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Human cytomegalovirus (HCMV) is accountable for high morbidity in neonates and immunosuppressed individuals. Due to the high genetic variability of HCMV, current prophylactic measures are insufficient. In this study, we employed a pan-genome and reverse vaccinology approach to screen the target for efficient vaccine candidates. Four proteins, envelope glycoprotein M, UL41A, US23, and US28, were shortlisted based on cellular localization, high solubility, antigenicity, and immunogenicity. A total of 29 B-cell and 44 T-cell highly immunogenic and antigenic epitopes with high global population coverage were finalized using immunoinformatics tools and algorithms. Further, the epitopes that were overlapping among the finalized B-cell and T-cell epitopes were linked with suitable linkers to form various combinations of multi-epitopic vaccine constructs. Among 16 vaccine constructs, Vc12 was selected based on physicochemical and structural properties. The docking and molecular simulations of VC12 were performed, which showed its high binding affinity (-23.35 kcal/mol) towards TLR4 due to intermolecular hydrogen bonds, salt bridges, and hydrophobic interactions, and there were only minimal fluctuations. Furthermore, Vc12 eliciting a good response was checked for its expression in Escherichia coli through in silico cloning and codon optimization, suggesting it to be a potent vaccine candidate.
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Herpes simplex virus type-1 (HSV-1), the etiological agent of sporadic encephalitis and recurring oral (sometimes genital) infections in humans, affects millions each year. The evolving viral genome reduces susceptibility to existing antivirals and, thus, necessitates new therapeutic strategies. Immunoinformatics strategies have shown promise in designing novel vaccine candidates in the absence of a clinically licensed vaccine to prevent HSV-1. However, to encourage clinical translation, the HSV-1 pan-genome was integrated with the reverse-vaccinology pipeline for rigorous screening of universal vaccine candidates. Viral targets were screened from 104 available complete genomes. Among 364 proteins, envelope glycoprotein D being an outer membrane protein with a high antigenicity score (> 0.4) and solubility (> 0.6) was selected for epitope screening. A total of 17 T-cell and 4 B-cell epitopes with highly antigenic, immunogenic, non-toxic properties and high global population coverage were identified. Furthermore, 8 vaccine constructs were designed using different combinations of epitopes and suitable linkers. VC-8 was identified as the most potential vaccine candidate regarding chemical and structural stability. Molecular docking revealed high interactive affinity (low binding energy: - 56.25 kcal/mol) of VC-8 with the target elicited by firm intermolecular H-bonds, salt-bridges, and hydrophobic interactions, which was validated with simulations. Compatibility of the vaccine candidate to be expressed in pET-29(a) + plasmid was established by in silico cloning studies. Immune simulations confirmed the potential of VC-8 to trigger robust B-cell, T-cell, cytokine, and antibody-mediated responses, thereby suggesting a promising candidate for the future of HSV-1 prevention. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-04022-6.
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This study explored the degradation potential of a yeast strain, Meyerozyma caribbica, alone and in combination with Bacillus velezensis and Priestia megaterium, found novel for lindane biodegradation. Isolated from hexachlorocyclohexane (HCH)-contaminated sites, M. caribbica, B. velezensis, and P. megaterium demonstrated lindane reduction efficiencies of 86.5%, 78.6%, and 77.5%, respectively, at 750 mg Lâ»1 within 10-day incubation period. Kinetic analysis revealed that M. caribbica followed the first-order degradation (r2 = 0.991; T1/2 = 4.3 days). Notably, M. caribbica exhibited the highest dechlorinase activity (9.27 U mLâ»1) in the cell supernatant. Co-cultivation as the mixed culture of M. caribbica and P. megaterium achieved maximum lindane reduction (90%) and dechlorinase activity (9.93 U mLâ»1). Whereas the mixed culture of M. caribbica and B. velezensis resulted in 80.9% reduction at 500 mg Lâ»1 lindane with dechlorinase activity of 6.77 U mLâ»1. Growth kinetics, modelled using the Monod equation, showed a maximum specific growth rate of 0.416 hâ»1 for the mixed culture of M. caribbica and P. megaterium at 750 mg Lâ»1 lindane. GC-MS analysis confirmed the presence of intermediate metabolites, viz., γ-pentachlorocyclohexane, 1,2,4-trichlorobenzene, 1,4-dichlorobenzene and maleyl acetate, validated successive dechlorination and oxidative-reduction processes during lindane biodegradation. The findings of the study highlighted the potential of these novel microbial strains and their mixed cultures for effective bioremediation of lindane-contamination.
