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OBJECTIVES/GOALS: The objectives are 1) to describe the creation and implementation of a Clinical Research Feasibility Program at the University of Miami Miller School of Medicine (UMMSOM), and 2) to share early findings demonstrating its effectiveness in improving research operations which may be helpful for other academic medical centers. METHODS/STUDY POPULATION: Many clinical trials are closed prematurely because of low accrual or not being able to meet the target enrollment. The Miami CTSI and UMMSOM Executive Dean for Research office collaborated to establish the Research Feasibility Committee (RFC) focusing on clinical trial selection with upfront feasibility and recruitment planning. Program implementation included: 1) selecting faculty with successful clinical trial track records as committee members; 2) developing processes, tools, and governance; 3) feasibility pilot testing; and 4) feasibility program roll out and refinement. The feasibility review process starts with the PI/Designee completing a REDCap study intake form, followed by an administrative review to ensure completeness of the form. The RFC chair assigns reviewers for the studies. RESULTS/ANTICIPATED RESULTS: The RFC went live on September 1, 2022 reviewing industry sponsor clinical research studies. The RFC conducts a systematic feasibility assessment of the study protocol, operational requirements, enrollment barriers, institutional resources, and study budget (if available) for all applicable research studies prior to IRB submission and contract negotiation at the UMMSOM. To date, the RFC has received over 270 submissions. Based on feedback from users, the committee has made changes to improve the comprehension of questions and added questions to ensure capturing of critical information to assess study feasibility. Initial metrics suggest simply implementing the review process has decreased the number of clinical trial submissions: average number of studies per quarter was 41 pre-RFC vs 24 post RFC. DISCUSSION/SIGNIFICANCE: The development and implementation of the RFC involved many stakeholders from the research enterprise. Clear and frequent communication to the research community was a key factor in the program’s success. The next phase is assessing the impact of the RFC, such as preserving vital resources for trials more likely to be successful.

The current study investigates the venom-delivery system of green and red morphotypes of the sea anemone Actinia equina to disclose its potential as a source of bioactive compounds. We compared the two morphotypes using electron and optical microscopy, proteomics, and toxicity assessment on zebrafish embryos. Specialized venom-injecting cells (nematocysts) are equally distributed and found in the tentacles of both varieties. Proteomics revealed proteins of interest in both red and green Actinia, yielding the three most abundant Gene Ontology (GO) terms related to the biological processes “proteolysis”, “hemolysis in another organism” and “lipid catabolic process”. Neurotoxins and cytolytic toxins similar to known cnidarian toxins like PsTX-60A and AvTX-60A, for instance, were identified in both types. Extracts from green and red anemones were toxic to zebrafish embryos, with green anemone venom appearing to be more potent. The findings highlight the presence of proteinaceous toxins in A. equina and the potential for different varieties to possess distinct bioactive compounds. Notably, pore-forming toxins are suggested for molecular probes and immunotoxins, making them valuable assets for potential biotechnological and biomedical purposes.

