Design and Protocol of the Renal Anhydramnios Fetal Therapy (RAFT) Trial.

Purpose: Anhydramnios secondary to anuria before 22 weeks of gestational age and congenital bilateral renal agenesis before 26 weeks of gestational age are collectively referred to as early-pregnancy renal anhydramnios. Early-pregnancy renal anhydramnios occurs in at least 1 in 2000 pregnancies and is considered universally fatal when left untreated because of severe pulmonary hypoplasia precluding ex utero survival The Renal Anhydramnios Fetal Therapy (RAFT) trial is a nonrandomized, nonblinded, multicenter clinical trial designed to assess the efficacy, safety, and feasibility of amnioinfusions for patients with pregnancies complicated by early-pregnancy renal anhydramnios. The primary objective of this study is to determine the proportion of neonates surviving to successful dialysis, defined as use of a dialysis catheter for ≥14 days.

Fetal interventions for congenital renal anomalies.

Congenital abnormalities of the kidney and urinary tract (CAKUT) represent 20% of prenatally diagnosed congenital abnormalities. Although the majority of these abnormalities do not require intervention either pre or postnatally, there is a subset of patients whose disease is so severe that it may warrant intervention prior to delivery to prevent morbidity and mortality. These cases consist of patients with moderate lower urinary tract obstruction (LUTO) in which vesicocentesis, shunting or cystoscopy are options and patients with early pregnancy renal anhydramnios (EPRA) in whom amnioinfusion therapy may be an option.

A Central Role for Lipocalin-2 in the Adaptation to Short-Bowel Syndrome Through Down-Regulation of IL22 in Mice.

Background & Aims: In short-bowel syndrome (SBS), inadequate intestinal adaptation is responsible for the majority of complications, including sepsis, liver failure, and death. In this study, we sought to further delineate the adaptive response to identify potential therapeutic targets.

Methods: We performed a 75% small-bowel resection (SBR) or sham operation on C57Bl/6J wild-type (WT), lipocalin-2 (LCN2), and interleukin 22 (IL22) mice.

Amnioinfusions to Treat Early Onset Anhydramnios Caused by Renal Anomalies: Background and Rationale for the Renal Anhydramnios Fetal Therapy Trial.

Anhydramnios caused by early anuria is thought to be universally fatal due to pulmonary hypoplasia. Bilateral renal agenesis and early fetal renal failure leading to anhydramnios constitute early pregnancy renal anhydramnios (EPRA). There have been successful reports of amnioinfusions to promote lung growth in the setting of EPRA.

Two Proximally Close Priority Candidate Genes for diplopodia-1, an Autosomal Inherited Craniofacial-Limb Syndrome in the Chicken: MRE11 and GPR83.

Next-generation sequencing (NGS) and expression technologies were utilized to investigate the genes and sequence elements in a 586 kb region of chicken chromosome 1 associated with the autosomal recessive diplopodia-1 (dp-1) mutation. This mutation shows a syndromic phenotype similar to known human developmental abnormalities (e.g.

An APOO Pseudogene on Chromosome 5q Is Associated With Low-Density Lipoprotein Cholesterol Levels.

Background: Elevated levels of low-density lipoprotein cholesterol (LDL-C) are a major risk factor for cardiovascular disease via its contribution to the development and progression of atherosclerotic lesions. Although the genetic basis of LDL-C has been studied extensively, currently known genetic variants account for only ≈20% of the variation in LDL-C levels.

Methods: Through an array-based association analysis in 1102 Amish subjects, we identified a variant strongly associated with LDL-C levels.

Optimal timing for elective resection of asymptomatic congenital pulmonary airway malformations.

Purpose: We sought to determine optimal timing for CPAM resection within the first year of life.

Methods: We queried the National Surgical Quality Improvement Program pediatric database from 2012 to 2015 for elective CPAM resections on patients less than 1year of age. Patients were divided by age in months: 1-3 (n=57), 4-6 (n=135), and 6-12 (n=214).

Skeletal Dysplasias: Growing Therapy for Growing Bones.