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Dépollution biologique de l'environnement , Lindane , Lindane/métabolisme , Polluants du sol/métabolisme , Microbiologie du sol , Insecticides/métabolisme , Cinétique , Bacillus/métabolismeRÉSUMÉ
INTRODUCTION: While a number of studies have examined the nutritional impacts of agroecological interventions, few have examined impacts on child development, maternal and child anemia, and men's dietary diversity. Moreover, there have been few such evaluations at scale. We evaluated the impact of a large-scale, multi-component food-based nutrition intervention involving homestead food production, nutrition counselling, cooking demonstrations, and crop planning exercises. METHODS: A cross-sectional assessment was conducted in 2021-2022 of 50 intervention villages where the nutrition-sensitive agroecology program had been implemented since 2018 and 79 control villages where only the agroecology program had been implemented. Data on self-reported dietary intake, caregiver-reported early child development, anthropometric measurements, and hemoglobin concentrations were collected using standardized procedures by trained Nutrition Farming Fellows, who were also responsible for implementing the program. RESULTS: A sample of 3,511 households (1,121 intervention and 2,390 control) participated in the survey. Dietary diversity scores (DDS) among women and men were mean (SD) 6.53 (±1.62) and 6.16 (±1.65), respectively, in intervention villages and 5.81 (±1.58) and 5.39 (±1.61), respectively, in control villages (p<0.01). DDS among children 6-24 months of age in intervention and control villages was 2.99 (±1.52) and 2.73 (±1.62), respectively (p<0.01). Children <2 years of age were less likely to be anemic in intervention versus control villages (59% versus 69%, p<0.01). Children 18-35 months age in intervention villages had higher child development scores than children in control villages (all p<0.05). CONCLUSION: Nutrition-sensitive agroecological programs may be effective in improving diets, nutrition, and child development in rural India.
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Agriculture , Développement de l'enfant , Régime alimentaire , État nutritionnel , Humains , Inde , Mâle , Femelle , Enfant d'âge préscolaire , Développement de l'enfant/physiologie , Études transversales , Agriculture/méthodes , Nourrisson , Adulte , Enfant , Population ruraleRÉSUMÉ
This review elucidates different bioremediation approaches used for degradation of HCH from contaminated sites. It highlights the significance of degradative pathways, microbial diversity and impact of different environmental factors for developing viable bioremediation strategies. The application of innovative biotechnological approaches and a thorough understanding of HCH biodegradation pathways show great promise for the creation of long-term solutions to HCH pollution and the restoration of polluted soil ecosystems. Bioremediation technologies viz. biostimulation, bioaugmentation, phytoremediation have been considered till date for treating HCH-contaminated sites. Different bacterial and fungal strains have been reported for degradation of HCH residues. However, these methods are limited to γ-HCH degradation, at laboratory scale and achieving lower success rate for large scale demonstration trials. This review presents a theoretical background for degradation of different HCH isomers in soil through plants, microbes and through their cooperative interactions. This work briefly overviews the substantial contamination of the environment by HCH residues, along with spontaneous evolution of degradation pathways through various HCH degrading microbes. Bioremediation mechanism and pathways of HCH degradation through plants and microbes have been discussed thoroughly. Through molecular and genetic investigations, the complex metabolic pathways used by these microbes, including reductive dechlorination, hydrolysis, and ring cleavage, has been clarified. This study seeks to give a thorough summary of recent discoveries and developments in bioremediation methods for soil HCH degradation. Numerous microbial consortia, including fungi, plants, and bacteria have been recognised as important participants in the transformation of HCH.
