MIR137 polygenic risk for schizophrenia and ephrin-regulated pathway: Role in lateral ventricles and corpus callosum volume.

Background/Objective. Enlarged lateral ventricle (LV) volume and decreased volume in the corpus callosum (CC) are hallmarks of schizophrenia (SZ). We previously showed an inverse correlation between LV and CC volumes in SZ, with global functioning decreasing with increased LV volume. This study investigates the relationship between LV volume, CC abnormalities, and the microRNA MIR137 and its regulated genes in SZ, because of MIR137's essential role in neurodevelopment. Methods. Participants were 1224 SZ probands and 1466 unaffected controls from the GENUS Consortium. Brain MRI scans, genotype, and clinical data were harmonized across cohorts and employed in the analyses. Results. Increased LV volumes and decreased CC central, mid-anterior, and mid-posterior volumes were observed in SZ probands. The MIR137-regulated ephrin pathway was significantly associated with CC:LV ratio, explaining a significant proportion (3.42 %) of CC:LV variance, and more than for LV and CC separately. Other pathways explained variance in either CC or LV, but not both. CC:LV ratio was also positively correlated with Global Assessment of Functioning, supporting previous subsample findings. SNP-based heritability estimates were higher for CC central:LV ratio (0.79) compared to CC or LV separately. Discussion. Our results indicate that the CC:LV ratio is highly heritable, influenced in part by variation in the MIR137-regulated ephrin pathway. Findings suggest that the CC:LV ratio may be a risk indicator in SZ that correlates with global functioning.

Use of cellular exosomes as a new carrier in breast cancer gene therapy.

BACKGROUND: Breast cancer is recognized as a major clinical challenge in gynecological diseases worldwide. Exosomes are small vesicles derived from multicellular bodies that are secreted by many cells into the extracellular environment and thus participate in intercellular communication through the transfer of genetic information such as encoded and non-encoded RNAs to target cells. Tumor-derived exosomes are thought to be a rich source of microRNAs (miRs) that can regulate the function of other cancer cells in the tumor microenvironment. However, the exact mechanisms by which tumor cell-derived exosomes affect their neighboring cells, as well as the bio-logical function of exosomal miRs in receptor cells, are not well understood. MATERIALS AND METHODS: In this study, after the overexpression of MiR-205 in breast cancer cells (MDA-MB-231 class), cell-derived exosomes were successfully isolated and characterized by electron microscopy and dynamic light scattering. RESULTS: The determination of MiR-205 expression levels in exosomes secreted from engineered cells confirmed the high expression of this miR in exosomes. It was also found that the treatment of tumor exosomes carrying this miR had an apoptotic induction effect and also had a significant effect on reducing the expression of Bcl-2 gene transcript in a time-dependent manner in breast cancer cells (P < 0.001). CONCLUSION: Overall, this study suggests that exosomal transfer of tumor suppressor miRs to cancer cells could be a suitable platform for nucleic acid transfer to these cells and be highly effective in cancer treatment.

Comparison of Thessaly Test with Joint Line Tenderness and McMurray Test in the Diagnosis of Meniscal Tears.

INTRODUCTION: Meniscus injuries are the most frequent problem of the knee. The aim of this study was to investigate the accuracy of the Thessaly test and comparing it with those of McMurray and Joint-line tenderness tests for diagnosing meniscal tears.Materials and methods: This study was designed as a prospective observational one done in an outpatient clinic at a university hospital. 106 patients with knee pain and 82 age-matched control were included during study period (from February 2014 to January 2015). Each patient was clinically examined with McMurray, Thessaly, and joint line tenderness tests. Then, the findings were matched by MRI and arthroscopic findings. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were calculated as main outcomes. RESULTS: Based on MRI, Thessaly was the most sensitive for medial meniscus tears (56.2%), while McMurray and joint-line tenderness were more specific (89.1% and 88.0%, respectively). For lateral meniscus tears, McMurray was the most sensitive (56.2%) and all were specific (McMurray 89.6%, Thessaly 88.4%, joint-line tenderness 90.2%). With arthroscopy, Thessaly was the most sensitive for medial meniscus (76.6%), while McMurray and joint-line tenderness were more specific (81.0%, and 81.0%). Agreement with arthroscopy was the highest with McMurray (for medial meniscus kappa=0.40, p<0.001, and for lateral meniscus kappa=0.38, p=0.002). CONCLUSION: The Thessaly can be used to screen for medial meniscus tears. McMurray and joint-line tenderness should be used for suspected medial meniscus tears. For lateral meniscus, McMurray is appropriate for screening and all the tests are useful in clinic.

