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Raísa Barbosa de Andrade,1 Catherine M Pirkle,2 Tetine Sentell,2 Diego Bassani,3 Marlos Rodrigues Domingues,4 Saionara MA Câmara1,5 1Postgraduate Program in Public Health, Faculty of Health Sciences of Trairi, Federal University of Rio Grande do Norte, Natal, Brazil; 2Office of Public Health Studies, University of Hawaii at Mānoa, Honolulu, HI, USA; 3Department of Paediatrics, Faculty of Medicine & Dalla Lana School of Public Health University of Toronto, Toronto, ON, Canada; 4Postgraduate Programme in Physical Education, Federal University of Pelotas, Pelotas, Brazil; 5Postgraduate Program in Rehabilitation Sciences, Faculty of Health Sciences of Trairi, Federal University of Rio Grande do Norte, Natal, BrazilCorrespondence: Saionara MA CâmaraFaculdade de Ciências da Saúde do Trairi, Universidade Federal do Rio Grande do Norte, Rua Teodorico Bezerra, s/n, Centro, Santa Cruz, RN, BrazilTel +55 84 99480-6888Email saionaraaires@gmail.comBackground: Adolescent pregnancy is a public health concern worldwide, particularly in low-income settings. Adolescent mothers face higher risks during pregnancy and delivery compared to adult mothers and yet, may also experience worse quality of obstetrical care. This study evaluates adherence to meeting Brazilian recommendations for prenatal care by comparing first-time adolescent versus adult mothers in a rural, low-income setting.Methods: Using data from the Adolescence and Motherhood Research (AMOR) project, we evaluated adherence to national recommendations as documented in the prenatal cards of 39 adolescents (13– 18 years) and 37 adults (23– 28 years) from a low-income area in northeast Brazil. Recommendations included ≥ 6 prenatal consultations, gestational age ≤ 12 weeks at the first visit, participation in 3 educational activities, 2 serology for syphilis (VDRL) and HIV, 1 Toxoplasmosis serology, 2 urine tests, 2 blood glucose and 2 hemoglobin/hematocrit (Hb/Ht) exams. Chi-square tests were used to compare the proportions of adolescents and adults with a record of these procedures in the prenatal cards.Results: Compared to adult women, the adolescent group had lower attainment of almost all recommended components of prenatal care compared to the adult group, with statistically significant differences for 2 blood glucose tests (46.2% vs 78.4%; p=0.004), 2 VDRL tests (30.8% vs 54.1%; p=0.040), 2 Hb/Ht exams (35.9% vs 83.8%; p< 0.001), and at least 6 consultations (84.6% vs 100%; p=0.013).Conclusion: Despite greater health risks of adolescent fertility, the prenatal cards of adolescent mothers presented a poorer record of adherence to recommendations for adequate prenatal care compared to adult mothers from a low-income setting of Brazil. Health policies for both health professionals and the target population are needed to ensure adequacy of prenatal care and appropriate risk reduction for this vulnerable population.Keywords: prenatal care, delivery of health care, health records, personal, pregnancy in adolescence

Electron injection by tunneling from a gold electrode and hole transport properties in polycrystalline MAPbI3 has been investigated using variable temperature experiments and numerical simulations. The presence of a large and unexpected band bending at the Au/MAPbI3 interface is revealed and attributed to the trapping of holes, which enhances the injection of electrons via tunneling. These results elucidate the role of volume and interface defects in state-of-the-art hybrid perovskite semiconductors. [ABSTRACT FROM AUTHOR]

