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PLoS Neglected Tropical Diseases Jul 2024When two species hybridize, the two parental genomes are brought together and some alleles might interact for the first time. To date, the extent of the transcriptomic...
When two species hybridize, the two parental genomes are brought together and some alleles might interact for the first time. To date, the extent of the transcriptomic changes in first hybrid generations, along with their functional outcome constitute an important knowledge gap, especially in parasite species. Here we explored the molecular and functional outcomes of hybridization in first-generation hybrids between the blood fluke parasites Schistosoma haematobium and S. bovis. Through a transcriptomic approach, we measured gene expression in both parental species and hybrids. We described and quantified expression profiles encountered in hybrids along with the main biological processes impacted. Up to 7,100 genes fell into a particular hybrid expression profile (intermediate between the parental expression levels, over-expressed, under-expressed, or expressed like one of the parental lines). Most of these genes were different depending on the direction of the parental cross (S. bovis mother and S. haematobium father or the reverse) and depending on the sex. For a given sex and cross direction, the vast majority of genes were hence unassigned to a hybrid expression profile: either they were differentially expressed genes but not typical of any hybrid expression profiles or they were not differentially expressed neither between hybrids and parental lines nor between parental lines. The most prevalent profile of gene expression in hybrids was the intermediate one (24% of genes assigned to a hybrid expression profile). These results suggest that transcriptomic compatibility between S. haematobium and S. bovis remains quite high. We also found support for an over-dominance model (over- and under-expressed genes in hybrids compared to parental lines) potentially associated with heterosis. In females in particular, processes such as reproductive processes, metabolism and cell interactions as well as signaling pathways were indeed affected. Our study hence provides new insight on the biology of Schistosoma hybrids with evidences supporting compatibility and heterosis.
PubMed: 38954732
DOI: 10.1371/journal.pntd.0012267 -
PloS One 2024Depression is a prevalent and debilitating mental illness affecting young women worldwide. This study aimed to identify psychosocial determinants of major depressive...
INTRODUCTION
Depression is a prevalent and debilitating mental illness affecting young women worldwide. This study aimed to identify psychosocial determinants of major depressive disorder (MDD) among young women in Bihar and Uttar Pradesh, India.
METHODS
Data from "Understanding the Lives of Adolescents and Young Adults" (UDAYA) study (2018-19) for young women aged 12-23 years, both married and unmarried was used for this paper. MDD was evaluated using the Patient Health Questionnaire PHQ-9 with a cut-off score of ≤10. The determinants of MDD were identified through multilevel binary logistic regression analysis.
RESULTS
The prevalence of MDD was 13.6% (95% CL 12.2-15.2) and 5.1% (95% CL 4.2-6.1) for young married women and unmarried girls, respectively. Among the young married women, community-level variables like dowry-related humiliation (1.74, 95% CI 1.15-2.64), and sexual assaults (2.15, 95% CI 1.24-3.73) were significantly associated with MDD. For unmarried girls, reporting of family violence <10% of participants (0.45, 95% CI 0.24-0.85), family violence (≥10% of participants) % (0.35 95% CI 0.19-0.68) and interpartner violence (>25% of participants) (0.42; 95% CI 0.23-0.74) remain significant predictors of MDD. At individual level, for both the groups, age, participation in decision making (on education), social capital (currently attending school/educational course and number of friends), self-efficacy, telephonic harassment, and physical activity were associated with MDD. Wealth index, job seeking, participation in decision making (on health-seeking), parental interactions and physical abuse (for unmarried girls only) and education, reported last sexual intercourse, pressure from the in-laws' to conceive (for young married women only) were associated with MDD.
CONCLUSIONS
For young married women, community level targeted interventions should focus on the social ecology to foster a sense of safe community environment. For unmarried girls, additionally, interventions should aim to optimize their family environment for effective mental health outcomes.
