Associations of a multidimensional polygenic sleep health score and a sleep lifestyle index on health outcomes and their interaction in a clinical biobank.

Sleep is a complex behavior regulated by genetic and environmental factors, and is known to influence health outcomes. However, the effect of multidimensional sleep encompassing several sleep dimensions on diseases has yet to be fully elucidated. Using the Mass General Brigham Biobank, we aimed to examine the association of multidimensional sleep with health outcomes and investigate whether sleep behaviors modulate genetic predisposition to unfavorable sleep on mental health outcomes. First, we generated a Polygenic Sleep Health Score using previously identified single nucleotide polymorphisms for sleep health and constructed a Sleep Lifestyle Index using data from self-reported sleep questions and electronic health records; second, we performed phenome-wide association analyses between these indexes and clinical phenotypes; and third, we analyzed the interaction between the indexes on prevalent mental health outcomes. Fifteen thousand eight hundred and eighty-four participants were included in the analysis (mean age 54.4; 58.6% female). The Polygenic Sleep Health Score was associated with the Sleep Lifestyle Index (ß=0.050, 95%CI=0.032, 0.068) and with 114 disease outcomes spanning 12 disease groups, including obesity, sleep, and substance use disease outcomes (p<3.3×10-5). The Sleep Lifestyle Index was associated with 458 disease outcomes spanning 17 groups, including sleep, mood, and anxiety disease outcomes (p<5.1×10-5). No interactions were found between the indexes on prevalent mental health outcomes. These findings suggest that favorable sleep behaviors and genetic predisposition to healthy sleep may independently be protective of disease outcomes. This work provides novel insights into the role of multidimensional sleep on population health and highlights the need to develop prevention strategies focused on healthy sleep habits.

The Role of Circadian Rhythms and Sleep in Anorexia Nervosa.

Importance: Observational studies have associated anorexia nervosa with circadian rhythms and sleep traits. However, the direction of causality and the extent of confounding by psychosocial comorbidities in these associations are unknown. Objectives: To investigate the association between anorexia nervosa and circadian and sleep traits through mendelian randomization and to test the associations between a polygenic risk score (PRS) for anorexia nervosa and sleep disorders in a clinical biobank. Design, Setting, and Participants: This genetic association study used bidirectional 2-sample mendelian randomization with summary-level genetic associations between anorexia nervosa (from the Psychiatric Genomics Consortium) and chronotype and sleep traits (primarily from the UK Biobank). The inverse-variance weighted method, in addition to other sensitivity approaches, was used. From the clinical Mass General Brigham (MGB) Biobank (n = 47 082), a PRS for anorexia nervosa was calculated for each patient and associations were tested with prevalent sleep disorders derived from electronic health records. Patients were of European ancestry. All analyses were performed between February and August 2023. Exposures: Genetic instruments for anorexia nervosa, chronotype, daytime napping, daytime sleepiness, insomnia, and sleep duration. Main Outcomes and Measures: Chronotype, sleep traits, risk of anorexia nervosa, and sleep disorders derived from a clinical biobank. Results: The anorexia nervosa genome-wide association study included 16 992 cases (87.7%-97.4% female) and 55 525 controls (49.6%-63.4% female). Genetic liability for anorexia nervosa was associated with a more morning chronotype (ß = 0.039; 95% CI, 0.006-0.072), and conversely, genetic liability for morning chronotype was associated with increased risk of anorexia nervosa (ß = 0.178; 95% CI, 0.042-0.315). Associations were robust in sensitivity and secondary analyses. Genetic liability for insomnia was associated with increased risk of anorexia nervosa (ß = 0.369; 95% CI, 0.073-0.666); however, sensitivity analyses indicated bias due to horizontal pleiotropy. The MGB Biobank analysis included 47 082 participants with a mean (SD) age of 60.4 (17.0) years and 25 318 (53.8%) were female. A PRS for anorexia nervosa was associated with organic or persistent insomnia in the MGB Biobank (odds ratio, 1.10; 95% CI, 1.03-1.17). No associations were evident for anorexia nervosa with other sleep traits. Conclusions and Relevance: The results of this study suggest that in contrast to other metabo-psychiatric diseases, anorexia nervosa is a morningness eating disorder and further corroborate findings implicating insomnia in anorexia nervosa. Future studies in diverse populations and with subtypes of anorexia nervosa are warranted.

Gynecological concerns and vaginal practices and exposures among transfeminine individuals who have undergone vaginoplasty.

