Universidad Central Del Caribe Research Articles

Phenotypic Heterogeneity of Patients With Marfan Syndrome in Puerto Rico: A Case Series.

Previous studies have reported on the cardiovascular, ocular, and musculoskeletal findings in patients with Marfan syndrome (MFS). This study aims to report the ocular and genotypic findings in patients with the syndrome in Puerto Rico. A chart review of a cohort of patients with the syndrome from Puerto Rico was done. Patients were examined by at least one of the authors (NJI). Fibrillin-1 (FBN1) full gene sequencing was done to all patients (Laboratory for Molecular Medicine, Center for Genetics and Genomics, Cambridge, MA). This study was approved by the Institutional Review Board of the Universidad Central del Caribe (approval number: 2024-07). Results: Six patients aged 28-79 years were examined. There were seven female and three male patients. The average visual acuity was 0.49 and 0.52 in the right eye (OD) and left eye (OS), respectively. The average refraction (spherical equivalent) was -1.28 sph OD and -1.07 sph OS. The average intraocular pressure was 14 mmHg in both eyes (OU). A patient had a dislocated lens OD; a patient had lens dislocation OU; and a patient had prosthesis OD and aphakia OS. Upon optical coherence tomography (OCT), the retinal nerve fiber layer (RNFL) average was 75.86 µm OD and 81.85 ​​µm OS; the average cup-to-disc (C/D) ratio was 0.41 and 0.35 in the right and left eye, respectively. Upon visual field testing, the average mean deviation (MD) was -6.27 dB OD and -8.55 dB OS. Our findings underscore the significant phenotypic and genotypic heterogeneity of patients with MFS in Puerto Rico. The identification of several mutations in the FBN1 gene in the Puerto Rican population demonstrates the need for an up-to-date approach to diagnose and co-manage patients with the syndrome. This study contributes to a deeper understanding of the genetic heritage of patients with the syndrome and highlights the potential for personalized therapeutic interventions.

Addressing medical student burnout through informal peer-assisted learning: a correlational analysis

BackgroundDespite the recognized advantages of Peer-Assisted Learning (PAL) in academic settings, there is a notable absence of research analyzing its effects on students' Academic Burnout. This study aims to cover this gap by assessing the underlying effectiveness of Informal Peer-Assisted Learning (IPAL) as a cooperative learning method, focusing on its potential to mitigate academic burnout among medical students.MethodsIn 2022, a cross-sectional study was conducted at the School of Medicine, Universidad Central del Caribe, in Puerto Rico. The research team gathered data from 151 participants, 49.19% of 307 total student body. This cohort included 76 female students, 71 male students, and 4 individuals saying other. The School Burnout Inventory questionnaire (SBI-9) was employed to assess Academic Burnout, along with an added query about self-reported IPAL. The SBI-9 underwent validation processes to ascertain its reliability and validity, incorporating the Exploratory Factor Analysis and Confirmatory Factor Analysis. Following this, the investigators conducted an analysis to determine the correlation between academic burnout levels and involvement in IPAL.ResultsThe validation process of the questionnaire affirmed its alignment with an eight-item inventory, encapsulating two principal factors that elucidate academic burnout. The first factor pertains to exhaustion, while the second encompasses the combined subscales of cynicism and inadequacy.The questionnaire shows high reliability (Cronbach's alpha = 0.829) and good fit indices (Comparative Fit Index = 0.934; Tucker-Lewis Index = 0.902; Standardized Root Mean Squared Residual = 0.0495; Root Mean Squared Error of Approximation = 0.09791; p-value < 0.001). The factors proven in the selected model were used to evaluate the correlation between Academic Burnout and IPAL. Students engaged in IPAL showed significantly lower academic burnout prevalence compared to those who never participated in such practices, with a mean academic burnout score of 44.75% (SD 18.50) for IPAL engaged students versus 54.89% (SD 23.71) for those who never engaged in such practices (p-value < 0.013). Furthermore, within the group engaged in IPAL, students displayed lower levels of cynicism/inadequacy 41.98% (SD 23.41) compared to exhaustion 52.25% (SD 22.42) with a p-value < 0.001.ConclusionsThe results of this study underscore a notable issue of academic burnout among medical students within the surveyed cohort. The investigation reveals a significant correlation between Academic Burnout and IPAL, suggesting that incorporating IPAL strategies may be beneficial in addressing burnout in medical education settings. However, further research is needed to explore potential causal mechanisms.

