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Aim To evaluate Klotho and SIRT1 expression in the heart and kidneys of rats with acute and chronic renovascular hypertension. Methods Four and sixteen weeks after the induction of renovascular hypertension by clipping the left renal artery, systemic blood pressure, serum angiotensin II level, and the expression of Klotho and SIRT1 proteins and oxidative stress indices in the heart and kidneys were assessed. Results SIRT1 level was significantly reduced in the ischemic (left) kidney in acute and chronic phases of hypertension. In the heart, it decreased in the acute phase, but increased in the chronic phase. Klotho levels in the heart and kidneys did not change significantly in either hypertension phase. Superoxide dismutase (SOD) activity in the heart significantly decreased, and SOD, total antioxidant capacity, and malondialdehyde in the ischemic kidney significantly increased during the development of hypertension. Serum angiotensin II level significantly increased in the acute phase of hypertension. Conclusion Development of renovascular hypertension was associated with a reduction of SIRT1 expression in the heart and ischemic kidney. As angiotensin II and SIRT1 counteract each other's expression, a SIRT1 reduction in the heart and kidney, along with the influence of systemic/local angiotensin II, seems to be partly responsible for hypertension development. A combination of SIRT1 agonists and angiotensin II antagonists may be considered for use in the treatment of renovascular hypertension.

Background and aims: The aim of the present study was to investigate the main causes of traumatic spinal cord injury (TSCI), along with the relationship between SCI patients’ demographic characteristics and related treatments. Methods: In general, 608 patients suffering from TSCI and referring to Ayatollah Kashani hospital, Shahrekord in 2016-2017 were enrolled in this cross-sectional study. Patients’ demographic characteristics, level of injury, the severity of the injury, injury cause, and duration of hospitalization (DOH) were obtained according to their files and medical records. Several months after discharge, the patients were examined by a neurosurgeon, and the treatment outcome was recorded in specific checklists. Results: The mean age of the injured individuals was 34.2±16.9 years and the majority of the injured (70.2%) were males. ASIA grades E and D were also reported in 50.3% and 25% of the injured at admission, respectively. Further, grade E injury was observed in 77.1% of the injured at discharge. Medicinal, non-surgical, and surgical treatments were used for 53.8%, 25.8%, and 20.4% of patients, respectively. The levels of injury, treatment strategy, and clinical outcomes were significantly different based on the ASIA grades at admission (P

The aim of this study was to determine the responses of appetite regulating hormones and body composition to different periods of resistance training (RT) and subsequent detraining in men with obesity. Thirty obese males were randomly assigned into two groups of 15 individuals which included the RT group (3 sessions per week, 4 sets of 8 repetitions with 80% of 1RM) and control group. Measurements were performed in five steps and each time after 10 h overnight fasting: before the start of the training program, after the 8, 16, and 24 weeks of RT, and finally after 2 weeks detraining. Between groups comparisons showed plasma concentrations of acylated ghrelin and insulin hormones, as well as body weight, BMI, WHR, and body fat percentage were significantly lower in the experimental group compared to the control group after 2, 4, and 6 months of RT (in all cases, p ≤ 0.05). However, after 4 and 6 months of RT, the levels of peptide YY was higher in the training group in comparison to the control group (p = 0.001 and p = 0.001, respectively). Within group changes indicated acylated ghrelin reduced (mean difference, −9.27 pg/dl; P = 0.001), while PYY increased (mean difference, 2.66 pg/dl; P = 0.001) after 6 months of RT compared to the pre-test. By increasing the duration of training, changes in the variables were more perceptible. After detraining, most of the changes were reversed. Performing RT by regulating appetite-related hormones can lead to weight loss and improvement of BMI in men with obesity.

Mit modernen Früherkennungsuntersuchungen lässt sich die Alzheimer-Krankheit (Alzheimer’s Disease, AD) lange vor Symptombeginn der Alzheimer-Demenz nachweisen. Patienten fragen immer häufiger nach entsprechenden diagnostischen Verfahren. Der Einsatz von Biomarkern für die Früherkennung der AD ist somit zunehmend klinisch bedeutsam. Dieser Artikel gibt einen Überblick über die derzeitigen prädiktiven Verfahren der Alzheimer-Demenz.

Long non-coding RNAs (lncRNAs) have a critical role in the regulation of cardiovascular function. Dysregulation of lncRNAs is implicated in the progression of cardiovascular diseases including myocardial infarction (MI). Regarding the beneficial effects of exercise (Ex) on the improvement of MI, this study aimed to investigate the effects of post-MI Ex on the expression of MI-associated lncRNAs: H19, myocardial infarction association transcript (MIAT), and growth arrest specific 5 (GAS5). MI was induced by left anterior descending (LAD) coronary artery ligation in male Wistar rats. One week later, rats were exercised under a moderate-intensity protocol for 4 weeks. In the end, hemodynamic parameters and cardiac function indices were measured. Assessment of fibrotic areas and apoptosis was performed by Masson's trichrome staining and immunohistochemistry, respectively. Expression of genes was evaluated by real-time PCR. Ex significantly reduced the fibrotic areas (P

Hypertension (HTN) is an important cause of cardiovascular-related morbidity and mortality. The present study was conducted to investigate the prevalence and incidence rate of pre-HTN, diagnosed and undiagnosed HTN, as well as its control and associated factors in adult population in southeast Iran. In a randomized household survey, 9987 participants aged 15-80 years were recruited into the study. HTN was confirmed through examination or using antihypertensive drug(s). Pre-HTN and HTN were defined as 120-139/80-89 and ≥140/90 mmHg for systolic and diastolic BP, respectively. The prevalence of pre-HTN was 28.5%. The prevalence of HTN was 19.2% (13.9% diagnosed and 5.3% undiagnosed). HTN increased with age (from 4% in 15-24 to 67.8% in 75-80 years). Men had higher pre-HTN (35.6% vs. 23.4%) and undiagnosed HTN (7.5% vs. 3.8%) than women. Of those diagnosed, 46.5% had uncontrolled BP, in which, women had better conditions than men (45.6% vs. 47.4%). Obesity, positive family history of HTN, anxiety, and low physical activity were the most significant predictors of HTN. The prevalence of pre-HTN decreased but there was no change in the prevalence of HTN during the last 5 years. The 5-year incidence rate/100 person-years of pre-HTN and HTN was 6.6 and 3.7, respectively. Although there are some promising signs of reducing pre-HTN and slowing HTN rise, currently, almost one-fifth of the adult population suffers from HTN. Given the poor BP control in patients with diagnosed HTN, especially in men, alarms that more effective interventions and strategies are needed to reduce deleterious consequences of HTN.

Introduction : Epicardial fat thickness (EFT) can reflect risk of cardiovascular disease particularly coronary artery disease (CAD). The aim of this study was to investigate the association of EFT assessed by echocardiography and presence as well as severity of CAD. Methods: Two hundred and twenty consecutive patients who candidate for coronary angiography because of possible CAD were studied. EFT was evaluated in standard parasternal long axis (PlAX) and parasternal short axis (PSAX) view from 3 cardiac cycles at the end of systole and diastole. The severity of CAD was defined in two ways: (1) SYNTAX score, (2) number of vessels with significant lesion. Results: PLAX (EFTS ) (EFT in systole) and PLAX (EFTd ) (EFT in diastole) were significantly higher in patients with CAD in comparison with patients without CAD (P = 0.046, P = 0.041 respectively). There was a significant correlation between PLAX (EFTS ) (P = 0.05), PLAX (EFTd ) (P = 0.04) and SYNTAX score. There was no statistically significant relationship between EFT and number of diseased vessel (P > 0.05). Multivariate analysis was done for adjusting the effects of confounding factors and it showed that EFT (OR: 10.53, P = 0.004) was significantly correlated severe CAD as assessed by the SYNTAX score. Conclusion: EFT assessed by transthoracic echocardiography was higher significantly in patients with CAD than in normal patients. EFT as an easily available and cost-effective echocardiographic feature might be useful to predict complexity of CAD.