Evaluation of thyroid dysfunction and autoimmunity in gestational diabetes mellitus and its relationship with postpartum thyroiditis.

AIMS: To evaluate thyroid dysfunction and autoimmunity in women with gestational diabetes and to investigate the frequency of postpartum thyroiditis in women with gestational diabetes. MATERIALS AND METHODS: A total of 350 women with gestational diabetes and 350 healthy pregnant women were enrolled in the study. We studied the thyroid hormone profiles of the women in each group during pregnancy (at 24-28 weeks' gestation) and after delivery (at 6 weeks, 3, 6 and 9 months, and 1 year postpartum). RESULTS: A total of 342 women with gestational diabetes and 313 healthy pregnant women completed the follow-up during pregnancy and 1 year after delivery. Of the women with gestational diabetes, 16.6% had thyroid dysfunction, while of the healthy pregnant women, 6.1% had thyroid dysfunction. The prevalence of postpartum thyroiditis was higher in the women with a history of gestational diabetes (19.6%) than in the healthy pregnant women (10.2%), and this difference was statistically significant. CONCLUSION: According to the results of the present study, the prevalence of postpartum thyroiditis was higher in women with a history of gestational diabetes than in healthy women. We recommend that all women with gestational diabetes and women who have previous thyroid dysfunction should be screened for thyroid hormonal abnormalities during pregnancy and for 1 year after pregnancy.

Assessment of renal involvement in patients with familial Mediterranean fever: a clinical study from Ardabil, Iran.

BACKGROUND AND AIM: Familial Mediterranean fever (FMF) is an autosomal recessive disease characterised by recurrent episodes of painful inflammation in the abdomen, chest or joints. The association between FMF and non-amyloid glomerulopathies are unusual. In this study, we describe our experiences and observations about renal involvement in patients with FMF. METHODS: A total of 108 patients with FMF was enrolled in the study. Twelve patients with FMF were referred to the Nephrology Service, for evaluation and assessment of the degree of renal involvement. All the 12 patients underwent percutaneous ultrasound-guided renal biopsies and genetic analysis. RESULTS: On microscopic examination of the kidney specimens, six patients were found to have amyloidosis, five focal segmental glomerulosclerosis and one patient membranoproliferative glomerulonephritis. It seems that in patients with FMF and renal amyloidosis, the response to treatment with colchicine is excellent, but in patients with FMF and focal segmental glomerulosclerosis, the response to treatment with colchicine is poor. We present an evidence-based algorithm, constructed based on literature review, to aid decision making in management of renal involvement in patients with FMF. CONCLUSION: The results of our study suggest that in patients with FMF and renal involvement, non-amyloid renal lesions should be considered in the differential diagnosis in addition to amyloidosis.

Mapping pain activation and connectivity of the human habenula.

The habenula, located in the posterior thalamus, is implicated in a wide array of functions. Animal anatomical studies have indicated that the structure receives inputs from a number of brain regions (e.g., frontal areas, hypothalamic, basal ganglia) and sends efferent connections predominantly to the brain stem (e.g., periaqueductal gray, raphe, interpeduncular nucleus). The role of the habenula in pain and its anatomical connectivity are well-documented in animals but not in humans. In this study, for the first time, we show how high-field magnetic resonance imaging can be used to detect habenula activation to noxious heat. Functional maps revealed significant, localized, and bilateral habenula responses. During pain processing, functional connectivity analysis demonstrated significant functional correlations between the habenula and the periaqueductal gray and putamen. Probabilistic tractography was used to assess connectivity of afferent (e.g., putamen) and efferent (e.g., periaqueductal gray) pathways previously reported in animals. We believe that this study is the first report of habenula activation by experimental pain in humans. Since the habenula connects forebrain structures with brain stem structures, we suggest that the findings have important implications for understanding sensory and emotional processing in the brain during both acute and chronic pain.

