• Perception of Access to Prenatal Care of Women Presenting to the Emergency Department During the First Trimester of Pregnancy

      Deason, Brandon; The University of Arizona College of Medicine - Phoenix; Bayless, Patricia (The University of Arizona., 2016-03-23)
      Background: Despite the large amount of research regarding prenatal care (PNC) in physicians’ offices, hospital outpatient clinics, and community health centers, there is a great paucity of information regarding the role the Emergency Department plays in PNC. Objective: To understand the factors associated with pregnant women’s choice to seek prenatal care in the Emergency Department. Methods: This study is an investigative examination of the attitudes towards and perceived barriers to PNC of women in the first trimester of pregnancy presenting to the Emergency Department at an urban level 1 trauma center. Survey questions examined demographic information and patient factors, such as how they found out about the pregnancy, if they had seen a doctor for this pregnancy, use of PNC in prior pregnancies, and whether they would utilize first trimester PNC in the future. Additionally, the survey contained a series of statements about the importance of PNC and factors affecting their utilization as rated on a 5 point Likert scale. All data was abstracted and coded into Excel. Descriptive statistics and 95% confidence intervals were calculated. Logistic regression was used to predict future PNC use. Results: A total of 74 patients who met the inclusion criteria were surveyed. Ninety‐three percent (CI 84‐97%) knew they were pregnant prior to presenting to the ED. Thirty‐seven percent (CI 27‐50%) had a prenatal visit prior to the index ED visit. Twelve percent (CI 6‐22%) reported they were at the ED for PNC, 70% (CI 59‐80%) for another OB/GYN issue, and 18% (CI 10‐28%) for a reason unrelated to pregnancy. However, 22% strongly agreed and 8% agreed that if they had PNC they would not have come to the ED that day. Predictors of future PNC use included knowledge of pregnancy prior to ED visit, number of pregnancies, belief that PNC is important for the mother’s health, knowledge of where to receive PNC, and belief that taking prenatal vitamins during pregnancy can help the baby. Conclusions: For the population of pregnant females presenting to an urban level 1 trauma emergency department during the first trimester of pregnancy, a large proportion (30%) reported they would not have come to the ED if they received PNC. This would represent a significant reduction in ED visits per year if these women received appropriate services. Future research would need to further delineate the perceived barriers to PNC in this population.
    • The Proportion of Adolescents Complaining of Anterior Knee Pain with Osteochondritis Dissecans and the Utility of Screening Radiographs in its Diagnosis.

      MacKenzie, James; The University of Arizona College of Medicine - Phoenix; Vaughn, Jeffrey M.; Shrader, M. Wade (The University of Arizona., 2016-04-01)
      Osteochondritis dissecans is a rare condition which can cause disabling knee pain in adolescents. Treatment and prognosis hinges upon the stage of the lesion and early detection is paramount 1‐3. Until recently, epidemiologic information regarding OCD in adolescents was unavailable. However in 2013 Kessler et al. demonstrated an incidence of 9.5/100,000 in the general adolescent population 4. Chief complains from patients with OCD usually localize pain to the knee joint line, but less commonly, patients may complain of anterior knee pain. This retrospective chart review looked at the amount of OCD diagnoses in adolescents specifically complaining of anterior knee pain without causative trauma in the years 2009 and 2010 at a major children’s hospital. It was noted that 7.5% of children with this presentation had a diagnosis of OCD. This number was over three orders of magnitude higher than the incidence seen in the general adolescent population as established by Kessler and may support the use of screening radiographs in this subset of patients to detect OCD in its early stages.
    • Racial/Ethnic Disparities in HIV Survival Among People Diagnosed with HIV in Arizona, 1998‐2012