Introduction Idiopathic generalised epilepsy (IGE) refers to a group of epilepsies resulting from the activation of neurons in the whole brain. This study aimed to evaluate the metabolite changes in thalamus as diagnostic biomarkers in IGE patients compared to healthy individuals using magnetic resonance spectroscopy (MRS) technique. Methods The MRS was performed on 35 IGE patients (26 women and 11 men) with average age of 32 (ranged from 18 to 43) and 35 healthy individuals (13 women and 22 men) with average age of 31 (ranged from 21 to 50) as the control group. The levels of N-acetylaspartate (NAA), creatine (Cr) and choline (Cho) were measured using MRS. The NAA/Cr and NAA/Cho ratios were calculated for all participants. These values were statistically compared using t-test between the groups. Results The NAA had significant lower values in IGE patients, 9.6 (SD = 0.8) and 9.9 (SD = 0.7) for right and left thalamus, respectively, compared to 10.9 (SD = 0.9) and 10.7 (SD = 0.9) in control group. The Cr values in the left side of thalamus were significantly higher in IGE patients (6.7 [SD = 0.8] versus 5.8 [SD = 0.5]); however, there was no difference in right thalamus. Measurements showed no difference for amounts of Cho between the groups in both sides of thalamus. The NAA/Cr ratio was 1.48 (SD = 0.14) and 1.48 (SD = 0.16) for right and left thalamus, respectively, in IGE patients in comparison with 1.83 (SD = 0.2) and 1.86 (SD = 0.26) in controls. There was no meaningful variation between the NAA/Cho ratio of the right and left thalamus among the groups. Conclusion Thalamic NAA, Cr and NAA/Cr ratio values in IGE patients showed statistical differences compared to healthy individuals. Evaluating metabolites variations in thalamus using MRS is suggested for differentiating IGE patients from healthy individuals.

Background Hypertension and diabetes are among the most important risk factors of cardiovascular diseases. Klotho and SIRT1 are known as anti-aging factors with beneficial effects on cardiovascular system. In this study we investigated the serum Klotho and SIRT1 levels in pre-diabetic and pre-hypertensive individuals and then in diabetic and hypertensive patients to see their relationship with these diseases. Method 229 individuals divided into six groups with similar gender and age distribution 1—Control (normal BP and FBS) 2—pre-diabetic (FBS between 100 and 125 mg/dl) 3—diabetic (FBS ≥ 126 mg/dl), 4—pre-hypertensive (SBP 120–139 or DBP 80–89 mm Hg) 5—hypertensive (SBP ≥ 140 or DBP ≥ 90 mm Hg), and 6—patients with combined hypertension/diabetes. Serum levels of Klotho and SIRT1 were measured by ELISA method. Results Serum Klotho and STRT1 levels decreased in pre-diabetes and returned to normal in diabetic patients. Their concentration increased in pre-hypertension and recovered to normal in hypertension. In the physiologic range of FBS there is a negative correlation between Klotho and SIRT1 with FBS. When pathologic ranges of FBS added to analysis, the negative correlation abolished/U shaped. Also an inverse U shape correlation observed between Klotho and SIRT1 with MAP in the range of normal to hypertensive BP levels. There was an overall positive relationship between the serum levels of Klotho and SIRT1 themselves. Conclusion The serum levels of the anti-aging proteins Klotho and SIRT1 increases or reduces at the onset of the disease, as a compensatory mechanism, but as the disease progresses their level recovers.

Background: Given the increasing use of waterpipe tobacco smoking in the world and its unknown effects on bone healing, this study investigated the repairing of femoral bone fractures in rats exposed to waterpipe tobacco smoking (WTS).Main Methods: This study involved 40 male Wistar rats that were divided into two groups, including the femoral fracture (Fx) and the Fx + WTS groups. Each group was divided into two subgroups that were evaluated for bone healing 28 and 42 days after femoral fracture. After fixing the fractured femur, the healing process was evaluated by radiography, pathological indicators, and a measurement of the blood levels of vascular endothelial growth factor (VEGF), parathyroid hormone (PTH), Ca ++, transforming growth factor-beta (TGF-β), and insulin-like growth factor 1 (IGF-1). Additionally, the density of VEGF and CD34 in fracture tissue was investigated by immunohistochemistry.Key Findings: Radiographic findings showed that factors related to the earlier stages of bone healing had higher scores in the Fx + WTS28 and 42 subgroups in comparison to the Fx groups. The density of VEGF and CD34 showed that the angiogenesis processes were different in the bone fracture area and callus tissue in the Fx +WTS subgroups. The serum levels of VEGF, TGF-β, and IGF-1 were significantly lower in the Fx +WTS42 group, and PTH in the Fx +WTS28 group was higher than that in the other groups.Significance: The findings showed the disturbance and delay in the femoral fracture union in rats exposed to hookah smoke. This is partly due to the reduction of molecular stimuli of bone synthesis and the attenuation of quantitative angiogenesis.

Orchitis as inflammation of testis occurs following traumatic injuries such as testicular torsion leading to high levels of oxidative stress and inflammation. Rosmarinus officinalis is a herb with anti-inflammatory and antioxidant properties. This study assessed therapeutic effects of rosemary following testicular torsion. A total of 36 male mice were categorised; control, torsion, rosemary (100 and 200 mg/kg) and torsion+rosemary groups. Torsion was induced surgically, and rosemary was gavaged. Total antioxidant capacity of extract was approved by Ferric Reducing Ability of Plasma. Malondialdehyde and Griess protocols were hired to assess oxidative stress. Finally, sperm parameters and testosterone levels were analysed. Immunofluorescent (of Tumour Necrosis Factor Alpha), hematoxylin and eosin stainings and expression of inflammatory genes (Interleukin-1α, Interleukin-1β, Interferon-γ) were also assessed. Data were analysed using SPSS (v. 19), and graphs were drawn by GraphPad Prism (v. 9). Significantly (p < .05), oxidative stress indices and inflammatory genes expression were increased in torsion group, and total antioxidant capacity was increased in rosemary groups. In torsion+rosemary groups, total antioxidant capacity, sperm parameters and testosterone levels were increased, and inflammatory gene expression decreased significantly (p < .05). Rosemary with anti-inflammatory and antioxidant properties accelerates testicular healing in torsion cases, especially in therapeutic dose of 200 mg/kg.

Arrhythmias are one of the leading causes of early death following myocardial infarction (MI) and heart failure. Graphene derivatives have emerged as an therapeutic target that have electrical conductivity. The study aimed to evaluate the impacts of polyethylene glycol-graphene quantum dots (GQDs-PEG) on arrhythmias created by MI in the rat. Animals were randomly assigned to five groups of sham, MI, and MI + GQDs-PEG at doses of 5, 10, and 20 mg/kg. MI was induced by the closure of the left anterior descending artery. The day after MI, animals were administered vehicle (phosphate buffered saline) or GQDs-PEG at different doses every other day for 2 weeks. On day 15, electrocardiogram (ECG), mean arterial pressure (MAP), and heart contractility indices were recorded by the PowerLab data acquisition system. GQDs-PEG 20 mg/kg increased contractility and improved the reduction of MAP in the MI group. The prolonged QT and QTc intervals, inverted T wave, and deviated ST segment were modified by GQDs-PEG 10 and 20 mg/kg in rats with MI. The amplitude of the Q wave was also decreased in a dose-dependent manner in the GQDs-PEG-treated rats. The results demonstrated that 2 weeks of treatment with GQDs-PEG normalized ECG abnormalities and improved left ventricular dysfunction in rats with MI.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by dyspnea and progressive loss of lung function. In this study, the preventive and therapeutic effects of methanolic ext...

