Regulation of MYC by CARD14 in human epithelium is a determinant of epidermal homeostasis and disease.

Caspase recruitment domain family member 14 (CARD14) and its variants are associated with both atopic dermatitis (AD) and psoriasis, but their mechanistic impact on skin barrier homeostasis is largely unknown. CARD14 is known to signal via NF-κB; however, CARD14-NF-κB signaling does not fully explain the heterogeneity of CARD14-driven disease. Here, we describe a direct interaction between CARD14 and MYC and show that CARD14 signals through MYC in keratinocytes to coordinate skin barrier homeostasis.

Filaggrin loss-of-function variants are associated with atopic dermatitis phenotypes in a diverse, early-life prospective cohort.

Loss-of-function (LoF) variants in the filaggrin (FLG) gene are the strongest known genetic risk factor for atopic dermatitis (AD), but the impact of these variants on AD outcomes is poorly understood. We comprehensively identified genetic variants through targeted region sequencing of FLG in children participating in the Mechanisms of Progression of Atopic Dermatitis to Asthma in Children cohort. Twenty FLG LoF variants were identified, including 1 novel variant and 9 variants not previously associated with AD.

Progressive accumulation of hyperinflammatory NKG2D NK cells in early childhood severe atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease that often precedes the development of food allergy, asthma, and allergic rhinitis. The prevailing paradigm holds that a reduced frequency and function of natural killer (NK) cell contributes to AD pathogenesis, yet the underlying mechanisms and contributions of NK cells to allergic comorbidities remain ill-defined. Here, analysis of circulating NK cells in a longitudinal early life cohort of children with AD revealed a progressive accumulation of NK cells with low expression of the activating receptor NKG2D, which was linked to more severe AD and sensitivity to allergens.

Temporal relationships between Staphylococcus aureus colonization, filaggrin expression, and pediatric atopic dermatitis.

Background: Atopic dermatitis (AD) is characterized by Staphylococcus aureus (S. aureus) colonization. Longitudinal early life data delineating relationships of S.

Progressive accumulation of hyperinflammatory NKG2D NK cells in early childhood severe atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease that often precedes the development of food allergy, asthma, and allergic rhinitis. The prevailing paradigm holds that a reduced frequency and function of natural killer (NK) cell contributes to AD pathogenesis, yet the underlying mechanisms and contributions of NK cells to allergic co-morbidities remain ill-defined. Herein, analysis of circulating NK cells in a longitudinal early life cohort of children with AD revealed a progressive accumulation of NK cells with low expression of the activating receptor NKG2D, which was linked to more severe AD and sensitivity to allergens.

Thymic stromal lymphopoietin rather than IL-33 drives food allergy after epicutaneous sensitization to food allergen.

Background: A major route of sensitization to food allergen is through an impaired skin barrier. IL-33 and thymic stromal lymphopoietin (TSLP) have both been implicated in epicutaneous sensitization and food allergy, albeit in different murine models.

Objective: We assessed the respective contributions of TSLP and IL-33 to the development of atopic dermatitis (AD) and subsequent food allergy in TSLP and IL-33 receptor (ST2)-deficient mice using an AD model that does not require tape stripping.

B cell repertoire in children with skin barrier dysfunction supports altered IgE maturation associated with allergic food sensitization.

The skin is a major immune organ and skin barrier dysfunction is a major risk factor for the development of the inappropriate immune response seen in allergic disease. Skin barrier disruption alters the landscape of antigens experienced by the immune system and the downstream impacts on the antibody repertoire remain poorly characterized, particularly for the IgE isotype responsible for allergic specificity and in early life, when allergic disease is developing. In this study, we sequenced antibody gene repertoires from a large and well-characterized cohort of children with atopic dermatitis and found that food sensitization was associated with lower mutation frequencies in the IgE compartment.

Differential and shared effects of eicosapentaenoic acid and docosahexaenoic acid on serum metabolome in subjects with chronic inflammation.

The omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) affect cell function and metabolism, but the differential effects of EPA and DHA are not known. In a randomized, controlled, double-blind, crossover study, we assessed the effects of 10-week supplementation with EPA-only and DHA-only (3 g/d), relative to a 4-week lead-in phase of high oleic acid sunflower oil (3 g/day, defined as baseline), on fasting serum metabolites in 21 subjects (9 men and 12 post-menopausal women) with chronic inflammation and some characteristics of metabolic syndrome. Relative to baseline, EPA significantly lowered the tricarboxylic acid (TCA) cycle intermediates fumarate and α-ketoglutarate and increased glucuronate, UDP-glucuronate, and non-esterified DHA.

Low ambient temperatures correlate with increased risk of hypoglycemia in patients with type 2 diabetes: An ecological study in Taiwan.

Little evidence is available about the relationship between ambient temperatures and hypoglycemia in Taiwan. The purpose of the present paper is to investigate whether there is an association between ambient temperatures and hypoglycemia in patients with type 2 diabetes.An ecological study was conducted to analyze the type 2 diabetes dataset of the Taiwan National Health Insurance Program.

Cell-free methylation markers with diagnostic and prognostic potential in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly malignant tumor with poor prognosis and high mortality. There is a dearth of effective early diagnostic tools, so liver resection surgery and liver transplantation are the only effective medical treatments. The most commonly used marker for HCC detection is serum alpha fetoprotein (AFP), which has low sensitivity and specificity.

