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Ras-related C3 botulinum toxin substrate 1 (Rac1) is a small GTPase belonging to the Rho family. It acts as a binary molecular switch regulating several cellular functions, including cell adhesion and migration. Malfunctions due to the P29S mutation in Rac1 increase the stability of the activated form of Rac1. This sustained activation can drive aberrant cellular processes associated with cancer, such as cell proliferation, survival, and migration. Therefore, finding an inhibitor that can inhibit the mutant form of the protein is very important. Rhein, a natural compound with diverse pharmacological properties, has been studied in relation to Rac1. However, specific interactions between Rhein and Rac1 have not been examined. In this study, we investigated the potential of Rhein, a natural compound, as an inhibitor of two forms of Rac1: the wild type and the P29S mutation, using molecular dynamics simulations. Results indicated that the P29S mutation led to structural changes in the Rac1 protein, which resulted in greater accessibility of the Rhein to the active site. In addition, the binding energy of Rhein to mutant Rac1 was more negative than the native protein. Therefore, it seems that the Rhein has a better inhibitory effect on the P29S-mutated form of the Rac1 protein.
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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 .
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Exossomos , Injeções Espinhais , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Traumatismos da Medula Espinal , Cordão Umbilical , Humanos , Traumatismos da Medula Espinal/terapia , Exossomos/metabolismo , Masculino , Feminino , Adulto , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Pessoa de Meia-Idade , Transplante de Células-Tronco Mesenquimais/métodos , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Cordão Umbilical/citologia , Transplante Homólogo/métodos , Adulto JovemRESUMO
Multiple sclerosis (MS) is a chronic neurodegenerative, inflammatory, and demyelinating disease of the central nervous system (CNS). Current medicines are not sufficient to control the inflammation and progressive damage to the CNS that is known in MS. These drawbacks highlight the need for novel treatment options. Cell therapy can now be used to treat complex diseases when conventional therapies are ineffective. Mesenchymal stem cells (MSCs) are a diverse group of multipotential non-hematopoietic stromal cells which have immunomodulatory, neurogenesis, and remyelinating capacity. Their advantageous effects mainly rely on paracrine, cell-cell communication and differentiation properties which introduced them as excellent candidates for MS therapy. Exosomes, as one of the MSCs secretomes, have unique properties that make them highly promising candidates for innovative approach in regenerative medicine. This review discusses the therapeutic potential of MSCs and their derived exosomes as a novel treatment for MS, highlighting the differences between these two approaches.
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Exossomos , Células-Tronco Mesenquimais , Esclerose Múltipla , Humanos , Células-Tronco Mesenquimais/metabolismo , Exossomos/metabolismo , Esclerose Múltipla/terapia , Esclerose Múltipla/patologia , Esclerose Múltipla/metabolismo , Transplante de Células-Tronco Mesenquimais , Animais , Comunicação CelularRESUMO
OBJECTIVE: Malignant gliomas constitute the most common type of primary malignant brain tumors. Most previous studies have evaluated the epidemiology of malignant gliomas in developed countries. Hence, there is a lack of evidence in this regard from developing countries. This study is the first epidemiological report on the status of malignant glioma in Iran between 2009 and 2017. METHODS: Data from the Iranian National Population-based Cancer Registry (covering 98% of the Iranian population) on CNS tumors recorded from 2009 to 2017 were used for analysis. Age-adjusted incidence rates were calculated by sex, tumor histology, tumor site, and year of diagnosis. Trend analysis of incidence rates was also performed. Survival data were recorded and the Cox proportional hazards model was used to evaluate underlying risk factors. RESULTS: A total of 8484 patients were diagnosed with malignant glioma between 2009 and 2017 in Iran. The overall age-adjusted incidence rate of malignant gliomas over the 9-year period was 1.71 per 100,000 persons. The most common histology of malignant gliomas was glioblastoma (81.4%). A significant increase in the incidence of malignant gliomas was found between 2009 and 2012. The median overall survival was 13.0 (95% CI 12.6-13.5) months over the study period. Older age groups, higher tumor grade, male sex, the first half of the study period, and receiving no treatment were significantly associated with worse prognoses. CONCLUSIONS: This study is the latest epidemiological report on the status of malignant gliomas in Iran. Although the overall incidence rate was lower than the rates in developed countries, several findings were consistent with those in prior reports.
