Development of carrier testing for common inborn errors of metabolism in the Wisconsin Plain population.

Purpose: This community project is an initiative through the University of Wisconsin Biochemical Genetics Clinic and the Wisconsin Newborn Screening Program to identify members of the Plain population who are at risk for having children with maple syrup urine disease (MSUD) or propionic acidemia (PA) or who have PA.

Methods: Because of the high prevalence of metabolic conditions in the Plain population and the importance of early intervention, a statewide outreach project was developed to provide targeted variant analysis of the common MSUD and PA pathogenic variants in this population through health-care provider distribution of blood spot testing kits. Awareness was achieved through outreach efforts with the state midwives guild and Plain population meetings.

Effects of carrageenan on cell permeability, cytotoxicity, and cytokine gene expression in human intestinal and hepatic cell lines.

Carrageenan (CGN) is a common food additive used for its gelling and thickening properties. The present study was done to evaluate intestinal permeability, cytotoxicity, and CGN-mediated induction of proinflammatory cytokines. A standard Caco-2 absorption model showed no CGN permeability or cytotoxicity at concentrations of 100, 500, and 1000 μg/mL.

Glycomacropeptide for nutritional management of phenylketonuria: a randomized, controlled, crossover trial.

Background: To prevent cognitive impairment, phenylketonuria requires lifelong management of blood phenylalanine (Phe) concentration with a low-Phe diet. The diet restricts intake of Phe from natural proteins in combination with traditional amino acid medical foods (AA-MFs) or glycomacropeptide medical foods (GMP-MFs) that contain primarily intact protein and a small amount of Phe.

Objective: We investigated the efficacy and safety of a low-Phe diet combined with GMP-MFs or AA-MFs providing the same quantity of protein equivalents in free-living subjects with phenylketonuria.

Tartrate-Resistant Acid Phosphatase Deficiency in the Predisposition to Systemic Lupus Erythematosus.

Objective: Mutations in the ACP5 gene, which encodes tartrate-resistant acid phosphatase (TRAP), cause the immuno-osseous disorder spondyloenchondrodysplasia, which includes as disease features systemic lupus erythematosus (SLE) and a type I interferon (IFN) signature. Our aims were to identify TRAP substrates, determine the consequences of TRAP deficiency in immune cells, and assess whether ACP5 mutations are enriched in sporadic cases of SLE.

Methods: Interaction between TRAP and its binding partners was tested by a yeast 2-hybrid screening, confocal microscopy, and immunoprecipitation/Western blotting.

Brief Report: Vitamin D Deficiency Is Associated With Endothelial Dysfunction and Increases Type I Interferon Gene Expression in a Murine Model of Systemic Lupus Erythematosus.

Objective: Patients with systemic lupus erythematosus (SLE) have an increased risk of cardiovascular disease (CVD) and impaired endothelial repair. Although vitamin D deficiency is associated with increased CVD risk in the general population, a causal relationship has not been demonstrated. We aimed to determine whether vitamin D deficiency directly modulates endothelial dysfunction and immune responses in a murine model of SLE.

Plasma exosome profiles from dairy cows with divergent fertility phenotypes.

Cell-to-cell communication in physiological and pathological conditions may be influenced by neighboring cells, distant tissues, or local environmental factors. Exosomes are specific subsets of extracellular vesicles that internalize and deliver their content to near and distant sites. Exosomes may play a role in the maternal-embryo crosstalk vital for the recognition and maintenance of a pregnancy; however, their role in dairy cow reproduction has not been established.

Conceptual framework for outcomes research studies of hepatitis C: an analytical review.

Hepatitis C virus infection is one of the main causes of chronic liver disease worldwide. Until recently, the standard antiviral regimen for hepatitis C was a combination of an interferon derivative and ribavirin, but a plethora of new antiviral drugs is becoming available. While these new drugs have shown great efficacy in clinical trials, observational studies are needed to determine their effectiveness in clinical practice.

TBC1D24 genotype-phenotype correlation: Epilepsies and other neurologic features.

Objective: To evaluate the phenotypic spectrum associated with mutations in TBC1D24.

Methods: We acquired new clinical, EEG, and neuroimaging data of 11 previously unreported and 37 published patients. TBC1D24 mutations, identified through various sequencing methods, can be found online (http://lovd.

ADA2 deficiency: case report of a new phenotype and novel mutation in two sisters.

The objective of this paper is to: describe the phenotype compound heterozygote for mutations in CECR1 in two children. We describe the clinical and immunological phenotype, including the assessment of ADA2 activity, cytokine expression, interferon-stimulated and neutrophil-stimulated gene signatures, and the results of CECR1 sequencing. The first patient presented with intermittent fever, cutaneous vasculitis, myalgia and muscle inflammation on MRI leading to a provisional diagnosis of periarteritis nodosa.