Topics: Humans; Female; Depressive Disorder, Major; Adolescent; Young Adult; India; Prevalence; Marriage; Child; Surveys and Questionnaires; Adult; Single Person
PubMed: 38954722
DOI: 10.1371/journal.pone.0306071 -
G3 (Bethesda, Md.) Jul 2024In aquaculture, sterile triploids are commonly used for production as sterility gives them potential gains in growth, yields and quality. However, they cannot be...
In aquaculture, sterile triploids are commonly used for production as sterility gives them potential gains in growth, yields and quality. However, they cannot be reproduced, and DNA parentage assignment to their diploid or tetraploid parents is required to estimate breeding values for triploid phenotypes. No publicly available software has the ability to assign triploids to their parents. Here, we updated the R package APIS to support triploids induced from diploid parents. First, we created new exclusion and likelihood tables that account for the double allelic contribution of the dam and the recombination that can occur during female meiosis. As the effective recombination rate of each marker with the centromere is usually unknown, we set it at 0.5 and found that this value maximises the assignment rate even for markers with high or low recombination rates. The number of markers needed for a high true assignment rate did not strongly depend on the proportion of missing parental genotypes. The assignment power was however affected by the quality of the markers (minor allele frequency, call rate). Altogether, 96 to 192 SNPs were required to have a high parentage assignment rate in a real rainbow trout dataset of 1232 triploid progenies from 288 parents. The likelihood approach was more efficient than exclusion when the power of the marker set was limiting. When more markers were used, exclusion was more advantageous, with sensitivity reaching unity, very low False Discovery Rate (<0.01) and excellent specificity (0.96-0.99). Thus, APIS provides an efficient solution to assign triploids to their diploid parents.
PubMed: 38954534
DOI: 10.1093/g3journal/jkae143 -
Longitudinal and Life Course Studies :... May 2024While a vast number of studies confirm the transmission of labour-market disadvantages from one generation to the next, less is known about how parents' interconnected...
While a vast number of studies confirm the transmission of labour-market disadvantages from one generation to the next, less is known about how parents' interconnected labour-market pathways co-evolve and shape the opportunities and obstacles for their children's future careers. This study uses a multidimensional view of intergenerational transmission by describing the most typical pathways of parents' occupational careers and assesses how these patterns are associated with their children's labour-market outcomes. Drawing on Swedish longitudinal register data, we used multichannel sequence analysis to follow a cohort of people born in 1985 (n = 72,409) and their parents across 26 years. We identified four parental earning models, differentiating between (1) dual earners with high wages, (2) dual earners with low-wage, (3) one-and-a-half-earners and (4) mother as the main breadwinner. Regression analysis shows strong intergenerational transmission among the most advantageous trajectories, with education as a key determinant for young people to become less dependent on family resources. This study stresses the importance of intra-couple perspectives in life course research to understand how inequalities are shaped and preserved across generations.
Topics: Humans; Female; Sweden; Male; Longitudinal Studies; Intergenerational Relations; Adult; Parents; Employment; Child; Socioeconomic Factors; Adolescent; Parent-Child Relations; Young Adult
PubMed: 38954424
DOI: 10.1332/17579597Y2024D000000021 -
Longitudinal and Life Course Studies :... Apr 2024In the United Kingdom, the COVID-19 pandemic in 2020 and 2021 led to two extended periods of school closures. Research on inequality of learning opportunity as a result...
Socio-economic differences in remote schoolwork during the COVID-19 pandemic: a trend analysis of the 2020 and 2021 school-closure periods using the UK Understanding Society data.