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RATIONALE: Probiotics have beneficial effects on the nervous system by modulating the gut-brain axis. Additionally, vitamin D supplementation presents a potential way for ameliorating neuropsychological disorders, particularly in regions with a high prevalence of vitamin D deficiency. OBJECTIVES: The current clinical trial aimed to investigate the role of co-administered supplementation of probiotics and Vitamin D on the different inflammatory aspects of patients with Parkinson's disease. METHODS: Forty-six patients with PD were recruited From the Functional Neurosurgery Research Center, Tehran, Iran. These patients were randomly allocated to one of the two treatment groups: Group A, who received probiotic/vitamin D supplements (n = 23), and Group B who received placebo capsules (n = 23) for 12 weeks. As primary outcomes, Interferon-Gamma (IFN-γ), interleukin 1 beta (IL-1ß), IL-6, IL-10, Tumor Necrosis Factor-Alpha (TNF-α), total antioxidant capacity (TAC), and malondialdehyde (MDA) in serum were evaluated at the baseline and the end of the trial. Moreover, Additional questionnaire-based factors including gastrointestinal symptom rating scale (GSRS), Beck Anxiety Inventory (BAI), and Unified Parkinson's Disease Rating Scale (UPDRS) were evaluated. RESULTS: Our findings demonstrated that the consumption of probiotic/vitamin D supplements leads to a significant decrease in IL-1ß, INF-γ, IL-6, and MDA levels, while showing a significant increase in IL-10 and TAC levels compared to the placebo group (P < 0.05). Additionally, it leads to a significant decrease in the disease severity, anxiety, and gastrointestinal problems in PD patients in comparison to the placebo group (P < 0.05). CONCLUSIONS: Given the acknowledged role of inflammation in the pathogenesis of Parkinson's disease on one hand, and the recognized anti-inflammatory and antioxidant effects associated with probiotics and vitamin D on the other hand, the concurrent administration of probiotics and vitamin D supplements emerges as a promising and potentially effective treatment option for individuals with PD.
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Doença de Parkinson , Probióticos , Vitamina D , Humanos , Probióticos/administração & dosagem , Masculino , Feminino , Vitamina D/administração & dosagem , Vitamina D/sangue , Pessoa de Meia-Idade , Idoso , Irã (Geográfico) , Índice de Gravidade de Doença , Método Duplo-Cego , Suplementos Nutricionais , Citocinas/sangue , Antioxidantes/administração & dosagem , Resultado do TratamentoRESUMO
Cellular ACE2 (cACE2), a vital component of the renin-angiotensin system (RAS), possesses catalytic activity to maintain AngII and Ang 1-7 balance, which is necessary to prevent harmful effects of AngII/AT2R and promote protective pathways of Ang (1-7)/MasR and Ang (1-7)/AT2R. Hemostasis of the brain-RAS is essential for maintaining normal central nervous system (CNS) function. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a viral disease that causes multi-organ dysfunction. SARS-CoV-2 mainly uses cACE2 to enter the cells and cause its downregulation. This, in turn, prevents the conversion of Ang II to Ang (1-7) and disrupts the normal balance of brain-RAS. Brain-RAS disturbances give rise to one of the pathological pathways in which SARS-CoV-2 suppresses neuroprotective pathways and induces inflammatory cytokines and reactive oxygen species. Finally, these impairments lead to neuroinflammation, neuronal injury, and neurological complications. In conclusion, the influence of RAS on various processes within the brain has significant implications for the neurological manifestations associated with COVID-19. These effects include sensory disturbances, such as olfactory and gustatory dysfunctions, as well as cerebrovascular and brain stem-related disorders, all of which are intertwined with disruptions in the RAS homeostasis of the brain.
