Philadelphia College of Osteopathic Medicine
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Investigating the Role of Inflammation and CD38 in SBMA Pathogenesis
No full textSpinal and Bulbar Muscular Atrophy (SBMA) is a progressive neuromuscular disorder caused by a polyglutamine expansion in the androgen receptor, leading to lower motor neuron degeneration and muscle atrophy. Mitochondrial and metabolic dysfunctions contribute to disease, including depletion of NAD+ levels in skeletal muscle. Our lab identified overactive hydrolase activity of CD38 as a major contributor to the loss of NAD+. Since CD38 is an immune modulator and impaired mitochondrial function induces inflammation, we evaluated circulating plasma cytokines in a mouse model of SBMA (AR100Q). We found elevated levels of some pro- and anti-inflammatory cytokines and reduced levels of some pro- and anti-inflammatory cytokines. However, the inflammatory marker, CD45 protein, levels did not change in AR100Q quadriceps after forced exercise. In an effort to reduce inflammation and restore metabolic function, we treated AR100Q mice with prednisone, but it had no effect on CD45 expression, CD38 activity, or metabolic function. We also examined whether ubiquitous genetic deletion of CD38 could rescue motor function as observed with pharmacological inhibition of CD38. Surprisingly, CD38 knockout did not improve motor function of AR100Q mice. This suggests that complete loss of CD38 protein, including both its cyclase and hydrolase function, may complicate the benefit of mainly targeting the overactive hydrolase activity of CD38. Our findings suggest a complex role between immune and metabolic dysregulation in SBMA. Future studies will focus on different strategies to support immune and metabolic function in SBMA and specifically inhibiting the hydrolase activity of CD38 to improve metabolism and motor function in SBMA patients
Using the Personal Health Inventory to Support Engagement in Mindfulness for Veterans with PTSD: Mixed Methods Secondary Data Analysis
Full text linkMindfulness has many potential benefits to physical and mental health but requires many hours of practice to attain the strongest benefits. Mindfulness interventions delivered within the context of primary care settings are often brief, so independent practice beyond the training context is important. Motivational factors are important predictors of sustained practice and different types of motivational factors are associated with different likelihood of sustained practice. The Personal Health Inventory (PHI) is a publicly available personal health planning tool that assesses motivational factors related to self-care behaviors like mindfulness. Our objective was to understand how the PHI can support patient engagement in a mindfulness training delivered in primary care. Three research questions guided the overall approach to (1) identify pre-class motivational factors for mindfulness, (2) explore how motivation relates to class attendance and mindfulness outcomes, and (3) understand mindfulness trainees’ post-class goals, particularly for sustained practice. For the second research question, we specifically hypothesized that factors aligning with motivational theory indicating higher motivation would predict higher class attendance and better mindfulness outcomes. We conducted an exploratory sequential merging mixed-methods secondary analysis of data from a randomized clinical trial of a brief mindfulness training in primary care. Data were collected in parallel, but analyzed sequentially with a primary qualitative matrix analysis first, followed by a targeted retrospective observational between-group pre-post quantitative design using groups identified from the qualitative analysis. PHIs were administered to 28 Veterans with PTSD before and after brief mindfulness classes. Outcome measures were collected via self-report and include the Five Factor Mindfulness Questionnaire (FFMQ-15). Data was collected between January 2019-July 2020. We used matrix analysis as the primary qualitative analysis of open-ended PHI responses and one-way ANOVAs for quantitative analysis of hypotheses. A joint display integrated open-ended and numeric pre-treatment PHI responses and yielded a three-step interpretation approach classifying mindfulness motivation. High motivation was associated with higher post-treatment mindfulness than low-moderate motivation, F(1,26)=3.857, p=0.049, based on a one-way analysis of variance. Motivation did not significantly predict class attendance. Qualitative analysis of post-mindfulness training goals reported on PHIs indicated that most trainees had goals that would benefit from referrals or ongoing treatment (e.g., goals to improve mental health or sleep). Less than half of mindfulness trainees described goals on their post-class PHIs to continue practicing mindfulness. The results of our joint display analysis process provide a concrete way to clinically interpret the PHI to support independent practice and therefore maximum benefits from mindfulness classes. Further, these results suggest that primary care-based mindfulness trainers may consider helping mindfulness trainees identify initial motivation for mindfulness and set post-training practice goals may maximize benefits from primary care mindfulness trainings
Exploring Psychological Impacts, Coping, and Conflict Resolution of Transnationalism on Parent-Child Relationships