Anatomical Variants of the Intercostobrachial Nerve and their Clinical Implications in Axillary Dissection

Currently, there are multiple treatment options for breast cancer including chemo‐ and radiotherapy. When these treatment options do not work, a radical mastectomy may be considered. This procedure includes an axillary lymph node dissection. During this type of dissection, the intercostobrachial nerve (ICBN) is commonly encountered. Originating from the T2 spinal level, the ICBN is a lateral cutaneous branch of the second intercostal nerve. After piercing the intercostal and the serratus anterior muscles, it traverses the axilla to the medial side of the arm and joins the medial cutaneous nerve of the arm. Here, we report ICBN variations on two distinct cadavers encountered during dissection of the axilla at the Department of Anatomy of the Universidad Central del Caribe School of Medicine. One of the ICBN has three branches on the left upper extremity, while another cadaver has two branches on the right upper extremity. It is important to be aware of these variations while performing an axillary lymph node dissection for breast cancer or any other procedure that involves the axillary region (e.g., regional nerve blocks). Lesions of the ICBN have been associated to post‐operative pain, paresthesia, and loss of upper extremity sensation in the dermatome supplied by this nerve. Therefore, preservation of the ICBN is an important aspect of axillary region procedures.

496 Transforming the pipeline towards independence in Clinical and Translational Research (CTR) through opportunities in research environments for underrepresented health professions faculty and students: The Title V Cooperative Project between University Puerto Rico Medical Sciences Campus and Universidad Central del Caribe (Title V Coop)

OBJECTIVES/GOALS: Diversity and interdisciplinarity are required for successful and transformational CTR. The Title V Coop developed a training curriculum for underrepresented in CTR health professions faculty and students, successfully integrating them in CTR teams. The curriculum exposed students to theory and then a practicum. METHODS/STUDY POPULATION: The curriculum and practicum included basic aspects of training in research including responsible conduct of research and the design of a proposal. The practicum focused on the organizing of a research team identified as a Clinical and Translational Mentoring Team (CTMT) and the implementation of the proposed project. Emphasis was placed on the importance of the mentor-mentee relationship, including peer mentoring. Participants were recruited from across all post-secondary institutions in Puerto Rico emphasizing the participation of faculty(UgF) and students (UgS) from undergraduate programs in health professions and the participation of graduate students GS) as peer mentors. Research mentors for each of the CTMTs were selected from faculty members that are established researchers. RESULTS/ANTICIPATED RESULTS: Twenty-seven (27) proposals from the CTMTs were approved. A total of one hundred and eight (108) participants were or are still engaged in the proposed research. Thirty-four faculty (34) members participated as mentors and three (3) peer reviewed publications have been done. Health professions and science fields represented by the participants include: Nursing, radiology technician, audiologist, medical students, basic science in biology or chemistry, public health and industrial microbiology among others. We will showcase the diversity in research topics and teams composition and their accomplishments. DISCUSSION/SIGNIFICANCE: The Title V Coop has been successful in integrating individuals from academic programs underrepresented in research into interdisciplinary and interprofessional research teams, launching a model for diversity and interdisciplinarity and representation of health professionals at all levels of research.

494 A Flexible and Transformational Approach for Learning Research and Communication Skills: The Center for Research Education and Science Communications Opportunities (CRESCO) of the Title V Cooperative Project between the University of Puerto Rico Medical Sciences Campus and the Universidad Central del Caribe (Title V Coop)

OBJECTIVES/GOALS: The Title V Coop developed CRESCO, a physical and virtual space in the libraries of the two cooperating institutions. Adopting a flexible and transformational approach, it offers services to support the development of research and information skills of undergraduate students and faculty who receive clinical-translational research (CTR) training. METHODS/STUDY POPULATION: Since 2016, CRESCO has been staffed by a multidisciplinary team composed of three librarians, a statistician, an instructional designer, and an IT specialist. The physical facilities of the two libraries were remodeled and equipped, and a central portal was created to provide services and access to resources on a 7/24 basis. Online tutorials, workshops, and mentoring services have been offered that address topics in statistics, literature search, plagiarism, and the use of several research software. Services statistics are collected, and a questionnaire is administered to evaluate the workshops. RESULTS/ANTICIPATED RESULTS: The main results include 12 online tutorials created in CTR areas and available in the CRESCO hub portal; 14,660 mentoring/consultations offered in statistics, the use of research-related software, and the search for scientific literature search; and 6 online workshops created in CTR areas, with 463 attendees. When evaluating online workshops, participants considered that their acquired learning was high or extremely high on the following topics: use of Intellectus Statistics (88%, n = 96); selection of statistical tests (81%, n = 92); use of Turnitin (85%, n = 76); literature search (91%, n = 58); and citations and references in Mendeley (90%, n = 67). DISCUSSION/SIGNIFICANCE: These results suggest that the flexible, multidisciplinary, and transformational approach of CRESCO has been successful in helping undergraduate students and faculty develop the skills necessary to conduct CTR projects.

