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A rapidly growing body of research spanning several scientific disciplines and countries converges to show that mental health problems among students are an increasing challenge for higher education institutions. Mental health problems among students threaten academic performance, degree completion and student well-being. Structural efforts aimed at building health-promoting, learning environments for all students are lacking in the literature. This study aims to identify and describe what is currently known about structural approaches to promote mental health or prevent mental health problems among students in higher educational settings. We conducted a scoping review of studies published in peer-reviewed journals between 2001 and 2021, which studied structural interventions to promote mental health or prevent mental health problems among students in higher educational settings. The search identified 8372 articles, and 27 were included in the final sample. Four broad categories of approach were identified: (1) inclusion and diversity approaches, (2) adaptations to the physical environment, (3) teaching health-related skills and behaviours and (4) adaptations to pedagogical practices and teaching approaches. The general finding from the studies reporting student perceptions was that students were favourable to the interventions to which they were exposed. Studies investigating pre- to post-test changes in well-being had mixed findings. Institutions aiming to support student mental health at the structural level should rigorously study and describe these approaches and their outcomes to advance our combined understanding of how we might design and deliver structural interventions to support students' mental health.

Abstract Microbial species must compete for space and nutrients to persist in the gastrointestinal (GI) tract, and our understanding of the complex pathobiont-microbiota interactions is far from complete. Klebsiella pneumoniae, a problematic, often drug-resistant nosocomial pathogen, can colonize the GI tract asymptomatically, serving as an infection reservoir. To provide insight on how K. pneumoniae interacts with the resident gut microbiome, we conduct a transposon mutagenesis screen using a murine model of GI colonization with an intact microbiota. Among the genes identified were those encoding a type VI secretion system (T6SS), which mediates contact-dependent killing of gram-negative bacteria. From several approaches, we demonstrate that the T6SS is critical for K. pneumoniae gut colonization. Metagenomics and in vitro killing assays reveal that K. pneumoniae reduces Betaproteobacteria species in a T6SS-dependent manner, thus identifying specific species targeted by K. pneumoniae. We further show that T6SS gene expression is controlled by several transcriptional regulators and that expression only occurs in vitro under conditions that mimic the gut environment. By enabling K. pneumoniae to thrive in the gut, the T6SS indirectly contributes to the pathogenic potential of this organism. These observations advance our molecular understanding of how K. pneumoniae successfully colonizes the GI tract.

OBJECTIVES: We investigated associations between bioaerosol exposures and work-shift changes in lung function and inflammatory markers among recycling workers. METHODS: Inhalable dust was measured with personal samplers and analyzed for endotoxin, bacteria, and fungi (incubated at 25 °C and 37 °C) levels. Lung function (FEV1, FVC) was measured before and after work-shifts and serum concentrations of inflammatory markers (CRP, SAA, CC16, IL1B, IL2, IL4, IL5, IL6, IL8, IL10, IL13, and TNF) after the shift. Associations were explored by linear mixed-effects models. RESULTS: We included 170 measurements from 88 production workers exposed to inhalable dust, endotoxin, bacteria, and fungi (25 °C and 37 °C) at geometric mean levels of 0.6 mg/m3, 10.7 EU/m3, 1.6×104 CFU/m3, 4.4×104 CFU/m3, and 103 CFU/m3, respectively, and 14 administrative workers exposed at 7-fold lower levels. No associations were observed between bioaerosol exposures and work-shift change in lung function. IL2, IL6, IL10, and TNF concentrations were positively associated with inhalable dust levels, SAA and IL6 with bacteria, CRP, SAA, IL8, and TNF with fungi (25 °C or 37 °C), with the latter being the only statistically significant finding (exp(β) 1.40, 95% confidence interval 1.01–1.96). CONCLUSIONS: This study of recycling workers exposed to bioaerosol levels generally below those of farmers and compost workers and above background levels did not indicate any acute effect on lung function. Several inflammatory markers tended to increase with exposure, suggesting a systemic effect. Future research should combine data from bioaerosol-exposed workers to uncover health risks that may form the basis for health-based occupational exposure limits.