BACKGROUND: Vaginoplasty is a gender-affirming surgery that is medically necessary for some transfeminine individuals. Little research exists describing vaginal health after the initial recovery from surgery, and evidence-based guidelines for vaginal care practices are unavailable. AIM: The study sought to describe self-reported gynecological concerns and vaginal care practices among transfeminine persons who have undergone vaginoplasty. METHODS: A total of 60 transfeminine participants 18+ years of age, living in Canada, and who had undergone vaginoplasty at least 1 year prior were recruited through social media, community groups, healthcare provider referrals, and study recontact. Participants completed a cross-sectional, online questionnaire detailing demographics, gynecological concerns, and genital practices and exposures. Hierarchical clustering was used to group participants based on behavioral practices and exposures. Associations between clusters and gynecological concerns were assessed. OUTCOMES: Outcomes included self-reported gynecological concerns within the past year, recent vulvar or vaginal symptoms (past 30 days), and behavioral practices/exposures, including douching with varied products and dilating. RESULTS: Participants reported a variety of concerns in the past year, including urinary tract infection (13%) and internal hair regrowth (23%). More than half (57%) had experienced at least 1 recent vaginal symptom, most commonly malodor (27%) and vaginal bleeding (21%). Of participants, 48% were dilating weekly and 52% reported douching in the past 30 days. Four distinct clusters of vaginal practices/exposures were identified: limited exposures; dilating, no douching; dilating and douching; and diverse exposures. No significant associations between cluster membership and gynecological concerns were identified, though cluster membership was significantly associated with surgical center (P = .03). Open-text write-ins provided descriptions of symptoms and symptom management strategies. CLINICAL IMPLICATIONS: The results provide insight for clinicians on common patient-reported gynecological concerns and current vaginal care practices and exposures, including symptom management strategies. STRENGTHS AND LIMITATIONS: This was the first study to investigate vaginal health and genital practices/exposures among a community sample of transfeminine individuals. As participants self-enrolled for a detailed survey and swab collection, individuals experiencing concerns were likely overrepresented. CONCLUSION: Transfeminine individuals reported a range of gynecological concerns outside of the surgical healing period. Genital practices/exposures varied across clusters, but no clear associations between clusters and symptoms were identified; instead, practice/exposure clusters were dependent on where the individual underwent vaginoplasty. There is a need for evidence to inform diagnostics, treatments, and vaginal care guidelines to support vaginal health.

Fecal microbiota transplantation is safe and tolerable in patients with multiple sclerosis: A pilot randomized controlled trial.

Background: Patients with MS have an altered gut microbiota compared to healthy individuals, as well as elevated small intestinal permeability, which may be contributing to the development and progression of the disease. Objective: We sought to investigate if fecal microbiota transplantation was safe and tolerable in MS patients and if it could improve abnormal intestinal permeability. Methods: Nine patients with MS were recruited and provided monthly FMTs for up to six months. The primary outcome investigated was change in peripheral blood cytokine concentrations. The secondary outcomes were gut microbiota composition, intestinal permeability, and safety (assessed with EDSS and MRI). Results: The study was terminated early and was subsequently underpowered to assess whether peripheral blood cytokines were altered following FMTs. FMTs were safe in this group of patients. Two of five patients had elevated small intestinal permeability at baseline that improved to normal values following FMTs. Significant, donor-specific, beneficial alterations to the MS patient gut microbiota were observed following FMT. Conclusion: FMT was safe and tolerable in this cohort of RRMS patients, may improve elevated small intestinal permeability, and has the potential to enrich for an MS-protective microbiota. Further studies with longer follow-up and larger sample sizes are required to determine if FMT is a suitable therapy for MS.

Use of Erector Spinae Fascial Plane Blocks in Enhanced Recovery for Open Abdominal Surgery.

BACKGROUND: Bilateral erector spinae fascial plane blocks (ESPB) offers a novel, alternative method of regional post-operative pain control to thoracic epidural analgesia (TEA). The aim of this study was to compare rates of postoperative hypotension, and other standard enhanced recovery after surgery (ERAS) endpoints, in patients receiving ESPB versus TEA for open hepatopancreaticobiliary (HPB) surgery. MATERIALS AND METHODS: This retrospective analysis compared historical controls of ERAS patients undergoing open HPB surgery with TEA versus ESPB. The incidence of postoperative hypotension and clinical outcomes, including opioid requirements, were compared. RESULTS: Forty patients receiving TEA were compared to 27 ESPB patients. Return of bowel function and length of stay (mean 7.2 versus7.4 days; P = 0.83) were similar. ESPB patients received less intraoperative colloid (142cc versus 340cc; P = 0.01) and had less postoperative hypotension versus TEA (22% versus 55%; P = 0.03). No ESPB patient required patient-controlled analgesia (versus 32.5% TEA; P< 0.001). ESPB MME requirements decreased over time, while TEA MME requirements increased over 72 hours (P = 0.019). CONCLUSIONS: ESPB is a novel method that shows promising outcomes in improving enhanced recovery parameters and minimizing opioid administration in open HPB surgery.

