The pervasive effects of timing of parental mental health disorders on adolescent deliberate self-harm risk

Children whose parents have mental health disorders are at increased risk for deliberate self-harm (DSH). However, the effect of timing of parental mental health disorders on adolescent DSH risk remains under-researched. The aim of this study was to investigate how parental hospital admissions for mental health disorders and/or DSH in different developmental periods impact on the child’s DSH risk in adolescence. A nested case-control sample was compiled from a total population cohort sample drawn from administrative health records in Western Australia. The sample comprised 7,151 adolescents who had a DSH-related hospital admission (cases), and 143,020 matched controls who hadn’t had a DSH-related hospital admission. The occurrence of parental hospital admissions related to mental health disorders and/or DSH behaviours was then analysed for the cases and controls. The timing of the parental hospital admissions was partitioned into four stages in the child’s life course: (1) pre-pregnancy, (2) pregnancy and infancy, (3) childhood, and (4) adolescence. We found that adolescents of a parent with mental health and/or DSH-related hospital admissions in all developmental periods except pregnancy and infancy were significantly more likely than controls to have a DSH-related hospital admission. Compared to parental hospital admissions that occurred during childhood and adolescence, those that occurred before pregnancy conferred a higher risk for adolescent DSH: adjusted odds ratio (aOR) = 1.25 for having only one parent hospitalised and 1.66 for having both parents hospitalised for mental health disorders; aOR = 1.97 for having any parent hospitalised for DSH, all being significant at the level of p < .001. This study shows that timing is important for understanding intergenerational transmission of DSH risk. The pre-pregnancy period is as critical as period after childbirth for effective intervention targeting adult mental health disorders and DSH, highlighting the important role of adult mental health services in preventing DSH risk in future generations

Non-linear relationship between maternal work hours and child body weight: Evidence from the Western Australian Pregnancy Cohort (Raine) Study

Using longitudinal data from the Western Australia Pregnancy Cohort (Raine) Study and both random-effects and fixed-effects models, this study examined the connection between maternal work hours and child overweight or obesity. Following children in two-parent families from early childhood to early adolescence, multivariate analyses revealed a non-linear and developmentally dynamic relationship. Among preschool children (ages 2 to 5), we found lower likelihood of child overweight and obesity when mothers worked 24 h or less per week, compared to when mothers worked 35 or more hours. This effect was stronger in low-to-medium income families. For older children (ages 8 to 14), compared to working 35–40 h a week, working shorter hours (1–24, 25–34) or longer hours (41 or more) was both associated with increases in child overweight and obesity. These non-linear effects were more pronounced in low-to-medium income families, particularly when fathers also worked long hours

Benchmarking hybrid assembly approaches for genomic analyses of bacterial pathogens using Illumina and Oxford Nanopore sequencing