Abstract Background Most households in low and middle income countries, including in India, use solid fuels (coal/coke/lignite, firewood, dung, and crop residue) for cooking and heating. Such fuels increase child mortality, chiefly from acute respiratory infection. There are, however, few direct estimates of the impact of solid fuel on child mortality in India. Methods We compared household solid fuel use in 1998 between 6790 child deaths, from all causes, in the previous year and 609 601 living children living in 1.1 million nationally-representative homes in India. Analyses were stratified by child's gender, age (neonatal, post-neonatal, 1-4 years) and colder versus warmer states. We also examined the association of solid fuel to non-fatal pneumonias. Results Solid fuel use was very common (87% in households with child deaths and 77% in households with living children). After adjustment for demographic factors and living conditions, solid-fuel use significantly increase child deaths at ages 1-4 (prevalence ratio (PR) boys: 1.30, 95%CI 1.08-1.56; girls: 1.33, 95%CI 1.12-1.58). More girls than boys died from exposure to solid fuels. Solid fuel use was also associated with non-fatal pneumonia (boys: PR 1.54 95%CI 1.01-2.35; girls: PR 1.94 95%CI 1.13-3.33). Conclusions Child mortality risks, from all causes, due to solid fuel exposure were lower than previously, but as exposure was common solid, fuel caused 6% of all deaths at ages 0-4, 20% of deaths at ages 1-4 or 128 000 child deaths in India in 2004. Solid fuel use has declined only modestly in the last decade. Aside from reducing exposure, complementary strategies such as immunization and treatment could also reduce child mortality from acute respiratory infections.

Abstract Background The prevalence of child sexual abuse (CSA) in the population has been poorly described in developing countries. Population data on child sexual abuse in Brazil is very limited. This paper aims to estimate lifetime prevalence of child sexual abuse and associated factors in a representative sample of the population aged 14 and over in a city of southern Brazil. Methods A two-stage sampling strategy was used and individuals were invited to respond to a confidential questionnaire in their households. CSA was defined as non-consensual oral-genital, genital-genital, genital-rectal, hand-genital, hand-rectal, or hand-breast contact/intercourse between ages 0 and 18. Associations between socio-demographic variables and CSA, before and after age 12, were estimated through multinomial regression. Results Complete data were available for 1936 respondents from 1040 households. Prevalence of CSA among girls (5.6% 95%CI [4.8;7.5]) was higher than among boys (1.6% 95%CI [0.9;2.6]). Boys experienced CSA at younger ages than girls and 60% of all reported CSA happened before age 12. Physical abuse was frequently associated with CSA at younger (OR 5.6 95%CI [2.5;12.3]) and older (OR 9.4 95%CI [4.5;18.7]) ages. CSA after age 12 was associated with an increased number of sexual partners in the last 2 months. Conclusion Results suggest that CSA takes place at young ages and is associated with physical violence, making it more likely to have serious health and developmental consequences. Except for gender, no other socio-demographic characteristic identified high-risk sub-populations.

Abstract Objective Children whose parents have psychiatric disorders experience an increased risk of developing psychiatric disorders, and have higher rates of developmental problems and mortality. Assessing the size of this population is important for planning of preventive strategies which target these children. Methods National survey data (CCHS 1.2) was used to estimate the number of children exposed to parental psychiatric disorders. Disorders were diagnosed using the World Psychiatric Health Composite International Diagnostic Interview (WMH-CIDI) (12 month prevalence). Data on the number of children below 12 years of age in the home, and the relationship of the respondents with the children, was used to estimate exposure. Parent-child relations were identified, as was single parenthood. Using a design-based analysis, the number of children exposed to parental psychiatric disorders was calculated. Results Almost 570,000 children under 12 live in households where the survey respondent met criteria for one or more mood, anxiety or substance use disorders in the previous 12 months, corresponding to 12.1% of Canadian children under the age of 12. Almost 3/4 of these children have parents that report receiving no mental health care in the 12 months preceding the survey. For 17% of all Canadian children under age 12, the individual experiencing a psychiatric disorder is the only parent in the household. Conclusion The high number of children exposed causes major concern and has important implications. Although these children will not necessarily experience adversities, they possess an elevated risk of accidents, mortality, and of developing psychiatric disorders. We expect these estimates will promote further research and stimulate discussion at both health policy and planning tables.

