A Distinct Type of Pilus from the Human Microbiome.

Pili are proteinaceous polymers of linked pilins that protrude from the cell surface of many bacteria and often mediate adherence and virulence. We investigated a set of 20 Bacteroidia pilins from the human microbiome whose structures and mechanism of assembly were unknown. Crystal structures and biochemical data revealed a diverse protein superfamily with a common Greek-key ß sandwich fold with two transthyretin-like repeats that polymerize into a pilus through a strand-exchange mechanism. The assembly mechanism of the central, structural pilins involves proteinase-assisted removal of their N-terminal ß strand, creating an extended hydrophobic groove that binds the C-terminal donor strands of the incoming pilin. Accessory pilins at the tip and base have unique structural features specific to their location, allowing initiation or termination of the assembly. The Bacteroidia pilus, therefore, has a biogenesis mechanism that is distinct from other known pili and likely represents a different type of bacterial pilus.

The leukocyte integrin antagonist Del-1 inhibits IL-17-mediated inflammatory bone loss.

Aging is linked to greater susceptibility to chronic inflammatory diseases, several of which, including periodontitis, involve neutrophil-mediated tissue injury. Here we found that aging-associated periodontitis was accompanied by lower expression of Del-1, an endogenous inhibitor of neutrophil adhesion dependent on the integrin LFA-1, and by reciprocal higher expression of interleukin 17 (IL-17). Consistent with that, IL-17 inhibited gingival endothelial cell expression of Del-1, thereby promoting LFA-1-dependent recruitment of neutrophils. Young Del-1-deficient mice developed spontaneous periodontitis that featured excessive neutrophil infiltration and IL-17 expression; disease was prevented in mice doubly deficient in Del-1 and LFA-1 or in Del-1 and the IL-17 receptor. Locally administered Del-1 inhibited IL-17 production, neutrophil accumulation and bone loss. Therefore, Del-1 suppressed LFA-1-dependent recruitment of neutrophils and IL-17-triggered inflammatory pathology and may thus be a promising therapeutic agent for inflammatory diseases.

PrEPárate: Evaluation of a Community-Driven PrEP Social Marketing Intervention Tailored to Latino/a/x Individuals.

Latino/a/x sexual minority men (SMM) and transgender women remain disproportionately impacted by HIV, with higher HIV incidence and lower uptake of pre-exposure prophylaxis (PrEP) than their non-Hispanic White peers. Disparities in PrEP uptake among Latino/a/x populations have been found to be due to structural, social, and personal barriers. Social marketing interventions have been shown to effectively address barriers and increase PrEP uptake in other populations, and thus offer potential as a tool to increase PrEP uptake for Latino/a/x populations. The PrEPárate campaign was developed through community based participatory research and ran from April to September 2022 in Cook County, Illinois. We conducted a mixed methods evaluation through surveys (N = 515) and semi-structured interviews with survey participants and community partners (N = 14). We examined cross-sectional associations of campaign exposure with PrEP awareness and uptake in adjusted multivariable regression models. We used rapid qualitative methods to analyze interviews and assess implementation outcomes following the RE-AIM framework. The campaign reached over 118,000 people on social media, with additional reach over public transit and local events. PrEPárate exposure was associated with increased PrEP awareness (aOR = 5.23; 95% CI [2.58, 10.63]) and PrEP uptake (aOR = 1.69; 95% CI [1.09, 2.62]). Survey respondents expressed that the campaign name, visuals, ambassadors, and distribution were effective in engaging the target audience. Community partners felt the campaign was implemented with fidelity to the original vision and identified future directions for PrEPárate. Social marketing campaigns, anchored in community engagement, may be an effective strategy to increase PrEP awareness and uptake among underserved Latino/a/x populations.