Therapeutic Area: ASCVD/CVD in Special Populations Background: Atherosclerosis is a significant cause of cardiovascular disease (CVD). People with HIV (PWH) have a greater risk of CVD and vascular events, including myocardial infarction (MI) and ischemic stroke. A strong association has been described between CAS in PWH, but the mechanism is incompletely understood. Methods: We performed a retrospective chart review of patients who received care at University of Miami/Jackson Memorial Hospital HIV clinics between 2017-2019 (N=1,166) and stratified patients into PWH with Normal Carotid Artery Ultrasound (CAUS) and Abnormal CAUS. PWH with Abnormal CAUS (N=24) was defined as patients with any degree of CAS reported by CAUS. PWH with Normal CAUS (N=13) was defined as patients with no CAS reported by CAUS. Data regarding demographic, clinical, imaging, and laboratory results was obtained. Results: The prevalence of PWH with CAS was 2.1%. PWH with an Abnormal CAUS were significantly older (63.7years vs. 55.5 years, p=0.049) and had a lower absolute CD8 count (700.2 cells/mm3 vs. 955.1 cells/mm3, p=0.037) compared to PWH with a Normal CAUS. Baseline characteristics are described in Table 1.Regarding the medical management of PWH who had CAS, 4.2% of patients were on Aspirin, 58.3% were on a statin, and no patients were on anticoagulation. 70.8% of PWH with CAS were on hypertension treatment, and of those, 33.3% were on a beta-blocker medication, 20.8% were on an angiotensin-converting enzyme inhibitor, and 33.3% were on an angiotensin receptor blocker. Conclusion: We found a CAS prevalence of 2.1%, greater than reported for the general population (1.5% Lancet 2020). Traditional CVD risk factors and HIV-related factors alone do not explain this finding. 4.2% of PWH CAS were on Aspirin (Class I recommendation for all patients with CAS), and 58.3% were on a statin (Class IA recommendation). Appropriate medical therapy needs to be emphasized in those with CAS to reduce the risk of vascular complications. The small sample size limits the results of this study, and further studies are needed to understand the risk factors and mechanisms leading to increased risk of vascular events and CVD in this population.

Therapeutic Area: Heart Failure Background: People with human immunodeficiency virus (PWH) have an improved life expectancy because of the wide availability of antiretroviral therapy (ART), resulting in an increased prevalence of heart failure (HF). Determining whether PWH and HF have specific associations to risk factors is critical because HF subtypes differ in the underlying mechanism, treatment, and prognosis. Methods: We performed a retrospective chart review of PWH who received care at the University of Miami/Jackson Memorial Hospital HIV clinics between 2017-2019 (N=1,166). Patients with an available echocardiogram or documented HF were included for analysis (n=305). Heart failure was defined as having an ejection fraction (EF)

BackgroundMany women with HIV (WWH) have suboptimal adherence to oral antiretroviral therapy (ART) due to multilevel barriers to HIV care access and retention. A long-acting injectable (LAI) version of ART was approved by the US Food and Drug Administration in January 2021 and has the potential to overcome many of these barriers by eliminating the need for daily pill taking. However, it may not be optimal for all WWH. It is critical to develop tools that facilitate patient-provider shared decision making about oral versus LAI ART modalities to promote women’s adherence and long-term HIV outcomes. ObjectiveThis study will develop and pilot test a web-based patient decision aid called i.ART+support (i.ARTs). This decision aid aims to support shared decision making between WWH and their providers, and help women choose between oral and LAI HIV treatment. MethodsThe study will occur in 3 phases. In phase 1, we will utilize a mixed methods approach to collect data from WWH and medical and social service providers to inform i.ARTs content. During phase 2, we will conduct focus groups with WWH and providers to refine i.ARTs content and develop the web-based decision aid. In phase 3, i.ARTs will be tested in a randomized controlled trial with 180 women in Miami, Florida, and assessed for feasibility, usability, and acceptability, as well as to evaluate the associations between receiving i.ARTs and viral suppression, ART pharmacy refills, and clinic attendance. ResultsThis study was funded in March 2021. Columbia University’s IRB approved the study protocols (approval number IRB-AAAT5314). Protocols for phase 1 interviews have been developed and interviews with service providers started in September 2021. We will apply for Clinicaltrials.gov registration prior to phase 3, which is when our first participant will be enrolled in the randomized controlled trial. This is anticipated to occur in April 2023. ConclusionsThis study is the first to develop a web-based patient decision aid to support WWH choices between oral and LAI ART. Its strengths include the incorporation of both patient and provider perspectives, a mixed methods design, and implementation in a real-world clinical setting. International Registered Report Identifier (IRRID)DERR1-10.2196/35646

