Designing multi-epitope vaccine against human cytomegalovirus integrating pan-genome and reverse vaccinology pipelines.

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.

The Current State of Pediatric Emergency Medicine Training in Emergency Medicine Residencies.

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.

Revelation of bioremediation approaches for hexachlorocyclohexane degradation in soil.

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.

Pesticide exposure and child growth in low- and middle-income countries: A systematic review.

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.

Encapsulated hydroxychloroquine and chloroquine into cyclic oligosaccharides are the potential therapeutics for COVID-19: insights from first-principles calculations.

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.

Identifying locations of re-entrant drivers from patient-specific distribution of fibrosis in the left atrium.

Clinical evidence suggests a link between fibrosis in the left atrium (LA) and atrial fibrillation (AF), the most common sustained arrhythmia. Image-derived fibrosis is increasingly used for patient stratification and therapy guidance. However, locations of re-entrant drivers (RDs) sustaining AF are unknown and therapy success rates remain suboptimal. This study used image-derived LA models to explore the dynamics of RD stabilization in fibrotic regions and generate maps of RD locations. LA models with patient-specific geometry and fibrosis distribution were derived from late gadolinium enhanced magnetic resonance imaging of 6 AF patients. In each model, RDs were initiated at multiple locations, and their trajectories were tracked and overlaid on the LA fibrosis distributions to identify the most likely regions where the RDs stabilized. The simulations showed that the RD dynamics were strongly influenced by the amount and spatial distribution of fibrosis. In patients with fibrosis burden greater than 25%, RDs anchored to specific locations near large fibrotic patches. In patients with fibrosis burden below 25%, RDs either moved near small fibrotic patches or anchored to anatomical features. The patient-specific maps of RD locations showed that areas that harboured the RDs were much smaller than the entire fibrotic areas, indicating potential targets for ablation therapy. Ablating the predicted locations and connecting them to the existing pulmonary vein ablation lesions was the most effective in-silico ablation strategy.

COVID-19 infection among emergency department healthcare providers in a large tertiary academic medical center following the peak of the pandemic.

The COVID-19 pandemic has spread through the US during the last few months exposing healthcare providers to possible infection. Here we report testing of emergency department (ED) healthcare providers (HCP) for exposure to COVID-19 through lateral flow point of care (POC) and lab-based enzyme-linked immunosorbent assay (ELISA), and RTq-PCR for evidence of acute infection. 138 ED HCP were tested between May 26th (approximately one month after the peak of COVID-19 first wave of cases) and June 14th. Enrolled ED HCP represented about 70% of the total ED HCP workforce during the study period. Subjects were tested with a POC COVID-19 antibody test, and standard ELISA performed by a university-based research lab. Subjects also provided a mid-turbinate swab and a saliva specimen for RTq-PCR. All subjects provided demographic information, past medical history, information about personal protective equipment (PPE) use, COVID-19 symptoms, as well as potential COVID-19 exposures during the previous 4 weeks, both in the ED, and outside the clinical setting. None of the HCP had positive RT-PCR results; 7 HCP (5%) had positive IgG for COVID-19; there was strong agreement between the lab-based ELISA (reference test) and the POC Ab test (P ≤ 0.0001). For the POC Ab test there were no false negatives and only one false positive among the 138 participants. There was no significant difference in demographic/ethnic variables, past medical history, hours worked in the ED, PPE use, or concerning exposures between seropositive and seronegative individuals. Moreover, there was no significant difference in reported symptoms between the two groups during the previous four weeks. The rate of COVID-19 seroconversion in our ED was 5% during the month following the pandemic's first wave. Based on questionnaire responses, differences in demographics/ethnicity, medical history, COVID-19 exposures, and PPE use were not associated with ED HCP having been infected with SARS-CoV-2. In the setting of our limited cohort of subjects the COVID-19 POC Ab test performed comparably to the ELISA lab-based standard.

Temperature dependent Young's modulus of ZnO nanowires.