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Lindane , Polluants du sol , Humains , Lindane/composition chimique , Lindane/métabolisme , Dépollution biologique de l'environnement , Sol , Écosystème , Bactéries/génétique , Bactéries/métabolisme , Champignons/génétique , Champignons/métabolisme , Polluants du sol/métabolismeRÉSUMÉ
BACKGROUND: Despite considerable evidence on a negative association between pregnancy pesticide exposure and child development in high-income countries, evidence from low- and middle-income countries (LMICs) is limited. Therefore, we assessed associations between pregnancy pesticide exposure and child development in rural Bangladesh and summarised existing literature in a systematic review and meta-analysis. METHODS: We used data from 284 mother-child pairs participating in a birth cohort established in 2008. Eight urinary pesticide biomarkers were quantified in early pregnancy (mean gestational age 11.6±2.9 weeks) as an index of pesticide exposure. The Bayley Scales of Infant and Toddler Development, Third Edition were administered at 20-40 months of age. Associations between creatinine-adjusted urinary pesticide biomarker concentrations and child development scores were estimated using multivariable generalised linear models. We searched ten databases up to November 2021 to identify prospective studies on pregnancy pesticide exposure and child development conducted in LMICs. We used a random-effects model to pool similar studies, including our original analysis. The systematic review was pre-registered with PROSPERO: CRD42021292919. RESULTS: In the Bangladesh cohort, pregnancy 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMPY) concentrations were inversely associated with motor development (-0.66 points [95% CI -1.23, -0.09]). Pregnancy 3,5,6-trichloro-2-pyridinol (TCPY) concentrations were inversely associated with cognitive development, but the association was small: -0.02 points (-0.04, 0.01). We observed no associations between 4-nitrophenol and 3-phenoxybenzoic acid (3-PBA) concentrations and child development. The systematic review included 13 studies from four LMICs. After pooling our results with one other study, we found consistent evidence that pregnancy 3-PBA concentrations were not associated with cognitive, language, or motor development. CONCLUSION: Evidence suggests that pregnancy exposure to some organophosphate pesticides is negatively associated with child development. Interventions to reduce in-utero pesticide exposure in LMICs may help protect child development.
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Pesticides , Grossesse , Nourrisson , Femelle , Humains , Pays en voie de développement , Développement de l'enfant , Cohorte de naissance , Études prospectives , BangladeshRÉSUMÉ
The BLOOM study (co-Benefits of Largescale Organic farming On huMan health) aims to determine if a government-implemented agroecology programme reduces pesticide exposure and improves dietary diversity in agricultural households. To achieve this aim, a community-based, cluster-randomised controlled evaluation of the Andhra Pradesh Community-managed Natural Farming (APCNF) programme will be conducted in 80 clusters (40 intervention and 40 control) across four districts of Andhra Pradesh state in south India. Approximately 34 households per cluster will be randomly selected for screening and enrolment into the evaluation at baseline. The two primary outcomes, measured 12 months post-baseline assessment, are urinary pesticide metabolites in a 15% random subsample of participants and dietary diversity in all participants. Both primary outcomes will be measured in (1) adult men ≥18 years old, (2) adult women ≥18 years old, and (3) children <38 months old at enrolment. Secondary outcomes measured in the same households include crop yields, household income, adult anthropometry, anaemia, glycaemia, kidney function, musculoskeletal pain, clinical symptoms, depressive symptoms, women's empowerment, and child growth and development. Analysis will be on an intention-to-treat basis with an a priori secondary analysis to estimate the per-protocol effect of APCNF on the outcomes. The BLOOM study will provide robust evidence of the impact of a large-scale, transformational government-implemented agroecology programme on pesticide exposure and dietary diversity in agricultural households. It will also provide the first evidence of the nutritional, developmental, and health co-benefits of adopting agroecology, inclusive of malnourishment as well as common chronic diseases. Trial registration: Study registration: ISRCTN 11819073 (https://doi.org/10.1186/ISRCTN11819073). Clinical Trial Registry of India CTRI/2021/08/035434.