RESUMEN: Los hombres de minorías sexuales y las mujeres transgénero latinos siguen siendo desproporcionadamente afectados por el VIH, con una incidencia de VIH más alta y un menor uso de la Profilaxis Pre-Exposición (PrEP) que sus pares blancos no hispanos. Se ha encontrado que las disparidades en la adopción de PrEP entre las poblaciones latinas se deben a barreras estructurales, sociales y personales. Las intervenciones de mercadeo social han demostrado ser efectivas para eliminar los obstáculos e incrementar el uso de PrEP en otras poblaciones, y por lo tanto son una potencial herramienta para aumentar el uso de PrEP en las poblaciones latinas. La campaña PrEPárate fue desarrollada a través de investigación participativa basada en la comunidad, y se llevó a cabo desde abril hasta septiembre de 2022 en el Condado de Cook, Illinois. Realizamos una evaluación de métodos mixtos a través de encuestas (N = 515) y entrevistas semiestructuradas con participantes de la encuesta y socios comunitarios (N = 14). Se examinaron las asociaciones transversales de la exposición a la campaña con la consciencia y el uso de PrEP en modelos de regresión multivariable ajustados. Utilizamos métodos cualitativos rápidos para analizar entrevistas y evaluar los resultados de la implementación usando el marco RE-AIM. La campaña alcanzó a más de 118,000 personas en redes sociales, con un alcance adicional en el transporte público y eventos locales. La exposición a PrEPárate se asoció con un aumento en la consciencia de PrEP (aOR = 5.23; IC del 95% [2.58, 10.63]) y el uso de PrEP (aOR = 1.69; IC del 95% [1.09, 2.62]). Las participantes de la encuesta expresaron que el nombre de la campaña, las visuales, los embajadores, y la distribución fueron eficaces para atraer al público. Los socios comunitarios sintieron que la campaña se implementó con fidelidad a la visión original e identificaron direcciones futuras para PrEPárate. Las campañas de mercadeo social, basados en el aporte de la comunidad, pueden ser una estrategia efectiva para aumentar la consciencia y el uso de PrEP entre las poblaciones latinas desatendidas.

Gut Dysbiosis in Experimental Kidney Disease: A Meta-Analysis of Rodent Repository Data.

SIGNIFICANCE STATEMENT: Alterations in gut microbiota contribute to the pathophysiology of a diverse range of diseases, leading to suggestions that chronic uremia may cause intestinal dysbiosis that contributes to the pathophysiology of CKD. Various small, single-cohort rodent studies have supported this hypothesis. In this meta-analysis of publicly available repository data from studies of models of kidney disease in rodents, cohort variation far outweighed any effect of experimental kidney disease on the gut microbiota. No reproducible changes in animals with kidney disease were seen across all cohorts, although a few trends observed in most experiments may be attributable to kidney disease. The findings suggest that rodent studies do not provide evidence for the existence of "uremic dysbiosis" and that single-cohort studies are unsuitable for producing generalizable results in microbiome research. BACKGROUND: Rodent studies have popularized the notion that uremia may induce pathological changes in the gut microbiota that contribute to kidney disease progression. Although single-cohort rodent studies have yielded insights into host-microbiota relationships in various disease processes, their relevance is limited by cohort and other effects. We previously reported finding metabolomic evidence that batch-to-batch variations in the microbiome of experimental animals are significant confounders in an experimental study. METHODS: To attempt to identify common microbial signatures that transcend batch variability and that may be attributed to the effect of kidney disease, we downloaded all data describing the molecular characterization of the gut microbiota in rodents with and without experimental kidney disease from two online repositories comprising 127 rodents across ten experimental cohorts. We reanalyzed these data using the DADA2 and Phyloseq packages in R, a statistical computing and graphics system, and analyzed data both in a combined dataset of all samples and at the level of individual experimental cohorts. RESULTS: Cohort effects accounted for 69% of total sample variance ( P <0.001), substantially outweighing the effect of kidney disease (1.9% of variance, P =0.026). We found no universal trends in microbial population dynamics in animals with kidney disease, but observed some differences (increased alpha diversity, a measure of within-sample bacterial diversity; relative decreases in Lachnospiraceae and Lactobacillus ; and increases in some Clostridia and opportunistic taxa) in many cohorts that might represent effects of kidney disease on the gut microbiota . CONCLUSIONS: These findings suggest that current evidence that kidney disease causes reproducible patterns of dysbiosis is inadequate. We advocate meta-analysis of repository data as a way of identifying broad themes that transcend experimental variation.

"No-one just does drugs during business hours!": evaluation of a 24/7 primary needle and syringe program in St Kilda, Australia.

