Beneficial Effects of Human Schwann Cell-Derived Exosomes in Mitigating Secondary Damage After Penetrating Ballistic-Like Brain Injury.

There is a growing body of evidence that the delivery of cell-derived exosomes normally involved in intracellular communication can reduce secondary injury mechanisms after brain and spinal cord injury and improve outcomes. Exosomes are nanometer-sized vesicles that are released by Schwann cells and may have neuroprotective effects by reducing post-traumatic inflammatory processes as well as promoting tissue healing and functional recovery. The purpose of this study was to evaluate the beneficial effects of human Schwann-cell exosomes (hSC-Exos) in a severe model of penetrating ballistic-like brain injury (PBBI) in rats and investigate effects on multiple outcomes. Human Schwann cell processing protocols followed Current Good Manufacturing Practices (cGMP) with exosome extraction and purification steps approved by the Food and Drug Administration for an expanded access single ALS patient Investigational New Drug. Anesthetized male Sprague-Dawley rats (280-350g) underwent PBBI surgery or Sham procedures and, starting 30 min after injury, received either a dose of hSC-Exos or phosphate-buffered saline through the jugular vein. At 48h after PBBI, flow cytometry analysis of cortical tissue revealed that hSC-Exos administration reduced the number of activated microglia and levels of caspase-1, a marker of inflammasome activation. Neuropathological analysis at 21 days showed that hSC-Exos treatment after PBBI significantly reduced overall contusion volume and decreased the frequency of Iba-1 positive activated and amoeboid microglia by immunocytochemical analysis. This study revealed that the systemic administration of hSC-Exos is neuroprotective in a model of severe TBI and reduces secondary inflammatory injury mechanisms and histopathological damage. The administration of hSC-Exos represents a clinically relevant cell-based therapy to limit the detrimental effects of neurotrauma or other progressive neurological injuries by impacting multiple pathophysiological events and promoting neurological recovery.

Large-scale bioreactor production of extracellular vesicles from mesenchymal stromal cells for treatment of acute radiation syndrome.

BACKGROUND: Hematopoietic acute radiation syndrome (H-ARS) occurring after exposure to ionizing radiation damages bone marrow causing cytopenias, increasing susceptibility to infections and death. We and others have shown that cellular therapies like human mesenchymal stromal cells (MSCs), or monocytes/macrophages educated ex-vivo with extracellular vesicles (EVs) from MSCs were effective in a lethal H-ARS mouse model. However, given the complexity of generating cellular therapies and the potential risks of using allogeneic products, development of an "off-the-shelf" cell-free alternative like EVs may have utility in conditions like H-ARS that require rapid deployment of available therapeutics. The purpose of this study was to determine the feasibility of producing MSC-derived EVs at large scale using a bioreactor and assess critical quality control attributes like identity, sterility, and potency in educating monocytes and promoting survival in a lethal H-ARS mouse model. METHODS: EVs were isolated by ultracentrifugation from unprimed and lipopolysaccharide (LPS)-primed MSCs grown at large scale using a hollow fiber bioreactor and compared to a small scale system using flasks. The physical identity of EVs included a time course assessment of particle diameter, yield, protein content and surface marker profile by flow-cytometry. Comparison of the RNA cargo in EVs was determined by RNA-seq. Capacity of EVs to generate exosome educated monocytes (EEMos) was determined by qPCR and flow cytometry, and potency was assessed in vivo using a lethal ARS model with NSG mice. RESULTS: Physical identity of EVs at both scales were similar but yields by volume were up to 38-fold more using a large-scale bioreactor system. RNA-seq indicated that flask EVs showed upregulated let-7 family and miR-143 micro-RNAs. EEMos educated with LPS-EVs at each scale were similar, showing increased gene expression of IL-6, IDO, FGF-2, IL-7, IL-10, and IL-15 and immunophenotyping consistent with a PD-L1 high, CD16 low, and CD86 low cell surface expression. Treatment with LPS-EVs manufactured at both scales were effective in the ARS model, improving survival and clinical scores through improved hematopoietic recovery. EVs from unprimed MSCs were less effective than LPS-EVs, with flask EVs providing some improved survival while bioreactor EVs provide no survival benefit. CONCLUSIONS: LPS-EVs as an effective treatment for H-ARS can be produced using a scale-up development manufacturing process, representing an attractive off-the-shelf, cell-free therapy.

