AG1478 Elicits a Novel Anti-Influenza Function via an EGFR-Independent, GBF1-Dependent Pathway.

Current options for preventing or treating influenza are still limited, and new treatments for influenza viral infection are urgently needed. In the present study, we serendipitously found that a small-molecule inhibitor (AG1478), previously used for epidermal growth factor receptor (EGFR) inhibition, demonstrated a potent activity against influenza both in vitro and in vivo. Surprisingly, the antiviral effect of AG1478 was not mediated by its EGFR inhibitory activity, as influenza virus was insensitive to EGFR blockade by other EGFR inhibitors or by siRNA knockdown of EGFR.

Evaluating Technology-Mediated Collaborative Workflows for Telehealth.

Goals: This paper discusses the need for a predictable method to evaluate gains and gaps of collaborative technology-mediated workflows and introduces an evaluation framework to address this need.

Methods: The Collaborative Space - Analysis Framework (CS-AF), introduced in this research, is a cross-disciplinary evaluation method designed to evaluate technology-mediated collaborative workflows. The 5-step CS-AF meta-process includes: (1) current-state workflow definition, (2) current-state (baseline) workflow assessment, (3) technology-mediated workflow development and deployment, (4) technology-mediated workflow assessment, (5) analysis and conclusions.

Alternaria induces airway epithelial cytokine expression independent of protease-activated receptor.

Background And Objective: A novel fungal allergen, Alternaria (Alt), has been previously shown to associate with the pathogenesis of allergic rhinitis and bronchial asthma, particularly in arid and semi-arid regions. Airway epithelial cells are among the first to encounter Alt, and epithelial cytokine production and subsequent airway inflammation are early events in the response to Alt exposure. However, the underlying mechanism is unclear.

The Club Cell Marker SCGB1A1 Downstream of FOXA2 is Reduced in Asthma.

Human SCGB1A1 protein has been shown to be significantly reduced in BAL, sputum, and serum from humans with asthma as compared with healthy individuals. However, the mechanism of this reduction and its functional impact have not been entirely elucidated. By mining online datasets, we found that the mRNA of was significantly repressed in brushed human airway epithelial cells from individuals with asthma, and this repression appeared to be associated with reduced expression of FOXA2.

Whole-Exome Sequencing for Diagnosis of Turner Syndrome: Toward Next-Generation Sequencing and Newborn Screening.

Context: Turner syndrome (TS) is due to a complete or partial loss of an X chromosome in female patients and is not currently part of newborn screening (NBS). Diagnosis is often delayed, resulting in missed crucial diagnostic and therapeutic opportunities.

Objectives: This study sought to determine if whole-exome sequencing (WES) as part of a potential NBS program could be used to diagnose TS.

Autosomal and X chromosome structural variants are associated with congenital heart defects in Turner syndrome: The NHLBI GenTAC registry.

Turner Syndrome (TS) is a developmental disorder caused by partial or complete loss of one sex chromosome. Bicuspid aortic valve and other left-sided congenital heart lesions (LSL), including thoracic aortic aneurysms and acute aortic dissections, are 30-50 times more frequent in TS than in the general population. In 454 TS subjects, we found that LSL are significantly associated with reduced dosage of Xp genes and increased dosage of Xq genes.

Proceedings from the Turner Resource Network symposium: the crossroads of health care research and health care delivery.

Turner syndrome, a congenital condition that affects ∼1/2,500 births, results from absence or structural alteration of the second sex chromosome. There has been substantial effort by numerous clinical and genetic research groups to delineate the clinical, pathophysiological, cytogenetic, and molecular features of this multisystem condition. Questions about the molecular-genetic and biological basis of many of the clinical features remain unanswered, and health care providers and families seek improved care for affected individuals.

Turner syndrome and associated problems in Turkish children: a multicenter study.

