University of North Texas
UNTHSC Scholar (University. of North Texas Health Science Center)Not a member yet
6724 research outputs found
Sort by
A Case of Neutrophilic Dermatosis of the Dorsal Hands with Post-Traumatic Onset
No full textBackground: Sweet Syndrome is an acute, febrile neutrophilic dermatosis that is characterized by painful, red papules and plaques, fever, and neutrophilia with histological findings of dermal neutrophilic infiltrate. Neutrophilic Dermatosis of the Dorsal Hands is a localized variant of Sweet Syndrome. Neutrophilic Dermatosis of the Dorsal Hands presents with focused papules and plaques on the dorsal hands, most commonly between the index finger and thumb, typically with fewer systemic manifestations. This condition presents significant diagnostic challenges as it can mimic infectious processes, potentially leading to delayed appropriate treatment. Case Information: A 64-year-old male presented to the emergency department with wounds on the bilateral hands. He reported injuring his right hand three weeks prior to presentation that then progressively enlarged over two weeks. The patient noticed the onset of a wound on his left hand despite no injury or trauma. One week before hospital admission, the patient was prescribed trimethoprim-sulfamethoxazole and clindamycin. Despite antimicrobial treatment his wounds continued to worsen. The patient reported that he had occasional fevers but denied other systemic symptoms. In the hospital he was given IV antibiotics and initial work-up complete blood count and complete metabolic panel were performed without clinically significant findings. X-ray of the hands showed soft tissue swelling with polyarticular degenerative joint disease. Blood and wound cultures showed no growth. Due to lack of clinical response, dermatology was consulted. Physical exam showed edematous red plaques with overlying hemorrhagic crust extending from the thumb to the dorsal hands bilaterally. Clinically, the presentation was consistent with neutrophilic dermatosis of the dorsal hands, however, to confirm the diagnosis and rule out infection biopsies were performed. The biopsies showed a neutrophilic infiltrate with spongiosis and eosinophils without fungal or atypical mycobacterial growth on cultures which confirmed the diagnosis. The patient was initiated on topical fluocinonide ointment twice daily under occlusion at the time of the biopsy. The patient reported significant improvement in pain within 1 day of receiving treatment. Conclusion: Neutrophilic Dermatosis of the Dorsal Hands requires high degree of clinical suspicion. Neutrophilic dermatosis is a disease of exclusion and must rule out other diseases that can present similarly including infection, vasculitis, and drug reactions. Most importantly, NDDH exhibits pathergy – worsening with trauma – as seen in this case where the condition occurred after injury. Early recognition and appropriate diagnosis can prevent unnecessary antibiotic and surgical interventions as well as prevent harmful interventions like debridement, which can exacerbate the condition. This case demonstrates a key diagnostic criterion of Neutrophilic Dermatosis of the Dorsal Hands – rapid improvement within 24 hours of appropriate therapy – while providing valuable insight into the variable progression and healing stages of this condition
UNTHSC Geriatrics ECHO Series: Clinical Training and Education on Age-Friendly Care for Primary Care Resident Physicians
No full textPurpose: Resident physicians must acquaint themselves with the challenges faced by the older adults during their residency. The UNTHSC Geriatrics ECHO Series, held through videoconferencing from August 2024 to June 2025, offers clinical training and education in geriatrics to residents in family medicine and internal medicine programs. The aim is to enable resident physicians to effectively assess and manage the 4Ms of age-friendly care (Matters Most, Mentation, Mobility, Medication), therefore improving care for older individuals. Methods: We are facilitating ten sessions for two participant groups. Each group meets once per month with a Tuesday and Thursday offering. The didactic content in the sessions is identical. We conduct anonymous surveys to evaluate the UNTHSC Geriatrics ECHO Series impact. We will conduct two surveys: a mid-year survey and an end-of-year survey. The mid-year survey was given after five sessions, and we will conduct an end-of-year survey after completion of the curriculum or ten sessions. Using a five-point Likert scale (Strongly Disagree, Disagree, Neither Agree nor Disagree, Agree, Strongly Agree), participants from both groups were asked to rate the value of didactics, case discussions, supplemental materials, and post-session summaries with resources in helping them learn more about