      Mun, Elijah; The University of Arizona College of Medicine - Phoenix; Gonzalez, Jonathan (The University of Arizona., 2016-03-25)
      Objectives. We described the racial/ethnic disparities in survival among people diagnosed with HIV in Arizona from 1998 to 2012. We determined whether these disparities widened when adjusting for AIDS diagnosis, age at diagnosis, year of diagnosis, and gender. Methods. We compared survival from all causes between Whites and Blacks, Hispanics, Native Americans, Asians, and Multiple/Other races via Kaplan‐Meier survival curves and Cox proportional hazard models controlling for various clinical factors. Results. Multiple/Other races (1.85), Native Americans (1.28), and Blacks (1.19) have statistically significant higher hazard ratios in all‐cause mortality than Whites. When adjusting for AIDS diagnosis, these disparities widened and also showed Hispanics to have greater mortality [Multiple/Other races (2.53), Native Americans (1.44), Blacks (1.43), and Hispanics (1.22)]. Conclusions. Racial/ethnic minorities with HIV, specifically Black, Native Americans, and Multiple races, have significantly decreased overall survival. These disparities widen when considering the AIDS population. Further studies and resources could help identify the cause of these disparities and help generate a solution to diminish the survival gap.
    • A Randomized Controlled Trial Comparing Preemptive Versus On Demand Administration of Analgesics After Mohs Surgery and Cutaneous Reconstruction

      Crow, Lauren; The University of Arizona College of Medicine - Phoenix; Brodland, David (The University of Arizona., 2016-03-23)
      BACKGROUND: Mohs Micrographic Surgery (MMS) affords a high cure rate for cutaneous carcinoma. OBJECTIVE: This study was designed to characterize the pain patients experience after MMS and reconstruction of the head and neck, and to determine if preemptive dosing of analgesics was superior to patient‐initiated dosing on an "as needed" basis. METHODS: A controlled trial of 200 subjects undergoing MMS and reconstruction of skin cancers on the head and neck were randomized to either receive acetaminophen at the time of discharge or to take it on an "as needed" basis. The two groups were evaluated for differences in peak pain, satisfaction with pain management, and the need for narcotic analgesic "rescue" postoperatively. RESULTS: Peak pain levels after surgery were surprisingly low and rated, on average, 2/10 using an analog pain scale. Peak pain occurred at four hours postoperatively for both subgroups and patients were satisfied with pain control 72.5% of the time. There was no significant difference in any of the parameters between the two dosing regimens. CONCLUSIONS: Mohs surgery peak pain typically occurs four hours postoperatively. Patient satisfaction with pain management was high with acetaminophen regardless of the dosing regimen. Preemptive analgesia with acetaminophen does not appear to be superior to "asneeded" regimens.
    • The Role of Injection Laryngoplasty (IL) in Treating Deep Interarytenoid Notch (DIN) Associated Dysphagia in Young Children

      Frantz, Garrett; The University of Arizona College of Medicine - Phoenix; Williams, Dana (The University of Arizona., 2016-04)
      BACKGROUND Deep Interarytenoid Notch (DIN) is the mildest form of laryngotracheoesophageal cleft defect and is frequently found in young children with dysphagia and aspiration. Treatment guidelines are not defined. Injection laryngoplasty (IL) is a surgical procedure injecting polymer gel into the issue around the defect. Our objective was to evaluate the efficacy of IL in pediatric populations with severe dysphagia and aspiration. METHODS We conducted a pilot retrospective chart review of DIN patients under 36 months who underwent IL at PCH. Severity of dysphagia before and after IL was measured using modified barium swallows (MBS) (scale 0‐10) and documented symptoms. Statistical analysis was done using paired two sample t‐test with a p value of 5 percent. RESULTS Patients with initial MBS above double honey (7) improved an average of 2.6 ±1.38 points while those with initial scores below 7 did not see a statistical change in MBS. At the end of the study period, the final MBS scores for both groups were statistically similar.CONCLUSIONS IL treatment for DIN associated dysphagia results in improvement of MBS scores and symptoms in toddlers with severe aspiration. Careful timing of IL impacts morbidity. Future prospective controlled studies are necessary to evaluate the role of IL and medical interventions in thickener wean and clinical improvement.
    • Safety and Visual Outcomes of Novel Abexterno Akreos® Single Pass Method of Transscleral Sutured Posterior Chamber IOL Implantation for Scleral Fixation of IOL

