Comparison of Glasgow Coma Scale and Full Outline of UnResponsiveness score for prediction of in-hospital mortality in traumatic brain injury patients: a systematic review and meta-analysis.

BACKGROUND: Currently, Glasgow Coma Scale (GCS) is used to assess patients' level of consciousness. Although this tool is highly popular in clinical settings, it has various limitations that reduce its applicability in certain situations. This had led researchers to look for alternative scoring systems. This study aims to compare the value of GCS and Full Outline of UnResponsiveness (FOUR) score for prediction of mortality in traumatic brain injury (TBI) patients through a systematic review and meta-analysis. METHOD: Online databases of Medline, Embase, Scopus, and Web of Science were searched until the end of July 2022 for studies that had compared GCS and FOUR score in TBI patients. Interested outcomes were mortality and unfavorable outcome (mortality + disability). Findings are reported as area under the curve (AUC) sensitivity, specificity, and diagnostic odds ratio. RESULTS: 20 articles (comprised of 2083 patients) were included in this study. AUC of GCS and FOUR score for prediction of in-hospital mortality after TBI was 0.92 (95% CI 0.80-0.91) and 0.91 (95% CI 0.88-0.93) respectively. The diagnostic odds ratio of the two scores for prediction of in-hospital mortality after TBI was 44.51 (95% CI 23.58-84.03) for GCS and 45.16 (95% CI 24.25-84.09) for FOUR score. As for prediction of unfavorable outcome after TBI, AUC of GCS and FOUR score were 0.95 (95% CI 0.93 to 0.97) and 0.93 (95% CI 0.91-0.95), respectively. The diagnostic odds ratios for prediction of unfavorable outcome after TBI were 66.31 (95% CI 35.05-125.45) for GCS and 45.39 (95% CI 23.09-89.23) for FOUR score. CONCLUSION: Moderate level of evidence showed that the value of GCS and FOUR score in the prediction of in-hospital mortality and unfavorable outcome is comparable. The similar performance of these scores in assessment of TBI patients gives the medical staff the option to use either one of them according to the situation at hand.

Mesenchymal Stem Cell-Conditioned Medium Promotes Functional Recovery Following Spinal Cord Injury: A Systematic Review and Meta-analysis.

Background: Considering the limitations of cell therapy, in case of adequate treatment efficacy, conditioned media (CM) may be a desirable alternative to cell therapy. Hence, the present systematic review and meta-analysis aims to evaluate the efficacy of mesenchymal stem cell-derived conditioned media (MSC-CM) in movement resolution following spinal cord injury (SCI) in animal models. Methods: A comprehensive search in the databases of Medline, Scopus, Web of Science, and Embase was completed until the end of March 2021. Animal studies that evaluate the efficacy of MSC-CM on movement resolution following SCI were defined as the inclusion criteria. Lack of an SCI-untreated group, CM derived from a source other than MSC, not assessing motor function, failure to report CM administered dose, a follow-up period of less than 4 weeks, duplicates, and review articles were counted as the exclusion criteria. Final results are presented as overall standardized mean difference (SMD) with a 95% confidence interval (CI). Results: From the 361 nonduplicate articles, data from 11 articles were entered into the present meta-analysis. The analyses showed that MSC-CM administration in SCI animal models promotes motor recovery (SMD=2.32; 95% CI: 1.55, 3.09; p<0.0001). Subgroup analysis was performed because of the noticeable heterogeneity between the studies (I2=80.97%, p<0.0001), depicting that antibiotic administration, delivery amount, delivery type, and follow-up time were the possible sources of heterogeneity. Moreover, multiple meta-regression demonstrated that in cases of delivery amount of more than 120 µL, the efficacy of MSC-CM administration in motor recovery is more than that of delivery amount of less than 120 µL (regression coefficient=3.30; 95% CI: 0.72, 5.89; p=0.019). Conclusions: Based on the results of the present study, it can be concluded that MSC-CM administration in SCI models improves motor recovery. The efficacy of this treatment strategy significantly increases at doses higher than 120 µL.

Effects of Ketamine and Lidocaine Infusion on Acute Pain after Elective Open Abdominal Surgery, a Randomized, Double-Blinded Study.

