Examining Cultural Competency and Sexual Abuse Training Needs Among Service Providers Working with Black and Latino Sexual Minority Men.

Black and Latino sexual minority men (SMM) with a history of childhood sexual abuse (CSA) may be reluctant to disclose such experiences or may appraise them as consensual because of cultural norms. Anticipated stigma, medical mistrust, and concerns that providers lack training in sexuality may complicate their efforts to obtain treatment for long-term health consequences of CSA. It is important to examine the training needs of service providers working with SMM who may disclose sexual abuse. Qualitative interviews were conducted with 35 substance use disorder (SUD) treatment and allied health service providers across the New York City area. Themes included the importance of training in cultural competence, trauma-informed care, and assessment of-and counseling for-CSA. Further education in these areas can enable providers to recognize indicators of abuse in their clients' sexual histories and to more effectively and safely respond to this information. Future studies are encouraged to test a trauma-informed approach to screening for CSA history with Black and Latino SMM who present to SUD treatment and allied health service providers. This research should consider provider perspectives in developing such an approach and will likely involve training and evaluation to ensure adequate preparedness and effective service delivery.

HDACi-dependent Microenvironmental Normalization Overcomes Tumor Burden-induced T-cell Exhaustion.

PURPOSE: T-cell exhaustion limits immunotherapy for the treatment of solid tumors. Although immune checkpoint blockade and adoptive T-cell therapy (ACT) can mediate tumor regression, their potency is often determined by tumor burden. Here, we identified tumor burden-related pathway changes that are conducive to T-cell exhaustion. We then determined whether microenvironmental reprogramming via epigenetic modulation could reverse T-cell exhaustion and improve immunotherapeutic responsiveness. EXPERIMENTAL DESIGN: We developed a murine syngeneic tumor model wherein an increased burden ablated therapeutic responsiveness to ACT, which corresponded with systemic induction of T-cell exhaustion. Transcriptome analysis of these large tumors allowed us to characterize changes to immunosuppressive pathway expression during class I histone deacetylase inhibitor MS-275 treatment. We then measured the therapeutic impact of MS-275 during ACT and assessed T-cell exhaustion by transcriptome/phenotypic analysis. RESULTS: ACT durably regressed small tumors but failed to control large tumors, which were associated with systemic T-cell exhaustion and ablation of T-cell responses. Large tumors were defined by an immunosuppressive pathway signature. MS-275 reversed this pathway signature and promoted durable regression of large tumors during ACT. Prototypical exhaustion marker Tim-3 was selectively upregulated in transferred T cells despite displaying a reduced exhaustion signature. Instead, we observed enhanced activation-dependent signaling correlating with enrichment of the IL2-STAT5 signaling axis. Activated CD8+ T-cell responses were predominantly skewed toward terminal effector cell-like CD44+ Tim-3hi TCF1- CD127- KLRG1+ differentiation. CONCLUSIONS: Tumor burden-induced pathway changes can be reversed through epigenetic reprogramming, enabling the conversion from T-cell exhaustion to effector lineage differentiation.

Facilitation of team-based care to improve HTN management and outcomes: a protocol for a randomized stepped wedge trial.