Skeletal dysplasias represent a large and diverse group of rare conditions affecting collagen and bone. They can be clinically classified based on radiographic and physical features, and many can be further defined at a molecular level (Bonafe et al., 2015).

TM6SF2 rs58542926 impacts lipid processing in liver and small intestine.

Unlabelled: The transmembrane 6 superfamily member 2 (TM6SF2) loss-of-function variant rs58542926 is a genetic risk factor for nonalcoholic fatty liver disease and progression to fibrosis but is paradoxically associated with lower levels of hepatically derived triglyceride-rich lipoproteins. TM6SF2 is expressed predominantly in liver and small intestine, sites for triglyceride-rich lipoprotein biogenesis and export. In light of this, we hypothesized that TM6SF2 may exhibit analogous effects on both liver and intestine lipid homeostasis.

Assignment of Functional Relevance to Genes at Type 2 Diabetes-Associated Loci Through Investigation of β-Cell Mass Deficits.

Type 2 diabetes (T2D) has been associated with a large number of genomic loci, many of which encompass multiple genes without a definitive causal gene. This complexity has hindered efforts to clearly identify functional candidate genes and interpret their role in mediating susceptibility to disease. Here we examined the relevance of individual genes found at T2D-associated loci by assessing their potential contribution to a phenotype relevant to the disease state: production and maintenance of β-cell mass.

Differential effects on β-cell mass by disruption of Bardet-Biedl syndrome or Alstrom syndrome genes.

Rare genetic syndromes characterized by early-onset type 2 diabetes have revealed the importance of pancreatic β-cells in genetic susceptibility to diabetes. However, the role of genetic regulation of β-cells in disorders that are also characterized by highly penetrant obesity, a major additional risk factor, is unclear. In this study, we investigated the contribution of genes associated with two obesity ciliopathies, Bardet-Biedl Syndrome and Alstrom Syndrome, to the production and maintenance of pancreatic β-cells.

Disruption of ldlr causes increased LDL-c and vascular lipid accumulation in a zebrafish model of hypercholesterolemia.

Hyperlipidemia and arterial cholesterol accumulation are primary causes of cardiovascular events. Monogenic forms of hyperlipidemia and recent genome-wide association studies indicate that genetics plays an important role. Zebrafish are a useful model for studying the genetic susceptibility to hyperlipidemia owing to conservation of many components of lipoprotein metabolism, including those related to LDL, ease of genetic manipulation, and in vivo observation of lipid transport and vascular calcification.

The cellular and molecular etiology of the craniofacial defects in the avian ciliopathic mutant talpid2.

talpid(2) is an avian autosomal recessive mutant with a myriad of congenital malformations, including polydactyly and facial clefting. Although phenotypically similar to talpid(3), talpid(2) has a distinct facial phenotype and an unknown cellular, molecular and genetic basis. We set out to determine the etiology of the craniofacial phenotype of this mutant.

Primary cilia in pancreatic development and disease.

Primary cilia and their anchoring basal bodies are important regulators of a growing list of signaling pathways. Consequently, dysfunction in proteins associated with these structures results in perturbation of the development and function of a spectrum of tissue and cell types. Here, we review the role of cilia in mediating the development and function of the pancreas.

Project brainstorm: using neuroscience to connect college students with local schools.

Neuroscience can be used as a tool to inspire an interest in science in school children as well as to provide teaching experience to college students.

Increased functional selectivity over development in rostrolateral prefrontal cortex.

Relational reasoning, or the ability to identify and consider relationships between multiple mental representations, is a fundamental component of high-level cognition (Robin and Holyoak, 1995). The capacity to reason with relations enables abstract thought and may be at the core of what makes human cognition unique (Penn et al., 2008).

Abnormal fMRI activation pattern during story listening in individuals with Down syndrome.

Down syndrome is characterized by disproportionately severe impairments of speech and language, yet little is known about the neural underpinnings of these deficits. We compared fMRI activation patterns during passive story listening in 9 young adults with Down syndrome and 9 approximately age-matched, typically developing controls. The typically developing group exhibited greater activation than did the Down syndrome group in classical receptive language areas (superior and middle temporal gyri) for forward > backward speech; the Down syndrome group exhibited greater activation in cingulate gyrus, superior and inferior parietal lobules, and precuneus for both forward speech > rest and backward speech > rest.