BACKGROUND: Primary needle and syringe programs (NSPs) have been integral for the prevention of blood-borne virus (BBV) transmission among people who inject drugs. Despite this, many people who inject drugs face barriers accessing these services, particularly after-hours when most services are closed. To our knowledge, the St Kilda NSP, in Melbourne, Victoria, is the only primary NSP providing 24/7 dedicated stand-alone face-to-face services for people who inject drugs in Australia. We conducted an evaluation of the St Kilda NSP to assess its role and effectiveness in meeting client needs. METHODS: Mixed research methods were used to conduct the evaluation. We analysed four quantitative data sets including the Victorian Needle and Syringe Program Information System data; NSP 'snapshot' survey data; and St Kilda NSP records of after-hours contacts and naloxone training events. Qualitative interviews were conducted with 20 purposively selected NSP clients, which were focused on individual needs, expectations and experiences accessing the service. Interviews were audio recorded and transcribed, and data were analysed thematically. A convergent research design was used to merge the five data sets. RESULTS: St Kilda NSP had 39,898 service contacts in 2018; 72% of contacts occurred outside business hours. Similarly, of 1,185,000 sterile needles and syringes dispatched, 71% were distributed outside business hours. Participants described valuing the after-hours service because drug use patterns did not always align with standard NSP opening hours and after-hours access afforded anonymity when collecting injecting equipment. Narratives highlighted several additional benefits of the 24/7 service, including: access to safer sex equipment; material support; naloxone training; referrals to specialist services; face-to-face emotional and social support from a non-judging worker; and for women involved in sex work in particular, being able to seek refuge when feeling unsafe on the streets. CONCLUSIONS: Our study provides evidence of the social and health benefits (beyond that of preventing BBV transmission) that can be gained through the provision of 24/7 primary NSP services. Findings support the need for the establishment of after-hours primary NSPs in other areas of Australia where active street-based drug markets operate outside business hours and concentrated numbers of people who inject drugs live and spend time.

Childhood adversity and racial discrimination forecast suicidal and death ideation among emerging adult Black men: A longitudinal analysis.

OBJECTIVES: Disproportionate exposure to childhood adversity and the effects of racial discrimination take a toll on Black American men's mental health. Despite increasing rates of suicidal behaviors and thoughts among young adult, Black American men, few longitudinal studies examine their risk for suicidal and death ideation (SDI). We tested a developmental model linking childhood adversity (experiences of deprivation and threatening experiences) and emerging adult exposure to racial discrimination to increases in SDI and examined a potential mechanism for these effects, negative relational schemas. METHOD: A sample of 504 Black men (Mage = 20.7) from rural Georgia were recruited with respondent-driven sampling and completed a baseline survey. Men participated in two additional follow-up surveys (Mage = 21.9 and Mage = 23.5). Hypotheses were tested using structural equation modeling. RESULTS: Analyses largely supported the proposed model. Childhood adversities were associated directly with reports of SDI. Childhood deprivation indirectly predicted SDI via negative schemas (ß = 0.03, 95% CI [.014, .046]). Racial discrimination also indirectly predicted SDI via negative relational schemas (ß = 0.01, 95% CI [.001, .018]). CONCLUSION: Study results suggest that clinical and preventive interventions for suicidality should target the influence of racism and adverse experiences and the negative relational schemas they induce. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Neuromuscular Performance and the Intensity of External Training Load During the Preseason in National Collegiate Athletic Association Division I Men's Collegiate Basketball Players.

ABSTRACT: Curtis, M, Kupperman, N, Westbrook, J, Weltman, AL, Hart, J, and Hertel, J. Neuromuscular performance and the intensity of external training load during the preseason in National Collegiate Athletic Association Division I men's collegiate basketball players. J Strength Cond Res XX(X): 000-000, 2024-The aim of the study was to determine whether acute changes in neuromuscular performance can be detected through countermovement jumps (CMJs) conducted pre- and postpractice sessions in conditions of high or low intensity measured by microsensors technology. Using an observational repeated measures design, data were collected from 10 male collegiate basketball players. Countermovement jump data were collected before and after practice exposures over 4 weeks of preseason. Select CMJ kinetics were compared in conditions of high and low training load intensity to detect neuromuscular performance changes in displacement of the center of mass and kinetics. Kinetic measures were categorized as output, underpinning, and strategy-related variables. We investigated "output" defined as displacement (jump height [JH]), "underpinning" defined as force-related (mean eccentric force, mean concentric force, force at zero velocity), and "strategy" defined as time-related (countermovement depth [CMD], eccentric duration (EccDur), concentric duration [ConcDur]) variables. There were significant condition × time interactions in CMJ variables namely eccentric mean force (EccForce), force at zero velocity (Force@0), CMDepth, EccDur, and ConcDur. In conditions of high intensity, players had significant, but small decreases in EccForce and Force@0, with small increases in CMD, EccDur, and ConDur, respectively. However, there were no significant decreases in JH. High-intensity practice exposures did not impact neuromuscular performance specific to "output," suggesting that collegiate basketball athletes can maintain JH despite alterations in "underpinning" and "strategy-related" variables. This could have relevance in understanding how fatigue associated with higher-intensity training exposures may potentially alter jump strategy and force production capacities due to external load intensity in collegiate basketball athletes.

