Examining the quality of news media reporting of complex mental illness in relation to violent crime in Australia.

PURPOSE: News reporting on mental illness can perpetuate stigma. An understanding of the current picture of such reporting is important to identify areas for improvement. This study investigated the quality of Australian news media coverage of complex mental illness in the context of crime and violence over a 2-year period, prior to the release of new media guidelines. METHODS: This research utilised a systematic search of Australian news articles that were published between July 2018 and July 2020 and reported on mental illness in relation to violent crime. Researchers developed a Mental Illness and Crime Reporting Quality Framework to determine quality scores for news articles according to 11 relevant factors in media guidelines. An additional 11 characteristics of articles were extracted for further descriptive analysis. RESULTS: One-hundred and twenty-eight Australian news articles met inclusion criteria. The average quality score was 50 (SD = 13.91) out of a possible maximum score of 100 (range 11-78). Strengths and weaknesses were identified as some criteria were consistently met, and other criteria were met rarely or not at all. There were emerging trends between quality scores and article characteristics, including publication source, though these analyses were not statistically significant. CONCLUSION: The findings indicate that Australian news coverage of complex mental illness and violent crime met half of the criteria of reporting guidelines that minimises risk of perpetuating or reinforcing stigma. This demonstrates significant opportunity to improve the overall quality of media reporting on crime and mental illness. Future research should evaluate the impact of the guidelines on the quality of news reporting after their implementation by utilising a similar methodology, using these findings as a baseline measure.

Central in vivo mechanisms by which C. difficile's proline reductase drives efficient metabolism, growth, and toxin production.

Clostridioides difficile (CD) is a sporulating and toxin-producing nosocomial pathogen that opportunistically infects the gut, particularly in patients with depleted microbiota after antibiotic exposure. Metabolically, CD rapidly generates energy and substrates for growth from Stickland fermentations of amino acids, with proline being a preferred reductive substrate. To investigate the in vivo effects of reductive proline metabolism on C. difficile's virulence in an enriched gut nutrient environment, we evaluated wild-type and isogenic ΔprdB strains of ATCC43255 on pathogen behaviors and host outcomes in highly susceptible gnotobiotic mice. Mice infected with the ΔprdB mutant demonstrated extended survival via delayed colonization, growth and toxin production but ultimately succumbed to disease. In vivo transcriptomic analyses demonstrated how the absence of proline reductase activity more broadly disrupted the pathogen's metabolism including failure to recruit oxidative Stickland pathways, ornithine transformations to alanine, and additional pathways generating growth-promoting substrates, contributing to delayed growth, sporulation, and toxin production. Our findings illustrate the central role for proline reductase metabolism to support early stages of C. difficile colonization and subsequent impact on the pathogen's ability to rapidly expand and cause disease.

The Effect of the Rate of Increase of Estrogen Replacement Therapy on Bone Mineral Density Accrual in Young Patients with Turner Syndrome.

BACKGROUND: Turner syndrome (TS) is caused by partial/complete X-chromosome monosomy with variable phenotypes, characterized by hypogonadism and short stature. To achieve pubertal changes, up to 50%-79% of patients with TS require estrogen replacement therapy (ERT), and 80% have low bone mineral density (BMD). Studies show that pubertal delays are associated with decreased BMD. Currently, guidelines suggest that ERT start at 12 years, increasing slowly, simulating pubertal progression. Many studies show that ERT increases BMD in adolescents with TS, but uncertainty remains as to how the rate of increase in ERT affects BMD. METHODS: Institutional review board approval was obtained from our institution for this retrospective chart review from 1991 to 2020. Charts were requested for the database using ICD 9-10 codes for TS and patients undergoing dual-energy X-ray absorptiometry. Biometric data and medical and treatment histories were extracted from charts. Multilevel random effects models were constructed to assess the time-dependent associations between ERT and bone density parameters. The primary independent variable of interest was the rate at which patients went from initiating ERT to reaching final doses. The primary dependent variables measured were total body BMD (tbBMD) and corresponding z-scores, calculated using dual-energy X-ray absorptiometry techniques. Analyses were done with SAS software (version 9.4, Cary, NC). RESULTS: Twenty-eight patients met the inclusion criteria. The mean age at TS diagnosis was 6.9 years; 8 patients had monosomy X, 16 had mosaic karyotypes, and 4 had unknown karyotypes. The average age for starting hormone replacement therapy was 14.1 years. Thirteen patients had spontaneous pubertal onset before starting hormone replacement therapy. tbBMD increased significantly with age (P = .03). However, change in BMD by age did not vary between patients who reached final adult doses of ERT within 0-2.5 years compared with patients who took 2.5-5.5 years (P = .7). Patients who took 2.5-5.5 years to reach final adult doses of ERT had a more negative trend in z-scores (-2.144) in comparison with patients who took 0-2.5 years (-1.776), although this difference did not reach statistical significance (P = .15). Future larger studies are needed to better understand the relationship between duration of ERT use and tbBMD. CONCLUSION: BMD in adolescents with TS increases with age. Neither absolute tbBMD values nor tbBMD z-scores increased faster when ERT doses were maximized within 2.5 years. This study identified a cohort of children under 12 years with TS who had not had any ERT or BMD measurements, a potential population for future larger prospective studies.

Estradiol-mediated protection against high-fat diet induced anxiety and obesity is associated with changes in the gut microbiota in female mice.