Abstract Background Transportation noise has been linked with breast cancer, but existing literature is conflicting. One proposed mechanism is that transportation noise disrupts sleep and the circadian rhythm. We investigated the relationships between road traffic noise, DNA methylation in circadian rhythm genes, and breast cancer. We selected 610 female participants (318 breast cancer cases and 292 controls) enrolled into the Malmö, Diet, and Cancer cohort. DNA methylation of CpGs (N = 29) in regulatory regions of circadian rhythm genes (CRY1, BMAL1, CLOCK, and PER1) was assessed by pyrosequencing of DNA from lymphocytes collected at enrollment. To assess associations between modeled 5-year mean residential road traffic noise and differentially methylated CpG positions, we used linear regression models adjusting for potential confounders, including sociodemographics, shiftwork, and air pollution. Linear mixed effects models were used to evaluate road traffic noise and differentially methylated regions. Unconditional logistic regression was used to investigate CpG methylation and breast cancer. Results We found that higher mean road traffic noise was associated with lower DNA methylation of three CRY1 CpGs (CpG1, CpG2, and CpG12) and three BMAL1 CpGs (CpG2, CpG6, and CpG7). Road traffic noise was also associated with differential methylation of CRY1 and BMAL1 promoters. In CRY1 CpG2 and CpG5 and in CLOCK CpG1, increasing levels of methylation tended to be associated with lower odds of breast cancer, with odds ratios (OR) of 0.88 (95% confidence interval (CI) 0.76–1.02), 0.84 (95% CI 0.74–0.96), and 0.80 (95% CI 0.68–0.94), respectively. Conclusions In summary, our data suggest that DNA hypomethylation in CRY1 and BMAL1 could be part of a causal chain from road traffic noise to breast cancer. This is consistent with the hypothesis that disruption of the circadian rhythm, e.g., from road traffic noise exposure, increases the risk of breast cancer. Since no prior studies have explored this association, it is essential to replicate our results. Graphical abstract

IntroductionMajor depression and alcohol use disorder affect millions of individuals worldwide and cause significant disability. They often occur together, and their co-occurrence is associated with more negative outcomes than each disorder on its own. Yet, there is a lack of knowledge on how to best treat co-occurring depression and alcohol use disorder. A pilot study was conducted to investigate the feasibility, credibility, patient satisfaction, preliminary effect, and potential negative effects of an integrated treatment for depression and alcohol use disorder, which has shown promising results in an earlier pilot trial.MethodsThe study was conducted at an outpatient unit in Stockholm, Sweden. Women (n=7) with current depression and alcohol use disorder were offered integrated group treatment that included evidence-based treatment for depression and alcohol use disorder. Criteria for feasibility were based on an earlier study, treatment credibility was measured using the Credibility/Expectancy Questionnaire and patient satisfaction with the Client Satisfaction Questionnaire.ResultsFeasibility, credibility, and patient satisfaction were high. Depression symptom severity and alcohol consumption decreased from baseline to follow up. Negative effects were reported in terms of increased adverse emotional experiences.DiscussionThe investigated integrated treatment for co-occurring depression and alcohol use disorder continues to show promise. Randomized clinical trials are needed to evaluate its effectiveness.

Obtaining a good functional fit with noisy data is difficult. This is especially true when the derivative of the fitted function is needed, which is often the case in engineering applications. One solution is to use smoothing splines. However, most conventional and readily available smoothing spline software implementations are cubic with a penalty on the 2nd order derivative, which results in poor and sometimes noisy derivatives. In this paper, we present new software that can be used to make smoothing splines with a penalty on the 1st, 2nd, 3rd, or 4th order derivatives. Furthermore, the presented software allows for applying constraints to the function to impose prior knowledge, including automatic parameter selection through cross-validation for an optimum and user-independent fit.

Analyzing the Danish media reception of Greta Thunberg’s speech at the UN’s climate action summit in 2019, this article illustrates how anger sticks to Thunberg and the youth climate movement, as well as how ‘their’ anger is problematized and pathologized. The anger ascribed to Thunberg is framed as a symptom of her autism spectrum diagnosis; as a ‘mental problem’ rather than a reaction to a political problem. Further, ‘her’ anger is portrayed as contagious, posing a risk to the health of other children, and ‘her’ anger becomes the source of ‘our’ concern. The article illustrates this by drawing attention to the emergence of the fi gure of ‘the impossible child’: an angry fi gure who is denied the positive affective status of the Child even though her childishness is constantly emphasized. She is not the innocent Child who must be protected but a problematic child whose dysregulated, pathological anger must be regulated to protect other children from her.

