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Differential Expression of Immune T-Cell Subpopulations and Pathologic Features in Dermatomyositis, Inclusion Body Myositis and Nonspecific Inflammatory Myopathies

Background: The immune T-cell subpopulations in inflammatory myopathies (IMs) play a crucial role in the lymphocytic environment. Objectives: This study aimed to investigate the prevalence of T-cells and MHC-I expression across different types of IMs. Methods: A retrospective cohort of 34 patients with dermatomyositis (DM), inclusion body myositis (IBM), and nonspecific IMs (NSIMs) was examined for CD4, CD8, and MHC-I expressions. The relationships between these subsets were analyzed. Results: The mean age of patients was 44 years. The cases were categorized into three subgroups: Dermatomyositis (n = 9), IBM (n = 9), and NSIM (n = 16). All muscle biopsies exhibited classical features of IM. In DM, the inflammatory infiltrate was present in both the perimysium and endomysium, whereas in IBM, the inflammation was predominantly localized to the endomysium. No statistically significant difference was observed in the distribution of CD4 and CD8 T-cells among the three subgroups (P-value = 0.358). However, CD4+ T-cells were more frequently seen in DM, while CD8+ T-cells were predominant in IBM. There were no notable differences in T-cell subpopulations among NSIM. Significant statistical differences in MHC-I expression patterns and mitochondrial abnormalities were identified among the three subsets (P-value < 0.05). Perifascicular pathology (PFP) was predominantly observed in all DM cases, whereas 5 out of 9 IBM cases exhibited rimmed vacuoles in their muscle biopsies. None of the DM cases showed rimmed vacuoles or protein aggregates. Mitochondrial abnormalities were exclusively identified in IBM cases. Conclusions: Immune T-cell subpopulations and pathological features differ distinctly among DM, IBM, and NSIM. CD4+ T-cells and PFP are predominant in DM, whereas CD8+ T-cells, rimmed vacuoles, and mitochondrial abnormalities are characteristic of IBM. MHC-I expression is present in all subsets, but its patterns are variable and unpredictable.

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Efficacy of Melatonin for the Treatment of Moderate to Severe Vincristine-Induced Neuropathy in in Children with Acute Lymphoblastic Leukemia: A Randomized Controlled Trial

Background: Acute lymphoblastic leukemia (ALL) is the most common cancer in children, accounting for 26% of pediatric blood malignancies. Vincristine is a widely used chemotherapy agent for ALL, but vincristine-induced peripheral neuropathy (VIPN) is the most prevalent and significant side effect associated with its administration. Objectives: This study aims to evaluate the efficacy of melatonin in treating VIPN in children with ALL. Methods: This randomized controlled trial included children aged 5 to 12 years with ALL who were clinically diagnosed with VIPN using the pediatric-modified total neuropathy score. Patients were randomly assigned to either a control or treatment group. The vincristine dose for each of the four treatment phases (induction, consolidation, maintenance, and intensification) was 1.5 mg/m², administered intravenously. Baseline and one-month post-treatment measurements included the CTCAE score (to assess VIPN), PedsQL child and parent scores (to evaluate quality of life), and pediatrics-modified total neuropathy (PEDs MTNs) scores. Patients received either 3 - 5 mg of melatonin or a placebo daily for one month. Results: A total of 20 patients (mean age: 7.45 ± 2.31; 55% female) were included, with 60% allocated to the treatment group. Baseline clinical and demographic data showed no significant differences between groups. The study found that melatonin administration at a dose of 3 mg daily for one month did not significantly improve VIPN in children with ALL. However, a significant difference was observed in pain scores after the intervention, with children in the placebo group reporting a significantly higher mean pain score compared to the treatment group (4 ± 2.39 vs. 2 ± 2.26, P = 0.041). Melatonin had a substantial and statistically significant impact on the quality of life of the children and their parents, as well as on the children’s pain scores. Conclusions: Although the CTCAE score was reduced, no significant difference was observed between the melatonin and placebo groups. However, melatonin demonstrated a positive effect on health-related quality of life and pain reduction in children with ALL diagnosed with VIPN.

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Neuropathology of Severe Depression in Long COVID-19 Infection; Possible Roles for Astrocytes, Creatine Kinase and Lactate Dehydrogenase Activity