In the United Kingdom, the COVID-19 pandemic in 2020 and 2021 led to two extended periods of school closures. Research on inequality of learning opportunity as a result of these closures used a single indicator of socio-economic status, neglecting important determinants of remote learning. Using data from the Understanding Society (USoc) COVID-19 surveys we analysed the levels and differentials in the uptake of remote schoolwork using parental social class, information technology (IT) availability in the home and parental working patterns to capture the distinct resources that families needed to complete remote schoolwork. This is also the first study to assess the extent to which the differentials between socio-economic groups changed between the first and second school-closure periods caused by the pandemic. We found that each of the three factors showed an independent association with the volume of remote schoolwork and that their effect was magnified by their combination. Children in families where the main parent was in an upper-class occupation, where both parents worked from home and where the children had their own IT spent more time doing remote schoolwork than other groups, particularly compared to children of single parents who work from home, children in families where the main parent was in a working-class occupation, where the child had to share IT, and where the parents did not work regularly from home. The differentials between socio-economic groups in the uptake of schoolwork were found to be stable between the two school-closure periods.
Topics: Humans; COVID-19; United Kingdom; Schools; Child; Male; Female; Socioeconomic Factors; Adolescent; SARS-CoV-2; Parents; Social Class; Education, Distance; Surveys and Questionnaires; Pandemics; Teleworking
PubMed: 38954421
DOI: 10.1332/17579597Y2024D000000012 -
American Journal of Clinical Dermatology Jul 2024Palmoplantar pustulosis (PPP), a refractory skin disease characterized by repeated eruptions of sterile pustules and vesicles on palms and/or soles, involves...
BACKGROUND
Palmoplantar pustulosis (PPP), a refractory skin disease characterized by repeated eruptions of sterile pustules and vesicles on palms and/or soles, involves interleukin-17 pathway activation. Brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, is being investigated for use in PPP treatment.
OBJECTIVE
The aim was to assess the efficacy and safety of brodalumab in Japanese PPP patients with moderate or severe pustules/vesicles.
METHODS
A phase 3, randomized, double-blind, placebo-controlled trial was conducted between July 2019 and August 2022, at 41 centers in Japan. Patients aged 18-70 years with a diagnosis of PPP for ≥ 24 weeks, a PPP Area Severity Index (PPPASI) score of ≥ 12, a PPPASI subscore of pustules/vesicles of ≥ 2, and inadequate response to therapy were included. Participants were randomized 1:1 to receive brodalumab 210 mg or placebo, subcutaneously (SC) at baseline, weeks 1 and 2, and every 2 weeks (Q2W) thereafter until week 16. Changes from baseline to week 16 in the PPPASI total score (primary endpoint) and other secondary skin-related endpoints and safety endpoints were assessed.
RESULTS
Of the 126 randomized patients, 50 of 63 in the brodalumab group and 62 of 63 in the placebo group completed the 16-week period. Reasons for discontinuation were adverse event (n = 6), withdrawal by patient/parent/guardian (n = 3), progressive disease (n = 3), and lost to follow-up (n = 1) in the brodalumab group and Good Clinical Practice deviation (n = 1) in the placebo group. Change from baseline in the PPPASI total score at week 16 was significantly higher (p = 0.0049) with brodalumab (least-squares mean [95% confidence interval {CI}] 13.73 [10.91-16.56]) versus placebo (8.45 [5.76-11.13]; difference [95% CI] 5.29 [1.64-8.94]). At week 16, brodalumab showed a trend of rapid improvement versus placebo for PPPASI-50/75/90 response (≥ 50%/75%/90% improvement from baseline) and Physician's Global Assessment 0/1 score: 54% versus 24.2%, 36.0% versus 8.1%, 16.0% versus 0.0%, and 32.0% versus 9.7%, respectively. Infection was the dominant treatment-emergent adverse event (TEAE); the commonly reported TEAEs were otitis externa (25.4%/1.6%), folliculitis (15.9%/3.2%), nasopharyngitis (14.3%/4.8%), and eczema (14.3%/12.9%) in the brodalumab/placebo groups, respectively. The severity of most TEAEs reported was Grade 1 or 2 and less frequently Grade ≥ 3.
CONCLUSIONS
Brodalumab SC 210 mg Q2W demonstrated efficacy in Japanese PPP patients. The most common TEAEs were mild infectious events.
