Help-Seeking Among Children Impacted by Commercial Sexual Exploitation: A Scoping Review.

This scoping review aims to summarize current research on help-seeking behaviors and patterns among children who have experienced commercial sexual exploitation of children (CSEC) victimization and/or are at high risk of exploitation. Because the literature on help-seeking specific to CSEC victimization is limited, the current review was expanded to summarize findings from help-seeking research for children who have experienced harms that often co-occur with CSEC, such as maltreatment and homelessness. The authors searched three large article databases (PsycInfo, Ovid MEDLINE, and Web of Science) for articles that were (a) empirical; (b) measured or used the term "help-seeking" in their framing and/or results; (c) included children between the ages of 12 and 18; (d) primarily focused on children from the United States; (e) published in English. Ultimately, 22 articles met all inclusion criteria and were included in the final review. Results suggest that cisgender white females are the most likely to seek help, followed by sexual and gender minority children. Cisgender male children were the least likely to engage in help-seeking behaviors. Universally, children were more likely to engage in informal help-seeking rather than formal help-seeking, with younger children being more likely to reach out to parents and older children more likely to reach out to friends. Importantly, ethnically diverse children were under-represented, leading to limited information about how and why these children seek help. Implications for help-seeking by children impacted by commercial sexual exploitation are discussed, providing guidance for programming and research related to CSEC prevention.

Depressive symptoms are associated with clinical outcomes in heart failure with reduced ejection fraction.

AIMS: The objective of this study was to examine associations between elevated depressive symptoms and increased risk of adverse clinical events patients with heart failure and reduced ejection fraction (HFrEF), as well as the potential contribution of health behaviours. METHODS AND RESULTS: One hundred forty-two men and women with HFrEF were enrolled through heart failure (HF) clinics and followed over time. At baseline and 6 months, depressive symptoms were assessed by the Beck Depression Inventory-II (BDI-II) and HFrEF disease activity by B-type natriuretic peptide (BNP). The Self-Care of Heart Failure Index (SCHFI) was used to assess HF self-care behaviours. Proportional hazards regression models assessed the contribution of depressive symptoms and HFrEF disease biomarkers on death or cardiovascular hospitalization. Over a median follow-up period of 4 years, 42 patients (30%) died, and 84 (60%) had cardiovascular hospitalizations. A 10-point higher baseline BDI-II score was associated with a 35% greater risk of death or cardiovascular hospitalization. Higher baseline BDI-II scores were associated with poorer HF self-care maintenance behaviours (R = -0.30, P < 0.001) and fewer daily steps (R = -0.19, P = 0.04), suggesting that elevated depressive symptoms may diminish important health behaviours. Increases in plasma BNP over 6 months were associated with worse outcomes. Changes in BDI-II and plasma BNP over 6 months were positively related (R = 0.25, P = 0.004). CONCLUSIONS: This study confirms that elevated depressive symptoms are associated with an increased likelihood of adverse clinical outcomes in patients with HFrEF. Poor health behaviours may contribute to the adverse association of elevated depressive symptoms with the increased hazard of adverse clinical outcomes.

More than a mask: Possible relationships between lifting of COVID-19 mask requirements and depression symptoms experienced by US adults with disabilities.

BACKGROUND: Lifting of masking restrictions at key periods during the COVID-19 pandemic may have disproportionately negatively impacted the mental health of individuals with disabilities. OBJECTIVE: This study examines the prevalence of depression-related symptoms in individuals with and without disabilities preceding and following the US rollback of COVID-19 masking mandates. METHODS: Pandemic-era data on reported symptoms of depression from the federal Household Pulse Survey from dates surrounding two major announcements on masking relaxations were analyzed. Possible interactions between disability status and type, age grouping, educational attainment, race/Hispanic ethnicity, and sex variables were considered. RESULTS: Following relaxation of major masking restrictions, people with disabilities experienced elevation in depression symptom presence while people without disabilities experienced lessening in these symptoms. Differences between people with and without disabilities were significant. CONCLUSIONS: Direct causation between masking mandate relaxations and changes in symptoms of depression cannot be drawn from the available data. However, when considered with greater vulnerabilities to COVID-19 experienced by many individuals with disabilities and dismissive rhetoric surrounding masking decisions, negative feelings arising from mandate changes may have led to elevations in symptoms of depression in people with disabilities in sharp contrast to people without disabilities who may have felt relief. Findings indicate future public health decision making, even in times of crisis, should be undertaken with as much caution as possible regarding and in partnership with populations already at risk.

