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    Salivary Exosomes in Health and Disease: Future Prospects in the Eye

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    Exosomes are a group of vesicles that package and transport DNA, RNA, proteins, and lipids to recipient cells. They can be derived from blood, saliva, urine, and/or other biological tissues. Their impact on several diseases, such as neurodegenerative, autoimmune, and ocular diseases, have been reported, but not fully unraveled. The exosomes that are derived from saliva are less studied, but offer significant advantages over exosomes from other sources, due to their accessibility and ease of collection. Thus, their role in the pathophysiology of diseases is largely unknown. In the context of ocular diseases, salivary exosomes have been under-utilized, thus creating an enormous gap in the literature. The current review discusses the state of exosomes research on systemic and ocular diseases and highlights the role and potential of salivary exosomes as future ocular therapeutic vehicles.The authors would like to acknowledge the following for their financial support: National Eye Institute, National Institutes of Health; (EY030028-04S1; D.K.)

    Use of Clinical Practice Guidelines and Quality Metrics to Assess Primary Care Management of Osteoporosis

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    Background: Clinical practice guidelines and quality measures provide recommendations for physicians addressing osteoporosis management. This study explored the alignment of osteoporosis clinical practice in a primary care geriatric clinic with recommended guidelines. Methods: This retrospective chart review included 388 patients 65 or older from a primary care geriatric clinic diagnosed with osteopenia or osteoporosis, with or without a fragility fracture. Data included history of falls and use of DXA scans, FRAX(R) fracture risk assessment tool, osteoporosis medication, and fall risk mitigation plans. Results: For age-related primary fracture prevention, 68% of women and 87% of men had documented DXA scans, and 45% of patients diagnosed with osteoporosis and 42% determined at high risk were prescribed osteoporosis medication. For secondary fracture prevention, 72% of women aged 67 to 85 had DXA scans and 21% were prescribed osteoporosis medication. Only 10% of patients with a history of falls had documented fall risk management plans. Conclusion: Although showing higher rates of primary and secondary prevention outcomes than did research results from general primary care, gaps were identified for high fracture risk patients and fall risk management documentation. Medical record review may not provide sufficient data to capture factors influencing decision-making for fracture prevention.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Participation in this publication was made possible for author, Kathlene Camp, by Grant Number K01HP33457 from the Health Resources and Services Administration (HRSA), an operating division of the U.S. Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the Health Resource and Services Administration or the U.S. Department of Health and Human Services

    Transgender Healthcare and The Impact of Increased Politicization of Medicine

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    Research Appreciation Day Award Winner - Texas College of Osteopathic Medicine, HSC Health, 2023 Health Care Delivery AwardPurpose Transgender (trans) people have a unique set of health needs that are often misunderstood and/or ignored in health settings. Such misunderstandings contribute to mental and physical health disparities when compared to the cisgender population, such as increased rates of anxiety, depression, suicide, substance abuse, adverse cardiovascular events, and other chronic health conditions. Addressing these disparities requires greater access to gender-affirming care (GAC) with providers who are comfortable and knowledgeable about trans individuals’ unique health needs. However, recently there has been an increase in anti-transgender legislation across the United States. This raises questions about provider regulation and ability to provide culturally appropriate care to trans patients, and potentially widening access and care disparities among trans individuals. Future providers, including medical students, who are being trained during moments of heightened anti-transgender politics, may not feel sufficiently prepared to care for trans patients. This exploratory study examined 1) current medical students’ knowledge and attitudes towards treating trans patients 2) gaps in transgender-focused content in medical curricula, and 3) medical trainings and their degree of impact on transgender healthcare. Methods A literature review was conducted by searching scholarly databases including PubMed using the terms related to transgender health, policy, medical students, gender-affirming care, health providers, and gender dysphoria. Articles that were 1) published after 2014 2) in English, and 3) available as full text were included. The search yielded 52 articles that were then reviewed for content on medical students’ knowledge and attitudes about trans patients, gaps in medical curricula, and perceived efficacy of trans-focused trainings and educational interventions. Results Existing literature suggests that trans health disparities are largely related to provider lack of knowledge and training. Despite potentially positive attitudes regarding this population, most medical students feel their curricula lacks transgender-centered content. This includes diagnosing gender dysphoria, hormone-therapy, puberty blockers, and sex reassignment surgeries. Although some students may feel knowledgeable about trans individuals’ needs overall, many report they still feel ill-prepared to work with trans patients. They request more clinical exposure to gain confidence with proper history taking and interview skills. When assessing the training modalities preferred by medical students, interactive interventions including direct communication with trans patients yield the greatest increase in perceived confidence levels. The most recommended training modalities for practicing physicians are attending professional conferences, acquiring direct clinical mentorship, and implicit bias self-awareness workshops. Conclusion This synthesis of current research highlights the need for increased trans-focused support in medical education, which will contribute to improving overall health outcomes, ease barriers, and ameliorate disparities for transgendered persons. In the current political context, physicians who provide GAC are faced with a unique set of social and legal challenges. Government intrusion of clinical decision-making may force physicians to forgo their obligations to transgender patients, thereby directly eliciting harm to an already marginalized population. Accordingly, current and future providers may need to engage in trans-focused advocacy efforts