TRIAL REGISTRATION
NCT04061252 (Date of Trial Registration: August 19, 2019).
PubMed: 38954226
DOI: 10.1007/s40257-024-00876-x -
Journal of Gastrointestinal Cancer Jul 2024Bexarotene, also recognized as Targretin, is categorized as a retinoid, a type of cancer drug. Nevertheless, the precise mechanisms of bexarotene in relation to colon...
BACKGROUND
Bexarotene, also recognized as Targretin, is categorized as a retinoid, a type of cancer drug. Nevertheless, the precise mechanisms of bexarotene in relation to colon cancer remain unclear. In colon cancer, SEZ6L2 was suggested as one of the biomarkers and targets. This study presents a comprehensive exploration of the role of SEZ6L2 in colon cancer.
METHODS
We utilized both TCGA data and a cohort of Chinese patients. In a meticulous analysis of 478 colon cancer cases, SEZ6L2 expression levels were examined in relation to clinical characteristics, staging parameters, and treatment outcomes. Additionally, we investigated the pharmacological impact of bexarotene on SEZ6L2, demonstrating a significant downregulation of SEZ6L2 at both mRNA and protein levels in colon cancer patients following bexarotene treatment.
RESULTS
SEZ6L2 consistently overexpresses in colon cancer, serving as a potential universal biomarker with prognostic significance, validated in a diverse Chinese cohort. In vitro, SEZ6L2 promotes cell viability without affecting migration. Bexarotene treatment inhibits SEZ6L2 expression, correlating with reduced viability both in vitro and in vivo. SEZ6L2 overexpression accelerates declining survival rates in an in vivo context. Bexarotene's efficacy is context-dependent, effective in parental cells but not with SEZ6L2 overexpression. Computational predictions suggest a direct SEZ6L2-bexarotene interaction, warranting further experimental exploration.
CONCLUSION
The study provides valuable insights into SEZ6L2 as a prognostic biomarker in colon cancer, revealing its intricate relationship with clinical parameters, treatment outcomes, and bexarotene effects. Context-dependent therapeutic responses emphasize the nuanced understanding required for SEZ6L2's role in colon cancer, paving the way for targeted therapeutic strategies.
PubMed: 38954188
DOI: 10.1007/s12029-024-01085-9 -
Prevention Science : the Official... Jul 2024Violence is a major public health problem globally, with the highest rates in low- and middle-income countries (LMICs) in the Americas and southern Africa. Parenting...
Violence is a major public health problem globally, with the highest rates in low- and middle-income countries (LMICs) in the Americas and southern Africa. Parenting programmes in high-income countries can diminish risk for violence, by reducing risk factors such as child aggression and harsh parenting, and increasing protective factors such as child cognitive development and school readiness. However, there is critical need to identify low-cost programmes with replicable benefits that work in real-world LMICs contexts. A three-arm, randomised, single-blind trial evaluated effects of two low-cost, group-based parenting programmes recommended for LMICs (ACT: Raising Safe Kids; DBS: dialogic book-sharing) on child aggression (primary outcome), child development, parenting, maltreatment, and stress. Participants were 369 children with medium-high levels of aggression (mean age 3.1 years at baseline) in poor households. Interventions were implemented in city health and education services in southern Brazil. Maternal reports, filmed observations, child tasks, and hair cortisol were assessed at baseline, 1-month post-intervention, and 8-month follow-up. Intention-to-treat analyses compared each of ACT and DBS with a control group. Three hundred sixty-eight (99.7%) participants completed follow-up assessments 8 months after the interventions. There was no effect of ACT (standardised mean difference, SMD 0.11, 95% CI - 0.05, 0.27) or DBS (SMD 0.05, 95% CI - 0.11, 0.21) on the primary outcome of child aggression. ACT reduced harsh parenting behaviour post-intervention (SMD - 0.23; 95% CI - 0.46, - 0.01), but not at follow-up. DBS improved book-sharing practices at both time points (e.g., maternal sensitivity at follow-up SMD 0.33; 95% CI 0.08, 0.57). There were no benefits of either programme for other parenting, child development, or stress outcomes. Two parenting programmes in Brazil had small effects on parenting practices but did not reduce child aggression or several other important risk/protective factors for violence. Effective early interventions that reduce violence in real-world LMIC settings are highly desirable but may be challenging to achieve.
