Unraveling Dysregulated Cell Signaling Pathways, Genetic and Epigenetic Mysteries of Parkinson's Disease.

Parkinson's disease (PD) is a prevalent and burdensome neurodegenerative disorder that has been extensively researched to understand its complex etiology, diagnosis, and treatment. The interplay between genetic and environmental factors in PD makes its pathophysiology difficult to comprehend, emphasizing the need for further investigation into genetic and epigenetic markers involved in the disease. Early diagnosis is crucial for optimal management of the disease, and the development of novel diagnostic biomarkers is ongoing. Although many efforts have been made in the field of recognition and interpretation of the mechanisms involved in the pathophysiology of the disease, the current knowledge about PD is just the tip of the iceberg. By scrutinizing genetic and epigenetic patterns underlying PD, new avenues can be opened for dissecting the pathology of the disorder, leading to more precise and efficient diagnostic and therapeutic approaches. This review emphasizes the importance of studying dysregulated cell signaling pathways and molecular processes associated with genes and epigenetic alterations in understanding PD, paving the way for the development of novel therapeutic strategies to combat this devastating disease.

Acute Ischemic Stroke in a Patient with Multiple Sclerosis after Initiating Teriflunomide Treatment: A Challenging Case.

Multiple sclerosis is an autoimmune disease of the central nervous system, during which vascular events, including atherosclerosis, are more common and progress faster. Teriflunomide (TFN) is an oral drug that studies have indicated has low side effects alongside high efficiency. In this article, a middle-aged woman with multiple sclerosis was introduced, whose medication was changed to TFN. Thirty-five days later, she presented with focal neurologic symptoms, and investigations reported a lacunar infarction. Having excluded potential causes of acute ischemic stroke, such as vascular and rheumatologic factors, the only identifiable factor was the introduction of a new medication. The process of conclusively attributing TFN as the causative agent requires further clarification in future studies.

The role of neurotransmitters in glioblastoma multiforme-associated seizures.

GBM, or glioblastoma multiforme, is a brain tumor that poses a great threat to both children and adults, being the primary cause of death related to brain tumors. GBM is often associated with epilepsy, which can be debilitating. Seizures and the development of epilepsy are the primary symptoms that have a severe impact on the quality of life for GBM patients. It is increasingly apparent that the nervous system plays an essential role in the tumor microenvironment for all cancer types, including GBM. In recent years, there has been a growing understanding of how neurotransmitters control the progression of gliomas. Evidence suggests that neurotransmitters and neuromodulators found in the tumor microenvironment play crucial roles in the excitability, proliferation, quiescence, and differentiation of neurons, glial cells, and neural stem cells. The involvement of neurotransmitters appears to play a significant role in various stages of GBM. In this review, the focus is on presenting updated knowledge and emerging ideas regarding the interplay between neurotransmitters and neuromodulators, such as glutamate, GABA, norepinephrine, dopamine, serotonin, adenosine, and their relationship with GBM and the seizures induced by this condition. The review aims to explore the current understanding and provide new insights into the complex interactions between these neurotransmitters and neuromodulators in the context of GBM-related seizures.

Neurological Involvements in COVID-19: A hospital-based study.

Objectives: The SARS-CoV-2 pandemic is the most challenging crisis in the contemporary world. Besides severe pulmonary involvement, the disease also has several extrapulmonary manifestations, and new signs and symptoms are associated with it every dayThe present study aimed to inquire about the frequency of neurological manifestations and risk factors of COVID-19. Materials & Methods: This retrospective, descriptive study included patients with neurological involvement admitted to the Alborz University of Medical Sciences academic hospitals from March 2020 to July 2020 with confirmed COVID-19 infection. The data included in the analysis were the patient's demographic information, underlying diseases, neurological manifestations, and laboratory findings. Results: The study included ninety-five patients with a mean age of fifty-nine. Neurological symptoms and signs were observed in 91.6% and 10.5% of the patients, respectively. The most frequently associated neurological symptoms of COVID-19 were fatigue (49.5%), headache (47.4%), and dizziness (45.3%). Furthermore, the most common neurological involvements included gait disorders (6.3%), cerebellar dysfunction (4.2%), and cerebrovascular accidents (3.15%). Positive troponin was shown to be the strongest predictor of neurological signs (OR=21, P=0.017), followed by WBC≥15,000 (OR = 20.75, P=0.018) and a history of respiratory disease (OR=7.42, P=0.007). Conclusion: Neurological symptoms were observed in more than 91% of the patients, while neurological signs were present in 10.5% of the COVID-19 patients. Additionally, positive troponin, WBC≥15,000, and a history of respiratory disease were the strongest predictors of neurological signs.

