series of prevalence of chewing tobacco use among individuals aged 15 years and older from 1990 to 2019 in 204 countries and territories, including age-sex specific estimates. We also compared these trends to those of smoked tobacco over the same time period. Findings In 2019, 273 & middot;9 million (95% uncertainty interval 258 & middot;5 to 290 & middot;9) people aged 15 years and older used chewing tobacco, and the global age-standardised prevalence of chewing tobacco use was 4 & middot;72% (4 & middot;46 to 5 & middot;01). 228 & middot;2 million (213 & middot;6 to 244 & middot;7; 83 & middot;29% [82 & middot;15 to 84 & middot;42]) chewing tobacco users lived in the south Asia region. Prevalence among young people aged 15-19 years was over 10% in seven locations in 2019. Although global age standardised prevalence of smoking tobacco use decreased significantly between 1990 and 2019 (annualised rate of change: -1 & middot;21% [-1 & middot;26 to -1 & middot;16]), similar progress was not observed for chewing tobacco (0 & middot;46% [0 & middot;13 to 0 & middot;79]). Among the 12 highest prevalence countries (Bangladesh, Bhutan, Cambodia, India, Madagascar, Marshall Islands, Myanmar, Nepal, Pakistan, Palau, Sri Lanka, and Yemen), only Yemen had a significant decrease in the prevalence of chewing tobacco use, which was among males between 1990 and 2019 (-0 & middot;94% [-1 & middot;72 to -0 & middot;14]), compared with nine of 12 countries that had significant decreases in the prevalence of smoking tobacco. Among females, none of these 12 countries had significant decreases in prevalence of chewing tobacco use, whereas seven of 12 countries had a significant decrease in the prevalence of tobacco smoking use for the period. Interpretation Chewing tobacco remains a substantial public health problem in several regions of the world, and predominantly in south Asia. We found little change in the prevalence of chewing tobacco use between 1990 and 2019, and that control efforts have had much larger effects on the prevalence of smoking tobacco use than on chewing tobacco use in some countries. Mitigating the health effects of chewing tobacco requires stronger regulations and policies that specifically target use of chewing tobacco, especially in countries with high prevalence. Copyright (c) 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Evaluation of optimum dose of anti-snake venom required and its outcome based on severity of envenomation in snakebite case

Background: Snakebite is an important occupational hazard in India as it is always been a land of poisonous snakes. The isssue which the physician confronts while treating a snake bite patient is assesment of degree of envenomation and requirement of ASV dose. Aims and Objectives: This study was taken to evaluate the optimum dose of anti-snake venom (ASV) required based on the severity of envenomation. Materials and Methods: Patients with a history of snakebite brought to the Department of General Medicine, Hassan, were included in this study. The study was conducted during the period from December 2014 to June 2016. The sample size of 80 patients was included in the study after fulfilling the inclusion criteria. Results: A total of 80 patients were included in the study. The majority of the victims were males (70%), age between 21 and 40 years (47.5%), and agriculture was the main occupation (67.3%). 51.25% did not identify the snake. The most poisonous were viper and cobra types which were 36.5% and 12.5%, respectively. A delay in lag time of 8.99±8.2 h was observed in severe envenomation. Overall, 51 cases (63.75%) had cellulitis, and 3 (3.75%) in the severe group required fasciotomy. Twenty percent had hematologic derangements. Ten percent of patients had developed renal failure and one required dialysis. 8.75% of patients developed respiratory failure and all required mechanical ventilation. The average dose of ASV vials used in mild, moderate, and severe envenomation was 9.04±3.51 vials, 18.5±5.27 vials, and 28.6±7.30 vials, respectively. The overall mortality rate was 5%. Conclusions: The optimum dose of ASV required in mild, moderate, and severe envenomation is 9.04±3.51 vials, 18.5±5.27 vials, and 28.6±7.30 vials, respectively to neutralize the circulating venom and lower the risk of development of serious complications

A STUDY TO ASSESS, MONITOR, AND REPORTING OF ADVERSE DRUG REACTIONS IN A TERTIARY CARE TEACHING HOSPITAL: HIMS, HASSAN

Objective: An adverse drug reaction (ADR) is an unwanted, undesirable effect of a medication that occurs during usual clinical use. ADR should be quickly identified and managed to limit their detrimental effects on the patient. This study was undertaken to characterize the pattern of ADRs reported through spontaneous reporting system at ADR reporting unit in a tertiary care teaching hospital. Methods: A prospective, observational study was conducted over 3 years between September, 2017 and August, 2019. The ADRs reported were from patients admitted inpatient department of hospital. Evaluation of patient demographics, drug and ADR characteristics, and outcome of the ADRs. Causality and severity assessment was done by the World Health Organization system and Naranjos scale. Results: 82 cases of ADRs were reported during the study period. More number of ADRs was from General Medicine and Pediatric departments, in which the most affected organ systems were the skin and the gastrointestinal tract. The antibiotic classes mostly accounted were cephalosporins. None of the ADR was fatal. Conclusion: ADRs to antibiotics are common and will be resulted in increased health-care cost due to the need of some interventions and increased length of hospital stay. The health-care system should promote proper documentation and periodic reporting to regional pharmacovigilance centers to ensure drug safety

Amperometric hydrogen peroxide and cholesterol biosensors designed by using hierarchical curtailed silver flowers functionalized graphene and enzymes deposits

Novel flower-like silver particles with triangular plates as building block along with functionalized graphene (straggled sheets) and enzymes horseradish peroxidase (HRP) or cholesterol oxidase (ChOx), were obtained on graphite electrode by galvanostatic electrodeposition method. The morphology of the electrodeposits has been characterized using scanning electron microscopy and energy-dispersive analysis of X-ray. The resulting biosensors named Nf/(HRP-f-graphene-Ag)/Gr and Nf/(ChOx-f-graphene-Ag)/Gr were evaluated for electrochemical activity using cyclic voltammetry (CV), differential pulse voltammetry (DPV) and chronoamperometry. Optimization of the interdependent experimental parameters such as pH and temperature were achieved and maintained constant throughout the experiments. An activation energy of 2.5 kJ mol -1 was obtained for Nf/(HRP-f-graphene-Ag)/Gr electrode while Nf/(ChOx-f-graphene-Ag)/Gr showed an activation energy of 2.06 and 3.12 kJ mol-1. Furthermore, the former electrode demonstrated a good linear range of 25 μM to 19.35 mM with rapid response time of 3 s and detection limit of 5 μM for hydrogen peroxide. Similarly, the Nf/(ChOx-f-graphene-Ag)/ Gr electrode revealed a linear range of 0.1-4.5 mM with rapid response time of 3 s and an excellent detection limit of 0.514 mM for cholesterol. Besides this, the Nf/(HRP-f-graphene-Ag)/Gr and Nf/(ChOx-f-graphene-Ag)/Gr electrodes displayed a Michaelis-Menten constant of 0.26 and 0.57 mM, respectively, suggesting high affinity and enzymatic activity. The enhanced performance of biosensors towards detection of substrate and rejection of interferents, provided an evidence for its high anti-interference ability. Additionally the biosensors exhibit long term storage stability and reproducibility with antifouling properties. © 2013 Springer-Verlag Berlin Heidelberg.