    QEEG Signatures are Associated with Nonmotor Dysfunctions in Parkinson's Disease and Atypical Parkinsonism: An Integrative Analysis

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    Parkinson's disease (PD) and atypical parkinsonism (AP), including progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), share similar nonmotor symptoms. Quantitative electroencephalography (QEEG) can be used to examine the nonmotor symptoms. This study aimed to characterize the patterns of QEEG and functional connectivity (FC) that differentiate PD from PSP or MSA, and explore the correlation between the differential QEEG indices and nonmotor dysfunctions in PD and AP. We enrolled 52 patients with PD, 31 with MSA, 22 with PSP, and 50 age-matched health controls to compare QEEG indices among specific brain regions. One-way analysis of variance was applied to assess QEEG indices between groups; Spearman's correlations were used to examine the relationship between QEEG indices and nonmotor symptoms scale (NMSS) and mini-mental state examination (MMSE). FCs using weighted phase lag index were compared between patients with PD and those with MSA/PSP. Patients with PSP revealed higher scores on the NMSS and lower MMSE scores than those with PD and MSA, with similar disease duration. The delta and theta powers revealed a significant increase in PSP, followed by PD and MSA. Patients with PD presented a significantly lower slow-to-fast ratio than those with PSP in the frontal region, while patients with PD presented significantly higher EEG-slowing indices than patients with MSA. The frontal slow-to-fast ratio showed a negative correlation with MMSE scores in patients with PD and PSP, and a positive correlation with NMSS in the perception and mood domain in patients with PSP but not in those with PD. Compared to PD, MSA presented enhanced FC in theta and delta bands in the posterior region, while PSP revealed decreased FC in the delta band within the frontal-temporal cortex. These findings suggest that QEEG might be a useful tool for evaluating the nonmotor dysfunctions in PD and AP. Our QEEG results suggested that with similar disease duration, the cortical neurodegenerative process was likely exacerbated in patients with PSP, followed by those with PD, and lastly in patients with MSA.This work was supported by the National Natural Science Foundation of China (NO: 81873777, 82071414), Initiated Foundation of Zhujiang Hospital (NO: 02020318005), Natural Science Foundation of Guangdong of China (NO: 2017A030311010) and Science and Technology Program of Guangdong of China (NO: 2020A0505100037) to Q.W; and the High-level Hospital Construction Research Project of Maoming People's Hospital (NO: xz2020009) and Science and Technology Program of Maoming City (NO: 2021S0026) to H.L.L

    Irvin M. Korr Collection

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    Finding aid for the Irvin M. Korr CollectionThis collection contains personal and professional records created by Irvin M. Korr, 1908-2000, with bulk dates of 1933-1995. Collection materials include published articles, a journal, yearbook, book, exit interview, tributes, and items related to Korr's work in the redesign of the Texas College of Osteopathic Medicine goals and curriculum. Photographs in the collection document the early years and early career of Irvin M. Korr, PhD

    Postpartum preeclamptic rats have hypertension and elevated cerebral oxidative stress