500 Building research knowledge base through training and elective courses in Clinical and Translational Research (CTR) as part of the Title V Cooperative Project (Title V Coop) between the University of Puerto Rico Medical Sciences Campus (UPR-MSC) and the Universidad Central del Caribe (UCC)

OBJECTIVES/GOALS: Research Education Towards Opportunities (RETO) Mentoring Offering Training Opportunities for Research (MOTOR) 1 – 2 and the elective courses (INTD 5998/ MDCL 101) in CTR of Title V Coop were designed to provide the participants from higher education institution (HEI) in Puerto Rico (PR), interdisciplinary – interprofesional knowledge in CTR. METHODS/STUDY POPULATION: Since April 2017, Research Education Towards Opportunities (RETO) and Mentoring Offering Training Opportunities for Research (MOTOR) 1 - 2 trainings were offered as part of the Title V Coop. In addition, since January 2020, as part of the institutionalization of the trainings in CTR, two elective courses (INTD 5998 and MDCL 101) were created-offered. The trainings/courses present the main concepts underlying CTR performance through lectures, workshops and presentations, in hybrid modalities, as well as the services-resources of the Center Research Education and Science Commnunication Opportunities (CRESCO). These programs have given students (undergraduate and graduate) and faculty the opportunity to get started in CTR and to integrate in Clinical and Translational Mentoring Teams (CTMT). RESULTS/ANTICIPATED RESULTS: Eight (8) cycles of RETO-MOTOR 1 and seven (7) cycles of RETO-MOTOR 2; two sessions of INTD 5998 and one session of MDCL 101 were offered. The RETO-MOTOR 1 training was completed by 219 participants and RETO-MOTOR 2 by 130 participants. The INTD 5998 course was completed by 22 students and the MDCL 101 course by 18 students. A total of 389 participants have been initiated in the CTR. Of the trainings, 90% indicated that the knowledge acquired in CTR was invaluable, 85% understand that the most significant achievement, as students, was present at a scientific conference, and 100% indicated interest in continuing to do CTR. Of the courses, 100% indicated that they were a good learning experience, helped them increase their knowledge in CTR, met their expectations and would recommend other students to take the course. DISCUSSION/SIGNIFICANCE: The RETO-MOTOR 1, RETO-MOTOR 2 trainings and CTR courses provide a based of research knowledge and valuable interprofessional experience for those who whish to start in the clinical and translational research. The Title V Cooperative Project provides this opportunity to undergraduate and graduate students such as faculty of HEI in PR.

4515 The Impact of First Level Training Cycles (FLTCs) on Clinical and Translational Research (CTR) in knowledge and interest in CTR of students (S) and faculty (F) from health professions and basic science programs island wide in Puerto Rico (PR)

OBJECTIVES/GOALS: To assess the impact of FLTCs on CTR on S and F from health professions and basic science academic programs island wide in Puerto Rico. Cycles supported by the Title V Cooperative Project at University of Puerto Rico-Medical Sciences Campus (UPRMSC) and Universidad Central del Caribe (UCC)(Title V). METHODS/STUDY POPULATION: After offering FLTCs in CTR to S and F from UPRMSC and UCC, Title V expanded it to S and F from other institutions island wide in PR. These FLTCs were offered the 2nd semester of 2018 and consisted of 20 hours of interdisciplinary sessions in: introduction to and definition of CTR; preparation of a CTR-presentation; how to interview/share a presentation of a CT researcher and to prepare a research question in CTR. To assess the knowledge of S and F in the above-mentioned skills and their continuation in the 2nd level of CTR training, surveys were administered: pre-test, at the beginning, post-test, sometime during the FLTCs, and satisfaction at the end of the FLTCs. RESULTS/ANTICIPATED RESULTS: Fifty eight (58) S/F from UPRMSC, UCC and 7 other institutions participated. Forty two (42,72%) answered a pre-test and 31/42 (74%) completed the post-test. Results showed that S/F: who correctly defined CTR increased from 7% to 77 %; their ability to identify a CT researcher increased from 10% to 83%. Fifty five percent (55 %) (21/38) S/F that were certified in the FLTCs, answered the satisfaction survey. One hundred percent (100%) indicated that the materials offered contributed in the identification of a CT researcher and a topic in CTR; 100% answered that the FLTCs contributed higher knowledge in and provided new skills in CTR. Moreover, 31/38 (82%) S/F started the 2nd level of training. DISCUSSION/SIGNIFICANCE OF IMPACT: The FLTCs were successful in increasing S/F knowledge of CTR and to further engage in 2nd level of trainings. Title V impact extended island wide, increasing the diversity of represented health professions and science fields among participants. The interventions were deemed to be of high quality.