Background: Most patients suffer from moderate to severe pain after elective laparotomy. They often require opioids to alleviate their pain. Opiates invariably induce certain side effects and, occasionally, dependence. Intraoperative infusion of lidocaine and low-dose ketamine reduces postoperative pain and analgesic requirements. This study aims to evaluate the effects of simultaneous infusion of lidocaine and ketamine during open abdominal surgery on the postoperative pain severity and analgesic consumption. Methods: In this randomized, double-blinded, single-center study that was performed in Iran, 80 patients scheduled for elective open abdominal surgery under general anesthesia were enrolled in two LK and P groups. Group LK (n=40) received lidocaine-ketamine infusion, and group P (n=40) received placebo (normal saline). Both infusions were started thirty minutes after initiation of surgery and were terminated once the surgery was completed. For postoperative pain management, patient-controlled analgesia (PCA), including fentanyl and paracetamol, was administered for both groups. All patients were evaluated for pain visual analogue scale (VAS) and total adjunctive analgesic (diclofenac suppository) consumption within the first 24 hours after the surgery. The data were analyzed using SPSS. P values <0.05 were considered significant. Results: Intraoperative infusion of Lidocaine and Ketamine resulted in desirable postoperative pain control. Patients of LK group demonstrated a significant reduction in the pain score at 1, 6, 12, 18, and 24 hours after termination of surgery (p<0.001). It also resulted in a decreased requirement for postoperative analgesics, as cumulative analgesic consumption was decreased meaningfully in the patients of LK group (p<0.001). Conclusion: Intravenous infusion of lidocaine and ketamine during elective open abdominal surgery reduces pain intensity and analgesic requirements in the first 24 hours postoperatively, without major additional side effects.

Comparison between surgery and fibrinolytic therapy in prosthetic valve thrombosis: A systematic review and meta-analysis.

BACKGROUND: Prosthetic valve thrombosis (PVT) is a rare but life-threatening complication. Surgery and fibrinolytic therapy (FT) are the two main treatment options for PVT. The choice between surgery and FT has always been a matter of debate. Previous studies have shown that although the mortality rate is higher in surgery, complications are less frequent than in FT. We aimed to perform a systematic review and meta-analysis to compare the results of surgery and FT in PVT. METHODS: A systematic review of the literature was performed through Medline, Embase, Scopus, and Web of Science, encompassing all studies comparing surgery and FT in PVT. The rate of each complication and risk ratio (RR) of complications in surgery and FT were assessed using random-effects models. RESULTS: Fifteen studies with 1235 patients were included in the meta-analysis. The pooled risk of the mortality was not significantly different between FT and surgery in patients with PVT (pooled RR = 0.78, 95% confidence interval [CI]: 0.38-1.60, I² = 61.4%). The pooled risks of thromboembolic events (pooled RR = 4.70, 95% CI: 1.83-12.07, I² = 49.6%) and major bleeding (pooled RR = 2.45, 95% CI: 1.09-5.50, I² = 41.1%) and PVT recurrence (pooled RR = 2.06 95% CI: 1.29-3.27, I² = 0.0%) were significantly higher in patients who received FT. CONCLUSION: Surgery may be safer and with fewer complications than FT for PVT treatment. However, randomized clinical trials are needed to determine the proper treatment for PVT.

Evaluation of health-related quality of life before and after total hip arthroplasty in the elderly in Iran: a prospective cohort study.

BACKGROUND: Owing to the direct impact of total hip arthroplasty (THA) on health-related quality of life (HRQOL) and the higher prevalence of THA in the elderly, this study aimed to compare HRQOL before, and after THA in the Iranian elderly. METHODS: The present prospective cohort study was performed on 161 THA candidates. Demographic data were extracted from records of patients. Before, 6, and 12 months after THA, a Short Form 36 health survey (SF-36) was used to assess HRQOL. Before THA, 6 and 12 months after THA, Physical (PCS), and mental component scores (MCS) were obtained from a hundred separately for each subscale of the questionnaire. The Paired t-test was used to compare HRQOL before and after THA. RESULTS: Both 6 and 12 months after THA, HRQOL was significantly increased compared to previous THA (P = 0.001). In the first half-year after THA, vitality and emotional state were not different from pre-surgery. However, 12 months after THA, these two subscales also were significantly improved. Although, 6 months after THA, the PCS has dramatically gone up compared to the previous THA (P = 0.012), despite MCS was remained steady. Nonetheless, by comparison with the before surgery, 12 months after THA, MSC notably improved (P = 0.048). CONCLUSION: HRQOL was appreciably improved by the THA in the elderly after 12 months. The improvement in HRQoL in the first 6 months after THA is related to the promotion in the physical aspect (PCS score), and in the second 6 months after THA is related to the promotion in the psychological aspect (MCS score).