No full textThe number of immigrants migrating to the United States has increased over the past 30 years. Many of these immigrants leave behind their spouses and children, creating transnational families. Researchers have focused on the experiences of transnational families, but there is a need for continued research to further explore the psychological impact of separation and reunification. The purpose of this study was to identify the possible psychological impact of the separation and reunification process experienced by transnational families, and the coping strategies used during the process. This study used a qualitative design to explore the experiences of transnational families who experienced separation due to parental migration. The participants included four Hispanic adolescents between the ages of 14 and 20 years old, and their parents. A semi-structured interview was used to interview the participants about the parent-child relationship, their experiences, and methods of coping. A qualitative method of grounded theory was used to analyze the interview transcripts. The following themes emerged from the interviews with the adolescents: psychological impacts of separation on children, reunification process, using their support system, and coping. The following themes emerged from the interviews with the parents: reason for migration, communication attempts, parental perception of children’s reactions to parental migration and reunification, parental coping, parents’ reactions to reunification, and the parent-child relationship. A better understanding of this population’s experiences can guide clinicians toward improving client care and identifying best practices for this population
Pediatric Anxiety Disorders: Therapy Process Predictors of Response to CBT
No full textCBT is moderately effective in the treatment of youth anxiety, yet there remains a sizeable number of youth who remain nonresponsive at posttreatment, and less than half achieve remission. Various patient-level variables have been examined concerning differential treatment outcomes for anxious youth, but fewer studies have examined therapy process variables. Using archival data, this study aimed to identify predictors of treatment response in youth with primary anxiety disorders who completed 16-weeks of CBT at a university-based clinic. Four samples of anxious youth, aged 7-17 were included in the analysis. Regression analyses revealed that increased skill acquisition and greater change in parent-reported coping efficacy were associated with disorder-specific improvement (CGI-I), while only change in parent-reported coping efficacy was associated with posttreatment symptom severity (CGI-S), degree of clinical significance and functional impairment of anxiety symptoms (CSR), and overall anxiety level (MASC). The results of the study suggest that mastery of therapeutic skills and more reliably, growth in a patient’s confidence to navigate anxiety-provoking situations are important for treatment response, though there may be additional processes contributing to favorable outcomes. Our findings add to a relatively small body of youth process-outcome literature that examines differential outcomes for anxious youth and contributes new insights into the relationship between process variables and youth treatment outcomes. Implications for future youth process-outcome studies are also provided
Krogh\u27s principle, glaucoma, and the ‘extremophile’ eye of whales (El principio de Krogh, el glaucoma y el ojo «extremófilo» de las ballenas)
No full text[No abstract available
Notalgia Paresthetica: Case Report
Full text linkNotalgia paresthetica (NP) is a dermatologic condition that causes pruritus of the skin on the medial border of the inferior scapula and/or upper back. It is a chronic neurologic dysesthesia caused by pain from nerve fiber damage at the thoracic spine, levels two to six. Patients can also experience paresthesia, allodynia, and pruritus that is exacerbated by heat. It has been shown in multiple case reports that thoracic nerve impingement could be responsible for this problem, specifically herniated intervertebral discs, vertebral changes, and osteoarthritic lesions. Multiple methods of treatment have been reported to be effective including topical steroids and anesthetics, oral gabapentin and antihistamines, and osteopathic manipulation. The authors report a case of a 50-year-old male with notalgia paresthetica who has undergone osteopathic manipulation. Stretching, osteopathic manipulation, and proper posture was shown to be effective for the patient to alleviate the symptoms. In addition to all of the treatment methods mentioned, stress management is a new recommendation for patients to help reduce their symptoms of NP. The noted treatments have been able to provide patients with short-term or immediate relief of symptoms, but a long-term solution or cure has yet to be determined
The role of the PTHrP/Ihh feedback loop in the unusual growth plate location in mammalian metatarsals and pisiforms.
Full text linkBACKGROUND: Longitudinal skeletal growth takes place in the cartilaginous growth plates. While growth plates are found at either end of conventional long bones, they occur at a variety of locations in the mammalian skeleton. For example, the metacarpals and metatarsals (MT) in the hands and feet form only a single growth plate at one end, and the pisiform in the wrist is the only carpal bone to contain a growth plate. We take advantage of this natural anatomical variation to test which components of the PTHrP/Ihh feedback loop, a fundamental regulator of chondrocyte differentiation, are specific to growth plate function.
RESULTS: Parathyroid hormone-like hormone (Pthlh), the gene that transcribes parathyroid hormone-related peptide (PTHrP), is expressed in the reserve zone of the growth plate-forming end of the MT. At the opposite end, the absence of a PTHrP+ reserve zone results in premature chondrocyte differentiation and Indian hedgehog (Ihh) expression. Pthlh is expressed in the reserve zone of the developing pisiform, confirming the existence of a true growth plate.
CONCLUSION: A pool of PTHrP+ reserve zone chondrocytes is a defining characteristic of growth plates, and its patterning may be key to evolved differences in growth plate location in the mammalian skeleton
Assessing Domestic Dogs as Potential Carriers of Group A Streptococcus for Zoonotic Transmission Risk to Humans
No full textIntroduction
While 2012 IDSA guidelines do not recommend canine testing for GAS pharyngitis, some anecdotal evidence suggests a potential zoonotic link between dogs and humans. One Health, an organization analyzing zoonotic diseases, largely lacks data pertaining to streptococcus, thus prompting this research which aims to update IDSA guidelines and analyze whether household canines are possible vectors of GAS pharyngitis.
