Samin Panahi

Application of RNA interference in treating human diseases

Gene silencing can occur either through repression of transcription, termed transcriptional gene silencing (TGS), or through translation repression andmRNA degradation, termed posttranscriptional gene silencing (PTGS). PTGS results from sequence-specific mRNA degradation in the cytoplasm without dramatic changes in transcription of corresponding gene in nucleus. Both TGS and PTGS are used to regulate endogenous genes. Interestingly, mechanisms for gene silencing also protect the genome from transposons and viruses. In this paper, we first review RNAi mechanism and then focus on some of its applications in biomedical research such as treatment for HIV, viral hepatitis, cardiovascular and cerebrovascular diseases, metabolic disease, neurodegenerative disorders and cancer.

Identification of wnt genes expressed in neural progenitor zones during zebrafish brain development

Wnt signaling regulates multiple aspects of vertebrate central nervous system (CNS) development, including neurogenesis. However, vertebrate genomes can contain up to 25 Wnt genes, the functions of which are poorly characterized partly due to redundancy in their expression. To identify candidate Wnt genes as candidate mediators of pathway activity in specific brain progenitor zones, we have performed a comprehensive expression analysis at three different stages during zebrafish development. Antisense RNA probes for 21 Wnt genes were generated from existing and newly synthesized cDNA clones and used for in situ hybridization on whole embryos and dissected brains. As in other species, we found that Wnt expression patterns in the embryonic zebrafish CNS are complex and often redundant. We observed that progenitor zones in the telencephalon, dorsal diencephalon, hypothalamus, midbrain, midbrain-hindbrain boundary, cerebellum and retina all express multiple Wnt genes. Our data identify 12 specific ligands that can now be tested using loss-of-function approaches.

Lef1-dependent hypothalamic neurogenesis inhibits anxiety

While innate behaviors are conserved throughout the animal kingdom, it is unknown whether common signaling pathways regulate the development of neuronal populations mediating these behaviors in diverse organisms. Here, we demonstrate that the Wnt/ß-catenin effector Lef1 is required for the differentiation of anxiolytic hypothalamic neurons in zebrafish and mice, although the identity of Lef1-dependent genes and neurons differ between these 2 species. We further show that zebrafish and Drosophila have common Lef1-dependent gene expression in their respective neuroendocrine organs, consistent with a conserved pathway that has diverged in the mouse. Finally, orthologs of Lef1-dependent genes from both zebrafish and mouse show highly correlated hypothalamic expression in marmosets and humans, suggesting co-regulation of 2 parallel anxiolytic pathways in primates. These findings demonstrate that during evolution, a transcription factor can act through multiple mechanisms to generate a common behavioral output, and that Lef1 regulates circuit development that is fundamentally important for mediating anxiety in a wide variety of animal species.

Transportation and Other Nonfinancial Barriers Among Uninsured Primary Care Patients

Introduction: Nonfinancial barriers are frequent causes of unmet need in health-care services. The significance of transportation barriers can weigh more than the issues of access to care. The purpose of this cross-sectional study was to examine transportation and other nonfinancial barriers among low-income uninsured patients of a safety net health-care facility (free clinic). Methods: The survey data were collected from patients aged 18 years and older who spoke English or Spanish at a free clinic, which served uninsured individuals in poverty in the United States. Results: Levels of transportation barriers were associated with levels of other nonfinancial barriers. Higher levels of nonfinancial barriers were associated with elevation in levels of stress and poorer self-rated general health. Higher educational attainment and employment were associated with an increase in other nonfinancial barriers. Conclusion: Focusing only on medical interventions might not be sufficient for the well-being of the underserved populations. Future studies should examine integrative care programs that include medical treatment and social services together and evaluate such programs to improve care for underserved populations.

Continuity of Care: Perspectives of Uninsured Free Clinic Patients

Background: Continuity of care is vital to the success of a health-care system because it improves patient satisfaction and health outcomes, and reduces hospitalizations and emergency room visits. Objective: The purpose of this study was to examine free clinic patients’ perspectives of continuity of care in the United States. Method: A convenience sample of free clinic patients who were the age of 18 or older and spoke English or Spanish participated in a self-administered survey from January to April in 2017 (N = 580). Results: Better instructions from providers were associated with higher levels of continuity of care (P < .01). Higher levels of stress and worse self-rated general health were related to lower levels of continuity of care (P < .05 for stress, P < .01 for general health). Being employed was associated with lower levels of continuity of care (P < .05). Non-US born English speakers and Spanish speakers rated continuity of care higher than US born English speakers (P < .01). Conclusion: Even if a patient is unable to see the same physician over time, quality instructions from a well-coordinated provider team may enhance continuity of care from patient perspectives. The social context of patients such as working poor individuals is very important for providers to understand in order to identify barriers to continuity of care.