      Wallman, Andrew; The University of Arizona College of Medicine - Phoenix; Monson, Bryan (The University of Arizona., 2016-04-20)
      We present the safety and efficacy of a novel transscleral sutured posterior chamber intraocular lens (TSSPCIOL) implantation approach utilizing 25 gauge vitrectomy and a foldable posterior chamber intraocular lens implant (AKREOS AO60, Bausch & Lomb). 80 consecutive eyes that underwent single surgeon TSSPCIOL implantation between October 2008 and July 2012 at a referral‐based retina institution were analyzed for best spectacle‐corrected visual acuity (BCVA) and safety indicators. Postoperative complications included retinal detachment in 2 eyes (2.5%), Irvine‐Gass cystoid macular edema in 3 eyes (3.75%), with 2 of those cases occurring late, persistent postoperative corneal edema in 1 eye (1.25%), hyphema in 2 eyes (2.5%) and 1 case of postoperative vitreous hemorrhage with spontaneous clearing. The modified external approach with AKREOS® TSSPCIOL placement with 25 gauge vitrectomy has relatively few complications, improves visual acuity in patients requiring TSSPCIOL, and offers several advantages over traditional anterior chamber or conventional scleral sutured techniques.
    • Skin Disorders Encountered at a Pediatric Homeless Clinic: A Retrospective Chart Review

      Balasuriya, Lilanthi; The University of Arizona College of Medicine - Phoenix; O’Haver, Judy (The University of Arizona., 2016-03-23)
      BACKGROUND AND SIGNIFICANCE: Limited information about skin problems in homeless children exists in the current literature. RESEARCH QUESTION: Our objective was to classify the types of skin conditions commonly seen in a pediatric homeless clinic as compared to that of a large tertiary care children’s hospital dermatology clinic. METHODS: We conducted a retrospective cohort study of all children treated by pediatric dermatologists at a homeless clinic, and compared the diagnoses to what was seen at a general pediatric dermatology clinic. RESULTS: There were 100 visits for 75 patients at the homeless clinic during the study period of 33 months. Within the homeless clinic visits, 62% of patient’s reported living in a shelter. In the homeless population the most common diagnoses were atopic dermatitis (31.0%), acne (27.0%), other dermatitis (7.0%), molluscum (6.0%), warts (5.0%) and nevi (4.0%). In the nonhomeless population, the most common diagnoses were atopic dermatitis (19.2%), contact dermatitis (9.7%), hemangioma (9.5%), acne (9.4%), nevus, non‐neoplastic (6.8%) and benign neoplasm of the skin (6.3%). CONCLUSION: Homeless and non‐homeless children suffer from similar conditions such as atopic dermatitis, acne and nevi. With the growing homeless pediatric population and their exposure to unsheltered environments, further studies are needed to investigate the skin conditions affecting this population.
    • A Study of the Vascular Basis of Alzheimer’s Disease: The Role of Beta Amyloid (Aβ) Proteins and Saturated Fatty Acids in Endothelial Dysfunction and Inflammation

