Scholarly Commons@CWRU

Case Western Reserve University

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    3487 research outputs found

    Barriers to Dental Utilization Among Medicaid-Enrolled Young Children from Primary Care Practices in Northeast Ohio

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    Objectives: To evaluate the individual and community factors that contribute to dental utilization among young children on Medicaid utilizing the Anderson Model and the Socio-Ecological Framework. Methods: This observational cross-sectional study was conducted using baseline data (socio-demographics, clinical dental need) from a cluster-randomized hybrid effectiveness-implementation trial among 1021 child–parent dyads recruited from primary care practices across northeast Ohio. The baseline data were then linked to dental Medicaid claims data (categorized as any dental visit, volume, and type in the past 12 months) and ICD-10 codes from the child\u27s EHR data (individual-level) together with Dental Health Provider Shortage Area (HPSA) status and Area Deprivation Index (ADI) which were obtained at the neighbourhood-level using home address of each dyad (community-level). Multivariable analyses using generalized estimating equations (GEE) accounted for clustering by practice, and models included individual-level alone, and individual + community-level factors to evaluate their effects on dental utilization. Results: Medicaid claims data indicated that among the 1021 children (mean age: 4.3 ± 1.1 years; 54.4% males; 43.8% Black, Non-Hispanic), a majority of children were seeing the dentist at least once a year by the age of 4 (56.1%). The mean ADI of their neighbourhoods was 109.22 (20.2) and 27.5% lived in a HPSA area. The GEE analyses revealed that individual factors such as older children, parents being married, and continuous Medicaid enrollment were associated with significantly higher dental utilization. Among community factors, being in a HPSA had an OR = 1.53 (CI: 1.03, 2.27) associated with higher dental utilization. Conclusions: Being in a HPSA was associated with higher dental utilization possibly due to dentists or safety net dental clinics in these areas accepting Medicaid-eligible children

    Beyond Collaborative Learning: A Comparison of Small Groups in Face-to-Face and Online Settings

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    Small group-based instructional approaches such as case-based learning (CBL) and team-based learning (TBL) are widely used in medical education to promote collaboration and team learning. During the pandemic, many medical schools shifted from face-to-face instruction to online settings. While CBL/TBL are intended to foster collaborative skills, it is unclear how its use evolves in an online setting and whether the online setting impacts students’ perceptions and behaviors in collaboration. This study examined how the change from in-person to online CBL/TBL impacted students’ collaboration. We used a mixed-methods sequential design, first collecting and analyzing retrospective cohort quantitative data with the Class of 2023 through peer evaluation surveys followed by six focus groups. Students’ assessment of their peers was generally positive. Nonparametric testing showed significant differences for two questions with less positive perceptions in the virtual setting compared to when students had in-person CBL/TBL. The focus group results identified several themes related to collaboration and learning communities. In the virtual setting, students not only lost collaboration opportunities with their group members in CBL/TBL, but also learning opportunities and social connections with other groups and the community as a whole. Virtual learning environments may have presented challenges for collaborative learning and the establishment of a sense of community

    Clinical and Sociodemographic Characteristics as Predictors for Quality of Life in Transmasculine and Transfeminine Individuals Receiving Gender-Affirming Hormone Therapy

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    Healthcare systems and providers have increasingly acknowledged the role and impact of social determinants in overall health. However, gender-diverse individuals face persistent health disparities due to their identities. There is limited research on the impact of clinical and sociodemographic characteristics on mood and quality of life (QoL) for transgender (TG) individuals. Our study aims to understand and better elucidate social and clinical characteristics of transmasculine (TM) and transfeminine (TF) individuals and their impact on quality of life and depressive symptoms. In this cross-sectional study, 298 TF and TM individuals on gender-affirming hormone therapy (GAHT) were surveyed about their demographic characteristics (age, gender identity, body mass index (BMI), and education), social needs, mood, and quality of life. Multivariable regression modelling was performed to assess the effect of each variable listed above on three domains of QoL (psychological, environmental, and physical) as well as depressive symptoms. We find that QoL scores are similar between TM and TF individuals, with scores in the psychological domain particularly low in both cohorts. TM individuals report higher rates of stress and restroom avoidance than TF individuals. In particular, psychological well-being (measured by the psychological domain of QoL and depressive symptoms) is significantly associated with increased BMI, financial instability, and stress in TM individuals while for TF individuals, psychological well-being is associated with stress and social integration. These data suggest that social circumstances are key drivers of QoL and psychological well-being among gender-diverse individuals receiving GAHT with specific differences between TF and TM individuals. This information may be utilized by healthcare providers and policymakers to address and improve clinical care and social policies to improve health equity for gender-diverse individuals