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    Background: Postpartum (PP) preeclamptic (PE) women have an increased risk for developing hypertension (HTN), cerebrovascular diseases, and chronic kidney diseases later in life. The timing and mechanisms that contribute to a rise in blood pressure (BP), cerebrovascular and kidney dysfunction in PP PE women is unknown and the focus of this study. Previous studies in our lab (PMID: 34727994) indicate PP PE rats at 10 weeks have HTN and decreased antioxidant capacity (AC). Our current study examines BP and oxidative stress (OS) in PP PE rats at an earlier time point, 6 weeks (PP6). Understanding changes in cerebral and renal OS may reveal the pathophysiology of HTN, cerebrovascular, and renal disease development in PP PE women. We hypothesize that BP, renal, and cerebral OS will increase in PP6 PE rats. Methods: Pregnant Sprague Dawley rats were divided into 2 groups: control (CON) normal pregnant rats, and PE rats, derived from the surgically induced placental ischemic (reduced uterine perfusion pressure) model of PE. All rats gave birth and weaned for 3 weeks. At PP6, BP was measured via carotid catheterization. Brain and kidney tissues were collected to measure OS (HSP-1, Cu/ZnSOD, and MnSOD proteins and AC) through colorimetric assays and western blots. Results: PP6 PE vs CON rats, BP was elevated (128±6 vs 106±4mmHg, p<0.05) and AC was decreased in systemic circulation (28.5±5.1 vs 36.9±4.5mM Trolox/mg protein, ns). In the brain, both HSP-1 and Cu/ZnSOD were unchanged between PP6 PE and CON rats, while the levels of MnSOD (88.9±2.0 vs 100±2.5 IU/protein/CON %, p<0.05) and AC were decreased (619.1±179.2 vs 850.2±50.3 mM Trolox/mg protein, ns) in PP6 PE vs CON rats. In the kidney, HSP-1 decreased (88.7±3.0 vs 100±4.0 IU/protein/CON %, ns) in PP6 PE vs CON, while Cu/ZnSOD levels remained unchanged. However, kidney MnSOD levels significantly increased (124.3±8.0 vs 100±2.7 IU/protein/CON %, p<0.05) alongside an increase in AC (791.0±165.4 vs 587.0±64.5mM Trolox/mg protein, ns) in PP6 PE vs CON rats. Conclusion: PP6 PE rats have HTN and increased cerebral OS. Despite changes in the brain, kidneys appear to be protected from OS due to a decrease in a reactive OS protein (HSP-1) and increases in antioxidant capacity and protein (MnSOD). Future studies will determine the relationship between brain OS, HTN, and cerebral damage/dysfunction to PP PE rats. Furthermore, future studies will be designed to elucidate the protective mechanisms of the kidney in PP6 PE rats. Findings of this study are clinically relevant and could be used to improve the maternal health of women after PE pregnancies. In addition, therapy designed to target organ specific OS may be helpful in preventing HTN, cerebrovascular, and chronic kidney diseases later in life for women who have experienced PE.This research was supported by the American Heart Association Early Career Development Awards [AHA 18CDA34110264 (Cunningham)]

    Optimizing Workflows to Enhance Principal Investigator Satisfaction and Boost Patient Recruitment

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    The success of a research study can be significantly compromised when principal investigators (PIs) express their dissatisfaction with the clinical research process. Additionally, poor communication between the PIs and research staff can lead to discouragement from participating in research. This communication barrier can also negatively impact subject recruitment and influence the overall success of the research study. In 2022, a survey conducted within the ophthalmology department at the University of Texas Southwestern Medical Center (UTSW) revealed a notable communication disconnect among the PIs, research staff, and clinic staff. This project aimed to reevaluate PI satisfaction, participation, and patient recruitment outcomes after introducing new workflows within the department, which facilitated a closer communication and collaboration with the clinical research staff. The Ophthalmology and Optometry clinical and research providers were administered the same survey as the previous year. Ten of the 35 providers responded, giving a 29% response rate. The responses revealed some improvement in some areas, such as PI's knowledge of resources available to conduct research and awareness of active enrolling studies. Other areas remained unchanged and in need of further work, such as a lack of a clear understanding of the research process and whom to contact to start a research study at UT Southwestern

    Using Microphysiological System for the Development of Treatments for Joint Inflammation and Associated Cartilage Loss-A Pilot Study

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    Osteoarthritis (OA) is a painful and disabling joint disease affecting millions worldwide. The lack of clinically relevant models limits our ability to predict therapeutic outcomes prior to clinical trials, where most drugs fail. Therefore, there is a need for a model that accurately recapitulates the whole-joint disease nature of OA in humans. Emerging microphysiological systems provide a new opportunity. We recently established a miniature knee joint system, known as the miniJoint, in which human bone-marrow-derived mesenchymal stem cells (hBMSCs) were used to create an osteochondral complex, synovial-like fibrous tissue, and adipose tissue analogs. In this study, we explored the potential of the miniJoint in developing novel treatments for OA by testing the hypothesis that co-treatment with anti-inflammation and chondroinducing agents can suppress joint inflammation and associated cartilage degradation. Specifically, we created a "synovitis"-relevant OA model in the miniJoint by treating synovial-like tissues with interleukin-1beta (IL-1beta), and then a combined treatment of oligodeoxynucleotides (ODNs) suppressing the nuclear factor kappa beta (NF-kappaB) genetic pathway and bone morphogenic protein-7 (BMP-7) was introduced. The combined treatment with BMP-7 and ODNs reduced inflammation in the synovial-like fibrous tissue and showed an increase in glycosaminoglycan formation in the cartilage portion of the osteochondral complex. For the first time, this study demonstrated the potential of the miniJoint in developing disease-modifying OA drugs. The therapeutic efficacy of co-treatment with NF-kappaB ODNs and BMP-7 can be further validated in future clinical studies.The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results

