Philadelphia College of Osteopathic Medicine
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Investigating Internalization, Intracellular Tracking, and Localization of NGR-Tagged Rubredoxin in HT-1080 Fibrosarcoma Cells
No full textFibrosarcoma is a highly aggressive soft tissue sarcoma characterized by poor response to conventional therapies and limited treatment options. CD13, a zinc-dependent metallopeptidase overexpressed in tumor vasculature and fibrosarcoma cells, presents a promising molecular target for receptor-specific drug delivery. This study examined the internalization dynamics and intracellular localization of a NGR-tagged Rubredoxin protein (NGR-Rb) in HT-1080 fibrosarcoma cells to inform tumor-targeted therapeutic design. Rubredoxin, a thermostable iron-sulfur protein from Pyrococcus furiosus, was selected for its compact size (~6 kDa), stability under oxidative and acidic conditions, and resistance to proteolytic degradation, qualities suited for the tumor microenvironment.
To evaluate receptor-mediated uptake, four fluorescently labeled rubredoxin constructs were tested: wild-type (pFJ5.1), NGR-tagged (pFJ08), strep II–tagged (pFJ42), and dual-tagged NGR + strep II (pFJ43). HT-1080 cells were pre-stained with MitoTracker or LysoTracker and pre-treated to establish three distinct uptake conditions: physiological temperature (37°C), low temperature (4°C), and Dynasore treatment at 37°C. Following preconditioning, cells were exposed to the rubredoxin constructs for internalization analysis, which was assessed using confocal microscopy. Co-localization analysis was performed using FIJI/ImageJ, including Manders’ tM1/tM2 coefficients, Pearson’s correlation, and Costes P-values.
Western blotting confirmed robust CD13 expression in HT-1080 cells. Among the constructs, the NGR-tagged constructs (pFJ08 and pFJ43) demonstrated lysosomal localization at 15 minutes under 37°C conditions. The pFJ08 exhibited moderate co-localization (tM1 = 0.610; tM2 = 0.420), confirming that the NGR motif alone supports potential CD13-specific uptake. The pFJ43 showed stronger co-localization (tM1 = 0.786; tM2 = 0.718), though the contribution of the strep II tag remains unclear. The pFJ5.1 and pFJ42 displayed minimal uptake and diffuse cytoplasmic distribution. NGR-tagged constructs retained surface docking under inhibitory conditions, supporting potential receptor- and energy-dependent internalization.
These results identify pFJ43 as the construct with the highest lysosomal co-localization among those tested, suggesting potential as a scaffold for future CD13-targeted delivery. However, since pFJ08 also showed uptake, further studies are needed to evaluate the impact of dual-tagging. Limitations include single-sample data for each condition and time point, as well as the need to refine fluorescence quenching protocols. Future work will incorporate replicates, optimized quenching, and additional controls to strengthen mechanistic interpretation
Augmentation of Transforming Growth Factor-β-induced Epithelial to Mesenchymal Transition by Interleukin-1β: Role of DNA Methylation
No full textLung cancer is a leading cause of cancer-related deaths worldwide. A better understanding of mechanisms related to tumor initiation, progression and metastasis could lead to better prevention and treatment regimens. Epithelial to mesenchymal transition (EMT) is related to metastasis and the development of therapy resistance. The aim of our study is to determine how inflammatory cytokine Interleukin-1 beta (IL-1β) enhances transforming growth factor beta (TGF-β) induced EMT in A549 lung adenocarcinoma cells, and whether regulation of DNA methylating or demethylating enzymes are involved in this enhancement. Cells in four treatment groups (IL-1β alone, TGF-β alone, IL-1β and TGF-β co-treatment and untreated control) were analyzed over a 96-hour period. Total RNA and genomic DNA were isolated at 24, 48, 72 and 96 hours. RT-PCR was used to measure mRNA levels of DNA methylating and DNA demethylating enzymes as well as established markers of EMT progression. Results of RT-PCR showed no significant difference in DNMT1 and DNMT3a mRNA expression between TGF-β alone and TGF-β-IL-1β cotreatment. However, IL-1β significantly decreased TET-1 mRNA expression as compared to untreated controls, and inhibited TGF-β induction of TET-1 at 24 and 48 hours. Inhibition of TET activity augmented TGF- β induced morphological changes but had no significant effect on CDH1/Ecadherin mRNA expression at 24 or 48 hours. Inhibition of cyclooxygenase-2 had no effect on the ability of IL-1β to augment TGF-β induced EMT
Predictors of Psychologists’ Self-Reported Knowledge and Self-perceived Competence in Treating Transgender Clients
Full text linkIt has been widely recognized that transgender (trans) and gender nonconforming (TGNC) populations face significantly greater rates of depression, anxiety, substance use, and suicidality than the general population. Despite these risks, little research has analyzed how psychologists are prepared to provide culturally competent therapy to trans clients or what predicts competence in treating this population. This study aimed to identify what factors predict psychologists’ selfperceived knowledge and self-perceived competence in working with trans clients. The study’s secondary aim was to collect information about how psychologists receive education related to trans clients. This study employed a correlational research design to examine predictors of selfperceived knowledge and competence related to working with trans clients. We hypothesized that recency of graduation, exposure to diverse clients during clinical training, engagement with TGNC clients in professional work, amount of time providing therapy at work, and attitudes/biases towards trans people (as measured by the Transgender Attitudes and Beliefs Scale) would predict self-perceived competence and self-perceived knowledge in working with trans populations (as measured by the Transgender Competency and Knowledge Scale). The implications of this study may help improve training related to building cultural competence and knowledge in graduate school and beyond. This study’s findings may also be useful in developing new assessment tools to evaluate cultural competence with TGNC clients