The vaginal microbiota is known to impact women's health, but the biological factors that influence the composition of the microbiota are not fully understood. We previously observed that levels of glycogen in the lumen of the vagina were higher in women that had a high body mass index (BMI). Vaginal glycogen is thought to impact the composition of the vaginal microbiota. We therefore sought to determine if BMI was associated having or not having bacterial vaginosis (BV), as determined by the Amsel criteria. We also hypothesized that increased blood glucose levels could lead to the previously-observed higher vaginal glycogen levels and therefore investigated if hemoglobin A1c levels were associated with BV. We analyzed data from the Women's Interagency HIV Study using multiple multivariable (GEE) logistic regression models to assess the relationship between BMI, BV and blood glucose. Women with a BMI >30 kg/m2 (obese) had a lower rate (multivariable adjusted OR 0.87 (0.79-0.97), p = 0.009) of BV compared to the reference group (BMI 18.5-24.9 kg/m2). There was a significantly lower rate of BV in post-menopausal obese women compared to the post-menopausal reference group, but not in pre-menopausal women. HIV- post-menopausal obese women had a significantly lower rate of BV, but this was not seen in HIV+ post-menopausal obese women. Pre-menopausal women with a higher hemoglobin A1c (≥6.5%) had a significantly lower rate (multivariable adjusted OR 0.66 (0.49-0.91), p = 0.010) of BV compared to pre-menopausal women with normal hemoglobin A1c levels (

OBJECTIVES/GOALS: The goal of this study is to describe the implementation of a formal research mentoring training program at Miami CTSI in collaboration with University of Colorado CTSI, to build effective mentor-mentee relationships that help build successful research careers for junior faculty. METHODS/STUDY POPULATION: The Miami CTSI Research Mentoring Training is a three-part series for early stage faculty and their mentors to strengthen mentoring skills and build successful relationships. The curriculum uses evidence-based strategies and is modeled after University of Colorado CTSIs CO-Mentor Training Program. The pilot training was conducted as a train-the-trainer program with subsequent workshops led by Miami CTSI faculty. The program has mentee-only, mentor-only, and joint sessions covering topics such as networking skills, managing financial aspects of an academic career, and career mapping. To assess program effectiveness, pre/post surveys were conducted and follow up surveys are planned. Data collected will assess participant diversity, research productivity, and mentoring relationship status. RESULTS/ANTICIPATED RESULTS: A total of 49 mentor-mentee teams from 18 departments participated in the training over two cohorts. An upcoming third cohort will be included in the analysis. Overall, 100% mentors and 86% mentees reported the overall value of the program as positive. Post-training, mentees reported an increase in confidence in creating career development plans and articulating career goals. Mentors reported an increase in confidence in providing guidance tailored to mentees needs. Mentees reported improvement in their knowledge of developing personal narratives and handling financial aspects of research; both mentors and mentees reported improvement in insights into achieving work-life balance. Follow up survey results will provide insight into the evolution of the mentoring relationships. DISCUSSION/SIGNIFICANCE: Miami CTSIs mentoring training demonstrated successful participation and positive feedback from mentors and mentees and is poised to become a critical component of the Miami CTSIs research career development pipeline.

The Prevalence of HSV-1 and HSV-2 among STD clinics in Miami is not known. The objective of this study was to evaluate infection rates of HSV 1 and 2, and to describe the socio-demographic characteristics, sexual orientation and co-infection with HIV and other STIs, in individuals attending a Sexually Transmitted Diseases (STD) clinic in Miami. A cross-sectional study of 663 patients tested for HSV type-specific serology or herpes culture during the year 2007 was performed. An overall infection rate of HSV-1 was 42.1% and 36.7% for HSV-2. Statistically higher infection rates for HSV-1and 2 were seen among Hispanics (56.7%, 54.4%) compared to non-Hispanic black (36.80%, 41.70%) and non-Hispanic white patients (6.1%, 3.5%) respectively. Females showed higher HSV-2 infection rates over males, 41.6% vs. 58.4%; p = 0.03. HSV-1 and 2 infection rates were 60.2% and 57.6% among foreign-born individuals, in contrast to 39.8% and 42.4% found among persons born in the United States. Our data shows high infection rates for HSV-1 and 2 in this community, and especially among the Hispanic population. Efforts to decrease acquisition among the Hispanic population should be a focus of future STI prevention programs.