Growth Factor Gene-Modified Cells in Spinal Cord Injury Recovery: A Systematic Review.

BACKGROUND: Numerous preclinical studies have been performed in recent years on the effects of the administration of growth factor gene-modified cells in spinal cord injury (SCI). However, findings of these studies are contradictory. OBJECTIVE: The present study aims to conduct a systematic review and meta-analysis of animal studies evaluating the effects of administration of growth factor gene-modified cells on locomotion recovery after SCI. METHODS: A search of the MEDLINE, Embase, Scopus, and Web of Science databases was conducted, including all animal studies until the end of 2020. Two researchers screened search results, summarized relevant studies and assessed risk of bias, independently. RESULTS: Thirty-three studies were included in the final analysis. Transplantation of growth factor gene-modified cells in the injured spinal cord resulted in a significant improvement in locomotion of animals compared with nontreated animals (standardized mean difference = 1.86; 95% confidence interval, 1.39-2.33; P < 0.0001)] and non-genetically modified cell-treated animals (standardized mean difference = 1.30; 95% confidence interval, 0.80-1.79; P < 0.0001). Transplantation efficacy of these cells failed to achieve significance in moderate lesions (P = 0.091), when using modified neural stem/progenitor cells (P = 0.164), when using synthetic neurotrophins (P = 0.086) and when the number of transplanted cells was less than 1.0 × 105 cells per animal (P = 0.119). CONCLUSIONS: The results showed that transplantation of growth factor gene- modified cells significantly improved locomotion in SCI animal models. However, there is a major concern regarding the safety of transplantation of genetically modified cells, in terms of overexpressing growth factors. Further studies are needed before any effort to perform a translational and clinical study.

The efficacy of GABAergic precursor cells transplantation in alleviating neuropathic pain in animal models: a systematic review and meta-analysis.

BACKGROUND: Current therapies are quite unsuccessful in the management of neuropathic pain. Therefore, considering the inhibitory characteristics of GABA mediators, the present systematic review and meta-analysis aimed to determine the efficacy of GABAergic neural precursor cells on neuropathic pain management. METHODS: Search was conducted on Medline, Embase, Scopus, and Web of Science databases. A search strategy was designed based on the keywords related to GABAergic cells combined with neuropathic pain. The outcomes were allodynia and hyperalgesia. The results were reported as a pooled standardized mean difference (SMD) with a 95% confidence interval (95% CI). RESULTS: Data of 13 studies were analyzed in the present meta-analysis. The results showed that administration of GABAergic cells improved allodynia (SMD = 1.79; 95% CI: 0.87, 271; P < 0.001) and hyperalgesia (SMD = 1.29; 95% CI: 0.26, 2.32; P = 0.019). Moreover, the analyses demonstrated that the efficacy of GABAergic cells in the management of allodynia and hyperalgesia is only observed in rats. Also, only genetically modified cells are effective in improving both of allodynia, and hyperalgesia. CONCLUSIONS: A moderate level of pre-clinical evidence showed that transplantation of genetically-modified GABAergic cells is effective in the management of neuropathic pain. However, it seems that the transplantation efficacy of these cells is only statistically significant in improving pain symptoms in rats. Hence, caution should be exercised regarding the generalizability and the translation of the findings from rats and mice studies to large animal studies and clinical trials.

Efficacy of adipose tissue-derived stem cells in locomotion recovery after spinal cord injury: a systematic review and meta-analysis on animal studies.