We benchmarked the hybrid assembly approaches of MaSuRCA, SPAdes, and Unicycler for bacterial pathogens using Illumina and Oxford Nanopore sequencing by determining genome completeness and accuracy, antimicrobial resistance (AMR), virulence potential, multilocus sequence typing (MLST), phylogeny, and pan genome. Ten bacterial species (10 strains) were tested for simulated reads of both mediocre- and low-quality, whereas 11 bacterial species (12 strains) were tested for real reads. Unicycler performed the best for achieving contiguous genomes, closely followed by MaSuRCA, while all SPAdes assemblies were incomplete. MaSuRCA was less tolerant of low-quality long reads than SPAdes and Unicycler. The hybrid assemblies of five antimicrobial-resistant strains with simulated reads provided consistent AMR genotypes with the reference genomes. The MaSuRCA assembly of Staphylococcus aureus with real reads contained msr(A) and tet(K), while the reference genome and SPAdes and Unicycler assemblies harbored blaZ. The AMR genotypes of the reference genomes and hybrid assemblies were consistent for the other five antimicrobial-resistant strains with real reads. The numbers of virulence genes in all hybrid assemblies were similar to those of the reference genomes, irrespective of simulated or real reads. Only one exception existed that the reference genome and hybrid assemblies of Pseudomonas aeruginosa with mediocre-quality long reads carried 241 virulence genes, whereas 184 virulence genes were identified in the hybrid assemblies of low-quality long reads. The MaSuRCA assemblies of Escherichia coli O157:H7 and Salmonella Typhimurium with mediocre-quality long reads contained 126 and 118 virulence genes, respectively, while 110 and 107 virulence genes were detected in their MaSuRCA assemblies of low-quality long reads, respectively. All approaches performed well in our MLST and phylogenetic analyses. The pan genomes of the hybrid assemblies of S. Typhimurium with mediocre-quality long reads were similar to that of the reference genome, while SPAdes and Unicycler were more tolerant of low-quality long reads than MaSuRCA for the pan-genome analysis. All approaches functioned well in the pan-genome analysis of Campylobacter jejuni with real reads. Our research demonstrates the hybrid assembly pipeline of Unicycler as a superior approach for genomic analyses of bacterial pathogens using Illumina and Oxford Nanopore sequencing.https://doi.org/10.1186/s12864-020-07041-

Parents' nonstandard work and child wellbeing: a critical review of the existing literature

The rising prevalence of nonstandard work among parents in the era of the 24-hour/7-day economy in developed countries has raised a concern about its possible impacts on children’s health and development. This paper provides a comprehensive and critical review of literature on this topic. To date researchers have examined (a) three developmental outcomes: mental health and behavioral problems, cognitive development, and childhood obesity; (b) family processes: parental time spent with children, parental monitoring, parent-child closeness, and the home environment and (c) other child outcomes: school engagement, extracurricular activities, and sleep patterns. Findings from research that used rigorous methodology show consistent associations between nonstandard work and poor child outcomes. This association is more pronounced in disadvantaged families and magnified when parents work nonstandard hours full-time. A similar association was found between nonstandard work and family processes. The paper discusses the strengths and limitations of existing research and directions for future research

HIV testing in re-education through labour camps in Guangxi Autonomous Region, China (a cross-sectional survey)

Objective: HIV testing is mandatory in re-education-through-labour camps (laojiaosuo) in China yet no studies have reported on the process. Methods: The survey response rate was 100% although 29 detainees were excluded because they were under 18 years of age. A cross-sectional face-to-face survey was conducted in three labour camps in Guangxi, located in the south-western region of China. Results: Of the 755 detainees surveyed, 725 (96%) reported having a blood test in the labour camps of whom 493 (68%) thought this included an HIV test. 61 detainees self-reported they were HIV infected, their status confirmed by medical records, if available. Of these, 53 (87%) recalled receiving post-test HIV education, and 15 (25%) were currently receiving HIV antiretroviral therapy. Pretest education on HIV was provided to 233/725 (32%) detainees. The study further reports on detainees’ reactions and feelings towards non-disclosure and disclosure of their HIV test results in the labour camps. Conclusions: Mandatory testing is almost universal in the labour camps although a proportion of detainees were unaware that this included an HIV test. HIV test results should be disclosed to all labour camp detainees to reduce their distress of not knowing and prevent misconceptions about their HIV status. Labour camps provide another opportunity to implement universal treatment (‘Test and Treat’) to prevent the spread of HIV

HIV Vulnerability in Out-of-School Adolescents and Youth in Yunnan, China

This study investigated multiple aspects of vulnerability to HIV in out-of-school adolescents and youth in Yunnan Province, a high HIV risk region in China. The findings show that socially disadvantaged adolescents and youth were overrepresented in the out-of-school young people in Yunnan. The out-of-school young people in Yunnan exhibited 1) limited knowledge about HIV transmission and prevention, 2) a high prevalence of unprotected sexual activity, 3) high exposure to illicit drugs and alcohol use and a high prevalence of drug use in themselves, and 4) limited access to health services. There is an indication of higher exposure to risk behaviours in the younger age group. The study population used multiple media, particularly television, internet and radio, to obtain information about HIV transmission and pre- vention, particularly in the younger age group. These media may be an effective way of reaching this population in fu- ture HIV education and prevention programs in the region

