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Relative abundances of bacterial species in the gut microbiome have been linked to many diseases. Species of gut bacteria are ecologically differentiated by their abilities to metabolize different glycans, making glycan delivery a powerful way to alter the microbiome to promote health. Here, we study the properties and therapeutic potential of chemically diverse synthetic glycans (SGs). Fermentation of SGs by gut microbiome cultures results in compound-specific shifts in taxonomic and metabolite profiles not observed with reference glycans, including prebiotics. Model enteric pathogens grow poorly on most SGs, potentially increasing their safety for at-risk populations. SGs increase survival, reduce weight loss, and improve clinical scores in mouse models of colitis. Synthetic glycans are thus a promising modality to improve health through selective changes to the gut microbiome. Here, the authors characterize the gut microbiome fermentation properties and therapeutic potential of chemically diverse synthetic glycans (SGs), showing they promote specific shifts in taxonomic and metabolite profiles, and exhibit therapeutic benefits in mouse models of colonic inflammation, together implying SGs as a potential avenue to treat disease by modulating the composition and metabolites produced by the gut microbiome.

The mammalian central nervous system (CNS) contains a remarkable array of neural cells, each with a complex pattern of connections that together generate perceptions and higher brain functions. Here we describe a large-scale screen to create an atlas of CNS gene expression at the cellular level, and to provide a library of verified bacterial artificial chromosome (BAC) vectors and transgenic mouse lines that offer experimental access to CNS regions, cell classes and pathways. We illustrate the use of this atlas to derive novel insights into gene function in neural cells, and into principal steps of CNS development. The atlas, library of BAC vectors and BAC transgenic mice generated in this screen provide a rich resource that allows a broad array of investigations not previously available to the neuroscience community.

Background Transgender (trans) women face constrained access to gender-affirming HIV prevention and care. This is fueled in part by the convergence of limited trans knowledge and competency with anti-trans and HIV-related stigmas among social and healthcare providers. To advance gender-affirming HIV service delivery we implemented and evaluated ‘ Transgender Education for Affirmative and Competent HIV and Healthcare (TEACHH)’ . This theoretically-informed community-developed intervention aimed to increase providers’ gender-affirming HIV prevention and care knowledge and competency and reduce negative attitudes and biases among providers towards trans women living with and/or affected by HIV. Methods Healthcare and social service providers and providers in-training (e.g., physicians, nurses, social workers) working with trans women living with and/or affected by HIV ( n  = 78) participated in a non-randomized multi-site pilot study evaluating TEACHH with a pre-post-test design. Pre- and post-intervention surveys assessed participant characteristics, intervention feasibility (e.g., workshop completion rate) and acceptability (e.g., willingness to attend another training). Paired sample t-tests were conducted to assess pre-post intervention differences in perceived competency, attitudes/biases, and knowledge to provide gender-affirming HIV care to trans women living with HIV and trans persons. Results The intervention was feasible (100% workshop completion) and acceptable (91.9% indicated interest in future gender-affirming HIV care trainings). Post-intervention scores indicated significant improvement in: 1) knowledge, attitudes/biases and perceived competency in gender-affirming HIV care (score mean difference (MD) 8.49 (95% CI of MD: 6.12–10.86, p  < 0.001, possible score range: 16–96), and 2) knowledge, attitudes/biases and perceived competency in gender-affirming healthcare (MD = 3.21; 95% CI of MD: 1.90–4.90, p  < 0.001, possible score range: 9–63). Greater change in outcome measures from pre- to post-intervention was experienced by those with fewer trans and transfeminine clients served in the past year, in indirect service roles, and having received less prior training. Conclusions This brief healthcare and social service provider intervention showed promise in improving gender-affirming provider knowledge, perceived competency, and attitudes/biases, particularly among those with less trans and HIV experience. Scale-up of TEACHH may increase access to gender-affirming health services and HIV prevention and care, increase healthcare access, and reduce HIV disparities among trans women. Trial registration ClinicalTrials.gov ( NCT04096053 ).

