The Updated Mouse Universal Genotyping Array Bioinformatic Pipeline Improves Genetic QC in Laboratory Mice.

The MiniMUGA genotyping array is a popular tool for genetic QC of laboratory mice and genotyping of samples from most types of experimental crosses involving laboratory strains, particularly for reduced complexity crosses. The content of the production version of the MiniMUGA array is fixed; however, there is the opportunity to improve array's performance and the associated report's usefulness by leveraging thousands of samples genotyped since the initial description of MiniMUGA in 2020. Here we report our efforts to update and improve marker annotation, increase the number and the reliability of the consensus genotypes for inbred strains and increase the number of constructs that can reliably be detected with MiniMUGA. In addition, we have implemented key changes in the informatics pipeline to identify and quantify the contribution of specific genetic backgrounds to the makeup of a given sample, remove arbitrary thresholds, include the Y Chromosome and mitochondrial genome in the ideogram, and improve robust detection of the presence of commercially available substrains based on diagnostic alleles. Finally, we have made changes to the layout of the report, to simplify the interpretation and completeness of the analysis and added a table summarizing the ideogram. We believe that these changes will be of general interest to the mouse research community and will be instrumental in our goal of improving the rigor and reproducibility of mouse-based biomedical research.

An interaction of inorganic arsenic exposure with body weight and composition on type 2 diabetes indicators in Diversity Outbred mice.

Type 2 diabetes (T2D) is a complex metabolic disorder with no cure and high morbidity. Exposure to inorganic arsenic (iAs), a ubiquitous environmental contaminant, is associated with increased T2D risk. Despite growing evidence linking iAs exposure to T2D, the factors underlying inter-individual differences in susceptibility remain unclear. This study examined the interaction between chronic iAs exposure and body composition in a cohort of 75 Diversity Outbred mice. The study design mimics that of an exposed human population where the genetic diversity of the mice provides the variation in response, in contrast to a design that includes untreated mice. Male mice were exposed to iAs in drinking water (100 ppb) for 26 weeks. Metabolic indicators used as diabetes surrogates included fasting blood glucose and plasma insulin (FBG, FPI), blood glucose and plasma insulin 15 min after glucose challenge (BG15, PI15), homeostatic model assessment for [Formula: see text]-cell function and insulin resistance (HOMA-B, HOMA-IR), and insulinogenic index. Body composition was determined using magnetic resonance imaging, and the concentrations of iAs and its methylated metabolites were measured in liver and urine. Associations between cumulative iAs consumption and FPI, PI15, HOMA-B, and HOMA-IR manifested as significant interactions between iAs and body weight/composition. Arsenic speciation analyses in liver and urine suggest little variation in the mice's ability to metabolize iAs. The observed interactions accord with current research aiming to disentangle the effects of multiple complex factors on T2D risk, highlighting the need for further research on iAs metabolism and its consequences in genetically diverse mouse strains.

Content and Performance of the MiniMUGA Genotyping Array: A New Tool To Improve Rigor and Reproducibility in Mouse Research.

The laboratory mouse is the most widely used animal model for biomedical research, due in part to its well-annotated genome, wealth of genetic resources, and the ability to precisely manipulate its genome. Despite the importance of genetics for mouse research, genetic quality control (QC) is not standardized, in part due to the lack of cost-effective, informative, and robust platforms. Genotyping arrays are standard tools for mouse research and remain an attractive alternative even in the era of high-throughput whole-genome sequencing. Here, we describe the content and performance of a new iteration of the Mouse Universal Genotyping Array (MUGA), MiniMUGA, an array-based genetic QC platform with over 11,000 probes. In addition to robust discrimination between most classical and wild-derived laboratory strains, MiniMUGA was designed to contain features not available in other platforms: (1) chromosomal sex determination, (2) discrimination between substrains from multiple commercial vendors, (3) diagnostic SNPs for popular laboratory strains, (4) detection of constructs used in genetically engineered mice, and (5) an easy-to-interpret report summarizing these results. In-depth annotation of all probes should facilitate custom analyses by individual researchers. To determine the performance of MiniMUGA, we genotyped 6899 samples from a wide variety of genetic backgrounds. The performance of MiniMUGA compares favorably with three previous iterations of the MUGA family of arrays, both in discrimination capabilities and robustness. We have generated publicly available consensus genotypes for 241 inbred strains including classical, wild-derived, and recombinant inbred lines. Here, we also report the detection of a substantial number of XO and XXY individuals across a variety of sample types, new markers that expand the utility of reduced complexity crosses to genetic backgrounds other than C57BL/6, and the robust detection of 17 genetic constructs. We provide preliminary evidence that the array can be used to identify both partial sex chromosome duplication and mosaicism, and that diagnostic SNPs can be used to determine how long inbred mice have been bred independently from the relevant main stock. We conclude that MiniMUGA is a valuable platform for genetic QC, and an important new tool to increase the rigor and reproducibility of mouse research.

Positional cyanosis reveals platypnea-orthodeoxia-syndrome.

Platypnea-orthodeoxia syndrome is a rare cause of dyspnea, which presents upon standing and resolves when supine. Etiology is multifactorial with a functional component and an anatomical shunt. The most commonly reported shunt is an atrial septal defect, however a shunt can occur in advanced hepatic or pulmonary disease. Treatment is dependent on the type and location of the shunt. In atrial septal defects percutaneous repair is preferred. To follow is a case of iatrogenic platypnea-orthodeoxia syndrome secondary to heart failure guideline directed medical therapy in a 79 year-old woman.

