Abnormal primary and permanent dentitions with ectodermal symptoms predict WNT10A deficiency.

BACKGROUND: The WNT10A protein is critical for the development of ectodermal appendages. Variants in the WNT10A gene may be associated with a spectrum of ectodermal abnormalities including extensive tooth agenesis. METHODS: In seven patients with severe tooth agenesis we identified anomalies in primary dentition and additional ectodermal symptoms, and assessed WNT10A mutations by genetic analysis. RESULTS: Investigation of primary dentition revealed peg-shaped crowns of primary mandibular incisors and three individuals had agenesis of at least two primary teeth. The permanent dentition was severely affected in all individuals with a mean of 21 missing teeth. Primary teeth were most often present in positions were succedaneous teeth were missing. Furthermore, most existing molars had taurodontism. Light, brittle or coarse hair was reported in all seven individuals, hyperhidrosis of palms and soles in six individuals and nail anomalies in two individuals. The anomalies in primary dentition preceded most of the additional ectodermal symptoms. Genetic analysis revealed that all seven individuals were homozygous or compound heterozygous for WNT10A mutations resulting in C107X, E222X and F228I. CONCLUSIONS: We conclude that tooth agenesis and/or peg-shaped crowns of primary mandibular incisors, severe oligodontia of permanent dentition as well as ectodermal symptoms of varying severity may be predictors of bi-allelic WNT10A mutations of importance for diagnosis, counselling and follow-up.

[Preventive effects of modified chitosan medical anti-adhesion membrane on postoperative intra-abdominal adhesion].

OBJECTIVE: To explore the preventive effects of modified chitosan medical anti-adhesion membrane on postoperative intra-abdominal adhesion. METHODS: A total of 86 patients with obstructive colorectal carcinoma undergoing emergent colostomy and second-stage anastomosis were randomly divided into 2 groups (n = 43 each). In the research group modified chitosan medical anti-adhesion membrane were put both at the area of operation and under the incision before abdomen closing, but not so in the control group. The recovery procedures were recorded including gut movement, degree and duration of abdominal pain and cases of adhesive ileus. During the reopening of abdominal cavities 3 to 6 months later, intestinal anastomosis was performed. And adhesive severity was graded blindly and the level of hydroxyproline measured within injured posterior peritoneum and adhesive tissue. RESULTS: As compared with the control, postoperative abdominal pain was weaker; the recovery of gut motor function and eating better ((3.3 ± 1.0) vs (4.2 ± 1.1) days, P < 0.05), the incidence of adhesive ileus lower (1(2.3%) vs 4(9.3%), P < 0.05), adhesion significantly lighter and the hydroxyproline level lower ((0.832 ± 0.071) vs (1.375 ± 0.108) µg/mg protein, P < 0.05) in the research group. CONCLUSION: Modified chitosan medical anti-adhesion membrane has preventive effects on postoperative intra-abdominal adhesion so as to decrease the incidence of adhesive ileus.

IFN-ß1b induces OAS3 to inhibit EV71 via IFN-ß1b/JAK/STAT1 pathway.

Enterovirus 71 (EV71) caused hand, foot and mouth disease (HFMD) is a serious threat to the health of young children. Although type I interferon (IFN-I) has been proven to control EV71 replication, the key downstream IFN-stimulated gene (ISG) remains to be clarified and investigated. Recently, we found that 2'-5'-oligoadenylate synthetases 3 (OAS3), as one of ISG of IFN-ß1b, was antagonized by EV71 3C protein. Here, we confirm that OAS3 is the major determinant of IFN-ß1b-mediated EV71 inhibition, which depends on the downstream constitutive RNase L activation. 2'-5'-oligoadenylate (2-5A) synthesis activity deficient mutations of OAS3 D816A, D818A, D888A, and K950A lost resistance to EV71 because they could not activate downstream RNase L. Further investigation proved that EV71 infection induced OAS3 but not RNase L expression by IFN pathway. Mechanically, EV71 or IFN-ß1b-induced phosphorylation of STAT1, but not STAT3, initiated the transcription of OAS3 by directly binding to the OAS3 promoter. Our works elucidate the immune regulatory mechanism of the host OAS3/RNase L system against EV71 replication.

Association of host pharmacodynamic effects with virologic response to pegylated interferon alfa-2a/ribavirin in chronic hepatitis C.