Mastering Anatomical Techniques: Enhancing anatomical skills

As medical schools attempt to find time in their curriculum to cover more content, they have sought to develop new methods of teaching gross anatomy. The amount of time spent studying gross anatomy has declined amidst controversy as to how and when teaching is best delivered. Moreover, previous studies have established that medical student interest in surgery has declined, along with their technical skills in anatomy. This loss of interest is due to several factors, such as the male‐dominance present in the field, the difficulty of obtaining high enough grades, and nationality. For this reason, the Anatomy Department of the Universidad Central del Caribe School of Medicine at Puerto Rico (UCC) decided to create a pilot project aimed at second‐ and third‐year medical students with surgical interest, providing them with an integrated apprenticeship and an opportunity to mentor first‐year students during their Human Gross and Developmental Anatomy (HGDA) course. Their responsibilities include preparing for dissection, instructing students during dissection on weekends, and tutoring to emphasize anatomical concepts. This provides students with a variety of learning opportunities and a set of skills that we believe are necessary to pursue a career in the surgical field. To evaluate the viability of this pilot project, we carried out a comparison of the scores obtained by first‐year medical students during the first block examination on the musculoskeletal system in 2017 and 2018. The academic performance of first‐year medical students in 2018 served as the experimental variable, while that of students in 2017 served as the control, since they did not receive any help during their first year. In addition to this, a survey addressing satisfaction was also developed for this first phase of the study. The latter was sent to all 74 first year medical students at UCC. The survey included a 5‐point questionnaire using a Likert scale response ranking. Preliminary positive results were obtained for both the academic performance comparison and the survey. These results represent an exciting opportunity for the development of innovative approaches for teaching and learning anatomy that transform the traditional didactic methods towards more engaging and stimulating methods of learning. The analysis of academic performance regarding the remaining three examination blocks (thorax, abdominopelvic cavity, and head and neck) are pending and will take place as the course progresses. Nevertheless, findings for this first phase of the project support our hypothesis that second‐ and third‐year medical students are a viable educational resource promoting professionalism, critical thinking, and instructions.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

3219 Integration of Undergraduate (US) and Graduate (GS) Students and Faculty (F) in Clinical and Translational Research (CTR) in Puerto Rico: The University of Puerto Rico-Medical Sciences Campus (UPR-MSC) and Universidad Central del Caribe (UCC) Experience

OBJECTIVES/SPECIFIC AIMS: The Title V Cooperative Project of the UPR-MSC and UCC has demonstrated that educational interventions in CTR are very effective in fulfilling the objective of promoting awareness, stimulate interest and increase the knowledge, skills and opportunities, to US, GS and F (participants) in CTR. METHODS/STUDY POPULATION: The training sessions (TS) offered through the Title V initiative have become an engine for the involvement in CTR for participants from higher education institutions island-wide. TS consisted of cycles –level 1 and 2–: Research Education Towards Opportunities (RETO,I,II) and Mentorship Offering Training Opportunities for Research (MOTOR,I,II), ending in the formation of the Clinical and Translational Mentoring Teams (CTMT)s, in which participants, paired by their research interests, were mentored by a well-established CT researchers in their research project, to be developed in the Intensive Development and Experiences in Advancement of Research and Increased Opportunities (IDEARIO). RESULTS/ANTICIPATED RESULTS: Up to date, 4 TS-level 1 and 2 TS-level 2 were offered. Eighty (80) participants completed level 1, distributed: 42 (52.5%) US in RETO, 21 (26.25%) GS and 17 (21.25%) F in MOTOR and 17 participants completed level 2, distributed: 4 (23.52%) US in RETO, 6 (25.29%) GS and 7 (41.17%) F in MOTOR. From which, 15, with 8 CT researchers, formed 5 CTMTs in different research areas – cardio, neuro, liver, renal, Zika–. DISCUSSION/SIGNIFICANCE OF IMPACT: US, GS and F were integrated in the active process throughout educational levels for their development in CTR.

3168 Clinical and Translational Mentoring Team (CTMT): Effective Strategy for the Development of Students – undergraduate (US) and graduate (GS) – and Faculty (F) of Health Sciences Programs (HSPs) in Clinical and Translational Research (CTR) in Puerto Rico

OBJECTIVES/SPECIFIC AIMS: The Title V Cooperative Project between the University of Puerto Rico- Medical Sciences Campus (UPR-MSC) and Universidad Central del Caribe (UCC) has trained US, GS and F (participants) of HSPs to engage them in CTR. METHODS/STUDY POPULATION: First stage of the training sessions (TS) dealt with the theory of CTR. After TS and responding to their research interests, as answered in a questionnaire, the participants formed a CTMT, under the mentorship of a well-established CT researcher. This, as a prelude to their hands-on experiences in Intensive Development and Experiences in Advancement of Research and Increased Opportunities (IDEARIO), for which a research proposal is needed. RESULTS/ANTICIPATED RESULTS: Five (5) CTMTs were formed in different research areas – cardio, neuro, liver, renal, Zika–, as submitted in their research concept papers.Eight (8) CT researchers are currently mentoring 2 US, 7 GS and 6 F of HSPs through the CTMTs. They have submitted a research proposal, as a bridge between the theory in the TS and the practice in IDEARIO. Five (5) proposals were received and 2 of them approved, while the other 3 are in the evaluation process. We will present the composition, research topics, development of research and the feedback of participants in IDEARIO and CTMTs. DISCUSSION/SIGNIFICANCE OF IMPACT: The CTMTs and their respective proposals are effective strategies for the mentoring of US, GS and F in CTR.