PubMed: 38954125
DOI: 10.1007/s11121-024-01698-3 -
Environmental Geochemistry and Health Jul 2024Radioactive nuclides cesium (Cs) and strontium (Sr) possess long half-lives, with Cs at approximately 2.3 million years and Sr at about 49 billion years. Their...
Radioactive nuclides cesium (Cs) and strontium (Sr) possess long half-lives, with Cs at approximately 2.3 million years and Sr at about 49 billion years. Their persistent accumulation can result in long-lasting radioactive contamination of soil ecosystems. This study employed geo-accumulation index (I), pollution load index (PLI), potential ecological risk index (PEPI), health risk assessment model (HRA), and Monte Carlo simulation to evaluate the pollution and health risks of Cs and Sr in the surface soil of different functional areas in a typical mining city in China. Positive matrix factorization (PMF) model was used to elucidate the potential sources of Cs and Sr and the respective contribution rates of natural and anthropogenic sources. The findings indicate that soils in the mining area exhibited significantly higher levels of Cs and Sr pollution compared to smelting factory area, agricultural area, and urban residential area. Strontium did not pose a potential ecological risk in any studied functional area. The non-carcinogenic health risk of Sr to the human body in the study area was relatively low. Because of the lack of parameters for Cs, the potential ecological and human health risks of Cs was not calculated. The primary source of Cs in the soil was identified as the parent material from which the soil developed, while Sr mainly originated from associated contamination caused by mining activities. This research provides data for the control of Cs and Sr pollution in the surface soil of mining city.
Topics: Risk Assessment; Mining; China; Soil Pollutants, Radioactive; Cesium Radioisotopes; Humans; Strontium Radioisotopes; Cesium; Cities; Soil; Monte Carlo Method; Radiation Monitoring
PubMed: 38954122
DOI: 10.1007/s10653-024-02046-8 -
Pediatric Surgery International Jul 2024To present the functional results after a transanal proximal rectosigmoidectomy in patients with severe idiopathic constipation in which medical treatment has failed.
PURPOSE
To present the functional results after a transanal proximal rectosigmoidectomy in patients with severe idiopathic constipation in which medical treatment has failed.
METHODS
Patients with severe idiopathic constipation who underwent transanal proximal rectosigmoidectomy (TPRS) at Children's Hospital Colorado between June 2019 and March 2024 were included in the study. We compared multiple pre- and post-operative outcome measures and the patient's bowel regimen before and after resection.
RESULTS
Fourteen patients underwent TPRS, 10 of whom were male. The average age at the time of surgery was 10.1 years (range 5-19). Seven patients have moderate to severe autism. Constipation-related clinic visits, family calls, procedural intervention, emergency room visits, and hospitalizations notably decreased frequency after TPRS. Laxative dosages and enema volume requirements were also reduced after surgery. Before surgery, all the patients suffered from daily fecal accidents, while post-operatively, all were completely free of stool accidents.
CONCLUSION
In our experience, for patients who suffer from severe medically refractory idiopathic constipation, TPRS has provided improvement in their symptoms and decreased the complications inherent to this chronic disease. Parents and patients attest to a profound positive transformation in their quality of life after surgery.
Topics: Humans; Constipation; Male; Female; Child; Adolescent; Child, Preschool; Rectum; Colon, Sigmoid; Young Adult; Treatment Outcome; Retrospective Studies; Quality of Life
PubMed: 38954056
DOI: 10.1007/s00383-024-05764-3