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Encéfalo , COVID-19 , Sistema Renina-Angiotensina , SARS-CoV-2 , Transdução de Sinais , Sistema Renina-Angiotensina/fisiologia , Humanos , COVID-19/metabolismo , COVID-19/complicações , Encéfalo/metabolismo , Transdução de Sinais/fisiologia , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , PandemiasRESUMO
INTRODUCTION: This study assessed the incidence and severity of side effects associated with coronavirus disease 2019 (COVID-19) vaccination among healthcare workers registered with the Medical Council of the Islamic Republic of Iran. METHODOLOGY: A retrospective cohort study was conducted on the healthcare workers focusing on the side-effects of COVID-19 vaccines from March to June 2021. Data were collected using online questionnaires. Multivariable logistic regression was used to assess the association between side effects of the vaccines and demographic variables, comorbidities, vaccine type, and history of COVID-19. RESULTS: Out of 42,018 people who were included, 55.85% reported at least one side effect after receiving the first vaccine dose. 4.59% of those with side effects sought diagnostic intervention or were referred to treatment centers. Multivariable logistic regression indicated that being a woman, higher education, having a history of COVID-19 infection, and having comorbidities increased the risk of side effects. The AstraZeneca vaccine significantly increased the risk of side effects compared to the Sputnik vaccine, while the Sinopharm vaccine decreased this risk. The risk of developing a side effect decreased with age. The risk of moderate and severe side effects was significantly associated with gender, younger age, comorbidities, and a history of COVID-19 infection. Moderate and severe side effects were less reported by those who received the Sinopharm vaccine. CONCLUSIONS: Clinical complications after COVID-19 vaccination, directly or indirectly caused by the vaccines, are common. However, the benefits of COVID-19 vaccines greatly outweigh the risk of reversible side effects, especially among the high-risk population.
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Vacinas contra COVID-19 , COVID-19 , Pessoal de Saúde , Humanos , Irã (Geográfico)/epidemiologia , Feminino , Masculino , Estudos Retrospectivos , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/administração & dosagem , Pessoal de Saúde/estatística & dados numéricos , Adulto , Pessoa de Meia-Idade , COVID-19/prevenção & controle , COVID-19/epidemiologia , SARS-CoV-2/imunologia , Adulto Jovem , Vacinação/estatística & dados numéricos , Vacinação/efeitos adversosRESUMO
Background: Malignant gliomas are known with poor prognosis and low rate of survival among brain tumors. Resection surgery is followed by chemotherapy and radiotherapy in treatment of gliomas which is known as the conventional treatment. However, this treatment method results in low survival rate. Vaccination has been suggested as a type of immunotherapy to increase survival rate of glioma patients. Different types of vaccines have been developed that are mainly classified in two groups including peptide vaccines and cell-based vaccines. However, there are still conflicts about which type of vaccines is more efficient for malignant glioma treatment. Methods: Phase â /â ¡ clinical trials which compared the efficacy and safety of various vaccines with conventional treatments were searched in databases through November 2022. Overall survival (OS) rate, progression free survival (PFS), and OS duration were used for calculation of pooled risk ratio (RR). In addition, fatigue, headache, nausea, diarrhea, and flu-like syndrome were used for evaluating the safety of vaccines therapy in glioma patients. Results: A total of twelve articles were included in the present meta-analysis. Comparison of OS rate between vaccinated groups and control groups who underwent only conventional treatments showed a significant increase in OS rate in vaccinated patients (I2 = 0%, RR = 11.17, 95% CI: 2.460-50.225). PFS rate was better in vaccinated glioma patients (I2 = 83%, RR = 2.87, 95% CI: 1.63-5.03). Assessment of safety demonstrated that skin reaction (I2 = 0.0%, RR = 3.654; 95% CI: 1.711-7.801, p-value = 0.0058) and flu-like syndrome were significantly more frequent adverse effects win vaccinated groups compared to the control group. Subgroup analysis also showed that vaccination leads to better OS duration in recurrent gliomas than primary gliomas, and in LGG than HGG (p-value = 0). On the other hand, personalized vaccines showed better OS duration than non-personalized vaccines (p-value = 0). Conclusion: Vaccination is a type of immunotherapy which shows promising efficacy in treatment of malignant glioma patients in terms of OS, PFS and duration of survival. In addition, AFTV, peptide, and dendritic cell-based vaccines are among the most efficient vaccines for gliomas. Personalized vaccines also showed considerable efficacy for glioma treatments.