Optimal technique for canine mesenchymal stem cells labeling with novel SPIO, MIRB™: for MRI detection of transplanted stem cells canine stroke model.

BACKGROUND: Cell-based therapy has emerged as a promising avenue for post-stroke recovery. A significant challenge lies in tracking the distribution and engraftment of transplanted cells within the target cerebral tissue. To address this, we turn to the potential of Brain MRI detection of mesenchymal stem cells (MSCs), achieved by labeling these cells with superparamagnetic iron oxide (SPIO). This is the first report of a technique to label canine MSCs using a commercially available SPIO, Molday ION Rhodamine B (MIRB), to optimize both viability and labeling efficacy for transplantation purposes." METHOD: Canine MSCs were incubated with addition of different MIRB concentration from 0, 10, 20, 30 µg Fe/ml. The cellular uptake of MIRB was confirmed through the analysis of fluorescent images and flow cytometry. The morphological characteristics of MSCs were assessed via microscopic visualization. Cellular viability was evaluated using both a cellometer and flow cytometry. RESULT: Fluorescent microscopic images of all MIRB incubated MSCs groups show >70% labeled cells with homogenous signal intensity. Notably, the morphology of MSCs remained unaltered in the 10 µg Fe/ml group compared to the control group. Furthermore, among the labeled groups, the 10 µg Fe/ml concentration exhibited the highest viability when assessed using two different flow cytometry methods (95.3%, p < 0.05). CONCLUSION: This study successfully labels canine MSCs with MIRB. The optimal concentration of 10 µg Fe/ml demonstrates optimal viability, labeling efficacy, and preserved cellular morphology.

Hepatocellular carcinoma surveillance may be associated with potential psychological harms in patients with cirrhosis.

BACKGROUND AND AIMS: The value of HCC surveillance is determined by the balance between benefits and harms; however, no studies have enumerated psychological harms. APPROACH AND RESULTS: We fielded surveys measuring psychological harms to patients with cirrhosis in a multicenter randomized trial of HCC surveillance outreach. All patients with positive or indeterminate surveillance results and matched patients with negative results were invited to complete surveys measuring (1) depression through the Patient Health Questionnaire-ninth version, (2) anxiety through State-Trait Anxiety Inventory, (3) HCC-specific worry through Psychological Consequences Questionnaire, and (4) decisional regret. Patients were classified into 4 groups: true positive (TP), false positive (FP), indeterminate, and true negative (TN). Multivariable longitudinal regression analysis using the generalized estimating equation method was performed to compare the means of measures across groups. We conducted 89 semistructured interviews in a subset of patients stratified by health system and test results. Of 2872 patients in the trial, 311 completed 1+ follow-up survey (63 FP, 77 indeterminate, 38 TP, and 133 TN). Moderate depression decreased in TN patients, increased in TP, and had intermittent but mild increases in those with FP and indeterminate results. High anxiety temporarily increased in patients with TP results but resolved over time and was stable in those with FP and indeterminate results. Decisional regret was low and did not differ across groups. In semistructured interviews, patients reported apprehension, anxiety, emotional distress, and coping related to HCC surveillance. CONCLUSIONS: Psychological harms of HCC surveillance appear mild but differ by test result. Future research should determine the impact of psychological harms on the value of HCC surveillance programs.

Academic performance of children in relation to gender, parenting styles, and socioeconomic status: What attributes are important.