BACKGROUND: There are well-established guidelines for treating hypertension (HTN), yet only half of patients with HTN meet the defined target of < 140/90. Team-based care (TBC) is an evidence-based strategy for improving blood pressure (BP) management and control. TBC is defined as the provision of health services by at least two health professionals "who work collaboratively with patients and their caregivers to accomplish shared goals to achieve coordinated, high-quality care". However, primary care practices experience challenges to implementing TBC principles and care processes; these are more pronounced in small independent practice settings (SIPs). Practice facilitation (PF) is an implementation strategy that may overcome barriers to adopting evidence-based TBC to improve HTN management in SIPs. METHODS: Using a stepped wedge randomized controlled trial design, we will test the effect of PF on the adoption of TBC to improve HTN management in small practices (< 5 FTE clinicians) in New York City, and the impact on BP control compared with usual care. We will enroll 90 SIPs and randomize them into one of three 12-month intervention waves. Practice facilitators will support SIPs to adopt TBC principles to improve implementation of five HTN management strategies (i.e., panel management, population health, measuring BP, supporting medication adherence, self-management). The primary outcome is the adoption of TBC for HTN management measured at baseline and 12 months. Secondary outcomes include the rate of BP control and sustainability of TBC and BP outcomes at 18 months. Aggregated data on BP measures are collected every 6 months in all clusters so that each cluster provides data points in both the control and intervention conditions. Using a mixed methods approach, we will also explore factors that influence the effectiveness of PF at the organization and team level. DISCUSSION: This study will provide much-needed guidance on how to optimize adoption and sustainability of TBC in independent primary care settings to reduce the burden of disease related to suboptimal BP control and advance understanding of how facilitation works to improve implementation of evidence-based interventions. TRIAL REGISTRATION: ClinicalTrials.gov; NCT05413252 .

Service provider interpretations of childhood sexual experiences among sexual minority men.

In this study, we report findings from a directed content analysis of service provider (SP) interpretations of early sexual experiences depicted in vignettes created from retrospective interviews with Black sexual minority men. Specifically, we explore whether SP recognize circumstances of abuse in the vignette narrators' sexual histories. Data for this analysis come from in-person qualitative interviews conducted with 35 providers working in substance abuse treatment and allied health service settings (e.g., mental health, HIV prevention and outreach) across the New York City area. The interviewees were asked to evaluate each of five vignettes depicting a range of early sexual experiences as described by the narrators [e.g., unwanted experiences with a male or female consistent with definitions of childhood sexual abuse (CSA), consensual sex with an older male or female]. Based on analysis of provider responses to the vignettes, we found that most recognized differences in age and authority as abuse indicators. Many of the providers struggled with assertions by vignette narrators that they had consented to the encounters-specifically those that could be considered abusive. Findings highlight areas to focus on in developing additional provider training, including the challenges of defining CSA, age and other factors that influence consent, and how cultural background and sexual minority status may shape men's appraisals of their experiences. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Polymorphisms in common antihypertensive targets: Pharmacogenomic implications for the treatment of cardiovascular disease.

The idea of personalized medicine came to fruition with sequencing the human genome; however, aside from a few cases, the genetic revolution has yet to materialize. Cardiovascular diseases are the leading cause of death globally, and hypertension is a common prelude to nearly all cardiovascular diseases. Thus, hypertension is an ideal candidate disease to apply tenants of personalized medicine to lessen cardiovascular disease. Herein is a survey that visually depicts the polymorphisms in the top eight antihypertensive targets. Although there are numerous genome-wide association studies regarding cardiovascular disease, few studies look at the effects of receptor polymorphisms on drug treatment. With 17,000+ polymorphisms in the combined target proteins examined, it is expected that some of the clinical variability in the treatment of hypertension is due to polymorphisms in the drug targets. Recent advances in techniques and technology, such as high throughput examination of single mutations, structure prediction, computational power for modeling, and CRISPR models of point mutations, allow for a relatively rapid and comprehensive examination of the effects of known and future polymorphisms on drug affinity and effects. As hypertension is easy to measure and has a plethora of clinically viable ligands, hypertension makes an excellent disease to study pharmacogenomics in the lab and the clinic. If the promises of personalized medicine are to materialize, a concerted effort to examine the effects polymorphisms have on drugs is required. A clinician with the knowledge of a patient's genotype can then prescribe drugs that are optimal for treating that specific patient.

Effects of Humor and Bystander Gender on Responses to Antigay Harassment.

Individuals perceived to be LGBTQ+ are at risk for harassment. Although bystanders who confront harassers and support targets of harassment may promote inclusivity, the use of humor to express antigay harassment may inhibit prosocial bystander intervention. Non-LGBTQ+ undergraduates (N = 326) were randomly assigned to respond to a scenario in which a male peer disparaged another peer with antigay comments involving either the presence or absence of humor. Results showed that bystanders reported less intent to intervene in the presence of humor than in its absence. Bystander gender moderated perceptions of humorous harassing speech but not intent to intervene. In the presence of humor, men but not women perceived antigay harassment as more amusing; they also perceived the harassing peer more favorably. To promote ally behavior, bystander education may explicitly address critical thinking about the functions and effects of disparaging humor.