2140 Clinical and translational research (CTR) platform for undergraduate health sciences programs (UHSP) at University of Puerto Rico-Medical Sciences Campus (UPR-MSC) and Universidad Central del Caribe (UCC): Pipeline for students and faculty

OBJECTIVES/SPECIFIC AIMS: The University of Puerto Rico-Medical Sciences Campus and Universidad Central del Caribe, through the Title V Cooperative Project, devised a clinical and translational research (CTR) platform to pipeline students/faculty of undergraduate health sciences programs into CTR. Educational interventions in CTR—introductory intervention (II) and Annual Symposium (AS)—were designed to promote awareness, stimulate interest of students and faculty in CTR. METHODS/STUDY POPULATION: In the II the participants (n=159) were surveyed before and after a presentation and panel discussion about CTR. In addition, after the sessions—plenary, panel, and workshop—about CTR, the participants of AS (n=42) were surveyed for satisfaction and learning experience in CTR. RESULTS/ANTICIPATED RESULTS: Most participants of the II, 134 (84.3%) were students. In total, 58 (58, 36.5%) completed the post II survey. Of these, 53.4% satisfactorily defined the CTR concept Versus only 31.0% that could define CTR in the pre survey, 47 (81.7%) were unable to identify a CTR researcher and 45 (78.3 %) expressed interest in learning about CTR. In total, 28 (28, 66.7%) participants of the AS completed the satisfaction survey, out of which 17 (60.6%) were students. One hundred percent (100%) agreed that the AS served as a vehicle to increase their knowledge in CTR. DISCUSSION/SIGNIFICANCE OF IMPACT: The educational interventions demonstrated to be an effective strategy to promote awareness and stimulate interest of students and faculty in CTR. In addition, the results obtained, provided valuable baseline information for the planning—development of training cycles in CTR.

2146 Training cycle in clinical and translational research (CTR) for undergraduate health sciences programs (HSUP) at University of Puerto Rico-Medical Sciences Campus (UPR-MSC) and Universidad Central del Caribe (UCC): Pathway for students and faculty

OBJECTIVES/SPECIFIC AIMS: Responding to the need and interest of students and faculty of the UHSP in learning about CTR, the Title V Cooperative Project between UPR-MSC and UCC, developed and offered a training cycle (TC) in CTR. METHODS/STUDY POPULATION: Undergraduate students (US), undergraduate faculty (UF), and graduate students (GS) were invited to register in: Research Education Towards Opportunities (RETO) and Mentorship Offering Training Opportunities for Research (MOTOR), which consisted of 20 hours of training in CTR, with interdisciplinary sessions in: Introduction and preparation of a presentation in CTR; Identify, interview and share a presentation of a CT researcher; participation in conferences and a summer camp in CTR. At the end of the TC, surveys—satisfaction and needs assessment—for training in CTR were administered. RESULTS/ANTICIPATED RESULTS: Thirty-three (33) registered in the TC, distributed: 13 (39.39%) US in RETO, 12 (36.36%) GS and 8 (24.24%) UF in MOTOR. Of these, 25 (75.75%) answered and submitted the on-line surveys and received a completion certificate. All (100%) were satisfied with the TC, and for 96% of the respondents, their expectations were fulfilled, and will continue in the TC. They selected critical review, scientific communication, and cultural diversity as thematic areas of interest. In addition, 60% of them selected neuroscience, cancer and medical imaging as main research areas of interest. DISCUSSION/SIGNIFICANCE OF IMPACT: The TC demonstrated to be an effective strategy to provide new knowledge, experiences, and interest in CTR. It also established a pathway for future engagement in CTR.

Preserving Skeletal Anatomical Structures from Cadaveric Specimens to Enhance the Anatomy Education with Emphasis in Arthrology.

INTRODUCTIONThe National Board of Medical Education considers the musculoskeletal system to be amongst the three most crucial subjects within an anatomy curriculum, therefore the necessary tools are required to properly instruct students on the subject. Common teaching methods include using bones and dissections to show the origins and insertions of muscles and their related neurovascular bundles, but given the complexity of these structures, some students are not able to visualize important details. Additionally, Universidad Central del Caribe has recently struggled to obtain enough specimens due to increases in student acceptances as well as declines in the supply of bodies to our board of donations. This potentially poses a paucity of bodies for upcoming classes. This study proposes a method that could allow our medical school not only to preserve structures that would otherwise be discarded, but also to broaden their functionality as a tool for learning gross anatomy.METHODSThe specimens used in this procedure had been previously used to teach dissection‐based anatomy and were in a fragile state that required their preservation in an embalming solution of formaldehyde, phenolic acid, glycerin, and water. These were rinsed and submerged in a solution of Sodium Hypochlorite (NaClO) to soften the tissues. Over the course of 6 weeks, the cadavers were monitored and dissected, either isolating those structures that make up the articulations or the tendons of muscles, depending on the tissues desired to be preserved. Once the desired structures were obtained, these were placed in a bleaching fluid to improve their appearance and then submerged in a preservative fluid preventing further decay.RESULTSThe approach we took for dealing with the structures proved to be successful. By removing most of the tissues that were susceptible to NaClO, we were able to isolate tendons from their muscles and expose the articulations that through normal dissecting methods would be hard to observe.CONCLUSIONThis approach provides a potential means for medical institutions to lengthen the use of aged cadavers and proposes an alternate method to enhance the study of hard to observe anatomical structures that are oftentimes concealed by an abundance of blood vessels, nerves and muscle tissue. The effectiveness of this method in studying anatomy have yet to be compared to traditional methods of cadaveric studies. However, it provides a simple alternative that is reliable for medical schools facing a cadaver shortage.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