Introduction Asthma is a chronic inflammatory disease of the airways. In this study, we evaluated the anti-inflammatory effects of myrtenol on the inflammatory indices in the pulmonary parenchyma and airways and on the inflammatory and oxidative indices of the bronchoalveolar lavage fluid (BALF) of asthmatic rats. Methods The allergic asthma was induced by sensitization (two weeks) followed by the inhalation of ovalbumin (four weeks). Animals were divided into two main groups: (1) Histopathology, and (2) measurement of inflammatory and oxidative biomarkers in the BALF. Each main group was subdivided into four subgroups: Control, Asthma, Asthma + Dexamethasone and Asthma + Myrtenol. (−)-Myrtenol (50 mg/kg) or Dexamethasone (2.5 mg/kg) was administered intraperitoneally once a day for one week, at the end of the inhalation period. On day 50, lung histopathologic parameters and inflammatory indices in BALF including INF-γ, IL-10, IL-1β, and TNF-α and oxidative stress biomarkers (MDA, SOD, and GPX) were measured. Result In the Asthma group, leukocyte infiltration, the thickness of smooth muscle and epithelium of airways wall and the number of goblet cells increased. Myrtenol reduced all of the above-mentioned indices except the epithelium thickness. It also inhibited the increase in BALF IL-1β, TNF-α and MDA and increased the levels of INF-γ, IL-10 and SOD. Conclusion Our results suggest that myrtenol reduced damage caused by experimental asthma by reducing the inflammatory indices, normalizing the level of interleukins and balancing oxidative stress in the lungs. It also prevented airway remodeling. Myrtenol may be suggested as a potent herbal medicine for the treatment of allergic asthma.

Introduction: Lung fibrosis is a progressive, fatal disease that is characterized by increasing fibroblasts proliferation and extracellular matrix precipitation. Studies have shown that cyclooxygenase- 2 (Cox-2) could play a crucial role in the pathogenesis of lung fibrosis. In the current study, the effect of thalidomide on bleomycin-induced pulmonary fibrosis was qualitatively studied in a laboratory animal model. Methods: Thirty-two adult male C57BL/6 mice were randomly assigned to the following four groups: Group one received 2 mg bleomycin, group two received bleomycin in addition to 4 mg of thalidomide; group three received 4 mg of thalidomide, and Group 4 received 0.1 mg of 0.5% carboxymethyl cellulose (CMC) via intraperitoneal (IP) administration. Finally, the expression of Cox-2 protein and the percentage of contact points of alveolar spaces and pulmonary connective tissue were determined. Results: Our results showed that in the Bleo + Thal group compared to the Bleo group, the percentage of contact points of pulmonary connective tissue decreased significantly (P

Background. Recent studies have suggested that angiogenic factors may affect vascular endothelial integrity. On the other hand, endothelial dysfunction is the main pathological mechanism in microvascular angina (MVA) or cardiac syndrome X. Therefore, we aimed to determine the levels of angiogenic factors in MVA patients. In addition, we investigated the effects of metoprolol, as a beta blocker agent, on the serum levels of these factors.Methods. Thirty patients with MVA (17 female/13 male; mean age: 55.53±9.18 years) and twenty healthy controls (14 female/6 male; mean age: 51.40±9.16 years) were enrolled.The serum amounts of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2) and tyrosine kinase-2 receptor (Tie-2) were measured in healthy controls, MVA patients at baseline and after metoprolol therapy (25 mg for one month) by enzyme-linked immunosorbent assay.Results. The levels of Ang-2 and Tie-2 were significantly higher in MVA patients at baseline in comparison with controls (Ang-2: 277.02±186.08 vs.164.46±49.83 ng/l, P=0.011; Tie-2: 28.97±18.85 vs. 14.90±4.05 ng/ml, P=0.002; respectively). But this difference in the Ang-1 levels was not significant (P=0.829). Additionally, the levels of angiogenic factors in MVA patients after metoprolol therapy were not significantly changed in comparison with the baseline status (P>0.05).Conclusion. Our results considered a possible role for angiogenic factors in the pathophysiology of MVA, which need ‎further investigation for elucidation. In addition, this study has not showed an effective role for metoprolol in changing the angiogenic factors levels as a therapeutic agent in MVA.

Background : Colorectal cancer (CRC) is one of the main cancer related morbidity wordwidth. New therapeutic strategies are required for CRC. Anthracycline drugs such as doxorubicin (DOX) remain one of the most active wide-spectrum and cost-effective drugs in cancer therapy. However, colorectal cancer (CRC) cells are inherently resistant to anthracyclines. Curcumin, the active component and yellow pigment, has been considered as anti-cancer agents with anti-proliferation, anti-invasion, and anti-angiogenesis properties. Previous data show that curcumin may played main role as therapeutic agent for colorectal cancer. We aimed to assess the possible sensitizing effects of curcumin in HCT-116 CRC cells treated with DOX. Methods ;HCT-116 cells were treated with different doses of curcumin and DOX in increasing concentrations and cytotoxicity were evaluated after 48 h by Water Soluble Tetrazolium Salts(WST-1) method. In double combination treatments (48 h), the mentioned concentration were utilized; D( Curcumin; 20 µM;DOX;5µM) C( Curcumin; 10 µM;DOX ;2.5µM ), B(Curcumin; 5 µM;DOX;1µM) and A(Curcumin; 2.5 µM;DOX;0.5µM). Results ; HCT-116 cells treatments with various concentrations of single agents (DOX and curcumin) decreased the cellular viability in a dose-dependent pattern. Here, we show that treatment of HCT-116 CRC cells with curcumin increases the efficacy of DOX-induced death in HTCT-116 cells. Curcumin treatments also results in higher cytotoxicity of DOX and the cell death percent in compared to higher doses in single treatments. Conclusion ; It could be concluded that Curcumin could acts as chemosensitiser towards the DOX therapy. So it might be used as adjuvant therapy to enhance DOX sensitivity in CRC cells.

