Boolean factor graph model for biological systems: the yeast cell-cycle network.

BACKGROUND: The desire to understand genomic functions and the behavior of complex gene regulatory networks has recently been a major research focus in systems biology. As a result, a plethora of computational and modeling tools have been proposed to identify and infer interactions among biological entities. Here, we consider the general question of the effect of perturbation on the global dynamical network behavior as well as error propagation in biological networks to incite research pertaining to intervention strategies. RESULTS: This paper introduces a computational framework that combines the formulation of Boolean networks and factor graphs to explore the global dynamical features of biological systems. A message-passing algorithm is proposed for this formalism to evolve network states as messages in the graph. In addition, the mathematical formulation allows us to describe the dynamics and behavior of error propagation in gene regulatory networks by conducting a density evolution (DE) analysis. The model is applied to assess the network state progression and the impact of gene deletion in the budding yeast cell cycle. Simulation results show that our model predictions match published experimental data. Also, our findings reveal that the sample yeast cell-cycle network is not only robust but also consistent with real high-throughput expression data. Finally, our DE analysis serves as a tool to find the optimal values of network parameters for resilience against perturbations, especially in the inference of genetic graphs. CONCLUSION: Our computational framework provides a useful graphical model and analytical tools to study biological networks. It can be a powerful tool to predict the consequences of gene deletions before conducting wet bench experiments because it proves to be a quick route to predicting biologically relevant dynamic properties without tunable kinetic parameters.

A probabilistic graphical model for system-wide analysis of gene regulatory networks.

MOTIVATION: The inference of gene regulatory networks (GRNs) from DNA microarray measurements forms a core element of systems biology-based phenotyping. In the recent past, numerous computational methodologies have been formalized to enable the deduction of reliable and testable predictions in today's biology. However, little focus has been aimed at quantifying how well existing state-of-the-art GRNs correspond to measured gene-expression profiles. RESULTS: Here, we present a computational framework that combines the formulation of probabilistic graphical modeling, standard statistical estimation, and integration of high-throughput biological data to explore the global behavior of biological systems and the global consistency between experimentally verified GRNs and corresponding large microarray compendium data. The model is represented as a probabilistic bipartite graph, which can handle highly complex network systems and accommodates partial measurements of diverse biological entities, e.g. messengerRNAs, proteins, metabolites and various stimulators participating in regulatory networks. This method was tested on microarray expression data from the M3D database, corresponding to sub-networks on one of the best researched model organisms, Escherichia coli. Results show a surprisingly high correlation between the observed states and the inferred system's behavior under various experimental conditions. AVAILABILITY AND IMPLEMENTATION: Processed data and software implementation using Matlab are freely available at https://github.com/kotiang54/PgmGRNs. Full dataset available from the M3D database.

Incidence and associated risk factors for premature death in the Tehran Lipid and Glucose Study cohort, Iran.

BACKGROUND: The incidence and associated risk factors for premature death were investigated in a population-based cohort study in Iran. METHODS: A total of 7245 participants (3216 men), aged 30-70 years, were included. We conducted Cox proportional hazards models to identify the risk factors for premature death. For each risk factor, hazard ratio (HR), 95% confidence intervals (95% CI) and population attributable fraction (PAF) were calculated. RESULTS: After a median follow-up of 13.8 years, 262 premature deaths (153 in men) occurred. Underlying causes of premature deaths were cardiovascular disease (CVD) (n = 126), cancer (n = 51), road injuries (n = 15), sepsis and pneumonia (n = 9) and miscellaneous reasons (n = 61). The age-standardized incident rate of premature death was 2.35 per 1000 person years based on WHO standard population. Hypertension [HR 1.40, 95% CI (1.07-1.83)], diabetes (2.53, 1.94-3.29) and current smoking (1.58, 1.16-2.17) were significant risk factors for premature mortality; corresponding PAFs were 12.3, 22.4 and 9.2%, respectively. Overweight (body mass index (BMI): 25-29.9 kg/m2) (0.65, 0.49-0.87) and obesity (BMI ≥30 kg/m2) (0.67, 0.48-0.94) were associated with decreased premature mortality. After replacing general adiposity with central adiposity, we found no significant risk for the latter (0.92, 0.71-1.18). Moreover, when we excluded current smokers, those with prevalent cancer/cardiovascular disease and those with survival of less than 3 years, the inverse association between overweight (0.59, 0.39-0.88) and obesity (0.67, 0.43-1.04), generally remained unchanged; although, diabetes still showed a significant risk (2.62, 1.84-3.72). CONCLUSIONS: Controlling three modifiable risk factors including diabetes, hypertension and smoking might potentially reduce mortality events by over 40%, and among these, prevention of diabetes should be prioritized to decrease burden of events. We didn't confirm a negative impact of overweight and obesity status on premature mortality events.