Objective: Turner syndrome (TS) is a chromosomal disorder caused by complete or partial X chromosome monosomy that manifests various clinical features depending on the karyotype and on the genetic background of affected girls. This study aimed to systematically investigate the key clinical features of TS in relationship to karyotype in a large pediatric Turkish patient population.

Methods: Our retrospective study included 842 karyotype-proven TS patients aged 0-18 years who were evaluated in 35 different centers in Turkey in the years 2013-2014.

Childhood somatic complaints predict generalized anxiety and depressive disorders during young adulthood in a community sample.

Background: Children with somatic complaints are at increased risk for emotional disorders during childhood. Whether this elevated risk extends into young adulthood - and to which specific disorders - has rarely been tested with long-term prospective-longitudinal community samples. Here we test whether frequent and recurring stomach aches, headaches, and muscle aches during childhood predict emotional disorders in adulthood after accounting for childhood psychiatric and physical health status and psychosocial adversity.

Pregnancy and cardiovascular risk for women with Turner syndrome.

Most women with Turner syndrome (TS) are infertile due to primary ovarian failure. However, approximately 5% experience spontaneous pregnancy, and recently, more women with TS have used assisted reproductive technology with donated oocytes (ART-OD) to become pregnant. The first generation of Turner patients undergoing ART-OD demonstrated a high rate of fatal aortic dissection in late pregnancy or postpartum.

X chromosome parental origin and aortic stiffness in turner syndrome.

Introduction: Aortic abnormalities contribute to increased morbidity and mortality of women with Turner syndrome (TS). Impaired aortic stiffness may prove to have clinical prognostic value in TS as is the case in other diseases such as Marfan syndrome, diabetes and hypertension. Additionally, the parental origin of the X chromosome in TS may influence aortic stiffness.

Sleep problems predict and are predicted by generalized anxiety/depression and oppositional defiant disorder.

Objective: We tested whether sleep problems co-occur with, precede, and/or follow common psychiatric disorders during childhood and adolescence. We also clarified the role of comorbidity and tested for specificity of associations among sleep problems and psychiatric disorders.

Method: Data came from the Great Smoky Mountains Study, a representative population sample of 1,420 children, assessed 4 to 7 times per person between ages 9 and 16 years for major Diagnostic and Statistical Manual-Fourth Edition (DSM-IV) disorders and sleep problems.

Anxiety sensitivity and risk-taking behavior.

High trait anxiety has been linked with risk-avoidant decision-making, though little is known regarding the specific facets of anxiety contributing to this negative association. Anxiety sensitivity (AS), a transdiagnostic vulnerability factor for anxiety-related pathology, may be particularly relevant to risk decision-making given that risk-taking behaviors generate heightened somatic arousal and produce many of the sensations feared by individuals with high AS. Two studies were conducted to investigate the relation between AS and risk decision-making.

Self-rated health and C-reactive protein in young adults.

Background: Poor self-rated health (SRH) and elevated inflammation and morbidity and mortality are robustly associated in middle- and older-aged adults. Less is known about SRH-elevated inflammation associations during young adulthood and whether these linkages differ by sex.

Methods: Data came from the National Longitudinal Study of Adolescent Health.

Spectrum of aortic valve abnormalities associated with aortic dilation across age groups in Turner syndrome.

Background: Congenital aortic valve fusion is associated with aortic dilation, aneurysm, and rupture in girls and women with Turner syndrome. Our objective was to characterize aortic valve structure in subjects with Turner syndrome and to determine the prevalence of aortic dilation and valve dysfunction associated with different types of aortic valves.

Methods And Results: The aortic valve and thoracic aorta were characterized by cardiovascular MRI in 208 subjects with Turner syndrome in an institutional review board-approved natural history study.

Bicuspid aortic valve and aortic coarctation are linked to deletion of the X chromosome short arm in Turner syndrome.

Background: Congenital heart disease (CHD) is a cardinal feature of X chromosome monosomy, or Turner syndrome (TS). Haploinsufficiency for gene(s) located on Xp have been implicated in the short stature characteristic of the syndrome, but the chromosomal region related to the CHD phenotype has not been established.

