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The aim of this study was to evaluate the death proportion and death risk of COVID-19 hospitalized patients over time and in different surges of COVID-19. This multi-center observational study was conducted from March 21, 2021 to October 3, 2021 which included the alpha and delta SARS-CoV-2 surges occurred in April and August in Tehran, respectively. The risk of COVID-19 death was compared in different months of admission. A total of 270,624 patients with COVID-19, of whom 6.9% died, were admitted to hospitals in Tehran province. Compared to patients admitted in March, a higher risk of COVID-19 death was observed among patients admitted to the hospital in July (HR 1.28; 95% CI 1.17, 1.40), August (HR 1.40; 95% CI 1.28, 1.52), September (HR 1.37; 95% CI 1.25, 1.50) and October (HR 4.63; 95% CI 2.77, 7.74). The ICU death proportion was 36.8% (95% CI: 35.5, 38.1) in alpha surge and increased significantly to 39.8 (95% CI 38.6, 41.1) in delta surge. The risk of COVID-19 death was significantly higher in delta surge compared to alpha surge (HR 1.22; 95% CI 1.17, 1.27). Delta surge was associated with a higher risk of death compared to alpha surge. High number of hospitalizations, a shortage of hospital beds, ICU spaces and medical supplies, poor nutritional status of hospitalized patients, and lack of the intensivist physicians or specialized nurses in the ICU were factors that contributed to the high mortality rate in the delta surge in Iran.

Neuropathic pain is a debilitating complication following spinal cord injury (SCI). Currently, effective treatments for SCI-induced neuropathic pain are highly lacking. This clinical trial aimed to investigate the efficacy of combined intrathecal injection of Schwann cells (SCs) and bone marrow–derived mesenchymal stem cells (BMSCs) in improving SCI-induced neuropathic pain. This study was a parallel-group, randomized, open-label, active-controlled phase II trial with two arms, including treatment and control groups. Patients with complete SCI-induced neuropathic pain in the treatment group received a single combined intrathecal injection of BMSCs and SCs. Study outcome measures were International SCI Pain Basic Data Set (ISCIPBDS) and World Health Organization (WHO) Quality of Life Assessment Instrument (WHOQOL-BREF). A total of 37 (55.2%) and 30 (44.8%) patients in the treatment and control groups were followed up for 6 months, respectively. Significant reductions in mean scores of interference items in the treatment group, including daily activities (P < 0.001), mood (P < 0.001), and sleep (P < 0.001), were found at 6 months after the injection compared with the control one. Similarly, pain frequency (P = 0.002), mean (P = 0.001), and worst (P = 0.001) numeric rating scale (NRS) pain intensity scores showed significant reductions in the treatment group after 6 months compared with the control one. Based on multiple regression analysis controlled for potential confounders, significant associations between changes in all outcome measures over the study period and the treatment group were found. This clinical trial indicated the efficacy of combined cell therapy in improving the neuropathic pain and quality of life in complete SCI patients. Future investigations should evaluate the effects of combination of this strategy with other existing therapies for SCI-induced neuropathic pain. This clinical trial was also registered prospectively at the Iranian Registry of Clinical Trials (IRCT20200502047277N8). Graphical Abstract