BACKGROUND: Considerable disparities exist on the use of adipose tissue-derived stem cells (ADSCs) for treatment of spinal cord injury (SCI). Hence, the current systematic review aimed to investigate the efficacy of ADSCs in locomotion recovery following SCI in animal models. METHODS: A search was conducted in electronic databases of MEDLINE, Embase, Scopus, and Web of Science until the end of July 2019. Reference and citation tracking and searching Google and Google Scholar search engines were performed to achieve more studies. Animal studies conducted on rats having SCI which were treated with ADSCs were included in the study. Exclusion criteria were lacking a non-treated control group, not evaluating locomotion, non-rat studies, not reporting the number of transplanted cells, not reporting isolation and preparation methods of stem cells, review articles, combination therapy, use of genetically modified ADSCs, use of induced pluripotent ADSCs, and human trials. Risk of bias was assessed using Hasannejad et al.'s proposed method for quality control of SCI-animal studies. Data were analyzed in STATA 14.0 software, and based on a random effect model, pooled standardized mean difference with a 95% confidence interval was presented. RESULTS: Of 588 non-duplicated papers, data from 18 articles were included. Overall risk of bias was high risk in 8 studies, some concern in 9 studies and low risk in 1 study. Current evidence demonstrated that ADSCs transplantation could improve locomotion following SCI (standardized mean difference = 1.71; 95%CI 1.29-2.13; p < 0.0001). A considerable heterogeneity was observed between the studies (I2 = 72.0%; p < 0.0001). Subgroup analysis and meta-regression revealed that most of the factors like injury model, the severity of SCI, treatment phase, injury location, and number of transplanted cells did not have a significant effect on the efficacy of ADSCs in improving locomotion following SCI (pfor odds ratios > 0.05). CONCLUSION: We conclude that any number of ADSCs by any prescription routes can improve locomotion recovery in an SCI animal model, at any phase of SCI, with any severity. Given the remarkable bias about blinding, clinical translation of the present results is tough, because in addition to the complexity of the nervous system and the involvement of far more complex motor circuits in the human, blinding compliance and motor outcome assessment tests in animal studies and clinical trials are significantly different.

Dual antiplatelet therapy before coronary artery bypass grafting in patients with myocardial infarction: a prospective cohort study.

BACKGROUND: Dual antiplatelet therapy (DAPT) in patients with MI who are candidates for early coronary artery bypass grafting (CABG) can affect intraoperative and postoperative outcomes. Therefore, the aim of this study was to evaluate the effect of DAPT up to the day before CABG on the outcomes during and after surgery in patients with MI. METHODS: In this prospective cohort study, 224 CABG candidate patients with and without MI were divided into two groups: (A) patients without MI who were treated with aspirin 80 mg/day before surgery (noMI-aspirin group; n = 124) and (B) patients with MI who were treated with aspirin 80 mg/day before surgery and clopidogrel (Plavix brand) at a dose of 75 mg/day (MI-DAPT group; n = 120). Dual or mono-antiplatelet therapy continued until the day before surgery. Patients were followed to assess in-hospital and 6-months outcomes. RESULTS: The in-hospital mortality in MI-DAPT group was similar with noMI-aspirin group (OR 4.2; 95% CI 0.9-20.5; p = 0.071). The prevalence of CVA (p = 0.098), duration of hospital stay (p = 0.109), postoperative ejection fraction level (p = 0.693), diastolic dysfunction grade (p = 0.651) and postoperative PAP level (p = 0.0364) did not show difference between two groups. No mild or severe bleeding was observed in the patients. Six-month follow up showed that number of readmissions (p = 0.801), number of cases requiring angiography (p = 0.100), cases requiring re-PCI (p = 0.156), need for re-CABG (p > 0.999) and CVA (p > 0.999) did not differ between the two groups. During the 6-month follow-up, out-hospital mortality did not differ significantly between the two groups (p = 0.446). CONCLUSIONS: A 6-month follow-up showed that DAPT with aspirin and clopidogrel before CABG in patients with MI has no effect on postoperative outcomes more than mono-APT with aspirin. Therefore, DAPT is recommended in the preoperative period for these patients.

Efficacy of adipose derived stem cells on functional and neurological improvement following ischemic stroke: a systematic review and meta-analysis.