What are the effects of parenting styles on academic performance and how unequal are these effects on secondary school students from different gender and socioeconomic status families constitute the theme of this paper. A cross-sectional and purposive sampling technique was adopted to gather information from a sample of 448 students on a Likert scale. Chi-square, Kendall's Tau-c tests and hierarchical multiple regression analyses were used to determine the extent of the relationship among the variables. Chi-square and Kendall's Tau-c (Tc) test results established that the socioeconomic status of the respondent's family explained variation in children's academic performance due to parenting style; however, no significant difference was observed in the academic performance of students based on gender. Furthermore, hierarchal multiple regression analysis established that the family's socioeconomic status, authoritative parenting, permissive parenting, the interaction of socioeconomic status and authoritative parenting, and the interaction of socioeconomic status and permissive parenting were significant predictors (P<0.05) of students' academic performance. These predictor variables explained 59.3 percent variation in the academic performance of children (R2 = 0.593). Results of hierarchal multiple regression analysis in this study ranked ordered the most significant predictors of the academic performance of children in the following order. Family socioeconomic status alone was the strongest predictor (ß = 18.25), interaction of socioeconomic status and authoritative parenting was the second important predictor (ß = 14.18), authoritative parenting alone was third in importance (ß = 13.38), the interaction of socioeconomic status and permissive parenting stood at fourth place in importance (ß = 11.46), and permissive parenting was fifth (ß = 9.2) in influencing academic performance of children in the study area. Children who experienced authoritative parenting and were from higher socioeconomic status families perform better as compared to children who experienced authoritarian and permissive parenting and were from low socioeconomic status families.

The Impact of Social Media on the Physical and Mental Well-Being of Medical Students During the COVID-19 Pandemic.

COVID-19 pandemic has increased social media engagement globally. This study examined the correlation between social media use and physical/mental health among university students, considering gender and academic year. Out of 146 responses, 119 were analyzed after excluding participants with pre-existing psychological conditions. Results showed a significant correlation between social media use and mental health for all participants (correlation coefficient = 0.30, p < 0.001), indicating a negative impact on mental health with increased use. Gender-specific analysis revealed a non-significant correlation among males (p = 0.21), while females exhibited a significant correlation (correlation coefficient = 0.32, p = 0.01), suggesting an adverse effect on their mental health. Regarding physical health, females displayed an even higher correlation (correlation coefficient = 0.40, p < 0.001), highlighting the negative influence of social media on their physical well-being. Conversely, no significant correlation was observed among males. Analyzing by academic year, both pre-clerkship and clerkship students showed a significant correlation between social media use and mental health (correlation coefficients of 0.26, p = 0.01, and 0.42, p = 0.03, respectively). Similarly, a significant correlation was found between social media use and physical health among pre-clerkship students (correlation coefficient = 0.34, p = 0.001), but not among clerkship students. In conclusion, this study provides evidence of the adverse impact of social media use on physical and mental health among university students, particularly among females and across different academic years. These findings underscore the importance of promoting healthy social media habits and raising awareness about the potential negative effects on well-being.

Career Plans of Internal Medicine Residents From 2019 to 2021.

This survey study examines career choices of internal medicine residents from 2019 to 2021 and compares them with findings from a decade earlier.

Financial Burden of Hepatocellular Carcinoma Screening in Patients with Cirrhosis.

BACKGROUND: The overall value of hepatocellular carcinoma screening is defined by the balance of benefits and harms. Studies have only reported physical harms with none describing financial harms. METHODS: We conducted a multicenter pragmatic randomized clinical trial of hepatocellular carcinoma screening outreach among 2872 patients with cirrhosis from March 2018 to April 2021. Patients with positive or indeterminate results and matched patients with negative results completed surveys at baseline and at follow-up measuring financial harms via Cancer Self-Administered Questionnaire and financial burden via Comprehensive Score for Financial Toxicity Functional Assessment of Chronic Illness Therapy. Univariable and multivariable longitudinal regression analyses were performed to compare changes in financial harms across groups: true positive, true negative, false positive, and indeterminate. Semistructured interviews were conducted in a subset of patients, sampled by center and test result. RESULTS: Of 311 patients who completed at least 1 follow-up survey (75% response rate), 37 had true positive, 133 true negative, 64 false positive, and 77 indeterminate results. Financial harms increased in true positive and false positive patients with no significant changes noted among those with true negative or indeterminate results. At follow-up, 21.8% of patients reported moderate-severe financial burden, which was not significantly associated with test results. Semistructured interviews revealed variation in the frequency and severity of financial harms based on test results, with increased harm in those with false positive results. CONCLUSIONS: Financial harms of hepatocellular carcinoma screening vary by test result and can pose a barrier that must be considered when determining the optimal screening program.

