Repeated exposure to heterologous hepatitis C viruses associates with enhanced neutralizing antibody breadth and potency

A prophylactic hepatitis C virus (HCV) vaccine that elicits neutralizing antibodies could be key to HCV eradication. However, the genetic and antigenic properties of HCV envelope (E1E2) proteins capable of inducing anti-HCV broadly neutralizing antibodies (bNAbs) in humans have not been defined. Here, we investigated the development of bNAbs in longitudinal plasma of HCV-infected persons with persistent infection or spontaneous clearance of multiple reinfections. By measuring plasma antibody neutralization of a heterologous virus panel, we found that the breadth and potency of the antibody response increased upon exposure to multiple genetically distinct infections and with longer duration of viremia. Greater genetic divergence between infecting strains was not associated with enhanced neutralizing breadth. Rather, repeated exposure to antigenically related, antibody-sensitive E1E2s was associated with potent bNAb induction. These data reveal that a prime-boost vaccine strategy with genetically distinct, antibody-sensitive viruses is a promising approach to inducing potent bNAbs in humans.     

Quantification in Patient Urine Samples of Felbamate and Three Metabolites: Acid Carbamate and Two Mercapturic Acids

PURPOSE: Previously we proposed and provided evidence for the metabolic pathway of felbamate (FBM), which leads to the reactive metabolite, 3-carbamoyl-2-phenylpropion-aldehyde. This aldehyde carbamate was suggested to be the reactive intermediate in the oxidation of 2-phenyl-1,3-propanediol monocarbamate to the major human metabolite 3-carbamoyl-2-phenylpropionic acid. In addition, the aldehyde carbamate was found to undergo spontaneous elimination to 2-phenylpropenal, commonly known as atropaldehyde. Moreover, atropaldehyde was proposed to play a role in the development of toxicity during FBM therapy. Evidence for atropaldehyde formation in vivo was reported with the identification of modified N-acetyl-cysteine conjugates of atropaldehyde in both human and rat urine after FBM administration. Identification of the atropaldehyde-derived mercapturic acids in urine after FBM administration is consistent with the hypothesis that atropaldehyde is formed in vivo and that it reacts with thiol nucleophiles. Based on the hypothesis that the potential for toxicity will correlate to the amount of atropaldehyde formed, we sought to develop an analytic method that would quantify the amount of relevant metabolites excreted in patient urine. METHODS: We summarize the results of an LC/MS method used to quantify FBM, 3-carbamoyl-2-phenylpropionic acid and two atropaldehyde-derived mercapturic acids in the patient population. RESULTS: Analysis was performed on 31 patients undergoing FBM therapy. The absolute quantities of FBM and three metabolites were measured. CONCLUSIONS: This method demonstrated sufficient precision for the identification of patients exhibiting "abnormal" levels of atropaldehyde conjugates and may hold potential for patient monitoring.     

Surgical treatment of renovascular hypertension and respective late results. A twenty years experience.

This paper presents the long term results following operative reconstruction for renovascular hypertension in 115 patients operated upon over a period of 20 years. There were 71 (61.7%) males and 44 (38.3%) females with a median age of 46 years (range 16-67). Renal revascularization was unilateral in 96 (83.4%) cases and bilateral in 19 (16.6%). Dacron knitted bypass grafts, were used in 51 and PTFE in 33 instances. Saphenous vein grafts were used in 11 patients. In 15 cases treatment was by local endarterectomy with concomitant angioplasty (12 unilateral and 3 bilateral). Simultaneous aortorenal reconstruction was undertaken in 38 (33%) patients. There were no deaths in the group with isolated renal artery reconstruction. In the group of aortorenal reconstructions, two deaths were encountered (5.7%). Postoperatively, blood pressure was either normal or improved in 83 (72%) patients at a mean follow-up period of 48.3 months (range 1-195 months). The best results were obtained in younger individuals with segmental renal artery lesions. Linear progression analysis, showed age to be a major determinant in the postoperative response to hypertension. There was a greater degree of long term success in patients with fibromuscular dysplasia, as compared to individuals with atherosclerosis. Crude survival probabilities, were 78% and 61% at 5 and 10 years respectively. Late deaths encountered in the present series, were mostly attributable to myocardial infarction (7.8%). In this series, the best results were obtained in individuals younger than 50 years of age, with segmental renal artery lesions.     