Genotype and Phenotype of Echinococcus granulosus Derived from Wild Sheep (Ovis orientalis) in Iran.

The aim of the present study is to determine the characteristics of genotype and phenotype of Echinococcus granulosus derived from wild sheep and to compare them with the strains of E. granulosus sensu stricto (sheep-dog) and E. granulosus camel strain (camel-dog) in Iran. In Khojir National Park, near Tehran, Iran, a fertile hydatid cyst was recently found in the liver of a dead wild sheep (Ovis orientalis). The number of protoscolices (n=6,000) proved enough for an experimental infection in a dog. The characteristics of large and small hooks of metacestode were statistically determined as the sensu stricto strain but not the camel strain (P=0.5). To determine E. granulosus genotype, 20 adult worms of this type were collected from the infected dog. The second internal transcribed spacer (ITS2) of the nuclear ribosomal DNA (rDNA) and cytochrome c oxidase 1 subunit (COX1) of the mitochondrial DNA were amplified from individual adult worm by PCR. Subsequently, the PCR product was sequenced by Sanger method. The lengths of ITS2 and COX1 sequences were 378 and 857 bp, respectively, for all the sequenced samples. The amplified DNA sequences from both ribosomal and mitochondrial genes were highly similar (99% and 98%, respectively) to that of the ovine strain in the GenBank database. The results of the present study indicate that the morpho-molecular features and characteristics of E. granulosus in the Iranian wild sheep are the same as those of the sheep-dog E. granulosus sensu stricto strain.

Feature engineering from meta-data for prediction of differentially expressed genes: An investigation of Mus musculus exposed to space-conditions.

Transcription profiling is a key process that can reveal those biological mechanisms driving the response to various exposure conditions or gene perturbations. In this work, we investigate the prediction of differentially expressed genes (DEGs) when exposed to conditions in space from a set of diverse engineered features. To do this, we collected DEGs and non-differentially expressed genes (NDEGs) of Mus musculus-based experiments on the GeneLab database. We engineered a diverse set of features from factors reported in the literature to affect gene expression. An extreme gradient boosting (XGBoost) model was trained to predict if a given gene would be differentially expressed at various levels of differential expression. The test results on a separate holdout dataset showed an area under the receiver operating characteristics curves (AUCs) of 0.90±0.07, averaged across the five selected percentages of the most and least differentially expressed genes. Subsequently, we investigated the impact of selection of features, both individually with a correlation-based feature-selection procedure and in groups with a combination procedure, on the prediction performance. The feature selection confirmed some known drivers of adaptation to radiation and highlighted some new transcription factors and micro RNAs (miRNAs). Finally, gene ontology (GO) analysis revealed biological processes that tend to have expression patterns most suitable for this approach. This work highlights the potential of detection of differentially expressed genes using a machine learning (ML) approach, and provides some evidence of gene expression changes being captured by a diverse feature set not related to the condition under study.

Rapid psychiatric readmission in youth: A five-year retrospective Cohort Study.

This study describes predictors of psychiatric readmission among youth, including rapid readmission within 30 days of discharge. A retrospective chart review identified demographic features, diagnoses, and reasons for initial admission among 1324 youth admitted to the child and adolescent psychiatric emergency unit at a Canadian children's hospital. 22% of youth had at least one readmission and 8.8% had at least one rapid readmission during the five-year period. Personality disorder (HR=1.64, 95% CI=1.07, 2.52) and self-harm concerns (HR=0.65, 95% CI=0.48, 0.89) predicted odds of readmission Reducing readmission is an important goal, particularly for youth with personality concerns.

Preventive effect of quercetin-Loaded nanophytosome against autistic-like damage in maternal separation model: The possible role of Caspase-3, Bax/Bcl-2 and Nrf2.