Identifying genetic differences between bipolar disorder and major depression through multiple GWAS.

Background: Accurate diagnosis of bipolar disorder (BD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A key reason is that the first manic episode is often preceded by a depressive one, making it difficult to distinguish BD from unipolar major depressive disorder (MDD). Aims: Here, we use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores that may aid early differential diagnosis. Methods: Based on individual genotypes from case-control cohorts of BD and MDD shared through the Psychiatric Genomics Consortium, we compile case-case-control cohorts, applying a careful merging and quality control procedure. In a resulting cohort of 51,149 individuals (15,532 BD cases, 12,920 MDD cases and 22,697 controls), we perform a variety of GWAS and polygenic risk scores (PRS) analyses. Results: While our GWAS is not well-powered to identify genome-wide significant loci, we find significant SNP-heritability and demonstrate the ability of the resulting PRS to distinguish BD from MDD, including BD cases with depressive onset. We replicate our PRS findings, but not signals of individual loci in an independent Danish cohort (iPSYCH 2015 case-cohort study, N=25,966). We observe strong genetic correlation between our case-case GWAS and that of case-control BD. Conclusions: We find that MDD and BD, including BD with a depressive onset, are genetically distinct. Further, our findings support the hypothesis that Controls - MDD - BD primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BD and, importantly, BD with depressive onset from MDD.

Mendelian segregation and high recombination rates facilitate genetic analyses in Cryptosporidium parvum.

Very little is known about the process of meiosis in the apicomplexan parasite Cryptosporidium despite the essentiality of sex in its life cycle. Most cell lines only support asexual growth of Cryptosporidium parvum (C. parvum), but stem cell derived intestinal epithelial cells grown under air-liquid interface (ALI) conditions support the sexual cycle. To examine chromosomal dynamics during meiosis in C. parvum, we generated two transgenic lines of parasites that were fluorescently tagged with mCherry or GFP on chromosomes 1 or 5, respectively. Infection of ALI cultures or Ifngr1-/- mice with mCherry and GFP parasites produced "yellow" oocysts generated by cross-fertilization. Outcrossed oocysts from the F1 generation were purified and used to infect HCT-8 cultures, and phenotypes of the progeny were observed by microscopy. All possible phenotypes predicted by independent segregation were represented equally (~25%) in the population, indicating that C. parvum chromosomes exhibit a Mendelian inheritance pattern. Unexpectedly, the most common pattern observed from the outgrowth of single oocysts included all possible parental and recombinant phenotypes derived from a single meiotic event, suggesting a high rate of crossover. To estimate the frequency of crossover, additional loci on chromosomes 1 and 5 were tagged and used to monitor intrachromosomal crosses in Ifngr1-/- mice. Both chromosomes showed a high frequency of crossover compared to other apicomplexans with map distances (i.e., 1% recombination) of 3-12 kb. Overall, a high recombination rate may explain many unique characteristics observed in Cryptosporidium spp. such as high rates of speciation, wide variation in host range, and rapid evolution of host-specific virulence factors.

Key subphenotypes of bipolar disorder are differentially associated with polygenic liabilities for bipolar disorder, schizophrenia, and major depressive disorder.

Bipolar disorder (BD) features heterogenous clinical presentation and course of illness. It remains unclear how subphenotypes associate with genetic loadings of BD and related psychiatric disorders. We investigated associations between the subphenotypes and polygenic risk scores (PRS) for BD, schizophrenia, and major depressive disorder (MDD) in two BD cohorts from Sweden (N = 5180) and the UK (N = 2577). Participants were assessed through interviews and medical records for inter-episode remission, psychotic features during mood episodes, global assessment of functioning (GAF, function and symptom burden dimensions), and comorbid anxiety disorders. Meta-analyses based on both cohorts showed that inter-episode remission and GAF-function were positively correlated with BD-PRS but negatively correlated with schizophrenia-PRS (SCZ-PRS) and MDD-PRS. Moreover, BD-PRS was negatively, and MDD-PRS positively, associated with the risk of comorbid anxiety disorders. Finally, SCZ-PRS was positively associated with psychotic symptoms during mood episodes. Assuming a higher PRS of certain psychiatric disorders in cases with a positive family history, we further tested the associations between subphenotypes in index BD people and occurrence of BD, schizophrenia, or MDD in their relatives using Swedish national registries. BD patients with a relative diagnosed with BD had: (1) higher GAF and lower risk of comorbid anxiety than those with a relative diagnosed with schizophrenia or MDD, (2) lower risk of psychotic symptoms than those with a relative diagnosed with schizophrenia. Our findings shed light on the genetic underpinnings of the heterogeneity in clinical manifestations and course of illness in BD, which ultimately provide insights for developing personalized approaches to the diagnosis and treatment.