A healthy working life is fundamental for individuals and society. To date, increasingly research connects the earlier, pre-working life to later working life experiences and beyond, recognizing that a worker’s health and exposure starts before the working life begins. The research, however, often lacks a fundamental understanding of (i) the underlying mechanisms and pathways accounting for differences in different life stages and (ii) the role of the social environment in shaping working life experiences. By integrating a life course perspective in our research and crossing disciplinary borders in rigorous, collaborative research, we may get a better understanding of the complex and dynamic interplay between work, environment and health. A life course perspective for work environment and health research A life course perspective in work environment and health research emphasizes the importance of prior life experiences, including the environments in which individuals were raised and exposed, their familial and educational backgrounds, and their physical and mental health status before entering the workforce (1, 2). Life course research in different disciplines has been instrumental in developing more robust causal models (3, 4), particularly for understanding developmental health trajectories and socioeconomic health inequalities (eg, 5–7). Adopting an interdisciplinary life course perspective in work environment and health research helps researchers answering questions as to whether and how the timing, duration, intensity, and context of past and present exposures (ie, pre-working, working, and non-working exposures) are associated with later life work and health outcomes. For instance, the ‘exposome paradigm’ is a concept used to describe the sum of occupational and environmental exposures an individual encounters throughout life, and how these exposures impact biology and health (8). In exposome research, a broad range of genetic, biological, chemical, physical, social and lifestyle factors is examined throughout the life course to provide a comprehensive picture of potential risk factors impacting working life health (9). In exposome research and beyond, it is important to examine how the exposure-outcome relationships are shaped by specific social, cultural and historical contexts (2). The conceptual framework of the ‘Social Exposome’ may help to integrate the social environment in conjunction with the physical environment into the exposome concept (10). Moreover, focusing on both historical and contemporary contexts is essential not only for advancing research but also for informing policy and practice, for example by identifying entry points for interventions. Exposures during the life course During the individual’s life course, several vulnerable time windows for the impact of a multitude of exposures that potentially harm, protect or promote health, eg, occupational, environmental and social, can be distinguished. The (combinations of) exposures may operate in different life stages and contexts and – directly or indirectly via intergenerational transmission – contribute to health (figure 1). The individual may be particulary sensitive to harmful exposures or adverse experiences during developmental life stages, ie, pre/perinatal, childhood, adolescence, pregnancy and menopause/andropause. Other life stages may reflect vulnerable time windows due to a clustering of exposures, eg, work and family demands during parenthood, or an accumulation of exposures during the (working) life course at retirement and post-retirement age. As illustrated in figure 1, occupational exposure(s) can be divided in exposure through the parents’ exposure (early in life) and an individuals’ own exposure (later in life). Already in the pre/perinatal life stage, occupational exposure starts through the intergenerational transmission of the parents’ occupational exposures. Current and bioaccumulated occupational exposure of chemicals and particles in the father at the time of conception can affect sperm quality. Together with the mother’s exposure to occupational exposures of chemicals and particles prior to conception – or chemicals, particles, physical factors, ergonomic load, organizational and (psycho-)social conditions at work during pregnancy – this may affect fetal development and later disease development during the child’s life course (11–15). During childhood, the growing child is exposed to parental occupational exposure(s), directly through chemicals and particles in the work clothes and skin or indirectly through organizational and psychosocial factors in the work environment that may increase the risk for mental and physical health problems in parents, which in turn may affect their parental rearing quality (16, 17). During adolescence and early adulthood, individuals usually encounter their first direct occupational exposures through their first (student) job or jobs. Already from this life stage, occupational exposures may accumulate during the (working) life course and may affect not only the active working life but also the post working life. Also important to note is that brain plasticity is not limited to childhood, adolescence or young adulthood as it persists throughout life. Some studies indicate that high physical and chemical exposure during this life stage, can increase the risk of disease later in life (18). A poor psychosocial school or work environment in younger years may also increase the risk of adverse labour market outcomes and mental health problems later in life (19, 20). In adulthood, men and women often start with (the planning of) family formation. Some occupational exposures affect fecundability, others can increase the risk of pregnancy-related disease, such as preeclampsia, hypertension or diabetes, or affect the offspring (21, 22). Chemicals, heat and stress-related exposures affect the ability to conceive. During pregnancy, the bodily and mental systems are vulnerable with changes in the endocrine and inflammation response that can dysregulate the HPA-axis, resulting in a prolonged stress response. The placenta can filter out many hazards, but not all toxicants, such as methylmercury and arsenic (23, 24). Physical exposure, such as noise and vibration, but also shift and night work can affect the womb and cause fetal growth restriction, preterm birth, and hearing impairment (eg, 12, 13, 25–27). During parenthood, occupational exposures may affect the parents’ (mental) health