      Buchanan, Jenna; The University of Arizona College of Medicine - Phoenix; Migrino, Raymond Q. (The University of Arizona., 2016-03-23)
      Background: Studies have shown that Alzheimer’s Disease (AD) is strongly associated with the presence of atherosclerosis risk factors, including hyperlipidemia (and associated increased free fatty acids), hypertension and diabetes. We tested the hypotheses that β‐ amyloid proteins (Aβ) or palmitic acid (PA), a saturated fatty acid and known atherosclerotic risk factor, cause impaired function and viability of human umbilical vein endothelial cells (HUVEC), and that together, they exert synergistic effects on HUVEC dysfunction. Methods: HUVEC were exposed for 18‐20 hours to vehicle, Aβ42 (2μM) ± PA (150μM) or PA (150μM) while some HUVEC were exposed to a 4‐hour pre‐treatment with PA (150mM) followed wash and treatment with vehicle ± Aβ42 (2μM) for 18‐20 hours. Outcomes measured included: (1) nitric oxide (NO) and measures of oxidative stress (superoxide) and nitrosative stress (peroxynitrite), (2) inflammatory and associated markers (interleukins (IL)‐6, IL‐8, Reaction for Advanced Glyocolytic End Products (RAGE) 1 and 2, and Matrix Metalloproteinases (MMP‐9) by PCR. Results: HUVECs exposed to either Aβ or PA showed impaired NO production and increased superoxide and peroxynitrite when compared to vehicle control. Co‐treatment with Aβ and PA did not cause a statistically significant change compared to Aβ or PA alone. HUVEC demonstrated variable inflammatory responses following exposure to either Aβ or PA. Treatment with PA resulted in upregulation of RAGE2 gene expression (p<0.003) and trend towards IL‐6 overexpression (p=0.059). Co‐treatment with both Aβ and PA led to an observed increase in inflammatory responses versus control, but the results did not reach statistical significance. Conclusion: Independent exposure of HUVECs to Aβ and PA caused decreased nitric oxide production and increased oxidative and nitrosative stress. HUVECs did not demonstrate Aβ‐ induced endothelial cell inflammation. Co‐treatment with 2μM Aβ and PA 150μM did not result in a synergistic or additive increase in endothelial cell inflammatory responses.
    • A Survey to Assess Parent Perspective of the Impact of a Gluten‐Free, Casein‐Free Diet on Their Child’s Symptoms of Autism Spectrum Disorder

      Wendt, Rebecca; The University of Arizona College of Medicine - Phoenix; Melmed, Raun; Savi, Christine (The University of Arizona., 2016-03-25)
      With the prevalence of Autism Spectrum Disorder (ASD) rising (approximately 1 in 45)1 treatment for the disorder becomes even more important. Families turn to both traditional and alternative medicinal sources for help. The Gluten‐Free, Casein‐Free (GFCF) diet is an example of an alternative therapeutic approach. Study Aims: Our aims were to design and begin initial validation of a survey to evaluate the use and efficacy of the GFCF diet in children with ASD with concurrent gastrointestinal (GI) symptomatology. We also aimed to assess feasibility of the survey in the target population through piloting the survey. This is the first step in determining association of the GFCF diet in children with ASD. Methods: A survey was developed with expert review, meant for completion by parents and primary caregivers of children with ASD. The survey content included demographics, treatments used, GI symptoms (as measured by a modified Rome III parent report form), food allergies and intolerances, and frequency of aberrant behaviors (as measured by the Aberrant Behavior Checklist). Questions regarding diet use (specifically gluten‐free diet, casein‐free diet, or GFCF) were included in the treatment modalities and as well as questions regarding compliance and length of time used. The survey was advertised to our target population and 38 completed responses were obtained for a pilot study. Results: The pilot study revealed questions which were not clear to the target population and required modifications. Data from the responses revealed 14/38 participants who attempted the GFCF diet or its variants with their child, 11 for 3 months or greater. Number of food intolerances was heightened among those who used the diet or its variants. Heightened ABC irritability subscores were noted among those with GI symptoms. Conclusions: The pilot survey developed for this project suggests that the use of the GFCF diet in children with ASD is not only common but also might be a useful therapeutic agent. The need for further validation of the tool is paramount.
    • Tearing Down the Wall: Identification of Biases as a First Step in Building a Team Mentality and Preparing Physician Assistant, Social Work, Nursing, and Medical Students to Participate in Interprofessional Education and Practice