Impaired Osteoblast Function in GPRC6A Null Mice

GPRC6A is a widely expressed orphan G protein–coupled receptor that senses extracellular amino acids, osteocalcin, and divalent cations in vitro. GPRC6A null (GPRC6A−/−) mice exhibit multiple metabolic abnormalities including osteopenia. To investigate whether the osseous abnormalities are a direct function of GPRC6A in osteoblasts, we examined the function of primary osteoblasts and bone marrow stromal cell cultures (BMSCs) in GPRC6A−/− mice. We confirmed that GPRC6A−/− mice exhibited a decrease in bone mineral density (BMD) associated with reduced expression of osteocalcin, ALP, osteoprotegerin, and Runx2-II transcripts in bone. Osteoblasts and BMSCs derived from GPRC6A−/− mice exhibited an attenuated response to extracellular calcium-stimulated extracellular signal-related kinase (ERK) activation, diminished alkaline phosphatase (ALP) expression, and impaired mineralization ex vivo. In addition, siRNA-mediated knockdown of GPRC6A in MC3T3 osteoblasts also resulted in a reduction in extracellular calcium-stimulated ERK activity. To explore the potential relevance of GPRC6A function in humans, we looked for an association between GPRC6A gene polymorphisms and BMD in a sample of 1000 unrelated American Caucasians. We found that GPRC6A gene polymorphisms were significantly associated with human spine BMD. These data indicate that GRPC6A directly participates in the regulation of osteoblast-mediated bone mineralization and may mediate the anabolic effects of extracellular amino acids, osteocalcin, and divalent cations in bone. © 2010 American Society for Bone and Mineral Research

Correlation functions quantify super-resolution images and estimate apparent clustering due to over-counting

We present an analytical method to quantify clustering in super-resolution localization images of static surfaces in two dimensions. The method also describes how over-counting of labeled molecules contributes to apparent self-clustering and how the effective lateral resolution of an image can be determined. This treatment applies to clustering of proteins and lipids in membranes, where there is significant interest in using super-resolution localization techniques to probe membrane heterogeneity. When images are quantified using pair correlation functions, the magnitude of apparent clustering due to over-counting will vary inversely with the surface density of labeled molecules and does not depend on the number of times an average molecule is counted. Over-counting does not yield apparent co-clustering in double label experiments when pair cross-correlation functions are measured. We apply our analytical method to quantify the distribution of the IgE receptor (Fc{\epsilon}RI) on the plasma membranes of chemically fixed RBL-2H3 mast cells from images acquired using stochastic optical reconstruction microscopy (STORM) and scanning electron microscopy (SEM). We find that apparent clustering of labeled IgE bound to Fc{\epsilon}RI detected with both methods arises from over-counting of individual complexes. Thus our results indicate that these receptors are randomly distributed within the resolution and sensitivity limits of these experiments.Comment: 22 pages, 5 figure

Risk factors for repetition of a deliberate self-harm episode within seven days in adolescents and young adults: A population-level record linkage study in Western Australia