and work-family balance (28, 29). Many chemical and physical exposures have now manifested in disease, eg, allergy, asthma and musculoskeletal diseases (28). During menopause in women, with a drastic decrease in oestrogen, and the slow testosterone decline in men (sometimes referred to as andropause), dysregulations of the hormone system may disrupt and affect the individual’s susceptibility for occupational exposures in a way similar to environmental exposures (30). Towards retirement, the total cumulative occupational exposure burden over the working life course and the current exposure will affect the ability to stay at work and in the labor market. Post retirement, most direct occupational exposures have ceased, but others may have (bio-) accumulated over time and may cause health problems that manifest after retirement (31, 32). Along with occupational exposures, a multitude of other exposures are present during the entire life course that may operate across different contexts to contribute to health (see figure 1). For instance, chemical, physical and social stressors during the life course leave traces (‘memories’) on the molecular and tissue levels that may affect later life health (33). Epigenetic marks act as heritable memories in the cell as they respond to different endogenous and exogenous signals and can be propagated from one generation of cells to the next generation of cells (33). Next to the epigenetic marks, the social environment and social determinants of health during the life course, eg, socio-economic and lifestyle factors, social relationships, social cohesion and support, are known to impact health and add to the multitude of exposures to be examined, among others in conjunction with the environmental exposome (eg, 34). In residential, family and school contexts, exposures such as air pollution, drinking water pollution, noise, artificial light at night, limited access to green space and crowding may play a role, as can adverse childhood experiences (eg, 35, 36). Moreover, on the overarching societal context, legislations, labor market conditions, norms, values and cultural aspects may affect worker health (2, 37). Main knowledge gaps and challenges Both conceptual and empirical challenges have to be tackled when conducting work environment and health research with an interdisciplinary life course perspective. On the conceptual level, different paradigms and nomenclature still exist in the various disciplines examining the impact of (occupational) exposures on later life health outcomes, which contributes to fragmented research and publication thereof in specialized journals. On the empirical level, questions arise such as: Is it feasible to examine mechanisms and pathways across different exposure levels considering a life course perspective? Is the follow-up duration of existing birth and other cohorts sufficient to address the dynamic interplay between the work environment and health? Are the multifaceted, constantly changing contexts captured? Effect sizes are often small on an individual level and statistical power decreases when several rare assumptions have to be fulfilled to examine clusters or combinations of exposures and contexts in relation to health outcomes. Big data, interdisciplinary research protocols and innovative, advanced statistical models to capture the life course perspective are needed to proceed beyond the exposome studies that are currently being finalized within the EU Horizon 2020 exposome call (https://www.humanexposome.eu). Moreover, a better understanding is needed of how occupational, environmental and social exposures affect individuals (i) in vulnerable time windows, eg, do exposures contribute to health advantages and/or disadvantages, and (ii) while transitioning between and within different life stages (38). Studies in different disciplines have focused on the childhood and retirement life stages, see eg, the research on the school-to-work transition or the work-to-retirement transition (39–41), but little is known about the menopause or andropause life stage. Last, rigorous examinations of different lifecourse models (eg, sensitive periods) and exposure models (eg, current, first, last, peak, single, chronic or accumulated), and their impact on health are needed within and across the different vulnerable time windows and life stages as exposure-outcome relationships may differ and thus call for targeted (preventive) policies and practices (42–44). Interdisciplinary research opportunities The challenges towards a better understanding of the complex and dynamic interplay between the work environment and health provide ample opportunities for rigorous, collaborative quantitative and in-depth qualitative life course research across different research strands. Researchers from different disciplines, such as occupational and environmental medicine, epidemiology, toxicology, health science, sociology, psychology, demography, public (mental) health, and genetics to name a few, should not shy away from the complexity, but embrace the opportunity to use their knowledge and skills to collectively address relevant research questions. Interdisciplinary research opportunities are already present today and will emerge even more in the years to come as more cohorts designed as birth cohorts or multi-generational cohorts mature (eg, LifelinesNext, 45). Researchers have or get access to (national) registers, databases with individual-level internal and external exposure information and neighbourhood-level exposure information or linkages of all these exposure and health data, allowing them to examine the impact of exposures in advanced causal models on later life health. To illustrate the value of and research opportunities with existing data, Ubalde-Lopez and colleagues (46) recently argued that parental work-related data collected in birth cohorts is a valuable yet underutilized resource that could be exploited more fruitfully in the collaboration between birth cohort research, occupational epidemiology and sociology. Having said that, the authors also refer to the possible constraints of eg, cross-national comparative research in terms of technical (ie, harmonization) and ethical challenges (46). In conclusion, to move research on the work environment and health forward, we call for a more integrated, interdisciplinary approach that considers the timing and accumulation of occupational, environmental and social exposures over the life course.