BACKGROUND: The evidence on the efficacy of adipose derived stem cells (ADSCs) in the treatment of stroke is controversial. Therefore, the aim of present systematic review and meta-analysis is to evaluate the efficacy of ADSCs administration in the treatment of animal models of ischemic stroke. METHODS: An extensive search was performed on electronic databases of Medline, Embase, Scopus, CENTRAL and Web of Science until December 31, 2018. Animal studies that used ADSCs in treatment of ischemic stroke were included. The data were recorded as mean and standard deviation and then a pooled standardized mean difference (SMD) with 95% confidence interval (95% CI) was reported. RESULTS: Twenty articles were included in the present meta-analysis. It was observed that administration of ADSCs improves motor function (SMD = 2.52, 95% CI: 1.67 to 3.37, p < 0.0001) and neurological status (SMD = 2.05, 95% CI: 1.33 to 2.78, p < 0.0001) in animals following an ischemic stroke. Multivariate meta-regression showed the model of stroke induction (p = 0.017) and the number of transplanted cells (p = 0.007) affect the efficacy of ADSCs administration on motor function improvement following the stroke. CONCLUSION: Moderate to high levels of evidence indicate a strong efficacy of ADSCs transplantation on motor function and neurological improvement following ischemic stroke in animal models. However, no reports regarding the dose-response effect of ADSCs administration on stroke exist in the literature. As a result, further pre-clinical studies are recommended to be conducted on the matter.

Dual Antiplatelet Therapy before Coronary Artery Bypass Grafting; a Systematic Review and Meta-Analysis.

INTRODUCTION: Currently, the basis of acute coronary syndrome (ACS) therapy is dual antiplatelet therapy (DAPT) with Aspirin as a nonsteroidal anti-inflammatory drug and clopidogrel as adenosine diphosphate receptor antagonists. Therefore, the aim of the present systematic review is to answer that should DAPT with Aspirin and clopidogrel be continued until coronary artery bypass grafting (CABG) in patients who have ACS? METHODS: The search for relevant studies in the present meta-analysis is based on three approaches: A) systematic searches in electronic databases, B) manual searches in Google and Google Scholar, and C) screening of bibliography of related original and review articles. The endpoints included mortality rate, myocardial infarction (MI), cerebrovascular accident (CVA), reoperation, re-exploration, other cardiac events, renal failure, length of ICU and hospital stay, chest tube drainage and blood product transfusion after CABG. RESULTS: After the initial screening, 41 articles were studied in detail, and finally the data of 15 studies were included in the meta-analysis. DAPT before CABG in patients with ACS does not increase the rate of mortality, CVA, renal failure, MI, and other cardiac events, but increases reoperation, re-exploration, length of ICU, and hospital stay. Chest tube drainage and blood product transfusion rate significantly increased in the DAPT group compared to the control group (non-antiplatelet or Aspirin alone). Increase in chest tube drainage and blood product transfusion rate indicates an increase in bleeding, so increase in reoperation, re-exploration to control bleeding, and, subsequently, increase in the length of ICU and hospital stay are expected. CONCLUSIONS: DAPT with Aspirin and clopidogrel before CABG in patients with ACS does not increase the rate of mortality, CVA, renal failure, MI, and other cardiac events despite more bleedings, and it may be suggested before CABG for better graft patency.

Combination of laser and human adipose-derived stem cells in repair of rabbit anal sphincter injury: a new therapeutic approach.

BACKGROUND: Anal sphincter injury leads to fecal incontinence. Based on the regenerative capability of laser and human adipose-derived stem cells (hADSCs), this study was designed to assess the effects of co-application of these therapies on anal sphincter recovery after injury. DESIGN: Male rabbits were assigned to equal groups (n = 7) including control, sphincterotomy, sphincterotomy treated with laser (660 nm, 90 s, immediately after sphincterotomy, daily, 14 days), hADSCs (2 × 106 hADSCs injected into injured area of the sphincter immediately after sphincterotomy), and laser + hADSCs. Ninety days after sphincterotomy, manometry and electromyography were performed, sphincter collagen content was evaluated, and Ki67, myosin heavy chain (MHC), skeletal muscle alpha-actin (ACTA1), vascular endothelial growth factor A (VEGFA), and vimentin mRNA gene expression were assessed. RESULTS: The laser + hADSCs group had a higher resting pressure compared with the sphincterotomy (p < 0.0001), laser (p < 0.0001), and hADSCs (p = 0.04) groups. Maximum squeeze pressure was improved in all treated animals compared with the sphincterotomized animals (p < 0.0001), without a significant difference between treatments (p > 0.05). In the laser + hADSCs group, motor unit numbers were higher than those in the laser group (p < 0.0001) but did not differ from the hADSCs group (p = 0.075). Sphincterotomy increased collagen content, but the muscle content (p = 0.36) and collagen content (p = 0.37) were not significantly different between the laser + hADSCs and control groups. Laser + hADSCs increased ACTA1 (p = 0.001) and MHC (p < 0.0001) gene expression compared with laser or hADSCs alone and was associated with increased VEGFA (p = 0.009) and Ki67 mRNA expression (p = 0.01) and decreased vimentin mRNA expression (p < 0.0001) compared with laser. CONCLUSION: The combination of laser and hADSCs appears more effective than either treatment alone for promoting myogenesis, angiogenesis, and functional recovery after anal sphincterotomy.