Polycystic ovary syndrome (PCOS) is one of the most important gynecological disorders among reproductive-age women. In patients with PCOS, the secretion rate and metabolism of androgens and estrogens are disrupted. With regards to the increasing prevalence of PCOS and associated physical and mental problems as well as the effects of changes in sex hormones in development of this disease, our aim is to investigate the effects of different herbal extracts on changes in the serum levels of sex hormones and ovarian tissue. To conduct this review, an extensive literature search was conducted using, relevant publications published between 1990 and 2017, and indexed in Google Scholar, PubMed, Elsevier, Scientific Information Database, and Science Direct were studied. The search terms used to retrieve the publications were as follows: Herbal medical extract، Names of medicinal plants ، polycystic ovary syndrome, PCOS, the mechanism of hormone. According to the evidence, herbal extracts containing phytoestrogens cause decrease in hyperandrogenism, insulin resistance, and ovary weight as well as increase in ovulation. Therefore, these plants can be partly effective in this syndrome via affecting the serum levels of different hormones and ovarian weight and morphology, representing an opportunity to investigate and discovery new bioactive products. Keywords: Medical herbs, Polycystic ovary syndrome, Sex hormones, Fertility

Introduction. The biocompatibility and potential application of graphene-based nanomaterials in biomedicine have been documented. The effects of polyethylene glycol-graphene quantum dots (GQDs-PEG) on cardiac function in rats with myocardial infarction (MI) were examined. Methods. Wistar rats were randomly assigned to two main groups, each consisting of sham-Veh., MI-Veh., and MI+GQDs-PEG at doses of 5, 10, and 20 mg/kg. MI was induced by the closure of the left anterior descending (LAD) coronary artery. After MI, GQDs-PEG were injected at different doses IP every other day for two weeks. In the end, hemodynamic and heart contractility indices were assessed. The levels of myocardial MDA (malondialdehyde), SOD (superoxide dismutase), GPX (glutathione peroxidase), and TAC (total antioxidant capacity) were measured by the ELISA method. The serum ALP, ALT, AST, creatinine, and urea levels were measured using the photometric method. The infarct size was assessed by TTC staining. Results. GQDs-PEG decreased the infarct size at doses of 10 and 20 mg/kg and recovered the MI-induced reductions of +dp/dt max and -dp/dt max in the study groups. GQDs-PEG normalized systolic blood pressure and left ventricular systolic pressure reduction at the dose of 20 mg/kg in the MI group. Heart SOD, GPX, and TAC increased in the GQDs-PEG 10 and 20 groups. Almost no signs of toxic effects due to GQDs-PEG administration were observed on the liver and kidneys. Conclusions. The results provided clear evidence that GQDs-PEG improve cardiac performance and hemodynamic parameters in rats with MI by reducing oxidative stress. GQDs-PEG is proposed as a therapeutic target for the treatment of MI.

Purpose: Pyroptosis, a form of inflammatory programmed cell death, is activated in diabetic patients. This study was conducted to investigate the effects of daily consumption of sodium butyrate (NaBut) and high-performance (HP) inulin supplementation, individually or in combination, on the expression of pyroptosis-related genes, microRNA (miR) 146a-5p, miR-9-5p and biomarkers of oxidative stress in patients with type 2 diabetes (T2DM). Methods: In this study, we conducted a randomized, double-blinded, placebo-controlled clinical involving sixty patients with type 2 diabetes. Participants received 600 mg/d of NaBut (group A), 10 g/d of HP inulin (group B), 600 mg/d of NaBut + 10 g/d of HP inulin (group C) or placebo (group D) for 45 consecutive days. We assessed the pyroptosis-related genes mRNA expression in peripheral blood mononuclear cells (PBMCs), as well as the plasmatic levels of miR-146a and miR-9 before and after the intervention. Moreover, blood samples of the patients at baseline and following the intervention were tested for total antioxidant capacity (TAC), superoxide dismutase (SOD) and catalase levels using enzyme-linked immunosorbent assay (ELISA). This study was registered on the Iranian Registry of Clinical Trials website (identifier: IRCT201605262017N29; https://www.irct.ir/). Results: Following butyrate supplementation, the relative expression levels of TLR2/4, NF-κB1, Caspase-1, NLRP3, IL-1β & IL-18 were significantly downregulated (p < 0.05). Furthermore, butyrate and concomitant use of butyrate and inulin caused a significant increase in the fold change of miR-146a and miR-9 compared with the placebo group (p < 0.05). Interestingly, the changes in total antioxidant capacity (p = 0.047) and superoxide dismutase (p = 0.006) were significantly increased after butyrate and concomitant use of butyrate and inulin supplement, respectively. Conclusion: In summary, the change in expression level of miR-146a-5p and miR-9-5p due to butyrate supplementation may have a pivotal role in alleviating of diabetes via inhibiting pyroptosis by targeting TLR2 and NF-κB1. These microRNAs might be considered as potential therapeutic targets in the treatment of type 2 diabetes but further researches is required to prove the link.

One of the prominent problems in clinical medicine is medication-induced acute kidney injury (AKI). Avoiding this problem can prevent patient harm and reduce healthcare expenditures. Several researches have been conducted to identify AKI-associated medications using statistical, data mining, and machine learning techniques. However, these studies are limited to assessing the impact of known nephrotoxic medications and do not comprehensively explore the relationship between medication combinations and AKI. In this paper, we present a population-based retrospective cohort study that employs automated data analysis techniques to identify medications and medication combinations that are associated with a higher risk of AKI. By integrating multivariable logistic regression, frequent itemset mining, and stratified analysis, this study is designed to explore the complex relationships between medications and AKI in such a way that has never been attempted before. Through an analysis of prescription records of one million older patients stored in the healthcare administrative dataset at ICES (an independent, non-profit, world-leading research organization that uses population-based health and social data to produce knowledge on a broad range of healthcare issues), we identified 55 AKI-associated medications among 595 distinct medications and 78 AKI-associated medication combinations among 7748 frequent medication combinations. In addition, through a stratified analysis, we identified 37 cases where a particular medication was associated with increasing the risk of AKI when used with another medication. We have shown that our results are consistent with previous studies through consultation with a nephrologist and an electronic literature search. This research demonstrates how automated analysis techniques can be used to accomplish data-driven tasks using massive clinical datasets.

Exercise training (Ex) has beneficial effects on cardiovascular diseases by increasing Klotho and SIRT1. This study aimed to investigate whether the beneficial impact of Ex on myocardial infarction (MI) is mediated through Klotho and SIRT1. Fifty-six Wistar rats were divided into 4 main groups of Sham, MI, Ex, and MI + Ex. MI was induced by the closure of the left anterior descending. Animals were trained by endurance exercise for 4 weeks. In the end, hemodynamic and heart contractility indices were assessed. The levels of Klotho and SIRT1 in the serum and heart were measured by enzyme-linked immunosorbent assay and Western blot, respectively. The ADAM17 level in the heart and kidneys was assessed by enzyme-linked immunosorbent assay. The infarct size and fibrosis area were assessed by triphenyltetrazolium chloride and Masson trichrome staining, respectively. Ex recovered the reduction of dp/dt max and dp/dt min and decreased myocardial infarct size and fibrotic area in the MI group. Ex normalized the increase in heart rate, systolic blood pressure, left ventricular systolic pressure, and left ventricular end diastolic pressure in the MI group. Ex also normalized the reduction of the levels of Klotho and SIRT1 in serum and heart in the MI group. The changes of Klotho and SIRT1 in serum were positively correlated. Ex also restored ADAM17 levels in the MI group. Ex improved cardiac function in the MI group and is associated with reduction of the infarct size and normalization of Klotho and SIRT1 levels. Regarding unidirectional changes in Klotho and SIRT1, these proteins may play a role in beneficial effects of Ex on MI recovery.

Objectives Graves’ disease (GD) is an autoimmune disease causing the overproduction of the thyroid hormone from thyroid gland. This disease is mainly the result of the production of antibodies against TSH receptors. Cytokines play an important role in orchestrating the pathophysiology in autoimmune thyroid disease. The regulatory role of IL-12 on TH1 cells has been proven. IL-27 and IL-35, members of IL-12 cytokine family, are two cytokines that have been newly discovered. IL-35 has been identified as a novel immunosuppressive and anti-inflammatory cytokine while IL-27 has both inflammatory and anti-inflammatory functions. The objective of the current study was to examine the changes in the serum level of the foregoing cytokines in GD patients in comparison to healthy controls. Materials and methods In this study, serum levels of IL-27 and IL-35 were determined by an ELISA method; anti TPO and anti Tg were measured by an RIA method in 40 new cases of Graves’s disease. The findings were compared with 40 healthy controls. Results The results showed a significant difference between IL-27 and IL-35 regarding their serum levels with P values of 0.0001 and 0.024, respectively; anti TPO and anti Tg levels of the cases were also significantly different from controls (p < 0.001). Conclusion The reduction in the serum levels of IL-27 and IL-35 in GD patients compared to normal subjects suggests the possible anti-inflammatory role of these cytokines in GD.