It is widely accepted in eukaryotes that the cleavage furrow only initiates after mitosis completion. In fission yeast, cytokinesis requires the synthesis of a septum tightly coupled to cleavage furrow ingression. The current cytokinesis model establishes that simultaneous septation and furrow ingression only initiate after spindle breakage and mitosis exit. Thus, this model considers that although Cdk1 is inactivated at early-anaphase, septation onset requires the long elapsed time until mitosis completion and full activation of the Hippo-like SIN pathway. Here, we studied the precise timing of septation onset regarding mitosis by exploiting both the septum-specific detection with the fluorochrome calcofluor and the high-resolution electron microscopy during anaphase and telophase. Contrarily to the existing model, we found that both septum and cleavage furrow start to ingress at early anaphase B, long before spindle breakage, with a slow ingression rate during anaphase B, and greatly increasing after telophase onset. This shows that mitosis and cleavage furrow ingression are not concatenated but simultaneous events in fission yeast. We found that the timing of septation during early anaphase correlates with the cell size and is regulated by the corresponding levels of SIN Etd1 and Rho1. Cdk1 inactivation was directly required for timely septation in early anaphase. Strikingly the reduced SIN activity present after Cdk1 loss was enough to trigger septation by immediately inducing the medial recruitment of the SIN kinase complex Sid2-Mob1. On the other hand, septation onset did not depend on the SIN asymmetry establishment, which is considered a hallmark for SIN activation. These results recalibrate the timing of key cytokinetic events in fission yeast; and unveil a size-dependent control mechanism that synchronizes simultaneous nuclei separation with septum and cleavage furrow ingression to safeguard the proper chromosome segregation during cell division.

Leptodactylus latinasus pertenece al grupo L. fuscus, cuyas especies construyen cámaras donde colocan un nido de espuma, donde luego se desarrollan los primeros estadios larvales. El objetivo de este trabajo fue describir la histología de ovarios vitelogénicos en hembras de Leptodactylus latinasus. Veintiocho hembras fueron procesadas, algunas al momento de ser colectadas en el campo, mientras que otras fueron colocadas en el laboratorio en presencia de machos, con cámaras de barro construídas artificialmente. Los ovarios fueron fijados en formol bufferado y procesados con técnicas histológicas de rutina. Se reconocen alteraciones ováricas en ovocitos vitelogénicos que impiden el proceso de reproducción, tales como: (1) pocos ovocitos vitelogénicos no atrésicos; (2) atresia periférica; (3) atresia invasiva hacia el centro de ovocitos con alteración del vitelo; (4) casi completa vacuolización lipídica, cuerpos apoptóticos; (5) desprendimiento de células foliculares en algunos ovocitos; (6) disminución del tamaño ovocitarios. Además, es notable la intromisión de los cuerpos grasos en los ovocitos, con vasos, células fibroblásticas y macrófagos. La atresia masiva de ovocitos observada en hembras vitelogénicas no fue descripta en otras especies de anuros. Esto estaría indicando que las condiciones para la ovulación no fueron óptimas. El amplexo y la ovoposición de esta especie ocurren en cámaras de barro, las cuales constituyen un microhábitat donde las condiciones serían las apropiadas para la reproducción. Así, los resultados obtenidos sugieren que si las condiciones microambientales no son favorables, no se produce la reproducción, y los ovarios sufren atrofia masiva.