Efficacy of fibroblast transplantation in the healing of cutaneous leishmaniasis scar: A case report.

Autologous fibroblast transplantation has been proven to be a promising method in wound healing with no side effects. This is the first study aimed to determine the efficacy and safety of autologous fibroblast cell injection to the atrophic scar caused by cutaneous leishmaniasis as an endemic disease in many middle-eastern countries. It causes chronic skin lesions and permanently disfiguring scars. Autologous fibroblasts were obtained from the patient's ear skin and were injected intradermally twice at 2-month intervals. Outcomes were measured using ultrasonography, VisioFace, and Cutometer. No adverse reaction was observed. The results showed improvements in epidermal thickness and density, melanin level, and skin lightening. Moreover, the skin elasticity in the scar area increased after the second transplantation. No improvement was observed in dermal thickness and density. A longer follow-up with more patients is recommended to investigate the effectiveness of fibroblast transplantation better.

Bone mineral density status in patients with recent-onset rheumatoid arthritis.

Background: Osteoporosis is a sizable comorbidity complication in Rheumatoid Arthritis (RA) sufferers. In the current study, the prevalence of osteopenia and osteoporosis in active RA sufferers and the association of disease-related factors of osteoporosis and reduced bone mineral density (BMD) have been examined. Methods: In this cross-sectional study, 300 new-onset symptoms (less than one year) RA patients without a history of glucocorticoids or DMARDs were selected. Biochemical blood measurements and BMD status were performed with dual-energy X-ray absorptiometry. According to the T-scores of the patients, they were divided into three groups: osteoporosis<-2.5, -2.5 < osteopenia <-1, and - 1 < normal. Also, the MDHAQ questionnaire, DAS-28, and FRAX criteria were calculated for all patients. Multivariate logistic regression was used to determine the associated factors of osteoporosis and osteopenia. Results: The Prevalence of osteoporosis and osteopenia was 27% (95%CI:22-32) and 45% (95%CI:39-51), respectively. The multivariate regression analysis showed that age could play a role as an associated factor for spine/hip Osteoporosis and Osteopenia. The female gender is also a predictor of Spine osteopenia Patients with Total hip Osteoporosis were more likely to have higher DAS-28 (OR 1.86, CI 1.16-3.14) and positive CRP (OR 11.42, CI 2.65-63.26). Conclusion: recent-onset RA patients are at risk for osteoporosis and its complications, regardless of using glucocorticoids or DMARDs. Demographic factors (e.g. age and female gender), patients' MDHAQ scores, and disease-related factors(e.g., DAS-28, positive CRP were associated with reduced BMD levels. Therefore, it is recommended that clinicians investigate early BMD measurements to have a reasonable judgment for further interventions. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01200-w.

Masitinib: The promising actor in the next season of the Amyotrophic Lateral Sclerosis treatment series.

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease with high mortality and morbidity rate affecting both upper and lower motor neurons (MN). Muscle force reduction, behavioral change, pseudobulbar affect, and cognitive impairments are the most common clinical manifestations of ALS. The main physiopathology of ALS is still unclear, though several studies have identified that oxidative stress, proteinopathies, glutamate-related excitotoxicity, microglial activation, and neuroinflammation may be involved in the pathogenesis of ALS. From 1995 until October 2022, only Riluzole, Dextromethorphan Hydrobromide (DH) with Quinidine sulfate (Q), Edaravone, and Sodium phenylbutyrate with Taurursodiol (PB/TUDCO) have achieved FDA approval for ALS treatment. Despite the use of these four approved agents, the survival rate and quality of life of ALS patients are still low. Thus, finding novel treatments for ALS patients is an urgent requirement. Masitinib, a tyrosine kinase inhibitor, emphasizes the neuro-inflammatory activity of ALS by targeting macrophages, mast cells, and microglia cells. Masitinib downregulates the proinflammatory cytokines, indirectly reduces inflammation, and induces neuroprotection. Also, it was effective in phase 2/3 and 3 clinical trials (CTs) by increasing overall survival and delaying motor, bulbar, and respiratory function deterioration. This review describes the pathophysiology of ALS, focusing on Masitinib's mechanism of action and explaining why Masitinib could be a promising actor in the treatment of ALS patients. In addition, Masitinib CTs and other competitor drugs in phase 3 CTs have been discussed.