Clinical and Epidemiologic Features of Severe Viral Gastroenteritis in Children: A 3-Year Surveillance, Multicentered Study in Taiwan With Partial Rotavirus Immunization.

The global epidemiological landscape of childhood acute gastroenteritis (AGE) is changing after the introduction of 2 effective rotavirus vaccines in 2006. A comprehensive evaluation for viral etiology of childhood AGE in Taiwan, where rotavirus vaccination was provided by the private sector since 2006, is lacking.From 2009 to 2011, children younger than 5 years of age with AGE who were hospitalized at 3 sentinel hospitals were enrolled in this surveillance study.

Effectiveness of 2 rotavirus vaccines against rotavirus disease in Taiwanese infants.

Background: Two rotavirus (RV) vaccines (Rotarix and RotaTeq) are available on the private market in Taiwan, but are not recommended for routine use. We examined RV vaccine effectiveness (VE) against severe RV acute gastroenteritis (AGE) among Taiwanese infants to inform policymakers on the potential benefits of national RV vaccine introduction.

Methods: From May 2009 to April 2011, a case-control assessment of VE against severe RV AGE was conducted at 3 hospital-based surveillance sites in Taiwan.

Cost-effectiveness of rotavirus vaccination programs in Taiwan.

Background: In Taiwan, two rotavirus vaccines are available on the private market, but are not included in the National Immunization Program (NIP). To help assess whether to include rotavirus vaccines in the NIP, we examined the potential impact and cost-effectiveness of vaccination, from the health care system perspective alone.

Methods: We used a Microsoft Excel-based model to assess rotavirus vaccination impact on rotavirus disease burden and the cost-effectiveness of 2-dose and 3-dose vaccination programs among a birth cohort of Taiwanese children followed for 5 years.

Risk factors for salmonella gastroenteritis in children less than five years of age in Taiwan.

Background: Nontyphoid Salmonella spp. have been among the most common pathogens of acute gastroenteritis in children in Taiwan. However, the principal sources of transmission remain poorly defined.

Age- and gender-specific population attributable risks of metabolic disorders on all-cause and cardiovascular mortality in Taiwan.

Background: The extent of attributable risks of metabolic syndrome (MetS) and its components on mortality remains unclear, especially with respect to age and gender. We aimed to assess the age- and gender-specific population attributable risks (PARs) for cardiovascular disease (CVD)-related mortality and all-cause mortality for public health planning.

Methods: A total of 2,092 men and 2,197 women 30 years of age and older, who were included in the 2002 Taiwan Survey of Hypertension, Hyperglycemia, and Hyperlipidemia (TwSHHH), were linked to national death certificates acquired through December 31, 2009.

Astrovirus gastroenteritis in hospitalized children of less than 5 years of age in Taiwan, 2009.

Background/purpose: Acute gastroenteritis is a common illness in children under 5 years old. Although rotavirus is a leading cause, other viruses including astrovirus are also important, but have been the subject of limited studies. This is a prospective study to investigate astrovirus gastroenteritis in hospitalized children in Taiwan.

A bean-free diet increases the risk of all-cause mortality among Taiwanese women: the role of the metabolic syndrome.

Objective: To evaluate the associations with chronic disease risk and mortality of the consequences of bean-free diets in Taiwanese adults with regard to gender.

Design: A sub-sample of the National Health Interview Survey (NHIS) in 2001 agreed to physical examination in the subsequent year. This group then took part in the Taiwanese Survey of Hyperglycaemia, Hyperlipidaemia and Hypertension (TwSHHH) in 2002.

Dietary intake and the risk of hyperuricemia, gout and chronic kidney disease in elderly Taiwanese men.

Introduction: This study was conducted to examine the relationship between dietary intake and the risk of chronic kidney disease (CKD), treated hyperuricemia (or gout) without CKD, and untreated hyperuricemia without CKD in elderly men.

Methods: The study population comprised 752 men aged 65 or older who had been included in the Elderly Nutrition and Health Survey (1999-2000) (Elderly NAHSIT).

Results: Statistical analysis using a polychotomous logistic regression model revealed that compared with the individuals in the normouricemic group, the individuals in the other groups exhibited a significant association between a higher prevalence of CKD and the following factors: advanced age, drug use for hypertension, egg and shellfish consumption and consumption of poultry with the skin and meat with fat.

Is impaired energy regulation the core of the metabolic syndrome in various ethnic groups of the USA and Taiwan?

Background: The metabolic syndrome (MetS) concept is widely used in public health and clinical settings without an agreed pathophysiology. We have re-examined the MetS in terms of body fuels, so as to provide a coherent cross-cultural pathogenesis.

Methods: National Health and Nutrition Examination Survey (NHANES 2001-2) with n = 2254 and Taiwanese National Health Interview Survey (NHIS) sub-set for hypertension, hyperglycemia and hyperlipidemia assessment (TwSHHH 2002), n = 5786, were used to compare different ethnicities according to NCEP-ATPIII (NCEP-tw) criteria for METS.

In addition to obesity and insulin resistance, microalbuminuria and diminished insulin secretion are linked with the metabolic syndrome in community-dwelling nondiabetic Taiwanese subjects.

Although insulin resistance and obesity are currently considered primary factors underlying development of the metabolic syndrome, microalbuminuria and inadequate insulin secretion may also be involved. The present study is the first to examine intercorrelations among these factors in a community-based Taiwanese population. An epidemiological survey of chronic diseases conducted in 1996 was utilized to evaluate 1340 community-dwelling, nondiabetic adults.