Objectives Our aim was to explore healthcare professionals’ (HCPs) expectations, concerns and educational needs regarding preparing for implementing the concept of couplet care, keeping newborns in need of intensive care together with their mothers in need of obstetrical care.Design A qualitative focus group study based on semistructured interviews. We analysed the data using reflexive thematic analysis. This study is part of a comprehensive research project and pre-implementation based on curriculum development principles and implementation theory.Setting We conducted four focus group interviews from May to June 2023 at a tertiary referral university hospital in Denmark.Participants Neonatologists, obstetricians, midwives and nurses (n=21) were recruited from neonatal and obstetric departments. Inclusion criteria: Neonatologists, obstetricians, midwives and nurses with various levels of postgraduate experience.Results We identified the overarching theme of building bridges in relation to HCPs’ expectations, concerns and educational needs and five subthemes: Enhancing meaningfulness through increased teamwork; compromising or improving patient safety; challenging professional comfort zones; encountering other cultural and ethical values; and recognising educational requirements.Conclusions HCPs widely support mother–newborn couplet care and emphasise the need for closer collaboration between neonatal and obstetric departments. Implementing couplet care is seen as meaningful, potentially enhancing the well-being of mothers and newborns and positively impacting HCPs’ job satisfaction. Key concerns include patient safety, quality of treatment and care and the well-being of HCPs navigating their skills, psychological safety and professional boundaries. While the importance of couplet care for early closeness and connection is acknowledged, challenges arise in meeting diverse maternal and neonatal needs. Additional research, especially in highly specialised settings, is necessary to understand the complexities associated with changing the care paradigm for newborns and mothers to be cared for together and in implementing couplet care. We found focus groups useful as a tool for needs assessment and uncovering and adapting practices to address challenges in implementing couplet care.

