Ferulic acid grafted into ß-cyclodextrin nanosponges ameliorates Paraquat-induced human MRC-5 fibroblast injury.

Paraquat (PQ) is a commercially important and effective herbicide in the world. Nevertheless, it has higher toxicity causing acute organ damage and different complications, mainly in the lungs and kidneys. Ferulic acid (FA), 4-hydroxy-3-methoxycinnamic acid imposes multiple pharmacological impacts. No protective effect of FA on PQ poisoning-caused human embryonic lung fibroblast damage has not been reported. Despite their many beneficial effects, FA is characterized by poor water solubility, low bioavailability, and phytochemical instability. To solve the problem, ß-cyclodextrin nanosponge (ß-CD NSs) was utilized to increase the solubility of FA so that it was grafted into ß-CD NSs to establish ß-CD@FA NSs. The purpose of this work was to examine for the first time the protective effect of ß-CD@FA NS on MRC-5 human lung cells damages induced by PQ poisoning. MTS assay was performed to investigate the viability of MRC-5 cells at different concentrations of FA/ß-CD@FA NSs when cells were co-cultured with 0.2 µg/mL PQ. The flow cytometry study was carried out to determine apoptosis. Malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) levels were detected using appropriate biochemistry kits. Compared with the PQ group, the cell activity, CAT, and SOD levels were significantly increased in the FA and chiefly in ß-CD@FA NSs intervention groups, whereas apoptosis and MDA levels were markedly decreased. The inflammatory factors tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and interleukin 22 (IL-22) were detected. The results demonstrate that ß-CD@FA NSs can inhibit PQ-induced cell damage by enhancing antioxidant stress capacity and regulation of inflammatory responses.

Reference range of testosterone and dehydroepiandrosterone sulfate levels in women during reproductive age in the Iranian population.

Backgrounds: To determine the average cutoff values of serum-free and total testosterone (FT, TT) and dehydroepiandrosterone sulfate (DHEAS) among healthy premenopausal women. Materials and Methods: Participants were women aged 18-55 years without signs and symptoms of hyperandrogenism (n = 489). Participants if Ferriman-Gallwey (FG) scores between 6 and 8 were considered a group located in the upper spectrum related to the normal hirsutism score (n = 30). DHEAS, TT, and FT levels were compared between different populations. Upper limits of 97.5 and 95 and lower limits of 5 and 2.5 percentiles were calculated to provide the reference intervals for DHEA, TT, and FT in the total sample and in the population with FG 6-8. Results: In the total population, the mean ± standard deviation (SD) serum FT, TT, and DHEAS levels were 1.40 ± 0.63 pg/mL, 0.42 ± 0.17 ng/mL, and 1.5 ± 0.97 µg/ml, respectively. The cutoff values of FT at 1.35 and TT at 0.49 were obtained for differentiating the patients with FG 6-8 scores from the normal population, with the corresponding specificity of 0.60, the sensitivity of 0.67, and area under the ROC curve (AUC) (confidence interval 95%) of 0.63 (0.52-0.73), P = 0.01 and 0.68 (0.58-0.78) P = 0.001, respectively. Conclusions: In our study, the mean ± SD serum FT level was 1.40 ± 0.63 pg/mL, the TT level was 0.42 ± 0.17 ng/mL, and the DHEAS level was 1.5 ± 0.97 µg/ml, in premenopausal women between 18 and 49 years of age. Furthermore, in a population with FG 6-8 score, a cutoff value of FT at 1.35 and TT at 0.49 was obtained. Although the irregular menstrual cycle did not change the reference range when compared with the normal group.

The association of exposure to air pollution with changes in plasma glucose indices, and incidence of diabetes and prediabetes: A prospective cohort of first-degree relatives of patients with type 2 diabetes.