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The complex impacts of prolonged morphine exposure continue to be a significant focus in the expanding area of addiction studies. This research investigates the effectiveness of a combined treatment using Cabergoline and Mdivi-1 to counteract the neuroadaptive changes caused by in vitro morphine treatment. The impact of Methadone, Cabergoline, and a combination of Cabergoline and Mdivi-1 on the cellular and molecular responses associated with Morphine-induced changes was studied in human Neuroblastoma (SK-N-MC) and Glioblastoma (U87-MG) cell lines that were exposed to prolong Morphine treatment. Cabergoline and Mdivi-1 combined treatment effectively influenced the molecular alterations associated with neuroadaptation in chronic morphine-exposed neural cells. This combination therapy normalized autophagy and reduced oxidative stress by enhancing total-antioxidant capacity, mitigating apoptosis, restoring BDNF expression, and balancing apoptotic elements. Our research outlines morphine's dual role in modulating mitochondrial dynamics via the dysregulation of the autophagy-apoptosis axis. This emphasizes the significant involvement of DRP1 activity in neurological adaptation processes, as well as disturbances in the dopaminergic pathway during in vitro chronic exposure to morphine in neural cells. This study proposes a novel approach by recommending the potential effectiveness of combining Cabergoline and Mdivi-1 to modulate the neuroadaptations caused by morphine. Additionally, we identified BDNF and PCNA in neural cells as potential neuroprotective markers for assessing the effectiveness of drugs against opioid toxicity, emphasizing the need for further validation. The study uncovers diverse effects observed in pretreated morphine glioblastoma cells under treatment with Cabergoline and methadone. This highlights the potential for new treatments in the DRD2 pathway and underscores the importance of investigating the interplay between autophagy and apoptosis to advance research in managing cancer-related pain. The study necessitates an in-depth investigation into the relationship between autophagy and apoptosis, with a specific emphasis on protein interactions and the dynamics of cell signaling.
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Apoptose , Autofagia , Cabergolina , Morfina , Quinazolinonas , Humanos , Autofagia/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Morfina/farmacologia , Cabergolina/farmacologia , Linhagem Celular Tumoral , Quinazolinonas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Dinâmica Mitocondrial/efeitos dos fármacos , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Glioblastoma/patologia , Fator Neurotrófico Derivado do Encéfalo/metabolismoRESUMO
Assessing the impact of coronavirus disease 2019 (COVID-19) reveals unique challenges for pregnant women, who experience distinct clinical manifestations and health outcomes compared to their non-pregnant counterparts. We aimed to evaluate the clinical features, disease severity, and health outcomes of COVID-19 in pregnant women and compare them to those of non pregnant women. In this population-based study, we included all women diagnosed with COVID-19 across the province of Tehran during the first two years of the epidemic. Descriptive statistics, the chi-squared test, and the logistic regression model were applied. Overall, 79,338 non-pregnant women and 3249 pregnant women diagnosed with COVID-19 were included. Pregnant women were most commonly in the age group of 25 - 34 years (54%, n = 1758), while the age group of 34-44 had the highest representation among non-pregnant women (56%, n = 44,492). After accounting for age and comorbidities, pregnancy was associated with an increased risk of requiring intensive care (odds ratio [OR] 1.38, confidence interval [CI] 1.223 - 1.564). However, the probability of dying due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was lower in pregnant women compared to non-pregnant women (OR 0.55, CI 0.394-0.793). Cough (41%) and fever (30%) were the most frequent clinical presentations in pregnant women, whereas cough (57%) and muscle ache (38%) were the most common symptoms in non-pregnant women. Furthermore, diarrhea (P < 0.001) and skin lesions (P < 0.001) were reported more frequently by pregnant patients than non-pregnant patients. A significant prevalence of diabetes (P < 0.001), hypertension (P < 0.001), cancers (P < 0.001), and chronic hematological diseases (P < 0.001) was observed in pregnant patients. In conclusion, COVID-19-infected pregnant women exhibit different clinical manifestations and a more severe clinical course but have better health outcomes compared to their non-pregnant counterparts.
