Outbreak of acute hepatitis C following the use of anti-hepatitis C virus--screened intravenous immunoglobulin therapy

BACKGROUND and AIMS: Hepatitis C virus (HCV) infection has been associated with intravenous (IV) immunoglobulin (Ig), and plasma donations used to prepare IV Ig are now screened to prevent transmission. Thirty-six patients from the United Kingdom received infusions from a batch of anti-HCV antibody-screened intravenous Ig (Gammagard; Baxter Healthcare Ltd., Thetford, Norfolk, England) that was associated with reports of acute hepatitis C outbreak in Europe. The aim of this study was to document the epidemiology of this outbreak. METHODS: Forty-six patients from the United Kingdom treated with Gammagard (34 exposed and 12 unexposed to the batch) returned epidemiological questionnaires. RESULTS: Eighty-two percent of the exposed patients (28 of 34) became positive for HCV RNA. Eighteen percent of the patients (6 of 34) who had infusions with this batch tested negative for HCV RNA, but 2 of the patients had abnormal liver function and subsequently seroconverted to anti-HCV antibody positive. Twenty-seven percent of the patients (9 of 34) developed jaundice, and 79% (27 of 34) had abnormal liver transferase levels. Virus isolates (n=21), including an isolate from the implicated batch, were genotype 1a and virtually identical by sequence analysis of the NS5 region, consistent with transmission from a single source. CONCLUSIONS: Hepatitis C infection can be transmitted by anti-HCV-screened IV Ig. Careful documentation of IV Ig batch numbers and regular biochemical monitoring is recommended for all IV Ig recipients

Mapping of serotype-specific, immunodominant epitopes in the NS-4 region of hepatitis C virus (HCV):use of type-specific peptides to serologically differentiate infections with HCV types 1, 2, and 3

The effect of sequence variability between different types of hepatitis C virus (HCV) on the antigenicity of the NS-4 protein was investigated by epitope mapping and by enzyme-linked immunosorbent assay with branched oligopeptides. Epitope mapping of the region between amino acid residues 1679 and 1768 in the HCV polyprotein revealed two major antigenic regions (1961 to 1708 and 1710 to 1728) that were recognized by antibody elicited upon natural infection of HCV. The antigenic regions were highly variable between variants of HCV, with only 50 to 60% amino acid sequence similarity between types 1, 2, and 3. Although limited serological cross-reactivity between HCV types was detected between peptides, particularly in the first antigenic region of NS-4, type-specific reactivity formed the principal component of the natural humoral immune response to NS-4. Type-specific antibody to particular HCV types was detected in 89% of the samples from anti-HCV-positive blood donors and correlated almost exactly with genotypic analysis of HCV sequences amplified from the samples by polymerase chain reaction. Whereas almost all blood donors appeared to be infected with a single virus type (97%), a higher proportion of samples (40%) from hemophiliacs infected from transfusion of non-heat-inactivated clotting factor contained antibody to two or even all three HCV types, providing evidence that long-term exposure may lead to multiple infection with different variants of HCV

Absence of platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) in vivo increases resistance to Salmonella enterica serovar Typhimurium in mice.

PECAM-1/CD31 is known to regulate inflammatory responses and exhibit pro- and anti-inflammatory functions. This study was designed to determine the functional role of PECAM-1 in susceptibility to murine primary in vivo infection with Salmonella enterica serovar Typhimurium and in in vitro inflammatory responses of peritoneal macrophages. Lectin profiling showed that cellular PECAM-1 and recombinant human PECAM-1-Ig chimera contain high levels of mannose sugars and N-acetylglucosamine. Consistent with this carbohydrate pattern, both recombinant human and murine PECAM-1-Ig chimeras were shown to bind S. Typhimurium in a dose-dependent manner in vitro. Using oral and fecal-oral transmission models of S. Typhimurium SL1344 infection, PECAM-1-/- mice were found to be more resistant to S. Typhimurium infection than wild-type (WT) C57BL/6 mice. While fecal shedding of S. Typhimurium was comparable in wild-type and PECAM-1-/- mice, the PECAM-1-deficient mice had lower bacterial loads in systemic organs such as liver, spleen, and mesenteric lymph nodes than WT mice, suggesting that extraintestinal dissemination was reduced in the absence of PECAM-1. This reduced bacterial load correlated with reduced tumor necrosis factor (TNF), interleukin-6 (IL-6), and monocyte chemoattractant protein (MCP) levels in sera of PECAM-1-/- mice. Following in vitro stimulation of macrophages with either whole S. Typhimurium, lipopolysaccharide (LPS) (Toll-like receptor 4 [TLR4] ligand), or poly(I·C) (TLR3 ligand), production of TNF and IL-6 by PECAM-1-/- macrophages was reduced. Together, these results suggest that PECAM-1 may have multiple functions in resistance to infection with S. Typhimurium, including binding to host cells, extraintestinal spread to deeper tissues, and regulation of inflammatory cytokine production by infected macrophages

A New View on Worst-Case to Average-Case Reductions for NP Problems

We study the result by Bogdanov and Trevisan (FOCS, 2003), who show that under reasonable assumptions, there is no non-adaptive worst-case to average-case reduction that bases the average-case hardness of an NP-problem on the worst-case complexity of an NP-complete problem. We replace the hiding and the heavy samples protocol in [BT03] by employing the histogram verification protocol of Haitner, Mahmoody and Xiao (CCC, 2010), which proves to be very useful in this context. Once the histogram is verified, our hiding protocol is directly public-coin, whereas the intuition behind the original protocol inherently relies on private coins

Targeting the PI3K/Akt signaling pathway in gastric carcinoma: A reality for personalized medicine?