Examining Executive Functions and Semantic Organization Across Occupation Types
Full text linkThis study examined the relationship between executive functioning, semantic organization, and occupational classification, focusing on whether individuals in professional roles (as defined by the Career Occupational Preference System; COPS) demonstrated stronger executive functioning and semantic organization during memory recall than those in non-professional roles. Participants completed the Booklet Category Test (BCT) to assess executive functioning, the California Verbal Learning Test–Second Edition (CVLT-II) to evaluate semantic organization using short-delay free recall (SDFR), and the Wechsler Adult Intelligence Scale–Fourth Edition (WAIS-IV) to measure IQ. Results showed no significant associations among the main variables. While higher BCT performance was linked to greater use of semantic clustering, this trend was nonsignificant, as were differences between professional and non-professional groups. Professional status was associated with higher IQ and somewhat stronger cognitive performance, but not at a significant level. These findings suggest that factors such as cognitive style, education, and task familiarity may play a greater role than occupation in shaping memory strategies. Thus, occupational category alone is not a reliable predictor of cognitive performance, supporting an individualized approach to neuropsychological assessment that accounts for personal and contextual variables to improve ecological validity
Ethical considerations of deep brain stimulation for treatment refractory schizophrenia: surveying stakeholders.
Full text linkINTRODUCTION: Ethical concerns have been raised by both current and historically controversial neurosurgical interventions for treatment-refractory schizophrenia and schizoaffective disorder (TR-SZ). Considering advances in next-generation deep brain stimulation (DBS), initial success in treating a few cases of TR-SZ, and how challenging trial enrollment is, transparency and disseminating knowledge about DBS is important, as is input from involved groups. Here information was presented about DBS as an experimental treatment option for TR-SZ to stakeholders to gauge enthusiasm after consideration of potential risks and benefits.
METHODS: Stakeholders were presented with information about DBS (total
RESULTS: Most (83%) research participants and presentation audience members agreed that DBS should be an option for TR-SZ and 40% thought the potential benefits outweigh the risks of DBS with at least a 41–60% response rate. Audience approval of DBS was similar for the PD (30%), SZ (52%) and the OCD case with psychosis (56%), but there was a higher rate of approval (77%) for the OCD case whose compulsions involved self-harm. The majority (73–86%) of the audience thought that they would want to try DBS if they had TR-PD, TR-OCD, or TR-SZ.
CONCLUSIONS: Despite difficulty in recruiting patients for DBS clinical trials for TR-SZ, the consensus among 83% of stakeholders was that DBS should be an option for people with severe TR-SZ. Our approach to disseminate general knowledge then gather opinions among diverse stakeholders was to ensure the development of DBS clinical trials for the new indication TR-SZ is a relevant option despite the known difficulties in enrollment. These findings may help prevent disparities in access to advanced DBS therapeutics.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12888-025-07128-0
Use of simulation for teaching biomedical sciences to undergraduate medical students- a scoping review.
No full textINTRODUCTION: The objective of this scoping review was to understand the methods, extent and type of evidence in relation to the use of simulation or SIM-based medical education pedagogies to teach biomedical sciences to undergraduate medical students in accredited medical schools, globally. The review considers literature published between 2014 and 2024.
INCLUSION CRITERIA: The review only considered reports about populations of students enrolled in accredited undergraduate medical education programs that train medical doctors, including DO/MD/MBBS/MBChB or equivalents in any country. Simulation, as a concept, is considered as reportedly used in the context of teaching knowledge, skills, or practice-related attitudes in biomedical science disciplines. Articles published in the English Language were considered.
METHODS: An initial search of the Cochrane and the Joanna Briggs Institute’s [JBI] Evidence-based Practice databases in October 2023 found no similar review. For this review, the primary databases searched included PubMed, ERIC, and Google Scholar. The JBI [Joanna Briggs Institute] SUMARI was the platform for screening, approval, extraction, synthesis, and review. For screening and appraisal, two members of the review team were required to approve an article.
RESULTS: A total of 18 articles were considered for this review out of the initial yield of 2,671. These included: 4 Analytical Cross-Sectional Studies- 2 from Australia, 1 from the USA, and 1 from China; 2 Systematic Review and Research Syntheses; 3 Randomized Controlled Trials- 1 from China and 2 from Italy; 6 Quasi-Experimental Studies- 1 from Taiwan, 1 from the Netherlands, 1 from the both China and United Kingdom, 1 from Sweden, 1 from Indonesia and 1 from the United States; and 3 Text and Opinion Studies. Findings highlight the growing use of simulation and technology-enhanced learning in medical education, improving competency, retention, and engagement. Simulation, aided by VR, AR, and PBL, enhances motivation and skills but cannot fully replace hands-on training. Limitations include inconsistent assessment impacts, cost challenges, and accessibility concerns.