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COVID-19 , Complicações Infecciosas na Gravidez , SARS-CoV-2 , Índice de Gravidade de Doença , Humanos , COVID-19/epidemiologia , Gravidez , Feminino , Adulto , Estudos Transversais , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/virologia , Irã (Geográfico)/epidemiologia , Adulto Jovem , Comorbidade , Pessoa de Meia-IdadeRESUMO
BACKGROUND AND OBJECTIVES: No study has evaluated the efficacy of using preoperative antiseptic dressings in reducing the rate of surgical site infection (SSI) in spine surgery thus far. To investigate the efficacy of the use of preoperative povidone-iodine-impregnated antiseptic dressings in patients undergoing instrumented posterolateral lumbar spinal fusion. METHODS: This was a randomized, nonblinded, active-controlled, parallel-group clinical trial. Patients were randomly assigned to the 2 study groups, including treatment and control. Patients in the treatment group received povidone-iodine-impregnated antiseptic dressing applied to the anticipated incision site 12 hours before the operation. The control group merely received the standard perioperative care with no additional intervention or placebo. Patients were followed up for 90 days, and SSIs were recorded. RESULTS: A total of 200 patients were included in this study (100 in each arm). Three cases of SSI were observed in the treatment group compared with 12 in the control one. A significant reduction in the postoperative rate of SSI was observed in the treatment group compared with the control one (P = .029). In addition to study intervention (P = .029), body mass index (P = .005), smoking status (P = .005), duration of the procedure (P = .003), American Society of Anesthesiologists class (P = .002), and diabetes mellitus (P < .001) were significantly associated with the postoperative rate of SSI. CONCLUSION: To the best of our knowledge, this study for the first time showed that preoperative use of antiseptic dressings is significantly effective in reducing the rate of SSI in instrumented posterior lumbar spinal fusion surgery. Future studies are warranted to evaluate the efficacy of different preparations or the effectiveness of the present one in patients undergoing spine procedures with other surgical characteristics.
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Sudden sensorineural hearing loss (SSNHL) is defined as hearing loss of more than 30 dB in less than 72 h. SSNHL is a frequent complaint and an emergency in otolaryngology. Various biomarkers have been used to determine the prognosis of SSNHL. This systematic review and meta-analysis aims to evaluate the relationship between the different biomarkers and the prognosis of SSNHL. We searched English-language literature up to October 2022 in four databases, including PubMed, Google Scholar, Cochrane, and Science Direct. This search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. This study was reported in the International Prospective Register of Systematic Reviews (PROSPERO) database (ID = CRD42022369538). All studies examining the role of neutrophil to lymphocyte ratio (NLR) concluded that higher NLR is associated with a worse prognosis. The results of studies regarding the relationship between platelet to lymphocyte ratio (PLR) and tumor necrosis factor (TNF) are controversial. Other factors shown to be associated with SSNHL include Glycated hemoglobin (HbA1C), blood glucose, iron levels, serum endocan, salusin-beta, and bone turnover biomarkers. This meta-analysis showed that PLR, NLR, and neutrophils were significantly different between recovered and non-recovered patients. PLR, NLR, and neutrophil count are reliable tools to assess the prognosis of patients with SSNHL.
