A birth cohort study

Funding Information: The MINA‐Brazil Study has been funded by the Brazilian National Council for Scientific and Technological Development (CNPq, grant number 407255/2013‐3) and the São Paulo Research Foundation (FAPESP, grant number 2016/00270‐6). Dr Matijasevich, Dr Antunes and Dr Cardoso are recipients of CNPq senior research scholarships. Mrs Maruyama and Mrs Pinheiro received doctoral scholarship from FAPESP (grant 2017/22723‐5) and CAPES, respectively. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Publisher Copyright: © 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.Objectives: Previous cohort studies have found a positive association between prolonged breastfeeding (≥12 months) on dental caries, but few of them analysed the mediated effect of sugar consumption on this association. This study investigated whether prolonged breastfeeding is a risk factor for caries at 2-year follow-up assessment (21–27 months of age) and whether this effect is mediated by sugar consumption. Methods: A birth cohort study was performed in the Brazilian Amazon (n = 800). Dental caries was assessed using the dmf-t index. Prolonged breastfeeding was the main exposure. Data on baseline covariables and sugar consumption at follow-up visits were analysed. We estimated the OR for total causal effect (TCE) and natural indirect effect (NIE) of prolonged breastfeeding on dental caries using the G-formula. Results: The prevalence of caries was 22.8% (95% CI: 19.8%–25.8%). Children who were breastfed for 12–23 months (TCE = 1.13, 95% CI: 1.05–1.20) and for ≥24 months (TCE = 1.27, 95% CI: 1.14–1.40) presented a higher risk of caries at age of 2 years than those breastfed <12 months. However, this risk was slightly mediated by a decreased frequency of sugar consumption at age of 2 years only for breastfeeding from 12 to 23 months (NIE; OR = 0.95, 95% CI: 0.91–0.97). Conclusions: In this study, the effect of prolonged breastfeeding on the increased risk of dental caries was slightly mediated by sugar consumption. Early feeding practices for caries prevention and promoting breastfeeding while avoiding sugar consumption should be targeted in the first 2 years of life.publishersversioninpres

Environment Biological and Health Care Efforts Influenced of Lymfatic Filariasis Incidence, Sarmi Distric

District Sarmi is the most endemic area of filariasis in Papua which has rate of microfilaria (mf) (47.06%) up to the year2012. In the Province Papua filarial worm is Wuchereria bancrofti and is transmitted through the bite of a mosquito vectors. Lymphatic filariasis does not cause death, but in chronic cases it causes disability, psychosocial problems, stigma, and decreased productivity. This study was aimed to analyze environment biological and health care efforts that influence the incidence of lymphatic filariasis. This study used case-control method. Samples comprised 32 case samples (mf +) and 32 control samples (mf-). Primary data were collected through interviews and observation. Data were analyzed using Chi-Square and continued with multivariate Logistic Regression. Statistical analysis obtained indicated two variables on the incidence of lymphatic filariasis limfatik in District Sarmi (health care efforts pvalue = 0.002, OR: 7.779, as well as the biological environment pvalue= 0.008, OR: 5.841). Significant variables were health services with sub-variables promotion, prevention and the environmental biology. Suggestion: Mosquito bites should be avoided, the vector should be controlled through mutual cooperation and health promotion should be implemented

Effect of ozone and antioxidants on wheat and its pathogen — Bipolaris sorokininana

Tropospheric ozone (O3) adversely affects growth and productivity of crops and also influences crop—pathogen interactions. Adverse effects of O3 on crops can be mitigated by antioxidants application. In the present study through lab and field experiments impact of O3 and antioxidants treatment to wheat was assessed on growth of Bipolaris sorokiniana (BS-75 strain) pathogen responsible for Spot blotch disease, pathogenesis related (PR) proteins and chitinase content. Results showed that growth of Bipolaris was significantly higher in elevated ozone (EO3) exposed plants as compared to control plants. Antioxidants — ascorbic acid (AA), tagetes extract (T) and quercetin (Q) application on culture media and wheat plants, respectively, retarded the growth of Bipolaris sorokiniana. Among the three antioxidants minimum growth of Bipolaris was observed in AA-treated plants as compared to control plants. Reduction in chitinase activity and PR proteins content due to EO3 treatment in wheat plants was 18% and 78%, respectively, as compared to control plants. Increase in chitinase activity and PR proteins content due to antioxidants treatment in wheat plants was 45% and 60%, respectively, as compared to control plants