Osteosarcoma, a bone cancer usually seen in children and young adults, is generally a high-grade malignancy presented by extreme metastases to the lungs. Osteosarcoma has a tendency for appearing in bones with rapid growth rate. The etiology of osteosarcoma is multifaceted and poorly understood. A molecular consideration of this disease will lead to a directed tumor treatment. The present treatment for osteosarcoma comprises of an arrangement of systemic chemotherapy and wide surgical resection. Survival rate is increased by the progress of destructive systemic chemotherapies. So, the development of new treatment approaches for metastatic osteosarcoma is essential. Immunomodulation has been used in clinical settings. Through targeting surface antigens expressed on tumor cells, particular antibodies and exploitation of cellular immunotherapy against sarcomas have been confirmed to be effective as cancer therapeutics. In this article, we have reviewed epidemiology, etiology, pathogenesis, diagnosis, and treatment of osteosarcoma and we have focused on different methods of immunotherapy including vaccines, cell-based immunotherapy, cytokines, and monoclonal antibodies.

Background: Health literacy (HL) refers to the capacity to access, understand, appraise and apply information for decision-making and acting in health-related matters. In the field of Alzheimer’s disease (AD), expanding technologies of early disease detection, disease course prediction and eventually personalized prevention confront individuals at-risk with increasingly complex information, which demand substantial HL skills. Here we report current findings of HL research in at-risk groups. Methods: Search strings, referring to HL, AD, amyloid and risk, were developed. A systematic review was conducted in PUBMED, Cochrane Library, PsycINFO, and Web of Science to summarize the state of evidence on HL in at-risk individuals for Alzheimer’s dementia. Eligible articles needed to employ a validated tool for HL, mention the concept or one dimension (access, understand, appraise and apply information for decision-making and acting). Results: 26 quantitative and 9 qualitative studies addressing at least one dimension of HL were included. Overall, there is evidence for a wish to gain knowledge about the own brain status and risk of dementia. Psychological distress may occur and the subjective benefit-risk estimation may be modified after risk disclosure. Effects on lifestyle and planning may occur. Overall understanding and appraisal of information related to AD risk seem variable with several impacting factors. In mild cognitive impairment (MCI) basic HL skill seem to be affected by cognitive dysfunction. Conclusions: Systematic assessment of HL in at-risk population for AD is sparse. Findings indicate the paramount importance of adequate communication with persons at risk, being sensitive to individual needs and preferences. Substantial research needs were identified.

Background Coronary artery disease is the leading cause of disability and mortality in Iran and worldwide. Tumor necrosis factor-alpha is a pro-inflammatory cytokine that plays a key role in inflammatory cascades and atherosclerosis. It regulates cytokine networks and adhesion molecule expression, and activates several signal transduction pathways, being also known as transducer of cardiovascular diseases, especially premature coronary artery disease. Objective The aim of the present study was to investigate tumor necrosis factor-alpha gene expression in Iranian Azeri Turkish patients with premature coronary artery disease (age ≤50 years). Material and methods Eighty four individuals (42 cases and 42 controls) were enrolled in the study. Total RNA was extracted from patients with premature coronary artery disease using RNX-Plus Solution (Cat. No.: RN7713C) and reverse transcribed into cDNA. The tumor necrosis factor-alpha mRNA expression level was evaluated using Real-Time PCR. Results The mean ± SE of fold in cases and controls were 1.1±1.08 and 1.6±3.4, respectively. The mean expression of tumor necrosis factor-alpha mRNA (fold) was not statistically different between the tested groups (P value 0.4). Outcomes Our outcome failed to find evidence for any association between tumor necrosis factor-alpha mRNA expression and premature coronary artery disease. Large scale, more detailed studies are further needed to prove our results and to propose other mechanisms in the pathophysiology of premature coronary artery disease.

Aims Kappa Opioid receptors (KORs) change the impact of apelin on the phosphorylated ERK1/2 (pERK1/2). However, the role of interaction between KOR and apelin receptors (APJ) on the cardiac contractility effects of apelin and in regulation of pERK1/2 and PKC in the heart of renovascular hypertensive (2K1C) rats is unknown. Main methods Hemodynamic factors, the heterodimerization of KOR and APJ, the expression of KOR mRNA and protein and pERK1/2 in the left ventricle of 2K1C rats were measured following APJ, KOR, PKC and Gi path inhibition by F13A, nor-BNI, chelerythrine and PTX respectively. Key findings Apelin in 40 and 60 μg/kg doses increased cardiac contractility, and reduced mean arterial pressure. The cardiac impacts in both doses were reduced by F13A, nor-BNI and chelerytrine and blocked by PTX. Hypertension increased the expression of KORs and heterodimerization of APJ and KOR, and reduced pERK1/2 in the left ventricle. Apelin, in both doses reduced (normalized) heterodimerization and recovered the reduction in pERK1/2. The recovery of ERK1/2 phosphorylation was accompanied by reduction of KOR and APJ heterodimerization. Significance 2K1C hypertension increased the expression of KORs and heterodimerization of APJ and KORs. The heterodimerization was associated by reduction of ERK phosphorylation and altered the cardiac inotropic and lusitropic effects of apelin. These changes may participate in pathophysiology of cardiac dysfunction in renovascular hypertension that is associated with subnormal level of serum apelin. Apelin- induced recovery of ERK1/2 phosphorylation and KOR-APJ dimerization may nominate apelin as a therapeutic goal in treatment of this kind of hypertension.

Apelin receptors (APJ) cross-talk with other G-protein-coupled receptors. However, the role of APJ interaction with opioid receptors (OPR) on the cardiovascular effects of apelin in hypertension is not clear. Renovascular hypertension was induced by placing a Plexiglas clip on the left kidney of rats. After 16 weeks, F13A (an APJ antagonist), naloxone (a general OPR inhibitor), and nor-binaltorphimine dihydrochloride (nor-BNI; a selective inhibitor of KOR) were given prior to injections of apelin at doses of 40 and 60 μg/kg. The arterial systolic/diastolic blood pressure and left ventricular contractility responses were then evaluated. The arterial systolic/diastolic blood pressure in sham and 2K1C rats was 110/71 mm Hg and 171/124 mm Hg, respectively. The hypotensive effects of apelin at both doses were inhibited by F13A and naloxone. Nor-BNI completely inhibited the effects of apelin 40 on arterial pressure, and decreased the effects of 60 μg/kg. KOR inhibition also prevented the compensation for the decrease in the left ventricle +dp/dt max and -dp/dt max caused by apelin 60. The simultaneous inhibition of OPR and APJ reduced arterial pressure and increased cardiac contractility. Findings showed that the OPR, particularly KOR, mediate the inotropic, lusitropic, and depressor effects of apelin. The interaction of the OPR and APJ augments the inotropic and vasodepressor effects of apelin. This interaction may have potential clinical applications in cardiac failure since opioids are currently used in the treatment of myocardial infarction and stroke, and apelin has been introduced as a potential therapeutic agent in cardiovascular complications.