The autism is an abnormality in the neuronal advance which starts before age 3 recognized by defective behaviors. This study aimed to make quercetin-loaded nanophytosomes (QNP) on behavioral deficits, cerebellar oxidative stress and apoptosis in an autistic-like model caused by maternal separation (MS). The newborn rats are randomly categorized into seven groups, including control, positive control, disease, and diseases treated with quercetin (10 and 40 mg/kg) and QNP (10 and 40 mg/kg). Pups exposed to MS for 3 h per day from postnatal days (PND) 1-9 showed behavioral impairment in adult rats compared to control group. The oral administration of quercetin and QNP was constantly started after the lactation period (21 postnatal days) for three weeks. Autistic-like behaviors, antioxidant parameters, and Nrf2, Bax/Bcl-2, and Caspase-3 expressions were surveyed in the cerebellum. Quercetin (40 mg/kg) treated improved some behavioral disorders. Also, the improvement of oxidative stress parameters, Nrf2 and apoptotic factors gene expression was observed in the cerebellum of quercetin (40 mg/kg) treated (p < 0.01). QNP treatment (10 and 40 mg/kg) significantly ameliorated anxiety-like behaviors, line crossing, and grooming index (p < 0.001), lipid peroxidation (p < 0.001), and increased catalase (CAT) (p < 0.001), superoxide dismutase (SOD) (p < 0.001), glutathione peroxidase (GPx) (p < 0.001) activity, and glutathione (GSH) levels (p < 0.05). Moreover, QNP significantly reduced Caspase-3 and Bax expression (p < 0.001), but increased Bcl-2, and Nrf2 expressions (p < 0.001). These findings indicated that QNP due to its high bioavailability was more effective than quercetin can be reduced autistic-like behavior, oxidative and apoptotic damages in the model of MS rats.

Nano-hesperetin attenuates ketamine-induced schizophrenia-like symptoms in mice: participation of antioxidant parameters.

RATIONALE: Antioxidant natural herb hesperetin (Hst) offers powerful medicinal properties. Despite having noticeable antioxidant properties, it has limited absorption, which is a major pharmacological obstacle. OBJECTIVES: The goal of the current investigation was to determine if Hst and nano-Hst might protect mice against oxidative stress and schizophrenia (SCZ)-like behaviors brought on by ketamine (KET). METHODS: Seven treatment groups (n=7) were created for the animals. For 10 days, they received distilled water or KET (10 mg/kg) intraperitoneally (i.p). From the 11th to the 40th day, they received daily oral administration of Hst and nano-Hst (10, 20 mg/kg) or vehicle. With the use of the forced swimming test (FST), open field test (OFT), and novel object recognition test (NORT), SCZ-like behaviors were evaluated. Malondialdehyde (MDA) and glutathione levels and antioxidant enzyme activities were assessed in the cerebral cortex. RESULTS: Our findings displayed that behavioral disorders induced by KET would be improved by nano-Hst treated. MDA levels were much lower after treatment with nano-Hst, and brain antioxidant levels and activities were noticeably higher. The mice treated with nano-Hst had improved outcomes in the behavioral and biochemical tests when compared to the Hst group. CONCLUSIONS: Our study's findings showed that nano-Hst had a stronger neuroprotective impact than Hst. In cerebral cortex tissues, nano-Hst treatment dramatically reduced KET-induced (SCZ)-like behavior and oxidative stress indicators. As a result, nano-Hst may have more therapeutic potential and may be effective in treating behavioral impairments and oxidative damage brought on by KET.

Disorganized symptoms and executive functioning predict impaired social functioning in subjects at risk for psychosis.

Predictors of social functioning deficits were assessed in 22 individuals "at risk" for psychosis. Disorganized symptoms and executive functioning predicted social functioning at follow-up. Early intervention efforts that focus on social and cognitive skills are indicated in this vulnerable population.

Diversity and burden of helminthiasis in wild ruminants in Iran.