A decade of viral mutations and associated drug resistance in a population of HIV-1+ Puerto Ricans: 2002-2011.

Puerto Rico has one of the highest rates of HIV/AIDS seen for any US state or territory, and antiretroviral therapy has been a mainstay of efforts to mitigate the HIV/AIDS public health burden on the island. We studied the evolutionary dynamics of HIV-1 mutation and antiretroviral drug resistance in Puerto Rico by monitoring the population frequency of resistance-associated mutations from 2002 to 2011. Whole blood samples from 4,475 patients were analyzed using the TRUGENE HIV-1 Genotyping Kit and OpenGene DNA Sequencing System in the Immunoretrovirus Research Laboratory at Universidad Central del Caribe. Results show that 64.0% of female and 62.9% of male patients had HIV-1 mutations that confer resistance to at least one antiretroviral medication. L63P and M184V were the dominant mutations observed for the protease (PRO) and reverse transcriptase (RT) encoding genes, respectively. Specific resistance mutations, along with their associated drug resistance profiles, can be seen to form temporal clusters that reveal a steadily changing landscape of resistance trends over time. Both women and men showed resistance mutations for an average of 4.8 drugs over the 10-year period, further underscoring the strong selective pressure exerted by antiretrovirals along with the rapid adaptive response of HIV. Nevertheless, both female and male patients showed a precipitous decrease for overall drug resistance, and for PRO mutations in particular, over the entire course of the study, with the most rapid decrease in frequency seen after 2006. The reduced HIV-1 mutation and drug resistance trends that we observed are consistent with previous reports from multi-year studies conducted around the world. Reduced resistance can be attributed to the use of more efficacious antiretroviral drug therapy, including the introduction of multi-drug combination therapies, which limited the ability of the virus to mount rapid adaptive responses to antiretroviral selection pressure.

DDEL-11SELECTIVE TARGETING OF GLIOBLASTOMA USING FOLATE-DECORATED NANO-PARTICULATE CYTOCHROME C DRUG CONSTRUCTS

DDEL-11. SELECTIVE TARGETING OF GLIOBLASTOMA USING FOLATE-DECORATED NANO-PARTICULATE CYTOCHROME C DRUG CONSTRUCTS Josue Davila1, Kimberleve Rolon Reyes1, Moraima Morales Cruz2, Michael Inyushin1, Yuriy Kucheryavykh1, Kai Griebenow2, and Lilia Kucheryavykh1; UniversidadCentraldel Caribe,Bayamon,Puerto Rico; University of Puerto Rico, Rio Piedras, Puerto Rico BACKGROUND: Glioblastoma (GBM) is one of the most malignant forms of brain cancers due to resistance to chemoand radiotherapy, mostly caused by enhanced resistance to apoptosis. We propose the development of targeted apoptosis-inducing drugs for glioblastomatreatment andapprobationof these drugs in glioblastoma cell lines and animal model. We developed nano-sized protein particles containing cytochrome C (NPs). For targeted delivery of the drug specifically to GBM cells we decorated the drug nano-particles with the ligand folic acid (FA). Many GBMs express Proton Coupled Folate Transporters that provide selective internalization of the designed NPs. Protein drug stability problems were countered by covalently decorating the constructs with glycans. RESULTS: Confocal imaging revealed the specific up-take of FITC tagged FA-NPs by GL261 cells, but not by primary cultured astrocytes. Examination of live brain slices encompassing glioblastoma tumor showed some non-specific accumulation of NPs in healthy tissue in two hours after application of FA-NPs, but 20-times less compared to the tumorarea.NPs, used invitro inconcentration of100 mg/ml,havenocytotoxic effect in astrocytes but cause 40% death in tumor cells. The use of NPs in combination with LY294002 (PI3K/AKT blocker), 50 mM, caused 90% death in tumor cells. In vivo TUNEL investigation of tumors generated in C57Bl/6 mice by implantation of GL261 cells revealed the strong signs of apoptosis after three days of in-site administration of NPs through the microosmotic pumps without the evident signs of apoptosis in healthy tissue. In CONCLUSION: We can state that the designed NPs demonstrate good specificity for GL261 cells, effectively cause the apoptosis in these cells when used in combination with LY294002, and give a good baseline for the development of efficient methods for treating GBM. Acknowledgement: NIH Grant Numbers 1SC2GM102040-01A1, SC2GM095410-01A1, 8G12MD007583-27, R25GM110513, Title V grant number P031S130068. Neuro-Oncology 17:v73–v77, 2015. doi:10.1093/neuonc/nov212.11 Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2015.