Predictors of 5 year survival rate in hepatocellular carcinoma patients.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common primary hepatic malignancies and growing challenges of global health. In this study, for the first time in Iran, we investigated the 5-year survival rate and prognostic factors in patients with HCC. MATERIALS AND METHODS: In this historical cohort study, we examined the medical records of 227 HCC patients who were registered in the central tumor registry of our institution from September 2007 to September 2017. Demographic data, clinical parameters, received treatments, and survival curves from time of diagnosis were evaluated. Kaplan-Meier was used for univariate analysis, and multivariable analysis was performed by Cox regression. RESULTS: A total of 208 (91.63%) patients were dead. The 5-year survival rate was estimated 19 (8.37%). The average follow-up in this study was 14.3 months. Overall median survival rate was 12.1 months. Univariate analysis showed that tumor size, metastasis, number of involved lymph node, hepatitis type, and treatment were significantly related to the survival rate, and Cox regression analysis revealed that the tumor size >3 cm (hazard ratio [HR] = 3.06, 95% confidence interval [CI] = 1.68-4.97; P = 0.027), involved lymph nodes >2 (HR = 4.12, 95% CI = 2.66-6.38; P = 0.001), metastasis (HR = 3.87, 95% CI = 3.13-6.54; P = 0.011), combination therapy with surgery and chemotherapy (HR = 0.4, 95% CI = 0.15-0.79; P = 0.023), and coinfection with hepatitis B virus and hepatitis C virus (HR = 2.11, 95% CI = 1.81-4.6; P = 0.036) are the most relevant prognostic factors with 5-year survival rate in patients with HCC. CONCLUSION: Results of this study will help estimate survival rates for patients with HCC according to their clinical status.

Co-administration of human adipose-derived stem cells and low-level laser to alleviate neuropathic pain after experimental spinal cord injury.

BACKGROUND: Evidence has suggested that human adipose-derived stem cells (hADSCs) and low-level laser has neuroprotective effects on spinal cord injury (SCI). Therefore, the combined effect of the hADSCs and laser on neuregeneration and neuropathic pain after SCI was investigated. METHODS: Forty-eight adult male Wistar rats with 200-250 g weight were used. Thirty minutes after compression, injury with laser was irritated, and 1 week following SCI, about 1 × 106 cells were transplanted into the spinal cord. Motor function and neuropathic pain were assessed weekly. Molecular and histological studies were done at the end of the fourth week. RESULTS: The combined application of hADSCs and laser has significantly improved motor function recovery (p = 0.0001), hyperalgesia (p < 0.05), and allodynia (p < 0.05). GDNF mRNA expression was significantly increased in hADSCs and laser+hADSC-treated animals (p < 0.001). Finally, co-administration of hADSCs and laser has enhanced the number of axons around cavity more than other treatments (p < 0.001). CONCLUSIONS: The results showed that the combination of laser and ADSCs could significantly improve the motor function and alleviate SCI-induced allodynia and hyperalgesia. Therefore, using a combination of laser and hADSCs in future experimental and translational clinical studies is suggested.

The Effect of Alpha-Tocopherol on Morphine Tolerance-induced Expression of c-fos Proto-oncogene from a Biotechnological Perspective.