Consumption of Vegetables Is Associated with Systemic Inflammation in Older Adults

It is hypothesized that healthy diets rich in fruits and vegetables (FV) can modulate the inflammatory status in older adults. However, to determine the actual impact of FV on inflammatory status, adiposity level and objectively assessed physical activity (PA) behaviors need to be considered. The aim of the present study was to explore associations between FV intake and biomarkers of systemic inflammation in older adults. Based on a sample of 233 older adults (65–70 years old), the following inflammatory biomarkers were assessed: C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), IL-10, IL-18, and monocyte chemoattractant protein-1 (MCP-1). FV intake was assessed by self-report, and PA behaviors encompassing time spent sedentary and in moderate-to-vigorous PA (MVPA) were determined using accelerometers. Associations between FV intake and inflammatory biomarkers were analyzed using stepwise linear regression models while adjusting for several covariates, including health-related food groups, adherence to the MVPA guidelines, total sedentary time, and waist circumference. While no significant associations were observed for the total FV intake, the vegetable intake was inversely associated with levels of IL6 (β = −0.15; p < 0.05). In contrast, fruit intake was not associated with any inflammatory biomarker. In conclusion, our findings indicate beneficial associations between vegetable intake and levels of a pro-inflammatory biomarker in older adults, which strengthens public health efforts to promote vegetable-rich diets in older adults to mitigate age-related systemic inflammation.     

Evaluation of FISH image analysis system on assessing HER2 amplification in breast carcinoma cases

HER2-positive breast cancer is characterized by aggressive growth and poor prognosis. Women with metastatic breast cancer with over-expression of HER2 protein or excessive presence of HER2 gene copies are potential candidates for Herceptin (Trastuzumab) targeted treatment that binds to HER2 receptors on tumor cells and inhibits tumor cell growth. Fluorescence in situ hybridization (FISH) is one of the most widely used methods to determine HER2 status. Typically, evaluation of FISH images involves manual counting of FISH signals in multiple images, a time consuming and error prone procedure. Recently, we developed novel software for the automated evaluation of FISH images and, in this study, we present the first testing of this software on images from two separate research clinics. To our knowledge, this is the first concurrent evaluation of any FISH image analysis software in two different clinics. The evaluation shows that the developed FISH image analysis software can accelerate evaluation of HER2 status in most breast cancer cases.     

Promoting Breast Cancer Screening Among Asian American Women: the Asian Grocery Store-Based Cancer Education Program

Asian American women's historically low breast cancer mortality rate has remained constant as rates decreased for all other races. From 2000 to 2004, a randomized controlled trial explored the Asian grocery store-based breast cancer education program's impact on Chinese, Filipino, Korean, and Vietnamese women (n?=?1,540). Women aged 40 and older and non-adherent for annual screening mammograms were more likely to schedule a mammogram after receiving the breast cancer education program than women randomized to the prostate cancer program (X ²?=?3.85, p?=?0.05). With the right program ingredients, late adopters of breast cancer screening can be prompted to change.     

Total versus selective hepatic vascular exclusion in major liver resections

BACKGROUND: Total hepatic vascular exclusion (THVE) and selective hepatic vascular exclusion (SHVE) are two effective techniques for bleeding control in major hepatic resections. Outcomes of the two procedures were compared. METHODS: Patients undergoing major liver resection were randomly allocated to the THVE and SHVE groups. Intraoperative hemodynamic changes and the postoperative course of the two groups were compared. RESULTS: During vascular clamping, the THVE group showed a significant elevation in pulmonary vascular resistance, systemic vascular resistance, intrapulmonary shunts, and a significant reduction in cardiac index, compared with the SHVE group (P <0.05). Patients undergoing THVE received more crystalloids and blood, showed more severe liver, renal and pancreatic dysfunction, and had a longer hospital stay than the SHVE group (P <0.05). CONCLUSIONS: Both techniques are equally effective in bleeding control in major liver resections. THVE is associated with cardiorespiratory and hemodynamic alterations and may be not tolerated by some patients. SHVE is well tolerated with fewer postoperative complications and shorter hospitalization time.     

Could a policy of provision of hip protectors to elderly nursing home residents result in cost savings in acute hip fracture care? The case of Ontario, Canada

Summary Hip fractures are an important problem in nursing homes. Hip protectors are external devices that decrease the risk of hip fracture in elderly nursing home residents. We estimated the overall healthcare cost savings from a hypothetical strategy of provision of hip protectors to elderly nursing home residents in Ontario, Canada. In a recent meta-analysis, we determined that a strategy of provision of hip protectors decreases the risk of hip fracture in nursing home residents. Introduction Our objective was to determine whether the provision of hip protectors to all Ontario nursing home residents aged ≥65 years could result in cost savings, stemming from reductions in initial hospitalizations for hip fracture. Methods We conducted a cost analysis from a Ministry of Health perspective (one year cycle length). The efficacy of the intervention was estimated from a meta-analysis of randomized controlled trials. Results A strategy of provision of hip protectors to all 60,775 elderly Ontario nursing home residents could result in an overall mean cost savings of 6.0 million Canadian dollars in one year (95% credibility interval, −26.4 million, 39.7 million), with a probability of cost savings of 0.63 (assuming no additional labor costs). In sensitivity analyses, decreasing hip protector price increased cost savings, whereas additional labor expenditures for application for hip protectors decreased cost savings. Conclusion In conclusion, if hip protectors can be provided to elderly Ontario nursing home residents without additional labor expenditures, there is a reasonable probability that such a strategy may result in healthcare cost savings.