Addressing Unmet Basic Needs to Improve Colposcopy Adherence Among Women With Abnormal Cervical Cancer Screening.

OBJECTIVES: The aims of the study were to identify unmet basic needs (BNs) among women referred to colposcopy, to assess patient acceptability/satisfaction with assistance from a navigator to address unmet BNs, and to estimate adherence to colposcopy. METHODS: Women were recruited between September 2017 and January 2019 from 2 academic colposcopy centers, one serving a rural and one an urban area. Basic needs were assessed by phone before colposcopy appointments and considered unmet if unlikely to resolve in 1 month. Colposcopy adherence prestudy and poststudy implementation was abstracted over 4-6 months from administrative records. After a lead-in phase of 25 patients at each site, a BN navigator was offered to new participants with 1 or more unmet BNs. Primary outcome was adherence to initial appointment. RESULTS: Among 100 women, 59% had 1 or more unmet BNs, with similar prevalence between urban and rural sites. Adherence to initial colposcopy was 83% overall, 72% at the rural clinic, and 94% at the urban clinic (p = .006). These adherence rates were improved from 4 months before study launch (30/59 [51%] rural clinic and 68/137 [50%] urban clinic). Although acceptability of BN navigation was greater than 96% and women felt that it helped them get to their colposcopy visit, having a navigator was not associated with adherence. Women reporting no unmet BNs had the lowest adherence compared with women with 1 or more unmet BNs, regardless of navigator assistance (p = .03). CONCLUSIONS: Disadvantaged women who need colposcopy have unmet BNs and value navigator assistance for initial appointments. However, when appointment scheduling includes telephone reminders and inquiring about BNs, a navigator may not add value.

Temporal and region-specific effects of sleep fragmentation on gut microbiota and intestinal morphology in Sprague Dawley rats.

Sleep is a fundamental biological process, that when repeatedly disrupted, can result in severe health consequences. Recent studies suggest that both sleep fragmentation (SF) and dysbiosis of the gut microbiome can lead to metabolic disorders, though the underlying mechanisms are largely unclear. To better understand the consequences of SF, we investigated the effects of acute (6 days) and chronic (6 weeks) SF on rats by examining taxonomic profiles of microbiota in the distal ileum, cecum and proximal colon, as well as assessing structural and functional integrity of the gastrointestinal barrier. We further assayed the impact of SF on a host function by evaluating inflammation and immune response. Both acute and chronic SF induced microbial dysbiosis, more dramatically in the distal ileum (compared to other two regions studied), as noted by significant perturbations in alpha- and beta-diversity; though, specific microbial populations were significantly altered throughout each of the three regions. Furthermore, chronic SF resulted in increased crypt depth in the distal ileum and an increase in the number of villi lining both the cecum and proximal colon. Additional changes were noted with chronic SF, including: decreased microbial adhesion and penetration in the distal ileum and cecum, elevation in serum levels of the cytokine KC/GRO, and depressed levels of corticotropin. Importantly, our data show that perturbations to microbial ecology and intestinal morphology intensify in response to prolonged SF and these changes are habitat specific. Together, these results reveal consequences to gut microbiota homeostasis and host response following acute and chronic SF in rats.

Early Sexual Experiences, Mental Health, and Risk Behavior among Black Non-Hispanic and Hispanic / Latino Men Who Have Sex with Men (MSM).