Changes in Sexual Behaviors Due to Mpox: a Cross-Sectional Study of Sexual and Gender Minority Individuals in Illinois.

The spread of the monkeypox virus (mpox) in 2022 primarily within the sexual networks of men who have sex with men (MSM) triggered a potentially stigmatizing public health response in the USA. Despite mpox being primarily spread through skin-to-skin contact, most messaging has promoted abstinence and/or reduction in sexual risk behaviors. More research is needed on decreases in sexual risk behaviors among sexual and gender minority (SGM) youth and young adults (YYA) related to the most recent mpox epidemic and whether there are factors associated with these decreases in sexual risk behavior. Participants within an ongoing cohort study of SGM YYA who reside in Illinois were offered the opportunity to participate in an mpox survey between September 10th and September 20th, 2022. Analyses looked at demographic factors associated with sexual activity since the start of the outbreak, as well as associations with two sexual risk reduction factors. Survey participation was 68.7% (322/469). Three-quarters of participants (82.6%) reported sexual activity since June 1st. Most sexually active participants (83.5%) adopted at least one sexual risk reduction behavior due to mpox. Black and Latinx individuals were less likely to be sexually active but more likely to report risk reduction behaviors (31.3% and 22.6%, respectively). Participants who received the mpox vaccine were more likely to report sexual activity. SGM YYA in Illinois reported that their sexual behaviors were impacted by the mpox outbreak. However, associations between vaccination and sexual behavior demonstrate that those who are vaccinated do adopt protective methods despite not decreasing sexual activity. Therefore, sex-positive communications and harm reduction messaging may be more appropriate as opposed to abstinence-only prevention, which can further stigmatize an already marginalized group.

Is use of opioid agonist treatment associated with broader primary healthcare use among men with recent injecting drug use histories following release from prison? A prospective cohort study.

BACKGROUND: A precipitous decline in health status among people recently released from prison is common. In Victoria, Australia, opioid agonist treatment (OAT) in the community involves frequent contact with primary care, potentially facilitating broader use of primary healthcare services. Among a cohort of men who injected drugs regularly pre-imprisonment, we estimated differences in rates of primary healthcare use and medication dispensation between people who did and did not receive OAT post-release. METHODS: Data came from the Prison and Transition Health Cohort Study. Three-month post-release follow-up interviews were linked with primary care and medication dispensation records. Generalised linear models were fit with one exposure (OAT: none/partial/complete) for 13 outcomes relating to primary healthcare use, pathology testing, and medication dispensation, adjusted for other covariates. Coefficients were reported as adjusted incidence rate ratios (AIRR). RESULTS: Analyses included 255 participants. Compared to no OAT use, both partial and complete OAT use were associated with increased rates of standard (AIRR: 3.02, 95%CI: 1.88-4.86; AIRR: 3.66, 95%CI: 2.57-5.23), extended (AIRR: 2.56, 95%CI: 1.41-4.67; AIRR: 2.55, 95%CI: 1.60-4.07) and mental health-related (AIRR: 2.71, 95%CI: 1.42-5.20; AIRR: 2.27, 95%CI: 1.33-3.87) general practitioner (GP) consultations, total medication (AIRR: 1.88, 95%CI: 1.19-2.98; AIRR: 2.40, 95%CI: 1.71-3.37), benzodiazepine (AIRR: 4.99, 95%CI: 2.81-8.85; AIRR: 8.30, 95%CI: 5.28-13.04) and gabapentinoid (AIRR: 6.78, 95%CI: 3.34-13.77; AIRR: 4.34, 95%CI: 2.37-7.94) dispensations, respectively. Partial OAT use was also associated with increased after-hours GP consultations (AIRR: 4.61, 95%CI: 2.24-9.48) and complete OAT use? with increased pathology utilisation (e.g. haematological, chemical, microbiological or immunological tissue/sample testing; AIRR: 2.30, 95%CI: 1.52-3.48). CONCLUSION: We observed higher rates of primary healthcare use and medication dispensation among people who reported partial and complete OAT use post-release. Findings suggest that access to OAT post-release may have a collateral benefit in supporting broader health service utilisation, underscoring the importance of retention in OAT after release from prison.