Risks of opioid abuse among uninsured primary care patients utilizing a free clinic

Abstract The annual number of opioid prescriptions for pain relief has been increasing in the United States. This increase has raised concerns about prescription opioid abuse and overdose. The purpose of this study was to examine opioid risks (risk factors that increase the chance of opioid abuse) among uninsured primary care patients utilizing a free clinic. Data were collected using a self-administered paper survey in the waiting room of the free clinic from May to July 2017 (N = 506). Higher levels of somatic symptoms were associated with higher levels of opioid risks. U.S.-born English speakers had higher levels of opioid risk than non–U.S.-born English speakers and Spanish speakers. Being employed was associated with higher levels of opioid risk while attending college or being postcollegiate was related to lower levels of opioid risk. Research surrounding best practices, prescription trends, and population risk is vital in driving health and social policy. Further research would benefit from examining where people are obtaining opioids. In addition, further research on opioid abuse among Hispanic populations would be beneficial. Finally, future studies should examine how prescribing practices are different among free clinic health professionals in comparison to health care professionals working in-patient or at for-profit clinics.

Improving Health of Diverse Populations

The issue for July 2018 mainly focuses on health of underserved populations in the United States (US), except three articles - one from Vietnam, one from the United Kingdom (UK), and the other from Poland. Three of the articles from the US - “Physical Activity Education for Adults with Refugee Background in the United States” “Targeting Diet and Physical Activity: Reaching Homeless Adults through Customized Interventions,” and “Prevalence of Sarcopenia and Sarcopenic Obesity Vary with Race/Ethnicity and Advancing Age” studied lifestyle-related issues among diverse populations. Physical activity is very important to control weight and reduce the risk of developing chronic diseases such as cardiovascular disease and diabetes. One of the negative health consequences from physical inactivity is obesity.

Perspectives of Health Care Services among Free Clinic Patients in the USA: A Qualitative Study

The United States (US) is the only developed country which does not have universal health insurance. Free healthcare clinics are operated largely by volunteers for the purpose of providing healthcare services to populations who are under- or un- uninsured in the US. Few qualitative studies have been conducted on patient experience and satisfaction at free clinics and, of those that do exist; most have been administered through focus groups. Thus, the purpose of this study is to explore perceptions and satisfaction among patients at a free clinic using a qualitative approach. Free clinic patients (N=649) participated in a survey with one open-ended question asking about their perceptions of the free clinic in 2017. This study analyzed the qualitative data from the openended question only. On average, the participants responded as being grateful and satisfied with the services provided by the free clinic. However, participants felt that they would benefit from further continuity of care and a higher number of medical providers, as well as more specialists. Future services to be modified or added, as indicated by the participants, include a greater variety of class times for health education and exercise classes, as well as the addition of urgent care services. To improve patient satisfaction, it is recommended to increase promotions for volunteer opportunities in addition to more training. Furthermore, it is necessary to give patients better access to referrals to community resources that offer the additional services that they are interested in.

Indigenous Peoples Heath in the United States of America: Review of Lifestyle Issues and the Implementation of Community-Based Participatory Research

The American Indian/ Alaskan Native (AI/AN) population is considered as an “invisible minority” as their health concerns are not addressed equitably compared to other racial/ ethnic minority populations. AI/AN individuals face high rates of nutritional challenges and chronic health conditions including diabetes and cardiovascular disease. The purpose of this paper is to review concerns about AI/AN health disparities and to propose strategies to reduce disparities. This is achieved by reviewing the evidence for health disparities experienced by AI/AN populations. The U.S. government has been working to improve health disparities for AI/AN individuals, through a number of federally run programs. We propose that one important strategy to reduce health disparities is use a community-based participatory research approach (CBPR). Because of the local input, CBPR is a powerful tool for addressing health disparities experienced by AI/AN populations. We further propose that CPBR should be focused on tribal consultation in policymaking, an increase in AI/AN stakeholders, and health disparities in lifestyle issues for AI/ AN people living in urban areas, in addition to reservations.

Stress Management Classes for Uninsured Free Clinic Patients in the United States

Objective: Stress has become a growing public health concern in the United States (US). Uninsured, low-income or minority patients utilizing a free clinic are exposed to stress disproportionately across various areas of life. Health promotion programs regarding stress management have the potential to benefit vulnerable, low income populations by reducing stressrelated health issues. The purpose of this study was to describe and evaluate the “stress-management” education class taught at a free clinic that provides healthcare to uninsured patients. Methods: Data for this study were collected by a prestress management class survey, field notes during the stress management class, and post-class survey at a free clinic for low-income, uninsured patients. The surveys and class took place in June 2018. Direct observations were based off the Theory of Planned Behavior (TPB). Results: Fifty-five stress management classes were offered with a total of 83 participants. Among the class participants, 71 filled out the survey. Free clinic patients experience cumulative negative situations. One strategy to cope with stress is to organize participant responsibilities. Main stressors among the participants included finances, family, emotions, work, health, social relationships, and a sense of not belonging. Conclusion: Providing resources regarding stressors would be a feasible solution for patients at free clinics. Future projects should work to develop stress management class which responds to the results of this study.