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Abstract Background Women who engage in sex work and use drugs (WSWUD) experience disproportionate HIV risks. Substance use treatment bridge clinics offer an opportunity to increase HIV pre-exposure prophylaxis (PrEP) delivery to WSWUD, but research on best practices is lacking. Therefore, we explored facilitators and barriers to PrEP across the PrEP care continuum in these settings. Methods Bridge clinic and affiliated harm reduction health service providers and WSWUD from Boston were recruited using passive and active outreach between December 2021 and August 2022. Participants were invited to take part in semi-structured phone or in-person interviews to explore HIV prevention and PrEP care experiences overall and within bridge clinic settings. Deductive codes were developed based on HIV risk environment frameworks and the Information-Motivation-Behavioral Skills model and inductive codes were added based on transcript review. Grounded content analysis was used to generate themes organized around the PrEP care continuum. Results The sample included 14 providers and 25 WSWUD. Most WSWUD were aware of PrEP and more than half had initiated PrEP at some point. However, most who initiated PrEP did not report success with daily oral adherence. Providers and WSWUD described facilitators and barriers to PrEP across the steps of the care continuum: Awareness, uptake, adherence, and retention. Facilitators for WSWUD included non-stigmatizing communication with providers, rapid wraparound substance use treatment and HIV services, having a PrEP routine, and service structures to support PrEP adherence. Barriers included low HIV risk perceptions and competing drug use and survival priorities. Provider facilitators included clinical note templates prompting HIV risk assessments and training. Barriers included discomfort discussing sex work risks, competing clinical priorities, and a lack of PrEP adherence infrastructure. Conclusion WSWUD and bridge clinic providers favored integrated HIV prevention and substance use services in harm reduction and bridge clinic settings. Harm reduction and bridge clinic programs played a key role in HIV prevention and PrEP education for WSWUD. Effective behavioral and structural interventions are still needed to improve PrEP adherence for WSWUD.

The biota of Sulawesi is noted for its high degree of endemism and for its substantial levels of in situ biological diversification. While the island's long period of isolation and dynamic tectonic history have been implicated as drivers of the regional diversification, this has rarely been tested in the context of an explicit geological framework. Here, we provide a tectonically informed biogeographical framework that we use to explore the diversification history of Sulawesi flying lizards (the Draco lineatus Group), a radiation that is endemic to Sulawesi and its surrounding islands. We employ a framework for inferring cryptic speciation that involves phylogeographic and genetic clustering analyses as a means of identifying potential species followed by population demographic assessment of divergence-timing and rates of bi-directional migration as means of confirming lineage independence (and thus species status). Using this approach, phylogenetic and population genetic analyses of mitochondrial sequence data obtained for 613 samples, a 50-SNP data set for 370 samples, and a 1249-locus exon-capture data set for 106 samples indicate that the current taxonomy substantially understates the true number of Sulawesi Draco species, that both cryptic and arrested speciations have taken place, and that ancient hybridization confounds phylogenetic analyses that do not explicitly account for reticulation. The Draco lineatus Group appears to comprise 15 species-9 on Sulawesi proper and 6 on peripheral islands. The common ancestor of this group colonized Sulawesi ~11 Ma when proto-Sulawesi was likely composed of two ancestral islands, and began to radiate ~6 Ma as new islands formed and were colonized via overwater dispersal. The enlargement and amalgamation of many of these proto-islands into modern Sulawesi, especially during the past 3 Ma, set in motion dynamic species interactions as once-isolated lineages came into secondary contact, some of which resulted in lineage merger, and others surviving to the present. [Genomics; Indonesia; introgression; mitochondria; phylogenetics; phylogeography; population genetics; reptiles.].

The presentations in this session of the Monticello II conference were aimed at summarizing what is known about asbestiform and non-asbestiform elongate mineral particles (EMPs) and mesothelioma risks based on evidence from experimental and epidemiology studies. Dr. Case discussed case reports of mesothelioma over the last several decades. Dr. Taioli indicated that the epidemiology evidence concerning non-asbestiform EMPs is weak or lacking, and that progress would be limited unless mesothelioma registries are established. One exception discussed is that of taconite miners, who are exposed to grunerite. Drs. Mandel and Odo noted that studies of taconite miners in Minnesota have revealed an excess rate of mesothelioma, but the role of non-asbestiform EMPs in this excess incidence of mesothelioma is unclear. Dr. Becich discussed the National Mesothelioma Virtual Bank (NMVB), a virtual mesothelioma patient registry that includes mesothelioma patients' lifetime work histories, exposure histories, biospecimens, proteogenomic information, and imaging data that can be used in epidemiology research on mesothelioma. Dr. Bernstein indicated that there is a strong consensus that long, highly durable respirable asbestiform EMPs have the potential to cause mesothelioma, but there is continued debate concerning the biodurability required, and the dimensions (both length and diameter), the shape, and the dose associated with mesothelioma risk. Finally, Dr. Nel discussed how experimental studies of High Aspect Ratio Engineered Nanomaterials have clarified dimensional and durability features that impact disease risk, the impact of inflammation and oxidative stress on the epigenetic regulation of tumor suppressor genes, and the generation of immune suppressive effects in the mesothelioma tumor microenvironment. The session ended with a discussion of future research needs.