Background: Increasing incidence rates of diabetes related to air pollution have been reported in high-income countries. However, few studies evaluated air pollution effect on plasma glucose indices, in addition to diabetes and prediabetes incidence in developing countries. This study investigated the association between exposure to common air pollutants and the changes plasma glucose indices over time. The incidence of type 2 diabetes (T2D) and prediabetes in future were also examined in association with exposure to air pollution. Materials and Methods: A total of 3828 first-degree relatives of patients with T2D who were prediabetes or had normal glucose tolerance (NGT) were enrolled in this study. Cox regression was used to assess the relationships between particulate matter (PM2.5 and PM10), nitrogen monoxide (NO), nitrogen dioxide, nitric oxides, sulfur dioxide (SO2), and ozone exposure and the incidence of T2D and prediabetes. We also applied a linear mixed model to assess the association between exposure to these air pollutants and changes in plasma glucose indices over time. Results: Air pollutants showed a significant positive association with changes in fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), and 2 h oral glucose tolerance (OGTT) in participants with NGT and prediabetes. The maximum increase in plasma glucose indices was associated with NO concentration. Our study also showed exposure to all air pollutants except SO2 was significantly associated with an increased risk of developing T2D and prediabetes (Hazard ratio > 1, P < 0.001). Conclusion: According to our results, exposure to air pollution increases the risk of T2D and prediabetes incidence in our population. The exposure to air pollutants was also associated with increasing trend in FPG, HbA1c, and OGTT levels in both groups of NGT and prediabetic participants.

Efficacy of fresh frozen plasma transfusion in comparison with conventional regimen in organophosphate poisoning treatment: a meta-analysis study.

OBJECTIVE: To evaluating the efficacy of fresh frozen plasma (FFP) in comparison with conventional regimen in the treatment of organophosphate (OP) poisoning. METHODS: PubMed, ScopeMed, Cochrane, Scopus, and Google Scholar databases were searched. The search strategy used the following key words "organophosphate" and "poisoning or toxicity", "(atropine and oxime)", "fresh frozen plasma", "clinical trial", "outcome". The treatment with atropine or/and oxime was considered conventional therapy. The length of hospitalization, the length of ICU admission, need for mechanical ventilation and its duration, clinical recovery point, choline esterase level, mortality rate, and intermediate syndrome (IMS) occurrence were the key outcomes of interest. Databases were searched during the period of 2003-2019. Five studies were included in the analysis. RESULTS: Pooling of data showed that the relative risk (RR) of mortality in OP poisoning for five included trials comparing FFP-treated group with conventional regimen therapy was [0.563 (95% CI (0.252, 1.255)]. The summary of RR for IMS in two studies was [RR: 1.34, 95% CI (0.655, 2.742)]. In addition, there was a non-significant mean difference (MD) in hospital stay [MD: -0.106, 95% CI (-0.434, 0.223)] in three included trials. A significant MD was observed in the length of ICU admission in two trials between FFP-treated group compared to the conventional treatment group [MD: -2.672, 95% CI (-4.189, -1.154)], but after random effects meta-analysis, the changes were not significant [MD: -2.015, 95% CI (-6.308, 2.277)]. The summary of fixed-effect meta-analysis for choline esterase level in three trails was [MD: -0.117, 95% CI (-0.468, 0.234)]. The RR of ventilation requirement for two included trials in the FFP-treated group comparing to the conventional regimen therapy was [0.84, 95% CI (0.691, 1.022)] while for ventilation duration in two studies was [MD: -0.183, 95% CI (-0.567, 0.201)]. CONCLUSION: The addition of FFP to conventional therapy did not improve the outcomes of mortality, IMS, hospital length of stay, cholinesterase levels, need or duration of mechanical ventilation, and only the length of ICU stay could affect in the treated group.

Papain grafted into the silica coated iron-based magnetic nanoparticles 'IONPs@SiO2-PPN' as a new delivery vehicle to the HeLa cells.