Thyrotoxic Periodic Paralysis With Hypokalemia: A Case Study.

Thyrotoxic periodic paralysis (TPP) is a rare life-threatening condition most commonly seen in individuals between the ages of 20-40 years. It is most prevalent in Hispanic and Asian populations. Here we present a case report of a young male patient admitted to our facility with an acute onset of paralysis. He was found to have new-onset hyperthyroidism and severe hypokalemia. TPP was exacerbated by the intake of a high-carbohydrate meal as well as a steroid injection within 24 hours of symptom onset.

Bone Marrow and Wharton's Jelly Mesenchymal Stromal Cells are Ineffective for Myocardial Repair in an Immunodeficient Rat Model of Chronic Ischemic Cardiomyopathy.

BACKGROUND: Although cell therapy provides benefits for outcomes of heart failure, the most optimal cell type to be used clinically remains unknown. Most of the cell products used for therapy in humans require in vitro expansion to obtain a suitable number of cells for treatment; however, the clinical background of the donor and limited starting material may result in the impaired proliferative and reparative capacity of the cells expanded in vitro. Wharton's jelly mesenchymal cells (WJ MSCs) provide a multitude of advantages over adult tissue-derived cell products for therapy. These include large starting tissue material, superior proliferative capacity, and disease-free donors. Thus, WJ MSC if effective would be the most optimal cell source for clinical use. OBJECTIVES: This study evaluated the therapeutic efficacy of Wharton's jelly (WJ) and bone marrow (BM) mesenchymal stromal cells (MSCs) in chronic ischemic cardiomyopathy in rats. METHODS: Human WJ MSCs and BM MSCs were expanded in vitro, characterized, and evaluated for therapeutic efficacy in a immunodeficient rat model of ischemic cardiomyopathy. Cardiac function was evaluated with hemodynamics and echocardiography. The extent of cardiac fibrosis, hypertrophy, and inflammation was assessed with histological analysis. RESULTS: In vitro analysis revealed that WJ MSCs and BM MSCs are morphologically and immunophenotypically indistinguishable. Nevertheless, the functional analysis showed that WJ MSCs have a superior proliferative capacity, less senescent phenotype, and distinct transcriptomic profile compared to BM MSC. WJ MSCs and BM MSC injected in rat hearts chronically after MI produced a small, but not significant improvement in heart structure and function. Histological analysis showed no difference in the scar size, collagen content, cardiomyocyte cross-sectional area, and immune cell count. CONCLUSIONS: Human WJ and BM MSC have a small but not significant effect on cardiac structure and function when injected intramyocardially in immunodeficient rats chronically after MI.

The impact of cell-based therapy on female sexual dysfunction: a systematic review and meta-analysis.

INTRODUCTION: Female sexual dysfunction (FSD) is a complex issue affecting women of all ages; it involves several overlapping body systems and profoundly affects quality of life. The use of cell-based therapy, such as mesenchymal stem cells, has recently been investigated as a potential treatment for FSD. OBJECTIVES: This systematic review and meta-analysis aim to assess FSD outcomes following cell-based therapy. METHODS: We evaluated peer-reviewed articles from multiple online databases through November 2022 to identify studies that used cell-based therapy and reported sexual function outcomes in women. We performed a meta-analysis using data pooled from 3 clinical trials at our institution: CRATUS (NCT02065245), ACESO (NCT02886884), and CERES (NCT03059355). All 3 trials collected data from the Sexual Quality of Life-Female (SQOL-F) questionnaire as an exploratory outcome. RESULTS: Existing literature on this topic is scarce. Five clinical studies and 1 animal study were included in the systematic review, and only 2 clinical studies were considered good quality: 1 reported significant SQOL-F improvement in women 6 months after cell therapy, and 1 reported posttherapy sexual satisfaction in all women. When individual patient data were pooled in a meta-analysis from 29 women across 3 trials at our institution, the SQOL-F was not significantly improved. CONCLUSION: Despite growing interest in cell-based therapy for women's sexual health, this important issue is understudied in the literature. The optimal route, source, and dose of cell therapy to produce clinically meaningful change have yet to be determined, and further research is needed in larger randomized placebo-controlled clinical trials.

