Ovarian HBV replication following ovulation induction in female hepatitis B carriers undergoing IVF treatment: A prospective observational study

Hepatitis B virus (HBV) can be found in ovarian tissues. This study compared HBV DNA levels in follicular fluid collected during oocyte retrieval with paired serum samples in HBV carriers after ovarian stimulation during IVF treatment for infertility. Sixty‐four HBV carrier women referred to the Assisted Reproductive Units of two Hong Kong hospitals were recruited. At oocyte retrieval, the follicular fluid aspirated from the first follicle was collected for study. In 22 women, the first follicular fluid sample from both ovaries was similarly collected and studied. These women were also tested for liver function test and HBeAg. In 28 (43.8%) women, HBV DNA was detected in follicular fluid and the level correlated with serum levels (Spearman's correlation P < .001). There was concordant detection of HBV DNA in both ovaries, and the levels were significantly correlated (Spearman's correlation P = .029). In 40% of women with FF HBV DNA, the follicular fluid:serum ratio was >1.0, suggesting stimulation of HBV replication. These women also had significantly different liver function test results. Increased HBV replication exists in 40% of women with HBV DNA detected in follicular undergoing ovarian stimulation during IVF treatment.     

Dichotomous role of pancreatic HUWE1/MULE/ARF-BP1 in modulating beta cell apoptosis in mice under physiological and genotoxic conditions

Aims/hypothesis

Diabetes mellitus represents a significant burden on the health of the global population. Both type 1 and type 2 diabetes share a common feature of a reduction in functional beta cell mass. A newly discovered ubiquitination molecule HECT, UBA and WWE domain containing 1, E3 ubiquitin protein ligase (HUWE1 [also known as MULE or ARF-BP1]) is a critical regulator of p53-dependent apoptosis. However, its role in islet homeostasis is not entirely clear.

Methods

We generated mice with pancreas-specific deletion of Huwe1 using a Cre-loxP recombination system driven by the Pdx1 promoter (Pdx1cre ⁺ Huwe1 ^fl/fl) to assess the in vivo role of HUWE1 in the pancreas.

Results

Targeted deletion of Huwe1 in the pancreas preferentially activated p53-mediated beta cell apoptosis, leading to reduced beta cell mass and diminished insulin exocytosis. These defects were aggravated by ageing, with progressive further decline in insulin secretion and glucose homeostasis in older mice. Intriguingly, Huwe1 deletion provided protection against genotoxicity, such that Pdx1cre ⁺ Huwe1 ^fl/fl mice were resistant to multiple-low-dose-streptozotocin-induced beta cell apoptosis and diabetes.

Conclusion/interpretation

HUWE1 expression in the pancreas is essential in determining beta cell mass. Furthermore, HUWE1 demonstrated divergent roles in regulating beta cell apoptosis depending on physiological or genotoxic conditions.     

Expression of Toll-Like Receptors 2 and 3 on Esophageal Epithelial Cell Lines and on Eosinophils During Esophagitis

Background  

The chronic disease eosinophilic esophagitis may be mediated by the innate immune system. Activation of toll-like receptors (TLRs) in other tissues is known to initiate eosinophil infiltration, thus TLRs may be a potential mediator of esophageal eosinophilia. Little is known about TLRs in the esophagus.     

IDH2 mutations are frequent in angioimmunoblastic T-cell lymphoma

Mutations in isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) occur in most grade 2 and 3 gliomas, secondary glioblastomas, and a subset of acute myelogenous leukemias but have not been detected in other tumor types. The mutations occur at specific arginine residues and result in the acquisition of a novel enzymatic activity that converts 2-oxoglutarate to D-2-hydroxyglutarate. This study reports IDH1 and IDH2 genotyping results from a set of lymphomas, which included a large set of peripheral T-cell lymphomas. IDH2 mutations were identified in approximately 20% of angioimmunoblastic T-cell lymphomas (AITLs), but not in other peripheral T-cell lymphoma entities. These results were confirmed in an independent set of AITL patients, where the IDH2 mutation rate was approximately 45%. This is the second common genetic lesion identified in AITL after TET2 and extends the number of neoplastic diseases where IDH1 and IDH2 mutations may play a role.     

Effects of aging and propofol on the cardiovascular component of the autonomic nervous system

Study ObjectivesTo determine the combined effects of aging and propofol on autonomic nervous system activity using heart rate variability (HRV) analysis.DesignProspective, two-parallel group, repeated-measures study.SettingOperating room of an academic hospital.PatientsASA physical status 1, 2, and 3 patients, including 14 young (< 65 yrs) and 14 elderly (> 65 yrs) patients. All patients were scheduled for general surgical procedures with general anesthesia.InterventionsEach patient received two successive propofol doses during induction (0.5 mg/kg and 1.5 mg/kg) with a time interval allowing the return of Bispectral Index (BIS) to awake values.MeasurementsPrimary outcomes were HRV parameters, which included normalized power spectral density at low frequency (LFnorm) and high frequency (HFnorm) bands and the ratio LF/HF. Secondary outcomes were BIS values, blood pressure, heart rate, respiratory rate, and body temperature.Main ResultsThe interaction of age and propofol dose level was significant [multivariate analysis of variance, F (3,74) = 4.72, P = 0.005], representing a combined effect of age and propofol dose level on the mean HRV parameters. Propofol induction decreased the HFnorm component and enhanced LFnorm and LF/HF in the younger group, but had no significant effect in the older group. Such an effect was not associated with a significant difference in systolic blood pressure (SBP) decrements between the younger and older groups. Within each group, propofol caused significant decreases in SBP compared with preinduction values. Heart rate did not change significantly during propofol administration between groups or within groups.ConclusionsPropofol and aging act in synergy to depress the activity of the cardiovascular component of the autonomic nervous system. However, a compensatory increase in sympathetic outflow was seen in young patients. Such counterbalance was not observed in the older group.