The mental health of officials who regularly examine child sexual abuse material: strategies for harm mitigation.

BACKGROUND: The current study aims to better understand the mental health and subjective well-being of investigators and forensic examiners exposed to child sexual abuse material (CSAM) by examining which components of this work are associated with elevated mental health conditions and decreased well-being, as well as the intra-personal and organizational variables that may mitigate harm and improve well-being. METHODS: Police investigators, forensic examiners, and others connected with the criminal justice system from across the United States who were exposed to CSAM as part of their professions (N = 500) completed an anonymous online survey. Participants were recruited through connections with the National Criminal Justice Training Center. RESULTS: Duration, frequency, amount, and content of CSAM exposure was not related to poorer mental health with the exception of exposure to violent CSAM which was related to elevated post-traumatic stress symptoms. Several agency-level practices and policies, such as the availability of an Officer Wellness Program and more frequently knowing the final case resolution, were related to better mental health and well-being. Harm mitigation strategies, such as talking to other officers investigating the case and taking breaks from the material being viewed, were also related to better mental health. CONCLUSIONS: Findings indicate that police agencies have options for implementing agency-level procedures and practices that have the potential to reduce the negative impact of CSAM investigations. Additionally, many investigators use strategies that are correlated with greater well-being, suggesting opportunities for improving training programs.

Dimethylthiourea as a Quencher in Hydroxyl Radical Protein Footprinting Experiments.

Hydroxyl radical protein footprinting (HRPF) is a mass-spectrometry-based method for studying protein structures, interactions, conformations, and folding. This method is based on the irreversible labeling of solvent-exposed amino acid side chains by hydroxyl radicals. While catalase is commonly used as a quencher after the labeling of a protein by the hydroxyl radicals to efficiently remove the remaining hydrogen peroxide, it has some disadvantages. Catalase quenching adds a relatively high amount of protein to the sample, limiting the sensitivity of the method due to dynamic range issues and causing significant issues when dealing with more complex samples. We evaluated dimethylthiourea (DMTU) as a replacement for catalase in the quenching HRPF reactions. We observed that DMTU is highly effective at quenching HRPF oxidation. DMTU does not cause the background protein issues that catalase does, resulting in an increased number of protein identifications from complex mixtures. We recommend the replacement of catalase quenching with DMTU for all HRPF experiments.

Meta-Analyses of Genome-Wide Association Studies for Postpartum Depression.

OBJECTIVE: Postpartum depression (PPD) is a common subtype of major depressive disorder (MDD) that is more heritable, yet is understudied in psychiatric genetics. The authors conducted meta-analyses of genome-wide association studies (GWASs) to investigate the genetic architecture of PPD. METHOD: Meta-analyses were conducted on 18 cohorts of European ancestry (17,339 PPD cases and 53,426 controls), one cohort of East Asian ancestry (975 cases and 3,780 controls), and one cohort of African ancestry (456 cases and 1,255 controls), totaling 18,770 PPD cases and 58,461 controls. Post-GWAS analyses included 1) single-nucleotide polymorphism (SNP)-based heritability ([Formula: see text]), 2) genetic correlations between PPD and other phenotypes, and 3) enrichment of the PPD GWAS findings in 27 human tissues and 265 cell types from the mouse central and peripheral nervous system. RESULTS: No SNP achieved genome-wide significance in the European or the trans-ancestry meta-analyses. The [Formula: see text] of PPD was 0.14 (SE=0.02). Significant genetic correlations were estimated for PPD with MDD, bipolar disorder, anxiety disorders, posttraumatic stress disorder, insomnia, age at menarche, and polycystic ovary syndrome. Cell-type enrichment analyses implicate inhibitory neurons in the thalamus and cholinergic neurons within septal nuclei of the hypothalamus, a pattern that differs from MDD. CONCLUSIONS: While more samples are needed to reach genome-wide levels of significance, the results presented confirm PPD as a polygenic and heritable phenotype. There is also evidence that despite a high correlation with MDD, PPD may have unique genetic components. Cell enrichment results suggest GABAergic neurons, which converge on a common mechanism with the only medication approved by the U.S. Food and Drug Administration for PPD (brexanolone).

