Australian SLPs' knowledge and actions regarding the early signs of autism: When does caution become gatekeeping?

Purpose: Speech-language pathologists (SLPs) are often the first point of contact for families of children with autism. Despite this, little is known about SLPs' understanding of autism and its early indicators. This study sought to investigate what Australian SLPs know about autism, the early indicators, and the actions they take when they identify these characteristics.

Polygenic risk scores for autoimmune related diseases are significantly different in cancer exceptional responders.

A small number of cancer patients respond exceptionally well to therapies and survive significantly longer than patients with similar diagnoses. Profiling the germline genetic backgrounds of exceptional responder (ER) patients, with extreme survival times, can yield insights into the germline polymorphisms that influence response to therapy. As ERs showed a high incidence in autoimmune diseases, we hypothesized the differences in autoimmune disease risk could reflect the immune background of ERs and contribute to better cancer treatment responses.

Prior opioid exposure influences parents' sharing of their children's CYP2D6 research results.

Aim: To determine parents' use of their children's CYP2D6 research result. We hypothesized that perceived utility, likelihood of sharing and actual sharing of results would differ between parents with children previously exposed (cases) or unexposed (controls) to opioids.

Methods: We returned results by phone (baseline).

Parental Perception of Self-Empowerment in Pediatric Pharmacogenetic Testing: The Reactions of Parents to the Communication of Actual and Hypothetical CYP2D6 Test Results.

Concerns about the ethical and social implications of genetics persist as more applications of genetic and genomic technology have become available. Pediatric testing for genetic influences on response to opioids like codeine is one area of application. We interviewed parents of children enrolled in a mixed-methods study following the communication of actual or hypothetical results for CYP2D6, which impacts opioid response.

Electronic Health Record Based Algorithm to Identify Patients with Autism Spectrum Disorder.

Objective: Cohort selection is challenging for large-scale electronic health record (EHR) analyses, as International Classification of Diseases 9th edition (ICD-9) diagnostic codes are notoriously unreliable disease predictors. Our objective was to develop, evaluate, and validate an automated algorithm for determining an Autism Spectrum Disorder (ASD) patient cohort from EHR. We demonstrate its utility via the largest investigation to date of the co-occurrence patterns of medical comorbidities in ASD.

Impact of an Electronic Template on Documentation of Obesity in a Primary Care Clinic.

Identification of obesity at well-child care (WCC) examinations is a step toward intervention. Studies have shown suboptimal documentation in primary care clinics that can improve with the use of electronic health records (EHRs). This study investigated the impact of a standardized EHR template on documentation of obesity at WCC visits and its impact on physician behavior.

A GWAS Study on Liver Function Test Using eMERGE Network Participants.

Introduction: Liver enzyme levels and total serum bilirubin are under genetic control and in recent years genome-wide population-based association studies have identified different susceptibility loci for these traits. We conducted a genome-wide association study in European ancestry participants from the Electronic Medical Records and Genomics (eMERGE) Network dataset of patient medical records with available genotyping data in order to identify genetic contributors to variability in serum bilirubin levels and other liver function tests and to compare the effects between adult and pediatric populations.

Methods: The process of whole genome imputation of eMERGE samples with standard quality control measures have been described previously.

Phenome-wide association study (PheWAS) in EMR-linked pediatric cohorts, genetically links PLCL1 to speech language development and IL5-IL13 to Eosinophilic Esophagitis.

Objective: We report the first pediatric specific Phenome-Wide Association Study (PheWAS) using electronic medical records (EMRs). Given the early success of PheWAS in adult populations, we investigated the feasibility of this approach in pediatric cohorts in which associations between a previously known genetic variant and a wide range of clinical or physiological traits were evaluated. Although computationally intensive, this approach has potential to reveal disease mechanistic relationships between a variant and a network of phenotypes.

EMR-linked GWAS study: investigation of variation landscape of loci for body mass index in children.

Unlabelled: Common variations at the loci harboring the fat mass and obesity gene (FTO), MC4R, and TMEM18 are consistently reported as being associated with obesity and body mass index (BMI) especially in adult population. In order to confirm this effect in pediatric population five European ancestry cohorts from pediatric eMERGE-II network (CCHMC-BCH) were evaluated.

Method: Data on 5049 samples of European ancestry were obtained from the Electronic Medical Records (EMRs) of two large academic centers in five different genotyped cohorts.

Combination lopinavir and ritonavir alter exogenous and endogenous bile acid disposition in sandwich-cultured rat hepatocytes.

Inhibition of the bile salt export pump (BSEP) can cause intracellular accumulation of bile acids and is a risk factor for drug-induced liver injury in humans. Antiretroviral protease inhibitors lopinavir (LPV) and ritonavir (RTV) are reported BSEP inhibitors. However, the consequences of LPV and RTV, alone and combined (LPV/r), on hepatocyte viability, bile acid transport, and endogenous bile acid disposition in rat hepatocytes have not been examined.

Endogenous bile acid disposition in rat and human sandwich-cultured hepatocytes.

Sandwich-cultured hepatocytes (SCH) are used commonly to investigate hepatic transport protein-mediated uptake and biliary excretion of substrates. However, little is known about the disposition of endogenous bile acids (BAs) in SCH. In this study, four endogenous conjugated BAs common to rats and humans [taurocholic acid (TCA), glycocholic acid (GCA), taurochenodeoxycholic acid (TCDCA), and glycochenodeoxycholic acid (GCDCA)], as well as two BA species specific to rodents (α- and β-tauromuricholic acid; α/β TMCA), were profiled in primary rat and human SCH.

Automated applications of sandwich-cultured hepatocytes in the evaluation of hepatic drug transport.

Predictions of the absorption, distribution, metabolism, excretion, and toxicity of compounds in pharmaceutical development are essential aspects of the drug discovery process. B-CLEAR is an in vitro system that uses sandwich-cultured hepatocytes to evaluate and predict in vivo hepatobiliary disposition (hepatic uptake, biliary excretion, and biliary clearance), transporter-based hepatic drug-drug interactions, and potential drug-induced hepatotoxicity. Automation of predictive technologies is an advantageous and preferred format in drug discovery.

Differential disposition of chenodeoxycholic acid versus taurocholic acid in response to acute troglitazone exposure in rat hepatocytes.

Inhibition of bile acid (BA) transport may contribute to the hepatotoxicity of troglitazone (TRO), a peroxisome proliferator-activated receptor gamma agonist. Typically, studies use taurocholic acid (TCA) as a model substrate to investigate effects of xenobiotics on BA disposition. However, TRO may differentially affect the transport of individual BAs, potentially causing hepatocyte accumulation of more cytotoxic BAs.

Exploring adoption with clients: the need for adoption education within the genetic counseling profession.

Genetic counselors and other health professionals may encounter adoption during any counseling session. They must be skilled in using appropriate language and understand how to approach and discuss this topic with clients. A thorough knowledge of adoption as an option for clients facing a prenatal or postnatal diagnosis is necessary when presenting individuals with non-biased information needed for informed decision-making.

An in vitro assay to assess transporter-based cholestatic hepatotoxicity using sandwich-cultured rat hepatocytes.

Drug-induced cholestasis can result from the inhibition of biliary efflux of bile acids in the liver. Drugs may inhibit the hepatic uptake and/or the biliary efflux of bile acids resulting in an increase in serum concentrations. However, it is the intracellular concentration of bile acids that results in hepatotoxicity, and thus serum concentrations may not necessarily be an appropriate indicator of hepatotoxicity.