Cell-based therapy to boost right ventricular function and cardiovascular performance in hypoplastic left heart syndrome: Current approaches and future directions.

Congenital heart disease remains one of the most frequently diagnosed congenital diseases of the newborn, with hypoplastic left heart syndrome (HLHS) being considered one of the most severe. This univentricular defect was uniformly fatal until the introduction, 40 years ago, of a complex surgical palliation consisting of multiple staged procedures spanning the first 4 years of the child's life. While survival has improved substantially, particularly in experienced centers, ventricular failure requiring heart transplant and a number of associated morbidities remain ongoing clinical challenges for these patients. Cell-based therapies aimed at boosting ventricular performance are under clinical evaluation as a novel intervention to decrease morbidity associated with surgical palliation. In this review, we will examine the current burden of HLHS and current modalities for treatment, discuss various cells therapies as an intervention while delineating challenges and future directions for this therapy for HLHS and other congenital heart diseases.

HIV Promotes Atherosclerosis via Circulating Extracellular Vesicle MicroRNAs.

People living with HIV (PLHIV) are at a higher risk of having cerebrocardiovascular diseases (CVD) compared to HIV negative (HIVneg) individuals. The mechanisms underlying this elevated risk remains elusive. We hypothesize that HIV infection results in modified microRNA (miR) content in plasma extracellular vesicles (EVs), which modulates the functionality of vascular repairing cells, i.e., endothelial colony-forming cells (ECFCs) in humans or lineage negative bone marrow cells (lin- BMCs) in mice, and vascular wall cells. PLHIV (N = 74) have increased atherosclerosis and fewer ECFCs than HIVneg individuals (N = 23). Plasma from PLHIV was fractionated into EVs (HIVposEVs) and plasma depleted of EVs (HIV PLdepEVs). HIVposEVs, but not HIV PLdepEVs or HIVnegEVs (EVs from HIVneg individuals), increased atherosclerosis in apoE-/- mice, which was accompanied by elevated senescence and impaired functionality of arterial cells and lin- BMCs. Small RNA-seq identified EV-miRs overrepresented in HIVposEVs, including let-7b-5p. MSC (mesenchymal stromal cell)-derived tailored EVs (TEVs) loaded with the antagomir for let-7b-5p (miRZip-let-7b) counteracted, while TEVs loaded with let-7b-5p recapitulated the effects of HIVposEVs in vivo. Lin- BMCs overexpressing Hmga2 (a let-7b-5p target gene) lacking the 3'UTR and as such is resistant to miR-mediated regulation showed protection against HIVposEVs-induced changes in lin- BMCs in vitro. Our data provide a mechanism to explain, at least in part, the increased CVD risk seen in PLHIV.

Intramyocardial cell-based therapy with Lomecel-B during bidirectional cavopulmonary anastomosis for hypoplastic left heart syndrome: the ELPIS phase I trial.

Aims: Hypoplastic left heart syndrome (HLHS) survival relies on surgical reconstruction of the right ventricle (RV) to provide systemic circulation. This substantially increases the RV load, wall stress, maladaptive remodelling, and dysfunction, which in turn increases the risk of death or transplantation. Methods and results: We conducted a phase 1 open-label multicentre trial to assess the safety and feasibility of Lomecel-B as an adjunct to second-stage HLHS surgical palliation. Lomecel-B, an investigational cell therapy consisting of allogeneic medicinal signalling cells (MSCs), was delivered via intramyocardial injections. The primary endpoint was safety, and measures of RV function for potential efficacy were obtained. Ten patients were treated. None experienced major adverse cardiac events. All were alive and transplant-free at 1-year post-treatment, and experienced growth comparable to healthy historical data. Cardiac magnetic resonance imaging (CMR) suggested improved tricuspid regurgitant fraction (TR RF) via qualitative rater assessment, and via significant quantitative improvements from baseline at 6 and 12 months post-treatment (P < 0.05). Global longitudinal strain (GLS) and RV ejection fraction (EF) showed no declines. To understand potential mechanisms of action, circulating exosomes from intramyocardially transplanted MSCs were examined. Computational modelling identified 54 MSC-specific exosome ribonucleic acids (RNAs) corresponding to changes in TR RF, including miR-215-3p, miR-374b-3p, and RNAs related to cell metabolism and MAPK signalling. Conclusion: Intramyocardially delivered Lomecel-B appears safe in HLHS patients and may favourably affect RV performance. Circulating exosomes of transplanted MSC-specific provide novel insight into bioactivity. Conduct of a controlled phase trial is warranted and is underway.Trial registration number NCT03525418.