Prospective study of retention in opioid agonist treatment and contact with emergency healthcare following release from prisons in Victoria, Australia.

BACKGROUND: People recently released from prison engage with emergency healthcare at greater rates than the general population. While retention in opioid agonist treatment (OAT) is associated with substantial reductions in the risk of opioid-related mortality postrelease, it is unknown how OAT affects contact with emergency healthcare. In a cohort of men who injected drugs regularly prior to imprisonment, we described rates of contact with ambulance services and EDs, and their associations with use of OAT, in the 3 months after release from prison. METHODS: Self-report data from a prospective observational cohort of men who regularly injected drugs before a period of sentenced imprisonment, recruited between September 2014 and May 2016, were linked to state-wide ambulance and ED records over a 3-month postrelease period in Victoria, Australia. We used generalised linear models to estimate associations between OAT use (none/interrupted/retained) and contact with ambulance and EDs postrelease, adjusted for other covariates. RESULTS: Among 265 participants, we observed 77 ambulance contacts and 123 ED contacts over a median of 98 days of observation (IQR 87-125 days). Participants who were retained in OAT between prison release and scheduled 3-month postrelease follow-up interviews had lower rates of contact with ambulance (adjusted incidence rate ratio (AIRR) 0.33, 95% CI 0.14 to 0.76) and ED (AIRR 0.43, 95% CI 0.22 to 0.83), compared with participants with no OAT use postrelease. Participants with interrupted OAT use did not differ from those with no OAT use in rates of contact with ambulance or ED. CONCLUSION: We found lower rates of contact with emergency healthcare after release among people retained in OAT, but not among people reporting interrupted OAT use, underscoring the benefits of postrelease OAT retention. Strategies to improve accessibility and support OAT retention after leaving prison are important for men who inject drugs.

Team Self-Maintenance during Long-Duration Space Exploration: A Conceptual Framework.

OBJECTIVE: We developed a conceptual framework of Team Self-Maintenance (TSM) within long-duration space exploration (LDSE), which we define as the process of monitoring, adjusting, and maintaining the psychological well-being of a team in the absence of external support. BACKGROUND: Specific to LDSE and isolated, confined, and extreme (ICE) environments, periods of routine can have a debilitating effect on the crew's well-being and performance, and TSM is a critical process for avoiding these detrimental effects. METHOD: Based on themes drawn from nine subject matter expert interviews combined with an extensive literature review on related concepts, we developed an integrative conceptual framework of the key inputs, processes, and outputs involved in TSM within LDSE contexts. RESULTS: Our TSM framework suggests team well-being as a key outcome that must be maintained during LDSE and information sharing, self-regulation, resource recovery, and emotional support as the key processes that enable team well-being. We also identify several contextual inputs that can serve as intervention points for enabling effective TSM. CONCLUSION: Our framework suggests that future research and practice aimed at effective LDSE should emphasize team well-being, rather than just performance, and that there are many open questions in terms of how teams will manage their own socio-emotional needs (e.g., conflict, recovery activities, and boredom) without external systems and support. APPLICATION: This conceptual framework describes the primary inputs, processes, and outcomes involved in the team self-maintenance process. This framework reflects context-specific theorizing most likely to be applicable only to LDSE contexts.

New records of Ornithodoros turicata (Ixodida: Argasidae) in rural and urban sites in the Mexican states of Aguascalientes and Zacatecas indicate the potential for tick-borne relapsing fever.

Soft ticks from the Ornithodoros genus are vectors of relapsing fever (RF) spirochetes around the world. In Mexico, they were originally described in the 19th century. However, few recent surveillance studies have been conducted in Mexico, and regions where RF spirochetes circulate remain vague. Here, the presence of soft ticks in populated areas was assessed in two sites from the Mexican states of Aguascalientes and Zacatecas. Argasidae ticks were collected, identified by morphology and mitochondrial 16S rDNA gene sequencing, and tested for RF borreliae. The specimens in both sites were identified as Ornithodoros turicata but no RF spirochetes were detected. These findings emphasize the need to update the distribution of these ticks in multiple regions of Mexico and to determine the circulation of RF borreliosis in humans and domestic animals.

Novel Supreme Drug-Eluting Stents With Early Synchronized Antiproliferative Drug Delivery to Inhibit Smooth Muscle Cell Proliferation After Drug-Eluting Stents Implantation in Coronary Artery Disease: Results of the PIONEER III Randomized Clinical Trial.