A thermal resonant method was developed to accurately determine the temperature-dependent Young's moduli of nanowires. In this method, the frequency spectra of a [0001]-oriented ZnO nanowire cantilever at elevated temperatures were measured using scanning laser Doppler vibrometry. The temperature-dependent Young's moduli were derived from the resonant frequencies using Euler-Bernoulli beam theory. It was found that the modulus of ZnO nanowires decreased linearly with the increase of temperature from 300 to 650 K, independent of the nanowire diameter ranged from 101 to 350 nm. The temperature coefficient that defines the linear relationship between the dimensionless modulus and temperature is [Formula: see text] which agrees with that of [Formula: see text] being calculated using molecular dynamics with a partially charged rigid ion model.

Multiple-metal exposure, diet, and oxidative stress in Uruguayan school children.

Oxidative stress (OS) is an important consequence of exposure to toxic metals but it is unclear to what extent low-level metal exposures contribute to OS in children. We examined the cross-sectional association between urinary concentrations of arsenic (As), cadmium (Cd), and lead (Pb) and urinary markers of OS: F2-8α isoprostane and 8-hydroxy-2-deoxy-guanosine (8-OHdG). We also tested effect modification by dietary intakes. Of the 211 children aged 6-8 years living in Montevideo who were eligible for the study because they had at least one OS marker measured via ELISA, 143 were included in a complete-case analysis. Urinary metals were measured with inductively coupled plasma mass spectrometry (ICP-MS: Pb, Cd) and high-performance liquid chromatography online with hydride generation ICP-MS (As-metabolites); concentrations were log2-transformed. All urinary markers were adjusted for specific gravity of urine. Two 24-h dietary recalls were conducted to estimate children's dietary intakes, including total fruit and vegetable consumption and vitamin C, zinc and fiber intake. Ordinary least square (OLS) and weighted quantile sum (WQS) regressions were used to estimate the association between metals and each OS marker as outcome. Metal exposure was generally low: median urinary As, Cd, Pb 9.6 µg/L, 0.06 µg/L and 1.9 µg/L, respectively. Median 8-isoprostane concentration was 1.1 and 8-OHdG 39.6 ng/mL. Log2-transformed urinary As concentrations were positively associated with 8-OHdG concentrations (10.90 [3.82, 17.97]) in covariate-adjusted OLS models which also took account of exposure to Cd and Pb. In WQS, a mixture index was also associated with higher 8-OHdG (8.71 [1.12, 16.3] for each 25% increase in index value), mostly driven by As exposure. There was little evidence of effect modification by dietary antioxidants. In sum, even at low-level, As exposure is associated with detectable oxidative damage to the DNA.

Pica is prevalent and strongly associated with iron deficiency among Hispanic pregnant women living in the United States.

INTRODUCTION: Anecdotal evidence suggests that pica occurs among Hispanic women in the United States, especially during pregnancy. However, the prevalence and socio-demographic and biological factors associated with pica in this population have not been adequately identified. METHODS: Trained, bilingual study personnel conducted structured interviews at public health clinics in Salinas Valley, California with 187 pregnant Hispanic women in their 2nd or 3rd trimesters of pregnancy. Hemoglobin was measured using Hemocue; concentrations of transferrin receptor (TfR) and alpha-1 acid glycoprotein (AGP) were measured in dried blood spots. Multivariable stepwise regression analyses were conducted with pica during pregnancy as the dependent variable and individual- and family-level factors as independent variables to identify significant associations. Additionally, multivariable models were built to explore the associations between pica and iron status (iron deficiency and anemia). RESULTS: Half of all participants (51.3%) had ever engaged in pica, and 37.6% had done so during the current pregnancy. Pica substances included large quantities of ice, frost, raw starches, and various earthen items. Pica during the current pregnancy was significantly associated with higher TfR concentrations [OR: 1.29; 95% CI: 1.11, 1.51] indicative of low iron stores and greater food insecurity [OR: 1.20, 95% CI: 1.03, 1.40]. Women who engaged in pica during the current pregnancy were more likely to be iron deficient [adjusted OR: 2.58; 95% CI: 1.19, 5.60], but not anemic [adjusted OR: 1.40; 0.60, 3.23]. CONCLUSIONS: Among pregnant Hispanic women, pica was prevalent and strongly associated with iron deficiency and food insecurity. Clinicians should screen for pica during pregnancy in Hispanic populations, and future studies should elucidate the underlying etiology and consequences of engaging in pica during pregnancy.