The present study aims at engineering, fabrication, characterization, and qualifications of papain (PPN) conjugated SiO2-coated iron oxide nanoparticles 'IONPs@SiO2-PPN'. Initially fabricated iron oxide nanoparticles (IONPs) were coated with silica (SiO2) using sol-gel method to hinder the aggregation and to enhance biocompatibility. Next, PPN was loaded as an anticancer agent into the silica coated IONPs (IONPs@SiO2) for the delivery of papain to the HeLa cancer cells. This fabricated silica-coated based magnetic nanoparticle is introduced as a new physiologically-compatible and stable drug delivery vehicle for delivering of PPN to the HeLa cancer cell line. The IONPs@SiO2-PPN were characterized using FT-IR, AAS, FESEM, XRD, DLS, and VSM equipment. Silica was amended on the surface of iron oxide nanoparticles (IONPs, γ-Fe2O3) to modify its biocompatibility and stability. The solvent evaporation method was used to activate PPN vectorization. The following tests were performed to highlight the compatibility of our proposed delivery vehicle: in vitro toxicity assay, in vivo acute systemic toxicity test, and the histology examination. The results demonstrated that IONPs@SiO2-PPN successfully reduced the IC50 values compared with the native PPN. Also, the structural alternations of HeLa cells exposed to IONPs@SiO2-PPN exhibited higher typical hallmarks of apoptosis compared to the cells treated with the native PPN. The in vivo acute toxicity test indicated no clinical signs of distress/discomfort or weight loss in Balb/C mice a week after the intravenous injection of IONPs@SiO2 (10 mg kg-1). Besides, the tissues architectures were not affected and the pathological inflammatory alternations detection failed. In conclusion, IONPs@SiO2-PPN can be chosen as a potent candidate for further medical applications in the future, for instance as a drug delivery vehicle or hyperthermia agent.

Premature pubarche as a first presentation of pituitary macroprolactinoma.

Prolactinoma is a rare tumor of childhood. Clinical presentations of prolactinoma include amenorrhea, delayed puberty, and galactorrhea. For the first time, in this case, elevated prolactin levels were associated with unexpected premature pubarche. We describe an 8-year, 7-month-old boy with acne and gradual appearance of pubic hair, corresponding to tanner stage 2. Hormonal tests showed severe hyperprolactinemia (prolactin = 246.8 µg/L and pooled prolactin = 175 µg/L and macroprolactin = 5 µg/L) and mildly elevated level of dehdroepiandrostenedion sulfate (DHEAS) and testosterone. Magnetic resonance imaging (MRI) findings confirmed the presence of a pituitary macroprolactinoma, measuring 14 mm × 12 mm × 8 mm on the right side of the pituitary gland. Cabergoline therapy was commenced (0.5 mg/week) and after 3 months, no evidence of pubarche progression was observed. Prolactin level and tumor size markedly reduced. At the 9-month follow-up visit, a normal MRI was reported. This case highlights that even when facing premature pubarche, careful examination is mandatory, and if no obvious etiology is found for premature pubarche, clinicians should consider prolactinoma.

Area under the curve during OGTT in first-degree relatives of diabetic patients as an efficient indicator of future risk of type 2 diabetes and prediabetes.

OBJECTIVE: To establish whether the area under the curve of an OGTT has a predictive role in identifying prediabetic and diabetic subjects among first-degree relatives (FDR) of patients with diabetes mellitus type 2 (DM). DESIGN, PATIENTS AND MEASUREMENTS: In a population-based cohort study, 766 FDR of diabetic patients with a normal glucose tolerance test (NGT) completed a 2-hour OGTT. They were followed up for 7 years and classified according to the American Diabetes Association criteria into: NGT, impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and DM. Relative risk (RR) and 95% confidence intervals (95%CI) were calculated based on logistic regression. Receiver operator characteristic (ROC) analysis along with AUC at different intervals and at time points during the OGTT was used to evaluate the risk of prediabetes and diabetes. RESULTS: Twenty-three subjects (3%) developed type 2 DM, 118 (29.3%) IFG, 81 (11.5%) IGT and 544 (71%) subjects remained NGT. AUC and mean difference of glucose in all high-risk groups demonstrated significant differences in both intervals and time points when compared to the NGT group. The cut-off values during OGTT to predict prediabetes and diabetes was determined as blood glucose more than 7.2 and 7.8 mmol/L at 30 and 60 minutes, respectively. The time point 60 has the highest predictive role for the development of diabetes, alone, and improved the performance of a prediction model containing multiple important clinical risk factors. CONCLUSION: The data suggest that the glycaemic response to an OGTT may predict the risk of development of diabetes in first-degree relatives of DM patients.