BACKGROUND: Accelerated endothelial healing after targeted antiproliferative drug delivery may limit the long-term inflammatory response of drug-eluting stents (DESs). The novel Supreme DES is designed to synchronize early drug delivery within 4 to 6 weeks of implantation, leaving behind a prohealing permanent base layer. Whether the Supreme DES is safe and effective in the short term and can improve long-term clinical outcomes is not known. METHODS: In an international, 2:1 randomized, single-blind trial, we compared treatment with Supreme DES to durable polymer everolimus-eluting stents (DP-EES) in patients with acute and chronic coronary syndromes. The primary end point was target lesion failure-a composite of cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization. The trial was designed to demonstrate noninferiority (margin of 3.58%) of the Supreme DES at 12 months compared with DP-EES (URL: https://www.clinicaltrials.gov; Unique identifier: NCT03168776). RESULTS: From October 2017 to July 2019, a total of 1629 patients were randomly assigned (2:1) to the Supreme DES (N=1086) or DP-EES (N=543). At 12 months, target lesion failure occurred in 57 of 1057 patients (5.4%) in the Supreme DES group and in 27 of 532 patients (5.1%) in the DP-EES group (absolute risk difference, 0.32% [95% CI, -1.87 to 2.5]; Pnoninferiority=0.002]. There were no significant differences in rates of device success, clinically driven target lesion revascularization, or stent thrombosis at 12 months, and the safety composite of cardiovascular death and target vessel myocardial infarction was 3.5% versus 4.6% (hazard ratio, 0.76 [95% CI, 0.46-1.25]) with Supreme DES compared with DP-EES, although rates of combined clinically and non-clinically driven target lesion revascularization at 12 months were higher with Supreme DES. CONCLUSIONS: Among patients with acute and chronic coronary syndromes undergoing percutaneous coronary intervention, the Supreme DES proved to be noninferior to the standard DP-EES. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03168776.

Kidney transplantation from triple-knockout pigs expressing multiple human proteins in cynomolgus macaques.

Porcine cells devoid of three major carbohydrate xenoantigens, αGal, Neu5GC, and SDa (TKO) exhibit markedly reduced binding of human natural antibodies. Therefore, it is anticipated that TKO pigs will be better donors for human xenotransplantation. However, previous studies on TKO pigs using old world monkeys (OWMs) have been disappointing because of higher anti-TKO pig antibodies in OWMs than humans. Here, we show that long-term survival of renal xenografts from TKO pigs that express additional human transgenes (hTGs) can be achieved in cynomolgus monkeys. Kidney xenografts from TKO-hTG pigs were transplanted into eight cynomolgus recipients without pre-screening for low anti-pig antibody titers. Two recipients of TKO-hTG xenografts with low expression of human complement regulatory proteins (CRPs) (TKO-A) survived for 2 and 61 days, whereas six recipients of TKO-hTG xenografts with high CRP expression (TKO-B) survived for 15, 20, 71, 135, 265, and 316 days. Prolonged CD4+ T cell depletion and low anti-pig antibody titers, which were previously reported important for long-term survival of αGal knock-out (GTKO) xenografts, were not always required for long-term survival of TKO-hTG renal xenografts. This study indicates that OWMs such as cynomolgus monkeys can be used as a relevant model for clinical application of xenotransplantation using TKO pigs.

Assessment of gait and balance impairment in people with spinocerebellar ataxia using wearable sensors.

OBJECTIVE: To explore the use of wearable sensors for objective measurement of motor impairment in spinocerebellar ataxia (SCA) patients during clinical assessments of gait and balance. METHODS: In total, 14 patients with genetically confirmed SCA (mean age 61.6 ± 8.6 years) and 4 healthy controls (mean age 49.0 ± 16.4 years) were recruited through the Massachusetts General Hospital (MGH) Ataxia Center. Participants donned seven inertial sensors while performing two independent trials of gait and balance assessments from the Scale for the Assessment and Rating of Ataxia (SARA) and Brief Ataxia Rating Scale (BARS2). Univariate analysis was used to identify sensor-derived metrics from wearable sensors that discriminate motor function between the SCA and control groups. Multivariate linear regression models were used to estimate the subjective in-person SARA/BARS2 ratings. Spearman correlation coefficients were used to evaluate the performance of the model. RESULTS: Stride length variability, stride duration, cadence, stance phase, pelvis sway, and turn duration were different between SCA and controls (p < 0.05). Similarly, sway and sway velocity of the ankle, hip, and center of mass differentiated SCA and controls (p < 0.05). Using these features, linear regression models showed moderate-to-strong correlation with clinical scores from the in-person rater during SARA assessments of gait (r = 0.73, p = 0.003) and stance (r = 0.90, p < 0.001) and the BARS2 gait assessment (r = 0.74, p = 0.003). CONCLUSION: This study demonstrates that sensor-derived metrics can potentially be used to estimate the level of motor impairment in patient with SCA quickly and objectively. Thus, digital biomarkers from wearable sensors have the potential to be an integral tool for SCA clinical trials and care.