BACKGROUND: The increase of oxidant compounds is the most well-known reasons for the tolerance to the analgesic properties of Morphine. Additionally, the production of proxy-nitrite impairs receptors, proteins and enzymes involved in the signaling pathways of analgesia, apoptosis and necrosis. Also, we revised all patents relating to opioid tolerance control methods. OBJECTIVE: The aim of this study was to assess the effects of Alpha-tocopherol as an anti-oxidant agent to reduce Morphine tolerance. METHOD: Forty male rats randomly divided into four groups. 10 mg/kg of morphine was injected subcutaneously to create the desired level of tolerance. After modeling, 70 mg/kg Alpha- Tocopherol was injected intraperitoneal. Also, the hot plate recorded pain threshold alterations was used to evaluate the behavioral test. All tissue samples were extracted from the spinal cord, thalamus and frontal cortex for molecular and gene expression evaluations. Also, the effect of Alpha- Tocopherol on the apoptosis and necrosis parameters was analyzed using nissl staining and tunel test. RESULTS: The time latency results showed that there were no significant differences in the different days in groups treated with Morphine plus Alpha-Tocopherol. However, our data highlighted that the pain threshold and their time latency in respond to it had substantially increased in comparison with the control group. Furthermore, we found that the Alpha-Tocopherol obviously decreased c-fos gene expression, especially in the spinal cord. CONCLUSION: Thus, co-administration of Alpha-Tocopherol with Morphine can decrease the adverse effects of nitrite proxy, which is released due to repeated injections of Morphine.

5-Year Survival Rates and Prognostic Factors in Patients with Synchronus and Metachronus Breast Cancer from 2010 to 2015

Introduction: Currently breast (BC) cancer is a serious medical problem in all countries of the world. Survival depends on many factors. The present study focused on 5-year survival and its related factors in patients with BC in Iran. Material and methods. The present analytical retrospective study was performed (from March 2010 until March 2015) on patients with BC followed for at least 6 months. The main variables assessed were tumor size, grade of lymph node involvement, metastasis, stage, history, human epidermal growth factor receptor expression, and tumor origin. Analysis of survival was accomplished using the Kaplan- Meier method. Results: Some 351 (80.2%) of the total of 438 individuals had unilateral and 87(19.8%) had bilateral cancer, 28 (35.6%) of the latter being synchronous and 56(64.4%) metachronous. Mean duration of follow-up was 47.44±28.19 months, during which 61 (17.3%) patients with unilateral and 18 with bilateral cancer eventually died. The 5-year survival rate in patients with unilateral BC was significantly higher than those with bilateral BC (Log-rank Test chi2= 3.11, p=0.032). In addition, with metachronous cases, the survival rate was 64.2% in comparison with 51.6% for synchronous BCs. Survival rate was significantly (p value =0.038) higher with metachronous than with synchronous cancers (Log-rank Test chi2=3.54, p=0.038). The highest survival rate was reported for BCs originating from lobule tissue and the lowest rate examples of interstitial tissue origin (Log-rank Test chi2=11.54, p=0.0001). Patients with earl stage lesions (M1) survived longer than with other stages (Log-rank Test chi2= 9.55, p=0.001). Conclusion: In this study, most women with BC had a positive family history and were married. The 5-year survival rate was lower with advanced stages of cancer. According to our findings, survival rates might improve if patients undergo screening and diagnosis is made at an early stage of the disease.

Hydrogen peroxide: a potent inducer of differentiation of human adipose-derived stem cells into chondrocytes.

Common protocols for chondrogenic differentiation of adipose-derived mesenchymal stem cells (ADSCs) are generally expensive and time-consuming and, so far, have not successfully recreated pure chondrocytes. We hypothesise that a low level of H2O2 may induce differentiation of ADSCs into chondrocytes in a shorter incubation time and relatively lower cost. Therefore, this study aimed to comparatively investigate the effectiveness of H2O2-containing or free medium in the induction of ADSCs to chondrocytes. ADSCs were isolated from the lipoaspirate of four healthy females and evaluated by immunophenotyping for their CD90, CD73, CD44, CD34, and CD45 cell surface markers. Chondrogenic differentiation was carried out using differentiation medium in the presence or absence of 10 and 50 µM H2O2 in normal and three-dimensional culture system. The intracellular contents of reactive oxygen species (ROS) were detected by flow cytometry and fluorescence microscopy. The hydroxyproline, was assessed as marker of collagen and the glycosaminoglycans (GAGs) content was both qualitatively detected and quantitatively determined. Real-time PCR was performed to determine the gene expression level of aggrecan (ACAN), type-II collagen, and transcription factor Sox9. H2O2-treated cells showed pre-chondrocyte morphology on day 1 and chondrocyte pellets were formed on day 14. H2O2-treated cells induced greater pellet sizes and showed significantly higher content of GAGs and hydroxyproline level compared with untreated cells. The gene expression levels of ACAN, collagen type-II, and Sox9 were markedly upregulated by H2O2. Our findings showed for the first time that H2O2-containing differentiation medium is potentially more effective than H2O2-free differentiation medium in the induction of chondrogensis of ADSCs.