Efficient Analysis of Proteome-Wide FPOP Data by FragPipe.

Monitoring protein structure before and after environmental alterations (e.g., different cell states) can give insights into the role and function of proteins. Fast photochemical oxidation of proteins (FPOP) coupled with mass spectrometry (MS) allows for monitoring of structural rearrangements by exposing proteins to OH radicals that oxidize solvent-accessible residues, indicating protein regions undergoing movement. Some of the benefits of FPOP include high throughput and a lack of scrambling due to label irreversibility. However, the challenges of processing FPOP data have thus far limited its proteome-scale uses. Here, we present a computational workflow for fast and sensitive analysis of FPOP data sets. Our workflow, implemented as part of the FragPipe computational platform, combines the speed of the MSFragger search with a unique hybrid search method to restrict the large search space of FPOP modifications. Together, these features enable more than 10-fold faster FPOP searches that identify 150% more modified peptide spectra than previous methods. We hope this new workflow will increase the accessibility of FPOP to enable more protein structure and function relationships to be explored.

Association of Depression Symptoms and Biomarkers of Risk on Clinical Outcomes in HFrEF.

BACKGROUND: Prior studies have demonstrated an association of depression with adverse clinical outcomes in patients with HFrEF, but the possible mechanisms responsible for the association are not unserstood. METHODS: 142 men and women with HFrEF were enrolled through HF clinics and followed over time. At baseline and 6-months, depression was assessed by the Beck Depression Inventory (BDI-II) and disease activity by B-type natriuretic peptide (BNP). Proportional Hazards Regression Models assessed the contribution of depressive symptoms and HFrEF disease biomarkers on death or cardiovascular hospitalization. RESULTS: Over a median follow-up period of 4 years, 42 patients (30%) died, and 84 (60%) had cardiovascular hospitalizations. A 10-point higher baseline BDI-II score was associated with a 35% higher hazard of death or cardiovascular hospitalization. Greater baseline BDI-II scores were associated with poorer HF self-care maintenance (R=-0.30, p<0.001) and fewer daily steps (R=-0.19, p=0.04), suggesting that depression may adversely affect important health behaviors. Increases in plasma BNP over 6 months were associated with worse outcomes. Changes in BDI-II score and plasma BNP over 6 months were positively correlated (R=0.25, p=0.004). CONCLUSIONS: This study underscores the importance of elevated depression symptoms and their association with an increased likelihood of adverse clinical outcomes in patients with HFrEF. Health behaviors may play a greater role than direct biobehavioral pathways in the adverse effects of depression on the HF disease trajectory and resultant clinical outcomes.

Men and women experience different barriers to care seeking for fecal incontinence.

BACKGROUND: Despite effective treatments for fecal incontinence (FI), FI remains underdiagnosed and undertreated. This study sought to characterize and compare rates of, delays in, experiences with, and barriers to care seeking for FI among men and women. METHODS: This study was a secondary analysis of electronic survey data collected from adults with FI. The survey included the use of a validated instrument to assess FI severity and questions that now comprise a validated instrument for assessing barriers to care seeking for FI in women. Descriptive analyses characterized differences between men and women. χ2 testing for categorical variables and t-testing for normally distributed continuous variables compared statistical differences. RESULTS: The sample (N = 548) was predominately female (84%), non-Hispanic White (90%), and insured (96%), with a mean Vaizey score (13.4 ± 5.3) consistent with moderate or severe FI. Care seeking rates (p = 0.81) and symptom duration before care seeking (p = 0.23) did not differ between women and men, but women were more likely than men to be told that effective treatments exist; most male and female respondents who sought care were offered treatment. Very few respondents had been asked about FI by a healthcare provider. Whereas normative thinking, limited life impact, and believing that a healthcare provider could not help were more common barriers to care seeking among men, avoidance, fear, and discouragement were more common in women. CONCLUSIONS: Men and women with FI seek care at similar rates and after experiencing symptoms for a similar duration of time. Very few patients with FI have been screened for it by a healthcare provider. Barriers to FI care seeking are different for women and men, and men are less likely than women to be informed about effective treatments by a healthcare provider.

Specificity of polygenic signatures across symptom dimensions in bipolar disorder: an analysis of UK Bipolar Disorder Research Network data.