Decreased estrogens during menopause are associated with increased risk of anxiety, depression, type 2 diabetes and obesity. Similarly, depleting estrogens in rodents by ovariectomy, combined with a high-fat diet (HFD), increases anxiety and adiposity. How estrogens and diet interact to affect anxiety and metabolism is poorly understood. Mounting evidence indicates that gut microbiota influence anxiety and metabolism. Here, we investigated the effects of estradiol (E) and HFD on anxiety, metabolism, and their correlation with changes in gut microbiota in female mice. Adult C57BL/6J mice were ovariectomized, implanted with E or vehicle-containing capsules and fed a standard diet or HFD. Anxiety-like behavior was assessed and neuronal activation was measured by c-fos immunoreactivity throughout the brain using iDISCO. HFD increased anxiety-like behavior, while E reduced this HFD-dependent anxiogenic effect. Interestingly, E decreased neuronal activation in brain regions involved in anxiety and metabolism. E treatment also altered gut microbes, a subset of which were associated with anxiety-like behavior. These findings provide insight into gut microbiota-based therapies for anxiety and metabolic disorders associated with declining estrogens in menopausal women.

Differential effects of Akkermansia-enriched fecal microbiota transplant on energy balance in female mice on high-fat diet.

Estrogens protect against weight gain and metabolic disruption in women and female rodents. Aberrations in the gut microbiota composition are linked to obesity and metabolic disorders. Furthermore, estrogen-mediated protection against diet-induced metabolic disruption is associated with modifications in gut microbiota. In this study, we tested if estradiol (E2)-mediated protection against obesity and metabolic disorders in female mice is dependent on gut microbiota. Specifically, we tested if fecal microbiota transplantation (FMT) from E2-treated lean female mice, supplemented with or without Akkermansia muciniphila, prevented high fat diet (HFD)-induced body weight gain, fat mass gain, and hyperglycemia in female recipients. FMT from, and cohousing with, E2-treated lean donors was not sufficient to transfer the metabolic benefits to the E2-deficient female recipients. Moreover, FMT from lean donors supplemented with A. muciniphila exacerbated HFD-induced hyperglycemia in E2-deficient recipients, suggesting its detrimental effect on the metabolic health of E2-deficient female rodents fed a HFD. Given that A. muciniphila attenuates HFD-induced metabolic insults in males, the present findings suggest a sex difference in the impact of this microbe on metabolic health.

Reconsidering the in vivo functions of Clostridial Stickland amino acid fermentations.

Stickland amino acid fermentations occur primarily among species of Clostridia. An ancient form of metabolism, Stickland fermentations use amino acids as electron acceptors in the absence of stronger oxidizing agents and provide metabolic capabilities to support growth when other fermentable substrates, such as carbohydrates, are lacking. The reactions were originally described as paired fermentations of amino acid electron donors, such as the branched-chain amino acids, with recipients that include proline and glycine. We present a redox-focused view of Stickland metabolism following electron flow through metabolically diverse oxidative reactions and the defined-substrate reductase systems, including for proline and glycine, and the role of dual redox pathways for substrates such as leucine and ornithine. Genetic studies and Environment and Gene Regulatory Interaction Network (EGRIN) models for the pathogen Clostridioides difficile have improved our understanding of the regulation and metabolic recruitment of these systems, and their functions in modulating inter-species interactions within host-pathogen-commensal systems and uses in industrial and environmental applications.

Protocol for using negative pressure isolator systems to study BSL-2 organisms in gnotobiotic murine models.

Here, we present a protocol for the use of negative pressure isolator systems to maintain defined association and contain BSL-2 pathogens in germ-free and gnotobiotic mouse studies. We describe setup and operation of negative pressure isolators with integrated microbiologic procedures, using the BSL-2 pathogen Clostridioides difficile as a working example. This approach supports experimental systems with defined-association mice and enables high-resolution mechanistic studies of pathogen-commensal interactions and their impacts on host phenotypes. For complete details on the use and execution of this protocol, please refer to Girinathan et al. (2021).

Distinct Changes in Gut Microbiota Are Associated with Estradiol-Mediated Protection from Diet-Induced Obesity in Female Mice.

A decrease in ovarian estrogens in postmenopausal women increases the risk of weight gain, cardiovascular disease, type 2 diabetes, and chronic inflammation. While it is known that gut microbiota regulates energy homeostasis, it is unclear if gut microbiota is associated with estradiol regulation of metabolism. In this study, we tested if estradiol-mediated protection from high-fat diet (HFD)-induced obesity and metabolic changes are associated with longitudinal alterations in gut microbiota in female mice. Ovariectomized adult mice with vehicle or estradiol (E2) implants were fed chow for two weeks and HFD for four weeks. As reported previously, E2 increased energy expenditure, physical activity, insulin sensitivity, and whole-body glucose turnover. Interestingly, E2 decreased the tight junction protein occludin, suggesting E2 affects gut epithelial integrity. Moreover, E2 increased Akkermansia and decreased Erysipleotrichaceae and Streptococcaceae. Furthermore, Coprobacillus and Lactococcus were positively correlated, while Akkermansia was negatively correlated, with body weight and fat mass. These results suggest that changes in gut epithelial barrier and specific gut microbiota contribute to E2-mediated protection against diet-induced obesity and metabolic dysregulation. These findings provide support for the gut microbiota as a therapeutic target for treating estrogen-dependent metabolic disorders in women.

Gut and vaginal microbiomes on steroids: implications for women's health.

This review discusses the interactions of steroids with the gut and vaginal microbiomes within each life phase of adult women and the implications for women's health. Each phase of a woman's life is characterized by distinct hormonal states which drive overall physiology of both host and commensal microbes. These host-microbiome interactions underlie disease pathology in disorders that affect women across their lifetime, including bacterial vaginosis, gestational diabetes, polycystic ovary syndrome (PCOS), anxiety, depression, and obesity. Although many associations between host health and microbiome composition are well defined, the mechanistic role of the microbiome in women's health outcomes is largely unknown. This review addresses potential mechanisms by which the microbiota influences women's health and highlights gaps in current knowledge.