Quantification of Plasma Cell-Free Circulating DNA at Different Stages of Colorectal Cancer.

Cell-free circulating DNAs (cfcDNAs) have been recognized as promising biomarkers for a number of cancers. This study aimed to quantify the cfcDNA in colorectal cancer to assess its potential value as biomarker. Quantification of baseline cfcDNA was determined as the amount of free glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in plasma, using quantitative real-time polymerase chain reaction (PCR). The calculated area under the curve (AUC) of receiver operating characteristic (ROC) for cfcDNA was 0.875 (95% CI, 0.811-0.94), which was indicative of a high discriminatory power (p < 0.001) and significant accuracy in distinguishing cancer patients from healthy individuals. The quantification of cfcDNA could be useful for clinical settings of CRC.

Homeodomain Protein Transforming Growth Factor Beta-Induced Factor 2 Like, X-Linked Function in Colon Adenocarcinoma Cells

Background: TGIF2LX (transforming growth factor beta-induced factor 2 like, X-linked) is a homeodomain (HD) protein that has been implicated in the negative regulation of cell signaling pathways. The aim of this study was to investigate the possible functions of TGIF2LX in colon adenocarcinoma cells. Methods: The human SW48 cell line was transfected with cDNA for the wild-type TGIF2LX gene and gene/protein over-expression was confirmed by microscopic analysis, real time RT-PCR and Western blotting techniques. In vitro cell proliferation was evaluated by MTT and BrdU assays. After developing a colon tumor model in nude mice, immunohistochemical (IHC) staining of tumor tissue was carried out for Ki-67 (proliferation) and CD34 (angiogenesis) markers. To predict potential protein partners of TGIF2LX, in-silico analysis was also conducted. Results: Obtained results showed over-expression of TGIF2LX as a potential transcription factor could inhibit either proliferation or angiogenesis (P<0.05) in colon tumors. In-silico results predicted interaction of TGIF2LX with other proteins considered important for cellular development. Conclusions: Our findings provided evidence of molecular mechanisms by which TGIF2LX could act as a tumor suppressor in colon adenocarcinoma cells. Thus, this gene may potentially be a promising option for colon cancer gene-based therapeutic strategies.

A new method for treating fecal incontinence by implanting stem cells derived from human adipose tissue: preliminary findings of a randomized double-blind clinical trial.

BACKGROUND: Anal sphincter defects are a major cause of fecal incontinence causing negative effects on daily life, social interactions, and mental health. Because human adipose-derived stromal/stem cells (hADSCs) are easier and safer to access, secrete high levels of growth factor, and have the potential to differentiate into muscle cells, we investigated the ability of hADSCs to improve anal sphincter incontinence. METHODS: The present randomized double-blind clinical trial was performed on patients with sphincter defects. They were categorized into a cell group (n = 9) and a control group (n = 9). Either 6 × 106 hADSCs per 3 ml suspended in phosphate buffer saline (treatment) or 3 ml phosphate buffer saline (placebo) was injected. Two months after surgery, the Wexner score, endorectal sonography, and electromyography (EMG) results were recorded. RESULTS: Comparing Wexner scores in the cell group and the control group showed no significant difference. In our EMG and endorectal sonography analysis using ImageJ/Fiji 1.46 software, the ratio of the area occupied by the muscle to total area of the lesion showed a 7.91% increase in the cell group compared with the control group. CONCLUSION: The results of the current study show that injection of hADSCs during repair surgery for fecal incontinence may cause replacement of fibrous tissue, which acts as a mechanical support to muscle tissue with contractile function. This is a key point in treatment of fecal incontinence especially in the long term and may be a major step forward. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT2016022826316N2 . Retrospectively registered 7 May 2016.