Application of dsRNA in cancer immunotherapy: current status and future trends.

Cancer cells create a microenvironment that prevents tumor rejection by the host's immune system. The activation of pattern recognition receptors (PRRs) can elicit an innate immune response and guide the adaptive immune response to overcome this. dsRNA analogs can trigger TLR3, RIG-I, MDA5, NLRP3 and several other PRRs to induce not only robust immune response against cancer but also programmed cell death.

The six-minute walk test is an excellent predictor of functional ambulation after total knee arthroplasty.

Background: The Six-minute walk (6 MW) and Timed-Up-and-Go (TUG) are short walk tests commonly used to evaluate functional recovery after total knee arthroplasty (TKA). However, little is known about walking capacity of TKA recipients over extended periods typical of everyday living and whether these short walk tests actually predict longer, more functional distances. Further, short walk tests only correlate moderately with patient-reported outcomes.

The effects of TLR activation on T-cell development and differentiation.

Invading pathogens have unique molecular signatures that are recognized by Toll-like receptors (TLRs) resulting in either activation of antigen-presenting cells (APCs) and/or costimulation of T cells inducing both innate and adaptive immunity. TLRs are also involved in T-cell development and can reprogram Treg cells to become helper cells. T cells consist of various subsets, that is, Th1, Th2, Th17, T follicular helper (Tfh), cytotoxic T lymphocytes (CTLs), regulatory T cells (Treg) and these originate from thymic progenitor thymocytes.

Changes in left atrial volume in diabetes mellitus: more than diastolic dysfunction?

Aim: To evaluate left atrial (LA) volume and function as assessed by strain and strain rate derived from 2D speckle tracking and their association with diastolic dysfunction (DD) in patients with diabetes mellitus (DM).

Methods And Results: Seventy three patients with DM were compared with age- and gender-matched normal controls; 30 patients with DM alone were compared to those with hypertension (HT) alone. The maximum LA volume, traditional measures of atrial function, 2D strain and strain rate were analysed.

Improvements in knee range and symptomatic and functional behavior after knee arthroplasty based on preoperative restriction in range.

Recovery of knee range and Oxford Knee Score post knee arthroplasty based on preoperative knee range is described. A total of 191 patients recruited across 5 hospitals were assessed preoperatively, at 8 weeks postoperatively and 1 year. Preoperative knee range was categorized into "low" (≤ 109), "moderate" (> 109 to ≤ 120), and "high" (> 120°) flexion and "normal" (± -5) and "restricted" (> +5°) terminal extension.

Mimotope ELISA for detection of broad spectrum antibody against avian H5N1 influenza virus.

Background: We have raised a panel of broad spectrum neutralizing monoclonal antibodies against the highly pathogenic H5N1 avian influenza virus, which neutralize the infectivity of, and afford protection against infection by, most of the major genetic groups of the virus evolved since 1997. Peptide mimics reactive with one of these broad spectrum H5N1 neutralizing antibodies, 8H5, were identified from random phage display libraries.

Method: The amino acid residues of the most reactive 12mer peptide, p125 (DTPLTTAALRLV), were randomly substituted to improve its mimicry of the natural 8H5 epitope.

Is discharge knee range of motion a useful and relevant clinical indicator after total knee replacement? Part 2.

Objective: Knee range of motion (ROM) at discharge from acute care is used as a clinical indicator following total knee replacement (TKR) surgery. This study aimed to assess the clinical relevance of this indicator by determining whether discharge knee ROM predicts longer-term knee ROM and patient-reported knee pain and function.

Methods: A total of 176 TKR recipients were prospectively followed after discharge from acute care.

Is discharge knee range of motion a useful and relevant clinical indicator after total knee replacement? Part 1.

Objectives: Knee range of motion (ROM) at the point of discharge from acute care is used as a clinical indicator to benchmark performance between hospital services after total knee replacement (TKR). The utility of the current benchmark, including whether discharge ROM varies between hospitals, is unknown. This study aimed to determine whether the benchmark [≥80 degrees flexion and ≤5 degrees fixed flexion (extension)] is realistic and whether the service provider is a predictor of knee ROM.

RNA Interference inhibits hepatitis B virus of different genotypes in vitro and in vivo.

Background: Hepatitis B virus (HBV) infection increases the risk of liver disease and hepatocellular carcinoma. Small interfering RNA (siRNA) can be a potential new tool for HBV therapy. Given the high heterogeneity of HBV strains and the sensitivity towards sequences changes of siRNA, finding a potent siRNA inhibitor against the conservative site on the HBV genome is essential to ensure a therapeutic application.

Immunomodulatory effects of dsRNA and its potential as vaccine adjuvant.

dsRNA can be detected by pattern recognition receptors, for example, TLR3, MDA-5, NLRP3 to induce proinflammatory cytokines responsible for innate/adaptive immunity. Recognized by endosomal TLR3 in myeloid DCs (mDCs), dsRNA can activate mDCs into mature antigen presenting cells (mAPCs) which in turn present antigen epitopes with MHC-I molecules to naïve T cells. Coadministration of protein and synthetic dsRNA analogues can elicit an antigen-specific Th1-polarized immune response which stimulates the CD8+ CTL response and possibly dampen Th17 response.

Low incidence of complications from endoscopic gastric variceal obturation with butyl cyanoacrylate.

Background & Aims: Endoscopic variceal obturation with tissue adhesive is used to control gastric variceal bleeding. We investigated the prevalence of serious complications from this therapy.

Methods: We performed a retrospective analysis of complications that occurred in 753 patients with gastric variceal hemorrhages who were hospitalized in 2 tertiary referral hospitals.

Performance of detecting IgM antibodies against enterovirus 71 for early diagnosis.

