The Psychological Rehabilitation impact through Dohsa-Hou Method on Motional Performance and Peers Relationship Self-Efficacy of Children suffering from Attention Deficit Hyperactivity Disorder (ADHD)

Introduction: The aim of the present research was to study the psychological rehabilitation impact through Dohsa-Hou on motional performance and  peer relationship self-efficacy of children suffering from ADHD at Zahedan City. Methods: The research is semi-experimental including pre-test, post-test and follow-up in two experiment and control groups. The research statistical population includes all children suffering from ADHD. 30 children 7-9 suffering from ADHD was selected through sampling. 15 children were assigned in control group and 15 children were assigned in experiment group randomly. Furthermore, another assessment was conducted through post-test and follow-up at the end. Dohsa-Hou treatment duration was 12 sessions in experiment group (3 sessions per week) and follow-up was conducted one week after the post-test. Data resulted from questionnaire were analyzed using SPSS-19 software and descriptive and inferential tests.Results: The results of analysis MANCOVA showed that psychological rehabilitation through Dohsa-Hou method has caused to increased motional performance and self-efficiency promotion of children suffering from (ADHD) in relationship with their peers (P≤0.01).Conclusion: Dohsa-Hou method is an effective treatment for promotion of their motional performance and self-efficiency in relationship with their peers.  Declaration of Interest: Non

CpG island methylation of TMS1/ASC and CASP8 genes in cervical cancer

<p>Abstract</p> <p>Background</p> <p>Gene silencing associated with aberrant methylation of promoter region CpG islands is an acquired epigenetic alteration that serves as an alternative to genetic defects in the inactivation of tumor suppressor and other genes in human cancers.</p> <p>Aims</p> <p>This study describes the methylation status of <it>TMS1</it>/<it>ASC </it>and <it>CASP8 </it>genes in cervical cancer. We also examined the prevalence of <it>TMS1</it>/<it>ASC </it>and <it>CASP8 </it>genes methylation in cervical cancer tissue and none - neo plastic samples in an effort to correlate with smoking habit and clinicopathological features.</p> <p>Method</p> <p>Target DNA was modified by sodium bisulfite, converting all unmethylated, but not methylated, cytosines to uracil, and subsequently amplified by Methylation Specific (MS) PCR with primers specific for methylated versus unmethylated DNA. The PCR product was detected by gel electrophoresis and combined with the clinical records of patients.</p> <p>Results</p> <p>The methylation pattern of the <it>TMS1</it>/<it>ASC </it>and <it>CASP8 </it>genes in specimens of cervical cancer and adjacent normal tissues were detected [5/80 (6.2%), 3/80 (3.75%)-2/80 (2.5%), 1/80 (1.2%) respectively]. No statistical differences were seen in the extent of differentiation, invasion, pathological type and smoking habit between the methylated and unmethylated tissues (<it>P </it>> 0.05).</p> <p>Conclusion</p> <p>The present study conclude that the frequency of <it>TMS1</it>/<it>ASC </it>and <it>CASP8 </it>genes methylation in cervical cancer are rare (< 6%), and have no any critical role in development of cervical cancer.</p

Strategies for whole-exome sequencing analysis in a case series study of familial male infertility

Background: Infertility is one of the common health issues around the world. The prevalence of male factor infertility among infertile couples is approximately 30%- 35%, of which genetic factors account for 15%. The family-based whole-exome sequencing (WES) approach can accurately detect novel variants. However, selecting an appropriate sample for data generation using WES has proven to be challenging in familial male infertility studies. The aim of this study was to identify types of pathogenic male infertility in cases of familial asthenozoospermia. Case: Two families with multiple cases were recruited for the purpose of WES. The study population included two affected cases in pedigree I and three affected cases in pedigree II. Two different variant callers (SAMtools and GATK) with a single-sample calling strategy (SSCS) and a multiple-sample calling strategy (MSCS), were applied to identify variant sites. Conclusion: In this study, we represented the results for variant prioritization of WES data without sequencing fertile siblings in the same pedigree by applying two different pipelines (homozygosity and linkage-based strategy). Using the aforementioned strategies, we prioritized annotated variants and generated a logical shortlist of private variants for each pedigree. Key words: Male infertility, Whole-exome sequencing, GATK, SAMtools