IAA-decorated CuO nanocarriers significantly improve Chickpea growth by increasing antioxidative activities.

Plant growth regulators tagged on metallic oxide nanoparticles (NPs) may function as nanofertilizers with reduced toxicity of NPs. CuO NPs were synthesized to function as nanocarriers of Indole-3-acetic acid (IAA). Powder X-ray diffraction (XRD) and scanning electron microscopy (SEM) revealed 30.4 nm size of NPs and sheet-like structure, respectively, of CuO-IAA NPs. Fourier-transform infrared spectroscopy (FTIR) confirmed CuO-IAA formation. IAA-decorated CuO NPs enhanced the physiological parameters of Chickpea plants, i.e., root length, shoot length, and biomass compared to naked CuO NPs. The variation in physiological response was due to change of phytochemical contents in plants. Phenolic content increased up to 17.98 and 18.13 µgGAE/mg DW at 20 and 40 mg/L of CuO-IAA NPs, respectively. However, significant decrease in antioxidant enzymes' activity was recorded compared to control. Presence of CuO-IAA NPs increased the reducing potential of plants at higher concentration of NPs, while decrease in total antioxidant response was observed. This study concludes that IAA conjugation to CuO NPs reduces toxicity of NPs. Furthermore, NPs can be explored as nanocarriers for plant modulators and slow release in future studies.

Successful Treatment of Cholecysto-Antral Fistula: A Case Report.

Cholecysto-antral fistula and gallstone ileus are rare complications of a common disease, gallbladder stone (GBS). This fistula is developed as a prolonged complication of cholelithiasis in which the gallbladder adheres to the adjacent antrum, and a stone erodes through the wall. Among the variety of cholecystoenteric fistulae, the cholecystoduodenal fistula occurs more commonly than the cholesysto-antral fistula. In this scientific study, we present a 98-year-old male patient who came to ER with a complaint of abdominal pain, vomiting, and constipation for five days. He was vitally stable and had normal laboratory results. The plain abdominal X-ray showed dilated loops with excessive gases. His computed tomography (CT) abdomen with contrast showed small bowel obstruction secondary to an impacted gallstone at the distal jejunum, fistulous communication between the gall bladder and the antrum, and pneumobilia. Our management included endoscopic retrieval of a single gallstone from the second part of the duodenum followed by open surgical enterolithotomy, partial cholecystectomy, and closing of the fistula. Despite our case sharing many aspects with the available literature, our case, to our knowledge, is the first case of ileus gallstone occurring in a 98-year-old patient. Cholecysto-antral fistula has not been widely published in the literature. The offending gallstone presented along with the radiological Mercedes Benz sign which does not present in all cases of GBS. Typically, the obstructing GBS stops at the terminal ileum, but in our case, it was dislodged in the distal jejunum with no previous biliary symptoms. Finally, we were able to remove another single GBS from the second part of the duodenum during the preoperative upper endoscopy. The clinical diagnosis may be missed due to the vague presentation of symptoms; hence imaging, especially of the CT abdomen is crucial in establishing the diagnosis, moreover, performing an upper endoscopy could have diagnostic and therapeutic benefits. In cases like this, the main surgical intervention should be to address the bowel obstruction, and cholecystectomy with fistula closure may be added if the patient's condition is stable with minimal inflammation and adhesion.

Prevalence and Determinants of Mental Health Problems and Mental Health Stigma Among Medical Students of Different Nationalities in Qatar.