      Bonfiglio, Chelsea; The University of Arizona College of Medicine - Phoenix; Hartmark-Hill, Jennifer (The University of Arizona., 2016-03-23)
      The Institute of Medicine’s landmark study on patient care outcomes, A Bridge to Quality, called for interprofessional education and practice that prepares healthcare students from different healthcare professions to collaborate for optimal patient safety. Additional benefits of interprofessional education include increased patient satisfaction and provider job satisfaction. Despite this knowledge, IPE interventions are not widely instituted in health professions education. In July of 2013, the Liaison Committee on Medical Education released a common standard for IPE in the US due to the realization that collaboration will play a large role in the careers of students across the health professions. More research is needed to demonstrate what components, sequencing, and frequency of interprofessional education contributes the greatest value to the competency goals established by the Interprofessional Education Collaborative. This study aims to determine if a novel curricular component, a program entitled, the “Medical Wall,” is able to demonstrate a positive impact on students’ interest and value for interprofessional education, and if the activity has a significant effect on student’s knowledge of barriers to effective team communication and collaboration, and their attitudes regarding the values and ethics of interprofessional collaboration as it relates to patient care. 196 MD, BSN and PA students were randomized into intervention and control groups. All students randomized into the intervention group were further randomized into mixed‐professions small groups who participated in the Medical Wall program, while their peers in the control group completed an alternate and unrelated activity. All participants took the validated pre‐ and post Readiness for Interprofessional Learning Scale survey to determine if there was significant intervention impact. The learning scale assessed four categories: Teamwork, Negative Professional Identity, Positive Professional Identity and Roles and Responsibilities. The “The Medical Wall” IPE intervention resulted in significant improvement in two out of four categories of the Readiness for Interprofessional Learning Scale compared to controls (p value set at <0.05). These results indicate that participation in a brief interprofessional education intervention is effective for enhancing Nursing, Physician Assistant, and M
    • The Use of Clinical Decision Rules to Reduce Unnecessary Head Ct Scans in Pediatric Populations

      Barrett, Jeffrey; The University of Arizona College of Medicine - Phoenix; Panchanathan, Sarada (The University of Arizona., 2016-04-20)
      Background: Head computed tomography (CT) imaging is the gold standard study for rapidly identifying emergent traumatic brain injuries (TBIs). Exposure to the ionizing radiation utilized in CT increases lifetime risk for developing neoplasms. Currently there is little consensus on appropriate use of CT imaging for children with mild head injury. Clinical decision rules (CDRs) have been developed to identify children at very low risk of clinically significant brain injury. While these CDRs have been validated, their implementation has not been as well studied. Objective: To evaluate the efficacy of two CDRs in decreasing CT scan rate without missing clinically significant brain injuries. The two CDRs used in this study were the Children's Head Injury Algorithm for the Prediction of Important Clinical Events (CHALICE) and the Pediatric Emergency Care Applied Research Network (PECARN) algorithm. Both variations of the PECARN criteria for age 2 years and older and age <2 years were studied. Design/Methods: The medical records for patients with the diagnosis of head injury evaluated at the Maricopa Medical Center Pediatric Emergency Department for all of 2011 and 2012 were reviewed. A total of 331 charts were identified. The PECARN and CHALICE inclusion criteria and algorithms were applied to these charts to determine if the patients met criteria for CT scan. Patients with suspected non‐accidental injuries were excluded. Results: Of 331 patients, 238 met the inclusion criteria for CHALICE. 96 (40.3%) had CT scans performed. According to the algorithm, only 52 (21.8%) met criteria, which is an absolute rate reduction of 18.5%. One TBI was missed. 129 patients met the inclusion criteria for PECARN age 2 years and older. 73 (56.6%) had CT scans performed. 61 (47.2%) met criteria resulting in an absolute rate reduction of 9.4%. No TBIs were missed. 74 patients met inclusion criteria for PECARN age <2 years. Of these, 25 (33.7%) had CT scans performed and the same number met criteria resulting in no change in number of scans. One TBI was missed. Conclusions: Both the CHALICE and PECARN CDRs have the potential to reduce scan rates in our home institution. The CHALICE CDR would have resulted in a greater reduction in CT scans. PECARN also would have reduced the number of scans in children 2 years and older, but not in children <2 years old. The TBI that did not meet CDR criteria was also missed by clinical suspicion and a CT scan done on a later encounter was suspicious for a non‐accidental injury.
    • The Utility of Hemoglobin A1c in Detecting Prediabetes in Obese Youth