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Agriculture biologique , Pesticides , Adolescent , Adulte , Enfant , Femelle , Humains , Nourrisson , Mâle , Agriculture , Fermes , Inde , Essais contrôlés randomisés comme sujetRÉSUMÉ
BACKGROUND: Several studies show that emergency medicine (EM) physicians are less comfortable caring for pediatric patients than adults. The state of pediatric training has not been comprehensively evaluated since 2000. OBJECTIVES: We sought to describe current pediatric education in EM residencies and to evaluate EM Program Director (PD) confidence in graduating trainees' abilities to care for pediatric patients. METHODS: We conducted an anonymous, cross-sectional survey study of EM PDs in August 2020. We collected program demographics, clinical rotations, and didactic methods. We used Likert scales to measure PD confidence in graduating residents' competence to care for pediatric and adult patients. RESULTS: We found e-mail addresses for 249 (93%) of 268 EM programs. One hundred nineteen (48%) PDs completed the survey. We include denominators to account for unanswered questions. Sixty-eight (59%) of 116 programs spend 10% to 20% of clinical time seeing pediatric patients. One hundred ten (91%) of 119 require a pediatric emergency medicine (PEM) rotation, 88/119 (83%) require pediatric intensive care, and 34/119 (29%) require neonatal intensive care. Seventy (62%) of 113 have curricula designed by PEM-trained faculty, 96/113 (85%) have PEM attendings teach lectures, and 77/113 (68%) spend 10% to 20% of didactic time on pediatric topics. Twenty-three (23%) of 106 PDs stated not all residents graduate with competence in pediatric resuscitation compared with 2/106 (2%) for adult resuscitation ( P < 0.05). CONCLUSIONS: Program directors report less confidence in graduating residents' competence in caring for pediatric patients compared with adult patients. We propose ideas to strengthen the quality of pediatric education in EM residencies.
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Médecine d'urgence , Internat et résidence , Médecine d'urgence pédiatrique , Adulte , Nouveau-né , Humains , Enfant , Médecine d'urgence pédiatrique/enseignement et éducation , Études transversales , Médecine d'urgence/enseignement et éducation , Programme d'études , Enquêtes et questionnairesRÉSUMÉ
Arsenic contamination in water and soil is becoming a severe problem. It is toxic to the environment and human health. It is usually found in small quantities in rock, soil, air, and water which increase due to natural and anthropogenic activities. Arsenic exposure leads to several diseases such as vascular disease, including stroke, ischemic heart disease, and peripheral vascular disease, and also increases the risk of liver, lungs, kidneys, and bladder tumors. Arsenic leads to oxidative stress that causes an imbalance in the redox system. Mycoremediation approaches can potentially reduce the As level near the contaminated sites and are procuring popularity as being eco-friendly and cost-effective. Many fungi have specific metal-binding metallothionein proteins, which are used for immobilizing the As concentration from the soil, thereby removing the accumulated As in crops. Some fungi also have other mechanisms to reduce the As contamination, such as biosynthesis of glutathione, cell surface precipitation, bioaugmentation, biostimulation, biosorption, bioaccumulation, biovolatilization, methylation, and chelation of As. Arsenic-resistant fungi and recombinant yeast have a significant potential for better elimination of As from contaminated areas. This review discusses the relationship between As exposure, oxidative stress, and signaling pathways. We also explain how to overcome the detrimental effects of As contamination through mycoremediation, unraveling the mechanism of As-induced toxicity.