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Perda Auditiva Neurossensorial , Perda Auditiva Súbita , Humanos , Biomarcadores , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Súbita/diagnóstico , Linfócitos , Neutrófilos , PrognósticoRESUMO
Background: Percutaneous transforaminal endoscopic discectomy (PTED) has become popular over the years due to its safety and low invasiveness. This surgery can be performed with different anesthesia techniques; however, the extent to which the surgeon and patient are satisfied with the analgesia is debatable. Objectives: This study investigated the efficiency of the S1 transforaminal epidural block. Methods: This retrospective study was conducted on 60 patients with L4 - L5 lumbar disc herniation who underwent PTED under the S1 transforaminal epidural block. All patients had clinical symptoms associated with unilateral radiculopathy and were candidates for surgery. Percutaneous transforaminal endoscopy and S1 epidural block were performed by a surgeon for all patients. Results: Of the 60 evaluated cases, 61.7% and 38.3% were female and male, respectively, with a mean age of 42.98 ± 10.79 years. The mean pain score before surgery was 7.83 ± 0.69, which decreased to 2.58 ± 0.65 during surgery and 0.50 ± 0.50 48 hours after surgery (P < 0.001). The mean duration of operation in these patients was 58.58 ± 16.95 minutes, and the mean onset time was 10.08 ± 3.12 minutes. Moreover, the mean bleeding was 124.17 ± 25.20 cc. Conclusions: The PTED with S1 epidural anesthesia is a simple, safe, and effective method that causes good analgesia during the operation and cooperates well with the surgeon in neurological monitoring due to patient consciousness.
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Lumbar spinal stenosis (LSS) is a prevalent cause of leg and back pain. In the youth, LSS is not common and mainly results from hereditary musculoskeletal disorders. Moreover, spinal fusion is a surgical approach to the treatment of LSS. Entrapment of surgical tools due to breakage is a rare yet important phenomenon in such operations. Therefore, neurological sequelae of these events need to be explored. The case was a 24-year-old male complaining of local back pain. Initially, he was diagnosed with LSS at L4 and L5. After the fusion of the vertebrae by the posterior spinal fusion (PSF) method, the patient's pain was resolved. However, the subject complained of worsening local back pain limiting his ability to do routine tasks. A few years later, radiographical evaluations indicated the possible presence of a surgical tool that could not be removed via surgery. During a third operation, the object was removed, and the patient's symptoms recovered. Immediate removal of entrapped surgical objects is necessary due to risks associated with migration and central nervous system damage. Comparing our results to other similar reports, we conclude that in cases of foreign object entrapment, neurological sequelae may be nonexistent or progressively worsen. Also, sequelae emerge either soon after the operation or emerge later. This complicates the diagnosis of such events and the decision of whether to subject the patient to additional neurosurgical operations to remove the tool. These variations may be observed due to the moving of the entrapped tool. Follow-up of neurological sequelae in spinal surgery patients is recommended.
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Neurosurgical practitioners undergo extensive and prolonged training to acquire diverse technical proficiencies, while neurosurgical procedures necessitate a substantial amount of pre-, post-, and intraoperative clinical data acquisition, making decisions, attention, and convalescence. The past decade witnessed an appreciable escalation in the significance of artificial intelligence (AI) in neurosurgery. AI holds significant potential in neurosurgery as it supplements the abilities of neurosurgeons to offer optimal interventional and non-interventional care to patients by improving prognostic and diagnostic outcomes in clinical therapy and assisting neurosurgeons in making decisions while surgical interventions to enhance patient outcomes. Other technologies including augmented reality, robotics, and virtual reality can assist and promote neurosurgical methods as well. Moreover, they play a significant role in generating, processing, as well as storing experimental and clinical data. Also, the usage of these technologies in neurosurgery is able to curtail the number of costs linked with surgical care and extend high-quality health care to a wider populace. This narrative review aims to integrate the results of articles that elucidate the role of the aforementioned technologies in neurosurgery.
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Today, with the development of neuroscience and the discovery of new secrets of the brain, the social sciences, including law, have made significant progress with the help of new findings in this science. One of the significant applications of neuroscience in modern criminal law is the explanation of the neurological dimensions of human free will, which in addition to creating a profound and scientific approach to the definition of this important element of criminal responsibility, can help ascertain the loss of free will causes. To this end, the present study is an attempt to answer this question in the context of the Iranian criminal justice system: What are the core causes of the loss of free will from the perspective of neurolaw? The paper strives to take an appropriate step toward the development of criminal justice. In this study, we found that mental disorders, coercion, drunkenness, somnambulism, and error are the core causes that can be assessed in particular ways using EEG and fMRI techniques, however, each with limitations.