Overexpression of GRP78 confers protection against neurocognitive impairment in HIV-infected polydrug users

Aims: Due to the high prevalence of stress and neurocognitive impairment (NCI) in HIV infected and drug abuse patients worldwide, there is a need to study these disorders and their impact on the immune response. We hypothesize that HIV polydrug users (PDU) will have greater impact in stress and NCI leading to Endoplasmic Reticulum (ER) stress related T-lymphocyte protein and pro-inflammatory cytokine expression. To test this hypothesis, we will (1) identify stress levels and cytokine profiling in NCI in HIV+ and HIV−PDU, (2) detect biomarkers associated with NCI, stress and HIV polydrug use. Methods: The initial population analysis in this study was: 10 HIV+PDU+ and 10 HIV−PDU+. NCI and stress were respectively measured physiologically (homocysteine and cortisol levels) and psychologically (MOCA, IHDS andmodified PERI scale) in HIV+PDU. Immunoproteomics and flow cytometry were used to detect ER stress markers and cytokine profiling. Gene expression and western blots were used to validate the ER stress gene and protein expression. Results: HIV+PDU+ had elevated cortisol levels (1.25 g/dL) as compared to HIV−PDU+ (0.107 g/dL). Moreover, HIV+PDU+ with no NCI had an increase expression of proinflammatory cytokines. Immunoproteomics revealed the overexpression of ER stress marker GRP78 in HIV+PDU+NCI− participants. To compare significant differences between the HIV+PDU+NCI−/NCI+ groups, two-way ANOVA statistical analysis with 0.05 p value was used. Conclusions: Our findings showed that HIV infection in PDU contributes negatively in NCI, moreover, identification of GRP78 overexpression in HIV+PDUswith no NCI highlights its cytoprotective role and the identification of ER stress markers that may serve as candidates for early diagnostic of NCI HIV+, and polydrug use. Financial support:NIH andNIMHD (G12MD007583) (N Boukli) to the Universidad Central del Caribe) and K05DA015799 (J.C. Anthony, sponsor) to Michigan State University.

Puerto Rican Residents Return to Island for Mental Health Tour

Puerto Rican Residents Return to Island for Mental Health Tour

Proceedings of the 1st Puerto Rico Biobanking Workshop.

The 1st Puerto Rico Biobanking Workshop took place on August 20st, 2014 in the Auditorium of the Comprehensive Cancer Center of the University of Puerto Rico, Medical Sciences Campus in San Juan Puerto Rico. The program for this 1-day, live workshop included lectures by three biobanking experts, followed by presentations from existing biobanks in Puerto Rico and audience discussion. The need for increasing biobanking expertise in Puerto Rico stems from the fact that Hispanics in general are underrepresented in the biobanks in existence in the US, which limits the research conducted specifically to understand the molecular differences in cancer cells compared to other better studied populations. In turn, this lack of information impairs the development of better diagnostic and therapeutic approaches for our population. Dr. James Robb, M.D., F.C.A.P., consulting pathologist to the National Cancer Institute (NCI) and the Office of Biorepositories and Biospecimen Research (OBBR), opened the workshop with a discussion on the basic aspects of the science of biobanking (e.g., what is a biobank; its goals and objectives; protocols and procedures) in his talk addressing the importance of banking tissues for advancing biomedical research. Next, Dr. Gustavo Stefanoff, from the Cancer Institutes Network of Latin America (RINC by its name in Spanish), explained the mission, objectives, and structure of the Network of Latin-American and Caribbean Biobanks (REBLAC by its name in Spanish), which despite limited resources and many challenges, currently accrue high quality human tissue specimens and data to support cancer research in the region. Dr. Robert Hunter-Mellado, Professor of Internal Medicine, Universidad Central del Caribe, followed with an examination of the ethical and regulatory aspects of biobanking tissues for future research, including informed consent of subjects; protection of human subjects rights; and balancing risks and benefit ratios. In the afternoon, the directors of existing biobanks in Puerto Rico (the Puerto Rico Biobank, the Comprehensive Cancer Center biobank, and an HIV-focused biobank at Universidad Central del Caribe) presented their experiences and challenges with establishing biobanks for research in Puerto Rico. In sum, this workshop presented opportunities to share knowledge in the science of biobanking, for further training, and of networking among the participants (34 from 4 different institutions), which will strengthen the collaborative links between investigators studying cancer in Latin America, the Caribbean, and the US.