BACKGROUND: Current definitions and clinical heterogeneity in bipolar disorder are major concerns as they obstruct aetiological research and impede drug development. Therefore, stratification of bipolar disorder is a high priority. To inform stratification, our analysis aimed to examine the patterns and relationships between polygenic liability for bipolar disorder, major depressive disorder (MDD), and schizophrenia with multidimensional symptom representations of bipolar disorder. METHODS: In this analysis, data from the UK Bipolar Disorder Research Network (BDRN) were assessed with the Operational Checklist for Psychotic Disorders. Individuals with bipolar disorder as defined in DSM-IV, of European ancestry (self-reported), aged 18 years or older at time of interview, living in the UK, and registered with the BDRN were eligible for inclusion. Psychopathological variables obtained via interview by trained research psychologists or psychiatrists and psychiatric case notes were used to identify statistically distinct symptom dimensions, calibrated with exploratory factor analysis and validated with confirmatory factor analysis (CFA). CFA was extended to include three polygenic risk scores (PRSs) indexing liability for bipolar disorder, MDD, and schizophrenia in a multiple indicator multiple cause (MIMIC) structural equation model to estimate PRS relationships with symptom dimensions. FINDINGS: Of 4198 individuals potentially eligible for inclusion, 4148 (2804 [67·6%] female individuals and 1344 [32·4%] male individuals) with a mean age at interview of 45 years (SD 12·03) were available for analysis. Three reliable dimensions (mania, depression, and psychosis) were identified. The MIMIC model fitted the data well (root mean square error of approximation 0·021, 90% CI 0·019-0·023; comparative fit index 0·99) and suggests statistically distinct symptom dimensions also have distinct polygenic profiles. The PRS for MDD was strongly associated with the depression dimension (standardised ß 0·125, 95% CI 0·080-0·171) and the PRS for schizophrenia was strongly associated with the psychosis dimension (0·108, 0·082-0·175). For the mania dimension, the PRS for bipolar disorder was weakly associated (0·050, 0·002-0·097). INTERPRETATION: Our findings support the hypothesis that genetic heterogeneity underpins clinical heterogeneity, suggesting that different symptom dimensions within bipolar disorder have partly distinct causes. Furthermore, our results suggest that a specific symptom dimension has a similar cause regardless of the primary psychiatric diagnosis, supporting the use of symptom dimensions in precision psychiatry. FUNDING: Wellcome Trust and UK Medical Research Council.

Microbiota produced indole metabolites disrupt host cell mitochondrial energy production and inhibit Cryptosporidium parvum growth.

Cryptosporidiosis is a leading cause of life-threatening diarrhea in young children in resource-poor settings. Susceptibility rapidly declines with age, associated with changes in the microbiota. To explore microbial influences on susceptibility, we screened 85 microbiota- associated metabolites enriched in the adult gut for their effects on C. parvum growth in vitro. We identified eight inhibitory metabolites in three main classes: secondary bile salts/acids, a vitamin B 6 precursor, and indoles. Growth restriction of C. parvum by indoles did not depend on the host aryl hydrocarbon receptor (AhR) pathway. Instead, treatment impaired host mitochondrial function and reduced total cellular ATP, as well as directly reduced the membrane potential in the parasite mitosome, a degenerate mitochondria. Oral administration of indoles, or reconstitution of the gut microbiota with indole producing bacteria, delayed life cycle progression of the parasite in vitro and reduced severity of C. parvum infection in mice. Collectively, these findings indicate that microbiota metabolites contribute to colonization resistance to Cryptosporidium infection.

Achieving integrated treatment: a realist synthesis of service models and systems for co-existing serious mental health and substance use conditions.

Approximately 30-50% of people with serious mental illness have co-existing drug or alcohol problems (COSMHAD), associated with adverse health and social care outcomes. UK guidelines advocate both co-occurring needs being met within mental health services, but uncertainty remains about how to operationalise this to improve outcomes. Various unevaluated service configurations exist in the UK. A realist synthesis was done to identify, test, and refine programme theories of how context shapes the mechanisms through which UK service models for COSMHAD work, for whom, and in what circumstances. Structured and iterative realist searches of seven databases identified 5099 records. A two-stage screening process identified 132 papers. Three broad contextual factors shaped COSMHAD services across 11 programme theories: committed leadership, clear expectations regarding COSMHAD from mental health and substance use workforces, and clear care-coordination processes. These contextual factors led to increased staff empathy, confidence, legitimisation, and multidisciplinary ethos, which improved care coordination and increased the motivation of people with COSMHAD to work towards their goals. Our synthesis highlights that integrating COSMHAD care is complex, and both individual and cultural behavioural shifts in leadership, workforce, and service delivery are essential to ensure people with COSMHAD receive compassionate, trauma-informed care that meets their needs.