Food insecurity (FI) impacts people with HIV (PWH) and those who use substances (i.e. drugs and alcohol). We evaluated the longitudinal association between FI and HIV transmission risks (unprotected sexual contacts and shared needles/syringes). Among 351 PWH who use substances in Russia, 51.6% reported FI and 37.0% past month injection drug use. The mean number of unprotected sexual contacts in the past 90 days was 13.4 (SD 30.1); 9.7% reported sharing needles/syringes in the past month. We did not find a significant association between mild/moderate FI (adjusted IRR = 0.87, 95% CI 0.47, 1.61) or severe FI (aIRR = 0.84, 95% CI 0.46, 1.54; global p = 0.85) and unprotected sexual contacts. We observed a significant association between severe FI and sharing needles/syringes in the past month (adjusted OR = 3.27, 95% CI 1.45, 7.39; p = 0.004), but not between mild/moderate FI and sharing needles/syringes in the past month (aOR = 1.40,95% CI 0.58, 3.38; p = 0.45). These findings suggest that severe FI could be a potential target for interventions to lower HIV transmission.

Objectives: This study examines how the transition to remote delivery during the spring of 2020 affected student learning in the basic communication course. Methods: Participants in three different course delivery modes (face-to-face, online, and live interactive) were enrolled in a public speaking course with standardized adaptive reading quizzes, exams, and speech assignments. Participants completed several measures over the course of the semester and had their responses paired up with their end-of-semester grade book data. Results: Results of this study indicate that students who were enrolled in a face-to-face course and transitioned online during the COVID-19 pandemic were outperformed by online and learning interactive students in several of the standardized assignments in the course. Conclusions: Overall, face-to-face (FtF) students performed four percentage points lower in the course than the learning interactive and online groups while also demonstrating more emotional interest in the course than the other two groups. Implication for Theory and/or Practice: In future transitions to remote learning, FtF students may experience greater disruption than existing online students. Instructors should be mindful of this finding in transitioning to remote learning during the semester.

BackgroundSouth Asians (SA) represent the fastest growing US immigrant group, and previous studies have indicated that they face disproportionately high burden of cardiometabolic disease. Cardiometabolic disease manifests as a syndemic or synergistic epidemic encompassing multiple disease clusters influenced by biological, social, and psychological factors stemming from the acculturative process. This process may exacerbate morbidity within immigrant subgroups. Our aim was to identify cardiometabolic risk profiles among SA using indicators of acculturation.MethodsWe conducted a latent class analysis on data from the Mediators of Atherosclerosis in South Asians Living in America study (N=771). A composite cardiometabolic disease outcome was constructed using prevalent hypertension, type 2 diabetes, and body mass index. Acculturation indicators included years living in the US, English language proficiency, dietary behaviors, preservation of cultural traditions, social and neighborhood support, maintenance of social relationships (i.e., friendships), and experiences of discrimination, along with proxies of acculturative stress (i.e., depressive symptomology, trait anxiety and anger). Social and environmental determinants of health, health behaviors, religiosity and spirituality served as covariates to further assess latent class membership.ResultsFour cardiometabolic risk profiles emerged: (1) lowest risk [73.8% of sample] characterized by high integration into both SA and US cultures; (2) the modest risk [13.4% of sample], exhibiting elevated levels of mental health distress and experiences of discrimination, and distancing themselves from both cultures; and the (3) moderate risk [8.9% of sample] and (4) highest risk [3.9% of sample], demonstrating greater assimilation into US culture. Compared to the lowest risk profile: the modest risk profile was associated with low-income and conflicting attitudes about religion/spirituality, while the moderate risk profile was characterized by lower income and educational attainment with positive behaviors and attitudes toward religion/spirituality.ConclusionFindings expand our understanding of immigrant cardiometabolic health as a syndemic issue wherein multiple co-occurring and interacting processes synergize to produce negative outcomes in already at-risk subpopulations. Furthermore, acculturation emerges as a crucial factor in understanding health disparities among immigrant and refugee groups in the US.