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In recent times, nonalcoholic fatty liver disease (NAFLD) has been considered one of the major causes of liver disease across the world. NAFLD is defined as the deposition of triglycerides in the liver and is associated with obesity and metabolic syndrome. Hyperinsulinemia, insulin resistance (IR), fatty liver, hepatocyte injury, unbalanced proinflammatory cytokines, mitochondrial dysfunction, oxidative stress, liver inflammation, and fibrosis are the main pathogenesis in NAFLD. Recent studies suggest that the action of intestinal microbiota through chronic inflammation, increased intestinal permeability, and energy uptake plays a vital role in NAFLD. Moreover, polycystic ovarian syndrome also causes NAFLD development through IR. Age, gender, race, ethnicity, sleep, diet, sedentary lifestyle, and genetic and epigenetic pathways are some contributing factors of NAFLD that can exacerbate the risk of liver cirrhosis and hepatocellular carcinoma (HCC) and eventually lead to death. NAFLD has various presentations, including fatigue, unexplained weight loss, bloating, upper abdominal pain, decreased appetite, headache, anxiety, poor sleep, increased thirst, palpitation, and a feeling of warmth. Some studies have shown that NAFLD with severe coronavirus disease 2019 (COVID-19) has poor outcomes. The gold standard for NAFLD diagnosis is liver biopsy. Other diagnostic tools are imaging tests, serum biomarkers, microbiota markers, and tests for extrahepatic complications. There are no specific treatments for NAFLD. Therefore, the main concern for NAFLD is treating the comorbid conditions such as anti-diabetic agents for type 2 diabetes mellitus, statins to reduce HCC progression, antioxidants to prevent hepatocellular damage, and bariatric surgery for patients with a BMI of >40 kg/m2 and >35 kg/m2 with comorbidities. Lifestyle and dietary changes are considered preventive strategies against NAFLD advancement. Inadequate treatment of NAFLD further leads to cardiac consequences, sleep apnea, chronic kidney disease, and inflammatory bowel disease. In this systematic review, we have briefly discussed the risk factors, pathogenesis, clinical features, and numerous consequences of NAFLD. We have also reviewed various guidelines for NAFLD diagnosis along with existing therapeutic strategies for the management and prevention of the disease.
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Atrial fibrillation (AF) inducibility, sustainability and response to pharmacological treatment of individual patients are expected to be determined by their ionic current properties, especially in structurally-healthy atria. Mechanisms underlying AF and optimal cardioversion are however still unclear. In this study, in-silico drug trials were conducted using a population of human structurally-healthy atria models to 1) identify key ionic current properties determining AF inducibility, maintenance and pharmacological cardioversion, and 2) compare the prognostic value for predicting individual AF cardioversion of ionic current properties and electrocardiogram (ECG) metrics. In the population of structurally-healthy atria, 477 AF episodes were induced in ionic current profiles with both steep action potential duration (APD) restitution (eliciting APD alternans), and high excitability (enabling propagation at fast rates that transformed alternans into discordant). High excitability also favored 211 sustained AF episodes, so its decrease, through prolonged refractoriness, explained pharmacological cardioversion. In-silico trials over 200 AF episodes, 100 ionic profiles and 10 antiarrhythmic compounds were consistent with previous clinical trials, and identified optimal treatments for individual electrophysiological properties of the atria. Algorithms trained on 211 simulated AF episodes exhibited >70% accuracy in predictions of cardioversion for individual treatments using either ionic current profiles or ECG metrics. In structurally-healthy atria, AF inducibility and sustainability are enabled by discordant alternans, under high excitability and steep restitution conditions. Successful pharmacological cardioversion is predicted with 70% accuracy from either ionic or ECG properties, and it is optimal for treatments maximizing refractoriness (thus reducing excitability) for the given ionic current profile of the atria.