Painful heat reveals hyperexcitability of the temporal pole in interictal and ictal migraine States.

During migraine attacks, alterations in sensation accompanying headache may manifest as allodynia and enhanced sensitivity to light, sound, and odors. Our objective was to identify physiological changes in cortical regions in migraine patients using painful heat and functional magnetic resonance imaging (fMRI) and the structural basis for such changes using diffusion tensor imaging (DTI). In 11 interictal patients, painful heat threshold + 1°C was applied unilaterally to the forehead during fMRI scanning. Significantly greater activation was identified in the medial temporal lobe in patients relative to healthy subjects, specifically in the anterior temporal pole (TP). In patients, TP showed significantly increased functional connectivity in several brain regions relative to controls, suggesting that TP hyperexcitability may contribute to functional abnormalities in migraine. In 9 healthy subjects, DTI identified white matter connectivity between TP and pulvinar nucleus, which has been related to migraine. In 8 patients, fMRI activation in TP with painful heat was exacerbated during migraine, suggesting that repeated migraines may sensitize TP. This article investigates a nonclassical role of TP in migraineurs. Observed temporal lobe abnormalities may provide a basis for many of the perceptual changes in migraineurs and may serve as a potential interictal biomarker for drug efficacy.

Cadaveric renal transplantation: a single-center experience.

INTRODUCTION: Renal transplantation remains the treatment of choice for end-stage renal disease (ESRD) in regard to patient survival. Iran was one of the first countries in the Middle East that began renal transplantation. METHODS: In a follow-up study, we enrolled all of our cadaveric renal transplant recipients from 2001 to 2007, namely, 39 cases. Related variables collected through checklists were entered into SPSS software version 16 and analyzed using the Kaplan-Meier method and by descriptive statistics. RESULTS: The mean age of the recipients was 35.18 +/- 14.27 years. Twenty-one patients (53.8%) were men. The underlying disease for development of ESRD was diabetes (7 cases, 21.2%), hypertension (24.2%), glomerulopathies (36.4%), polycystic disease (PKD; 2.6%), and 5 (15.2%) were unknown. Four recipients (10.3%) were hospitalized again because of acute tubular necrosis after transplantation. An acute rejection episode was diagnosed in 7 (17.9%) graft recipients. Surgical complications after transplantation were as follows: urinoma, lymphocele, and surgical site leakage (each 1 case). One-year patient survival rate was 89.7% in this study; 4 recipients died within 1-9 months after transplantation. Death-censored 1-year graft survival rate was 100%. DISCUSSION: The survival rate of cadaveric transplant was in an acceptable range.

Relationship of pharmacist interaction with patient knowledge of dispensed drugs and patient satisfaction.

A prospective survey of pharmacists' tasks and patients' knowledge and satisfaction was conducted in 35 randomly selected community pharmacies in Tabriz, Islamic Republic of Iran. The total pharmacist interaction received a mean score of 3.05 out of 5. Providing written directions for use attained the highest score of 0.98 out of 1. Patients scored 3.18 out of 5 for knowledge about their medicines. There was a close correlation between patients' knowledge of dispensed drugs and pharmacist interaction (r = 0.95). Mean total prescription filling time was 7.6 min, but only 1.4 min was spent on pharmacist-patient counselling. The interaction between pharmacist and patient increases patients' knowledge about dispensed medicines and their satisfaction with the pharmacist's activities.

Relationship of pharmacist interaction with patient knowledge of dispensed drugs and patient satisfaction

A prospective survey of pharmacists' tasks and patients' knowledge and satisfaction was conducted in 35 randomly selected community pharmacies in Tabriz, Islamic Republic of Iran. The total pharmacist interaction received a mean score of 3.05 out of 5. Providing written directions for use attained the highest score of 0.98 out of 1. Patients scored 3.18 out of 5 for knowledge about their medicines. There was a close correlation between patients' knowledge of dispensed drugs and pharmacist interaction [r = 0.95]. Mean total prescription filling time was 7.6 min, but only 1.4 min was spent on pharmacist-patient counselling. The interaction between pharmacist and patient increases patients' knowledge about dispensed medicines and their satisfaction with the pharmacist's activities

Interaction of anionic dyes and cationic surfactants with ionic liquid character.

