Philadelphia College of Osteopathic Medicine
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Using cimetidine to mitigate cisplatin-induced ototoxicity.
No full textGiven the well-established role of organic cation transporter 2 (OCT2) in cisplatin uptake to the inner ear cells, and the fact that cimetidine is an FDA-approved drug with well-established inhibitory activity against OCT2, we hypothesized that inhibiting OCT2-mediated cisplatin uptake with cimetidine could eliminate or alleviate cisplatin-mediated ototoxicity. Our preliminary data showed that cisplatin can reduce the viability of House Ear Institute-Organ of Corti 1 (HEI-OC1) cells in a dose-dependent manner, and cimetidine can effectively counteract this cisplatin-induced toxicity without affecting cisplatin\u27s effect on cancer cells. Therefore, combined application of these drugs could ameliorate cisplatin ototoxicity with minimal impact on their anti-cancer effect
Improving Patient Engagement through Whole Health: Veteran Perspectives on a Values Assessment Tool
Full text linkAmidst rising rates of costly chronic diseases, a growing emphasis for integrated primary care settings is offering proactive, person-centered, and whole-person care. Through its Whole Health approach, the Veterans Health Administration (VA) is a leading force in this movement. VA’s Whole Health focuses on delivering patient-centered care that engages and empowers Veterans to improve health outcomes. The Personal Health Inventory (PHI) is a brief, whole-person focused, values assessment of what matters most that can lead to personalized health planning. Using a concurrent triangulation (convergent) mixed methods design, we examined the perspectives of 25 post-9/11 Veterans using semi-structured telephone interviews. Qualitative and quantitative questions covered independent PHI completion including acceptability, preferred methods to enhance feasibility (including feedback on a brief introductory overview), and potential impact on healthcare experience. Matrix analysis informed by rapid qualitative analysis was used to analyze responses, and quantitative data were integrated using a joint display. We found that average ratings of acceptability were high across domains for the PHI and independent PHI completion was feasible. The PHI was helpful for prompting reflection and possible action, and highly relevant to what Veterans value in healthcare. Strategies that were identified to improve feasibility and acceptability of independent PHI completion included using the introductory overview piloted with this sample and discussing a completed PHI with the healthcare team. The PHI could help support patient/provider communication and understanding, increase self-awareness and motivation, and help tailor/plan treatment options. Overall, Veterans perceive completion of the PHI as acceptable, feasible, and beneficial. Future directions for research include implementation of the PHI, evaluations of applied use for discussions of what matters most to patients as supported by various members of the integrated primary care team, and expansion to non-VA integrated primary care settings
Psychometric Development of Scales Measuring Attitudes About and Interest in Integrated Healthcare Clinical Practice
Full text linkThe landscape of integrated healthcare models continues to evolve, and with these changes, providers are facing the challenge of adopting approaches to care that may not have been taught in their training. With interprofessional education on the rise, some providers often struggle to modify their clinical methodology to accommodate an interdisciplinary team-based care format. In an effort to better understand the attitudes and interest levels that may affect a provider’s engagement in these models of care, the Integrated Health Attitudes and Interest Scales were developed. Using a best practices model, items for the measure were created by the investigators and were independently reviewed by an expert panel of clinical psychologists. It was determined that both scales achieved content and construct validity as determined by a factor analysis. Prior to the time of the initial investigation, it is believed no other measure exists that assesses for these factors
The Management of Upper-Extremity Xylazine-Associated Wounds.
No full textPURPOSE: Xylazine has been associated with necrotic soft tissue wounds that have placed a challenging burden on patients who inject drugs in the Philadelphia region\u27s health care system over the last few years. An analysis of our initial experience is being presented to guide future treatment and directions for future research.
METHODS: A retrospective review of 55 patients with patient-reported xylazine use and associated upper-extremity wounds at a single institution was performed. Patient demographics, treatments, and outcomes are presented.
RESULTS: A large percentage of patients with xylazine-associated wounds were homeless (40%), had concomitant psychiatric diagnoses (26%), and had a history of tobacco use (84%). Comorbidities included 5% who were human immunodeficiency virus-positive and 67% who were hepatitis C virus-positive. The median number of hospital admissions per patient for xylazine-associated wounds was 3, with an average of 5.9 (range: 1-44 admissions). The median length of stay per hospital admission was 3 days, with an average of 5.3 days (range: 1-75). Among all included patients, 33 of 55 patients (60%) were treated nonoperatively with local wound care. Of the 22 patients who underwent surgery, there was a surgical complication rate of 59%, primarily related to continued wound issues, infections, and graft failures. The overall rate of patients who left the hospital against medical advice (AMA) was 49%. However, the mortality rate was 0%. Most surgical patients left AMA during their postoperative period hospital stay (64%) and demonstrated continued drug use per review of their hospital records (68%).
CONCLUSIONS: Patients presenting with xylazine-associated wounds have a high incidence of homelessness, psychiatric diagnoses, tobacco smoking, hepatitis C virus, and a predilection both toward leaving the hospital AMA and repeated drug use. These variables create inherent challenges to reconstructive surgery, yielding a subsequently high complication rate identified in most surgically managed patients.
TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic study IV
Exploratory arthroscopic evaluation of joint injuries creates a cellular environment that leads to accelerated osteoarthritic changes: A pilot study
No full textExploratory knee arthroscopy is a minimally invasive procedure used for the diagnosis of knee joint pathologies. However, emerging evidence suggests that the continuous irrigation of the joint required for visibility during this procedure may dilute synovial fluid, contributing to cellular and metabolic changes consistent with early osteoarthritis pathogenesis. To address the challenge of studying cellular-level effects in vitro, our lab optimized a three-dimensional, serum-free culture model for primary, human articular chondrocytes (HC-a) and measured key extracellular matrix proteins to monitor their metabolism. Optimal production of the target endpoints was observed when passage 3 HC-a were encapsulated in alginate beads at a density of 1.5x106 cells per 1 mL of alginate and cultured in serum-free medium for a period of 24 hours. Using this optimized culture model, we reared HC-a in varying dilutions of artificial synovial fluid (ASF), similar to what chondrocytes experience during exploratory arthroscopy. We measured sulfated proteoglycan, type II collagen, and matrilin-3 (a potential marker of OA pathogenesis), production in cultures reared in 100% ASF, 50% ASF/saline, 66% saline-diluted ASF, or saline-only conditions. Type II collagen and matrilin-3 increased protein production when cultured in dilute ASF and saline-only conditions. Sulfated proteoglycan production exhibited a significant increase only when HC-a were cultured in saline alone. These data indicate that damaging cellular effects occur when synovial fluid concentrations are altered, thus implicating exploratory arthroscopy in potential osteoarthritis progression
(In)Animate: Exploring the Relationship Between Obsessivecompulsive Disorder, Perceived Thought Control, and Anthropomorphism
Full text linkIntroduction: Ritual behaviors help manage uncertainty and anxiety by providing a sense of control, but rigid engagement in such behaviors can indicate obsessivecompulsive disorder (OCD). Most OCD research has focused on harm-avoidance versus not-just-right-experiences (NJREs), with exposure and ritual prevention (ERP) being less effective for those without clear feared outcomes. Anthropomorphizing, or assigning human traits to objects, complicates OCD treatment, particularly for those with hoarding behaviors.
Objectives: This study aimed to examine the relationship between OCD with and without hoarding behaviors ( saving behavior) and anthropomorphism. Given ERP’s role in OCD treatment, understanding how anthropomorphism affects OCD is crucial. It was hypothesized that (a) individuals with saving OCD (OCD+) would exhibit higher anthropomorphism than non-saving OCD (OCD-), (b) both OCD groups would report higher thought suppression than controls, and (c) OCD+ would show higher levels of both anthropomorphism and thought suppression.
Methods: An online survey assessed anthropomorphism using the IDAQ, OCD with the OCI-R, saving behavior with the SIR, thought suppression with the WBSI, and demographic information.
Results: OCD+ participants showed significantly higher anthropomorphism and greater difficulty controlling thoughts compared to OCD- and control groups. They also reported the highest levels of both thought suppression and anthropomorphism.
Discussion: These findings suggest that saving behaviors in OCD are associated with difficulty controlling thoughts and a stronger tendency to anthropomorphize, potentially making it harder to discard possessions. These results emphasize the need for tailored approaches in ERP for individuals with anthropomorphic tendencies
Elevated Neutrophil-to-Lymphocyte Ratios in Schizophrenia: Insights from a Precision Medicine Cohort (Preprint)
Full text linkSystemic inflammation has been increasingly implicated in the pathophysiology of schizophrenia. The neutrophil-to-lymphocyte ratio (NLR), a readily available marker of systemic inflammation, has not been thoroughly investigated in large, demographically-matched schizophrenia cohorts. Using data from the All of Us Research Program, we analyzed participants with schizophrenia (n = 396) matched to controls (n = 396) by sex, race, and age. NLR was calculated as the ratio of each participant’s median neutrophil count to median lymphocyte count across all available measurements, excluding extreme values (NLR \u3e 7). Distribution normality was assessed using the Shapiro–Wilk test, and group differences were evaluated with the Mann–Whitney U and Welch’s t-tests. Median NLR was significantly higher in schizophrenia compared to controls (2.07 vs. 1.83; Mann–Whitney U p = 0.0067, Welch’s t-test p = 0.0329), with both groups demonstrating non-normal distributions (Shapiro–Wilk p \u3c 0.001). These findings indicate elevated systemic inflammation in schizophrenia and support the potential of NLR as a simple, scalable biomarker for immune dysregulation in the setting of acute psychosis, in addition to the broader course of the illness. Future work should explore NLR’s utility in tracking disease progression, treatment response, and relapse risk, ultimately bridging immune and psychiatric research toward more personalized care
Loss of RhoB Alters Retinal Function and Intraocular Pressure Regulation
No full textPurpose : RhoB, a small GTPase, is involved in apoptosis, intracellular transport, and angiogenesis, with implications in cancer, diabetes, and retinopathy of prematurity. RhoA, part of the same Rho GTPase family as RhoB has been previously studied in its role of intraocular pressure. Previous studies have shown RhoA’s role in the Rho/ROCK pathway regulating intraocular pressure. However, RhoB’s role in the retina, especially during stress or aging, remains underexplored. Previous studies have shown using supplemental oxygen during the critical period reduces photoreceptor death, while hypoxia increases it. This study investigates how the absence of RhoB (RhoB-/-) affects retinal neurons in response to oxygen fluctuations during retinal development and aging.
