Safety of Intraparenchymal Injection of Allogenic Placenta Mesenchymal Stem Cells Derived Exosome in Patients Undergoing Decompressive Craniectomy Following Malignant Middle Cerebral Artery Infarct, A Pilot Randomized Clinical Trial.

Background: Malignant middle cerebral artery infarct (mMCAI) largely contributes to high mortality and physical disability among adults. Surviving individuals may not have proper outcomes and suffer from severe lasting disabilities. Utilization of stem cells and paracrine factor for regenerative purposes is considered as a potential strategy for patients with neurological deficits. While preclinical stroke studies have shown that mesenchymal stem cells (MSCs) reduce post-treatment neurological deficits and prevent disability and also promote recovery, few randomized clinical trials (RCT) have assessed exosome therapy in humans. Methods: In this RCT, we assessed the safety of intraparenchymal injection placenta MSC-derived Exosome in mMCAI patients with average age of 62 years between January, 2019, till September, 2020. The study was done in a single-center as an open-label RCT, with a 3-months follow-up. Primary outcomes assessed the safety and also disability indexes were followed. Results: Five mMCAI patients were included with mean NIHSS: 17.6 ± 5.02. The mean MRS was 3.25 ± 0.95 in three patients. No serious adverse events were observed. Hematoma or local reaction as excessive edema were not seen at the site of injection. Conclusions: Intraparenchymal implantation of MSC-EXO showed no post-interventional adverse effects in five ischemic stroke patients. It is proposed Local injection Exosome treatment following mMCAI can be safe and in future, it would be applied as a supportive, restorative and preventive treatment in patients who suffer from acute ischemic stroke and post ischemic disability.

A systematic review of extracellular vesicles as non-invasive biomarkers in glioma diagnosis, prognosis, and treatment response monitoring.

The present systematic review was done to investigate the possible application of Extracellular vesicles (EVs) in the diagnosis, prognosis, and treatment response monitoring of gliomas using available literature to wrap up the final applicable conclusion in this regard. we searched PubMed/MEDLINE, Scopus, and ISI Web of Science databases. Authors evaluated the quality of the included studies by the QUADAS-2 tool. In total, 2037 published datasets were retrieved through systematic search. Upon screening for eligibility, 35 datasets were determined as eligible. Exosome was the EV-subtype described in the majority of studies, and most datasets used serum as the primary EVs isolation source. EVs isolation was primarily conducted by ultracentrifugation. 31 datasets reported that EVs hold considerable potential for being used in diagnostics, with the majority reporting different types of miRNAs as biomarkers. Besides, 8 datasets reported that EVs could be a potential source of prognostic biomarkers. And finally, 3 datasets reported that EVs might be a reliable strategy for monitoring therapy response in glioma patients. According to the findings of the current systematic review, it seems that miR-301, miR-21, and HOTAIR had the highest diagnostic accuracy. However, heterogeneous and limited evidence regarding prognosis and treatment response monitoring precludes us from drawing a practical conclusion regarding EVs.

Preoperative Mechanical Bowel Evacuation Reduces Intraoperative Bleeding and Operation Time in Spinal Surgery.

STUDY DESIGN: Randomized clinical trial. PURPOSE: In this study, we evaluated the effect of mechanical evacuation of the bowels prior to operation on intraoperative bleeding. OVERVIEW OF LITERATURE: Bleeding is the most significant complication in patients undergoing spinal surgery. METHODS: We randomly divided 108 individuals planned to undergo spinal surgery into two age-, sex-, and co-morbidity (especially preoperative hemoglobin [Hb])-matched groups of 54. The treatment group was administered polyethylene glycol (PEG) before the operation, whereas the control group was not. The exact amount (mL) of bleeding during operation, operative time, and approximate amount of blood transfused were recorded. The volume of bleeding and Hb level were also recorded 24 and 48 hours postoperatively. RESULTS: T-tests revealed that intraoperative bleeding, the volume of transfusion, and operative time were significantly lower in the treatment group than in the control group. Statistically significant correlations of intraoperative bleeding with age, body mass index (BMI), preoperative Hb levels, operative time, the volume of transfusion, hospitalization time, and 24- and 48-hour postoperative bleeding were observed (p =0.001, all). Repeated measures analysis of covariance after adjusting the covariate variables revealed that the volume of bleeding showed a near-significant trend in the treatment group compared with that in the control group (p =0.056). Diabetic females had the highest bleeding amount between the groups (p =0.03). Bleeding was higher in patients with higher BMI (p =0.02) and was related to operative time (p =0.001) in both the groups. CONCLUSIONS: Preoperative gastrointestinal tract evacuation by PEG administration can decrease intraoperative bleeding in spinal surgeries; however, more research is imperative regarding PEG administration in surgical procedures for this purpose.

Opium Addiction and Ischemic Stroke in Isfahan, Iran: A Case-Control Study.

BACKGROUND: The effect of opium addiction (OA) on cerebrovascular disease is controversial. The aim of this study was to clarify this relationship in Iranian patients with ischemic stroke. METHODS: In a case-control study, 672 patients with ischemic stroke and 293 controls without a previous history of cerebrovascular or cardiovascular diseases were compared. OA as well as other risk factors such as diabetes mellitus (DM), hypertension (HTN), hyperlipidemia, tobacco smoking (TS) were compared between the 2 groups. RESULTS: OA percentage, TS, TS amount (pack/year), HTN and DM history were significantly higher in the case group compared to controls (p < 0.05). After regression analysis between risk factors, a significant difference remained between 2 groups with regards to HTN (OR 4.21, 95% CI 3.05-5.81, p < 0.001), TS (OR 2.33, 95% CI 1.51-3.59, p < 0.001), and OA (OR 2.36, 95% CI 1.16-4.85, p = 0.018). CONCLUSION: Our study showed OA is a risk factor for stroke. However, a follow-up study with a larger cohort is required to confirm the results.