Introduction: Past studies have shown high prevalence of mental illness among medical students. This is often linked to the demands of the medical curriculum, and to mental health stigma that prevents students from seeking help. This study aimed to examine experiences of mental health problems among medical students of different nationalities in Qatar and to uncover sociodemographic factors related to their prevalence and associated stigma. Methods: A cross-sectional online survey was conducted with medical students in their second through fifth years at the College of Medicine at Qatar University. The survey began with a consent form, and those agreed to take the survey were directed to the questionnaire. The survey comprised 64 items across three sections. The first section collected sociodemographic data. The second section screened depressive symptoms using the PHQ-9; anxiety symptoms using GAD-7; and psychological distress symptoms using Kessler-6. The third section included 27 questions adopted from Schwenk et al, which evaluate students' perceptions of stigma and their attitudes toward seeking help with their mental health. Results: One hundred and eighty-two students participated in the study. The prevalence of self-reported symptoms of severe depression, anxiety, and psychological distress was 4.4% (95% CI 2-9), 10.4% (95% CI 7-16), and 39.6% (95% CI 33-47), respectively; the prevalence of high stigma was 31.9% (95% CI 25-39). Parental education, repetition of an academic year, progress in medical studies, gender, and nationality had statistically significant correlations with mental health problems and stigma. Conclusion: In addition to the impact of the requirements of medical study, the high prevalence of reported mental illness among medical students is impacted by sociodemographic factors and the mental health stigma that constitutes a barrier to seeking help. Preventive wellbeing programs should be an essential component of medical curricula.

Systematic review of the therapeutic use of Schwann cells in the repair of peripheral nerve injuries: Advancements from animal studies to clinical trials.

Objective: To systematically evaluate the literature on the therapeutic use of Schwann cells (SC) in the repair of peripheral nerve injuries. Methods: The Cochrane Library and PubMed databases were searched using terms [("peripheral nerve injury" AND "Schwann cell" AND "regeneration") OR ("peripheral nerve injuries")]. Studies published from 2008 to 2022 were eligible for inclusion in the present study. Only studies presenting data from in-vivo investigations utilizing SCs in the repair of peripheral nerve injuries qualified for review. Studies attempting repair of a gap of ≥10 mm were included. Lastly, studies needed to have some measure of quantifiable regenerative outcome data such as histomorphometry, immunohistochemical, electrophysiology, or other functional outcomes. Results: A search of the PubMed and Cochrane databases revealed 328 studies. After screening using the abstracts and methods, 17 studies were found to meet our inclusion criteria. Good SC adherence and survival in conduit tubes across various studies was observed. Improvement in morphological and functional outcomes with the use of SCs in long gap peripheral nerve injuries was observed in nearly all studies. Conclusion: Based on contemporary literature, SCs have demonstrated clear potential in the repair of peripheral nerve injury in animal studies. It has yet to be determined which nerve conduit or graft will prove superior for delivery and retention of SCs for nerve regeneration. Recent developments in isolation and culturing techniques will enable further translational utilization of SCs in future clinical trials.

Optimal Technique for Introducing Schwann Cells Into Peripheral Nerve Repair Sites.

Peripheral nerve injury (PNI) is found in a relatively large portion of trauma patients. If the injury is severe, such as with the presence of a long segmental gap, PNI can present a challenge for treatment. The current clinical standard of nerve harvest for the repair of long segmental gap PNI can lead to many potential complications. While other methods have been utilized, recent evidence indicates the relevance of cell therapies, particularly through the use of Schwann cells, for the treatment of PNI. Schwann cells (SCs) are integral in the regeneration and restoration of function following PNI. SCs are able to dedifferentiate and proliferate, remove myelin and axonal debris, and are supportive in axonal regeneration. Our laboratory has demonstrated that SCs are effective in the treatment of severe PNI when axon guidance channels are utilized. However, in order for this treatment to be effective, optimal techniques for cellular placement must be used. Thus, here we provide relevant background information, preclinical, and clinical evidence for our method in the treatment of severe PNI through the use of SCs and axon guidance channels.