Abstract Parkinson’s disease (PD) is a neurodegenerative disease characterized by progressive motor symptoms and alpha-synuclein (αsyn) aggregation in the nervous system. For unclear reasons, PD patients with certain GBA1 mutations (GBA-PD) have a more aggressive clinical progression. Two testable hypotheses that can potentially account for this phenomenon are that GBA1 mutations promote αsyn spread or drive the generation of highly pathogenic αsyn polymorphs (i.e., strains). We tested these hypotheses by treating homozygous GBA1 D409V knockin (KI) mice with human α-syn-preformed fibrils (PFFs) and treating wild-type mice (WT) with several αsyn-PFF polymorphs amplified from brain autopsy samples collected from patients with idiopathic PD and GBA-PD patients with either homozygous or heterozygous GBA1 mutations. Robust phosphorylated-αsyn (PSER129) positive pathology was observed at the injection site (i.e., the olfactory bulb granule cell layer) and throughout the brain six months following PFF injection. The PFF seeding efficiency and degree of spread were similar regardless of the mouse genotype or PFF polymorphs. We found that PFFs amplified from the human brain, regardless of patient genotype, were generally more effective seeders than wholly synthetic PFFs (i.e., non-amplified); however, PFF concentration differed between these two studies, which might also account for the observed differences. To investigate whether the molecular composition of pathology differed between different seeding conditions, we performed Biotinylation by Antibody Recognition on PSER129 (BAR-PSER129). We found that for BAR-PSER129, the endogenous PSER129 pool dominated identified interactions, and thus, very few potential interactions were explicitly identified for seeded pathology. However, we found Dynactin Subunit 2 (Dctn2) interaction was shared across all PFF conditions, and NCK Associated Protein 1 (Nckap1) and Adaptor Related Protein Complex 3 Subunit Beta 2 (Ap3b2) were unique to PFFs amplified from GBA-PD brains of heterozygous mutation carriers. In conclusion, both the genotype and αsyn strain had little effect on overall seeding efficacy and global PSER129-interactions.

Abstract Parkinson’s disease (PD) is associated with aggregation of misfolded α-synuclein and other proteins, including tau. We designed a cross-sectional study to quantify the brain binding of [11C]PBB3 (a ligand known to bind to misfolded tau and possibly α-synuclein) as a proxy of misfolded protein aggregation in Parkinson’s disease (PD) subjects with and without cognitive impairment and healthy controls (HC). In this cross-sectional study, nineteen cognitively normal PD subjects (CN-PD), thirteen cognitively impaired PD subjects (CI-PD) and ten HC underwent [11C]PBB3 PET. A subset of the PD subjects also underwent PET imaging with [11C](+)DTBZ to assess dopaminergic denervation and [11C]PBR28 to assess neuroinflammation. Compared to HC, PD subjects showed higher [11C]PBB3 binding in the posterior putamen but not the substantia nigra. There was no relationship across subjects between [11C]PBB3 and [11C]PBR28 binding in nigrostriatal regions. [11C]PBB3 binding was increased in the anterior cingulate in CI-PD compared to CN-PD and HC, and there was an inverse correlation between cognitive scores and [11C]PBB3 binding in this region across all PD subjects. Our results support a primary role of abnormal protein deposition localized to the posterior putamen in PD. This suggests that striatal axonal terminals are preferentially involved in the pathophysiology of PD. Furthermore, our findings suggest that anterior cingulate pathology might represent a significant in vivo marker of cognitive impairment in PD, in agreement with previous neuropathological studies.

Abstract Pou6f2 is a genetic connection between central corneal thickness (CCT) in the mouse and a risk factor for developing primary open-angle glaucoma. POU6F2 is also a risk factor for several conditions in humans, including glaucoma, myopia, and dyslexia. Recent findings demonstrate that POU6F2-positive retinal ganglion cells (RGCs) comprise a number of RGC subtypes in the mouse, some of which also co-stain for Cdh6 and Hoxd10. These POU6F2-positive RGCs appear to be novel of ON–OFF directionally selective ganglion cells (ooDSGCs) that do not co-stain with CART or SATB2 (typical ooDSGCs markers). These POU6F2-positive cells are sensitive to damage caused by elevated intraocular pressure. In the DBA/2J mouse glaucoma model, heavily-labeled POU6F2 RGCs decrease by 73% at 8 months of age compared to only 22% loss of total RGCs (labeled with RBPMS). Additionally, Pou6f2 −/− mice suffer a significant loss of acuity and spatial contrast sensitivity along with an 11.4% loss of total RGCs. In the rhesus macaque retina, POU6F2 labels the large parasol ganglion cells that form the magnocellular (M) pathway. The association of POU6F2 with the M-pathway may reveal in part its role in human glaucoma, myopia, and dyslexia.