Efficient Analysis of Proteome-wide FPOP Data by FragPipe.

Monitoring protein structure before and after perturbations can give insights into the role and function of proteins. Fast photochemical oxidation of proteins (FPOP) coupled with mass spectrometry (MS) allows monitoring of structural rearrangements by exposing proteins to OH radicals that oxidize solvent accessible residues, indicating protein regions undergoing movement. Some of the benefits of FPOP include high throughput and lack of scrambling due to label irreversibility. However, the challenges of processing FPOP data have thus far limited its proteome-scale uses. Here, we present a computational workflow for fast and sensitive analysis of FPOP datasets. Our workflow combines the speed of MSFragger search with a unique hybrid search method to restrict the large search space of FPOP modifications. Together, these features enable more than 10-fold faster FPOP searches that identify 50% more modified peptide spectra than previous methods. We hope this new workflow will increase the accessibility of FPOP to enable more protein structure and function relationships to be explored.

A mixed methods study to understand perinatal mental healthcare referral decisions among midwives and health visitors in the UK.

Background: In the UK approximately half of women requiring perinatal mental health (PNMH) care do not receive treatment despite having routine contact with midwives (MWs) and health visitors (HVs). Limited research has been undertaken regarding MWs'/HVs' decision-making around referring women for secondary PNMH care. In particular, the impact that the level of local secondary PNMH services may have on MWs'/HVs' referral decisions is unexplored. Aim: To understand MWs'/HVs' decision-making in relation to referring women with identified PNMH problems, to identify barriers and facilitators to effective and timely referrals including any impact of the local secondary PNMH service provision. Methods: Participants were recruited from four National Health Service (NHS) Trusts in England, located across two geographical areas, that provided different types of PNMH services. One area had PNMH services that met National Institute for Health and Care Excellence (NICE) guidelines; the other area had no secondary PNMH services. A sequential mixed methods design was used: In-depth semi-structured interviews with practising MWs/HVs (n = 24) to explore their approach to PNMH referral decision-making, analysed using thematic analysis; Questionnaire offered to all practising MWs/HVs in the two geographical areas to measure factors that may impact on PNMH referral decision-making allowing for statistical comparisons to be made between the professional groups/geographical areas. Findings: Three themes were identified from the interviews that impacted on MWs'/HVs' PNMH referral decision-making: identifying need; education, skills and experience; and referral pathways.Questionnaire response rate 13.1% (n = 99). The most reported facilitators to referral decision-making were a trusted relationship between MWs/HVs and women and routine enquiry about women's mental health; the most reported barriers were stigma associated with mental ill-health and women's perceived fear of child removal. Conclusion: Fundamental to MWs'/HVs' decision-making was their perceived relationship between themselves and women. Although PNMH service provision is important for women to ensure they receive appropriate PNMH care, service provision appeared less important to MWs'/HVs' referral decision-making than how maternity/health visiting services were delivered. Further important factors to MWs/HVs were to the ability to provide continuity of carer with women allowing MWs/HVs to identify women who would benefit from referral for secondary PNMH care.

Microbiota-produced indole metabolites disrupt mitochondrial function and inhibit Cryptosporidium parvum growth.

Cryptosporidiosis is a leading cause of life-threatening diarrhea in young children in resource-poor settings. To explore microbial influences on susceptibility, we screened 85 microbiota-associated metabolites for their effects on Cryptosporidium parvum growth in vitro. We identify eight inhibitory metabolites in three main classes: secondary bile salts/acids, a vitamin B6 precursor, and indoles. Growth restriction of C. parvum by indoles does not depend on the host aryl hydrocarbon receptor (AhR) pathway. Instead, treatment impairs host mitochondrial function and reduces total cellular ATP, as well as directly reducing the membrane potential in the parasite mitosome, a degenerate mitochondria. Oral administration of indoles, or reconstitution of the gut microbiota with indole-producing bacteria, delays life cycle progression of the parasite in vitro and reduces the severity of C. parvum infection in mice. Collectively, these findings indicate that microbiota metabolites impair mitochondrial function and contribute to colonization resistance to Cryptosporidium infection.