Enterovirus 71 (EV71) infection is more likely to induce severe complications and mortality than other enteroviruses. Methods for detection of IgM antibody against EV71 had been established for years, however, the performance of the methods in the very early diagnosis of EV71 infection had not been fully evaluated, which is especially meaningful because of the short incubation period of EV71 infection. In this report, the performance of an IgM anti-EV71 assay was evaluated using acute sera collected from 165 EV71 infected patients, 165 patients infected with other enteroviruses, and more than 2,000 sera from healthy children or children with other infected diseases.

Role of heat-shock protein 90 in hepatitis E virus capsid trafficking.

p239 is a virus-like particle constituted from hepatitis E virus (HEV) recombinant proteins. It can be used as a surrogate for HEV and as an investigative tool to study cellular interactions because of its ability to adsorb to and penetrate HepG2 cellular membranes. Our objective was to use p239 to define the role of HEV capsid proteins during the early stages of infection.

A rapid test for the detection of influenza A virus including pandemic influenza A/H1N1 2009.

A new rapid diagnostic test for detection of influenza A virus was evaluated with four sets of experiments: first, a comparison with a commercial diagnostic kit against a panel of virus strains was conducted; second, the kit was tested against a collection of 40 strains of influenza A virus isolated from five different host species and 26 strains of other respiratory viruses used as controls; third, the kit was tested against specimens collected in the field obtained from human and chicken; and fourth, the kit was tested against the novel pandemic influenza A/H1N1 2009 clinical specimens obtained from admitted to hospital patients. The test kit displayed a sensitivity of 88% for both human specimens and avian specimens. The corresponding specificity was 99.

Novel double-antigen sandwich immunoassay for human hepatitis B core antibody.

A novel diagnostic immunoassay testing procedure for hepatitis B virus core antibody (anti-HBc) using homogeneous purified full-length hepatitis B virus core antigen (HBcAg) capsids obtained from Escherichia coli was compared with Abbott Architect anti-HBc chemiluminescent microparticle immunoassay (CMIA; indirect method) against a library of specimens. A monoclonal anti-HBc neutralization confirmatory assay was then used to determine the degree of discordance between specimens. The new assay was found to be superior in both sensitivity and specificity.

Molecular characteristics of occult hepatitis B virus from blood donors in southeast China.

The characteristics of 30 carriers with occult hepatitis B virus (HBV) infection (OBI) were compared with those of 30 individuals diagnosed as being HBV carriers at the time of blood donation, 60 asymptomatic carriers, and 60 chronic hepatitis patients. The prevalence of genotype C was significantly higher in carriers with OBIs than in any other HBsAg-positive (HBsAg(+)) group (P < 0.001).

Decreased NK cell frequency in chronic hepatitis C does not affect ex vivo cytolytic killing.

Prior studies have suggested that natural killer (NK) cell function might be impaired in chronic hepatitis C virus (HCV) infection. Circulating NK cell frequency and cytolytic activity were examined freshly ex vivo in HCV-infected and uninfected subjects. Surprisingly, the intrinsic cytolytic activity of peripheral blood NK-enriched cells was similar between HCV-infected and uninfected groups (P = .

Prognostic indicators of breakthrough hepatitis during lamivudine monotherapy for chronic hepatitis B virus infection.

Background: Breakthrough hepatitis (BTH), defined as a flare of transaminases alanine aminotransferase [ALT]) can occur during lamivudine monotherapy for hepatitis B virus (HBV) infection. There have been many reports of lamivudine-resistant mutations within the C domain of the viral reverse transcriptase; however, the appearance of these mutants is not necessarily correlated with BTH during lamivudine therapy.

Methods And Results: Entire serial HBV genomic sequences before and during lamivudine therapy for 4 patients with BTH and 1 patient without BTH were analyzed and showed changes in the pre-S region.

The activity of grepafloxacin in two murine models of Mycobacterium avium infection.

The activity against Mycobacterium avium complex (MAC) of varying doses of grepafloxacin (GRE; 25 mg/kg, 50 mg/kg, 100 mg/kg, and 200 mg/kg) were compared to clarithromycin (CLA; 100 mg/kg and 200 mg/kg), ethambutol (EMB; 100 mg/kg), and rifabutin (RBT; 10 mg/kg) using an intranasal (IN) infection model compared to an intravenous (IV) infection model. Beige mice (C57BL6/J-Lyst bg J/+) were infected intranasally with about 10(6) organisms and for the IV model about 10(7) organisms. Treatment for both models was started 1 week postinfection and given by gavage 5 days/week for 4 weeks.

PCR-probe capture hybridization assay and statistical model for SEN virus prevalence estimation.

SEN viruses (SENV) are newly discovered blood-borne single-stranded circular DNA viruses that may play a role in liver disease. To date, no serologic assays are available for the detection of SENV antigens or antibodies. We report on a rapid and sensitive molecular assay for the detection of four SENV strains (SENV-A, -C, -D, -H).

Investigation of SEN virus infection in patients with cryptogenic acute liver failure, hepatitis-associated aplastic anemia, or acute and chronic non-A-E hepatitis.

SEN virus (SENV) has been tentatively linked to transfusion-associated non-A-E hepatitis. We investigated SENV's role in unexplained hepatitis in other settings. Polymerase chain reaction amplification was used to detect 2 SENV variants (SENV-D and SENV-H) in 1706 patients and control subjects.

Activity of clarithromycin alone and in combination in a murine model of Mycobacterium kansasii infection.

Activities of clarithromycin alone and in combination with rifampicin, gatifloxacin or linezolid were evaluated against Mycobacterium kansasii in a murine infection model. Clarithromycin was the most active single agent. Rifampicin and gatifloxacin had similar activities, but were less active than clarithromycin.