Adherence to hydroxyurea medication by children with sickle cell disease (SCD) using an electronic device: a feasibility study.

Adherence to hydroxyurea (HU) is a significant modifying factor in sickle cell vaso-occlusive pain. We conducted a study using an electronic medication container-monitor-reminder device (GlowCap™) to track adherence and determine whether use of this device affected rates of HU adherence. Subjects were regular attendees to our clinic.

Clinical, radiological and possible pathological overlap of cystic leukoencephalopathy without megalencephaly and Aicardi-Goutières syndrome.

Background: Cystic leukoencephalopathy without megalencephaly is a disorder related in some cases to RNASET2 mutations and characterized by bilateral anterior temporal subcortical cysts and multifocal lobar white matter lesions with sparing of central white matter structures. This phenotype significantly overlaps with the sequelae of in utero cytomegalovirus (CMV) infection, including the presence of intracranial calcification in some cases. Aicardi-Goutières syndrome (AGS) is another inherited leukodystrophy with cerebral calcification mimicking congenital infection.

Role of Extracellular Vesicles and microRNAs on Dysfunctional Angiogenesis during Preeclamptic Pregnancies.

Preeclampsia is a syndrome characterized by hypertension during pregnancy, which is a leading cause of morbidity and mortality in both mother and newborn in developing countries. Some advances have increased the understanding of pathophysiology of this disease. For example, reduced utero-placental blood flow associated with impaired trophoblast invasion may lead to a hypoxic placenta that releases harmful materials into the maternal and feto-placental circulation and impairs endothelial function.

Clinical relevance of the discrepancy in phenylalanine concentrations analyzed using tandem mass spectrometry compared with ion-exchange chromatography in phenylketonuria.

Introduction: Metabolic control of phenylketonuria (PKU) and compliance with the low-phenylalanine (phe) diet are frequently assessed by measuring blood phe concentrations in dried blood spots (DBS) collected by patients instead of plasma phe concentrations.

Objective: Our objective was to investigate the difference in blood phe concentrations in DBS collected by subjects and analyzed using either a validated newborn screening tandem mass spectrometry (MS/MS) protocol or ion-exchange chromatography (IEC) compared to plasma phe concentrations obtained simultaneously and analyzed using IEC.

Design: Three to four fasting blood samples were obtained from 29 subjects with PKU, ages 15-49 years.

Placental biomarkers and angiogenic factors in oral fluids of patients with preeclampsia.

Objectives: The objectives of this study are to explore the feasibility of measuring endothelial and placental biomarkers in saliva and gingival crevicular fluid (GCF) and to determine if patients with preeclampsia (PE) have a different profile of these biomarkers in oral fluids.

Method: A case-control study was conducted, including patients with PE (n = 10) and a control group with normal pregnancies randomly selected (n = 20) admitted at the Sótero del Río Hospital in Santiago, Chile. A complete periodontal and obstetric history that involved the collection of oral fluids was performed at the same gestational age.

Spondyloenchondrodysplasia Due to Mutations in ACP5: A Comprehensive Survey.

Purpose: Spondyloenchondrodysplasia is a rare immuno-osseous dysplasia caused by biallelic mutations in ACP5. We aimed to provide a survey of the skeletal, neurological and immune manifestations of this disease in a cohort of molecularly confirmed cases.

Methods: We compiled clinical, genetic and serological data from a total of 26 patients from 18 pedigrees, all with biallelic ACP5 mutations.

Exploring Students' Perceptions of the Educational Value of Formative Objective Structured Clinical Examination (OSCE) in a Nutrition Program.

Introduction: Objective Structured Clinical Examinations (OSCEs) are valuable teaching tools in various disciplines including nutrition. OSCEs increase students' confidence, improve their communication and counseling skills, and can predict clinical strength and identify weaknesses prior to clinical placement. This study explored the impact of three OSCE experiences with nutrition students and evaluated the use of this type of formative assessment.

PI3K/AKT Pathway and Brain Malformations.

Investigators from Seattle Children's Research Institute, University of Washington, and collaborating institutions sought to evaluate 10 genes in the PI3K/AKT pathway as it relates epileptogenic brain malformations in patients with megalencephaly, hemimegalencephaly, and focal cortical dysplasia.

An Orientation Program for Clinical Adjunct Faculty.

Having highly competent clinical faculty in an institution of higher learning is a prerequisite for graduating safe nurses in the future. The purpose of this project was to increase each clinical nurse's knowledge and skills for the new role of clinical adjunct nursing faculty. Successful implementation of this program will help promote consistency in effective job performance of clinical adjunct faculty and facilitate achievement of the projected goals and outcomes.