Black and Latino men who have sex with men (MSM) are disproportionately affected by childhood sexual abuse (CSA). Investigating these histories is often confounded by underreporting and varied definitions of abuse. Unrecognized abuse may manifest in unhealthy ways, specifically psychological distress, substance use, and high-risk sexual behaviors. Black and Hispanic/Latino MSM in New York City discussed formative sexual experiences in in-person interviews. Eligible men reported a sexual experience occurring before age 16 with a man or woman 18 or older at the time. Among interviewees (n = 61), men living with HIV were significantly younger at the time of their first sexual experience with a male partner compared to HIV-negative men. Approximately half of interviewees (47.5%) scored at or above the diagnostic cutoff for post-traumatic stress disorder (PTSD). Hispanic/Latino men had increased odds of scoring at or above the diagnostic cutoff for PTSD compared to Black non-Hispanic men. Further, nearly half of interviewees (46%) scored at or above the diagnostic cutoff for harmful drug use or possible drug dependence. Study findings have implications for future research using an indirect approach to uncovering potential sexual abuse during childhood, and associations with adult health outcomes.

Lipid, water, and protein composition to facilitate kinetic modeling of the auditory pathway.

Environments combining JP-8 jet fuel exposure with heightened ambient noise may accelerate hearing loss induced by noise. To reduce animal use and facilitate kinetic modeling of this military aviation fuel, tissue-specific parameters are required, including water, protein, and lipid content. However, tissues involved in hearing, including cochlea, brainstem, frontal, and temporal lobe, have not been characterized before. Therefore, water content was determined by lyophilization of rat auditory tissues and the protein of the freeze dried remainder was quantified using a bicinchoninic acid assay. Lipids were extracted from fresh-frozen rat auditory tissues and separated into neutral lipids, free fatty acids, neutral phospholipids, and acidic phospholipids using solid phase extraction. Phospholipid fractions were confirmed by 31 P nuclear magnetic resonance analysis showing distinct phospholipid profiles. Lipid content in reference tissues, such as kidney and adipose, confirmed literature values. For the first time, lipid content in the rat auditory pathway was determined showing that total lipid content was lowest in cochlea and highest in brainstem compared with frontal and temporal lobes. Auditory tissues displayed distinct lipid fraction profiles. The information on water, protein, and lipid composition is necessary to validate algorithms used in mathematical models and predict partitioning of chemicals of future interest into these tissues. This research may reduce the use of animals to measure partition coefficients for prospective physiological models.

Understanding the Impact of Childhood Sexual Abuse on Men's Risk Behavior: Protocol for a Mixed-Methods Study.

BACKGROUND: Childhood sexual abuse (CSA) remains a critical public health issue among black and Latino men who have sex with men (MSM), as it is associated with multiple negative outcomes including substance misuse, poor mental health, revictimization, and high-risk sexual behavior. Most CSA research with MSM relies on quantitative assessment that often precludes consideration of cultural variations in how formative sexual experiences are understood and is based on inconsistent or overly restrictive definitions of abuse, and therefore may fail to detect certain abusive experiences (eg, those involving female perpetrators), which can have harmful health consequences if they remain unrecognized. OBJECTIVE: The objective of this study is to overcome existing limitations in the literature by drawing on perspectives of black and Latino MSM and men who have sex with men and women (MSMW), as well as relevant service providers to better understand the role of, and the need to include, sexual abuse histories (eg, CSA) in treatment and counseling settings, with the long-term goal of improving assessment and health outcomes. METHODS: We will conduct mixed-methods interviews, framed by an intersectionality approach, with 80 black and Latino men (40 MSM and 40 MSMW) in New York City (NYC), exploring appraisals of their formative sexual experiences, including those described as consensual but meeting criteria for CSA. We will also interview 30 local service providers representing substance abuse treatment, mental health care, and HIV prevention and outreach. RESULTS: The study was launched in May 2017. CONCLUSIONS: This formative research will inform testable approaches to assessing and incorporating sexual abuse history into substance abuse treatment and other health and mental health services used by men with such histories.

Therapeutic response analysis in dogs with naturally occurring osteoarthritis.