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Acute promyelocytic leukemia (APML) is defined as a balanced chromosomal translocation between chromosomes 15 and 17 t(15;17)(q24;q21), which results in the formation of promyelocytic leukemia-retinoic acid receptor-alpha (PML-RARA) fusion protein. A widespread recommendation for APML treatment is combined all-trans retinoic acid (ATRA)/arsenic trioxide (ATO) therapy. Differentiation syndrome (DS), or retinoic acid syndrome, is one of the well-known complications of APML treated with ATRA or ATO. The presenting symptoms of APML-induced DS are diverse, and rare symptoms are easily misdiagnosed. However, unexplained fever, dyspnea, weight gain > 5 kg, leukocytosis, acute renal failure, and a chest radiograph demonstrating pleural or pericardial effusion are the most common manifestations of DS. Early recognition and prompt initiation of corticosteroids are key factors in the management of DS. As soon as ATRA/ATO therapy is started, prophylactic treatment with steroids has been recommended to minimize the severity of DS. It is proposed that ATRA/ATO should be stopped or held once the signs and symptoms of DS develop. This case report describes a 45-year-old male who was diagnosed with APML after he developed episodes of hematuria and nose bleeding at home. The patient was also given an empiric steroid along with ATRA/ATO to lessen the intensity of DS. Our study suggests that early initiation of prophylactic steroid treatment can improve the prognosis and mortality of patients with APML-induced DS.
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Individuals with human immunodeficiency virus (HIV) disease frequently suffer from anemia. The causes include anemia of chronic disease, vitamin B12 and iron deficiency, opportunistic infections (Mycobacterium tuberculosis, Pneumocystis jiroveci), HIV-related bone marrow suppression, AIDS-associated malignancies, and antiretroviral therapy (ART), specifically zidovudine. In HIV patients with advanced immunodeficiency, failure to produce neutralizing antibodies can lead to chronic parvovirus B19 (B19) infection. Normally, in persons with intact immunity, the progression of B19 is self-limited. However, in chronic B19 infection, it can lead to pure red cell aplasia (PRCA) and chronic anemia. In human immunodeficiency virus (HIV)-infected patients, B19-related anemia is rare and underdiagnosed. It has a great response to intravenous immunoglobulin (IVIG) therapy. Hence, early diagnosis and prompt treatment can significantly reduce mortality. In this article, we described the case of a 25-year-old male with HIV infection who presented with a headache. He had severe normocytic anemia with a low reticulocyte count. The workup for blood loss, hemolysis, hemoglobinopathy, and iron deficiency was negative. Because of extremely low reticulocytopenia with severe anemia, the investigations favored multiple myeloma, parvovirus infection, and bone marrow aspiration biopsy. He was tested for parvovirus B19 deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) test due to insufficient seroconversion. It turned out to be positive and he was treated with IVIG therapy.
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BACKGROUND: In low- and middle-income countries (LMICs), pesticides are widely used in agricultural and residential settings. Little is known about how pesticides affect child growth. OBJECTIVES: To systematically review and synthesise the evidence on the associations between pesticide exposure and adverse birth outcomes and/or impaired postnatal growth in children up to 5 years of age in LMICs. METHODS: We searched 10 databases from inception through November 2021. We included cohort and cross-sectional studies investigating associations between self-reported or measured prenatal or postnatal pesticide exposure and child growth (postnatal child linear/ponderal growth, and/or birth outcomes). Two researchers screened studies, extracted data, and assessed certainty using GRADE. The protocol was preregistered with PROSPERO (CRD42021292919). RESULTS: Of 939 records retrieved, 31 studies met inclusion criteria (11 cohort, 20 cross-sectional). All studies assessed prenatal exposure. Twenty-four studies reported on birth weight. Four found positive associations with organochlorines (0.01-0.25 standardised mean difference (SMD)) and two found negative associations (-0.009 SMD to -55 g). Negative associations with organophosphates (-170 g, n = 1) and pyrethroids (-97 to -233 g, n = 2) were also documented. Two (out of 15) studies reporting on birth length found positive associations with organochlorines (0.21-0.25 SMD) and one found negative associations (-0.25 to -0.32 SMD). Organophosphate exposure was negatively associated with birth length (-0.37 cm, n = 1). Organophosphate exposure was also associated with higher risk/prevalence of low birth weight (2 out of nine studies) and preterm birth (2 out of six studies). Certainty of the evidence was "very low" for all outcomes. CONCLUSION: The limited literature from LMICs shows inconclusive associations between prenatal pesticide exposure, child growth, and birth outcomes. Studies with accurate quantitative data on exposure to commonly used pesticides in LMICs using consistent methodologies in comparable populations are needed to better understand how pesticides influence child growth.