geriatrics. We also invited participants to share their experiences with Geriatrics ECHO. Results: Five sessions were held prior to the mid-year survey for both the Tuesday and Thursday participant groups, respectively. For the Tuesday group, 18 family medicine residents participated, while 21 internal medicine residents took part in the Thursday Participant Group. In Tuesday's group, 7 out of 18 family residents participated in the mid-year survey, and all 7 (100%) strongly agreed that the didactics and case discussions were beneficial in enhancing their geriatrics knowledge. On Thursday, the participant group, out of 21 participants, had 7 engage in the mid-year survey. Among them, 4 of 7 (57%) strongly agreed that case discussions were beneficial, while 3 of 7 (42.8%) strongly agreed that didactics were effective in enhancing their understanding of aging issues. In both questionnaires, 6 out of 14 residents (42.8%) reported their experiences and indicated that they will apply the knowledge acquired from these sessions in their future careers. Conclusions: Through videoconferencing, the UNTHSC Geriatrics ECHO Series effectively raised residents' awareness and understanding of the problems of older people, and it gave them the confidence to evaluate and address the 4Ms of Age-Friendly care. This knowledge not only assists them during their residency but will also be applied in their future careers, even if they are not specialists in geriatrics, thereby enhancing healthcare outcomes for older adults. Nonetheless, a weakness of the study is that the conclusions are solely based on self-reported data from a limited number of resident physicians
Hypopituitarism and Other Endocrinopathies as a Consequence of Septo-Optic Dysplasia
No full textBackground: Septo-optic dysplasia (SOD) is a rare disorder that affects early brain development. It is characterized and diagnosed by the presence of at least 2 out of the following 3: optic nerve hypoplasia, agenesis of the septum pellucidum, and pituitary hypoplasia. SOD only affects 1 in 10,000 births [2], and there are few cases in the literature of patients with SOD in the U.S. who are adults in stable condition. Case Presentation: We present a 29-year-old F with PMH of panhypopituitarism, diabetes insipidus, adrenocortical insufficiency, and congenital hypothyroidism secondary to septo-optic dysplasia of the brain. The patient initially presented to the endocrinologist in 2022 for management of her thyroid and pituitary glands. According to anecdotal birth history from her parents, the patient was born with no complications and was kept in the hospital for a few days for an abnormal APGAR score; she was eventually discharged with no definitive diagnosis or clues of underlying pathology. As the months progressed, her parents noticed that she was not meeting her developmental milestones and was developing progressive vision loss, prompting further medical evaluation. For years, a diagnosis could not be determined and she was managed symptomatically for her developmental delay. At age 3, she developed hypocortisolism followed by diabetes insipidus at age 5. At age 7, from a combination of physical exam findings, hormone levels, and MRI, a formal diagnosis of septo-optic dysplasia was reached. Currently, the patient is in stable condition and is under the constant care of her mother and father. This patient's thyroid, vasopressin, and adrenal axes are affected; she also is being managed for class II obesity complicated by cognitive impairment. She is currently being treated with levothyroxine, desmopressin, hydrocortisone, insulin, and vitamin D. Conclusions: This case highlights the effective management of severe septo-optic dysplasia (SOD) in an adult patient, with the clinical condition remaining stable over time. Her stable condition is in large part due to her diagnosis in childhood and proper management since then. This case outlines the specifics of her treatment regimen, which is not illustrated in the current literature. Future studies should be conducted to investigate optimal treatment interventions depending on the stage of the disease
Rodents exposed to an impoverished environment display sex differences in blood pressure, brain and kidney inflammation in adulthood