The role of endothelial progenitor cells in transient ischemic attack patients for future cerebrovascular events.

BACKGROUND: The role of endothelial progenitor cells (EPCs) in the maintenance of vascularization following ischemic brain after experimental stroke has been established. Accordingly, in this study, we evaluated the role of circulating EPCs in transient ischemic attack (TIA) patients for future cerebrovascular (CV) events. MATERIALS AND METHODS: The level of circulating EPCs (staining markers: CD34, CD309) were determined using flow cytometry at 24 h after TIA in thirty consecutive patients. The EPCs level was also evaluated once in thirty healthy volunteers. Over a period of 12 months, all patients were evaluated by an experienced neurologist for recurrent TIA, stroke or death induced by CV disorders. RESULTS: Circulating EPCs increased in patients group following the first attack of TIA when compared with controls. By analysis of covariance, cardiovascular event history, hyperlipidemia, and statin therapy remained significant independent predictors of EPCs. The mean (standard deviation) duration of follow-up was 10.5 (3.1) months (range, 2-12 months). During follow-up, a total of three patients died due to CV accident and four patients experienced again recurrent TIA. By analyzing data with Cox regression, EPC did not predict the future CV events in TIA patients. CONCLUSION: Increased incidence of future CV events did not occur in those patients with elevated EPCs in the first attack of TIA. The significant predicting factors of EPCs were cardiovascular event history, hyperlipidemia, and statin therapy.

Long term administration of thiamine disulfide improves FOXO1/PEPCK pathway in liver to reduce insulin resistance in type 1 diabetes rat model.

OBJECTIVE: The main objective of this study was to find if thiamine disulfide (TD) lowers blood glucose level and improves insulin resistance (IR) in liver and muscle in rats with chronic type 1 diabetes (T1DM) using euglycemic-hyperinsulinemic clamp technique. METHODS: A total of fifty male Wistar rats were assigned to five groups consisted of: non-diabetic control (NDC), diabetic control (DC), diabetic treated with thiamine disulfide (D-TD), diabetic treated with insulin (D-insulin), and diabetic treated with both TD and insulin (D-insulin+TD). Diabetes was induced by a 60 mg/kg dose of streptozotocin. Blood glucose levels, pyruvate tolerance test (PTT), intraperitoneal glucose tolerance test (IPGTT), levels of glycosylated hemoglobin (HbA1c), glucose infusion rate (GIR), liver and serum lipid profiles, liver glycogen stores, liver enzymes ([ALT], [AST]), and serum calcium and magnesium levels. were evaluated. Additionally, gene expression levels of phosphoenolpyruvate carboxykinase (Pepck), forkhead box O1 (Foxo1), and glucose transporter type 4 (Glut4) were assessed in liver and skeletal muscle tissues. RESULTS: Blood glucose level was reduced by TD treatment. In addition, TyG index, HOMA-IR, serum and liver lipid profiles, HbA1c levels, and expressions of Foxo1 and Pepck genes were decreased significantly (P<0.05) in all the treated groups. However, TD did not influence Glut4 gene expression, but GIR as a critical index of IR were 5.0±0.26, 0.29±0.002, 1.5±0.07, 0.9±0.1 and 1.3±0.1 mg.min-1Kg-1 in NDC, DC, D-TD, D-insulin and D-insulin+TD respectively. CONCLUSIONS: TD improved IR in the liver primarily by suppressing gluconeogenic pathways, implying the potential use of TD as a therapeutic agent in diabetes.

Clinico-epidemiological evaluation of pharmaceutical/non-pharmaceutical poisoning in a referral poisoning emergency in the Central part of Iran.