The purpose of the study was to establish the psychometric properties of the Iranian-Children Participation Questionnaire (I-CPQ) among parents (n = 120) of preschool children with cerebral palsy. The mean age of the preschool children was 5.1 years old. The confirmatory factor analysis was conducted in two stages, and the values of all goodness of fit tests reached an acceptable level (greater than 0.9), and achieved an acceptable root mean square error of approximation model fit value of 0.05. The results of convergent validity with the Vineland Adaptive Behavior Scale for all subtests were significant. Internal consistency was acceptable to excellent (α: 0.66–0.85), and test–retest reliability was excellent (ICC: 0.92–0.98). We concluded that the I-CPQ demonstrated good psychometric properties and utility for assessing participation of Iranian preschool children with cerebral palsy.

Introduction: Intrauterine growth restriction (IUGR) is a major clinical issue for pregnant women. The purpose of this study was to evaluate color Doppler indices of the proximal and distal parts of the middle cerebral artery (MCA) of the fetus. Methods: In this cross-sectional study, 350 pregnant patients, with gestation age of 32-40 who were suspected to have intrauterine growth restriction, participated. The patients were referred for color Doppler sonography at the Imam Reza Hospital (Kermanshah, Iran) from May 2011 to September 2012. The following indices were measured for the proximal and distal part of the MCA: pulsatility index (PI), resistive index (RI), fetal heart rate (FHR), systolic to diastolic (S/D) ratio, and peak systolic velocity (PSV). The data were analyzed applying Tukey's-test, Paired-Samples t-test, and simple linear regression analysis using SPSS 19. Results: Average age of the mother, the frequency of pregnancy, and fetus gestational age were 27.79±0.17 years, 2.09±1.3, and 34.19±2.52 weeks, respectively. For gestation age of 36 weeks, significant difference was found between the Doppler indices of the proximal parts as well as for the distal parts (p

This case report deals with a 25-year-old woman who suffered from a long-term borderline personality disorder and from acute suicidal tendencies, including the intentional consumption of poisonous plants. When questioned during her self-referral to the psychiatric emergency department, she denied any suicide attempt or consumption of poisonous agents. Due to her medical history, her admission was followed by an intensive medical observation. During this observation period, the patient suffered an episode of acute respiratory insufficiency, which was followed by cardiac arrest. All resuscitation attempts were futile. Due to the unexplained nature of her death, the case was referred to the criminal investigation department. All findings of the routine systematic toxicological analysis of the patient’s blood sample, including immunochemical examinations and a high-performance liquid chromatography general unknown screening for drugs, were in accordance with the patient’s medication regimen and did not indicate a lethal overdose of any drug. During the analytical examinations, the deceased’s mother informed the psychiatric outpatient service of having found yew leaves in her daughter’s clothes and at her flat. The liquid chromatography--tandem mass spectrometry target analysis for yew pseudo-alkaloids (taxine B/isotaxine B) yielded a combined concentration of 110 µg/L. No autopsy was performed, because no criminality was suspected. In conclusion, it seems most plausible to conclude that the patient died of yew intoxication.

Papillon-Lefevre syndrome (PLS) is a rare recessive autosomal disease which occurs with palms and soles hyperkeratosis as well as primary and permanent teeth periodontal loss. Recently, it has been proved that a mutation at Cathepsin gene C is the genetic cause of PLS. All primary and permanent teeth of the patients are lost at ages 2 or 3 because of serious alveolar bone destruction. This paper presents a complete case of prosthetic treatment of an 8-year old girl with PLS.

Family with sequence similarity 83 member H (FAM83H) protein-coding geneplay an essential role in the structural organization, calcification of developing enamel, and keratin cytoskeleton disassembly by recruiting Casein kinase 1 alpha (CSNK1A1) to keratin filaments. In this study, we have applied CRISPR Cas9 nickase (D10A) to knockout (KO) the Fam83h gene in NMRI outbred mice. We generated homozygous Fam83h KO mice (Fam83h Ko/Ko) through a premature termination codon, which was validated by Sanger sequencing in F0 generation. Next, we also bred the FAM83H KO for two generations. Reverse-transcription polymerase chain reaction and Western blot analysis approved the Fam83h KO mice. The Fam83h KO mice had evidence of normal morphology at the cervical loops, secretory and maturation stages, and mandibular molars. In comparison with the normal wild-type mice (Fam83h W/W), the F2 homozygous KO (Fam83h Ko/Ko) had sparse, scruffy coats with small body size and decreased general activity. Also, they had the natural reproductive ability and natural lifespan. In addition, delay in opening the eyes and dry eyes among infant mice were seen. The F1 heterozygous mice looked comparable to the normal wild-type mice (Fam83h W/W), which showed autosomal recessive inheritance of these phenotypes. The KO of FAM83H had controversial effects on the development of teeth and the formation of enamel. The phenotype defect in dental development and the enamel formation were seen in three mice among four generations. It can be concluded that null FAM83H in outbred mice not only showed the reported phenotypes in null inbred mouse but also showed normal lifespan and reproductive ability; dental deficiency in three homozygous mice; and the symptoms that were similar to the symptoms of dry eye syndrome and curly coat dog syndrome in all four evaluated KO generations.

Present investigation was carried out to evaluate the mRNA level of TNF receptor type 1 (TNFR1) and TNF receptor type 2 (TNFR2) in peripheral-blood cells in patients with premature CAD over healthy controls. BACKGROUND: TNFα as a pleiotropic cytokine could be concerned in cardiovascular pathophysiology regarding its special effects on endothelial cells. TNFα exerts its activities through its receptors, TNFR1 and TNFR2. METHODS: Totally, 40 patients with premature CAD and 40 healthy controls were studied. The qRT-PCR technique was used to determine the mRNA level of TNFR1 and TNFR2 in tested groups. RESULTS: The results of this study show that the relative expression was 1.32 ± 0.34 in cases and 1.11 ± 0.16 in controls for TNFR1. The relative expression was 0.96 ± 0.13 in cases and 1.49 ± 0.41 in controls for TNFR2. There is no signifi cant difference in the level of gene expression in the studied groups regarding TNFR1 and TNFR2 genes (p > 0.05). CONCLUSION: It can be concluded that the mRNA levels of TNFR1 and TNFR2 were not associated with CAD risk. Studies with more details, larger sample size, and new risk loci are necessary to reveal disease-causing mechanisms in the pathogenesis of CAD (Fig. 3, Ref. 21). Text in PDF www.elis.sk.

Background Healthcare workers including physicians, dentists, nurses and laboratory workers are considered to be among the groups at the risk of blood-borne pathogen transmission. Thus, it is necessary to evaluate the Knowledge, Attitude, and Practices (KAP) of dentists regarding infection control and basic principles. Methods This cross-sectional study recruited 106 dentists in Sanandaj, Iran. The dentists’ KAP regarding hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV/AIDS were evaluated. Chi-square test, student’s t-test, and one-way ANOVA were used to assess differences between the groups. Data were analyzed in Stata 12. Results The results showed that the majority of the subjects in the study population (53.8%) were female. The mean ± standard deviation (SD) for age and work experience was 39.6 ± 9.80 and 10.6 ± 8.7 years, respectively. The mean ± SD for knowledge, attitude and practices of participants was 37.3 ± 3.01, 22.9 ± 4.80 and 24.07 ± 5.06, respectively. The results also indicated that dentists’ higher level of knowledge about HBV, HCV and HIV/AIDS was significantly influenced by work experience (≥10 years; P

Melatonin (MT) (N-acetyl-5-methoxytryptamine) is a lipophilic and hydrophilic indoleamine with various physiologic functions MT presents in all cells and tissues and distributes in all cell compartments. Liver is the only organ of circulating MT metabolism. The roles of MT in various liver pathologies have been extensively studied, and it is believed that oxidative stress (OS) and lipid peroxidation (LPO) are the key causing factors of almost all conditions compromising liver function, including nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), diabetes, liver fibrosis and cirrhosis. MT improves energy production and reduces apoptosis OS and LPO in liver. MT protects liver against OS through multiple ways: inhibition of inflammatory cytokines, direct scavenge of free radicals, stimulation of antioxidant enzymes, decrease of mitochondrial electron leakage and synergistic function with other classical antioxidants. © 2016, Oriental Scientific Publishing Company. All rights reserved.