Recent studies have indicated the existence of an extensive trans-genomic trans-mural co-metabolism between gut microbes and animal hosts that is diet-, host phylogeny- and provenance-influenced. Here, we analyzed the biodiversity at the level of small subunit rRNA gene sequence and the metabolic composition of 18 Mbp of consensus metagenome sequences and activity characteristics of bacterial intra-cellular extracts, in wild Iberian lynx (Lynx pardinus) fecal samples. Bacterial signatures (14.43% of all of the Firmicutes reads and 6.36% of total reads) related to the uncultured anaerobic commensals Anaeroplasma spp., which are typically found in ovine and bovine rumen, were first identified. The lynx gut was further characterized by an over-representation of 'presumptive' aquaporin aqpZ genes and genes encoding 'active' lysosomal-like digestive enzymes that are possibly needed to acquire glycerol, sugars and amino acids from glycoproteins, glyco(amino)lipids, glyco(amino)glycans and nucleoside diphosphate sugars. Lynx gut was highly enriched (28% of the total glycosidases) in genes encoding α-amylase and related enzymes, although it exhibited low rate of enzymatic activity indicative of starch degradation. The preponderance of β-xylosidase activity in protein extracts further suggests lynx gut microbes being most active for the metabolism of β-xylose containing plant N-glycans, although β-xylosidases sequences constituted only 1.5% of total glycosidases. These collective and unique bacterial, genetic and enzymatic activity signatures suggest that the wild lynx gut microbiota not only harbors gene sets underpinning sugar uptake from primary animal tissues (with the monotypic dietary profile of the wild lynx consisting of 80-100% wild rabbits) but also for the hydrolysis of prey-derived plant biomass. Although, the present investigation corresponds to a single sample and some of the statements should be considered qualitative, the data most likely suggests a tighter, more coordinated and complex evolutionary and nutritional ecology scenario of carnivore gut microbial communities than has been previously assumed.

Metabolic syndrome (MetS) has become a major public health concern. Because of their numerous health-promoting biological properties, polyphenols are potential candidates to ameliorate MetS and, recently, the incorporation of these compounds into widely consumed foodstuffs has emerged as a potential strategy to enhance their intake. Therefore, we aimed to assess the potential beneficial effects of biscuits enriched with the citrus polyphenols hesperidin and naringenin (HN) in rats that were fed either standard chow (STD) or an obesogenic cafeteria diet (CAF) for 16 weeks. The STD and CAF groups were supplemented with either control or HN biscuits for the final 8 weeks of the study. CAF-fed rats developed MetS, characterized by obesity, insulin resistance, hypertension and dyslipidemia. HN supplementation in CAF-fed rats ameliorated hypertension and insulin resistance and significantly reduced body weight, mesenteric adiposity, total cholesterol, LDL-C and oxidative stress. Hence, HN biscuits may be a promising functional food against MetS.

Metabolic syndrome (MetS) is a global epidemic concern. Polyphenols are proposed as good candidates for its prevention, although their mechanisms are not fully understood. The gut microbiota seems to play a key role in polyphenol beneficial effects. Here, we assessed the effects of the citrus polyphenol hesperidin combining an untargeted metabolomics approach, which has an inherent potential to elucidate the host-microbiome interplay, with extensive anthropometric and biochemical characterizations and integrating metabolomics results with our previous 16S rRNA bacterial sequencing data. The rats were fed either a standard or an obesogenic cafeteria diet (CAF) for 17 weeks. After nine weeks, rats were supplemented with vehicle; low- (H1), or high- (H2) hesperidin doses. CAF animals developed MetS features. Hesperidin supplementation in CAF rats decreased the total cholesterol, LDL-C, and free fatty acids. The highest hesperidin dose also ameliorated blood pressure, insulin sensitivity, and decreased markers of arterial stiffness and inflammation. Metabolomics revealed an improvement of the lipidomic profile, decreases in circulating amino acids, and lower excretions of inflammation- and oxidative stress-related metabolites. Bacteroidaceae increases in the CAF-H2 group paralleled higher excretions of microbial-derived metabolites. Overall, our results provide detailed insights into the molecular effects of hesperidin on MetS and suggest that it is a promising prebiotic for the treatment of MetS and related conditions.