Objective Neurological and functional impairments are commonly observed in individuals with spinal cord injury (SCI) due to insufficient regeneration of damaged axons. Exosomes play a crucial role in the paracrine effects of mesenchymal stem cells (MSCs) and have emerged as a promising therapeutic approach for SCI. Thus, this study aimed to evaluate the safety and potential effects of intrathecal administration of allogeneic exosomes derived from human umbilical cord MSCs (HUC-MSCs) in patients with complete subacute SCI. Methods This study was a single-arm, open-label, phase I clinical trial with a 12-month follow-up period. HUC-MSCs were extracted from human umbilical cord tissue, and exosomes were isolated via ultracentrifugation. After intrathecal injection, each participant a underwent complete evaluation, including neurological assessment using the American Spinal Injury Association (ASIA) scale, functional assessment using the Spinal Cord Independence Measure (SCIM-III), neurogenic bowel dysfunction (NBD) assessment using the NBD score, modified Ashworth scale (MAS), and lower urinary tract function questionnaire. Results Nine patients with complete subacute SCI were recruited. The intrathecal injection of allogeneic HUC-MSCs-exosomes was safe and well tolerated. No early or late adverse event (AE) attributable to the study intervention was observed. Significant improvements in ASIA pinprick ( P -value = 0.039) and light touch ( P -value = 0.038) scores, SCIM III total score ( P -value = 0.027), and NBD score ( P -value = 0.042) were also observed at 12-month after the injection compared with baseline. Conclusions This study demonstrated that intrathecal administration of allogeneic HUC-MSCs-exosomes is safe in patients with subacute SCI. Moreover, it seems that this therapy might be associated with potential clinical and functional improvements in these patients. In this regard, future larger phase II/III clinical trials with adequate power are highly required. Trial registration Iranian Registry of Clinical Trials, IRCT20200502047277N1. Registered 2 October 2020, https://en.irct.ir/trial/48765 .

Type 1 Interferons (IFNs) have been associated with positive effects on Coronaviruses. Previous studies point towards the superior potency of IFNβ compared to IFNα against viral infections. We conducted a three-armed, individually-randomized, open-label, controlled trial of IFNβ1a and IFNβ1b, comparing them against each other and a control group. Patients were randomly assigned in a 1:1:1 ratio to IFNβ1a (subcutaneous injections of 12,000 IU on days 1, 3, 6), IFNβ1b (subcutaneous injections of 8,000,000 IU on days 1, 3, 6), or the control group. All three arms orally received Lopinavir/Ritonavir (400 mg/100 mg twice a day for ten days) and a single dose of Hydroxychloroquine 400 mg on the first day. Our utilized primary outcome measure was Time To Clinical Improvement (TTCI) defined as the time from enrollment to discharge or a decline of two steps on the clinical seven-step ordinal scale, whichsoever came first. A total of 60 severely ill patients with positive RT-PCR and Chest CT scans underwent randomization (20 patients to each arm). In the Intention-To-Treat population, IFNβ1a was associated with a significant difference against the control group, in the TTCI; (HR; 2.36, 95% CI 1.10–5.17, P-value = 0.031) while the IFNβ1b indicated no significant difference compared with the control; HR; 1.42, (95% CI 0.63–3.16, P-value = 0.395). The median TTCI for both of the intervention groups was five days vs. seven days for the control group. The mortality was numerically lower in both of the intervention groups (20% in the IFNβ1a group and 30% in the IFNβ1b group vs. 45% in the control group). There were no significant differences between the three arms regarding the adverse events. In patients with laboratory-confirmed SARS-CoV-2 infection, as compared with the base therapeutic regiment, the benefit of a significant reduction in TTCI was observed in the IFNβ1a arm. This finding needs further confirmation in larger studies. Trial Registration Number: ClinicalTrials.gov, NCT04343768. (Submitted: 08/04/2020; First Online: 13/04/2020) (Registration Number: NCT04343768).

Abstract Background Patients with Parkinson’s disease (PD) are at higher risk of COVID-19 infection as most of them are at older age. The goal of this study is to update the pooled prevalence of COVID-19 infection in patients with PD.MethodsTwo researchers systematically searched PubMed, Scopus, EMBASE, Web of Science, Google Scholar, and also gray literature including references of the included studies which were published before September 2021. We extracted data regarding the total number of participants, first author, publication year, the country of origin, mean age, number with COVID-19, symptoms, hospitalization, and death.ResultsWe found 1693 articles by literature search; after deleting duplicates, 798 remained. Thirty articles remained for meta-analysis. The pooled prevalence of COVID-19 infection in PD cases was 5% (95%CI: 4–6%) (I2 = 98.1%, P < 0.001). The pooled prevalence of fever in cases with PD was 4% (95%CI: 2–6%) (I2 = 96%, P < 0.001). The pooled prevalence of cough in cases with PD was 3% (95%CI: 2–4%) (I2 = 95.9%, P < 0.001). The pooled prevalence of hospitalization in cases with COVID-19 infection was 49% (95%CI: 29–52%) (I2: 93.5%, P < 0.001). The pooled prevalence of mortality in COVID-19 cases was 12% (95%CI: 10–14%) (I2 = 97.6%, P < 0.001).ConclusionThe results of this systematic review and meta-analysis show that the pooled prevalence of COVID-19 infection in PD cases is 5% besides hospitalization and mortality rates which are 49% and 12%.