Methods : C57Bl/6JRhoB -/- (RhoB -/-) and control wild type (C57Bl/6J) mice were exposed to varying oxygen conditions (12% oxygen, 21% oxygen, and 75% oxygen) from postnatal day 7 (P7) to P20. Immunofluorescence was performed at P12, P16, P28, and 1 year to quantify apoptotic cell death. Scotopic electroretinography (ERG) was conducted at P27 and 1 year. Intraocular pressure (IOP) was measured in mice at 4 weeks and aging mice (9-12months) using a tonometer.
Results : At P12, RhoB-/- mice exhibited significantly increased apoptotic cell death in the ONL, INL, and GCL compared to controls at 21% oxygen. By P28, RhoB-/- mice showed more extensive GCL cell death across all oxygen conditions (p\u3c 0.05). Although visual function was impaired in RhoB-/- mice at 21% oxygen and 12% oxygen. 75% oxygen partially restored function. In 1 year old mice, RhoB-/- had 4 times more photoreceptor death and significantly elevated IOP (18.3 mmHg in RhoB-/- vs. 11.9 mmHg in controls). Electroretinography revealed poorer retinal function in RhoB-/- mice at P27 and 1 year, as indicated by reduced A- and B-wave amplitudes.
Conclusions : RhoB-/- mice display significant retinal degeneration, including increased cell death and impaired visual function. Being in 75% oxygen during the critical period partially alleviates these effects. Additionally, RhoB-/- mice experience elevated intraocular pressure and progressive visual dysfunction with aging. Further histological analysis is needed to determine the underlying retinal changes and the mechanisms leading to ocular hypertension in these mice.
Purpose : RhoB, a small GTPase, is involved in apoptosis, intracellular transport, and angiogenesis, with implications in cancer, diabetes, and retinopathy of prematurity. RhoA, part of the same Rho GTPase family as RhoB has been previously studied in its role of intraocular pressure. Previous studies have shown RhoA’s role in the Rho/ROCK pathway regulating intraocular pressure. However, RhoB’s role in the retina, especially during stress or aging, remains underexplored. Previous studies have shown using supplemental oxygen during the critical period reduces photoreceptor death, while hypoxia increases it. This study investigates how the absence of RhoB (RhoB-/-) affects retinal neurons in response to oxygen fluctuations during retinal development and aging.
Methods : C57Bl/6JRhoB -/- (RhoB -/-) and control wild type (C57Bl/6J) mice were exposed to varying oxygen conditions (12% oxygen, 21% oxygen, and 75% oxygen) from postnatal day 7 (P7) to P20. Immunofluorescence was performed at P12, P16, P28, and 1 year to quantify apoptotic cell death. Scotopic electroretinography (ERG) was conducted at P27 and 1 year. Intraocular pressure (IOP) was measured in mice at 4 weeks and aging mice (9-12months) using a tonometer.
Results : At P12, RhoB-/- mice exhibited significantly increased apoptotic cell death in the ONL, INL, and GCL compared to controls at 21% oxygen. By P28, RhoB-/- mice showed more extensive GCL cell death across all oxygen conditions (p\u3c 0.05). Although visual function was impaired in RhoB-/- mice at 21% oxygen and 12% oxygen. 75% oxygen partially restored function. In 1 year old mice, RhoB-/- had 4 times more photoreceptor death and significantly elevated IOP (18.3 mmHg in RhoB-/- vs. 11.9 mmHg in controls). Electroretinography revealed poorer retinal function in RhoB-/- mice at P27 and 1 year, as indicated by reduced A- and B-wave amplitudes.
Conclusions : RhoB-/- mice display significant retinal degeneration, including increased cell death and impaired visual function. Being in 75% oxygen during the critical period partially alleviates these effects. Additionally, RhoB-/- mice experience elevated intraocular pressure and progressive visual dysfunction with aging. Further histological analysis is needed to determine the underlying retinal changes and the mechanisms leading to ocular hypertension in these mice
Experiences of Latina Single Mothers Raising Children with Autism Spectrum Disorder: A Qualitative Study
Full text linkAutism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder in children. Although the prevalence of ASD among Latino children and single mother households has increased in recent years, there is limited research that explores the experiences of Latina single mothers raising children with ASD. This qualitative study utilized a phenomenological approach to gain a better understanding of the experiences of Latina single mothers raising children with ASD, using the ecological framework to conceptualize their experiences within their cultural and environmental contexts. Semistructured interviews were conducted individually with nine single Latina mothers. The data collected during these semi-structured interviews were analyzed and classified into emerging themes. The study resulted in a better understanding of the factors that influence the experiences of Latina single mothers raising children with ASD