Chronic hepatitis B (CHB) is characterized by high levels of hepatitis B virus (HBV) surface antigen (HBsAg) in blood circulation. A major goal of CHB interventions is reducing or eliminating this antigenemia; however, there are currently no approved methods that can do this. A novel family of compounds with a dihydroquinolizinone (DHQ) scaffold has been shown to reduce circulating levels of HBsAg in animals, representing a first for a small molecule. Reductions of HBsAg were a result of the compound's effect on HBsAg mRNA levels. However, commercial development by Roche of a DHQ lead compound, RG-7834, was stopped due to undisclosed toxicity issues. Herein we report our effort to convert the systemic RG7834 compound to a hepatoselective DHQ analog to limit its distribution to the bloodstream and thus to other body tissues.

Hyaluronic acid of various molecular weights has been in use for the treatment of osteoarthritis knee pain for decades. Worldwide, these products are regulated as either as drugs or devices and in some countries as both. In the US, this class of products is regulated as Class III medical devices, which places specific regulatory requirements on developers of these materials under a Pre-Market Approval process, typically requiring data from prospective randomized controlled clinical studies. In 1984 pharmaceutical manufacturers became able to file an Abbreviated New Drug Application for approval of a generic drug, thus establishing standards for demonstrating equivalence to an existing chemical entity. Recently, the first biosimilar, or ‘generic biologic’, was approved. Biosimilars are biological products that are approved by the FDA because they are ‘highly similar’ to a reference product, and have been shown to have no clinically meaningful differences from the reference product. For devices, Class II medical devices have a pathway for declaring equivalence to an existing product by filing a 510 k application for FDA clearance. However, until recently no equivalent regulatory pathway was available to Class III devices. In this paper, we consider the critical mechanical performance parameters for intra-articular hyaluronic products to demonstrate indistinguishable characteristics. Analogous to the aforementioned pathways that allow for a demonstration of equivalence, we examine these parameters for an existing, marketed device and compare molecular weight and rheological properties of multiple batches of a similar product. We propose that this establishes a scientific rationale for establishing Class III medical device equivalence.

Legionella species are abundant in the environment and are increasingly recognized as a cause of severe pneumonia. Increases in cases of community-acquired legionellosis in the greater Philadelphia metropolitan area (GPMA) led to concern that changing environmental factors could influence occurrence of disease. We evaluated the association between weather patterns and occurrence of legionellosis in the GPMA, using both traditional Poisson regression analysis and a case-crossover study approach. The latter approach controls for seasonal factors that could confound the relationship between weather and occurrence of disease and permits the identification of acute weather patterns associated with disease. A total of 240 cases of legionellosis were reported between 1995 and 2003. Cases occurred with striking summertime seasonality. Occurrence of cases was associated with monthly average temperature (incidence rate ratio [IRR] per degree Celsius, 1.07 [95% confidence interval [CI], 1.05-1.09]) and relative humidity (IRR per 1% increase in relative humidity, 1.09 [95% CI, 1.06-1.12]) by Poisson regression analysis. However, case-crossover analysis identified an acute association with precipitation (odds ratio [OR], 2.48 [95% CI, 1.30-3.12]) and increased humidity (OR per 1% increase in relative humidity, 1.08 [95% CI, 1.05-1.11]) 6-10 days before occurrence of cases. A significant dose-response relationship for occurrence of cases was seen with both precipitation and increased humidity. Although, in the GPMA, legionellosis occurred predominantly during summertime, the acute occurrence of disease is best predicted by wet, humid weather. This finding is consistent with the current understanding of the ecological profile of this pathogen and supports the contention that sporadic legionellosis occurs through contamination of water sources.

An outbreak of norovirus gastroenteritis affected passengers on two consecutive cruises of ship X and continued on 4 subsequent cruises despite a 1-week sanitization. We documented transmission by food and person-to-person contact; persistence of virus despite sanitization onboard, including introductions of new strains; and seeding of an outbreak on land.

An outbreak of multidrug-resistant Salmonella enterica serotype Typhimurium infections occurred in Pennsylvania and New Jersey. A case-control study implicated pasteurized milk from a dairy, and an inspection indicated the potential for contamination after pasteurization. Dairy cattle are the likely reservoir, and milk may be an important vehicle of Salmonella transmission to humans.

(1972). The Blind “See” the World of Nature on the Braille Trail. Journal of Health, Physical Education, Recreation: Vol. 43, No. 1, pp. 85-85.