No full textPurpose: Poverty, a low-resourced state, is a common adverse childhood experience (ACE) or early life stress (ELS). People that experienced childhood poverty are at greater risk for developing hypertension (HTN) during adulthood, with sex differences. Multiple human and animal models of ELS display a strong positive correlation with inflammation and blood pressure (BP). However, this association is not widely examined in rodents that have experienced an impoverished environment. The objective of this study is to investigate the changes in BP, parasympathetic activity, and inflammation in the brain and kidneys of rodents exposed to an impoverished environment, using the limited bedding and nesting (LBN) model. We hypothesize that LBN males (M) will display an increase in BP, pro-inflammatory cytokines, and decrease in high frequency heart rate variability (HF HRV; parasympathetic activity) compared to control (CON) M. LBN females (F) will display no changes in these parameters compared to CON F. Methods: The LBN model mimics childhood poverty by creating an impoverished environment with a reduction of bedding and nesting material on postnatal days 2-9. The LBN rats had ~80% less bedding and nesting material compared to the CON. After weaning, the offspring were separated by sex and treatment: LBN M (n=8), CON M (n=8), LBN F (n=8), and CON F (n=8). Using colorimetric assays, tumor necrotic factor-alpha (TNF-α) and interleukin-17 (IL-17) were measured in the brain (cerebrum, brain stem, and cerebellum) and kidney (cortex and medulla) of adult LBN and CON rats at 16-18 weeks of age. Results: LBN M displayed an increase in BP (140 ± 3 vs 117 ± 5 mmHg; p=0.001) compared to CON M. LBN F had no changes in BP vs CON F (ns). HF HRV was increased in both LBN groups vs CON (F (1, 25) = 4.408; p=0.05). IL-17 in the cerebrum (1.93 ± 0.13 vs 2.96 ± 0.34 mg/mL/mg protein; p=0.02) and brain stem (2.04 ± 0.35 vs 4.43 ± 1.23 mg/mL/mg protein; p=0.04) were decreased in LBN M vs CON M. Furthermore, TNF-α was decreased in the cerebrum (268.81 ± 17.99 vs 334.28 ± 20.91 pg/mL/mg protein; p=0.04), brain stem (90.26 ± 19.65 vs 166.52 ± 16.59 pg/mL/mg protein; p=0.04), and cerebellum (71.90 ± 16.43 vs 206.79 ± 73.65 pg/mL/mg protein; p=0.04) of LBN M vs CON M. No changes in brain IL-17 or TNF-α were observed in LBN F vs CON F (ns). The kidney cortex and medulla showed no changes in IL-17 and TNF-α in LBN vs CON and/or M vs F (ns). Conclusions: LBN F revealed no changes in BP and inflammation in the brain and kidneys. Parasympathetic activity (HF HRV) was increased in LBN M and LBN F rats. Despite the increase in parasympathetic activity, LBN M exhibited an elevation in BP and surprisingly a decrease in IL-17 & TNF-α in the brain. Perhaps, the increase in parasympathetic activity and decrease in pro-inflammatory cytokines are working together to lower BP. Contrarily, the increase in parasympathetic activity alone in LBN F may blunt the increase in BP expected with LBN treatment
Case Report of Chronic Pancreatitis and Autoimmune Cholangitis in a 78-year-old male.
No full textA 78-year-old male presented with painless jaundice and was found to have elevated alkaline phosphatase level. To evaluate for a high suspicion of pancreatic cancer, an EUS and ERCP were conducted. These studies revealed a pancreatic genu mass, biliary strictures, and features of chronic pancreatitis. Brush Cytology and FNA were benign. Due to continued concern for malignancy, a repeat EUS was done 4 months later with similar findings of chronic pancreatitis and FNA was benign again. The patient did well for 2 years, though ALP remained elevated. Two years from initial presentation, the patient presented with 3-week history of pruritis, fatigue, and mild jaundice. ERCP was strongly suggestive of autoimmune primary sclerosing cholangitis. There was no common bile duct stricture found. A stent was placed for good measure, but did not seem to help. Due to the unexpected finding of PSC and no history of inflammatory bowel disease, IgG-4 was checked and was significantly elevated to 610 (normal 1-123). Given a very high suspicion for autoimmune cholangitis, the patient was started on a slow prednisone taper. After 6-months of prednisone, tapered down to 25 mg/day, patient reported no pruritis nor jaundice, and his alkaline phosphatase level improved
Evaluation of Anti-Cancer Activity of Copper-Tolfenamic Acid Against Ovarian Cancer Cells
No full textPurpose: Ovarian cancer typically originates from epithelial cells within the ovaries and can spread throughout the body through metastasis. Metastatic ovarian cancer has a 20% 5-year survival rate. Currently, there aren’t many effective treatments for ovarian cancer and there is an urgent need to develop increasingly effective treatments to combat later stages of ovarian cancer at the cellular level. Survivin, an inhibitor of apoptotic proteins, induces resistance to radiation and chemotherapies and is associated with the poor prognosis of multiple cancer types. Experimental strategies to directly target Survivin were not successful. Transcription factor Specificity protein 1 (Sp1) regulates several cancer-related proteins, including Survivin. Our laboratory and others demonstrated the Sp1 inhibitory response of a non-steroidal anti-inflammatory drug, Tolfenamic Acid (TA). Our laboratory also showed that a