Design: We used cardiac MRI to diagnose cardiovascular abnormalities in four non-mosaic karyotype groups based on 50-metaphase analyses: 45,X (n=152); 46,X,del(Xp) (n=15); 46,X,del(Xq) (n=4); and 46,X,i(Xq) (n=14) from peripheral blood cells.

Single-nucleotide polymorphism array genotyping is equivalent to metaphase cytogenetics for diagnosis of Turner syndrome.

Purpose: Turner syndrome is a developmental disorder caused by partial or complete monosomy for the X chromosome in 1 in 2,500 females. We hypothesized that single-nucleotide polymorphism (SNP) array genotyping could provide superior resolution in comparison to metaphase karyotype analysis to facilitate genotype-phenotype correlations.

Methods: We genotyped 187 Turner syndrome patients with 733,000 SNP marker arrays.

High levels of education and employment among women with Turner syndrome.

Background: Turner Syndrome (TS) is due to X chromosome monosomy and affects ~1 per 2500 females at birth. The major features are short stature and primary ovarian failure. Short stature and monosomy for a maternal X chromosome have been implicated in impaired functionality in adult life; however, data on adult outcomes in TS are limited.

Multilocus loss of DNA methylation in individuals with mutations in the histone H3 lysine 4 demethylase KDM5C.

Background: A number of neurodevelopmental syndromes are caused by mutations in genes encoding proteins that normally function in epigenetic regulation. Identification of epigenetic alterations occurring in these disorders could shed light on molecular pathways relevant to neurodevelopment.

Results: Using a genome-wide approach, we identified genes with significant loss of DNA methylation in blood of males with intellectual disability and mutations in the X-linked KDM5C gene, encoding a histone H3 lysine 4 demethylase, in comparison to age/sex matched controls.

Perturbation of the transforming growth factor β system in Turner syndrome.

Objective: To measure components of the circulating transforming growth factor β (TGFβ) system in patients with Turner syndrome (TS) compared to relevant controls and to ascertain correlation with endocrine and cardiovascular parameters.

Methods: TGFβ1, TGFβ2 and endoglin (a vascular TGF receptor component) were measured using enzyme-linked immunoassays in the sera of 40 subjects with TS and 40 healthy volunteer women. The cardiovascular phenotype in TS subjects was extensively characterized by cardiac magnetic resonance (MR) and echo.

N-terminal pro-brain natriuretic peptide levels and aortic diameters.

Background: Women with X-chromosome monosomy or Turner syndrome (TS) are at increased risk for aortic dilation and dissection. To better understand the pathology and develop tools to monitor the risk of aortic disease, we investigated N-terminal pro-brain natriuretic peptide (BNP) (NT-proBNP) levels in women with TS and healthy female controls.

Methods: We evaluated NT-proBNP levels in women with karyotype-proven TS and healthy female volunteers in relation to ascending aortic diameter and descending aortic diameter measured by cardiovascular magnetic resonance imaging.

Genomic imprinting and Turner syndrome.

The term 'genomic imprinting' refers to selective repression of transcription from distinct chromosomal regions determined by their maternal or paternal inheritance. There are two potentially important aspects of imprinting that may manifest in individuals with X monosomy, or Turner syndrome (TS). Given that men are monosomic for Xm while women are mosaic for Xm:Xp, genomic imprinting of important X-linked genes should be associated with sexually dimorphic traits, e.

Trends in GH use in a Turner syndrome natural history study.

The present observations are derived from 273 girls and women aged 7-40 years participating in the National Institutes of Health natural history study of Turner syndrome (TS) in the interval 2001-2011. There was a higher percentage of GH use among individuals in the pediatric age group (7-17, n = 118, 83%) compared to young adult women with prior GH use (18-40, n = 155, 61%). The major factor in this divergence seems to be a trend toward earlier diagnosis of TS in the younger age group.