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Criminosos , Transtornos Mentais , Humanos , Direito Penal , Irã (Geográfico) , Autonomia PessoalRESUMO
BACKGROUND: Patients with glioblastoma multiforme (GBM) and other patients with cancer are at a greater risk of developing severe complications as a result of coronavirus disease 2019 (COVID-19) infection. Therefore, it is crucial to adjust therapeutic approaches to reduce exposure and complications and achieve the most appropriate treatment outcomes. OBJECTIVE: Our goal was to help physicians to make decisions based on the latest data in the literature. METHOD: We provide a comprehensive review of the literature on the current issues of GBM and COVID-19 infection. RESULTS: The mortality of patients with diffuse glioma as a result of COVID-19 infection was 39%, which is higher than in the general population. The statistics showed that 84.5% of patients with diagnosed brain cancer (mostly GBM) and 89.9% of their caregivers received COVID-19 vaccines. The decision to apply different therapeutic approaches must be made individually based on age, tumor grade, molecular profile, and performance status. The advantages and disadvantages of adjuvant radiotherapy and chemotherapy after the surgery should be evaluated carefully. In the setting of the follow-up period, special considerations must be considered to minimize COVID-19 exposure. CONCLUSIONS: The pandemic altered medical approaches worldwide, and the management of patients in an immunocompromised state, such as patients with GBM, is challenging; therefore, special considerations must be considered.
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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 × 105 ADSCs; the second dosing cohort (n = 3) received 5 × 105 ADSCs; the third dosing cohort (n = 6) received 10 × 105 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/ .
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Neoplasias Encefálicas , Glioblastoma , Transplante de Células-Tronco Hematopoéticas , Humanos , Glioblastoma/genética , Glioblastoma/terapia , Irã (Geográfico) , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patologia , Recidiva Local de Neoplasia/terapia , Recidiva Local de Neoplasia/patologia , Terapia Genética/métodosRESUMO
The spinal hydatid cyst is a benign pathology but has considerable morbidity. It should be considered as a differential diagnosis in patients having signs and symptoms of spinal compression, particularly in endemic areas.
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Introduction: The prognosis for glioblastoma multiforme (GBM), a malignant brain tumor, is poor despite recent advancements in treatments. Suicide gene therapy is a therapeutic strategy for cancer that requires a gene to encode a prodrug-activating enzyme which is then transduced into a vector, such as mesenchymal stem cells (MSCs). The vector is then injected into the tumor tissue and exerts its antitumor effects. Case presentation: A 37-year-old man presented to our department with two evident foci of glioblastoma multiforme at the left frontal and left parietal lobes. The patient received an injection of bone marrow-derived MSCs delivering the herpes simplex virus thymidine kinase (HSV-tk) gene to the frontal focus of the tumor, followed by ganciclovir administration as a prodrug for 14 days. For follow-up, the patient was periodically assessed using magnetic resonance imaging (MRI). The growth and recurrence patterns of the foci were assessed. After the injection on 09 February 2019, the patient's follow-up appointment on 19 December 2019 MRI revealed a recurrence of parietal focus. However, the frontal focus had a slight and unremarkable enhancement. On the last follow-up (18 March 2020), the left frontal focus had no prominent recurrence; however, the size of the left parietal focus increased and extended to the contralateral hemisphere through the corpus callosum. Eventually, the patient passed away on 16 July 2020 (progression-free survival (PFS) = 293 days, overall survival (OS) = 513 days). Conclusion: The gliomatous focus (frontal) treated with bone marrow-derived MSCs carrying the HSV-TK gene had a different pattern of growth and recurrence compared with the non-treated one (parietal). Trial registration: IRCT20200502047277N2. Registered 10 May 2020-Retrospectively registered, https://eng.irct.ir/trial/48110.