Fluid reasoning and the developing brain.

Fluid reasoning is the cornerstone of human cognition, both during development and in adulthood. Despite this, the neural mechanisms underlying the development of fluid reasoning are largely unknown. In this review, we provide an overview of this important cognitive ability, the method of measurement, its changes over the childhood and adolescence of an individual, and its underlying neurobiological underpinnings.

Effects of prenatal methamphetamine exposure on verbal memory revealed with functional magnetic resonance imaging.

Objective: Efforts to understand specific effects of prenatal methamphetamine (MA) exposure on cognitive processing are hampered by high rates of concomitant alcohol use during pregnancy. We examined whether neurocognitive systems differed among children with differing prenatal teratogenic exposures when they engaged in a verbal memory task.

Patients And Methods: Participants (7-15 years) engaged in a verbal paired associate learning task while undergoing functional magnetic resonance imaging.

Altered frontal-parietal functioning during verbal working memory in children and adolescents with heavy prenatal alcohol exposure.

This study evaluated the neural basis of verbal working memory (WM) function in a group of 20 children and adolescents with fetal alcohol spectrum disorders (FASDs) and 20 typically developing comparison participants using functional magnetic resonance imaging (fMRI). Both groups showed prominent activation in the frontal-parietal-cerebellar network known to be important for verbal WM. Despite equivalent behavioral performance between groups, alcohol-exposed individuals showed increased activation relative to typically developing individuals in left dorsal frontal and left inferior parietal cortices, and bilateral posterior temporal regions during verbal WM.

Relationships between brain activation and brain structure in normally developing children.

Dynamic changes in brain structure, activation, and cognitive abilities co-occur during development, but little is known about how changes in brain structure relate to changes in cognitive function or brain activity. By using cortical pattern matching techniques to correlate cortical gray matter thickness and functional brain activity over the entire brain surface in 24 typically developing children, we integrated structural and functional magnetic resonance imaging data with cognitive test scores to identify correlates of mature performance during orthographic processing. Fast-naming individuals activated the right fronto-parietal attention network in response to novel fonts more than slow-naming individuals, and increased activation of this network was correlated with more mature brain morphology in the same fronto-parietal region.

Neurodevelopmental changes in verbal working memory load-dependency: an fMRI investigation.

Development of working memory (WM) aptitude parallels structural changes in the frontal-parietal association cortices important for performance within this cognitive domain. The cerebellum has been proposed to function in support of the postulated phonological loop component of verbal WM, and along with frontal and parietal cortices, has been shown to exhibit linear WM load-dependent activation in adults. It is not known if these kinds of WM load-dependent relationships exist for cerebro-cerebellar networks in developmental populations, and whether there are age-related changes in the nature of load-dependency between childhood, adolescence, and adulthood.

Functional magnetic resonance imaging of verbal learning in children with heavy prenatal alcohol exposure.

We examined functional MRI activation patterns corresponding to verbal paired associate learning in a group of 11 children with heavy prenatal alcohol exposure compared with 16 typically developing children. Among the typically developing children, prominent activation was observed in the left medial temporal lobe, left dorsal frontal lobe and bilateral posterior temporal cortices during learning and recall. Analyses revealed significantly less activation in left medial and posterior temporal regions and significantly more activation in right dorsal frontal cortex in the alcohol-exposed children relative to controls, even when group differences in memory test performance were statistically controlled.

Mapping cerebellar vermal morphology and cognitive correlates in prenatal alcohol exposure.

Prenatal exposure to alcohol can result in neuroanatomical and neurocognitive deficits. High-resolution magnetic resonance imaging, surface-based image analytic methods, and neuropsychological measures were used to characterize the cerebellar vermis and to evaluate potential cognitive correlates of vermal morphology in 21 children and adolescents with prenatal alcohol exposure and 21 normally developing individuals. Alcohol-exposed individuals showed statistically significant reductions in the midline sagittal areas of the anterior vermis and posterior-inferior vermis, and significant displacement of the anterior and posterior-inferior vermal regions.