The interactions of an imidazolium based ionic liquid (IL), namely 1-dodecyl-3-methylimidazolium chloride [C12 mim][Cl] with two sulfonated anionic dyes, azocarmine G and methyl orange, are studied spectrophotometrically in both acidic and basic media. ILs (with some surface active character) can interact with the above dyes and cause considerable shifts in their spectra. These interactions are then compared with some surfactant-dye interactions. Evolving factor analysis (EFA) and multivariate curve resolution-alternating least squares (MCR-ALS) are used for complete resolution of the measured spectrophotometric data. The concentration and spectral profiles of all species were calculated without any assumption of the chemical models. The spectral variation of dye solutions as a function of IL concentrations below and above the critical aggregation concentration (CAC) is analyzed using MCR-ALS as a soft-modeling technique. The ion pair formation constants between ILs and dyes were calculated using the obtained concentration profiles.

Antiarrhythmic and arrhythmogenic effects of L-carnitine in ischemia and reperfusion.

Isolated rat hearts were subjected to 30-min coronary artery occlusion followed by 120-min reperfusion. The hearts (n=8-12) were perfused with Krebs-Henseleit solution enriched with L-carnitine (0.5, 2.5 and 5 mM) for 10 min before and after ischemia or reperfusion and for the whole period of ischemia and reperfusion. Two-hour perfusion with L-carnitine during ischemia/reperfusion markedly (p<0.05) and dose-dependently decreased the incidence of ventricular tachycardia (VT, maximum 65%). The incidence of reperfusion ventricular fibrillation (VF) also decreased from 63% (control) to 17% in hearts perfused with 5 mM L-carnitine, as reflected by a significant (p<0.05) decline in VF duration from 218+/-99 sec in control to 19+/-19 sec. Perfusion of etomoxir (palmitoylcarnitinetransferase-1 inhibitor) along with L-carnitine reversed the antiarrhythmogenic action of L-carnitine. Interestingly, short time preischemic administration of L-carnitine produced a concentration-dependent arrhythmogenic effects on both ischemia and reperfusion-induced arrhythmias. These results show that L-carnitine produced a protective effect against reperfusion arrhythmias only when it was perfused for the whole period of the experiment. This protective action was reversed by concomitant use of etomoxir, suggesting that the efficacy of L-carnitine is due to its mitochondrial action but cannot be solely attributed to increased fatty acid oxidation.

Efficient electrocatalysis of L-cysteine oxidation at carbon ionic liquid electrode.

The electrochemistry of L-cysteine (CySH) in neutral aqueous media was investigated using carbon ionic liquid electrode (CILE). Comparative experiments were carried out using glassy carbon electrodes. At CILE, highly reproducible and well-defined cyclic voltammograms were obtained for l-cysteine with a peak potential of 0.49V vs Ag/AgCl, showing that CILE manifests a good electrocatalytic activity toward oxidation of l-cysteine. A linear dynamic range of 2-210microM with an experimental detection limit of 2microM was obtained. The method was successfully applied to the determination of l-cysteine in a sample of soya milk. Cysteine oxidation at CILE does not result in deactivation of the electrode surface. Mechanistic studies showed that, at CILE, the overall CySH oxidation is controlled by the oxidation of the CyS(-) electroactive species.

Ultra trace adsorptive stripping voltammetric determination of atrazine in soil and water using mercury film electrode.

In situ mercury film electrode produced in the presence of thiocyanate has been shown extremely useful for highly sensitive adsorptive stripping voltammetric measurements of atrazine down to sub-microg L(-1) level. Operational parameters have been optimized and the stripping voltammetric performance has been investigated using square wave scans. The adsorptive stripping response is linear over the range of 0.5-60 microg L(-1) atrazine, with a detection limit of 0.024 microg L(-1). The method has been applied to the determination of atrazine in soil and water samples.

CCD camera full range pH sensor array.

Changes in colors of an array of optical sensors that responds in full pH range were recorded using a CCD camera. The data of the camera were transferred to the computer through a capture card. Simple software was written to read the specific color of each sensor. In order to associate sensor array responses with pH values, a number of different mathematics and chemometrics methods were investigated and compared. The results show that the use of "Microsoft Excel's Solver" provides results which are in very good agreement with those obtained with chemometric methods such as artificial neural network (ANN) and partial least square (PLS) methods.