A Birth Cohort Study

Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.BACKGROUND: Relatively few Amazonian infants have clinical malaria diagnosed, treated and notified before their first birthday, either because they are little exposed to an infection or remain asymptomatic once infected. Here we measure the proportion of children who have experienced Plasmodium vivax infection and malaria by 2 years of age in the main transmission hotspot of Amazonian Brazil. METHODS: We measured IgG antibodies to 3 blood-stage P. vivax antigens at the 1- and 2-year follow-up assessment of 435 participants in a population-based birth cohort. Children's malaria case notifications were retrieved from the electronic database of the Ministry of Health. We used multiple Poisson regression models to identify predictors of serologically proven P. vivax infection and clinical vivax malaria during the first 2 years of life. RESULTS: Overall, 23 [5.3%; 95% confidence interval (CI): 3.5-7.8%) children had antibodies to ≥2 antigens detected during at least one follow-up assessment, consistent with past P. vivax infection(s). Fifteen (3.4%; 95% CI: 2.1-5.6%) children had clinical vivax episodes notified during the first 2 years of life; 7 of them were seronegative. We estimate that half of the infections remained unnotified. Children born to women who experienced P. vivax infection during pregnancy were more likely to be infected and develop clinical vivax malaria, while those breast-fed for ≥12 months had their risk of being P. vivax-seropositive (which we take as evidence of blood-stage P. vivax infection during the first 2 years of life) decreased by 79.8% (95% CI: 69.3-86.7%). CONCLUSION: P. vivax infections in early childhood are underreported in the Amazon, are associated with anemia at 2 years of age, and appear to be partially prevented by prolonged breastfeeding.publishersversionepub_ahead_of_prin

Work‒family interface in the context of career success: A qualitative inquiry

Work–family researchers are increasingly recognizing the need to expand their focus to advance the field. One population largely neglected by work‒family researchers is individuals who have been extremely successful in their careers. In addition, organizational career scholars have largely neglected the interplay between employees’ work and family lives. This study contributes to the work‒family literature by studying work‒family interface (WFI) in the context of career success. We sought to explore the lived experiences of 28 distinguished professors who are among the top 2‒5% scholars in their field, to provide an in-depth understanding of their WFI and the prominent factors affecting it over their careers. Our findings have theoretical implications for both work‒family and career success literature

Pathogenic variants of Valosin-containing protein induce lysosomal damage and transcriptional activation of autophagy regulators in neuronal cells

Aim: Mutations in the valosin-containing protein (VCP) gene cause various lethal proteinopathies that mainly include inclusion body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD) and amyotrophic lateral sclerosis (ALS). Different pathological mechanisms have been proposed. Here, we define the impact of VCP mutants on lysosomes and how cellular homeostasis is restored by inducing autophagy in the presence of lysosomal damage. Methods: By electron microscopy, we studied lysosomal morphology in VCP animal and motoneuronal models. With the use of western blotting, real-time quantitative polymerase chain reaction (RT-qPCR), immunofluorescence and filter trap assay, we evaluated the effect of selected VCP mutants in neuronal cells on lysosome size and activity, lysosomal membrane permeabilization and their impact on autophagy. Results: We found that VCP mutants induce the formation of aberrant multilamellar organelles in VCP animal and cell models similar to those found in patients with VCP mutations or with lysosomal storage disorders. In neuronal cells, we found altered lysosomal activity characterised by membrane permeabilization with galectin-3 redistribution and activation of PPP3CB. This selectively activated the autophagy/lysosomal transcriptional regulator TFE3, but not TFEB, and enhanced both SQSTM1/p62 and lipidated MAP1LC3B levels inducing autophagy. Moreover, we found that wild type VCP, but not the mutants, counteracted lysosomal damage induced either by trehalose or by a mutant form of SOD1 (G93A), also blocking the formation of its insoluble intracellular aggregates. Thus, chronic activation of autophagy might fuel the formation of multilamellar bodies. Conclusion: Together, our findings provide insights into the pathogenesis of VCP-related diseases, by proposing a novel mechanism of multilamellar body formation induced by VCP mutants that involves lysosomal damage and induction of lysophagy

Genetic determinants of survival in progressive supranuclear palsy: a genome-wide association study.