UNLABELLED: Patients receiving therapy for chronic hepatitis C virus (HCV) infection frequently experience cytopenias and weight loss. We retrospectively assessed the pharmacodynamic effects of pegylated interferon (PEG-IFN) alfa-2a and ribavirin by evaluating the relationship between changes in hematologic parameters, body weight, and virologic response. Patients with HCV genotypes 1, 4, 5, or 6 receiving 24 or 48 weeks of PEG-IFN alfa-2a and ribavirin therapy were pooled from four phase 3/4 trials. Maximum decreases in hemoglobin level, neutrophil count, platelet count, and weight during therapy were assessed according to virologic response category (sustained virologic response [SVR], relapse, breakthrough, and nonresponder) and race/ethnicity. Of 1,778 patients analyzed, more than half were male, non-Hispanic Caucasian, and infected with HCV genotype 1; had a baseline HCV RNA >800,000; and had alanine aminotransferase levels ≤3 × the upper limit of normal. Virologic responders (SVR, relapse, and breakthrough) experienced greater maximum decreases from baseline in hemoglobin level, neutrophil count, platelet count, and weight compared with nonresponders; however, no clear trend was observed between SVR, relapse, and breakthrough. After adjusting for drug exposure and treatment duration, only decreases in neutrophil count remained associated with virologic response. Significantly greater declines in neutrophil (P < 0.0001) and platelet (P < 0.005) count were observed at weeks 4, 12, and 24 of therapy in virologic responders compared with nonresponders. This difference between responders and nonresponders was also observed among racial/ethnic groups, although statistical significance was not consistent across all groups. CONCLUSION: This post hoc analysis of HCV patients treated with PEG-IFN alfa-2a and ribavirin shows that maximum decreases from baseline in hematologic parameters and weight loss were associated with virologic response. However, after adjusting for drug exposure and accounting for duration of therapy, only neutropenia was independently associated with virologic response.

Histologic outcomes in hepatitis C-infected patients with varying degrees of virologic response to interferon-based treatments.

UNLABELLED: Patients with chronic hepatitis C with partial virologic response or nonresponse to interferon-based therapies can experience treatment-related improvements in liver histology. This retrospective analysis assessed the histologic response to treatment in patients with varying degrees of virologic response (sustained virologic response [SVR], breakthrough, relapse, or nonresponse), time to hepatitis C virus (HCV) RNA undetectability, and duration of viral suppression. Patients (HCV genotypes 1-6) with baseline and follow-up liver biopsies from eight phase 2 to phase 4 interferon-based trials were analyzed. Blinded biopsies were evaluated by a single pathologist. Improvements or worsening of METAVIR necroinflammatory activity and fibrosis were defined as increase or decrease of ≥1 grading category from baseline to 24 weeks after end of treatment. A majority of the 1571 patients with paired biopsy data were white, male, with HCV genotype 1/4, baseline HCV RNA levels >800,000 IU/mL, and baseline alanine aminotransferase levels ≤3 × upper limit of the normal range; mean baseline activity and fibrosis scores were 1.8 and 1.7, respectively. Overall, 80% of patients received peginterferon alfa-2a monotherapy or peginterferon alfa-2a/ribavirin combination therapy. Mean treatment duration was 46 weeks. There was a positive correlation between the degree of virologic response and improvements in METAVIR activity and fibrosis, and an inverse correlation with worsening activity and fibrosis (all comparisons, P < 0.0001). Patients with SVR had the greatest histologic benefit. As a combined group, relapsers and patients with breakthrough had significantly greater benefits than nonresponders (activity, P = 0.0001; fibrosis, P = 0.003). Consistent with these results, a better histologic response was correlated with a shorter time to undetectable HCV RNA and a longer duration of viral suppression (all comparisons, P < 0.0001). CONCLUSION: In patients with chronic hepatitis C who were treated with interferon-based therapies, histologic benefits may be observed even in the absence of an SVR.

Risk factors associated with prolonged recovery and delayed healing after third molar surgery.

PURPOSE: We sought to identify the demographic, oral health, and surgical risk factors associated with prolonged recovery after third molar surgery using health-related quality of life (HRQOL) and clinical outcomes. PATIENTS AND METHODS: HRQOL responses from patients and clinical outcomes were obtained after third molar surgery. Criteria were selected for HRQOL outcomes that separated patients with from those without prolonged recovery. Delayed clinical healing was indicated by a patient having at least 1 postsurgery visit with treatment. Risk assessment models for prolonged HRQOL recovery and delayed clinical healing were developed using stepwise logistic regression analysis. RESULTS: We included 547 subjects with HRQOL and clinical outcome data in this analysis. Age, gender, and occlusal plane position were statistically significantly associated with prolonged recovery for early symptoms, oral function, and pain. Recovery for lifestyle was prolonged only if both lower third molars were below the occlusal plane before surgery. Age, gender, prior symptoms related to the third molars, and the surgeon's perception of difficulty were statistically significant predictors of delayed clinical recovery. CONCLUSIONS: Certain demographic and oral health conditions available to the surgeon before surgery, and characteristics of the surgery itself, increase the risk of a prolonged recovery for HRQOL outcomes and delayed clinical outcomes after third molar surgery.