Fistulectomy and primary sphincteroplasty in complex anal fistula treatment: a hospital-based long-term follow-up study.

BACKGROUND: Currently, there is no agreement on the best treatment for complex anal fistulas with the least recurrence and lowest complication rate. The aim of this study was to evaluate the long-term recurrence and incontinence after fistulectomy and primary sphincteroplasty (FIPS) in a group of patients with complex perianal fistula. METHODS: This prospective observational study was done at the colorectal ward of Taleghani Hospital of Tehran from January 2010 to December 2020. Patients with anal fistula who underwent FIPS were studied. After surgery, patients were evaluated regularly by a colorectal surgeon for fistula recurrence and incontinence. Recurrence was described as a new fistula tract formation after the initial cure and failure of healing in the operation site or any purulent discharge from the fistula tract and openings. In addition, the patient's continence was assessed based on the Wexner score. RESULTS: There were 335 patients (66 men and 269 women, mean age 42.74 ± 12.44 years), 191 of them with low fistula and 144 with high fistula. Thirteen patients (3.90%) experienced recurrence (all had a low fistula). Thirty-nine patients (11.64%), 19 patients with high and 20 patients with low fistula, had a Wexner score ≥ 3 during the follow-up. Fifteen patients were lost to follow-up. Male patients (OR = 2.67, 95% CI 0.84, 8.45, p = 0.094, adjusted OR = 4.41, 95% CI 1.05, 18.48, p = 0.042), patients with low fistula (p = 0.001), and recurrent cases had a significantly higher rate of recurrence (OR = 10.38, 95% CI 3.24-33.20 p ≤ 0.001, adjusted OR = 23.36, 95% CI 4.35-125.39, p ≤ 0.001). A significant correlation between body mass index > 35 kg/m2 and incontinence was found (OR = 4.40, 95% CI 1.35, 14.33, p = 0.014). CONCLUSIONS: In the present study, an acceptable healing rate and a low percentage of complications following FIPS were seen in patients with complex anal fistula. Randomized clinical trials with appropriate follow-up duration and sample size comparing different surgical methods in these patients are needed to confirm these results.

Modulation of autophagy by melatonin via sirtuins in stroke: From mechanisms to therapies.

Sirtuins perform an important effect on the neural cell fate following stroke. Several mechanisms that have been correlated with stroke are oxidative stress, apoptosis, necrosis and autophagy. Autophagy is usually regarded as unitary of the neural cell survival mechanisms. Recently, the importance of the sirtuins effect on autophagy by antioxidant agents for stroke treatment mentioned in various studies. One of these agents is melatonin. Melatonin can modulate autophagy by changing on sirtuin pathways. Melatonin and its metabolites adjust various sirtuins pathways related to apoptosis, proliferation, metastases, autophagy and inflammation in case of stroke. In this review, we will discuss about the modulation of autophagy by melatonin via sirtuins in stroke.

Paratubal endosalpingiosis: a case report.

INTRODUCTION: Endosalpingiosis is a rare condition and its pathogenesis and clinical significance are not fully understood. The unfamiliar presentation of this disease can misguide health care professionals. The reports available on this matter describe it as a disease of older age. In the majority of the cases it is an incidental finding in those with other concurrent gynecologic conditions. PRESENTATION OF CASE: Here we report the case of a 14-year-old female who presented with abdominal pain and no specific past medical history. Imaging and physical examination were highly suggestive of appendicitis. With the initial diagnosis of acute abdomen, she underwent surgery. During the surgery gastrointestinal tract organs were found to be normal and in gynecological examination, the ovaries were normal, however the fallopian tube revealed a twisted paratubal cyst which was removed and sent to the laboratory for further investigation. On the basis of the cellular pathology, tubal like epithelium in the cyst was found and patient diagnosed with endosalpingiosis. DISCUSSION: We suggest that in our case, the lesion possibly originated from the metaplasia of coelomic membrane into tubal cells. There are studies suggesting that co-occuring diseases should be considered when the diagnosis of endosalpingiosis is established and further studies are needed in regard to this matter. CONCLUSION: Endosalpingiosis, although being a rare condition, should be included in our differential diagnosis since co-existing comorbidities are a possibility in patients with endosalpingiosis and can be of great importance.