Iron and Zinc Supplementation Does Not Impact Urinary Arsenic Excretion in Mexican School Children.

OBJECTIVE: To examine the role of iron and zinc in arsenic excretion and metabolism in children. STUDY DESIGN: An analysis of urinary arsenic (UAs) concentrations from a double-blind randomized trial originally testing the efficacy of iron and zinc for lowering blood lead levels in children. A 2 × 2 factorial design was used, with children randomized individually, stratified by sex and classroom, to receive 30?mg ferrous fumarate (n?=?148), 30?mg zinc oxide (n?=?144), iron and zinc together (n?=?148), or placebo (n?=?151). Of the 602 children enrolled, 527 completed the 6-month treatment, and 485 had both baseline and final UAs values. The baseline total UAs concentration ranged from 3.2 to 215.9?µg/L. RESULTS: At baseline, children in the highest tertile of serum ferritin concentration had higher excretion of dimethylarsinic acid (DMA; 1.93?±?0.86%; P?

Association of blood lead levels with urinary F2-8α isoprostane and 8-hydroxy-2-deoxy-guanosine concentrations in first-grade Uruguayan children.

Oxidative stress (OS) is a potential molecular mechanism for lead-induced toxicities, yet, we have limited understanding of the relation between low-level lead (Pb) exposure and OS, especially in children. This cross-sectional study examines the association between blood lead level (BLL) and two OS markers-urinary F2-8α isoprostane or isoprostane (a marker of lipid peroxidation) and 8-hydroxy-2-deoxy-Guanosine or 8-OH-dG (a marker of DNA damage) in 211 children, aged 5-8 years, from Montevideo, Uruguay. The role of dietary intakes of vitamin C and zinc in modifying the relation between BLL and OS was also examined. The mean (SD) BLL of the study children was 4.7 (2.2) µg/dL, with 30.2% children having BLL ≥5 µg/dL, the current reference level set by the US Centre for Disease Control for identifying, monitoring and management of children with elevated BLL. In covariate-adjusted analysis, there was a weak positive association between BLL and urinary isoprostane (adjusted for specific gravity) [ß=0.09, p<0.1]. No association was found between children's BLL and urinary 8-OH-dG. Interactions between dietary intakes of vitamin C or zinc and BLL on OS biomarkers were not consistent. However, when BLL and vitamin C or BLL and zinc were modeled together, BLL was independently associated with isoprostane concentration [ß=0.10, p<0.05] but vitamin C or zinc intake was not. These findings suggest that there may be a potential adverse effect of BLL on OS in children with low-level Pb exposure. There is a need to study the effects of Pb on other OS measures, as well as the role of OS in mediating low-level Pb toxicity on functional outcomes.

Integrating pan-genome and reverse vaccinology to design multi-epitope vaccine against Herpes simplex virus type-1.

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.

Exploring the potential of Meyerozyma caribbica and its combined application with bacteria for lindane bioremediation.

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 L⁻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 mL⁻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 mL⁻1). Whereas the mixed culture of M. caribbica and B. velezensis resulted in 80.9% reduction at 500 mg L⁻1 lindane with dechlorinase activity of 6.77 U mL⁻1. Growth kinetics, modelled using the Monod equation, showed a maximum specific growth rate of 0.416 h⁻1 for the mixed culture of M. caribbica and P. megaterium at 750 mg L⁻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.

Evidence of potential impacts of a nutrition-sensitive agroecology program in Andhra Pradesh, India, on dietary diversity, nutritional status, and child development.

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.

Pregnancy pesticide exposure and child development in low- and middle-income countries: A prospective analysis of a birth cohort in rural Bangladesh and meta-analysis.

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.

Co-Benefits of Largescale Organic farming On huMan health (BLOOM): Protocol for a cluster-randomised controlled evaluation of the Andhra Pradesh Community-managed Natural Farming programme in India.

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.

Parvovirus Infection Leading to Severe Anemia in an Adult Patient With HIV Disease.

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.

Role of Prophylactic Steroids in Differentiation Syndrome.

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.

In-silico drug trials for precision medicine in atrial fibrillation: From ionic mechanisms to electrocardiogram-based predictions in structurally-healthy human atria.

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.