Assessing of plasma levels of iron, zinc and copper in Iranian Parkinson's disease.

BACKGROUND: Trace elements have long been suspected to be involved in Parkinson's disease (PD) pathogenesis, but their exact roles have been remained controversial. In this study, we assessed the levels of copper (Cu), iron (Fe) and zinc (Zn) in different stage of PD patients. MATERIALS AND METHODS: Serum concentrations of iron, copper and zinc were measured in 109 patients with PD by colorimetric methods. Staging of the disease was evaluated according to Hoehn and Yahr (H and Y) and Unified PD Rating Scale III (UPDRS). RESULTS: Severity values of PD measured by UPRDSIII and HY stages with mean ± SD were 22.9 ± 1.81 and 1.8 ± 1.1, respectively. Mean ± SD values of iron, zinc and copper are 100.7 ± 289.2, 68.3 ± 5.32, and 196.8 ± 162.1 µg/dl, respectively. Serum iron level in most of the patients was normal (76.6%). Whereas zinc concentration in most participants was below the normal range (64.5%) and serum Cu in the majority of patients had a high normal concentration (42.7%) and did not significantly differ among various PD stages. CONCLUSION: The result of this study does not confirm strong correlation between PD stages and serum levels of tested trace elements. The actual correlations between these elements and PD and whether modulating of these agents levels could be an effective approach in the treatment of this disease remain to be elucidated.

The role of stem cell therapy in multiple sclerosis: An overview of the current status of the clinical studies.

The complexity of multiple sclerosis (MS) and the incompetence of a large number of promised treatments for MS urge us to plan new and more effective therapeutic approaches that aim to suppress ongoing autoimmune responses and induction of local endogenous regeneration. Emerging data propose that hematopoietic, mesenchymal, and neural stem cells have the potential to restore self-tolerance, provide in situ immunomodulation and neuroprotection, as well as promote regeneration. Thus, in this article, we will first provide an overview of the cell sources for proposed mechanisms that contribute to the beneficial effects of stem cell transplantation, the ideal route and/or timing of stem cell-based therapies for each main stem cell group, and finally, an overview of the current status of stem cell research in clinical trial stages in MS by comparable and healthy therapeutic effects of different stem cell therapies for MS patients.

Genomic rearrangement screening of the BRCA1 from seventy Iranian high-risk breast cancer families.

BACKGROUND: The second leading cause of cancer deaths in women is breast cancer. Germline mutations in susceptibility breast cancer gene BRCA1 increase the lifetime risk of breast cancer. Eighty-one large genomic rearrangements (LGRs) have been reported up to date in BRCA1 gene, and evaluation of these rearrangements helps with precise risk assessment in high-risk individuals. In this study, we have investigated LGRs in BRCA1 among Iranian high-risk breast cancer families. MATERIALS AND METHODS: Seventy patients with breast cancer who were identified negative for point mutations or small deletions/insertions of BRCA1 gene were selected. Deletions and duplications of BRCA1 gene were evaluated using multiplex ligation-dependent probe amplification (MLPA). RESULTS: Two deletions, deletion of exons 1A/1B-2 and exon 24, were detected in two patients with breast cancer. The former alteration was found in a woman with a strong family history of breast cancer while the latter one was detected in a woman with early onset of breast cancer. CONCLUSION: Although our data confirm that LGRs in BRCA1 comprise a relatively small proportion of mutations in hereditary breast cancer in the Iranian population, MLPA analysis might be considered for screening of LGRs in high-risk individuals. It is worth to note that our results are consistent with previous studies in various Asian and European countries.

The comparative study of Yaz and Ovocept-ld on patients with simple ovarian cysts referring to Iran-Isfahan Shariati Hospital.

BACKGROUND: Functional ovarian cysts include follicular, corpus luteum, and theca lutein cysts are the most common adnexal masses (about 50%) in women of reproductive age. Treatment with the combined monophasic oral contraceptives reduces functional ovarian cysts. Yaz (drospirenone/ethinyl estradiol) is a low-dose combined oral contraceptive pill containing 20 µg ethinyl estradiol and 3 mg drospirenone. In addition to contraceptive effects, Yaz has anti-mineralocorticoid and anti-adrenergic effects. Ovocept- low-dose LD is also a low-dose combined oral contraceptive drug containing 30 µg ethinyl estradiol and 3 mg norgestrol. Ovocept-LD has some side-effects such as weight gain, spotting, breast tenderness, nausea, and headache. MATERIALS AND METHODS: Being a clinical study, the present research was carried out on 42 patients with the simple ovarian cysts from 2010 to 2012. 84 Patients were assigned to A and B groups. Group A received Yaz once a day for a period of 28 days and group B received Ovocept-LD once a day for a period of 21 days. After treating by Yaz and Ovocept-LD, Cysts were evaluated by ultrasound. Results were analyzed by the SPSS software. A P < 0.05 was considered the significance threshold. RESULTS: Obtained results indicated that both Yaz and Ovocept-LD had an effect on the simple ovarian cysts. Statistical tests, however, has shown that the effect of Yaz has been significantly more than that of Ovocept-LD. CONCLUSION: Given the faster and better recovery effect, and the lesser side effects of Yaz as compared to Ovocept-LD, it is recommended to use Yaz for the simple ovarian cysts.