ABSTRACT Raman spectroscopy, a robust and non‐invasive analytical method, has demonstrated significant potential for monitoring biopharmaceutical production processes. Its ability to provide detailed information about molecular vibrations makes it ideal for the detection and quantification of therapeutic proteins and critical control parameters in complex biopharmaceutical mixtures. However, its application in Saccharomyces cerevisiae fermentations has been hindered by the inherent strong fluorescence background from the cells. This fluorescence interferes with Raman signals, compromising spectral data accuracy. In this study, we present an approach that mitigates this issue by deploying Raman spectroscopy on cell‐free media samples, combined with advanced chemometric modeling. This method enables accurate prediction of protein concentration and key process parameters, fundamental for the control and optimization of biopharmaceutical fermentation processes. Utilizing variable importance in projection (VIP) further enhances model robustness, leading to lower relative root mean squared error of prediction (RMSEP) values across the six targets studied. Our findings highlight the potential of Raman spectroscopy for real‐time, on‐line monitoring and control of complex microbial fermentations, thereby significantly enhancing the efficiency and quality of S. cerevisiae‐based biopharmaceutical production.

Background The univentricular heart with a predominant right ventricle morphology (uRV) has been associated with a higher rate of adverse cardiovascular events. It remains to be determined whether the specific type of uRV influences outcomes. Methods and Results A North American multicenter retrospective cohort study was conducted by the Alliance for Adult Research in Congenital Cardiology on individuals with a uRV and total cavopulmonary connection Fontan. The incidence of a composite outcome consisting of all‐cause mortality, cardiac transplantation, atrial arrhythmias, or thromboembolic events was compared among patients with Fontan palliation who had hypoplastic left heart syndrome (HLHS) versus other forms of uRV (non‐HLHS). All components of the composite outcome were classified by a blinded adjudicating committee. Competing risks were taken into account in time‐to‐event analyses. A total of 171 patients with uRV of whom 76 (44.4%) had HLHS were followed for 10.2±5.7 years. The composite outcome occurred in 7.1 versus 2.1 cases per 100 person‐years in patients with HLHS versus non‐HLHS (P

Calculations of point defect energetics with Density Functional Theory (DFT) can provide valuable insight into several optoelectronic, thermodynamic, and kinetic properties. These calculations commonly use methods ranging from semi-local functionals with a-posteriori corrections to more computationally intensive hybrid functional approaches. For applications of DFT-based high-throughput computation for data-driven materials discovery, point defect properties are of interest, yet are currently excluded from available materials databases. This work presents a benchmark analysis of automated, semi-local point defect calculations with a-posteriori corrections, compared to 245 “gold standard” hybrid calculations previously published. We consider three different a-posteriori correction sets implemented in an automated workflow, and evaluate the qualitative and quantitative differences among four different categories of defect information: thermodynamic transition levels, formation energies, Fermi levels, and dopability limits. We highlight qualitative information that can be extracted from high-throughput calculations based on semi-local DFT methods, while also demonstrating the limits of quantitative accuracy.

Parechoviruses are small, nonenveloped, singlestranded RNA viruses belonging to the large Picomaviridae family that circulate worldwide; primary infections occur mainly in children Nineteen human parechovirus types have been classified as [...]

Niche-derived factors regulate tissue stem cells, but apart from the mechanosensory pathways, the effect of niche geometry is not well understood. We used organoids and bioengineered tissue culture platforms to demonstrate that the conical shape of Lgr5+ small intestinal stem cells (ISCs) facilitate their self-renewal and function. Inhibition of non-muscle myosin II (NM II)-driven apical constriction altered ISC shape and reduced niche curvature and stem cell capacity. Niche curvature is decreased in aged mice, suggesting that suboptimal interactions between old ISCs and their niche develop with age. We show that activation of NM IIC or physical restriction to young topology improves in vitro regeneration by old epithelium. We propose that the increase in lateral surface area of ISCs induced by apical constriction promotes interactions between neighboring cells, and the curved topology of the intestinal niche has evolved to maximize signaling between ISCs and neighboring cells.

Background: Hexavalent chromium (Cr(Ⅵ)) is classified as a group 1 human carcinogen and increases the risk of lung cancer. Non-coding RNAs (ncRNAs) have key regulatory roles in lung cancer, but less is known about their relation to Cr(Ⅵ) exposure. Objectives: We aimed to 1) measure the expression of lung cancer-related circulating ncRNAs in exposed workers and controls; 2) assess associations between ncRNAs expression and Cr concentrations in red blood cells (RBC) and urine; and 3) evaluate correlations between the ncRNAs. Methods: The study included 111 Cr(VI) exposed workers and 72 controls recruited from the SafeChrom project. Cr concentrations were measured in RBC (biomarker of long-term exposure) and urine (biomarker of short-term exposure) samples. Long ncRNA (lncRNA) and microRNA (miRNA) were extracted from plasma followed by deoxyribonuclease treatment, complementary DNA synthesis, and quantitative real‐time polymerase chain reaction using target-specific assays for three lncRNAs (H19, MALAT1, NORAD), and four miRNAs (miR-142-3p, miR-15b-5p, miR-3940-5p, miR-451a). Results: Expression levels of lncRNAs MALAT1 and NORAD, and all four miRNAs, were significantly lower in Cr(VI) exposed workers compared with controls, and correlated significantly with RBC-Cr concentrations (rS = −0.16 to −0.38). H19 was non-significantly increased in exposed workers but significantly correlated with miR-142-3p (rS = −0.33) and miR-15b-5p (rS = −0.30), and NORAD was significantly positively correlated with all four miRNAs (rS = 0.17 to 0.46). In multivariate regression models adjusting for confounders, expressions of lncRNAs MALAT1 and NORAD and all miRNAs were still significantly lower in the exposed group compared with controls, and the expression decreased with increasing RBC-Cr concentrations. Conclusions: Cr(VI) exposure was inversely and in a dose–response manner associated with the expression of circulating non-coding RNA, which suggests ncRNAs as potential biomarkers for Cr(VI)-induced toxicity. Correlations between miRNAs and lncRNAs suggest that they participate in the same lncRNA-miRNA-messenger RNA regulatory axes, which may play important roles in Cr(VI) carcinogenesis.