    Development of a Selective Novel Fluorescent Substrate for Sodium-Dependent Transporters

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    Aim: To synthesize, characterize, and validate 6FGA, a fluorescent glucose modified with a Cyanine5.5 at carbon-6 position, for probing the function of sodium-dependent glucose transporters, SGLT1 and SGLT2. Main methods: The synthesis of fluorescent glucose analogue was achieved through “click chemistry” of Cyanine5.5-alkyne and 6-azido-6-deoxy-D-glucose. Cell system studies were conducted to characterize the in vivo transport properties. Key findings: Optical analyses revealed that 6FGA displayed similar spectral profiles to Cyanine5.5 in DMSO, allowing for concentration determination, thus supporting its utility in quantitative kinetic studies within biological assays. Uptake studies in cell system SGLT models, LLC-PK1 and HEK293 cells, exhibited concentration and time-dependent behavior, indicating saturation at specific concentrations and durations which are hallmarks of transported-mediated uptake. The results of cytotoxicity assays suggested cell viability at micromolar concentrations, enabling usage in assays for at least 1 h without significant toxicity. The dependence of 6FGA uptake on sodium, the co-transported cation, was demonstrated in LLC-PK1 and HEK293 cells. Fluorescence microscopy confirmed intracellular localization of 6FGA, particularly near the nucleus. Competition studies revealed that glucose tends to weakly reduce 6FGA uptake, although the effect did not achieve statistical significance. Assessments using standard SGLT and GLUT inhibitors highlighted 6FGA\u27s sensitivity for probing SGLT-mediated transport. Significance: 6FGA is a new fluorescent glucose analog offering advantages over existing probes due to its improved photophysical properties, greater sensitivity, enabling subcellular resolution and efficient tissue penetration in near-infrared imaging. 6FGA presents practicality and cost-effectiveness, making it a promising tool for nonradioactive, microplate-based assays at investigating SGLT-mediated glucose transport mechanisms

    Exploration of Epileptic Networks in Temporal Lobe Encephaloceles with Stereotactic EEG: Electroclinical Characteristics and Surgical Outcomes

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    Objective: Temporal lobe encephaloceles (TLEN) have been implicated as a cause of temporal lobe epilepsy (TLE), the treatment which is primarily surgical; however, there is no clear consensus on the optimal surgical approach, because it is unclear whether TLE related to TLEN can be addressed by a restricted encephalocele resection or if a more extensive resection is required. The aim of the current article is to report the clinical and electrophysiological profile of patients with TLE secondary to TLEN who underwent stereotactic electroencephalography (SEEG) implantation to identify the epileptogenic network. Methods: A retrospective review was performed of patients with TLE related to TLEN who underwent SEEG implantation. Medical charts were reviewed for demographic data, the results of noninvasive and invasive investigations, and operative details. Surgical outcomes were based on Engel classification with at least 6 months follow-up. Results: Nine patients were identified. The mean age at epilepsy onset was 28 years (range, 15–41 years), and 7/9 patients were female. Scalp EEG revealed interictal epileptiform activity most often maximum in the frontotemporal and/or temporal regions. A discrete TLEN was often not identified on initial imaging, but was identified during re-review or at the time of surgery. Seizure onset zones during SEEG were localized to the mesial temporal structures, the temporal pole, or both. One patient became seizure-free following SEEG and another refused further surgery. Of the 7 patients who underwent epilepsy surgery, 5/7 underwent an anterior temporal lobectomy—surgical outcomes were favorable, with 5/7 achieving Engel I outcomes. Significance: Invasive SEEG monitoring demonstrated ictal onsets may not be restricted to the TLEN, and often the temporal pole and mesial structures are involved at seizure onset. Ictal propagation patterns vary significantly, which may be related to the underlying pathology and explain the variability in semiology. These findings may inform surgical treatment options. Plain language summary: Temporal lobe encephaloceles can cause intractable epilepsy, although their presence may be missed on routine imaging. The management of encephaloceles is primarily surgical; however, the optimal surgical approach can be unclear. Invasive monitoring with SEEG may help characterize the epileptogenic network and result in more optimal surgical outcomes