Novel mutations of PCCA and PCCB genes found by whole-exome sequencing related to propionic acidemia patients

Propionic acidemia (PROP) is an autosomal recessive inherited metabolic deficiency caused by multimeric mitochondrial enzyme propionyl‐coenzyme A (CoA) carboxylase (PCC). PCC enzyme contains a and b subunits, encoded by the PCCA and PCCB genes that mutations in both subunits are related to propionic acidemia. About 50% of disease-causing variants have been found in PCCA and most mutations related to propionic acidemia are missense mutations. The present study involves three families that are suspicious to hereditary propionic acidemia syndrome. The first family has four, the second family has one, and the third family has two passed-away children. All these families were diagnosed with the same clinical conditions such as poor feeding, vomiting, hypotonia, and lethargy. In the process of finding and confirming the mutation, pathological tests and whole-exome sequencing and sanger sequencing were done. In order to pathological tests and whole-exome sequencing, this is the first report of three novel variants related to propionic acidemia: 1. Novel pathogenic homozygous NM_000532.5: c.503_505del: p.Glu168del mutation of the PCCB exon5 gene, 2. Novel pathogenic homozygous splicing NM_000282:c.1900- 1G&gt;A mutation of PCCA exon22 and exon21, 3. Novel compound heterozygous pathogenic NM_000532.5: c.503_505del: p.Glu168del and likely pathogenic NM_000532.5:c.539T&gt;C: P.F180S mutation of the PCCB exon5 gene. The study shows that PCCA and PCCB have a great role in hereditary propionic acidemia and the results of the present study may be of importance in genetic counseling and finding the best treatment of this syndrome. DOI: http://dx.doi.org/10.5281/zenodo.737427

Analysis of methylation and mRNA expression status of FADD and FAS genes in patients with oral squamous cell carcinoma

Background: Apoptosis is an important mechanism that is responsible for the physiological deletion of harmful, damaged, or unwanted cells. Changed expression of apoptosis-related genes may lead to abnormal cell proliferation and finally to tumorigenesis. Our aims were to analyze the promoter methylation and gene expression profiles of FADD and FAS genes in risk of OSCC. Material and Methods: we analyze the promoter methylation status of FADD and FAS genes using Methylation - Specific PCR (MSP) in 86 OSCC tissues were kept in paraffin and 68 normal oral tissues applied as control. Also, FADD and FAS genes expression were analyzed in 19 cases and 20 normal specimens by Real-Time Reverse- Transcripts PCR. Results: Aberrant promoter methylation of FADD and FAS genes were detected in 12.79 % (11 of 86) and 60.46 % (52 of 86) of the OSCC cases, respectively, with a significant difference between cases and healthy controls for both FADD and FAS genes ( P <0.001). The gene expression analysis showed statistically significant difference between cases and healthy controls for both FADD ( p <0.02) and FAS ( p <0.007) genes. Conclusions: To the best our knowledge, the data of this study are the first report regarding, the effect of promoter hypermethylation of the FADD and FAS genes in development of OSCC. To confirm the data, it is recommended doing further study in large sample sizes in various genetic populations

Mimicry and well known genetic friends: molecular diagnosis in an Iranian cohort of suspected Bartter syndrome and proposition of an algorithm for clinical differential diagnosis.

