Patient-derived precision cut tissue slices from primary liver cancer as a potential platform for preclinical drug testing.

Background: The exploitation of anti-tumour immunity, harnessed through immunomodulatory therapies, has fundamentally changed the treatment of primary liver cancer (PLC). However, this has posed significant challenges in preclinical research. Novel immunologically relevant models for PLC are urgently required to improve the translation from bench to bedside and back, explore and predict effective combinatorial therapies, aid novel drug discovery and develop personalised treatment modalities.

Novel therapeutic strategies for chronic hepatitis B.

The last few years have seen a resurgence of activity in the hepatitis B drug pipeline, with many compounds in various stages of development. This review aims to provide a comprehensive overview of the latest advances in therapeutics for chronic hepatitis B (CHB). We will discuss the broad spectrum of direct-acting antivirals in clinical development, including capsids inhibitors, siRNA, HBsAg and polymerase inhibitors.

A review of alcohol-pathogen interactions: New insights into combined disease pathomechanisms.

Progression of chronic infections to end-stage diseases and poor treatment results are frequently associated with alcohol abuse. Alcohol metabolism suppresses innate and adaptive immunity leading to increased viral load and its spread. In case of hepatotropic infections, viruses accelerate alcohol-induced hepatitis and liver fibrosis, thereby promoting end-stage outcomes, including cirrhosis and hepatocellular carcinoma (HCC).

Dental School Patient Preferences for Receiving and Returning Patient Satisfaction Surveys.

The aims of this study were to investigate dental school patient, parent, and caregiver preferences for receiving and returning patient satisfaction surveys and to determine how modes of receiving and returning surveys impacted return rates. Two studies were conducted, both of which are reported. In Study 1, adult patients, parents of child patients, and caregivers of patients with special needs were asked to indicate their preferred mode of receiving and returning surveys.

Peg-Interferon Lambda Treatment Induces Robust Innate and Adaptive Immunity in Chronic Hepatitis B Patients.

Unlabelled: IFN-lambda (IFNλ) is a member of the type III IFN family and is reported to possess anti-pathogen, anti-cancer, and immunomodulatory properties; however, there are limited data regarding its impact on host immune responses . We performed longitudinal and comprehensive immunosurveillance to assess the ability of pegylated (peg)-IFNλ to augment antiviral host immunity as part of a clinical trial assessing the efficacy of peg-IFNλ in chronic hepatitis B (CHB) patients. These patients were pretreated with directly acting antiviral therapy (entecavir) for 12 weeks with subsequent addition of peg-IFNλ for up to 32 weeks.

How are allied health notes used for inpatient care and clinical decision-making? A qualitative exploration of the views of doctors, nurses and allied health professionals.

Background: Inpatient care is dependent upon the effective transfer of clinical information across multiple professions. However, documented patient clinical information generated by different professions is not always successfully transferred between them. One obstacle to successful information transfer may be the reader's perception of the information, which is framed in a particular professional context, rather than the information per se.

Alisporivir inhibition of hepatocyte cyclophilins reduces HBV replication and hepatitis B surface antigen production.

Background & Aims: Cyclophilins are host factors required for hepatitis C virus replication. Cyclophilin inhibitors such as alisporivir have shown strong anti-hepatitis C virus activity in vitro and in clinical studies. However, little is known about whether hepatocyte cyclophilins are involved in the hepatitis B virus (HBV) life cycle.

Identification of serum cytokine profiles associated with HBeAg seroconversion following antiviral treatment interruption.

The major shortcoming of nucleos(t)ide analogue therapy for chronic hepatitis B (CHB) is the frequent requirement for indefinite therapy. Withdrawal of treatment can result in viral rebound with an alanine aminotransferase (ALT) flare leading to hepatic decompensation, while in others this can lead to hepatitis B e antigen (HBeAg) seroconversion. The aim of the study was to identify host immune profiles associated with these different outcomes.

Novel mechanism of antibodies to hepatitis B virus in blocking viral particle release from cells.

Unlabelled: Antibodies are thought to exert antiviral activities by blocking viral entry into cells and/or accelerating viral clearance from circulation. In particular, antibodies to hepatitis B virus (HBV) surface antigen (HBsAg) confer protection, by binding circulating virus. Here, we used mathematical modeling to gain information about viral dynamics during and after single or multiple infusions of a combination of two human monoclonal anti-HBs (HepeX-B) antibodies in patients with chronic hepatitis B.

CD8(+) T cell control of hepatitis B virus replication: direct comparison between cytolytic and noncytolytic functions.

Resolution of hepatitis B virus (HBV) infection was believed to be attributed to the cytotoxic T cell-mediated killing of infected hepatocytes. However, studies in HBV transgenic mice and HBV-infected chimpanzees revealed that T cell control of HBV replication also involves cytokine-mediated noncytolytic mechanisms. The relative role of cytolytic and noncytolytic functions of virus-specific CD8(+) T cells during interaction with HBV-producing hepatocytes is not well understood.

Programmed death 1 expression during antiviral treatment of chronic hepatitis B: Impact of hepatitis B e-antigen seroconversion.

Unlabelled: Hyperexpression of the programmed death 1 (PD-1) molecule is a hallmark of exhausted T-cells, having a negative impact on T-cell activation and function. We studied longitudinally 18 hepatitis B e antigen (HBeAg)-positive patients undergoing treatment with direct antivirals (telbivudine or lamivudine) to determine the relationship between treatment-induced viremia reduction and HBeAg seroconversion with respect to PD-1 levels and T-cell reactivity. PD-1 expression was assessed by (1) flow cytometry and (2) quantitative real-time polymerase chain reaction; hepatitis B virus (HBV)-specific CD8+ T-cells were quantitated by pentamer staining; T-cell reactivity to HBV antigens was determined by interferon gamma (IFNgamma) and interleukin 10 (IL-10) enzyme-linked immunosorbent spot (ELISPOT) assays; and central/effector memory phenotypes were defined by phenotypic markers.

Genotoxicity and toxicity of the potential cancer-preventive agent polyphenon E.

The potential health benefits of green tea continue to attract public and scientific interests and are attributed in part to polyphenolic catechin constituents. Polyphenon E (Poly E) is a decaffeinated green tea catechin mixture containing about 50% epigallocatechin gallate and 30% other catechins. We evaluated the toxicity and genotoxicity of Poly E by using two in vitro assays: bacterial mutagenesis in a Salmonella typhimurium-E.

Synergistic bone marrow toxicity of pyrimethamine and zidovudine in murine in vivo and in vitro models: mechanism of toxicity.

Pyrimethamine (Pyr) is commonly used for treatment of toxoplasmic encephalitis in AIDS patients; however, in two clinical studies, an increased number of deaths were observed when Pyr was coadministered with zidovudine (ZDV). The BALB/c mouse was chosen as a model to study the mechanism underlying the unexpected toxicity from coadministration of these drugs. Daily administration by oral gavage of 60 mg/kg Pyr and 240 mg/kg ZDV resulted in 100% lethality after 30 days.

Patterns of oral care in dental school and general dental practice.

This study compared patterns of oral care provided by predoctoral dental students for patients seeking treatment at the University of Washington (UW) with patterns reported for general dental offices by the Washington Dental Service (WDS). Dental care included about 5 million services provided to 880,317 patients by 2,803 WDS general dentists and about 45,600 dental services provided to 9,488 patients by 155 UW dental students during 1999. There was high fidelity between databases and randomly surveyed patient records for treatment provided in both UW (95 percent) and WDS (97 percent) populations.