Rheumatoid arthritis (RA) is one of the common and severe autoimmune diseases related to joints. This chronic autoimmune inflammatory disease, leads to functional limitation and reduced quality of life, since as there is bone and cartilage destruction, joint swelling and pain. Current advances and new treatment approaches have considerably postponed disease progression and improved the quality of life for many patients. In spite of major advances in therapeutic options, restrictions on the routes of administration and the necessity for frequent and long-term dosing often result in systemic adverse effects and patient non-compliance. Unlike usual drugs, nanoparticle systems are planned to deliver therapeutic agents especially to inflamed synovium, so avoiding systemic and unpleasant effects. The present review discusses about some of the most successful drugs in RA therapy and their side effects and also focuses on key design parameters of RA-targeted nanotechnology-based strategies for improving RA therapies.

Article type: Original Article Background: Gliomas are the most common primary neoplasms of the central nervous system. Relative cerebral blood volume (rCBV) could estimate high-grade Gliomas computed with dynamic susceptibility contrast MR imaging which it is artificially lowered by contrast extravasation through a disrupted blood-brain barrier. Objectives: Our intent was to clarify the usefulness of diffusion-weighted magnetic resonance imaging (DWI) and perfusion weighted magnetic resonance imaging (PWI) in the grading of Gliomas. Materials and Methods: Both PWI and DWI with a three-tesla scanner investigated nineteen consecutive patients with Gliomas. The means of rCBV and ADC values have been compared among the tumor groups with t-test and ROC curve analysis to determine threshold values of Gliomas grading. Results: Mean maximum rCBV were 2.71±1.41 for low grades (I & II), and 8.14±2.58 for high grades (III & IV) Gliomas (p=0.001). Mean minimum ADC were 1.47±.46 ×10 3 mm 2 /s for low grades (I & II), and .47±.38×10 3 mm 2 /s for high grades (III & IV) Gliomas (p=0.001). We can get 0.94×10 3 mm 2 /s for minimum ADC and 3.85 for maximum rCBV as a difference cutoff point between low and high-grade Gliomas. Conclusion: Combination of both DWI and PWI techniques, with measurement of minimum ADC and maximum rCBV can be used to distinguish between high grade and low-grade Glioma tumors.

INTRODUCTION Today, the use of electromagnetic waves in medical diagnostic devices, such as magnetic resonance imaging (MRI), has increased, and many of its biological effects have been reported. The aim of the present study was to assess the biological effects of 1.5 Tesla (T) magnetic resonance imaging (MRI) on fertility and reproductive parameters. METHODS Eighty adult male and female NMRI mice (NMRI: Naval Medical Research Institute) of age 6-8 weeks were studied and randomly divided into two study and control groups. After confirmation of pregnancy, the mice in the study group were exposed to the MRI (1.5 T) machine's waves over the next three weeks, once a week for 36 minutes. One day and thirty-five days after the last radiation, the mice were killed in order to do the in vitro fertilization (IVF) by neck beads' displacement and the impact on the evolution of embryos, and its quality was studied. Data were analyzed using SPSS version 20 and the significance level of less than 0.05 was considered. RESULTS Embryo morphometry showed that the total diameter and the cytoplasm diameter of the study group embryos suffered significant reduction compared to the control group, 1 day after the last irradiation (p < 0.05), but the diameter of the perivitelline space of this group's embryos had a significant increase (p < 0.05). The qualitative results during 35 days after irradiation showed that morphologically parameters of the embryos in the study group had no significant differences from the control group. CONCLUSION Exposure to MRI irradiation can transiently disturb the development of mouse embryos and fertility, but these effects are reversible 35 days after the last irradiation.

In order to evaluate the correlation of B7-H4 and B7-H1 with renal cell carcinoma (RCC), we analyzed B7-H1 and B7-H4 expressions and their clinical significance by immunohistochemical method. Our result indicated that B7-H4-positive staining was detected in 58.13 % of RCC tissues (25 tissues tumors), and there were 18 tissues of patients without detectable B7-H4. Furthermore, 21 cases (48.83 %) were B7-H1-positive. Positive tumor expressions of B7-H4 and B7-H1 were markedly related to advanced TNM stage (P = 0.001; P = 0.014), high grade (P = 0.001; P = 002), and larger tumor size (P = 0.002; P = 024) in RCC tissues than patients with B7-H4-negative and B7-H1-negative in RCC tissues. The patients with B7-H1 and B7-H4-positive expressions were found to be markedly correlated with the overall survival of the patients (P

Acute kidney injury (AKI) is a common complication in hospitalized patients and can result in increased hospital stay, health-related costs, mortality and morbidity. A number of recent studies have shown that AKI is predictable and avoidable if early risk factors can be identified by analyzing Electronic Health Records (EHRs). In this study, we employ machine learning techniques to identify older patients who have a risk of readmission with AKI to the hospital or emergency department within 90 days after discharge. One million patients&rsquo, records are included in this study who visited the hospital or emergency department in Ontario between 2014 and 2016. The predictor variables include patient demographics, comorbid conditions, medications and diagnosis codes. We developed 31 prediction models based on different combinations of two sampling techniques, three ensemble methods, and eight classifiers. These models were evaluated through 10-fold cross-validation and compared based on the AUROC metric. The performances of these models were consistent, and the AUROC ranged between 0.61 and 0.88 for predicting AKI among 31 prediction models. In general, the performances of ensemble-based methods were higher than the cost-sensitive logistic regression. We also validated features that are most relevant in predicting AKI with a healthcare expert to improve the performance and reliability of the models. This study predicts the risk of AKI for a patient after being discharged, which provides healthcare providers enough time to intervene before the onset of AKI.

Introduction: Klotho allele status is associated with increased risk of cardiovascular diseases, diabetes and hypertension. Objectives: To determine if serum klotho level was lower among diabetic and hypertensive patients compared to control group. Patients and Methods: This was a cross-sectional study of 90 participants. Thirty pure diabetic patients and 30 participants with pure hypertension were compared with the healthy control group. Multiple logistic regressions were used to examine the association between serum klotho and diabetes and hypertension. We also tested the cut off point of serum klotho to predict hypertension and diabetes by using ROC (receiver operating characteristic) curve. Results: The level of serum klotho was significantly lower in diabetic and hypertensive patients. Participants with higher klotho were less likely to have diabetes and hypertension [OR: 0.48, 95% CI (0.22-0.81)] even after adjustment for covariates. ROC curve for diabetes and hypertension indicated 0.8 area under the curve which was statistically significant. Conclusion: This study found that serum klotho was associated with lower odds of diabetes and hypertension. Further longitudinal studies are necessary to confirm this finding.