Deciphering the low abundance microbiota of presumed aseptic hip and knee implants.

16S rRNA gene sequencing of DNA extracted from clinically uninfected hip and knee implant samples has revealed polymicrobial populations. However, previous studies assessed 16S rRNA gene sequencing as a technique for the diagnosis of periprosthetic joint infections, leaving the microbiota of presumed aseptic hip and knee implants largely unstudied. These communities of microorganisms might play important roles in aspects of host health, such as aseptic loosening. Therefore, this study sought to characterize the bacterial composition of presumed aseptic joint implant microbiota using next generation 16S rRNA gene sequencing, and it evaluated this method for future investigations. 248 samples were collected from implants of 41 patients undergoing total hip or knee arthroplasty revision for presumed aseptic failure. DNA was extracted using two methodologies-one optimized for high throughput and the other for human samples-and amplicons of the V4 region of the 16S rRNA gene were sequenced. Sequencing data were analyzed and compared with ancillary specific PCR and microbiological culture. Computational tools (SourceTracker and decontam) were used to detect and compensate for environmental and processing contaminants. Microbial diversity of patient samples was higher than that of open-air controls and differentially abundant taxa were detected between these conditions, possibly reflecting a true microbiota that is present in clinically uninfected joint implants. However, positive control-associated artifacts and DNA extraction methodology significantly affected sequencing results. As well, sequencing failed to identify Cutibacterium acnes in most culture- and PCR-positive samples. These challenges limited characterization of bacteria in presumed aseptic implants, but genera were identified for further investigation. In all, we provide further support for the hypothesis that there is likely a microbiota present in clinically uninfected joint implants, and we show that methods other than 16S rRNA gene sequencing may be ideal for its characterization. This work has illuminated the importance of further study of microbiota of clinically uninfected joint implants with novel molecular and computational tools to further eliminate contaminants and artifacts that arise in low bacterial abundance samples.

The Effect of Gender-Affirming Medical Care on the Vaginal and Neovaginal Microbiomes of Transgender and Gender-Diverse People.

Transgender and gender diverse individuals may seek gender-affirming medical care, such as hormone therapy or surgery, to produce primary and/or secondary sex characteristics that are more congruent with their gender. Gender-affirming medical care for transmasculine individuals can include testosterone therapy, which suppresses circulating estrogen and can lead to changes in the vaginal epithelium that are reminiscent of the post-menopausal period in cisgender females. Among transfeminine individuals, gender-affirming medical care can include vaginoplasty, which is the surgical creation of a vulva and neovaginal canal, commonly using penile and scrotal skin. The effect of gender-affirming medical care on the vagina of transmasculine individuals and on the neovagina of transfeminine individuals is poorly characterized. This review summarizes what is known of the epithelium and local microbiota of the testosterone-exposed vagina and the neovagina. We focus on potential pathogens and determinants of gynecological health and identify key knowledge gaps for future research.

Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients.

Abiraterone acetate (AA) is an inhibitor of androgen biosynthesis, though this cannot fully explain its efficacy against androgen-independent prostate cancer. Here, we demonstrate that androgen deprivation therapy depletes androgen-utilizing Corynebacterium spp. in prostate cancer patients and that oral AA further enriches for the health-associated commensal, Akkermansia muciniphila. Functional inferencing elucidates a coinciding increase in bacterial biosynthesis of vitamin K2 (an inhibitor of androgen dependent and independent tumor growth). These results are highly reproducible in a host-free gut model, excluding the possibility of immune involvement. Further investigation reveals that AA is metabolized by bacteria in vitro and that breakdown components selectively impact growth. We conclude that A. muciniphila is a key regulator of AA-mediated restructuring of microbial communities, and that this species may affect treatment response in castrate-resistant cohorts. Ongoing initiatives aimed at modulating the colonic microbiota of cancer patients may consider targeted delivery of poorly absorbed selective bacterial growth agents.

COVID-19 global pandemic planning: Decontamination and reuse processes for N95 respirators.

IMPACT STATEMENT: There is a critical shortage of personal protective equipment (PPE) around the globe. This article describes the safe collection, storage, and decontamination of N95 respirators using hydrogen peroxide vapor (HPV). This article is unique because it describes the HPV process in an operating room, and is therefore, a deployable method for many healthcare settings. Results presented here offer creative solutions to the current PPE shortage.

Expired probiotics: what is really in your cabinet?