Psychiatric well-being among men leaving prison reporting a history of injecting drug use: A longitudinal analysis.

BACKGROUND: Community reintegration from prison is typically stressful, with several health and social outcomes impacting psychiatric well-being during this time, often exacerbated among individuals with histories of drug use. Longitudinal data was used to assess change in psychiatric well-being over 2 years following release from prison among men who reported a recent history of injecting drug use. METHODS: Data for this study come from the Prison and Transition Health cohort study of 400 men recruited in prison prior to release and followed up over three time points. Psychiatric well-being was assessed using the 12-item General Health Questionnaire. We calculated change in individual General Health Questionnaire scores between interviews and identified covariates associated with General Health Questionnaire score using linear mixed-effects regression. RESULTS: Data from 690 follow-up interviews among 326 participants were included in analyses. There was considerable variation in individuals' General Health Questionnaire scores. Moving accommodation frequently and frequent illicit drug injections were associated with an increase in General Health Questionnaire score (i.e. decline in psychiatric well-being). Two or more prior adult imprisonment episodes, social supports and past month primary healthcare attendance were associated with a decrease in General Health Questionnaire score. CONCLUSION: Our findings identify health, social and structural influences on psychiatric well-being after release from prison that can inform re-entry programmes to support community reintegration.

The Transition to Fatherhood, Contextual Stress, and Substance Abuse: A Prospective Analysis of Rural, Emerging Adult Black American Men.

Background: Among Black American emerging adult men (∼aged 18-25), the early transition to fatherhood is often marred by numerous contextual stressors related to racial discrimination and socioeconomic instability. The strain of transitioning to fatherhood while experiencing high levels of contextual stress may evidence escalations in substance misuse over time as men may turn to substances to cope with the stress of complex life transitions. However, research examining these associations are scarce. Objective: This study aimed to investigate the influence of contextual stress on the association between fatherhood and substance misuse. Hypotheses were tested using multiple linear regression with 3 waves of data from 476 Black American men aged 19 to 22 at baseline living in resource-poor communities in the rural South. Results: Results demonstrated that fatherhood status was associated, prospectively, with Black American fathers' substance misuse when exposure to contextual stress was high but not low. Conclusions: Findings underscore the need for substance misuse prevention programs to (a) support Black American fathers in coping with race-related stress and (b) integrate robust socioeconomic stability services in order in disrupt patterns of future substance misuse by improving Black American men's experience of the transition to fatherhood.

Expanding the Traumatic Stress Framework to Incorporate a Socioecological Family Systems Perspective.

Over the past few decades, there has been a growing interest among systemic researchers and clinicians to address issues related to psychological traumatic stress. Yet, research in this area has largely focused on intrapersonal and physiological processes in conceptualizing traumatic stress and its various outcomes. Despite the usefulness of intrapersonally focused models of traumatic stress, this approach has its limitations. Emerging evidence indicates that both proximal contexts, such as family, and distal socioecological contexts, such as political and environmental systems, can have a profound effect on traumatic stress risk, presentation, and recovery. In the present article, we review and synthesize emerging research on traumatic stress and integrate findings from intrapersonally and systemically focused models of traumatic stress. We propose and present evidence for what we term the dynamic socioecological framework of traumatic stress, a heuristic framework for conceptualizing the interactions between different forms of traumatic stress. This framework puts forward the dimensions of traumatic stress typology, severity, and timing, underscoring how traumatic stress risk, presentation, and recovery are highly dependent upon the systems in which people are embedded. We conclude with a discussion of the research and clinical implications of this conceptual framework.