CONCLUSION: Simulation and technology-enhanced learning improve engagement, skills, and retention in medical education. Integration with traditional methods maximizes effectiveness. Virtual simulations aided by technologies, VR or AR offer immersive experiences but require careful implementation
Motivation and experiences of individuals with opioid use disorder and chronic pain using medical cannabis for 12 months.
No full textBACKGROUND: The objective of this qualitative study was to better understand the experiences of individuals living with opioid use disorder (OUD) and chronic pain using medical cannabis (MC) for 12 months.
METHODS: Perspectives were captured via 10 key informant interviews conducted after 12 months of treatment with MC RESULTS: Key themes identified regarding the reasons for initially pursuing MC included: (1) cannabis supply safety; (2) a desire to reduce or eliminate prescription medication usage for pain, OUD and mood; (3) to induce feelings of calm or relaxation; and (4) to improve levels of chronic pain. At 12 months, key themes identified surrounding their lived experiences with MC use were: (1) reductions in pain levels; (2) positive changes in emotional regulation and mood; (3) improvements in sleep quality and duration; and (4) reductions in cravings to use illicit drugs. The primary concerns expressed by interviewees surrounding MC use at 12 months related to changes in weight and appetite, and the cost of MC products.
CONCLUSIONS: These qualitative data provide targets for future quantitative investigations of the potential mechanisms by which MC can impact recovery in the context of OUD
Integrating Peer Specialists in Primary Care: Narrative Review with Illustrative Examples, and Pragmatic Recommendations to Support Implementation
No full textBehavioral health peer support specialists, peers, are health care system employees with lived experience of mental health or substance use concerns who are trained and hired to support others with behavioral health concerns in behavioral health clinics and medical settings. Peer-delivered services have a long history and research consistently demonstrates evidence of varied benefits for a wide range of patients. Peers are increasingly being hired to work within primary care settings to support the needs of primary care patients with behavioral health concerns and enhance the interdisciplinary nature of integrated primary care teams. However, integration of peers into this new setting can be challenging for both the peers and the primary care teams. Both peers and primary care staff can be uncertain of how peers are intended to function within primary care teams, how they can help the clinic and patients, what challenges to expect when integrating peers, and how to best support full integration of peers. This narrative review aims to facilitate integration of peers in primary care by describing the current literature on (1) primary care peer roles and functions; (2) primary care peer-delivered interventions; (3) benefits of peers for primary care patients and clinics; and (4) integration challenges, enablers, and successful implementation strategies for peers in primary care. A hypothetical case example for a peer specialist at a VA Medical Center is used throughout the article to illustrate key concepts. Clinical and administrative implications are discussed
Differentiating Chronic Neuropathic Rib Pain: A Case Report
No full textBACKGROUND: Rib cage pain can be challenging to diagnose due to a wide variety of etiologies in the area. Intercostal neuromas are a potential source of pain in the thoracic region. In the setting of blunt intercostal trauma, intercostal neuromas should be higher on the differential.
CASE REPORT: We describe the case of a 69-year-old man with severe thoracic pain for 10 years due to intercostal neuroma who had extensive medical workup over the course of 10 years prior to the diagnosis causing his chronic pain. He received definitive treatment with surgical resection of his intercostal neuroma.
CONCLUSIONS: This article highlights the need to consider neuroma formation in the setting of blunt trauma and the benefits of diagnosis provided by musculoskeletal ultrasound
An Exploratory Approach to Understanding Assessment Errors on Measures of Executive Functioning
Full text linkThe global risk of dementia due to longer lifespans and increased medical interventions necessitates accurate diagnosis of cognitive decline. Thus, the utilization of neuropsychological testing to diagnose disorders of cognitive decline should seek to ascertain multiple data, including success/failure of cognitive tasks and evaluation of error patterns. The purpose of this study was to examine the frequency of executive function (EF) errors across diagnoses of cognitive decline (age-related cognitive decline [ARCD], mild cognitive impairment [MCI], vascular dementia [VaD], frontotemporal dementia [FTD], Lewy body dementia [LBD], and Alzheimer’s disease [AD]) and to examine whether the specific types of EF errors (intrusion, perseveration, stimulus-bound responses, and set-loss) differ across the diagnoses. This study also explored the roles of mental health history and educational attainment as variables to determine differences across diagnoses. It was hypothesized that rates of errors would not differ between the diagnoses of dementia (VAD, FTD, LBD, AD), but that there would be differences between the types of errors. It was also hypothesized that mental illness would be more associated with a diagnosis of dementia in comparison to ARCD and MCI. Lastly, it was hypothesized that education levels would not differ amongst the diagnoses of dementia. The results of this study have implications for the development of neuropsychological test batteries with older adult patients and further expand the understanding of the role of mental health and education on cognitive decline