The pattern of poisoning varies in different societies. In this study, we investigated the clinical-epidemiological features and outcomes of poisoned patients based on the substances involved, whether pharmaceutical or non- pharmaceutical toxins. This cross-sectional study involved a retrospective chart review of all poisoned patients who presented to the poisoning emergency hospital in the center of Iran between January 2015 and December 2019. We collected data on socio-demographics, the nature of the poisoning, and the outcomes. Backward stepwise binary regression analysis was conducted to predict the mortality. Throughout the study period, 5777 patients with acute poisoning met the inclusion criteria. Of these, 3524 cases (61%) were attributed to pharmaceutical, and 2253 cases (39%) were due to non-pharmaceutical poisoning. The majority of pharmaceutical poisonings (82.9%) were intentional, whereas non-pharmaceutical poisonings accounted for 46.2% of intentional exposures (P < 0.001). Patients with non-pharmaceutical poisoning were predominantly men, older in age, and had a history of addiction compared to those with pharmaceutical poisoning (P < 0.001). In binary logistic regression analysis, patients poisoned by non-pharmaceutical substances had a significantly higher risk of mortality [Odds ratio, 3.14; (95% CI 1.39-7.10); P = 0.006] compared to those poisoned by pharmaceutical substances (P < 0.001). The pattern of poisoning differs in terms of age and gender when comparing pharmaceutical to non-pharmaceutical poisoning. Patients poisoned by non-pharmaceutical may have a worse outcome compared to those poisoned by pharmaceutical substances.

Time-dependent effect of oral morphine consumption on the development of cytotrophoblast and syncytiotrophoblast cells of the placental layers during the three different periods of pregnancy in Wistar rats.

UNLABELLED: Previous studies have shown that morphine abuse during pregnancy cancause a delay in the development of the placenta and embryo and also bring about birth defects. The present study investigates the effect of the duration of maternal morphine consumption during pregnancy, as well as the impacts of morphine abuse on the development of placental layers during the three different periods of pregnancy in Wistar rats. MATERIALS AND METHODOLOGY: Female Wistar rats have been used in the present study. Experimental groups received morphine (0.05 mg/mL of drinking water) after one night of coupling with male rats for mating. On 9th, 10th, and 14th days of pregnancy, pregnant animals were killed, and placentas were removed and fixed. The cells of the placentas layers were calculated by light microscope and MOTIC and SPSS software. RESULTS: The maternal surface thickness of the placenta was significantly increased, whereasthe fetal surface thickness of placenta was significantly decreased with morphine consumption with a time-dependent manner in experimental groups, compared to control groups. Moreover, the number of trophoblast cells increased in both maternal and fetal surfaces of placenta with respect to the duration of morphine consumption which was overt in the experimental groups compared to the control groups. CONCLUSION: In general, the time-dependent effects of oral morphine consumption can inhibit the development and natural functioning of cytotrophoblast and syncytiotrophoblast cells of the placental layers.

Thr698Thr (nt2369) polymorphism on CACNA1A gene and head pain severity in familial migraine.

BACKGROUND: Migraine is a common neurological disorder with a significant genetic component. Less information is known about the contribution of minor genetic variations, such as single nucleotide polymorphism (SNP) on the migraine process. In the present study, we aim to investigate the role of CACNA1A gene polymorphism on severity and related factors in family positive migraine patients. MATERIALS AND METHODS: We included 74 common migraine patients consequently. Headache severity was evaluated according to Headache Impact Test (HIT6) questionnaire and quality of life of patients was investigated according to MSQ (Migraine-Specific Quality of Life Questionnaire v2.1) questionnaire. Thirty patients with positive family history of migraine were selected and sequencing analysis after DNA extraction was performed. RESULTS: Direct sequencing revealed a known SNP G to A transition in the exon 16 (nt2369, G → A) in 9 patients. There was no significantly correlation between polymorphism and type of migraine, severity, frequency, duration and quality of life in family positive migraine. Evaluated migraine severity by HIT6 questioner couldn't act as a risk factor for this polymorphism (OR: 0.93, CI%95 0.82-1.06 P = 0.3). CONCLUSION: In Iranian population no significant association was seen between Thr698Thr (nt2369) polymorphism and head pain severity in familial migraine. Confirmation of this hypothesis needs further investigation.

Malnutrition is associated with depression in rural elderly population.