copper complex of TA was more effective than TA against pancreatic cancer in preclinical models. Based on these results, we hypothesize that Cu-TA will have an efficient anti-proliferative effect against ovarian cancer cells. This study aims to explore the effectiveness of Cu-TA in the inhibition of Sp1 and Its impact on the growth of ovarian cancer cells, ES-2 and SKOV3. Methods: ES-2/SKOV3 cells were cultured and treated with increasing concentrations of Cu-TA or TA. Cell Titer Glo luminescence kit was used to measure the cell viability after 48 h. IC50 values were obtained via GraphPad Prism Software. R2 Genomics Visualization Platform was accessed to obtain Kaplan-Meier survival curves showing the association of Sp1 expression and Ovarian Cancer patient survival. Protein extracts were prepared from clinical specimens (Primary and Ovarian Tumors) using a Cell Lysis Buffer (Invitrogen) and the expression of Sp1 and Survivin was determined by Western blot analysis. Results: The R2 genomics data showed that the patients with low Sp1 expression survived longer than those with high expression (p-value: 8.83x10^-4). Our laboratory showed that ovarian tumors expressed high expression of Sp1 and survivin when compared to normal tissue . Cu-TA’s IC50 values were much lower than TA. Conclusions: Online data suggested the role of Sp1 in the poor prognosis of ovarian cancer patients. Cu-TA is more effective than TA and inhibits ovarian cancer cell growth at lower dosages. This study suggests that Cu-TA can be effective against ovarian cancer cells potentially targeting Sp1 expression. The experiments to test underlying mechanisms are currently under investigation
Investigating the Mechanism Behind Metronidazole Inactivation in Enterococcus faecalis
No full textPurpose: Originally a first-line choice of treatment for Clostridiodes difficile colitis, metronidazole (MTZ), a 5-nitroimidazole class antibiotic, has since fallen from its place as a mainstay due to decreasing clinical efficacy rates. Updated clinical guidelines now recommend using vancomycin or fidaxomicin instead. In this study, we investigated the idea that the human gut microbiota, primarily Enterococcus faecalis, has contributed to MTZ’s downfall. Methods: We used GC-MS and a spectrophotometric assay to confirm that E. faecalis OG1RF metabolized MTZ and, through random mutant screenings, found that the aroC chorismate synthase encoding gene had an attenuated degradation phenotype, which suggested that menaquinone synthesis was required for MTZ metabolization. The need for menaquinone synthesis was confirmed upon chemical supplementation of aro
Family-centered approach to extremely preterm (EPT) infants.
No full textPurpose: Extremely Preterm (EPT) infants are born at 22–23-weeks gestational age. Morbidity and mortality have significantly improved for this population internationally, however, historically, decisions around resuscitation and active intensive care for EPT infants were at the discretion of individual providers. In 2022, a formal EPT guideline was started, with family goals of care and shared decision making as the primary drivers. This guideline introduced standardized information to promote informed decision making and elevated family voices in aligning the care plan with their values. This study explores how implementation of a formal EPT guideline focused on family-centered care influenced infant outcomes. Methods: A retrospective chart review was done for 43 infants born between 22-23 weeks in a Level IV NICU. 14 Infants from Epoch 1 (pre EPT guideline; 01/18-12/21) were compared to 29 from Epoch 2 (post EPT guideline; 01/22-07/24). Observed clinical outcomes included antenatal steroid use, mortality, natural death, and code status. Results: In Epoch 1, 14 EPT infants were resuscitated (3.5/year) compared to 29 EPT infants in Epoch 2 (11.28/year). Between Epoch 1 to 2, the percentage of infants who received 2 doses of antenatal steroids (ANS) increased from 42% to 71%, the percentage of infants who survived increased from 28.5% to 58%, the percentage of deaths following withdrawal of life-sustaining therapies increased from 30% to 55%, deaths after code decreased from 70% to 45%. In infants with withdrawal of life-sustaining therapies, 0/3 in Epoch 1 and 2/6 in Epoch 2 had a documented code status change in the medical record. Conclusions: An institutional policy focused on goal concordant care with families of EPT infants resulted in improved patient outcomes: more EPT infants being resuscitated, receiving ANS, and surviving to discharge. Of infants who died, more deaths occurred after withdrawal of life-sustaining therapies in Epoch 2. The findings of this study highlight the benefit of incorporating patient-centered care into intensive care settings
Novel Anti-cN1A Antibody in Myopathy Diagnosis