CK1δ is a serine-threonine kinase involved in several pathological conditions including neuroinflammation and neurodegenerative disorders like Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis. Specifically, it seems that an inhibition of CK1δ could have a neuroprotective effect in these conditions. Here, a series of [1,2,4]triazolo[1,5-a][1,3,5]triazines were developed as ATP-competitive CK1δ inhibitors. Both positions 2 and 5 have been explored leading to a total of ten compounds exhibiting IC 50 s comprised between 29.1 µM and 2.08 µM. Three of the four most potent compounds (IC 50  < 3 µM) bear a thiophene ring at the 2 position. All compounds have been submitted to computational studies that identified the chain composed of at least 2 atoms (e.g., nitrogen and carbon atoms) at the 5 position as crucial to determine a key bidentate hydrogen bond with Leu85 of CK1δ. Most potent compounds have been tested in vitro, resulting passively permeable to the blood-brain barrier and, safe and slight neuroprotective on a neuronal cell model. These results encourage to further structural optimize the series to obtain more potent CK1δ inhibitors as possible neuroprotective agents to be tested on models of the above-mentioned neurodegenerative diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Nirmatrelvir was the first protease inhibitor specifically developed against the SARS-CoV-2 main protease (3CLpro/Mpro) and licensed for clinical use. As SARS-CoV-2 continues to spread, variants resistant to nirmatrelvir and other currently available treatments are likely to arise. This study aimed to identify and characterize mutations that confer resistance to nirmatrelvir. To safely generate Mpro resistance mutations, we passaged a previously developed, chimeric vesicular stomatitis virus (VSV-Mpro) with increasing, yet suboptimal concentrations of nirmatrelvir. Using Wuhan-1 and Omicron Mpro variants, we selected a large set of mutants. Some mutations are frequently present in GISAID, suggesting their relevance in SARS-CoV-2. The resistance phenotype of a subset of mutations was characterized against clinically available protease inhibitors (nirmatrelvir and ensitrelvir) with cell-based, biochemical and SARS-CoV-2 replicon assays. Moreover, we showed the putative molecular mechanism of resistance based on in silico molecular modelling. These findings have implications on the development of future generation Mpro inhibitors, will help to understand SARS-CoV-2 protease inhibitor resistance mechanisms and show the relevance of specific mutations, thereby informing treatment decisions., Competing Interests: D.v.L. is founder of ViraTherapeutics GmbH. D.v.L serves as a scientific advisor to Boehringer Ingelheim and Pharma KG. E.H. and D.v.L have received an Austrian Science Fund (FWF) grant in the special call “SARS urgent funding”. E.H. is a registered consultant at Guidepoint. S.A.M and R.S.H. are inventors on the patent application “Live cell assay for protease inhibition”, application number WO/2022/094463. J.P., X.H. and D.W. are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. X.H. and D.W. hold stocks of Merck & Co., Inc., Rahway, NJ, USA. X.H. and D.W. are inventors on the patent application “Coronavirus replicons for antiviral screening and testing”. This work is not in any way sponsored or to any extent influenced by any of the authors’ employment statuses. All other authors declare they have no competing interests., (Copyright: © 2024 Costacurta et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Prediction of pharmacokinetic (PK) properties is crucial for drug discovery and development. Machine-learning (ML) models, which use statistical pattern recognition to learn correlations between input features (such as chemical structures) and target variables (such as PK parameters), are being increasingly used for this purpose. To embed ML models for PK prediction into workflows and to guide future development, a solid understanding of their applicability, advantages, limitations, and synergies with other approaches is necessary., Areas Covered: This narrative review discusses the design and application of ML models to predict PK parameters of small molecules, especially in light of established approaches including in vitro-in vivo extrapolation (IVIVE) and physiologically based pharmacokinetic (PBPK) models. The authors illustrate scenarios in which the three approaches are used and emphasize how they enhance and complement each other. In particular, they highlight achievements, the state of the art and potentials of applying machine learning for PK prediction through a comphrehensive literature review., Expert Opinion: ML models, when carefully crafted, regularly updated, and appropriately used, empower users to prioritize molecules with favorable PK properties. Informed practitioners can leverage these models to improve the efficiency of drug discovery and development process.