BACKGROUND: Aging induces physiological changes and affects all of organs. Nutritional status and mental health deteriorate with aging. As malnutrition and depression are main problem in elderly this study was performed to assess the association between malnutrition and depression among rural elderly. MATERIALS AND METHODS: Three hundred and seventy rural elderly aged over 60 years were examined in a cross-sectional study by systematic sampling method and using mini nutritional assessment (MNA), which is a standard questionnaire for evaluating nutrition status. Depression was evaluated by a validated questionnaire in the elderly. Correlation between Socio-demographic characteristic, diseases, and nutrition status was obtained by t-test, Chi-square test and logistic regression in elderly population. RESULTS: Mean ± SD age was 70.6 ± 7.3 years. Frequency of malnutrition was similar in both genders. According to MNA, 3.8% of subjects suffered from malnutrition, 32.7% were at risk of malnutrition and 63.5% were well-nourished. Nutrition status correlated with body mass index (P = 0.028) and depression (P = 0.001). The risk of severe depression in patients with malnutrition was 15.5 times higher than non-depressed persons (odd ratio: 15.5; 95% CI: 2.9-82.5). CONCLUSION: Depression could act as a powerful risk for malnutrition in elderly population that it should be controlled by physicians.

Enalapril protects endothelial cells against induced apoptosis in Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease in which endothelial cell (EC) can be affected. In brain, functional changes in ECs contribute to reductions in resting blood flow. Furthermore, angiotensin-converting enzyme inhibitors (ACE-I) have beneficial effects on endothelial dysfunction. This is the first study that presents direct experimental evidence associating endothelial apoptosis as a basis of AD pathogenesis and response to an ACE-I therapy. MATERIALS AND METHODS: Human umbilical vein ECs (HUVECs) were treated with sera from AD patients and sera from healthy volunteers (each group, n = 10). Apoptosis was determined by annexin V-propidium iodide staining and cell death detection kit. The effect of 50 µM enalapril on endothelial apoptosis was assessed. Nitrite (NO2 (-)) levels were determined in the culture supernatants. RESULTS: Enalapril suppressed the induction of apoptosis by the serum of patients only when used before treating HUVECs with the sera of AD. Mean ± SD of apoptosis induction in the control group was 6.7 ± 3.69; in the group treated with sera of AD for 24 h was 47.78 ± 0.65; in the group wherein sera from AD was added (pretreatment) after exposure of HUVECs by 50 µM enalapril for 24 h was 26.6 ± 2.63; and in the group wherein HUVECs were exposed in the sera of AD for 24 h and then 50 µM enalapril was added to these cells for another 24 h (post-treatment) was 56.87 ± 5.51. Also, the mean ± SD of NO2 (-) concentration showed significantly greater levels of dissolved NO2/NO3 metabolite in the culture media of untreated HUVECs by enalapril (1.03 ± 0.06) as compared with control (0.26 ± 0.13; P < 0.05), while the rate of nitric oxide (NO) significantly decreased when enalapril was presented in culture both in the pretreatment (0.07 ± 0.003) and in the post-treatment group (0.06 ± 0.005; P < 0.05). CONCLUSION: It could be concluded that EC treated with sera from AD patients activates apoptosis in HUVECs; this effect was reversed by enalapril pretreatment. This can be proposed as a therapeutic approach for Alzheimer's patients.

Association between serum biochemical levels, related to bone metabolism and Parkinson's disease.

BACKGROUND: Vitamin D insufficiency and serum calcium disturbance have been reported to be more common in Parkinson's disease (PD) patients than in healthy control subjects, which may be due to a chronic disease or reduced mobility contributes to these relatively disturbances. Because of the high-vitamin D insufficiency in our population, we aimed to compare a biochemical levels which are related to bone metabolism, in PD patients in comparison with age-matched healthy controls, for the 1(st) time in a Middle East population. MATERIALS AND METHODS: This case-control study was involved 105 (20 were excluded) PD patients, who were age- and -sex matched with 112 controls. 25-hydroxyvitamin D (25OHD) and parathyroid hormone analyzed by enzyme immunoassay; another laboratory data including, calcium, phosphorous, and alkaline phosphatase were performed by spectrophotometric methods. RESULTS: There was no significant difference in 25OHD between PD patients and control group (P = 0.071). 25OHD level was not significantly different in PD patients compared to controls {odds ratio 1.003, (confidence interval [CI], 0.98-1.02), P value 0.793}. None of the other biochemical levels did not induce more chance for PD, only we observed in men has more risk of PD than women (odds ratio 2.53, [CI, 1.27-5.03], P value 0.008). CONCLUSION: Our data do not support a possible role of vitamin D insufficiency in PD. Regarding to variable changes in biochemical markers in PD patients than in controls; further studies are suggested to determine any plausibility role of them as a causal relationship or as an outcome of PD.