    Thioredoxin: An Antioxidant, A Therapeutic Target and A Possible Biomarker

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    Study by Haga et al. on the utility of neonatal serum thioredoxin-1 (TRX-1) levels as a biomarker of bronchopulmonary dysplasia (BPD)/ retinopathy of prematurity (ROP) is the first of its kind. A biomarker is considered to enable the detection of a pathological condition or its severity and ideally, should have the capacity to be detected in the pre-disease state or during the diseased state. Premature infants who develop BPD are exposed to supplemental O2 and show marked evidence of oxidant stress as suggested by elevated glutathione disulfide (GSSG) concentrations.1 Upon preterm delivery, an infant breathing even atmospheric oxygen of 21% undergoes a sudden increase in lung O2 levels which perturbs the hypoxia-mediated signaling necessary for lung development in utero. Oxidative stress occurs in cells as a result of imbalance between the production and accumulation of reactive oxygen species (ROS).2 ROS are generated in cells routinely as by-products of oxygen metabolism. However, environmental stressors such as ionizing radiation, pollutants, heavy metals and exposure to hyperoxia greatly increase ROS production. Though ROS have physiological roles such as cell signaling, excessive accumulation results in oxidative stress and cell damage. Antioxidant systems such as superoxide dismutase, glutathione (GSH), glutaredoxin, heme oxygenase and thioredoxin (TRX) systems protect cells from the pathological effects of ROS.3 A deficiency in mounting efficient antioxidant responses to hyperoxia leads to increased susceptibility to oxidant injury. This is a problem seen in preterm infants who are more susceptible to the effects of oxidant injury due to developmental deficits in antioxidants.4 In this context, an understanding of the antioxidant systems is critical, and one such important system is thioredoxin

    Time to Blood Pressure Control and Predictors Among Patients Receiving Integrated Treatment for Hypertension and HIV Based on an Adapted WHO HEARTS Implementation Strategy at a Large Urban HIV Clinic in Uganda

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    In this cohort study, we determined time to blood pressure (BP) control and its predictors among hypertensive PLHIV enrolled in integrated hypertension-HIV care based on the World Health Organization (WHO) HEARTS strategy at Mulago Immunosuppression Clinic in Uganda. From August 2019 to March 2020, we enrolled hypertensive PLHIV aged ≥18 years and initiated Amlodipine 5 mg mono-therapy for BP (140–159)/(90–99) mmHg or Amlodipine 5 mg/Valsartan 80 mg duo-therapy for BP ≥ 160/90 mmHg. Patients were followed with a treatment escalation plan until BP control, defined as BP \u3c 140/90 mmHg. We used Cox proportional hazards models to identify predictors of time to BP control. Of 877 PLHIV enrolled (mean age 50.4 years, 62.1% female), 30% received mono-therapy and 70% received duo-therapy. In the monotherapy group, 66%, 88% and 96% attained BP control in the first, second and third months, respectively. For patients on duo-therapy, 56%, 83%, 88% and 90% achieved BP control in the first, second, third, and fourth months, respectively. In adjusted Cox proportional hazard analysis, higher systolic BP (aHR 0.995, 95% CI 0.989-0.999) and baseline ART tenofovir/lamivudine/efavirenz (aHR 0.764, 95% CI 0.637–0.917) were associated with longer time to BP control, while being on ART for \u3e10 years was associated with a shorter time to BP control (aHR 1.456, 95% CI 1.126–1.883). The WHO HEARTS strategy was effective at achieving timely BP control among PLHIV. Additionally, monotherapy anti-hypertensive treatment for stage I hypertension is a viable option to achieve BP control and limit pill burden in resource limited HIV care settings

    Association of GLP-1 Receptor Agonists and Hepatocellular Carcinoma Incidence and Hepatic Decompensation in Patients with Type 2 Diabetes