Methods
Through an observational cross-sectional study, single-sample clustering was used to swab the oropharynx of domestic canines for GAS. Results were recorded as positive, negative, or invalid for GAS. An additional survey collected data from the owner on dog breeds, symptoms, socialization habits, and history of strep throat in household members. The prevalence of GAS colonization among the canine population was analyzed using chi-square testing, and survey responses were reviewed.
Results
The study analyzed 201 canines, resulting in negative GAS swabs for all 201 samples. Of these, 85.1% of dogs had no obvious respiratory symptoms, and 95% were considered as “indoor” pets. Seven pet owners endorsed contracting one or more episodes of GAS pharyngitis after acquiring their dog without a history of prior occurrence. This trend seemed to be a more common complaint among pet owners of “outdoor” dogs or those with increased interaction with other canines.
Conclusion
A chi-square test was not conducted due to the absence of positive results, thus suggesting that dogs in the studied population were unlikely to serve as reservoirs for GAS pharyngitis in humans. However, descriptive and frequency data collected from the owners’ survey illuminate other areas in which to focus future investigations. Further research should include refined sampling techniques, such as identifying patients with recurrent GAS pharyngitis and screening their entire household for GAS colonization, including all pets
Unraveling Amyotrophic Lateral Sclerosis (ALS): Mechanisms, Pharmacology, and Advances in Treatment
No full textAmyotrophic Lateral Sclerosis (ALS) is a progressive and fatal neurodegenerative disease that selectively affects motor neurons, leading to muscle weakness, paralysis, and respiratory failure. With an incidence of 2–3 per 100,000 annually, ALS primarily presents in middle age and follows a rapidly progressive course, resulting in a 2–5 year median survival post-diagnosis. While 90% of cases are sporadic, 10% are familial, often linked to mutations in SOD1, C9ORF72, TARDBP, and FUS, which disrupt key neuronal processes such as glutamate excitotoxicity, mitochondrial dysfunction, oxidative stress, and protein misfolding. These mechanisms contribute to motor neuron degeneration and form the basis for emerging targeted therapies. The diagnosis of ALS remains clinical, requiring evidence of both upper and lower motor neuron involvement. Upper motor neuron signs include spasticity, hyperreflexia, and Babinski’s sign, while lower motor neuron signs manifest as muscle atrophy, fasciculations, and weakness. Electromyography (EMG) and nerve conduction studies (NCS) are critical for detecting motor neuron loss, and newer imaging techniques such as diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) hold promise for early diagnosis and monitoring. Despite advancements in understanding ALS pathophysiology, Riluzole (a glutamate modulator) and Edaravone (an antioxidant) remain the only FDA-approved treatments, offering limited survival benefits. However, emerging therapies such as gene editing (CRISPR-based approaches), antisense oligonucleotides (Tofersen for SOD1 mutations), and novel neuroprotective agents (AMX0035, targeting mitochondrial and endoplasmic reticulum stress) are currently being explored. Additionally, biomarkers like neurofilament light chain (NfL) in plasma and cerebrospinal fluid (CSF) are improving early detection and patient stratification in clinical trials. The economic and clinical burden of ALS remains high due to its rapid progression, lack of curative treatments, and need for multidisciplinary care, including respiratory and nutritional support. Future research must focus on identifying novel drug targets, optimizing biomarker use, and integrating precision medicine approaches to improve patient outcomes. Interdisciplinary collaboration in genetics, neuroscience, and clinical research is crucial to accelerating therapeutic discovery and, ultimately, finding a cure for this devastating disease
Gun Violence Communication Training in Two Philadelphia Urban Healthcare Centers
No full textContext: The ramifications of gun violence extend beyond individual victims to encompass their families and surrounding communities. While resources and counseling services are available, a significant barrier exists in the form of limited awareness and access for both families and their clinicians.
Objectives: The goal of this study was to analyze the effect of a clinician education initiative on patient reported outcomes related to physician discussions about gun violence, specifically focusing on prevention and resource availability.
Methods: This quality-improvement study assessed the impact of a clinician-focused educational intervention on gun violence communication. The intervention, implemented in two urban healthcare centers in Philadelphia, included office enhancements (handouts and posters) and lunchtime presentations regarding gun violence prevalence, prevention strategies, local support resources, and impacts on mental health for patients and their families. Patient and clinician surveys were administered at baseline, mid-intervention, and post-intervention. Anonymous patient surveys were distributed during three non-consecutive weeks within a three-month period.
Results: Of the 542 patients seen over the 3 weeks of survey collection, 428 completed surveys (79% response) and 275 (64.3%) reported experiences of gun violence. Additionally, 268 participants (63%) requested more information on resources concerning the impact of gun violence. Pre- and post-program comparisons showed a 17.2% increase in patient awareness of gun violence materials, a 12.1% increase in gun violence discussions with clinicians (reaching 19.3% post-program), and a 9.7% increase in prevention strategy discussions (reaching 14.3% post-program). By the end of the program clinicians reported increased satisfaction and confidence when talking to patients about gun violence.
Conclusions: Clinician education and waiting room resources helped to aid in gun violence discussions. Although this is a good first step in addressing the issue of gun violence, this issue is multi-faceted and involves many social determinants of health. A comprehensive, holistic approach is crucial for supporting affected individuals and families