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Pesticides , Naissance prématurée , Pyréthrines , Enfant , Études transversales , Pays en voie de développement , Femelle , Humains , Nouveau-né , Organophosphates , Pesticides/toxicité , Grossesse , Naissance prématurée/induit chimiquementRÉSUMÉ
BACKGROUND: The use of pesticides in agriculture has been associated with the destruction of biodiversity and damage to human health. A marked reduction in pesticide use is urgently required globally, but whether this can be achieved rapidly and at scale is unclear. We aimed to assess whether government-legislated and funded organic farming training in Andhra Pradesh, India, reduced pesticide use by farmers and sales of pesticides by pesticide retailers. METHODS: We did a cross-sectional survey between Aug 11 and Nov 26, 2020, among farmers and pesticide retailers in Kurnool District of Andhra Pradesh (India). We assessed the impact of the Andhra Pradesh Community Managed Natural Farming (APCNF) programme, which aims to transition 100% of the agricultural land of Andhra Pradesh (population approximately 49 million, 6 million of whom are farmers) to organic farming practices by 2030. We did cross-sectional phone interview surveys of farmers and face-to-face surveys of pesticide retailers. We used multivariable Poisson regression models to estimate relative risks (RRs) and logistic regression models to estimate odds ratios (ORs). FINDINGS: 962 farmers were invited to participate, of whom 894 (93%) consented (709 conventional farmers and 149 APCNF farmers). 47 pesticide retailers were invited to participate, of whom 38 (81%) consented. APCNF farmers had practised APCNF for a median of 2 years (IQR 1-3). APCNF farmers were less likely to use pesticides than conventional farmers (adjusted RR 0·65 [95% CI 0·57-0·75]), although pesticide use remained high among both APCNF and conventional farmers (73 [49%] of 148 APCNF farmers vs 695 [99%] of 700 conventional farmers; p<0·0001). APCNF farmers had lower pesticide expenditures than conventional farmers (median US$0 [IQR 0-170] for APCNF farmers vs $175 [91-281] for conventional farmers; p=0·0001). Increased frequency of meeting with agricultural extension workers was associated with reduced pesticide use among ACPNF farmers. Seven (18%) of 38 retailers reported a decrease in sales of pesticides in the past 4 years; no difference in the odds of reporting a decrease in pesticide sales in the past 4 years was identified between APCNF retailers and conventional retailers (OR 0·95 [95% CI 0·58-1·57]). INTERPRETATION: Despite a major government drive for organic agriculture, about half of APCNF farmers continued to use pesticides and no impact on pesticide sales at local retailers was observed. A combination of policy instruments (eg, bans on highly hazardous pesticides), not solely training for farmers, might be needed to eliminate pesticide use in agriculture. FUNDING: Scottish Funding Council and UK Research and Innovation.
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Exposition professionnelle , Pesticides , Études transversales , Gouvernement , Connaissances, attitudes et pratiques en santé , Humains , Agriculture biologiqueRÉSUMÉ
Novel-Coronavirus (COVID-19) outburst has become a worldwide pandemic which threaten the scientific community to design and discover efficient and effective treatment strategies against this deadly virus (SARS-CoV-2). Still now, there is no antiviral therapy or drug available in the market which can efficiently combat the infection caused by this virus. In this respect, using available drugs by screening with molecular docking and molecular dynamics studies not only minimizes lengthy chemical trials but also reduces discovery cost for the pharmaceutical industry. During the COVID-19 pandemic situations hydroxychloroquine, chloroquine known as HCQ and CQ tablets have gained popularity as for the treatment coronavirus (COVID-19) but the main threatening effect of HCQ, CQ use lies on their side effects like blistering, peeling, loosening of the skin, blurred vision stomach pain, diarrhea, chest discomfort, pain, or tightness, cough or hoarseness which require immediate medical attention. Encapsulation of HCQ and CQ drugs by the cyclic macromolecules such as α and ß-Cyclodextrin, to form host-guest complexes is very effective strategy to mask the cytotoxicity of certain drugs and alleviating and modulating side effects of drug applications. In the present work, we have encapsulated the HCQ and CQ drugs α and ß-Cyclodextrin and made a comprehensive analysis of stability, optical properties. Details analysis verified that between QC and HCQ, HQC showed stronger affinity towards ß-Cyclodextrin. This strategy can reduce the side effect of HCQ and CQ thereby offers a new way to use these drugs. We hope the present study should help the researchers to develop potential therapeutics against the novel coronavirus.