Background: The incidence of depression has increased significantly during the COVID-19 pandemic. Some individuals infected with COVID-19 develop persistent neurological and neuropsychiatric symptoms approximately 12 weeks after the acute infection, a condition known as long COVID-19 syndrome. However, the underlying pathogenesis remains unclear. Glial fibrillary acidic protein (GFAP), creatine kinase (CK), and lactate dehydrogenase (LDH) are enzymes abundant in the central nervous system (CNS), playing important roles in neuronal energy homeostasis. Objectives: This study aimed to investigate the correlation between serum GFAP, CK, and LDH levels and depression in patients with long COVID-19 syndrome. Methods: This cross-sectional study involved 150 patients (75 males and 75 females). The Beck Depression Inventory-II (BDI-II) was used, along with standardized peripheral serum assessments. Serum GFAP, CK, and LDH levels were measured using customized direct ELISA. Data were matched by age and sex, and analyzed using Spearman non-parametric tests to assess the correlation between variables. Results: The serum level of GFAP was significantly higher in both males and females with severe depression compared to those with mild depression (282 ± 3 pg/mL, 280 ± 2.9 pg/mL, P = 0.001). The mean serum CK level was 239 ± 24.05 U/L in males and 142 ± 18.08 U/L in females (P < 0.0001). Furthermore, a significant positive correlation was found between CK serum levels and Beck scores (r = 0.33, 95% CI = 0.176 to 0.469), with a similar pattern observed for LDH (r = 0.22, 95% CI = 0.042 to 0.358). GFAP, CK, and LDH levels were higher in male patients. Conclusions: This study identified potential neurobiological mechanisms in CNS-related long COVID syndrome, suggesting that elevated astrocyte activity, along with increased serum CK and LDH levels, may contribute to the neurobiological issues seen in depressed long COVID survivors. Men appeared to be more susceptible to these changes than women. Further research is essential.

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Fish Species Spinal Cord Injury Models Utility for Research: A Systematic Review of Methodologies and Outcomes

Context: Spinal cord injury (SCI) is a devastating condition that results in severe disability and significant comorbidities. The complex pathophysiology of SCI repair and difficulties understanding neural regeneration are treatment challenges. Objectives: The aim of this study is to systematically review the diverse applications of various fish species as models for SCI research. Evidence Acquisition: PRISMA guidelines were used to review observational and interventional studies that utilized fish species as SCI models, published from inception to July 2023. Two independent reviewers screened and performed the data extraction. One independent reviewer assessed the risk of bias for the included studies. Results: Five thousand six hundred and thirty-three records were reviewed, and 144 met the inclusion criteria and were categorized by fish species. The majority of studies employed complete transection injuries, with the remainder being crush injuries, laser injuries, electro-ablations, and demyelination with substances. Zebrafish (Danio rerio) were most commonly utilized 102/144 (71%), primarily with larval models. Other models included Lamprey (Petromyzon marinus and Lethenteron reissneri); Goldfish (Carassius auratus); European eel (Anguilla Anguilla); Knifefish (Apteronotus leptorhynchus and Apteronotus albifrons); Sailfin Molly (Poecilia latipinna); and African turquoise killifish (Nothobranchius furzeri). Conclusions: This systematic review highlights that fish models, particularly zebrafish, goldfish, and European eels, are important models for further defining SCI pathophysiology and regenerative processes. These models provide a less complex model to gain insights into apoptosis and glial networks.

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Cognition in Schizophrenia: Exploring the Dynamics of Improvement and the Influencing Determinants

Background: Cognitive impairments are fundamental characteristics of schizophrenia, significantly impacting the overall functioning of individuals with the disorder. However, the trajectory of cognitive deficits and the factors influencing their changes over the course of treatment remain poorly understood. Objectives: The present study aimed to investigate the changes in cognitive status of patients with schizophrenia and the factors that influence these changes following hospitalization and treatment. Methods: The study utilized a longitudinal design, enrolling thirty hospitalized patients (15 males and 15 females) from the psychiatric inpatient unit of a general educational hospital. Cognitive assessments were conducted upon admission and discharge. A Generalized Estimating Equation (GEE) model was used to analyze the data, accounting for demographic and clinical variables such as age, gender, Body Mass Index (BMI), family history, and smoking status. Results: The findings revealed a reduction in cognitive deficits following hospitalization and treatment. Significant improvements were observed in verbal memory, working memory, and executive function. However, older patients showed poorer performance in motor speed, verbal fluency, and symbol coding compared to younger patients. Male patients and smokers demonstrated lower cognitive functioning, particularly in verbal fluency, symbol coding, and executive function. Conclusions: This study highlighted the positive effect of comprehensive inpatient treatment on reducing cognitive impairments in individuals with schizophrenia. While improvements were noted in several cognitive domains, the persistence of certain deficits, particularly in relation to demographic factors (age, gender, and smoking status), underscores the need for further research and tailored cognitive rehabilitation interventions. A personalized, multidimensional approach to managing cognitive deficits in schizophrenia could lead to better functional outcomes and enhance the quality of life for affected individuals.