OBJECTIVE: Reporting the rate of positive (+) and negative (-) responders based on an objective outcome measure of pain-related functional disability/lameness in dogs with naturally occurring osteoarthritis (OA), and the relationship between initial lameness severity and the odds of being a (+) responder. STUDY DESIGN: Retrospective analysis of published peer-reviewed clinical trials in dogs with naturally occurring OA. ANIMALS: Dogs (n = 213) with hip and/or stifle afflicted-joints. METHODS: A responder analysis was undertaken using a previously determined cut-off value of ±2.0% of body weight using the peak of vertical force (PVF). Among the selected trials, PVF was acquired under similar conditions. Therapeutic approaches were therapeutic diets, natural health products and nonsteroidal anti-inflammatory drugs. RESULTS: Among dogs receiving a therapeutic approach as described above (n = 121), 62.8% [95% confidence interval, 53.9-70.9] were defined as (+) responders, whereas 11.6% [7.0-18.5] were (-) responders, accounting for a net (+) response rate by 51.2% [42.0-60.4]. In dogs receiving a negative control (n = 92), the net (+) response rate was 1.1% [0.0-5.9]. The number needed to treat was 4, and the effect size 0.7 [0.4-1.0]. The odds ratio of being a (+) responder under the therapeutic approaches was 2.85 [1.57-5.17] (p < 0.001). For every less severe lameness manifested with an increment in PVF by 1% body weight, the chance of being a (+) responder following treatment decreased by 9% (odds ratio 0.91 [0.86-0.97], p = 0.006). CONCLUSION AND CLINICAL RELEVANCE: The rate of (+) responder optimizes decision making for the management of pain-related clinical signs of OA. Evidence-based medicine was further supported by clinical metrics based on an objective outcome measure of pain-related functional disability/lameness. This study also revealed that dogs with a mild lameness are less prone to be improved, emphasizing the need to carefully manage OA dogs in spite of a more subtle affliction.

Lixisenatide as add-on therapy to basal insulin.

Many patients with type 2 diabetes mellitus do not achieve target glycosylated hemoglobin A1c levels despite optimally titrated basal insulin and satisfactory fasting plasma glucose levels. Current evidence suggests that HbA1c levels are dictated by both basal glucose and postprandial glucose levels. This has led to a consensus that postprandial glucose excursions contribute to poor glycemic control in these patients. Lixisenatide is a once-daily, prandial glucagon-like peptide 1 (GLP-1) receptor agonist with a four-fold affinity for the GLP-1 receptor compared with native GLP-1. Importantly, lixisenatide causes a significant delay in gastric emptying time, an important determinant of the once-daily dosing regimen. An exendin-4 mimetic with six lysine residues removed at the C-terminal, lixisenatide has pronounced postprandial glucose-lowering effects, making it a novel incretin agent for use in combination with optimally titrated basal insulin. Lixisenatide exerts profound effects on postprandial glucose through established mechanisms of glucose-dependent insulin secretion and glucagon suppression in combination with delayed gastric emptying. This review discusses the likely place that lixisenatide will occupy in clinical practice, given its profound effects on postprandial glucose and potential to reduce glycemic variability.

Choosing between GLP-1 Receptor Agonists and DPP-4 Inhibitors: A Pharmacological Perspective.

In recent years the incretin therapies have provided a new treatment option for patients with type 2 diabetes mellitus (T2DM). The incretin therapies focus on the increasing levels of the two incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). This results in increased glucose dependent insulin synthesis and release. GLP-1 receptor agonists such as liraglutide and exenatide exert an intrinsic biological effect on GLP-1 receptors directly stimulating the release of insulin from pancreatic beta cells. DPP-4 inhibitors such as sitagliptin and linagliptin prevent the inactivation of endogenous GLP-1 and GIP through competitive inhibition of the DPP-4 enzyme. Both incretin therapies have good safety and tolerability profiles and interact minimally with a number of medications commonly prescribed in T2DM. This paper focuses on the pharmacological basis by which the incretin therapies function and how this knowledge can inform and benefit clinical decisions. Each individual incretin agent has benefits and pitfalls relating to aspects such as glycaemic and nonglycaemic efficacy, safety and tolerability, ease of administration, and cost. Overall, a personalized medicine approach has been found to be favourable, tailoring the incretin agent to benefit and suit patient's needs such as renal impairment (RI) or hepatic impairment (HI).