This paper aimed to investigate the diversity and burden of helminthiasis in Ovis orientalis (n = 26), Capra aegagrus (n = 29) and Gazella subgutturosa (n = 24) grazed in 37 National Parks in 9 provinces of Iran. The organs and body cavities infected by helminths included gastrointestinal tract, peritoneal cavity, heart, liver and lungs. The contents were extracted and washed under running water and intestinal and lung-isolated nematodes were cleared in lactophenol and subsequently fixed, and cestodes were stained with alum carmine and mounted en face in Berlese's fluid under slight pressure between a microscopic slide and cover slip. The helminth species identified in this study include: intestinal nematodes (Marshallagia marshalli, Teladorsagia circumcincta, Ostertagia ostertagi, Nematodirus oiratianus, Nematodirella longispiculata, Skrjabinema ovis, Trichuris ovis, Trichuris discolor, Parabronema skrjabini), lungworms (Protostrongylus rufescens, Cystocaulus ocreatus), adult cestodes (Moniezia expansa, Helicometra giardi, Avitellina centripunctata, Stilesia globipunctata) and metacestodes (Cysticercus spp., hydatid cyst, Cysticercus tenuicollis). The proportion of the different helminth species ranged from low to moderate (3.45-46.15%) and the intensity of helminth isolation from the different ruminants ranged between 2 and 20. All the taxa identified in our study have been reported in wild animal species around the world. The presence of Cysticercus spp. with cardiac involvement in G. subgutturosa and all helminths of C. aegagrus was reported for the first time in Iran. A significant reduction was observed in worm burden, compared with previous studies in Iran, indicating changes in wildlife host-parasite systems, which can be linked to many reasons including climate changes, public health policies (e.g., strategic anthelmintic use in domestic ruminants), anthropogenic factors and environmental changes (e.g., urbanization or agricultural expansion, physical barriers), as well as vegetation growth and host availability.

Applications of Aspect-based Sentiment Analysis on Psychiatric Clinical Notes to Study Suicide in Youth.

Understanding and identifying the risk factors associated with suicide in youth experiencing mental health concerns is paramount to early intervention. 45% of patients are admitted annually for suicidality at BC Children's Hospital. Natural Language Processing (NLP) approaches have been applied with moderate success to psychiatric clinical notes to predict suicidality. Our objective was to explore whether machine-learning-based sentiment analysis could be informative in such a prediction task. We developed a psychiatry-relevant lexicon and identified specific categories of words, such as thought content and thought process that had significantly different polarity between suicidal and non-suicidal cases. In addition, we demonstrated that the individual words with their associated polarity can be used as features in classification models and carry informative content to differentiate between suicidal and non-suicidal cases. In conclusion, our study reveals that there is much value in applying NLP to psychiatric clinical notes and suicidal prediction.

ZnO-nanocatalyst Promoted the Production of Imidazole Derivatives via four-component Reaction of Aminoacid: Study of Antioxidant and Antimicrobial Activity.

AIM AND OBJECTIVE: In current research, imidazole derivatives are synthesized via a new process of four component reaction of trichloroacetonitrile, amides, alkyl bromides and amino acids catalyzed by zinc oxide nanoparticles (ZnO-NPs) as a simple and recyclable catalyst in water at room temperature. Among investigated compounds, compounds 5b have good results relative to butylated hydroxytoluene (BHT) and 2-tert-butylhydroquinone (TBHQ) as standard antioxidant. The achieved outcomes of disk diffusion experiment showed that these compounds avoided the growth of bacterial. MATERIALS AND METHODS: In this research, all chemicals are purchased from Fluka (Buchs, Switzerland) and employed with any purification. For measuring infrared spectroscopy and melting point, a Shimadzu IR-460 spectrometer and Electrothermal 9100 apparatus are utilized respectively. BRUKER DRX-400 AVANCE spectrometer is used for giving the 1H, and 13CNMR spectra at 400.1 and 100 MHz respectively. For recording mass spectra, A FINNIGAN-MAT 8430 spectrometer with an ionization potential of 70 eV was utilized. The scanning electron microscopy (SEM) employing a Holland Philips XL30 microscope was used for determination of ZnO nanocomposites morphology. X-ray diffraction (XRD) analysis at room temperature using a Holland Philips Xpert X-ray powder diffractometer, with CuKα radiation (λ=0.15406 nm), with 2θ ranging from 20 to 80° was employed for characterization of crystalline structure of Fe3O4/CuO nanocomposites. Scherrer's formula; D= 0.9λ/ß cosθ was employed for calculating the average crystallite size where D is the diameter of the nanoparticles, λ (CuKα) =1.5406 Å and ß is the fullwidth at half-maximum of the diffraction lines. A general way to prepare of compounds 5 The trichloroacetonitrile 1 (2 mmol) and amides 2 (2 mmol) mixed with ZnO-NPs (10 mol%) in water (5 mL). after 45 min amino acids 3 (2 mmol) was added to previous mixture at room temperature. After 30 min α-haloketones 4 (2 mmol) was added to mixture and stirred for 3 h. After 3 h, the reaction is completed and TLC confirms progress of the reaction. At last, the solid residue was collected by filtration and cleaned with EtOAC to removing ZnO-NPs and after evaporating solvent and washing solid with Et2O compounds 5 afforded as pure product. RESULTS: Without employing catalyst, these reactions have low yield and busy mixture. The synthesis of compound 5a as sample reaction and displayed the ZnO nanoparticles (10 mol%) is the best catalyst for sample reaction and H2O is the very better than other solvent in sample raection. Structures of 5 are confirmed by IR, 1H NMR, 13C NMR mass spectra. CONCLUSION: In summary, imdazole derivatives were produced in excellent yield from the reaction of trichloroacetonitrile, amides, alkyl bromides and amino acids using ZnO-NPs in water at room temperature. In addition, the power of synthesized imidazole as antioxidant was determined by radical trapping of DPPH and power of reducing ferric analyzes. The tested imidazoles display good radical trapping of DPPH but exhibitted moderate FRAP relative to BHT and TBHQ as synthetic antioxidants.The outcomes of disk diffusion experiment exhibite that synthesized imidazole avoided the bacterial growth. The superiorities of this procedure are environmental, high yield of product and low amounts of catalyst and short time of reaction.