Objective: The risk of repetition of deliberate self-harm peaks in the first 7 days after a deliberate self-harm episode. However, thus far no studies have examined the risk factors for repeating deliberate self-harm during this short-term period. We aimed to investigate the effects of socio-demographic factors, self-harm method and mental health factors in adolescents (10-19 years old) and young adults (20-29 years old). Methods: We used data linkage of population-wide administrative records from hospital inpatients and emergency departments to identify all the deliberate self-harm-related episodes that occurred in adolescents and young adults in Western Australia from 2000 to 2011. Logistic regression with generalised estimating equations was used for the analyses. Results: The incidence of repeating deliberate self-harm within the first 7 days after an index episode was 6% (403/6,768) in adolescents and 8% (842/10,198) in young adults. Socio-demographic risk factors included female gender and socioeconomic disadvantage. Compared with non-poisoning, self-poisoning predicted increased risk of having a repeated deliberate self-harm episode in males, but not in females. Borderline personality, impulse-control and substance use disorders diagnosed within one week before and one week after an index deliberate self-harm episode conferred the highest risk, followed by depressive and anxiety disorders. Having a preceding deliberate self-harm episode up to 7 days before an index episode was a strong predictor for the future repetition of a deliberate self-harm episode.Conclusion: Having a repeated deliberate self-harm episode within the first 7 days was related to a wide range of factors present at an index deliberate self-harm episode including socio-demographic characteristics, deliberate self-harm method and co-existing psychiatric conditions. These factors can inform risk assessments tailored to adolescents and young adults respectively to reduce the repetition of deliberate self-harm within a short but critical period, potentially contributing to reduce the repetition of deliberate self-harm in the long term

Up-regulation of transporters and enzymes by the vitamin D receptor ligands

ABSTRACT The effects of 1␣,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] on gene expression and function were studied in Caco-2 cells. Microarray analyses, real-time quantitative polymerase chain reactions, and Western blotting were used to determine the mRNA and protein expression of transporters and enzymes after 1,25(OH) 2 D 3 or vehicle (0.1% ethanol) treatment for 1, 3, 6, and 10 days. The mRNA and protein expressions of the apical sodium-dependent bile acid transporter, oligopeptide transporter 1, multidrug resistance-associated protein (MRP) 3, and sulfotransferase 1E1 remained unchanged with 1,25(OH) 2 D 3 treatment, whereas those for CYP3A4, multidrug resistance protein 1, and MRP2 were significantly increased (P Ͻ 0.05). 1,25(OH) 2 D 3 treatment significantly enhanced MRP4 protein expression by increasing protein stability without affecting mRNA expression, as confirmed in cycloheximide experiments. Marked increase in 6␤-hydroxylation of testosterone by CYP3A4 was also observed in the 6-day 1,25(OH) 2 D 3 -treated (100 nM) cell lysate. The transport of [ 3 H]digoxin, the P-glycoprotein (P-gp) substrate, after treatment with 100 nM 1,25(OH) 2 D 3 for 3 days revealed a higher apparent permeability (P app ) value in the basal (B)-to-apical (A) direction over that of vehicle treatment (15.1 Ϯ 0.53 ϫ 10 Ϫ6 versus 11.8 Ϯ 0.58 ϫ 10 Ϫ6 cm/s; P Ͻ 0.05), whereas the P app in the A-to-B direction was unchanged; the efflux ratio was increased (from 5.8 to 8.0). Reduced cellular retention of 5-(and-6)-carboxy-2Ј,7Ј-dichlorofluorescein, suggestive of higher MRP2 activity, was observed in the 3-day 100 nM 1,25(OH) 2 D 3 -treated cells over controls. Higher protein expression of CYP3A4, MRP2, P-gp, and MRP4 was also observed after a 6-day treatment with other vitamin D analogs (100 nM 1␣-hydroxyvitamin D 3 , 1␣-hydroxyvitamin D 2 or Hectorol, and 25-hydroxyvitamin D 3 ) in Caco-2 cells, suggesting a role of 1,25(OH) 2 D 3 and analogs in the activation of enzymes and transporters via the vitamin D receptor. The intestine plays an important role in the absorption of orally administered drugs. The expression and proximity of metabolic enzymes and efflux transporters in the enterocyte contribute to intestinal first-pass removal and delimit the tissue accumulation of endo-and xenobiotics. In the small intestine, cytochrome P450 3A4 (CYP3A4) accounts for approximately 70% of total cytochrome P450 content and is responsible for the metabolism of approximately 50% of drugs currently in us