There is limited research targeting communication interventions for children with severe/profound intellectual and multiple disabilities. This study addressed outcomes from a communication course for parents of children with severe/profound intellectual and multiple disabilities and follows up on a previous publication by Rensfeldt Flink et al. (2020). Potential observable changes in the children's and parents' communicative behavior were studied as well as the parents' experiences of the intervention process and the effect of the course on parent--child communication. A mixed-methods design with a case-study framework was used. Two mother--child dyads participated. Data were collected before, during, and after the course. Video-recorded repeated play interactions by the dyads were coded and analyzed for the mothers' responsivity and use of augmentative and alternative communication and the children's interactive engagement. Longitudinal interview data from the mothers were analyzed thematically. No clear signs of behavioral change were observed in the coded video data. However, thematic analyses showed that the mothers experienced changes to communicative behaviors. Moreover, the course affected both mothers' reasoning about communication with their child and their child's communicative needs. The mothers' narratives contributed insights into how reflective processes might guide action in parent-mediated communication interventions. The implications for research and clinical practice are discussed.

Abstract Background Congenital heart defects (CHD) are structural defects of the heart affecting approximately 1% of newborns. They exhibit low penetrance and non-Mendelian patterns of inheritance as varied and complex traits. While genetic factors are known to play an important role in the development of CHD, the specific genetics remain unknown for the majority of patients. To elucidate the underlying genetic risk, we performed a genome wide association study (GWAS) of CHDs in general and specific CHD subgroups using the FinnGen Release 10 (R10) (N > 393,000), followed by functional fine-mapping through eQTL and co-localization analyses using the GTEx database. Results We discovered three genome-wide significant loci associated with general CHD. Two of them were located in chromosome 17: 17q21.32 (rs2316327, intronic: LRRC37A2, Odds ratio (OR) [95% Confidence Interval (CI)] = 1.17[1.12–1.23], p = 1.5 × 10–9) and 17q25.3 (rs1293973611, nearest: BAHCC1, OR[95%CI] = 4.48[2.80–7.17], p = 7.0 × 10–10), respectively, and in addition to general CHD, the rs1293973611 locus was associated with the septal defect subtype. The third locus was in band 1p21.2 (rs35046143, nearest: PALMD, OR[95%CI] = 1.15[1.09–1.21], p = 7.1 × 10–9), and it was associated with general CHD and left-sided lesions. In the subgroup analysis, two additional loci were associated with septal defects (rs75230966 and rs6824295), and one with left-sided lesions (rs1305393195). In the eQTL analysis the variants rs2316327 (general CHD), and rs75230966 (septal defects) both located in 17q21.32 (with a LD r2 of 0.41) were both predicted to significantly associate with the expression of WNT9B in the atrial appendage tissue category. This effect was further confirmed by co-localization analysis, which also implicated WNT3 expression in the atrial appendage. A meta-analysis of general CHD together with the UK Biobank (combined N = 881,678) provided a different genome-wide significant locus in LRRC37A2; rs16941382 (OR[95%CI] = 1.15[1.11–1.20], p = 1.5 × 10–9) which is in significant LD with rs2316327. Conclusions Our results of general CHD and different CHD subcategories identified a complex risk locus on chromosome 17 near BAHCC1 and LRRC37A2, interacting with the genes WNT9B, WNT3 and MYL4, may constitute potential novel CHD risk associated loci, warranting future experimental tests to determine their role.