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Evaluation the Impressionability of Acellular Scaffolds in Presence of Different Combination of Umbilical Cord Blood Stem Cells and Platelet Rich Fibrin in Repair of Knee Defects in Rabbit (Novel Method with Xeno-Material Elements

Background: Currently, the use of xenogeneic and allogeneic compounds in the treatment of musculoskeletal diseases is common. Repairing bone and cartilage remains a significant challenge for orthopedic surgeons. One of the principal goals of tissue engineering is the development of appropriate scaffolds that can promote tissue regeneration. Various cells and genes are involved in bone and cartilage regeneration, and new scaffolds can induce these processes during osteoregeneration. Objectives: The aim of this study is to evaluate the effects of umbilical cord blood stem cells (USCs) and platelet-rich fibrin (PRF) using acellular scaffolds in the repair of knee defects in rabbits. Methods: In this study, the femoral patella of 12 male New Zealand rabbits was drilled, and they were divided into four groups: (1) control (rabbits with femoral defects), (2) acellular osteochondral (AO), (3) AO + PRF, and (4) AO + USCs / platelet-rich fibrin. Different scaffolds were implanted into their knees, and after six months, histological evaluations were conducted. To further investigate the effects of scaffolds on bone and cartilage, gene expression levels of Col 1, Col X, Runx2, SOX9, and ALP were measured using real-time PCR. Results: All the implanted materials contributed to knee repair. In terms of statistical analysis, the use of USCs and platelet-rich fibrin with natural scaffolds such as Acellular Osteochondral provided better results for repairing bone and cartilage. The evaluation of specific bone regeneration genes (COLI, RUNX2) and the histological results from the implanted site in experimental osteochondral defects indicated that the most effective knee repair occurred in the group treated with cell-free osteochondral scaffolds, USCs, and platelet-rich fibrin. Conclusions: This study demonstrates that the combination of biomaterials and xenografts can accelerate the regeneration process.

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Characteristics of Functional Connections and Topographical Properties Distinguished the Healthy State and Obsessive-Compulsive Disorder

Background: Obsessive-compulsive disorder (OCD) is characterized by alterations in brain connectivity, particularly within the default mode network (DMN) and the salience network (SN). Investigating these connectivity differences can provide a deeper understanding of the neural mechanisms underlying OCD. Methods: This cross-sectional study involved 58 patients diagnosed with OCD and 38 healthy control subjects, totaling 96 participants. Resting-state functional MRI (fMRI) data were acquired and analyzed using the CONN toolbox to examine functional connectivity within intrinsic resting-state networks. Graph theory metrics were applied to evaluate node connections and the overall network topology. Clinical symptoms were assessed using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), and their correlations with connectivity patterns and graph-theory parameters were analyzed. Results: The OCD patients and healthy controls were matched in terms of age, gender, marital status, socioeconomic status, and handedness. However, OCD patients had significantly worse general health, quality of life, and higher levels of depression and anxiety. Network analyses revealed altered whole-brain connectivity in OCD patients, particularly within the DMN and the frontoparietal network. The most significant between-group connectivity differences were observed between the posterior parietal cortex (PPC) and the precuneus. Disruptions in the DMN, specifically altered connectivity between the medial prefrontal cortex and posterior cingulate cortex, and changes in the SN involving the anterior insula and anterior cingulate cortex, were significantly correlated with the severity of OCD symptoms. Conclusions: The findings suggest that OCD is associated with distinct alterations in DMN connectivity, which may play a critical role in the disorder's pathophysiology. These disruptions offer potential targets for therapeutic intervention. Further research is needed to explore these connectivity changes in larger cohorts and at various stages of OCD to better understand their clinical significance.

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The Effects of Subchronic Methamphetamine Administration on the NLRP3 Inflammasome, Memory Function, and Hippocampal Morphology

Background: While it is established that addictive doses of methamphetamine correlate with inflammation-mediated neurotoxic pathways, the extent of toxicity resulting from subchronic administration at lower doses remains uncertain. Objectives: This study aimed to investigate the subtle effects of daily subchronic methamphetamine (MA) administration on neuroinflammatory processes, cognitive dimensions, gene expression, and hippocampal morphology. Methods: The experimental study employed a longitudinal design with three groups (G1B, G2B, G3B) receiving methamphetamine (5 mg/kg, intraperitoneally, once daily) for 1, 2, or 3 weeks, respectively. Corresponding control groups (G1A, G2A, G3A) received 0.2 mL of normal saline. Spatial learning, novel object recognition, and passive avoidance tests were conducted to assess spatial, recognition, and fear avoidance memories. Hippocampal morphology was evaluated using Nissl staining, and the expressions of NLRP3, ASC, and caspase-1 genes were measured as markers of neuroinflammation. Results: Statistical analyses, including one-way and two-way ANOVA, showed that subchronic low-dose administration of MA led to significant activation of the inflammasome (NLRP3, ASC, and caspase-1), which may have resulted in pyramidal cell death in the hippocampus. The hippocampal structure in the CA1 region was completely disrupted. Spatial memory and passive avoidance learning were impaired in the MA groups, while recognition memory remained unaffected. Conclusions: The findings suggest that prolonged administration of 5 mg/kg of methamphetamine may be associated with significant inflammasome activation, pyramidal cell death, and mild cognitive decline. Contrary to previous evidence, even lower doses of methamphetamine taken over an extended period could be neurotoxic.

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