F344/NTac Rats Chronically Exposed to Bromodichloroacetic Acid Develop Mammary Adenocarcinomas With Mixed Luminal/Basal Phenotype and Tgfß Dysregulation.

Breast cancer is the most common cancer and the second-leading cause of cancer mortality in women in the United States. A recent 2-year National Toxicology Program carcinogenicity study showed an increased incidence of proliferative mammary lesions (hyperplasia, fibroadenoma, adenocarcinoma) in F344/NTac rats exposed to bromodichloroacetic acid (BDCA), a disinfection by-product in finished drinking water with widespread human exposure. We hypothesized that the increase in mammary tumors observed in BDCA-exposed F344/NTac rats may be due to underlying molecular changes relevant for human breast cancer. The objective of the study was to compare (1) gene and protein expression and (2) mutation spectra of relevant human breast cancer genes between normal untreated mammary gland and mammary tumors from control and BDCA-exposed animals to identify molecular changes relevant for human cancer. Histologically, adenocarcinomas from control and BDCA-exposed animals were morphologically very similar, were estrogen/progesterone receptor positive, and displayed a mixed luminal/basal phenotype. Gene expression analysis showed a positive trend in the number of genes associated with human breast cancer, with proportionally more genes represented in the BDCA-treated tumor group. Additionally, a 5-gene signature representing possible Tgfß pathway activation in BDCA-treated adenocarcinomas was observed, suggesting that this pathway may be involved in the increased incidence of mammary tumors in BDCA-exposed animals.

Genetic covariation of the marine fungal symbiont Haloguignardia irritans (Ascomycota, Pezizomycotina) with its algal hosts Cystoseira and Halidrys (Phaeophyceae, Fucales) along the west coast of North America.

The fungal endophyte Haloguignardia irritans induces gall formation on the brown algal genera Cystoseira and Halidrys occurring from Oregon to Baja California, Mexico. Here we examine genetic covariation and compare rDNA phylogenies to investigate the coevolutionary histories of H. irritans and its algal hosts. Despite recognition of H. irritans as a single morphological species, internal transcribed spacer rDNA sequences representative of its geographic range are characterized by sequence variation at the intraspecific to intrageneric levels. An assessment of parallel cladogenesis between endophyte and host phylogenies provides evidence for a combination of independent fungal divergence and host jumping, similar to that observed in terrestrial lichens. Our results suggest that reduced gene flow due to geographic isolation is a major contributing factor to more concerted covariation observed at one island site, rather than to differences among algal host species alone. Because geography and its effects on gene flow can create heterogeneous mosaics of coevolution for symbioses in terrestrial environments, our results support the notion that conservation efforts toward the maintenance of genetic diversity in marine environments should likewise consider geographic complexity and its effects on coevolving marine species.

The spin doctors: an invitation to health care professionals to reflect on the organizational dynamics of the Last Supper and why Judas was not the traitor.

The dynamics of The Last Supper are used to describe how organizations' members frequently make unethical, organizationally destructive decisions and then become "spin doctors" who collude in creating explanations that deflect attention from their contributions to the ensuing debacles. The implications of that process for a variety of organizations, including those engaged in health care, are discussed.

Survey of veterinarians' recommendations for treatment and control of intestinal parasites in dogs: public health implications.

A systematic, random sample of 450 small and mixed-animal practitioners was selected from the client list of a prominent veterinary pharmaceutical and animal health company. A telephone survey was conducted, using a standard questionnaire, to assess whether current veterinary practices concerning prophylaxis and treatment of canine roundworm (Toxocara canis) and hookworm (Ancylostoma spp) infections are adequate to prevent transmission to human beings. Analysis of results focused on 3 questions related to prevention: practitioner's frequency of client education regarding zoonotic potential of roundworms and hookworms, pup age at which veterinarian recommends first anthelmintic treatments, and proportion of veterinarians recommending prophylactic drug administration for pups and nursing bitches. Despite the proven association of household pet dogs and human toxocariasis, only a third (148/450) of veterinarian respondents routinely discussed the potential zoonotic hazards of canine roundworms with their clients. A total of 29% (130/450) of veterinarians surveyed either never discussed these potential hazards or discussed them only when asked by their clients. With regard to anthelmintic treatment practices, 31% (140/450) of veterinarians surveyed recommended that pups first be examined and treated for intestinal parasites within 4 weeks of age. Thirty-three percent (163/450) recommended first examination and deworming at 5 to 6 weeks of age, and 36% (163/450) suggested that it be done at or after 7 weeks of age. Less than half (208/450) of veterinarians administered anthelmintics prophylactically to at least some pups and dogs. Sixty-four percent (287/450) of respondents recommended routine testing and treatment of nursing bitches.(ABSTRACT TRUNCATED AT 250 WORDS)