Durante las últimas décadas, ha habido un interés cada vez mayor entre los investigadores y los profesionales clínicos sistémicos en abordar los problemas relacionados con el estrés traumático psicológico. Sin embargo, las investigaciones en esta área se han centrado en gran medida en los procesos intrapersonales y fisiológicos a la hora de conceptualizar el estrés traumático y sus diferentes resultados. A pesar de la utilidad de los modelos intrapersonales de estrés traumático, este enfoque tiene sus limitaciones. Hay nuevos indicios de que los contextos proximales, como la familia, y los contextos socioecológicos distales, como los sistemas políticos y ambientales, pueden tener un efecto profundo en el riesgo, la presentación y la recuperación del estrés traumático. En el presente artículo, analizamos y sintetizamos las investigaciones nuevas sobre estrés traumático e integramos los resultados de los modelos intrapersonales y sistémicos de este tipo de estrés. Proponemos y presentamos pruebas para lo que llamamos el marco socioecológico dinámico del estrés traumático, un marco heurístico para conceptualizar las interacciones entre las diferentes formas de estrés traumático. Este marco propone los aspectos de tipología, intensidad y desarrollo cronológico del estrés traumático, subrayando cómo el riesgo, la presentación y la recuperación del estrés traumático son sumamente dependientes de los sistemas en los cuales están integradas las personas. Terminamos con un debate de la investigación y las consecuencias clínicas de este marco conceptual.

Dyadic effects of enacted stigma, internalized homophobia, and communal coping on depressive symptoms among cisgender sexual minority male couples.

The present study investigated the dyadic direct and indirect effects of enacted stigma on depressive symptoms via internalized homophobia and whether communal coping moderated the effects of enacted stigma on internalized homophobia and depressive symptoms. Hypotheses were tested using actor-partner interdependence models with a sample of 543 cisgender sexual minority male couples. Results showed both partners' enacted stigma experiences were associated with elevated levels of internalized homophobia via actor and partner effects. Internalized homophobia was only associated with elevated depressive symptoms via actor effects. Indirect effects analysis suggested that internalized homophobia mediated the actor and partner influence of enacted stigma on depressive symptoms. Communal coping moderated the direct effects of enacted stigma on internalized homophobia and attenuated the conditional indirect actor and partner effects of enacted stigma on depressive symptoms. Findings underscore the role of intimate relationship processes in understanding the impacts of enacted stigma on depressive symptoms.

En el presente estudio se investigaron los efectos diádicos directos e indirectos del estigma externo en los síntomas depresivos mediante la homofobia internalizada, y si el afrontamiento comunitario moderó los efectos del estigma externo en la homofobia internalizada y los síntomas depresivos. Se comprobaron hipótesis utilizando modelos de interdependencia actor-pareja con una muestra de 543 parejas masculinas cisgénero pertenecientes a minorías sexuales. Los resultaros indicaron que las experiencias de estigma externo de ambos integrantes de la pareja estuvieron asociadas con niveles elevados de homofobia internalizada mediante efectos en el actor y la pareja. La homofobia internalizada solo estuvo asociada con síntomas depresivos elevados mediante efectos en el actor. El análisis de efectos indirectos indicó que la homofobia internalizada medió la influencia del estigma externo del actor y la pareja en los síntomas depresivos. El afrontamiento comunitario moderó los efectos directos del estigma externo en la homofobia internalizada y atenuó los efectos condicionales indirectos del estigma externo en los síntomas depresivos del actor y la pareja. Los resultados subrayan el papel que desempeñan los procesos relacionales íntimos a la hora de comprender los efectos del estigma externo en los síntomas depresivos.

The transcription factor T-bet regulates intestinal inflammation mediated by interleukin-7 receptor+ innate lymphoid cells.

Mice lacking the transcription factor T-bet in the innate immune system develop microbiota-dependent colitis. Here, we show that interleukin-17A (IL-17A)-producing IL-7Rα(+) innate lymphoid cells (ILCs) were potent promoters of disease in Tbx21(-/-)Rag2(-/-) ulcerative colitis (TRUC) mice. TNF-α produced by CD103(-)CD11b(+) dendritic cells synergized with IL-23 to drive IL-17A production by ILCs, demonstrating a previously unrecognized layer of cellular crosstalk between dendritic cells and ILCs. We have identified Helicobacter typhlonius as a key disease trigger driving excess TNF-α production and promoting colitis in TRUC mice. Crucially, T-bet also suppressed the expression of IL-7R, a key molecule involved in controlling intestinal ILC homeostasis. The importance of IL-7R signaling in TRUC disease was highlighted by the dramatic reduction in intestinal ILCs and attenuated colitis following IL-7R blockade. Taken together, these data demonstrate the mechanism by which T-bet regulates the complex interplay between mucosal dendritic cells, ILCs, and the intestinal microbiota.