The popularity of using probiotics has surged, since they became widely accepted as safe and help improve general health. Inevitably, some of these products are used after expiration when microbial cell viability is below the recommended effective dose. Given that probiotics must be live microorganisms administered in adequate amounts, the aim of this study was to measure viability in expired products and assess how packaging and storage conditions impact efficacy, if at all. Thirty-three expired probiotic products were evaluated, of which 26 were stored in conditions recommended by the manufacturer. The viable microbial cells were enumerated and representative isolates identified by 16S and internally transcribed spacer rRNA gene sequencing. While the products had a mean past expiration time of 11.32 (1-22) years, 22 still had viable contents, and 5 were within or above the original product cell count claim. Product formulation and the number of species present did not appear to impact the stability of the products. However, overall packaging type, storage conditions and time since expiry were found to affect viability. All products with viable cells had the strain stipulated on the label. Despite some selected probiotic products retaining viability past their expiry date (indicating long-term storage is possible), the total counts were mostly well below that required for efficacious use as recommended by the manufacturer. Consuming expired probiotics may not yield the benefits for which they were designed.

A pilot study of fascia Bowen therapy for 8-11 year-old boys with developmental coordination disorder.

BACKGROUND: Developmental coordination disorder (DCD), also known as dyspraxia, is a disorder emerging in childhood characterised by motor skill impairments. The motor difficulties often produce negative effects in other areas of life, such as poor self-esteem and reduced social interactions. One treatment used for DCD is fascia Bowen therapy, which involves stimulating the fascia tissues of the body using finger and thumb rolling movements over the skin to improve overall muscle movement. However, no studies to date have been reported testing the effectiveness of fascia Bowen in DCD. METHODS: The present pilot study tested the effectiveness of 6 weeks of fascia Bowen in 10 boys aged 8-11 years with DCD. None of the boys had ever received treatment in any form before this study. Motor skills were assessed using the Movement Assessment Battery for Children-2 (MABC-2) and the DCD questionnaire, and psycho-social functioning was measured using the Self-Perception Profile, Spence Social Skills Questionnaire, and Strengths and Difficulties Questionnaire. All measures of interest were assessed before and after the therapy. RESULTS: Results showed significant improvement in motor function post-intervention, with 60% of the children no longer clinically being classified as having a movement difficulty on the MABC-2. However, no significant improvements were seen in psycho-social measures, at least within the short time-frame of the therapy in the current study. CONCLUSIONS: The current pilot study revealed improvements in motor functioning after fascia Bowen therapy, across both performance and questionnaire measures, but that these improvements did not extend to wider areas of life. Further research in DCD is needed to test the effectiveness of fascia Bowen in larger studies with expanded ages and both genders over longer periods, including the generalisation of results of these longer interventions to different areas of life beyond motor ability.

Inflatable Penile Prostheses Implantation: Does Antibiotic Exposure Matter?

BACKGROUND: Inflatable penile prosthetic (IPP) infections are unusual but carry high patient morbidity and healthcare costs. AIM: To increase the bactericidal effect of IPP tubing material to prevent future bacterial infections and to determine whether this effect is time-dependent. METHODS: A modified disk diffusion assay was developed to measure the zones of inhibition against Escherichia coli, Proteus mirabilis, Staphylococcus aureus, and Staphylococcus epidermidis when tubing was immersed in gentamycin, ampicillin, tetracycline, kanamycin, erythromycin, or ciprofloxacin. To further assess the efficacy of this approach, IPP tubing was exposed to ampicillin or ciprofloxacin for 30 seconds, 2 minutes, 10 minutes, or 60 minutes. OUTCOMES: Bacterial zones of inhibition against IPP tubing material exposed to various treatments. RESULTS: IPP tubing was more effective against Gram-positive bacteria (S aureus and S epidermidis) then Gram-negative bacteria (E coli and P mirabilis). Immersing IPP tubing material in ampicillin or ciprofloxacin increased bactericidal effect of tubing material against Gram-positive and Gram-negative bacteria, respectively. The observed inhibitory effect was time dependent. CLINICAL TRANSLATION: Exposing IPP to a specific antimicrobial directly before implantation increases the bactericidal properties of the material, potentially decreasing the likelihood of infection. STRENGTHS & LIMITATIONS: This study is limited in that it is in vitro experimentation observing the effect of a single strain of each bacterium. Although the strains used were clinically relevant, further analysis is required to determine whether these results were strain specific. CONCLUSION: Immersing IPP material into an antibiotic solution, such as ampicillin or ciprofloxacin, increases the bactericidal properties and may aid in the prevention of infection. Chanyi RM, Alzubaidi R, Leung EJY, Wilcox HB, Brock GB, Burton JP. Inflatable Penile Prostheses Implantation: Does Antibiotic Exposure Matter? Sex Med 2018;6;248-254.