Frequent activation of phosphatidylinositol-3 kinases (PI3K)/Akt/mTOR signaling pathway in gastric cancer (GC) is gaining immense popularity with identification of mutations and/or amplifications of PIK3CA gene or loss of function of PTEN, a tumor suppressor protein, to name a few; both playing a crucial role in regulating this pathway. These aberrations result in dysregulation of this pathway eventually leading to gastric oncogenesis, hence, there is a need for targeted therapy for more effective anticancer treatment. Several inhibitors are currently in either preclinical or clinical stages for treatment of solid tumors like GC. With so many inhibitors under development, further studies on predictive biomarkers are needed to measure the specificity of any therapeutic intervention. Herein, we review the common dysregulation of PI3K/Akt/mTOR pathway in GC and the various types of single or dual pathway inhibitors under development that might have a superior role in GC treatment. We also summarize the recent developments in identification of predictive biomarkers and propose use of predictive biomarkers to facilitate more personalized cancer therapy with effective PI3K/Akt/mTOR pathway inhibition

Positive exercise test?

markdownabstractA 46-year-old male was referred for exercise testing after he was evaluated in the emergency department because of progressive fatigue, dyspnoea on exertion and chest pain with tingling of the left arm. He was an otherwise healthy man who was a professional climber. He had no cardiovascular risk factors and was not using any medication. On physical examination he was normotensive and the cardiovascular examination was normal. His troponin level was normal. A bicycle exercise test was performed to rule out ischaemia. He exercised for 13 min and 40 sec, reaching 242 Watt (reference value 208 Watt) with a maximum heart rate of 167 beats/min (96% of predicted maximal heart rate) and a blood pressure of 187/92 mmHg. The test was stopped because of fatigue. He had no chest pain. Two recordings of the exercise test are shown here (Fig. 1a, b). __Questions__ Is this a positive test for ischaemia? What is the prognosis

Potential role of IL-37 in atherosclerosis

© 2017 Elsevier Ltd. IL-37 is a member of the IL-1 family, but unlike most other members of this family of cytokines, it has wide-ranging anti-inflammatory properties. Initially shown to bind IL-18 binding protein and prevent IL-18-mediated inflammation, its known role has been expanded to include distinct pathways, both intracellular involving the transcription factor Smad3, and extracellular via binding to the orphan receptor IL-1R8. A number of recent publications investigating the role of IL-37 in atherosclerosis and ischemic heart disease have revealed promising therapeutic value of the cytokine. Although research concerning the role of IL-37 and its mechanism in atherosclerosis is relatively scant, there are a number of well-known atherosclerotic processes that this cytokine can mediate with the potential of modulating the disease progression itself. This review will probe in detail the effects of IL-37 on important pathological processes such as inflammation, dysregulated lipid metabolism, and apoptosis, by analyzing existing data as well as exploring the potential of this cytokine to influence these properties

Estimating logged-over lowland rainforest aboveground biomass in Sabah, Malaysia using airborne LiDAR data

Unprecedented deforestation and forest degradation in recent decades have severely depleted the carbon storage in Borneo. Estimating aboveground biomass (AGB) with high accuracy is crucial to quantifying carbon stocks for Reducing Emissions from Deforestation and Forest Degradation-plus implementation (REDD+). Airborne Light Detection and Ranging (LiDAR) is a promising remote sensing technology that provides fine-scale forest structure variability data. This paper highlights the use of airborne LiDAR data for estimating the AGB of a logged-over tropical forest in Sabah, Malaysia. The LiDAR data was acquired using an Optech Orion C200 sensor onboard a fixed wing aircraft. The canopy height of each LiDAR point was calculated from the height difference between the first returns and the Digital Terrain Model (DTM) constructed from the ground points. Among the obtained LiDAR height metrics, the mean canopy height produced the strongest relationship with the observed AGB. This single-variable model had a root mean squared error (RMSE) of 80.02 t ha-1 or 22.31% of the mean AGB, which performed exceptionally when compared with recent tropical rainforest studies. Overall, airborne LiDAR did provide fine-scale canopy height measurements for accurately and reliably estimating the AGB in a logged-over forest in Sabah, thus supporting the state's effort in realizing the REDD+ mechanism

INSTITUTIONS AND THE INTERNATIONAL DIFFUSION OF INFORMATION TECHNOLOG

The production and use of information technology (IT) in developed countries is wcll established and growing at a rapid pace. Newly industrializing countries are adopting both IT production and use as national goals. Developing countries are beginning to formulate plans to do the same. The institutional role in the international diffusion of IT is not well understood, but it is clear from the literature on innovation that the institutional role is critical. The paper makes four points. First, a traditional and fairly rigorous way of thinking about innovations - the economic perspective deriving from Schumpeter and Hicks - has been shown by studies from economic history and sociology/communications of innovation to be inadequate for explaining the dynamics of innovative change. The missing element is understanding of differential roles played by institutions. Second, among those promoting the need for institutional intervention there has been a debate about whether innovation is primarily supply-pushed or demand-pulled. The answer to the question has important institutional implications. The evidence, again mostly from economic history, shows it to be both, in iterative fashion. Thus institutions can intervene meaningfully on both sides. Third, there are two major forms of institutional intervention: influence and regulation. The possible intervention actions of institutions can be encompassed by a 2 x 2 matrix with supply-push and demand-pull on one dimension and influence and regulation on the other. Finally, if government wants to intervene, there are six classes of roles that might be pursued to affect innovation