Early initiation of alcohol and illicit drug use: Associations with psychopathology among inpatient substance users

s / Drug and Alcohol Dependence 146 (2015) e202–e284 e227 for these projections in context-induced reinstatement of heroin seeking. Financial support: NIDA/IRP. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.083 The effect of high stress on T-cell protein expression in chronic drug users: HIV implications Nawal Boukli, Sheila Lopez, Madeline Rodriguez, Eddy Rios Microbiology and Immunology, Universidad Central Del Caribe, Bayamon, United States Aims: Stress anddrugusemaywork in synergy toaffect immune response. We aim to (1) group chronic poly drug users (PDU) according to psychological, physiological and immunological characteristics, and (2) examine stress impact on plasma cytokine profile and protein expression of T-lymphocytes from HIV+ and HIV− PDUs. Methods: In non-PDU HIV−HCV− controls (n=10) and PDU samples (n=47; 20% female, age 18–35 years), stresswasmeasured by the PERI and cortisol/DHEA quantification. Cellular immune response has been evaluated by CD4/CD8 quantification. Protein expression alterations were detected through proteomics. Results: HIV−HCV− (18), HIV+HCV− (7), HIV−HCV+ (13), HIV+HCV+ (9) and non PDU HIV−HCV− control group (10). PERI scale scores were related to low and high cortisol levels. Immunologically, among 18 HIV−HCV− PDU 100% had >410 CD4 cell counts/ l; 5 of 7 HIV+HCV− PDU had high CD4 counts; all 10 non-PDU HIV−HCV− had normal CD4 cell counts. The proteomic data identified proteins showing altered expression mainly in oxidative stress, proteolytic and glycolytic enzymes, inhibitors and structural proteins in the group of PDU+ with high stress as compared to those with low stress values. Conclusions: Our findings allowed the identification of several proteinmarkers candidates for early diagnostic and/or treatment of PDU under stress. Further, the scientific processes implemented to stratify PDU+ and PDU− users according to physiological, immunological and psychologicalmeasurements are important to correlate with the protein profile of the participant groups. This will contribute to the deeper understanding of the effect of stress in the PDU and underlying mechanisms for drug of abuse prevention. Financial support: Supported by NCRR (5G12RR003035), NIMHHD (8G12MD007583), NIDA (2R24DA013335; R25DA030310). http://dx.doi.org/10.1016/j.drugalcdep.2014.09.084 Early initiation of alcohol and illicit drug use: Associations with psychopathology among inpatient substance users Nadia Bounoua, Bina Ali, Aaron Lim, William Lechner, Julia M. Shadur, J.W. Felton, L. MacPherson, C.W. Lejuez University of Maryland, College Park, College Park,

Vital signs: A national study of the addiction treatment profession

s / Drug and Alcohol Dependence 140 (2014) e169–e251 e191 Estimating capacity requirements for substance use treatment systems: Population-based approach Brian R. Rush1, J. Tremblay2, C. Fougere1 1 Centre for Addiction and Mental Health, Toronto, ON, Canada 2 Universite du Quebec a Trois-Rivieres, Trois-Rivieres, QC, Canada Aims: Development of a needs-based planning model for substance use services and supports across Canada that aligns with the estimated needs of the populations of local health regions and yields estimates of required treatment capacities along the continuum of care. Methods: (1) Estimate the number of people in need of substance use treatment, by problem severity, within a given year by using population survey data. Estimate the probable help-seeking population based on a synthesis of the literature. Estimate the optimal trajectory of cases across several defined categories of treatment services, including SBIRT, to yield the number of people to plan for in each service setting. Conduct a gap analysis between the estimated capacity and the current capacity of substance use services at five pilot sites across Canada. Results: The model development process and gap analyses at the five pilot sites yielded fairly consistent results. Results indicate that withdrawal management services appear to be over-supplied in many regions. The current supply of low-threshold community services such as brief treatment closely reflect the model’s estimates; however, gaps appear to exist for more intensive community services such as day treatment. Significant gaps also appear to exist for residential services across Canada. Gap analysis results were corroborated by staff at the pilot sites. Results also indicate the need for more systematic SBIRT processes to engage clients in the treatment system. Conclusions: The model appears to have face value when applied to Canada as a whole; however, regional context should be taken into account when applying the model to local jurisdictions. We anticipate that the model will serve as a valuable tool for substance use treatment system planners to use in discussions and decisions about funding and resource allocation. Next steps include model adjustments using more precise regional data and incorporating the model into a larger needs assessment process. Financial support: Health Canada’s Drug Treatment Funding Program, Project no. 6559-15-2009/10350002. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.533 Vital signs: A national study of the addiction treatment profession Olivia Ryan1, K. Summers3, Michael S. Shafer2, Heather J. Gotham1, M. Cruz4 1 UMKC, Kansas City, MO, United States 2 Arizona State University, Phoenix, AZ, United States 3 University of Iowa, Iowa City, IA, United States 4 Universidad Central del Caribe, Bayamon, United