Introduction Hashimoto's thyroiditis (HT) is an autoimmune disorder of thyroid gland characterized by loss of thyroid functions and structure. Accumulation of lymphocytes and other immune mediators is a preliminary step in HT development. Fc receptor-like (FCRL)-3 gene have recently shown a significant association with HT. The aim of this study was to evaluate the FCRL3 single nucleotide polymorphisms (SNPs), rs7528684 and rs11264799, in Iranian patients with HT. Methods Genomic DNA was extracted from whole blood of 322 individuals with HT and 302 healthy individuals. The FCRL3 gene rs7528684 and rs11264799 SNPs were evaluated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results We found that the rs7528684 SNP was statistically associated with risk of HT. In patients, the frequencies of CC genotype and C allele were significantly higher than healthy controls (CC vs. TT + CT, OR = 2.33, 95% CI = 1.57–3.46, p Conclusions These data showed an association between FCRL3 CC genotype and C allele of rs7528684 SNP and susceptibility to HT, supporting the important role of FCRL3 variants in HT development.

Background Multiple sclerosis is a chronic incapacitating disease of the central nervous system, it has been reported that the disturbance in the development and function of Treg subpopulations is associated with the disability status in the RRMS. Accordingly, in the current study, the objective was to specify nanocurcumin effects on Treg cells frequency, and function in patients with RRMS. Methods and materials 50 patients with RRMS were enrolled in this study in which 25 were treated for at least six months with nanocurcumin capsules while the other half received placebo capsules as the control group. The blood sample was collected prior to the administration of nanocurcumin and placebo capsules and following six months. At baseline and after a six-month treatment, the frequency of Treg lymphocytes, the expression of transcription factor related to these cells and the secretion levels of cytokines were assessed by flowcytometry, real-time PCR and ELISA, respectively. Results A significant reduction was observed in the proportion of peripheral Treg cell frequency, and the levels of TGF-β, IL-10 and FoxP3 expression in patients with RRMS. Our data revealed that the frequency of Treg cells (p = .0027), the expression of FoxP3 (p = .0005), TGF-β (p = .0005), and IL-10 (p = .0002) and the secretion levels of the TGF-β (p = .033), and IL-10 (p = .029) in cultured PBMCs are increased in nanocurcumin-treated group compared to placebo group. Conclusion The results of the current work indicated that nanocurcumin is capable of restoring the frequency and function of Treg cells in MS patients.

The huge rate of road accidents in Iran demonstrates the necessity of implementing prevention interventions in this field. Traffic signs are communication tools for passing information to the road users. However, misunderstanding of their messages could be a major cause of road accidents. The aim of the present study was to measure the usability of traffic signs used in rural and urban areas of Iran. 356 Iranians licensed drivers (39.0 years ± 9.7) were requested to rate their estimation about the effectiveness of the 20 selected traffic signs on the Persian version of System Usability Score (SUS). The mean of usability score for all signs were 59.37 ± 15.3. Mean usability score of Indication signs was higher than two other groups (63.2 ± 29.3) followed by Mandatory signs (60.9 ± 13.5). Warning signs had the lowest level of usability (53.9 ± 15.2). Except two signs (“Unguarded railway crossing in 200 m”) with the SUS score of less than 50 and “Camping” with the SUS score of higher than 70, the effectiveness of all signs was assessed to be at moderate level (50 > SUS < 70). It could be concluded that the majority of Iran traffic signs are marginally usable for Iranian population. Taking into account ergonomic features in designing traffic signs, could result in increasing sign effectiveness and decreasing road accidents. Appropriate strategies should be implemented to design more user-friend traffic signs.

Objective Numerous studies suggest that health literacy (HL) plays a crucial role in maintaining and improving individual health. Empirical findings highlight the relation between levels of a person's HL and her/his clinical outcome. To date, the role of HL in persons at-risk for psychosis has not been systematically reviewed. Methods We conducted a systematic review using a mixed-methods approach to analyse a variety of study types. Peer-reviewed publications were systematically searched in PUBMED, Cochrane Library, PsycINFO and Web of Science. Results The search string returned 10587 publications. After screening, 15 quantitative, four qualitative studies and two reviews were included. Only one study assessed HL as primary outcome, assessing knowledge and beliefs about psychosis among the general population. In the other studies, sub-dimensions of HL were investigated. None of the publications operationalized HL or it's sub-dimensions with a validated measure. Conclusions A lack of understanding of their condition, and fear of stigmatization, were associated with a delay in help-seeking among people with clinical-high-risk state for psychosis. Family members, school personnel, general practitioners and the internet play a crucial role in the HL process. Considerable barriers in obtaining adequate specialist support emphasize the urgent need of a "HL environment" for persons at risk for psychosis.

Although ovarian cancer is a highly chemosensitive disease, it is only infrequently cured. One of the major reasons lies in the presence of drug-resistant cancer stem-like cells, sufficient to fuel recurrence. We phenotyped cancer stem-like cells by flow cytometry and immunohistochemistry in 55 matched samples before and after taxane/platinum-based neoadjuvant chemotherapy. All used markers of stemness (ALDH1, CD24, CD117, CD133) isolated low frequencies of malignant cells. ALDH1 was the most valuable marker for tracking stemness in vivo. The enrichment of ALDH1 expression after treatment was associated with a poor response to chemotherapy, with platinum resistance and independently prognosticated unfavorable outcome. Our results suggest that increased ALDH1 expression after treatment identifies patients with aggressive tumor phenotypes.

Recently identified Fc receptor-like (FCRL) molecules are new members of the immunoglobulin superfamily dominantly expressed by B cells. Although FCRL expression patterns have been studied in normal and malignant cells, their biological functions and roles remain to be clearly identified in humans. Research has particularly focused on FCRL gene polymorphisms in autoimmune diseases, however, their involvement in the pathogenesis of autoimmune diseases is an interesting field for investigation. In the present study, we have investigated the gene expression profiles of FCRL1, 2, and 4 in 2 common thyroid diseases, Hashimoto's thyroiditis (HT) and Graves' disease (GD). FCRL1, 2, and 4 expressions were determined in peripheral blood samples of 55 HT patients, 40 GD patients and equal numbers of normal subjects by quantitative real-time PCR. Our results showed downregulation of FCRL1 and upregulation of FCRL2 transcripts in both HT and GD groups compared to healthy counterparts. Overexpression of FCRL4 was observed only in GD patients compared to controls. A significant correlation was observed between all FCRL gene expression levels in HT patients. Only FCRL2 and 4 had a correlation in GD patients. In addition, FCRL1, 2, and 4 gene expressions showed no correlations with the level of anti-thyroid peroxidase antibody (anti-TPO) or anti-thyroglobulin (anti-Tg) antibody from patients' sera. In conclusion, expressions of activating or inhibitory FCRL1, 2, and 4 showed significant alterations in HT and GD patients compared to healthy subjects.

Introduction: Hepatic encephalopathy (HE) is a brain disorder with impairment of cognitive and motor functions caused by liver failure. The aim of this study was to evaluate changes in nociception threshold as well as gene expression of mu-opioid receptor 1 (MOR1) in rat liver after induction of HE. Materials and Methods: The male rats (280-320 g) were randomly divided into three groups of control (non-operated), sham (operated without common bile duct ligation) and a group with a common bile duct ligation (BDL) as an experimental model of HE. Changes in nociception threshold were assessed on day 21 of BDL, using a hotplate test. On day 21 of BDL, rats were weighed, sacrificed and total liver tissue was dissected and weighed, then percentage of liver to body weight was measured. In addition, blood samples were collected for biochemical analysis of serum, and a piece of the liver of each rat was dissected for evaluating the MOR1 gene expression. Results: The results showed that nociception threshold, percentage of liver to body weights, and serum levels of total bilirubin were significantly increased in the HE model group compared to the sham group (P