No full textBackground: Inclusion Body Myositis (IBM) is a complex degenerative disease characterized by progressive muscle weakness and gradual degeneration of the muscle fibers. Diagnosis is based on patient presentation, muscle groups involved, identification of selective antibodies for the disorder, and muscle biopsy. Cases present with characteristic sparing or affectation of certain muscle groups based on hereditary or sporadic etiology. Additionally, this disorder may present itself in conjunction with other rheumatological disorders such as sclerosis or Systemic Lupus Erythematosus (SLE), leading to a multifaceted presentation similar to Mixed Sclerosis. Confirmation is histological, with characteristic dead cellular materials absent in other causes of myositis. Still, clinical diagnosis is challenging due to the symptomatic overlap with other conditions and poor specificity of diagnostic markers. Case Presentation: A 73-year-old male was referred to the rheumatology clinic by cardiology for evaluation of proximal muscle weakness in his legs due to suspicion of statin-induced myopathy. The patient, on long-term statin therapy due to coronary artery disease, complained of persistent proximal muscle weakness in the lower extremities. He also reported myalgia, extreme fatigue, and difficulty climbing stairs. Despite being advised to stop atorvastatin, his symptoms persisted. The patient’s medical history included coronary artery disease, hypertension, and hyperlipidemia, managed with lisinopril. On physical examination, the patient exhibited 4/5 strength in the lower extremities while retaining 5/5 strength in other muscle groups. Laboratory assessment revealed negative ANA and HMGCR, ruling out statin-induced myopathy. Based on positive testing for the novel anti-cN1A antibody and generalized muscle atrophy on MRI, the patient was presumed to have IBM. The patient was started on azathioprine and high-dose prednisone for his muscle weakness, leading to symptom improvement at follow-up. Conclusion: This case highlights the value of the novel anti-cN1A antibody in the diagnosis of inclusion body myositis, especially in patients with complex medical histories and overlapping risk factors for myopathy
Developing inhibitors of the guanosine triphosphate hydrolysis accelerating activity of Regulator of G protein Signaling-14
No full textRegulator of G protein Signaling-14 (RGS14), an intracellular inactivator of G protein-coupled receptor (GPCR) signaling, is considered an undruggable protein, given its shallow and relatively featureless protein-protein interaction interface combined with a distal allosteric site prone to nonspecific inhibition by thiol-reactive compounds. Here, we identify and validate a tractable chemotype that selectively and non-covalently inhibits RGS14 GTPase-accelerating protein (GAP) activity. Combining structure-guided virtual screening, ligand docking across multiple receptor conformers, and enrichment validation, we progressed from a first-generation active, Z90276197, to over 40 second-generation analogs with improved potency. These inhibitors are predicted to engage the solvent-exposed canyon" in the RGS14 RGS-box that interacts with the Galpha switch I region. Binding pose predictions underscored the importance of non-polar interactions and shape complementarity over polar interactions in engaging this Galpha-binding canyon and revealed an "ambidextrous" pattern of R1-and R2-group orientations. GAP inhibition was confirmed in fluorescence-based and gold-standard radioactive GTP hydrolysis assays. Two second-generation analogs, Z55660043 and Z55627844, inhibited RGS14 GAP activity in both assays and without measurable cytotoxicity. Deep learning-based scoring of predicted docking poses further supported observed affinity gains from R3-group additions. One analog demonstrated favorable in vivo pharmacokinetics and CNS penetration. Collectively, our findings establish tractable, non-covalent, small molecule inhibition of a G protein regulatory interface and illustrate how machine learning-enhanced docking can guide ligand optimization for shallow protein surfaces. This work opens the door to future development of RGS14 inhibitors as potential therapeutics for central nervous system and metabolic disorders."Work was supported in part by the US National Institute on Drug Abuse (R01 grant DA048153, to D. P. S), a Team Science award from the HSC Division of Research and Innovation (to K. A. E., L. C.-P., and D. P. S.), the Israel Science Foundation (ISF) and the Azrieli Foundation (grant 3512/19 to M. K.), a grant from the Council for Higher Education through the Data Science Research Center at the University of Haifa (to M. K.), and an HSC Presidential Endowment to the Chair of Pharmacology and Neuroscience (to D. P. S.)