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[This corrects the article DOI: 10.3389/fphys.2021.733139.].
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Atrial fibrillation (AF) is the most common cardiac arrhythmia and currently affects more than 650,000 people in the United Kingdom alone. Catheter ablation (CA) is the only AF treatment with a long-term curative effect as it involves destroying arrhythmogenic tissue in the atria. However, its success rate is suboptimal, approximately 50% after a 2-year follow-up, and this high AF recurrence rate warrants significant improvements. Image-guidance of CA procedures have shown clinical promise, enabling the identification of key patient anatomical and pathological (such as fibrosis) features of atrial tissue, which require ablation. However, the latter approach still suffers from a lack of functional information and the need to interpret structures in the images by a clinician. Deep learning plays an increasingly important role in biomedicine, facilitating efficient diagnosis and treatment of clinical problems. This study applies deep reinforcement learning in combination with patient imaging (to provide structural information of the atria) and image-based modelling (to provide functional information) to design patient-specific CA strategies to guide clinicians and improve treatment success rates. To achieve this, patient-specific 2D left atrial (LA) models were derived from late-gadolinium enhancement (LGE) MRI scans of AF patients and were used to simulate patient-specific AF scenarios. Then a reinforcement Q-learning algorithm was created, where an ablating agent moved around the 2D LA, applying CA lesions to terminate AF and learning through feedback imposed by a reward policy. The agent achieved 84% success rate in terminating AF during training and 72% success rate in testing. Finally, AF recurrence rate was measured by attempting to re-initiate AF in the 2D atrial models after CA with 11% recurrence showing a great improvement on the existing therapies. Thus, reinforcement Q-learning algorithms can predict successful CA strategies from patient MRI data and help to improve the patient-specific guidance of CA therapy.
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Persistence of hexachlorocyclohexane (HCH) pesticide is a major problem for its disposal. Soil microflora plays an important role in remediating contaminated sites. Keeping concepts of microbial- and phyto-remediation together, the difference between soil microflora with and without association of HCH accumulating plant species was studied. Metagenomic analysis among the non-plant soil (BS) (∑HCH 434.19 mg/g), rhizospheric soil of shrubs (RSS) (∑HCH 157.31 mg/g), and rhizospheric soil of trees (RSD) (∑HCH 105.39 mg/g) revealed significant differences in microbial communities. Shrubs and trees occurred at a long-term dumpsite accumulated α- and ß- HCH residues. Plant rhizospheric soils exhibited high richness and evenness with higher diversity indices compared to the non-plant soil. Order Rhizobiales was most abundant in all soils and Streptomycetales was absent in the BS soil. Proteobacteria and Ascomycota were highest in BS soil, while Actinobacteria was enriched in both the plant rhizospheric soil samples. In BS soil, Pseudomonas, Sordaria, Caulobacter, Magnetospirillum, Rhodospirillum were abundant. While, genera Actinoplanes, Streptomyces, Bradyrhizobium, Rhizobium, Azospirillum, Agrobacterium are abundant in RSD soil. Selected plants have accumulated HCH residues from soil and exerted positive impacts on soil microbial communities in HCH contaminated site. This study advocates microbe-assisted plant-based bioremediation strategy to remediate HCH contamination.