Hepatitis B core-related antigen: A novel and promising surrogate biomarker to guide anti-hepatitis B virus therapy

The current requirement for biomarkers to detect hepatitis B virus (HBV) infection is polarized. One is a fully-automated and highly sensitive measurement system; the other is a simple system for point-of-care testing (POCT) in resource-limited areas. Hepatitis B core-related antigen (HBcrAg) reflects intrahepatic covalently closed circular DNA and serum HBV DNA. Even in patients with undetectable serum HBV DNA or HBsAg loss, HBcrAg may remain detectable. Decreased HBcrAg levels are associated with reduction of the occurrence of hepatocellular carcinoma (HCC) in chronic hepatitis B. Recently, a fully-automated, novel high-sensitivity HBcrAg assay (iTACT-HBcrAg, cut-off value: 2.1 logIU/mL) has been developed. This attractive assay has been released in Japan very recently. iTACT-HBcrAg can be useful for monitoring HBV reactivation and prediction of HCC occurrence, as an alternative to HBV DNA. Moreover, monitoring HBcrAg may be suitable for determining the therapeutic effectiveness of approved drugs and novel drugs under development. Presently, international guidelines recommend anti-HBV prophylaxis for pregnant women with high viral loads to prevent mother-to-child transmission of HBV. However, >95% of HBV-infected individuals live in countries where HBV DNA quantification is not available. Worldwide elimination of HBV needs the scaling-up of examination and medication services in resource-limited areas. Based on this situation, a rapid and easy HBcrAg assay as a POCT is valuable. This review provides the latest information regarding the clinical use of a new surrogate marker, HBcrAg, in HBV management, based on iTACT-HBcrAg or POCT, and introduces novel agents targeting HBV RNA/protein

Oral bacteria in the occluded arteries of patients with Buerger disease

ObjectiveRecent studies have suggested that infectious organisms play a role in vascular diseases. In this study, to explore a possible link between oral infection and Buerger disease, we investigated whether oral (periodontal) bacteria were present in occluded arteries removed from patients with characteristic Buerger disease.MethodsFourteen male patients with a smoking history who had developed characteristics of Buerger disease before the age of 50 years were included in this study. Occluded arteries, including superficial femoral (n = 4), popliteal (n = 2), anterior tibial (n = 4), and posterior tibial (n = 4) arteries, were removed and studied. A periodontist performed a periodontal examination on each patient and collected dental plaque and saliva samples from them at the same time. The polymerase chain reaction method was applied to detect whether seven species of periodontal bacteria—Porphyromonas gingivalis, Tannerella forsythensis, Treponema denticola, Campylobacter rectus, Actinobacillus actinomycetemcomitans, Prevotella intermedia, and Prevotella nigrescens—were present in the occluded arteries and oral samples. In addition, arterial specimens from seven control patients were examined by polymerase chain reaction analysis.ResultsDNA of oral bacteria was detected in 13 of 14 arterial samples and all oral samples of patients with Buerger disease. Treponema denticola was found in 12 arterial and all oral samples. Campylobacter rectus, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythensis, and Prevotella nigrescens were found in 14% to 43% of the arterial samples and 71% to 100% of the oral samples. A pathologic examination revealed that arterial specimens showed the characteristics of an intermediate-chronic-stage or chronic-stage lesion of Buerger disease. All 14 patients with Buerger disease had moderate to severe periodontitis. None of the control arterial samples was positive for periodontal bacteria.ConclusionsThis is the first study to identify oral microorganisms in the lesions of Buerger disease. Our findings suggest a possible etiologic link between Buerger disease and chronic infections such as oral bacterial infections

Web-based System for Designing Game-based Evacuation Drills

A game-based evacuation drill (GBED) using the program Real-World Edutainment is effective disaster education. For the successful GBED, an evacuation scenario and digital materials are important. We are developing a web-based system to design GBEDs through community survey, digital material creation and evacuation scenario composition. This system works with a standard web browser and allows a wide range of people to participate in the GBED design process through simple operations

Protein Aggregation and Protein Instability Govern Familial Amyotrophic Lateral Sclerosis Patient Survival

The nature of the “toxic gain of function” that results from amyotrophic lateral sclerosis (ALS)-, Parkinson-, and Alzheimer-related mutations is a matter of debate. As a result no adequate model of any neurodegenerative disease etiology exists. We demonstrate that two synergistic properties, namely, increased protein aggregation propensity (increased likelihood that an unfolded protein will aggregate) and decreased protein stability (increased likelihood that a protein will unfold), are central to ALS etiology. Taken together these properties account for 69% of the variability in mutant Cu/Zn-superoxide-dismutase-linked familial ALS patient survival times. Aggregation is a concentration-dependent process, and spinal cord motor neurons have higher concentrations of Cu/Zn-superoxide dismutase than the surrounding cells. Protein aggregation therefore is expected to contribute to the selective vulnerability of motor neurons in familial ALS

Hepatitis B Core-Related Antigen and New Therapies for Hepatitis B

The hepatitis B core-related antigen (HBcrAg) is an unprecedented novel HBV biomarker that plays an essential role in reflecting covalently closed circular DNA (cccDNA) in chronic hepatitis B (CHB) because its levels correlate with intrahepatic cccDNA and serum HBV DNA. In this review, we describe the clinical application of serum HBcrAg in CHB patients, with a particular focus on new therapies targeting intrahepatic HBV replication. (1) HBcrAg can be detected in clinical cases where serum HBV DNA is undetectable during anti-HBV therapy. (2) A highly sensitive HBcrAg assay (iTACT-HBcrAg) may be useful for monitoring HBV reactivation, as an alternative to HBV DNA. (3) Decreased HBcrAg levels have been significantly associated with promising outcomes in CHB patients, reducing the risk of progression or recurrence of hepatocellular carcinoma. Additionally, we focus on and discuss several drugs in development that target HBV replication, and monitoring HBcrAg may be useful for determining the therapeutic efficacies of such novel drugs. In conclusion, HBcrAg, especially when measured by the recently developed iTACT-HBcrAg assay, may be the most appropriate surrogate marker, over other HBV biomarkers, to predict disease progression and treatment response in CHB patients