      Srivastava, Sarika; The University of Arizona College of Medicine - Phoenix; McClellan, Donald (The University of Arizona., 2016-03-25)
      Introduction. The incidence and prevalence of Type 2 diabetes mellitus has been steadily increasing over the past ten years, and is currently approximately 4.1 per 1000 12‐19 year olds in the US2. This increase has been linked to obesity and a sedentary lifestyle. Prediabetes, in the pediatric population is defined as having a fasting plasma glucose concentration ≥ 100 to 125 mg/dL or 2‐hour glucose concentration during an oral glucose tolerance test ≥ 140 mg/dL but <200 mg/dL. Aims. The goal of this study is to describe the sensitivity and specificity of hemoglobin A1c at various thresholds to identify prediabetes, as defined by impaired fasting glucose and/or impaired glucose tolerance; the population included in this study consist of obese youth referred to the Division of Endocrinology and Diabetes at Phoenix Children’s Hospital for weight‐related issues. We anticipate describing various levels of sensitivity and specificity of hemoglobin A1c in comparison with gold standard tests, such that it can be used to propel further studies to ultimately reduce the immense patient burden of fasting in the pediatric population. Methods. We conducted a retrospective cross‐sectional chart review and employed receiver operating characteristic (ROC) curve analysis of data including but not limited to hemoglobin A1c, fasting plasma glucose, and 2‐hr post‐prandial plasma glucose. The benefits of this study include the potential of reducing the patient burden of fasting prior to examination. This review will determine, if any, the potential value in being able to use hemoglobin A1c clinically to detect prediabetes in pediatric patients; determining this may provide critical information to improve the monitoring and screening of prediabetes. Conclusions. Compared to the gold standards of fasting plasma glucose and oral glucose tolerance tests, we found that hemoglobin A1c had a low sensitivity and specificity for identifying prediabetes.
    • Variability in the Interpretation of Elbow Fractures in Children

      Kraynov, Liliya; The University of Arizona College of Medicine - Phoenix; Zebulon, Timothy; Bulloch, Blake (The University of Arizona., 2016-03-25)
      Background and Significance The first physician to encounter a child with an elbow fracture is usually the emergency medicine (EM) physician. Many hospitals may not have access to immediate orthopedic consultation or “real-time” radiology reads, therefore, EM physicians have a great responsibility for an accurate diagnosis. Unfortunately, many EM physicians have little training in pediatric orthopedic injuries. The elbow's anatomy and radiographic features of the growing elbow increase the difficulty in determining an accurate diagnosis and proper treatment. Inaccurate interpretation of elbow fractures in children may lead to unnecessary or improper medical decisions. Accurate interpretation is especially important in rural settings where patients may need transportation to facilities with higher levels of care. Research Question This study aims to survey EM physicians and determine if certain elbow fractures are diagnosed inaccurately more frequently and if some physician characteristics share a relationship with the accuracy of diagnosis of pediatric fractures. The characteristics include area of specialization, annual ED volume, years of experience post residency training, and working in an academic versus non-academic department. Different types of fractures, including type 1 supracondylar, type 2 supracondylar, type 3 supracondylar, medial epicondyle, lateral epicondyle, and olecranon along with uninjured elbows were evaluated to determine if a particular type was misdiagnosed more frequently. Methods A 16-question multiple-choice paper survey was distributed to physicians working in academic and non-academic centers within adult or pediatric emergency departments. Questions included radiographs and asked the physician to determine which fracture existed, if any.Results Lateral epicondyle fractures were the most likely fractures to be misdiagnosed (22.12%), while type 3 supracondylar fractures were the most likely to be accurately diagnosed (95.5%). There was no significant difference in accuracy of diagnosis based on physicians working either in an academic department, non-academic department, or both. Those physicians who were board certified or board eligible in two or more specialties had a higher mean percent correct, as well as those who worked in pediatric emergency medicine. Conclusions While this study served to start clarifying the most frequently misdiagnosed pediatric fractures and whether physicians with particular characteristics were more likely to diagnose fractures accurately, further steady is necessary to draw a definitive conclusion. This study does shed light on which pediatric elbow fractures physicians misdiagnose more frequently. It is important for all emergency medicine physicians to keep in mind the types of fractures that are most commonly misdiagnosed as it can affect medical decision-making. This is an area where additional education about elbow fractures in the developing pediatric elbow may be needed.
    • Visual Findings in Neovascular Macular Degeneration Refractory to Bevacizumab after Intravitreal Aflibercept Therapy