Current Developments in the Chemical Upcycling of Waste Plastics Using Alternative Energy Sources.

The management of plastics waste is one of the most urgent and significant global problems now. Historically, waste plastics have been predominantly discarded, mechanically recycled, or incinerated for energy production. However, these approaches typically relied on thermal processes like conventional pyrolysis, which are energy-intensive and unsustainable. In this Minireview, some of the latest advances and future trends in the chemical upcycling of waste plastics by photocatalytic, electrolytic, and microwave-assisted pyrolysis processes are discussed as more environmentally friendly alternatives to conventional thermal reactions. We highlight how the transformation of different types of plastics waste by exploiting alternative energy sources can generate value-added products such as fuels (H2 and other carbon-containing small molecules), chemical feedstocks, and newly functionalized polymers, which can contribute to a more sustainable and circular economy.

Keys to Unlock the Enigma of Ocular Toxocariasis: A Systematic Review and Meta-analysis.

PURPOSE: Ocular toxocariasis (OT) is a zoonotic infection caused by larval stages of Toxocara canis and T. cati. The current review and meta-analysis aimed to evaluate the global prevalence of OT. METHODS: Five English (PubMed, Scopus, Science Direct, Web of Science, and Google Scholar) databases were explored and 101 articles met the inclusion criteria. RESULTS: The pooled prevalence (95% confidence interval) of OT was higher in immunological studies (9%. 6-12%) than in studies that applied ophthalmic examination (1%. 1-2%). The lower middle-income level countries had the highest prevalence (6%. 2-12%) as well as the African region (10%. 7-13%). The highest infection rate (4%. 2-7%) was detected in the 1-25 mean age group. CONCLUSION: Regular anthelminthic treatment of cats and dogs, and removal of animal feces from public places must be considered.

A Brain-Inspired Framework for Evolutionary Artificial General Intelligence.

From the medical field to agriculture, from energy to transportation, every industry is going through a revolution by embracing artificial intelligence (AI); nevertheless, AI is still in its infancy. Inspired by the evolution of the human brain, this article demonstrates a novel method and framework to synthesize an artificial brain with cognitive abilities by taking advantage of the same process responsible for the growth of the biological brain called "neuroembryogenesis." This framework shares some of the key behavioral aspects of the biological brain, such as spiking neurons, neuroplasticity, neuronal pruning, and excitatory and inhibitory interactions between neurons, together making it capable of learning and memorizing. One of the highlights of the proposed design is its potential to incrementally improve itself over generations based on system performance, using genetic algorithms. A proof of concept at the end of this article demonstrates how a simplified implementation of the human visual cortex using the proposed framework is capable of character recognition. Our framework is open source, and the code is shared with the scientific community at http://www.feagi.org.

A psychosocial assessment and management tool for children and youth in crisis.