Mutation analysis of CACNA1A gene in Iranian migrainous and review literatures.

BACKGROUND: There are contrary results about the role of CACNA1A gene in the causation of common migraine in different populations. However, migraine may be genetically heterogeneous and more studies in different families and populations are required for a definite conclusion. The aim of this study was to surveyed leukocyte genomic DNA mutation of CACNA1A in Iranian migraine patients with [MA] and without aura [MO] who has family history of migraine and we performed a narrative review of all studies that evaluated CACNA1A gene, non-hemiplegic migraine [MA and MO] and FHM [familial hemiplegic migraine]. MATERIALS AND METHODS: The 30 patients with family history of migraine were selected for mutations analysis for CACNA1A gene by PCR method. For review, we searched MEDLINE-PUBMED, ISI, Scopus and Cochrane databases up to December 2012. RESULTS: Mutation analysis of the 4 exons of the CACNA1A gene in these patients revealed no mutations in this gene. Direct sequencing revealed a polymorphism previously reported G to A transition in the exon 16 [nt2369, G→A] in 9 patients. In review, the correlation of FHM loci [CACNA1A gene] with MA and MO has been showed in different population and only small population from Caucasians presented this correlation. CONCLUSION: CACNA1A is most likely not a major susceptibility gene for common migraine in Iranian maigrainous. It's essential to study more on larger series and covering all 47 exons of the CACNA1A gene to confirm this hypothesis.

Evaluation of neural gene expression in serum treated embryonic stem cells in Alzheimer's patients.

BACKGROUND: Previous studies confirmed that neural gene expression in embryonic stem cells (ESC) could influence by chemical compounds through stimulating apoptotic pathway. We aimed to use ESCs-derived neural cells by embryoid body formation as an in vitro model for determination of neural gene expression changes in groups that treated by sera from Alzheimer's patients and compare with healthy individuals. MATERIALS AND METHODS: ESC line which was derived from the C57BL/6 mouse strain was used throughout this study. ESC-derived neural cells were treated with serum from Alzheimer's patient and healthy individual. Neural gene expression was assessed in both groups by quantitative real-time polymerase chain reaction analysis. The data was analyzed by SPSS Software (version 18). RESULTS: Morphologically, the reducing in neurite out-growth was observed in neural cells in group, which treated by serum from Alzheimer's patient, while neurite growth was natural in appearance in control group. Microtubule-associated protein 2 and glial fibrillary acidic protein expression significantly reduced in the Alzheimer's patient group compared with the control group. Nestin expression did not significantly differ among the groups. CONCLUSION: Neural gene expression could be reduced in serum treated ESC in Alzheimer's patients.

A Clinical-Epidemiological Study on Beta-Blocker Poisonings Based on the Type of Drug Overdose.

Background: Beta-blockers carry a high risk of potentially causing fatal poisoning if overdosed. We aimed to assess the clinical and epidemiological characteristics of patients with beta-blocker poisoning. Methods: Patients were categorized based on the type of drug poisoning into propranolol, other beta-blockers, and the combination of beta-blocker groups, respectively. Demographic data, drug toxicity, and clinical, laboratory, and treatment information of different groups were compared. Results: During the study period, 5086 poisoned patients were hospitalized, of whom 255 (5.1%) had beta-blocker poisoning. Most patients were women (80.8%), married (50.6%), with a history of psychiatric disorders (36.5%), previous suicide attempts (34.6%), and intentional type of exposure (95.3%). The mean ± SD age of the patients was 28.94 ± 11.08 years. Propranolol toxicity was the most common among different beta-blockers (84.4%). There was a significant difference in age, occupation, education level, and history of psychiatric diseases with respect to the type of beta-blocker poisoning (P < 0.05). We observed changes in the consciousness level and need for endotracheal intubation only in the third group (combination of beta-blockers). Only 1 (0.4%) patient had a fatal outcome in toxicity with the combination of beta-blockers. Conclusion: Beta-blocker poisoning is not common in our poisoning referral center. Propranolol toxicity was most common among different beta-blockers. Although symptoms are not different among defined beta-blocker groups, more severe symptoms are observed in the combination of the beta-blocker group. Only one patient had a fatal outcome in the toxicity with the combination of the beta-blocker group. Therefore, poisoning circumstances have to investigate thoroughly to screen coexposure with combined drugs.