Palliative day care programs in Canada and the United Kingdom Palliative Day Care Programs (PDCPs) offer people with advanced illnesses a place to receive medical, social, and emotional support while continuing to live at home. Fifty years after the first PDCP opened, this study examined which features of these programs have remained the same and which have changed, through an international comparison of four PDCPs in the United Kingdom and five in Canada. Using secondary analysis of 54 interviews with managers and professionals, we found that core elements—such as administrative structure, palliative care philosophy, and multidisciplinary teams—have endured over time. However, the populations served, models of care, and degree of institutionalization continue to evolve. While adapting to patients’ changing needs is essential, increasing pressure to demonstrate value for funding could unintentionally undermine the social and community values that make PDCPs unique, and that help people live meaningfully at home despite advanced illness.

IntroductionEducational workshops are a promising strategy to increase healthcare providers’ ability to provide gender-affirming care for transgender (trans) people. This strategy may also reduce healthcare providers’ stigma towards trans people and people living with HIV. There is less evidence, however, of educational workshops that address HIV prevention and care among trans women. This protocol details development and pilot testing of the Transgender Education for Affirmative and Competent HIV and Healthcare intervention that aims to increase gender-affirming HIV care knowledge and perceived competency, and to reduce negative attitudes/biases, among providers.Methods and analysisThis community-based research (CBR) project involves intervention development and implementation of a non-randomised multisite pilot study with pre–post test design. First, we conducted a qualitative formative phase involving focus groups with 30 trans women and individual interviews with 12 providers to understand HIV care access barriers for trans women and elicit feedback on a proposed workshop. Second, we will pilot test the intervention with 90–150 providers (n=30–50×3 in-person settings). For pilot studies, primary outcomes include feasibility (eg, completion rate) and acceptability (eg, workshop satisfaction). Secondary preintervention and postintervention outcomes, assessed directly preceding and following the workshop, include perceived competency, attitudes/biases towards trans women with HIV, and knowledge needed to provide gender-affirming HIV care. Primary outcomes will be summarised as frequencies and proportions (categorical variables). We will conduct paired-sample t-tests to explore the direction of preintervention and postintervention differences for secondary outcomes.Ethics and disseminationThis study has been approved by the University of Toronto HIV Research Ethics Board (Protocol Number: 00036238). Study findings will be disseminated through community forums with trans women and service providers; manuscripts submitted to peer reviewed journals; and conferences. Findings will inform a larger CBR research agenda to remove barriers to engagement in HIV prevention/care among trans women across Canada.Trial registration numberNCT04096053; Pre-results.

BackgroundIschemia is known to be a major contributor for anastomotic leaks and indocyanine green (ICYG) fluorescence angiography has been utilized to assess perfusion. Experienced esophageal surgeons have clinically assessed the gastric conduit with acceptable outcomes for years. We sought to examine the impact of ICYG in a surgeon’s decision-making during esophagectomy.MethodsWe queried a prospectively maintained database to identify patients who underwent robotic esophagectomy. Time to initial perfusion, time to maximum perfusion, and residual ischemia were measured and used as a guide to resection of residual stomach. During esophagectomy the surgeon identified the anticipated line of ischemic demarcation (LOD) prior to ICYG injection. The distance between the surgeon’s LOD and ICYG LOD was measured.ResultsWe identified 312 patients who underwent robotic esophagectomy, 251 without ICYG and 61 with ICGY. There were no differences in age, sex, race, body mass index, histology, stage, or neoadjuvant therapy use between groups. The incidence of anastomotic leak did not differ between groups (non-ICYG, 5.2% vs. ICYG, 6.6%), p = 0.67. The initial perfusion time was ≥ 10 s and max perfusion was > 25 s in all the patients in the ICYG that developed anastomotic leaks. All patients were noted to have at least 1 cm of residual gastric ischemia. Fifteen patients underwent independent surgeon evaluation of the ischemic LOD prior to ICYG. Differential distances were noted in 12 (80%) patients with a mean distance between surgical line of demarcation and ICYG LOD of 0.77 cm.ConclusionWhile the implementation of ICYG during esophagectomy demonstrates no significant improvements in anastomotic leak rates compared to historical controls, surgeon’s decision-making is impacted in 80% of cases resulting in additional resection of the gastric conduit. Elevated times to initial perfusion and maximum perfusion were associated with increased gastric ischemia and anastomotic leaks.

Middle ear myoclonus is a rare condition attributed to abnormal, repetitive contractions of the middle ear muscles including the tensor tympani and/or stapedius muscles. This condition generates objective tinnitus that is characterized by a \"clicking\" noise that is audible to both the patient and an outside observer. No specific pathophysiologic process has been identified as the cause of middle ear myoclonus, making its diagnosis and treatment challenging. In this report, we present a presumptive case of COVID-19-associated middle ear myoclonus in a 10-year-old male.