BACKGROUND: The genetic basis of variation in the progression of primary tauopathies has not been determined. We aimed to identify genetic determinants of survival in progressive supranuclear palsy (PSP). METHODS: In stage one of this two stage genome-wide association study (GWAS), we included individuals with PSP, diagnosed according to pathological and clinical criteria, from two separate cohorts: the 2011 PSP GWAS cohort, from brain banks based at the Mayo Clinic (Jacksonville, FL, USA) and in Munich (Germany), and the University College London PSP cohort, from brain banks and the PROSPECT study, a UK-wide longitudinal study of patients with atypical parkinsonian syndromes. Individuals were included if they had clinical data available on sex, age at motor symptom onset, disease duration (from motor symptom onset to death or to the date of censoring, Dec 1, 2019, if individuals were alive), and PSP phenotype (with reference to the 2017 Movement Disorder Society criteria). Genotype data were used to do a survival GWAS using a Cox proportional hazards model. In stage two, data from additional individuals from the Mayo Clinic brain bank, which were obtained after the 2011 PSP GWAS, were used for a pooled analysis. We assessed the expression quantitative trait loci (eQTL) profile of variants that passed genome-wide significance in our GWAS using the Functional Mapping and Annotation of GWAS platform, and did colocalisation analyses using the eQTLGen and PsychENCODE datasets. FINDINGS: Data were collected and analysed between Aug 1, 2016, and Feb 1, 2020. Data were available for 1001 individuals of white European ancestry with PSP in stage one. We found a genome-wide significant association with survival at chromosome 12 (lead single nucleotide polymorphism rs2242367, p=7·5 × 10-10, hazard ratio 1·42 [95% CI 1·22-1·67]). rs2242367 was associated with survival in the individuals added in stage two (n=238; p=0·049, 1·22 [1·00-1·48]) and in the pooled analysis of both stages (n=1239; p=1·3 × 10-10, 1·37 [1·25-1·51]). An eQTL database screen revealed that rs2242367 is associated with increased expression of LRRK2 and two long intergenic non-coding RNAs (lncRNAs), LINC02555 and AC079630.4, in whole blood. Although we did not detect a colocalisation signal for LRRK2, analysis of the PSP survival signal and eQTLs for LINC02555 in the eQTLGen blood dataset revealed a posterior probability of hypothesis 4 of 0·77, suggesting colocalisation due to a single shared causal variant. INTERPRETATION: Genetic variation at the LRRK2 locus was associated with survival in PSP. The mechanism of this association might be through a lncRNA-regulated effect on LRRK2 expression because LINC02555 has previously been shown to regulate LRRK2 expression. LRRK2 has been associated with sporadic and familial forms of Parkinson's disease, and our finding suggests a genetic overlap with PSP. Further functional studies will be important to assess the potential of LRRK2 modulation as a disease-modifying therapy for PSP and related tauopathies. FUNDING: PSP Association, CBD Solutions, Medical Research Council (UK)

Exercise recommendations for people with bone metastases: Expert consensus for healthcare providers and clinical exercise professionals

Purpose: Exercise has been underutilized in people with advanced or incurable cancer despite the potential to improve physical function and reduce psychosocial morbidity, especially for people with bone metastases because of concerns over skeletal complications. The International Bone Metastases Exercise Working Group (IBMEWG) was formed to develop best practice recommendations for exercise programming for people with bone metastases on the basis of published research, clinical experience, and expert opinion. Methods: The IBMEWG undertook sequential steps to inform the recommendations: (1) modified Delphi survey, (2) systematic review, (3) cross-sectional survey to physicians and nurse practitioners, (4) in-person meeting of IBMEWG to review evidence from steps 1-3 to develop draft recommendations, and (5) stakeholder engagement. Results: Recommendations emerged from the contributing evidence and IBMEWG discussion for pre-exercise screening, exercise testing, exercise prescription, and monitoring of exercise response. Identification of individuals who are potentially at higher risk of exercise-related skeletal complication is a complex interplay of these factors: (1) lesion-related, (2) cancer and cancer treatment–related, and (3) the person-related. Exercise assessment and prescription requires consideration of the location and presentation of bone lesion(s) and should be delivered by qualified exercise professionals with oncology education and exercise prescription experience. Emphasis on postural alignment, controlled movement, and proper technique is essential. Conclusion: Ultimately, the perceived risk of skeletal complications should be weighed against potential health benefits on the basis of consultation between the person, health care team, and exercise professionals. These recommendations provide an initial framework to improve the integration of exercise programming into clinical care for people with bone metastases

Evolving Synaptic Plasticity with an Evolutionary Cellular Development Model

Since synaptic plasticity is regarded as a potential mechanism for memory formation and learning, there is growing interest in the study of its underlying mechanisms. Recently several evolutionary models of cellular development have been presented, but none have been shown to be able to evolve a range of biological synaptic plasticity regimes. In this paper we present a biologically plausible evolutionary cellular development model and test its ability to evolve different biological synaptic plasticity regimes. The core of the model is a genomic and proteomic regulation network which controls cells and their neurites in a 2D environment. The model has previously been shown to successfully evolve behaving organisms, enable gene related phenomena, and produce biological neural mechanisms such as temporal representations. Several experiments are described in which the model evolves different synaptic plasticity regimes using a direct fitness function. Other experiments examine the ability of the model to evolve simple plasticity regimes in a task -based fitness function environment. These results suggest that such evolutionary cellular development models have the potential to be used as a research tool for investigating the evolutionary aspects of synaptic plasticity and at the same time can serve as the basis for novel artificial computational systems