BACKGROUND: Bartter Syndrome is a rare, genetically heterogeneous, mainly autosomal recessively inherited condition characterized by hypochloremic hypokalemic metabolic alkalosis. Mutations in several genes encoding for ion channels localizing to the renal tubules including SLC12A1, KCNJ1, BSND, CLCNKA, CLCNKB, MAGED2 and CASR have been identified as underlying molecular cause. No genetically defined cases have been described in the Iranian population to date. Like for other rare genetic disorders, implementation of Next Generation Sequencing (NGS) technologies has greatly facilitated genetic diagnostics and counseling over the last years. In this study, we describe the clinical, biochemical and genetic characteristics of patients from 15 Iranian families with a clinical diagnosis of Bartter Syndrome. RESULTS: Age range of patients included in this study was 3 months to 6 years and all patients showed hypokalemic metabolic alkalosis. 3 patients additionally displayed hypercalciuria, with evidence of nephrocalcinosis in one case. Screening by Whole Exome Sequencing (WES) and long range PCR revealed that 12/17 patients (70%) had a deletion of the entire CLCNKB gene that was previously identified as the most common cause of Bartter Syndrome in other populations. 4/17 individuals (approximately 25% of cases) were found to suffer in fact from pseudo-Bartter syndrome resulting from congenital chloride diarrhea due to a novel homozygous mutation in the SLC26A3 gene, Pendred syndrome due to a known homozygous mutation in SLC26A4, Cystic Fibrosis (CF) due to a novel mutation in CFTR and apparent mineralocorticoid excess syndrome due to a novel homozygous loss of function mutation in HSD11B2 gene. 1 case (5%) remained unsolved. CONCLUSIONS: Our findings demonstrate deletion of CLCNKB is the most common cause of Bartter syndrome in Iranian patients and we show that age of onset of clinical symptoms as well as clinical features amongst those patients are variable. Further, using WES we were able to prove that nearly 1/4 patients in fact suffered from Pseudo-Bartter Syndrome, reversing the initial clinical diagnosis with important impact on the subsequent treatment and clinical follow up pathway. Finally, we propose an algorithm for clinical differential diagnosis of Bartter Syndrome

Role of DNA methylation in head and neck cancer

Head and neck cancer (HNC) is a heterogenous and complex entity including diverse anatomical sites and a variety of tumor types displaying unique characteristics and different etilogies. Both environmental and genetic factors play a role in the development of the disease, but the underlying mechanism is still far from clear. Previous studies suggest that alterations in the genes acting in cellular signal pathways may contribute to head and neck carcinogenesis. In cancer, DNA methylation patterns display specific aberrations even in the early and precancerous stages and may confer susceptibility to further genetic or epigenetic changes. Silencing of the genes by hypermethylation or induction of oncogenes by promoter hypomethylation are frequent mechanisms in different types of cancer and achieve increasing diagnostic and therapeutic importance since the changes are reversible. Therefore, methylation analysis may provide promising clinical applications, including the development of new biomarkers and prediction of the therapeutic response or prognosis. In this review, we aimed to analyze the available information indicating a role for the epigenetic changes in HNC

Contribution of LATS1 and LATS2 promoter methylation in OSCC development

The aberrant DNA methylation of the tumor suppressor genes involved in DNA Damage Response (DDR) signaling and cell cycle regulation may lead to the tumorigenesis. Our purpose here is to analyze the promoter methylation and mRNA expression levels of LATS1 and LATS2 (LATS1/2) genes in OSCC. Promoter methylation status of LATS1/2 genes was evaluated in 70 OSCC paraffin-embedded tissues and 70 normal oral samples, using Methylation Specific PCR (MSP). LATS1/2 mRNA expression profiles were also investigated in 14 OSCC patients and 14 normal samples, using real-time PCR. In both candidate genes, promoter methylation assessment revealed significant relationship between cases and controls (OR = 2.24, 95 % CI = 1.40–3.54, P = 0.001; LATS1 and OR = 15.5, 95%CI = 3.64–64.76, P < 0.001; LATS2). As well as, the evaluation of mRNA expression levels showed decreased expression in OSCC tissues in compare to control tissues. (Mean ± SD 1.74 ± 0.14 in OSCC versus 2.10 ± 0.24 in controls, P < 0.001; LATS1 and Mean ± SD 1.36 ± 0.077 in OSCC versus 1.96 ± 0.096 in controls, P < 0.001; LATS2). To the best our knowledge, this is the first report regarding the down-regulation of LATS1/2 through promoter methylation in OSCC. It is suggested to explore the down-stream transcription factors of both genes for finding the molecular mechanism of this deregulation in OSCC