Correction to: The One Health Approach to Toxoplasmosis: Epidemiology, Control, and Prevention Strategies.

This article was originally published electronically on the publisher's internet portal (currently SpringerLink) on April 3, 2019 without open access.

The One Health Approach to Toxoplasmosis: Epidemiology, Control, and Prevention Strategies.

One Health is a collaborative, interdisciplinary effort that seeks optimal health for people, animals, plants, and the environment. Toxoplasmosis, caused by Toxoplasma gondii, is an intracellular protozoan infection distributed worldwide, with a heteroxenous life cycle that practically affects all homeotherms and in which felines act as definitive reservoirs. Herein, we review the natural history of T. gondii, its transmission and impacts in humans, domestic animals, wildlife both terrestrial and aquatic, and ecosystems. The epidemiology, prevention, and control strategies are reviewed, with the objective of facilitating awareness of this disease and promoting transdisciplinary collaborations, integrative research, and capacity building among universities, government agencies, NGOs, policy makers, practicing physicians, veterinarians, and the general public.

Lingual liability: macroglossia and dyspnoea as the harbinger of systemic AL (light-chain) cardiac amyloidosis.

A 58-year-old man presented with a chief complaint of tongue indentations and discomfort. Otolaryngology treated him for oral thrush with counselling to avoid tongue biting. In addition, the patient reported dyspnoea described as a decrease in tolerance of his physical activities. Due to continued increase in tongue size and worsening dyspnoea, he underwent a tissue biopsy with findings consistent with amyloidosis. Further evaluation with a bone marrow biopsy revealed underlying multiple myeloma. Echocardiography revealed abnormal ventricular wall thickness, with a reduced left ventricular chamber size, dilated atria and Doppler findings with restrictive filling patterns indicative of cardiac amyloidosis. The patient was initiated on chemotherapy for his multiple myeloma and supportive therapy for his cardiac amyloidosis. Light-chain amyloidosis (AL) is a systemic disease characterised by irreversible deposition of amyloid in tissues throughout the body; when there is cardiac involvement, it can result in heart failure with a poor prognosis. Early diagnosis of cardiac amyloidosis can lead to prolonged survival.

Incremental benefits of a daily report card intervention over time for youth with disruptive behavior.

This study examined the percentage of children who respond positively to a daily report card (DRC) intervention and the extent to which students achieve incremental benefits with each month of intervention in a general education classroom. Participants were 66 children (87% male) with attention-deficit hyperactivity disorder or disruptive behavior problems who were enrolled in a school-based intervention program in rural, low-income school districts in a Midwest state. The DRC was implemented by each child's teacher, who received consultation from a graduate student clinician, school district counselor, or school district social worker. A latent class analysis using growth-mixture modeling identified two classes of response patterns (i.e., significant improvement and significant decline). Results indicated that 72% of the sample had all of their target behaviors classified as improved, 8% had all of their targets classified as declining, and 20% had one target behavior in each class. To examine the monthly incremental benefit of the DRC, individual effect sizes were calculated. Results for the overall sample indicated that most children experience a benefit of large magnitude (.78) within the first month, with continued incremental benefits through Month 4. The differential pattern of effect sizes for the group of improvers and the group of decliners offer data to determine when and if the DRC should be discontinued and an alternative strategy attempted. Evidence-based guidelines for practical implementation of the DRC are discussed.

Science to practice in underserved communities: the effectiveness of school mental health programming.

This study examined the effectiveness of a treatment program comprised of several components based on evidence-based treatments (EBTs) for disruptive behavior problems delivered to youth participating in a school mental health program in an underserved community in the Appalachian region. Participants were 117 children in kindergarten through 6th grade including 91 children (78% male) from 5 schools who were consecutively referred to the intervention program and 26 children (73% male) from 3 schools in which program implementation was delayed for 1 year. Treatment outcome was measured via parent and teacher ratings of child symptoms and functioning. The treatment condition resulted in significant reduction in hyperactivity/impulsivity and early aggressive and delinquent behavior, as well as significant improvement in several other functional domains. Results suggest that EBTs can retain their effectiveness when transported to a community context.

School-based mental health programming for children with inattentive and disruptive behavior problems: first-year treatment outcome.

This article examines the effectiveness of an evidence-based behavioral treatment package for children with inattentive and disruptive behavior problems when delivered in the context of a school-based mental health program. Child symptomatology and functioning are assessed in a treatment group (n = 30) and a waitlist control group (n = 12) across multiple time points (fall, winter, and spring). Treatment includes a daily report card procedure, year-long teacher consultation, and parenting sessions. According to the parent report, treated children show marked reductions in hyperactive and impulsive, oppositional or defiant and aggressive behavior, and marked improvement in peer relationships. Teachers observe treatment-related group differences in inattention, academic functioning, and the student-teacher relationship. Feasibility and acceptability data have implications for transporting evidence-based treatments to community settings and for integrating mental health services into the culture of the school community.

Effectiveness research in the context of school-based mental health.

There are many challenges to transporting evidence-based treatments from laboratories into real-world settings. However, if we hope to make our evidence-based treatments accessible and available to children and usable by community professionals, effectiveness research is imperative. We argue that schools represent an ideal real world setting in which to conduct such research. The goals of this paper are to present the advantages of conducting effectiveness research in the school setting and to encourage clinical researchers to engage in effectiveness research in this "location," as there are benefits to children, pre-service professionals, communities, and researchers. We attempt to further advance the literature by discussing the challenges associated with this work and by providing a case example (The Youth Experiencing Success in School [Y.E.S.S.] Program) that demonstrates real world application of our recommendations.