Indirect determination of hexavalent chromium ion in complex matrices by adsorptive stripping voltammetry at a mercury electrode.

A sensitive method for the determination of chromium ion(VI) in complex matrices such as crude oil and sludge is presented based on the decreasing effect of Cr(VI) on cathodic adsorptive stripping peak height of Cu-adenine complex. Under the optimum experimental conditions (pH 7.5 Britton-Robinson buffer, 5x10(-5)M copper, 8x10(-6)M adenine and accumulation potential -250mV versus Ag/AgCl), a linear decrease of the peak current of Cu-adenine was observed, when the chromium(VI) concentration was increased from 5mugL(-1) to 120mugL(-1). Detection limit of 2mugL(-1) was achieved for 120s accumulation time. The relative standard deviations (R.S.D., %) were 1.8% and 4% for chromium(VI) concentrations of 18mugL(-1) and 100mugL(-1), respectively. The method was applied to the determination of chromium(VI) in the presence of high levels of chromium(III), in various real samples such as crude oil, crude oil tank button sludge, waste water and tap water samples. Effects of foreign ions and surfactants on the voltammetric peak and the influences of instrumental and analytical parameters were investigated in detail. The accuracy of the results was checked by ICP and/or AA.

Single-step calibration, prediction and real samples data acquisition for artificial neural network using a CCD camera.

An artificial neural network (ANN) model is developed for simultaneous determination of Al(III) and Fe(III) in alloys by using chrome azurol S (CAS) as the chromogenic reagent and CCD camera as the detection system. All calibration, prediction and real samples data were obtained by taking a single image. Experimental conditions were established to reduce interferences and increase sensitivity and selectivity in the analysis of Al(III) and Fe(III). In this way, an artificial neural network consisting of three layers of nodes was trained by applying a back-propagation learning rule. Sigmoid transfer functions were used in the hidden and output layers to facilitate nonlinear calibration. Both Al(III) and Fe(III) can be determined in the concentration range of 0.25-4mugml(-1) with satisfactory accuracy and precision. The proposed method was also applied satisfactorily to the determination of considered metal ions in two synthetic alloys.

Enhancement of dissolution rate and anti-inflammatory effects of piroxicam using solvent deposition technique.

Piroxicam solid depositions were prepared by means of the solvent deposition technique using different concentrations of microcrystalline cellulose as carrier material. The solvent deposition system (SDS) with drug to carrier ratio of 1:9 had a rapid dissolution rate in vitro. When this SDS was administered perorally to rats with a previous experimentally induced inflammation in their paws, it exhibited a pronounced anti-inflammatory action. X-ray diffraction and infrared (IR) spectroscopy showed no differences in the crystal state of piroxicam in SDS formulation and physical mixture of piroxicam and carrier. The increase in the dissolution rate and consequent enhancement of anti-inflammatory effect of piroxicam in SDS were attributed to the reduced particle size of drug deposited on the carrier and enhanced wettability of the particles brought about by the carrier.

Potent anti-inflammatory activities of hydroalcoholic extract from aerial parts of Stachys inflata on rats.

Extracts obtained from aerial parts of Stachys inflata have been used in Iranian folk medicine in infective, rheumatic and other inflammatory disorders. In the present study, the anti-inflammatory properties of total methanol extract isolated from aerial parts of Stachys inflata were investigated in two well-characterised inflammatory models in rats, carrageenan-induced paw oedema and formalin-induced paw licking. Intraperitoneal injection of the extract, 60 min before induction of inflammation, revealed a dose-related inhibition of carrageenan-induced rat paw oedema over the dose range 50-200 mg/kg. In the formalin test, the extract (50, 100 and 200 mg/kg) had no effect against the first phase (0-5 min) of the formalin-induced pain, but all three doses produced a significant blockade of the second phase (P < 0.001). Myeloperoxidase (MPO) activity was determined, and a histopathological study was carried out in paw tissue 4 h after induction of inflammation. The hydroalcoholic extract (200 mg/kg) substantially reduced MPO activity (P < 0.05), which was increased in the control group. Histological examination showed a marked reduction in tissue injury and inhibition in neutrophil infiltration in rats treated with the extract (200 mg/kg).