Neuromodulation, the targeted regulation of nerve activity, has emerged as a promising approach for treating various neurological and psychiatric disorders. While deep brain stimulation has shown efficacy, its invasive nature poses substantial risks, including surgical complications and high costs. In contrast, non-invasive neuromodulation techniques, particularly those utilizing magnetic fields (MFs), have gained increasing attention as safer, more accessible alternatives. Magnetothermal stimulation has emerged as an innovative method that enables precise modulation of neuronal ion channels through localized heating induced by interaction of MF with biological tissues. This review discusses the principles of MF-based neuromodulation and highlights the critical role of ion channels in synaptic transmission, and the therapeutic potential of these advanced techniques. Additionally, it highlights key challenges such as spatial targeting precision, safety considerations, and the long-term effects of magnetic exposure on brain function. The findings presente the promise of MF-based neuromodulation as a non-invasive, highly targeted therapeutic strategy for conditions such as epilepsy, movement disorders, and neurodegenerative diseases, with potential applications in chronic pain management and future clinical interventions.

Background Glioblastoma multiforme (GBM) is associated with remarkably poor prognosis, and its treatment is challenging. This investigation aimed to evaluate the safety of suicide gene therapy using allogeneic adipose tissue-derived mesenchymal stem cells (ADSCs) carrying herpes simplex virus-thymidine kinase (HSV-TK) gene for the first time in patients with recurrent GBM. Methods This study was a first-in-human, open-label, single-arm, phase I clinical trial with a classic 3 + 3 dose escalation design. Patients who did not undergo surgery for their recurrence were included and received this gene therapy protocol. Patients received the intratumoral stereotactic injection of ADSCs according to the assigned dose followed by prodrug administration for 14 days. The first dosing cohort (n = 3) received 2.5 × 10 5 ADSCs; the second dosing cohort (n = 3) received 5 × 10 5 ADSCs; the third dosing cohort (n = 6) received 10 × 10 5 ADSCs. The primary outcome measure was the safety profile of the intervention. Results A total of 12 patients with recurrent GBM were recruited. The median follow-up was 16 (IQR, 14-18.5) months. This gene therapy protocol was safe and well tolerated. During the study period, eleven (91.7%) patients showed tumor progression, and nine (75.0%) died. The median overall survival (OS) was 16.0 months (95% CI 14.3–17.7) and the median progression-free survival (PFS) was 11.0 months (95% CI 8.3–13.7). A total of 8 and 4 patients showed partial response and stable disease, respectively. Moreover, significant changes were observed in volumetric analysis, peripheral blood cell counts, and cytokine profile. Conclusions The present clinical trial, for the first time, showed that suicide gene therapy using allogeneic ADSCs carrying the HSV-TK gene is safe in patients with recurrent GBM. Future phase II/III clinical trials with multiple arms are warranted to validate our findings and further investigate the efficacy of this protocol compared with standard therapy alone. Trial registration : Iranian Registry of Clinical Trials (IRCT), IRCT20200502047277N2. Registered 8 October 2020, https://www.irct.ir/ .

Astrocytomas, the most prevalent primary brain tumors, can be divided by histology and malignancy levels into four following types: pilocytic astrocytoma (grade I), diffuse fibrillary astrocytoma (grade II), anaplastic astrocytoma (grade III), and glioblastoma multiforme (grade IV). For high grade astrocytomas (grade III and grade IV), blood vessels formation is considered as the most important property. The distribution of cannabinoid receptors type 1 (CB1) and cannabinoid receptor type 2 (CB2) in blood vessels and tumor tissue of astrocytoma is still controversial. Asrocytoma tissues were collected from 45 patients under the condition of tumor-related neurosurgical operation. The expression of CB1 and CB2 receptors was assessed using immunofluorescence, quantitative real-time RT-PCR and western blotting. The results indicated an increased expression of CB1 receptors in tumor tissue. There was a significant difference in the mount of CB2 receptors in blood vessels. More was observed in the grade III and glioblastoma (grade IV) than astrocytoma of grade II and control. This study suggested that, the expression increase of cannabinoid receptors is an index for astrocytoma malignancy and can be targeted as a therapeutic approach for the inhibition of astrocytoma growth among patients.