Effect of Long-Term Oxygen Therapy on Reducing Rehospitalization of Patients with Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

INTRODUCTION: The aim of this work is to evaluate whether the addition of home oxygen therapy (HOT) would reduce readmission in chronic obstructive pulmonary disease (COPD) patients. METHODS: PubMed, ScopeMed, Cochrane, Scopus, and Google Scholar databases were searched. The search strategy used the following keywords "chronic obstructive pulmonary disease", the intervention "long-term oxygen therapy", and the outcome "readmission" combined with the AND operator. The Newcastle-Ottawa Scale and Jadad Scale were used for assessing the quality of cohort studies and clinical trials, respectively. A random-effects model was employed in this study after calculating the standard errors by 95% confidence intervals. The I2 statistic and Cochran's Q-test were used to measure heterogeneity. To address heterogeneity, subgroup analyses were carried out according to the length of LTOT, which was classified as "over 8 months" and "under 8 months". RESULTS: Seven studies were included in the analysis. In the pooled analysis, the RR [CI95%, p value], heterogeneity criteria for readmission reduced by 1.542 [1.284-1.851, < 0.001], I2 = 60%, and 1.693 [1.645-1.744, < 0.001], I2 = 60% for patients with a length of LTOT treatment under and above 8 months, respectively. A sensitivity analysis was conducted by systematically omitting each study, and it showed no influential studies. Egger's test indicated no publication bias (p = 0.64). CONCLUSIONS: Based on our results in this systematic review, long-tern oxygen therapy (LTOT) at home was associated with a significantly lower risk ratio of hospital readmission. However, the sample sizes in the studies necessitate larger RCTs to evaluate the effect of LTOT on readmission in COPD patients.

Acute pesticide poisoning in the central part of Iran: A 4-year cross-sectional study.

Objectives: Intoxication with pesticides is a well-known public health problem. We aimed to describe the demographic and toxico-clinical characteristics and outcomes of patients with pesticide poisoning. Methods: This retrospective cross-sectional study was performed in Khorshid Hospital affiliated with Isfahan University of Medical Sciences, Isfahan, Iran. All patients with pesticide poisoning (insecticides, herbicides, fungicides, rodenticides, and acaricides) were evaluated. The patients' demographic, toxicological, clinical, and laboratory findings from March 2016 until March 2021 were collected and analyzed. Results: During the study period, 25,659 patients with acute poisoning were admitted, of which, 1567 (6.1% of the total poisoning) with pesticide poisoning were included. The mean ± SD age of the patients was 31.34 ± 13.7 years and 55.3% were men (male/female ratio = 1.23). In approximately 75% of the patients, poisoning occurred by suicidal attempts, while in 14.3% (n = 224), it was accidental. Insecticides caused about 51.30% of the poisonings. However, rodenticides were most commonly used in completed suicide attempts (79.9%). The frequency of previously attempted suicide, and self-harming was different among the patients with respect to the type of pesticide poisoning (p < 0.05). Previous suicidal attempts (35.3%) and self-harming (17.3%) were reported more in patients poisoned with the combination of pesticides. Half of the patients were employed. Nausea and vomiting (56.7%, n = 889) were the most common clinical manifestations; 8.3% (n = 130) of the patients died, 64 of whom had rodenticide poisoning. Conclusion: The prevalence of pesticide poisoning was relatively low; most were insecticide poisoning. Poisoning occurred most through attempted suicide. Rodenticides and herbicides had higher mortality rates than other pesticides. Patients with previously attempted suicide and self-harming behavior may use a combination of pesticides.