      Moazez, Carmel; The University of Arizona College of Medicine - Phoenix; Reddy, Rahul (The University of Arizona., 2016-03-25)
      Neovascular (wet) age‐related macular degeneration (AMD) is associated with blindness in patient populations above 55 years of age, affecting approximately 2 million Americans. Intravitreal (IV) bevacizumab is widely employed in the treatment of wet AMD. Development of a novel pharmacologic intervention to match bevacizumab’s indications is possible with the advent of aflibercept. This study evaluated the optical coherence tomographic (OCT) findings and intraocular pressure after IV aflibercept therapy in patients with wet AMD refractory to IV bevacizumab therapy. This retrospective review of 29 patient records (30 eyes) demonstrated that 73% of patients did not show an increase in OCT. Furthermore, 83% of patients did not demonstrate an increase in intraocular pressure (IOP) and all patients had an IOP of 20 or less after three months of therapy. This study further explores the mean change per patient in retinal thickness via OCT as well as intraocular pressure. The results of this study demonstrate that aflibercept can improve visual findings in patients refractory to bevacizumab and therefore we recommend that patients be switched to it. Further, it is safe to use in patients with glaucoma as it will not increase the IOP.
    • Vitamin D, Resveratrol, and Control of LCE3 Genes with Implications for Psoriasis

      Batie, Shane; The University of Arizona College of Medicine - Phoenix; Whitfield, G. Kerr (The University of Arizona., 2016-03-23)
      Psoriasis (Psx) is a chronic inflammatory skin disease with abnormal keratinocyte proliferation and differentiation. One genetic risk factor for psoriasis (denoted PSORS4) is a deletion of LCE3B and LCE3C genes encoding structural proteins in terminally differentiated keratinocytes. Analogs of the hormonal form of vitamin D, 1,25‐dihydroxyvitamin D3 (1,25D) are routinely used to treat Psx, a skin disease that affects over 7 million patients in the US. However, this therapy, even when combined with an anti‐inflammatory (e.g., betamethasone), is ineffective in some patients, particularly those with a severe disease phenotype, underscoring the need for better agents. Further, the mechanism of action of vitamin D analogs is not understood, although their ability to reduce proliferation and promote differentiation of psoriatic keratinocytes is both valued in therapy and is complementary to anti‐inflammatory agents. Given that 1,25D acts via the vitamin D receptor (VDR) to regulate gene expression, this project is focused on elucidating expression alterations in psoriasisrelevant genes mediated by the 1,25D‐liganded VDR in human keratinocytes. Whereas VDR activity is increased when bound to 1,25D, less is known about the ability of other nutritionallyderived lipids to act on VDR. The current study is designed to: 1) evaluate resveratrol, an antioxidant found in the skin of red grapes, as an effector of VDR signaling and potent activator of LCE gene transcription in human keratinocytes, and 2) determine whether resveratrol acts synergistically with 1,25D to regulate the expression of LCE3 genes, with the potential to boost skin repair and ameliorate the symptoms of psoriasis.