OBJECTIVES: To evaluate the psychometric properties of HEARTSMAP, an emergency psychosocial assessment and management tool, and its impact on patient care and flow measures. METHODS: We conducted the study in two phases: first validating the tool using extracted information from a retrospective cohort, then evaluating implementation on a prospective cohort of youth presenting with mental health complaints to a tertiary Pediatric Emergency Department (PED). In phase 1, six PED clinicians applied HEARTSMAP to extracted narratives and we calculated inter-rater agreement for referral recommendations using Cohen's Kappa and the sensitivity and specificity for identifying youth requiring psychiatric consultation and hospitalization. In phase 2, PED clinicians prospectively used HEARTSMAP and we assessed the impact of the tool's implementation on patient-related outcomes and Emergency department (ED) flow measures. RESULTS: We found substantial agreement (κ=0.7) for cases requiring emergent psychiatric consultation and moderate agreement for cases requiring community urgent and non-urgent follow-up (κ=0.4 each). The sensitivity was 76% (95%CI: 63%, 90%) and specificity was 65% (95%CI: 55%, 71%) using retrospective cases. During pilot implementation, 62 patients received HEARTSMAP assessments: 46 (74%) of HEARTSMAP assessments triggered a recommendation for ED psychiatry assessment, 39 (63%) were evaluated by psychiatry and 13 (21%) were admitted. At follow-up, all patients with HEARTSMAP's triggered recommendations had accessed community resources. For those hospitalized for further psychiatric care at their index or return visit within 30 days, 100% were initially identified by HEARTSMAP at the index visit as requiring ED psychiatric consultation. CONCLUSIONS: HEARTSMAP has strong reliability, and when applied prospectively is a safe and effective management tool.

Trend of cardiovascular risk factors in the older Iranian population: 2002-2014.

AIM: Current study aimed to investigate the sex-stratified secular trend of cardiovascular disease risk factors among an older population in Iran during a median follow-up period of 8.76 years. METHODS: A total of 1490 participants (733 women) aged ≥60 years were evaluated in four study phases of 2002-2005, 2005-2008, 2008-2011 and 2011-2014. The trends of cardiovascular disease risk factors for each sex were estimated using generalized estimating equations. RESULTS: The age-adjusted prevalence of diabetes, hypertension, central obesity, and chronic kidney disease at the baseline was 24%, 43%, 55%, and 32% in men and 31%, 57%, 60% and 53% in women, respectively, and had noticeable upward trend during the study period to reach 35%, 56%, 61% and 51% in men, and 42%, 71%, 74% and 67% in women, respectively. However, lipid profile parameters showed favorable trends. Despite the increasing trend in drug consumption, approximately 27% of women with diabetes and 37% of men with diabetes did not use antidiabetic medication, respectively; the results were 23% and 35% for hypertensive women and men, respectively. Among men, there was a decreasing trend towards low physical activity, from 40% at baseline to 26% at the most recent follow up. The prevalence of smoking remained steady throughout follow up. CONCLUSIONS: Despite the benefits of lipid lowering, the status of other risk factor profiles are often suboptimal in both sexes. There remains much room for improvement in risk factors management, particularly for hypertension, smoking and adiposity status, and a need for an intervention. Geriatr Gerontol Int 2018; 18: 130-137.

Epigenetic Aberration of FMR1 Gene in Infertile Women with Diminished Ovarian Reserve.

OBJECTIVES: The diminished ovarian reserve (DOR) is a condition characterized by a reduction in the number and/or quality of oocytes. This primary infertility disorder is usually accompanied with an increase in the follicle-stimulating hormone (FSH) levels and regular menses. Although there are many factors contributing to the DOR situation, it is likely that many of idiopathic cases have genetic/epigenetic bases. The association between the FMR1 premutation (50-200 CGG repeats) and the premature ovarian failure (POF) suggests that epigenetic disorders of FMR1 can act as a risk factor for the DOR as well. The aim of this study was to analyze the mRNA expression and epigenetic alteration (histone acetylation/methylation) of the FMR1 gene in blood and granulosa cells of 20 infertile women. MATERIALS AND METHODS: In this case-control study, these women were referred to the Royan Institute, having been clinically diagnosed as DOR patients. Our control group consisted of 20 women with normal antral follicle numbers and serum FSH level. All these women had normal karyotype and no history of genetic disorders. The number of CGG triplet repeats in the exon 1 of the FMR1 gene was analyzed in all samples. RESULTS: Results clearly demonstrated significantly higher expression of the FMR1 gene in blood and granulosa cells of the DOR patients with the FMR1 premutation compared to the control group. In addition, epigenetic marks of histone 3 lysine 9 acetylation (H3K9ac) and di-metylation (H3K9me2) showed significantly higher incorporations in the regulatory regions of the FMR1 gene, including the promoter and the exon 1, whereas tri-metylation (H3K9me3) mark showed no significant difference between two groups. CONCLUSIONS: Our data demonstrates, for the first time, the dynamicity of gene expression and histone modification pattern in regulation of FMR1 gene, and implies the key role played by epigenetics in the development of the ovarian function.