The acceptance rate in the ICNJ was 46% (rejection rate: 54%) in 2022 and the average peer review time was around three weeks. Overall, 32 papers, including 16 (50%) original articles, 8 (25%) case reports, 6 (18.75%) review articles, and 2 (6.25%) letters to the Editor were published in 2022. The most published topics in 2022 were COVID-19 (6 papers), mental health, and cancers. Most publications focused on COVID-19, as a common topic worldwide. Some of the articles were published as editorial letters.1,2 There were papers about COVID-19 and mental health1 and COVID-19 and headache.2 Six review papers were about “Upper Extremity Function After Stroke”, “Neurological Complications of COVID-19”, “Neuropathic Pain”, “Public Acceptance of the COVID-19 Vaccination”, “Consciousness in Sleep” and Molecular and Cellular Basis in Neurodegenerative Diseases”.3-8 Moreover, ICNJ presents eight rare, complex and challenging neurological and neurosurgical cases (“Fahr Syndrome and Syncope”, “Acute Hemifacial by Haemorrhagic Schwannoma”, “Multilevel Lumbar Spondylolisthesis”, “Convulsion Presentation of Parietal Meningioma”, “Coil Embolization in Pseudoaneurysm of the Supraglenoid Internal Carotid Artery”, “Physical Therapy for Erectile Dysfunction and Sensation”, “Traumatic Unilateral Basal Ganglia Haemorrhage”, and “Parenchymal Infarction After Subacute Subdural Hematoma Evacuation”).9-16 The editors and editorial board members of the journal believe that the publication of these cases can help develop good hypotheses for further studies in the future. Sixteen published original articles present new and novel assessments, diagnostic methods, prevention, treatment, and approaches of neurological disease, and valuable epidemiological features and findings to be used worldwide.17-32 The International Clinical Neuroscience Journal is supported by Universal Scientific Education and Research Network (USERN). The goal of (ICNJ) is to continue publishing high quality and novel studies especially in areas of tissue engineering, molecular biology, personalized medicine, degenerative diseases and neuromodulation. We would like to invite all researchers from around the world to contribute to this journal. We appreciate the contributions of all the researchers and scientists who trusted the ICNJ.

BackgroundCoronavirus infection is a novel respiratory disease affecting people across the world. Although the majority of patients present with fever, dyspnea, cough, or myalgia, various signs and symptoms have been reported for this disease. Recently, neurological symptoms have been noticed in patients with COVID-19 with unknown etiology. However, the occurrence of strokes in young and middle aged patients with COVID-19 is not fully explained.MethodsIn this series, six patients younger than 55 years of age with diagnosis of stroke and a confirmed diagnosis of COVID-19 were evaluated for symptoms, lab data, imaging findings, and outcomes from March 2020 to the end of April 2020 from all stroke cases in a tertiary academic hospital. Patients older than 55 and all others who had evidence of cardiac abnormalities (arrhythmia/valvular) were excluded.ResultsFever, myalgia, cough, and dyspnea were the most common clinical symptoms noted in 66.66% (4/6), 66.66% (4/6), 50% (3/6), and 50% (3/6) of the patients, respectively. The mean ± standard deviation (SD) of National Institutes of Health Stroke Scale (NIHSS) for the patient was 10.16 ± 7.13 (ranged 5–24). The most involved area was middle cerebral artery (MCA) (five in MCA versus one in basal ganglia) and the majority of our patients had a low lung involvement score (mean ± SD: 13.16 ± 6.49 out of 24). Finally, one patient was deceased and rest discharged.ConclusionStroke may be unrelated to age and the extent of lung involvement. However, different factors may play roles in co-occurrence of stroke and COVID-19 and its outcome. Future studies with long-term follow-up and more cases are needed to assess prognostic factors.