Progressive accumulation of hyperinflammatory NKG2Dlow 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. This was most notable in children co-sensitized to food and aeroallergens, a risk factor for development of asthma. Individual-level longitudinal analysis in a subset of children revealed coincident reduction of NKG2D on NK cells with acquired or persistent sensitization, and this was associated with impaired skin barrier function assessed by transepidermal water loss. Low expression of NKG2D on NK cells was paradoxically associated with depressed cytolytic function but exaggerated release of the proinflammatory cytokine tumor necrosis factor-α. These observations provide important insights into a potential mechanism underlying the development of allergic comorbidity in early life in children with AD, which involves altered NK cell functional responses, and define an endotype of severe AD.

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. Because aberrant DNA methylation of genes and miRNAs occurs early in most cancers, we explored whether circulating methylation markers could be promising clinical tools for HCC diagnosis. Using a whole-genome approach, we identified many hyper-methylated miRNAs in HCC. Furthermore, three abnormally methylated genes and one miRNA were combined to establish a methylation predictive model and tested for its diagnostic and prognostic potential in HCC. Using plasma samples, the predictive model exhibited high sensitivity and specificity (> 80%) for HBV-related HCC. Most importantly, nearly 75% of patients who could not be diagnosed with AFP at 20 ng/mL were detected by this model. Further, the predictive model exhibited an exceedingly high ability to predict 5-year overall survival in HCC patients. These data demonstrate the high diagnostic and prognostic potential of methylation markers in the plasma of HCC patients.

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. Stool specimens were tested for rotavirus, norovirus, enteric adenovirus, and astrovirus. The epidemiologic and clinical information was collected by questionnaire-based interviews and chart reviews.Viral agents were detected in 1055 (37.5%) of 2810 subjects, with rotavirus (21.2%) being the leading cause of disease, followed by norovirus (14.9%), enteric adenovirus (3.74%), astrovirus (2.10%), and a mixture of at least 2 of 4 above-mentioned viruses (4.06%). The majority (56%) of the viral AGE occurred in children <2 years of age. Rotavirus and norovirus were detected more frequently in cool seasons (P < 0.0001 for both), whereas no seasonal variation was observed for adenovirus and astrovirus. Adult households with diarrhea and a Vesikari score >10 were independent factors respectively associated with an increased risk of norovirus (adjusted odds ratio [aOR] 9.034, P = 0.0003) and rotavirus (aOR, 3.284, P < 0.0001) infections. Rotavirus immunization and female gender were protective factors against rotavirus (aOR, 0.198, P < 0.0001) and astrovirus (aOR, 0.382, P = 0.0299) infections, respectively.Rotavirus and norovirus are the 2 most important viral agents of childhood AGE in Taiwan with partial rotavirus immunization. In addition, different enteric viruses are associated with distinct epidemiologic and clinical features.

Epidemiology and clinical peculiarities of norovirus and rotavirus infection in hospitalized young children with acute diarrhea in Taiwan, 2009.

BACKGROUND/PURPOSE: Acute diarrhea is one of the most common morbidities in pediatrics worldwide. We conducted a study to investigate the incidence of norovirus in young children hospitalized with acute diarrhea in Taiwan and its clinical peculiarity compared with rotavirus gastroenteritis. METHODS: Between January and December, 2009, patients younger than 5 years and admitted to hospital with acute diarrhea were randomly selected; and their stool samples were collected and tested for presence of rotavirus and norovirus by enzyme immunoassay and reverse transcription-polymerase chain reaction, respectively. The clinical manifestations and laboratory findings of the enrolled patients were analyzed. RESULTS: A total of 989 cases were enrolled with a mean age of 21.6 ± 13.7 months and a male proportion of 56.0%. Rotavirus and norovirus was detected in 20.2% and 14.6% of all patients, respectively. Genogroup II was the predominant strain of norovirus (80.6%). Children aged 6-36 months accounted for the majority of patients positive for rotavirus and norovirus (73.0% and 81.3%, respectively). The incidences of norovirus and rotavirus infection were higher during winter and early spring. Most patients with rotavirus and norovirus diarrhea experienced vomiting (74.9%vs. 74.8%, respectively) and fever (94.7%vs. 71.3%, respectively). CONCLUSION: Most young diarrheal patients presenting with vomiting were likely to have norovirus or rotavirus infection. Patients with norovirus diarrhea experienced an absence of, or low-grade fever and longer duration of vomiting compared with those positive for rotavirus infection. A family history of current gastroenteritis may suggest the possibility of norovirus infection.