Abstract Whole-body physical exercise has been shown to promote retinal structure and function preservation in animal models of retinal degeneration. It is currently unknown how exercise modulates retinal inflammatory responses. In this study, we investigated cytokine alterations associated with retinal neuroprotection induced by voluntary running wheel exercise in a retinal degeneration mouse model of class B1 autosomal dominant retinitis pigmentosa, I307N Rho. I307N Rho mice undergo rod photoreceptor degeneration when exposed to bright light (induced). Our data show, active induced mice exhibited significant preservation of retinal and visual function compared to inactive induced mice after 4 weeks of exercise. Retinal cytokine expression revealed significant reductions of proinflammatory chemokines, keratinocyte-derived chemokine (KC) and interferon gamma inducible protein-10 (IP-10) expression in active groups compared to inactive groups. Through immunofluorescence, we found KC and IP-10 labeling localized to retinal vasculature marker, collagen IV. These data show that whole-body exercise lowers specific retinal cytokine expression associated with retinal vasculature. Future studies should determine whether suppression of inflammatory responses is requisite for exercise-induced retinal protection.

ABSTRACTStigma that people with HIV who inject drugs experience negatively impacts HIV and substance use care, but stigma’s association with sharing injection equipment is not known. This is a cross-sectional analysis of data from two studies of people with HIV reporting drug injection (N = 319) in St. Petersburg, Russia (September 2018-December 2020). We used logistic regression to examine associations between HIV stigma and substance use stigma scores (categorised into quartiles) and past 30-day equipment sharing, adjusting for demographic and clinical characteristics. Secondary analyses examined associations of arrest history and social support with sharing equipment. Almost half (48.6%) of participants reported sharing injection equipment. Among groups who did and did not share, mean HIV stigma (2.3 vs 2.2) and substance use stigma (32 vs 31) scores were similar. Adjusted analyses detected no significant associations between HIV stigma quartiles (global p-value = 0.85) or substance use stigma quartiles (global p-value = 0.51) and sharing equipment. Neither arrest history nor social support were significantly associated with sharing equipment. In this cohort, sharing injection equipment was common and did not vary based on stigma, arrest history, or social support. To reduce equipment sharing, investments in sterile injection equipment access in Russia should be prioritised over interventions to address stigma.

Cardiac shape modeling is a useful computational tool that has provided quantitative insights into the mechanisms underlying dysfunction in heart disease. The manual input and time required to make cardiac shape models, however, limits their clinical utility. Here we present an end-to-end pipeline that uses deep learning for automated view classification, slice selection, phase selection, anatomical landmark localization, and myocardial image segmentation for the automated generation of three-dimensional, biventricular shape models. With this approach, we aim to make cardiac shape modeling a more robust and broadly applicable tool that has processing times consistent with clinical workflows. Cardiovascular magnetic resonance (CMR) images from a cohort of 123 patients with repaired tetralogy of Fallot (rTOF) from two internal sites were used to train and validate each step in the automated pipeline. The complete automated pipeline was tested using CMR images from a cohort of 12 rTOF patients from an internal site and 18 rTOF patients from an external site. Manually and automatically generated shape models from the test set were compared using Euclidean projection distances, global ventricular measurements, and atlas-based shape mode scores. The mean absolute error (MAE) between manually and automatically generated shape models in the test set was similar to the voxel resolution of the original CMR images for end-diastolic models (MAE = 1.9 ± 0.5 mm) and end-systolic models (MAE = 2.1 ± 0.7 mm). Global ventricular measurements computed from automated models were in good agreement with those computed from manual models. The average mean absolute difference in shape mode Z-score between manually and automatically generated models was 0.5 standard deviations for the first 20 modes of a reference statistical shape atlas. Using deep learning, accurate three-dimensional, biventricular shape models can be reliably created. This fully automated end-to-end approach dramatically reduces the manual input required to create shape models, thereby enabling the rapid analysis of large-scale datasets and the potential to deploy statistical atlas-based analyses in point-of-care clinical settings. Training data and networks are available from cardiacatlas.org.

Current indications for pulmonary valve replacement (PVR) in repaired tetralogy of Fallot (rTOF) rely on cardiovascular magnetic resonance (CMR) image-based indices but are inconsistently applied, lead to mixed outcomes, and remain debated. This study aimed to test the hypothesis that specific markers of biventricular shape may discriminate differences between rTOF patients who did and did not require subsequent PVR better than standard imaging indices. In this cross-sectional retrospective study, biventricular shape models were customized to CMR images from 84 rTOF patients. A statistical atlas of end-diastolic shape was constructed using principal component analysis. Multivariate regression was used to quantify shape mode and imaging index associations with subsequent intervention status (PVR, n = 48 vs. No-PVR, n = 36), while accounting for confounders. Clustering analysis was used to test the ability of the most significant shape modes and imaging indices to discriminate PVR status as evaluated by a Matthews correlation coefficient (MCC). Geometric strain analysis was also conducted to assess shape mode associations with systolic function. PVR status correlated significantly with shape modes associated with right ventricular (RV) apical dilation and left ventricular (LV) dilation (p