Parasitic Infections of Bicoloured White-toothed Shrew (Crocidura leucodon) from Dasht-e-Razan, Western Iran.

BACKGROUND: The prevalence and intensity of endo and ectoparasites in shrews inhabiting in the Dasht-e Razan of Hamedan Province, Iran, were determined in this study. METHODS: By live traps, 64 shrews belong to species bicoloured white-toothed shrews (Crocidura leucodon) were trapped during 2010-2012. Captured animals were euthanized and their gender recorded. The blood thick and thin smears were stained with Geimsa and examined for protozoan parasites. Then, ectoparasites were collected and preserved in 70% ethanol and after necropsies; different organs were examined for helminthes. RESULTS: The prevalence of collected helminthes of Crocidura leucodon were; Capillaria crociduri (18.7%), Vigisolepis secunda (26.5%), Coronacantus sp (15.6%), Capillaria hokkaidensis (45.3%), and its ectoparasites were; Nymphs of three species of ticks; Haemaphysalis sp (32.8%), Ornitodoros sp (23.4%), Hyalomma sp (9.4%), one species of louse, Polyplax reclinata (18.7%) and one species of flea Leptopsylla sp (39.1%). Among the collected parasites, all helminthes and one sucking louse, P. reclinata are reported for the first time in Iran. Statistically analysis with the Chi-square test did not show any significant relation between gender and endoparasites (P>0.05), but the ectoparasites had significant differences with gender (P<0.05). No significant correlation was found between the altitude and the parasite species richness (Spearman's test: P>0.05). CONCLUSION: This study reports 9 species of parasites and 5 species of them were identified for the first time in Iran and some of them are vectors of several important zoonoses agents.

Sex-specific incidence rates and risk factors of premature cardiovascular disease. A long term follow up of the Tehran Lipid and Glucose Study.

OBJECTIVES: To investigate the risk factors for premature cardiovascular disease (CVD) and to quantify their population attributable fractions (PAFs) among an Iranian population during a median follow-up of 12years. METHODS: A total of 2235 men and 3703 women, aged ≥30years, free of CVD at baseline were entered into the study. Premature CVD was defined as having a history of CVD events before the age of 55 and 65 for men and women, respectively. Multivariate Cox proportional hazard regression models were used to determine the risk factors associated with premature CVD events. RESULTS: During the study, incident rates of premature CVD were 4.8 and 3.9 per 1000 person years for men and women, respectively. Low HDL-C [Hazard ratio: 1.74, 95% confidence interval: 1.11-2.74], hypercholesterolemia [3.01: 2.02-4.49], current smoker [1.68: 1.12-2.51], family history of premature CVD [2.04: 1.36-3.07], hypertension [1.65: 0.97-2.81, P=0.06] and type 2 diabetes(T2D) [1.98: 1.16-3.40] were significant predictors among men; the corresponding PAFs were 32.7, 29.4, 19.4, 14.9, 8.7 and 7.9%, respectively. Among women, T2D [3.02: 2.08-4.39], hypercholesterolemia [1.65: 1.19-2.29], being overweight [1.79: 1.01-3.17], hypertension [1.54: 1.01-2.34], family history of premature CVD [1.65: 1.19-2.29], high physical activity [0.67: 0.46-0.96] and prediabetes [1.48: 1.00-2.18] were significant predictors; the corresponding PAFs were 25.4, 22.5, 18.5, 16.8, 11.4, -10.3 and 9.1%, respectively. CONCLUSIONS: Considering the high burden imposed on health system by cardio-metabolic risk factors, dietary, behavioral and pharmacological interventions are need to be initiated early to prevent premature CVD, taking into account the sex-related differences between risk factors.