Epistasis between a set of variations located in the TAAR6 and HSP-70 genes toward schizophrenia and response to antipsychotic treatment

Suggestive associations have been reported between trace amines and heat shock proteins, and a disrupted pathophysiology that enhances the risk of psychosis and that modifies responses to antipsychotic treatments. Our group previously reported genetic studies on TAAR6 and HSP-70 separately in patients with schizophrenia. In the current study, we investigated possible epistasis between the same set of variations in a sample of 281 patients diagnosed with schizophrenia and 288 healthy controls. We applied the generalized multifactor dimensionality reduction (MDR) method and controlled covariates significantly associated with both diagnosis and treatment efficacy. To the best of our knowledge, epistasis between the present set of variations in schizophrenia has not been tested before. We found significant associations with both the risk of disease and response to treatment. However, the insufficiently balanced accuracy of the applied tests suggests that, despite significantly different genetic variations between cases and controls, these factors have a poor predictive value. Explanations for these findings and possible future directions are also discussed.     

Autosomal recessive otofaciocervical syndrome type 2 with novel homozygous small insertion in PAX1 gene

Otofaciocervical syndrome (OTFCS) is described as a single gene disorder of both autosomal dominant and autosomal recessive inheritance. The major clinical features of OTFCS include ear malformations (external/middle/inner ear), facial dysmorphism, shoulder girdle abnormalities, vertebral anomalies, and mild intellectual disability. The autosomal recessive form of OTFCS syndrome (OTFCS2) has been recently reported to be caused due to homozygous mutations in PAX1 gene. Here we report a third family of OTFCS2 phenotype wherein whole exome sequencing identified a novel homozygous small insertion in PAX1 as the underlying genetic cause.     

Genetic Variants Within Key Nodes of the Cascade of Antipsychotic Mechanisms: Effects on Antipsychotic Response and Schizophrenia Psychopathology in a Naturalistic Treatment Setting in Two Independent Korean and Italian Samples

Introduction

Schizophrenia (SCZ) is one of the most disabling psychiatric disorders. Genetic factors play an important role in both SCZ liability and its treatment outcome. In the present paper, we investigated the effects of several single nucleotide polymorphisms (SNPs) within ten strong candidate genes involved with antipsychotics (APs) mechanisms of action.

Methods

Two independent samples were investigated in the present study. Totals of 176 SCZ subjects and 326 controls of Korean ancestry, and 83 SCZ subjects and 194 controls of Italian ancestry were recruited and genotyped. SCZ risk and other parameters were also investigated.

Results

Concerning APs response, only a nominal association with HOMER1 rs3822568 in the Korean sample was found. In the haplotype analysis, rs9801117 C–rs12668837 C–rs4621754 A haplotype within ESYT2 and NCAPG2 genes was associated with APs response in the same sample. As for secondary outcomes, rs7439 within PKDCC and rs12668837 within NCAPG2 were associated with SCZ risk in the Italian sample. In the haplotype analysis, rs2788478 G–rs2657375 T–rs1039621 A within the region between WDR60 and ESYT genes and rs2013 C (ESYT2)–rs6459896 A (NCAPG2) haplotypes were associated with SCZ in the same sample. No association was found in the Korean sample. Finally, our exploratory data suggest a possible modulation of HOMER1, ARC, BDNF, TXNRD2, WDR60, and ESYT2 genes in the APs response to specific symptom clusters.

Conclusion

Our results did not support a primary role for the genes investigated in the APs response. On the other hand, our secondary results suggest a possible involvement of NACPG2 and PKDCC in SCZ liability. Finally, our exploratory findings may deserve further investigations in specific studies.

     

Ultrasound of Adnexal Masses

Current advancements in imaging technology, especially three-dimensional/four-dimensional ultrasound and contrast-enhanced imaging, have increased the diagnostic yield of adnexal masses. The benefit of ultrasound is the characterization of an adnexal mass, suggesting the probable etiology of the mass. Masses may be divided as solid, cystic, or complex. It is predominantly the solid and complex masses that need a thorough evaluation. The role of color-flow imaging is now gaining importance and criteria for distinguishing between benign and malignant masses are often possible. Availability of a scoring system enables the differentiation of small adnexal masses. Several benign lesions may present as complex masses but can be distinguished and diagnosed on sonography. The availability of 3D ultrasound has been of great use to understand spatial relations and vascular morphology. Sonography allows a more detailed assessment of morphologic features of an adnexal mass. With a benign-appearing adnexal mass on sonography, the need for any further diagnostic tests is often obviated.     

Predictors of in-hospital length of stay after laparoscopic ventral hernia repair: results of multivariate logistic regression analysis

Aim  

To identify variables that predict in-hospital length of stay (LOS) after laparoscopic ventral hernia repair (LVHR).     

A Noninvasive Clinical Scoring Model Predicts Risk of Nonalcoholic Steatohepatitis in Morbidly Obese Patients

Background  

A simple model to predict nonalcoholic steatohepatitis (NASH) in patients with nonalcoholic fatty liver disease is desirable to optimize the selection of patients for liver biopsy. We investigated a large group of morbidly obese patients to derive a scoring system based on simple clinical and laboratory variables.     

Predictors of attrition with buprenorphine/naloxone treatment in opioid dependent youth

Background

In opioid dependent youth there is substantial attrition from medication-assisted treatment. If youth at risk for attrition can be identified at treatment entry or early in treatment, they can be targeted for interventions to help retain them in treatment.

Methods

Opioid dependent adolescents and young adults (n = 152), aged 15–21, were randomized to 12 weeks (BUP, n = 74) or 2 weeks of detoxification (DETOX, n = 78) with buprenorphine/naloxone (Bup/Nal), both in combination with 12 weeks of psychosocial treatment. Baseline and early treatment related predictors of treatment attrition were identified in each group using bivariate and multivariate logistic regression.

Results

In the DETOX group 36% left between weeks 2 and 4, at the end of the dose taper, while in the BUP group only 8% left by week 4. In the BUP group, early adherence to Bup/Nal, early opioid negative urines, use of any medications in the month prior to treatment entry, and lifetime non-heroin opioid use were associated with retention while prior 30-day hallucinogen use was associated with attrition. In the DETOX group, only use of sleep medications was associated with retention although not an independent predictor. A broad range of other pre-treatment characteristics was unrelated to attrition.

Conclusions

Prompt attention to those with early non-adherence to medication or an early opioid positive urine, markers available in the first 2 weeks of treatment, may improve treatment retention. Extended Bup/Nal treatment appeared effective in improving treatment retention for youth with opioid dependence across a wide range of demographics, and pre-treatment clinical characteristics.