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    Background & aims: Hepatocellular carcinoma (HCC) is a leading cause of cancer death. HCC is preventable with about 70% of HCC attributable to modifiable risk factors. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), Food and Drug Administration–approved medications for treating type 2 diabetes mellitus (T2DM), have pleiotropic effects on counteracting risk factors for HCC. Here we evaluate the association of GLP-1RAs with incident HCC risk in a real-world population. Methods: This retrospective cohort included 1,890,020 patients with a diagnosis of T2DM who were prescribed GLP-1RAs or other non-GLP-1RA anti-diabetes medications and had no prior diagnosis of HCC. Incident (first-time) diagnosis of HCC and hepatic decompensating events during a 5-year follow-up was compared between cohorts of patients prescribed GLP-1 RAs vs other anti-diabetes medications. Time-to-first-event analysis was performed using Kaplan-Meier survival analysis with hazard ratio and 95% confidence interval calculated. Results: GLP-1RAs were associated with a lower risk of incident HCC with hazard ratio of 0.20 [0.14–0.31], 0.39 [0.21–0.69], 0.63 [0.26–1.50] compared with insulin, sulfonylureas, and metformin, respectively. GLP-1RAs were associated with a significantly lower risk of hepatic decompensation compared with 6 other anti-diabetes medications. Reduced risks were observed in patients without and with different stages of fatty liver diseases, with more profound effects in patients without liver diseases. Similar findings were observed in patients with and without obesity and alcohol or tobacco use disorders. GLP-1RA combination therapies were associated with decreased risk for HCC and hepatic decompensations compared with monotherapies. Conclusions: GLP-1RAs were associated with a reduced risk of incident HCC and hepatic decompensation compared with other anti-diabetes medications in patients with T2DM. These findings provide supporting evidence for future studies to investigate the underlying mechanisms and their clinical use

    Physiological Role for S-nitrosylation of RyR1 in Skeletal Muscle Function and Development

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    Excitation-contraction coupling in skeletal muscle myofibers depends upon Ca2+ release from the sarcoplasmic reticulum through the ryanodine receptor/Ca2+-release channel RyR1. The RyR1 contains ∼100 Cys thiols of which ∼30 comprise an allosteric network subject to posttranslational modification by S-nitrosylation, S-palmitoylation and S-oxidation. However, the role and function of these modifications is not understood. Although aberrant S-nitrosylation of multiple unidentified sites has been associated with dystrophic diseases, malignant hyperthermia and other myopathic syndromes, S-nitrosylation in physiological situations is reportedly specific to a single (1 of ∼100) Cys in RyR1, Cys3636 in a manner gated by pO2. Using mice expressing a form of RyR1 with a Cys3636→Ala point mutation to prevent S-nitrosylation at this site, we showed that Cys3636 was the principal target of endogenous S-nitrosylation during normal muscle function. The absence of Cys3636 S-nitrosylation suppressed stimulus-evoked Ca2+ release at physiological pO2 (at least in part by altering the regulation of RyR1 by Ca2+/calmodulin), eliminated pO2 coupling, and diminished skeletal myocyte contractility in vitro and measures of muscle strength in vivo. Furthermore, we found that abrogation of Cys3636 S-nitrosylation resulted in a developmental defect reflected in diminished myofiber diameter, altered fiber subtypes, and altered expression of genes implicated in muscle development and atrophy. Thus, our findings establish a physiological role for pO2-coupled S-nitrosylation of RyR1 in skeletal muscle contractility and development and provide foundation for future studies of RyR1 modifications in physiology and disease

    Prostate-Specific Antigen Testing Patterns and Prostate Cancer Stage at Diagnosis in Older Ohio Cancer Patients

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    Background: Prostate cancer (PCa) screening recommendations do not support prostate-specific antigen (PSA) screening for older men. Such screening often occurs, however. It is, therefore, important to understand how frequently and among which subgroups screening occurs, and the extent of distant stage PCa diagnoses among screened older men. Methods: Using the 2014–2016 linked Ohio Cancer Incidence Surveillance System (OCISS) and Medicare administrative database, we identified men 68 and older diagnosed with PCa and categorized their PSA testing in the three years preceding diagnosis as screening or diagnostic. We conducted multivariable logistic regression analysis to identify correlates of screening PSA and to determine whether screening PSA is independently associated with distant stage disease. Results: Our study population included 3034 patients (median age: 73 years). 62.1% of PCa patients underwent at least one screening-based PSA in the three years preceding diagnosis. Older age (75–84 years: aOR [95% CI]: 0.84 [0.71, 0.99], ≥ 85: aOR: 0.27 [0.19, 0.38]), and frailty (aOR: 0.51 [0.37, 0.71]) were associated with lower screening. Screening was associated with decreased odds of distant stage disease (aOR: 0.55 [0.42, 0.71]). However, older age (75–84 years: aOR: 2.43 [1.82, 3.25], ≥ 85: aOR: 10.57 [7.05, 15.85]), frailty (aOR: 5.00 [2.78, 9.31]), and being separated or divorced (aOR: 1.64 [1.01, 2.60]) were associated with increased distant stage PCa. Conclusion: PSA screening in older men is common, though providers appear to curtail PSA screening as age and frailty increase. Screened older men are diagnosed at earlier stages, but the harms of screening cannot be assessed

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