A hallmark of neurodegenerative proteinopathies is the formation of misfolded protein aggregates that cause cellular toxicity and contribute to cellular proteostatic collapse. Therapeutic options are currently being explored that target different steps in the production and processing of proteins implicated in neurodegenerative disease, including synthesis, chaperone-assisted folding and trafficking, and degradation via the proteasome and autophagy pathways. Other therapies, like mTOR inhibitors and activators of the heat shock response, can rebalance the entire proteostatic network. However, there are major challenges that impact the development of novel therapies, including incomplete knowledge of druggable disease targets and their mechanism of action as well as a lack of biomarkers to monitor disease progression and therapeutic response. A notable development is the creation of collaborative ecosystems that include patients, clinicians, basic and translational researchers, foundations and regulatory agencies to promote scientific rigor and clinical data to accelerate the development of therapies that prevent, reverse or delay the progression of neurodegenerative proteinopathies.

PurposeWe built Bayesian Network (BN) models to explain roles of different patient-specific factors affecting racial differences in breast cancer stage at diagnosis, and to identify healthcare related factors that can be intervened to reduce racial health disparities.MethodsWe studied women age 67–74 with initial diagnosis of breast cancer during 2006–2014 in the National Cancer Institute’s SEER-Medicare dataset. Our models included four measured variables (tumor grade, hormone receptor status, screening utilization and biopsy delay) expressed through two latent pathways-a tumor biology path, and health-care access/utilization path. We used various Bayesian model assessment tools to evaluate these two latent pathways as well as each of the four measured variables in explaining racial disparities in stage-at-diagnosis.ResultsAmong 3,010 Black non-Hispanic (NH) and 30,310 White NH breast cancer patients, respectively 70.2% vs 76.9% were initially diagnosed at local stage, 25.3% vs 20.3% with regional stage, and 4.56% vs 2.80% with distant stage-at-diagnosis. Overall, BN performed approximately 4.7 times better than Classification And Regression Tree (CART) (Breiman L, Friedman JH, Stone CJ, Olshen RA. Classification and regression trees. CRC press; 1984) in predicting stage-at-diagnosis. The utilization of screening mammography is the most prominent contributor to the accuracy of the BN model. Hormone receptor (HR) status and tumor grade are useful for explaining racial disparity in stage-at diagnosis, while log-delay in biopsy impeded good prediction.ConclusionsMammography utilization had a significant effect on racial differences in breast cancer stage-at-diagnosis, while tumor biology factors had less impact. Biopsy delay also aided in predicting local and regional stages-at-diagnosis for Black NH women but not for white NH women.

Background: Ground reaction force vectors (GRFv), lack of pelvic control, and gluteus medius strength have the potential to affect the load on the knee with single-leg activities. Previous research has shown trigger point dry needling (TDN) and electrical TDN have produced increases in muscle strength. To date, no trials have been found showing an effect on pelvic stabilization following TDN. Purpose: The purpose of this study was to determine how electrical trigger point dry needling to the gluteus medius muscle will affect muscle function, pelvic stability, and GRFv during a single leg drop test. Methods: This pilot study used a quantitative experimental design consisting of 17 subjects to compare performance of a single leg step down before and after the use of dry needling to the gluteus medius muscle. Noraxon® Ulitum-wireless motion sensors and Noraxon MyoResearch 3.20 were used to obtain GRFv and pelvic tilt angle. Subjects also had gluteus medius strength tested using a hand held dynamometer before and after TDN with a Pointer Excel II LT Stimulator. Results: Following the dry needling intervention, no significant difference was found in hip abduction strength, lateral pelvic tilt range, and GRFz, as a p-value > 0.05 (0.72, 0.8, 0.51) was found following a paired t-test. Discussion/Conclusion: Inadequate sample size is one limitation to this study which may have contributed to the results shown. Further consideration of palpating for a latent versus active trigger point prior to TDN could have been further explored as it may play a role in results. Results from similar studies showed increases in muscle strength following TDN. Varying needle techniques should be further explored to determine the most effective method. More research is recommended in order to obtain a better picture of TDN and its effects on these variables.