    Effects of bile duct ligation on the inhibitory control of supraoptic vasopressin neurons

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    Dilutional hyponatremia due to increased plasma arginine vasopressin (AVP) is associated with liver cirrhosis. However, plasma AVP remains elevated despite progressive hypoosmolality. This study investigated changes to inhibitory control of supraoptic nucleus (SON) AVP neurons during liver cirrhosis. Experiments were conducted with adult male Sprague-Dawley rats. Bile duct ligation was used as a model of chronic liver cirrhosis. An adeno-associated virus containing a construct with an AVP promoter and either green fluorescent protein (GFP) or a ratiometric chloride indicator, ClopHensorN, was bilaterally injected into the SON of rats. After 2 weeks, rats received either BDL or sham surgery, and liver cirrhosis was allowed to develop for 4 weeks. In vitro, loose patch recordings of action potentials were obtained from GFP-labeled and unlabeled SON neurons in response to a brief focal application of the GABA(A) agonist muscimol (100 muM). Changes to intracellular chloride ([Cl]i) following muscimol application were determined by changes to the fluorescence ratio of ClopHensorN. The contribution of cation chloride cotransporters NKCC1 and KCC2 to changes in intracellular chloride was investigated using their respective antagonists, bumetanide (BU, 10 muM) and VU0240551 (10 muM). Plasma osmolality and hematocrit were measured as a marker of dilutional hyponatremia. The results showed reduced or absent GABA(A) -mediated inhibition in a greater proportion of AVP neurons from BDL rats as compared to sham rats (100% inhibition in sham vs. 47% in BDL, p = .001). Muscimol application was associated with increased [Cl]i in most cells from BDL as compared to cells from sham rats (chi(2) = 30.24, p < .001). NKCC1 contributed to the impaired inhibition observed in BDL rats (p < .001 BDL - BU vs. BDL + BU). The results show that impaired inhibition of SON AVP neurons and increased intracellular chloride contribute to the sustained dilutional hyponatremia in liver cirrhosis.This work was funded by R01 HL142341 to JTC

    Evaluating student responses to incorporate Vulnerable Patient Population centered content into the curriculum

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    Purpose: Vulnerable patient populations are considered groups of people who cannot access healthcare resources or services due to social barriers. Despite advances in the healthcare system and medical education, providers still report feeling less comfortable caring for these patients, and medical students around the country report not feeling this topic is adequately addressed in their curricula. The goal of this project was to evaluate students’ responses to introducing an optional curriculum dedicated to discussing four vulnerable populations (Transgender Patients, Incarcerated Patients, Housing Insecure Patients, and Intellectually and Developmentally Disabled Patients). Our expectation is that students will feel more comfortable being a part of these patient’s healthcare teams, and determine the value of providing students with a manageable curriculum focused on these topics. Methods: The tested curriculum consists of four modules, with each dedicated to one of the populations. Each module consists of a pre-recorded video lecture, a supplemental article, and an optional 30 minute interactive session with a content expert who is currently a healthcare provider focused on each population. Texas College of Osteopathic Medicine students voluntarily participated in this evaluation activity. A literature review was performed to create the content outline and objectives. This information was presented in a short pre-recorded video lecture taught by peers. Supplemental articles were chosen to pair with each video. After completing the modules, participants had the option to a virtual interactive meeting where a content expert that works with each of these patient populations had 30 minutes to talk about their experiences and answer questions. The students then consented to an anonymous post-survey to evaluate if they feel that taking this course has benefited their educational experience and if they feel more prepared to be a part of a healthcare team for these patients. All content and materials were reviewed by content experts. Results: 26 students signed up to take the course, and 20 students completed the modules and attended the optional content expert session. Of those 20 students, 90% completed the post-course survey. The survey showed that students feel vulnerable patient populations are important to learn about, that each population has specific healthcare considerations that should be taught, and that a course similar to this is beneficial to their education. Participants reported feeling more informed about caring for these patients and have taken away information that will be valuable in their future practice. Conclusion: Medical students feel that vulnerable patient populations and their barriers to healthcare are important topics that should be discussed in medical school curriculums. Students recognize that each population has specific healthcare needs that should be individualized to them, and that incorporating a course that discusses this would be beneficial to their classroom and clinical training. The participating students reported that they gained new, useful knowledge that will help them be more supportive for these patients, and wish to see similar content incorporated into the curriculum and expanded on in the future. In conclusion these results are interesting and suggest conducting a research study in the future

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