A comparison of the efficiency of ELISA and selected primer sets to detect Norovirus isolates in southern Ireland over a four-year period (2002-2006): variation in detection rates and evidence for continuing predominance of NoV GII.4 genotype

Norovirus (NoV) gastroenteritis occurs in all age groups and is the most common cause of gastroenteritis in the community. However, detection methods and rates vary widely, and few data are available to compare these, particularly in Ireland. Detection of noroviruses through antigen and molecular-based strategies was carried out on 135 suspected NoV-positive samples, collected over the course of three NoV outbreaks, from 2002 to 2006, in the southern region of Ireland. A commercially available ELISA and a panel of six primer sets were evaluated to determine their suitability for NoV detection in Irish clinical samples. The key findings of this study were the detection of both GGI and GGII noroviruses by ELISA, but the detection of only GGII noroviruses by RT-PCR. In addition to this, a variation in the levels of detection from 9.4 % to 17.3 % was observed for conventional PCR assays, while a detection rate of 46.3 % was observed for the real-time PCR assay. A proportion (17.8 %) of samples were found to be negative by all detection strategies, suggesting the possibility of reporting false positives for these samples or low-copy positives that do not often repeat. Sequencing information from selected samples also revealed nucleotide polymorphisms, compromising efficient primer binding in the case of one primer pairing. Phylogenetic analysis of the partial polymerase gene identified NoV GII.4 as the dominant genotype, in accordance with previous NoV studies in Ireland. Investigating the NoV diversity of the circulating strains and the dynamics of strain replacement is important to better assess the efficacy of future NoV vaccines and to facilitate the early detection of changes in circulating NoV strains.     

Effects of intravenous N-acetylprocainamide on hemodynamics and left ventricular function in man

N-acetylprocainamide (NAPA) is the active metabolite of procainamide currently undergoing evaluation for its antiarrhythmic properties. Its effects on hemodynamic variables and on ventricular function in man are poorly defined. The effects of intravenously administered NAPA (18 mg/kg over 30 minutes; mean plasma level 40.2 +/- 6.2 micrograms/ml) on hemodynamics and left ventricular ejection fraction (LVEF) assessed by radionuclide ventriculography were therefore determined in 14 patients undergoing diagnostic cardiac catheterization. The peak effects of the drug with respect to most measured variables were seen at 30 minutes and were still apparent at 60 minutes. NAPA increased heart rate (3% at 10 minutes; p less than 0.01), decreased mean pulmonary arterial pressure (14%; p less than 0.05) and capillary wedge pressure (27%; p less than 0.01), decreased mean arterial pressure (12%; p less than 0.01), cardiac index (8%; p less than 0.01), LV dp/dtmax (9%; p less than 0.05), and stroke work index (17%; p less than 0.01). The LVEF increased 5% (p less than 0.05). There was a trend for the systemic vascular resistance to decrease, but this did not reach statistical significance. The data show that NAPA exerts relatively weak peripheral arteriolar and venodilator effects associated with a mild reduction in contractility and cardiac output but an increase in LVEF in patients with preserved ventricular function.     

Maternal ethanol exposure is associated with decreased plasma zinc and increased fetal abnormalities in normal but not metallothionein-null mice

BACKGROUND: Ethanol profoundly affects fetal development, and this is proposed to be due primarily to a transient fetal zinc (Zn) deficiency that arises from the binding of Zn by metallothionein (MT) in the maternal liver. Zn homeostasis and fetal outcome were investigated in normal (MT+/+) and metallothionein-null (MT-/-) mice in response to ethanol exposure. METHODS/RESULTS: Mice were treated with saline or ethanol (0.015 m/g intraperitoneally at 0 and 4 hr) on day 8 of gestation (Gd8), and the degree of fetal dysmorphology was assessed on Gd18. The incidence of external abnormalities was significantly increased in offspring from MT+/+ dams exposed to ethanol, where 27.4% of fetuses were affected. MT-/- ethanol-, MT+/+ saline-, and MT-/- saline-treated dams had fetuses in which the frequencies of abnormalities were 2.2, 6.4, and 6.9%, respectively. To investigate Zn homeostasis, nonpregnant mice were killed at intervals over 16 hr after ethanol injection. Liver MT concentrations in MT+/+ mice were increased 20-fold by 16 hr, with a significant elevation evident by 4 hr, whereas liver Zn levels were also significantly increased by 2 hr and maintained for 16 hr. In parallel with these changes, plasma Zn concentrations in MT+/+ mice decreased by 65%, with minimum levels of 4.5+/-0.3 micromol/liter at 8 hr. Conversely, MT-/- mice exhibited increased plasma Zn concentrations, with peak values of 20.8+/-0.3 observed at 4 hr. CONCLUSION: These findings link the teratogenic effect of ethanol to the induction of maternal MT and the limitation of fetal Zn supply from the plasma.     

Radioproteomics in patients with ovarian cancer

Radioproteomics is the integration of proteomics, the systematic study of the protein expression of an organism, with radiomics, the extraction and analysis of large numbers of quantitative features from medical images. This article examines this developing field, and it’s application in high grade serous ovarian carcinoma. Seminal proteomic studies in the area of ovarian cancer, such as the PROVAR and CPTA studies are discussed, along side recent research, such as that highlighting the central role of methyltransferase nicotinamide N-methyltransferase as the metabolic regulation of cancer progression in the tumour stroma. Finally, this article considers a novel, hypothesis generating approach to integrate CT-based qualitative and radiomic features with proteomic analysis, and the future direction of the field. Combined advances in radiomic, proteomic and genomic analysis has the potential to signal the age of true precision medicine, where treatment is centered specifically on the molecular profile of the tumour, rather than based on empirical knowledge, thus altering the course of a disease that has the highest mortality of all cancers of the female reproductive system.     

The Noncolonic Microbiome: Does it Really Matter?

About 100 trillion microorganisms compose the microbiome of the gastrointestinal tract and are predominantly found within the colon. Until recently, few bacteria were thought to inhabit the normal healthy esophagus and stomach. However, contemporary studies using molecular techniques have contradicted these assumptions. In this review, we summarize the pertinent findings of these studies that demonstrate established, complex mixed-microbial communities within the foregut in both health and disease. These studies contribute to improved understanding of interactions between the host immunity and the microbiome that may ultimately allow for novel therapeutic targets.