Phylogenetic clustering of hepatitis C virus among people who inject drugs in Vancouver, Canada.

UNLABELLED: Little is known about factors associated with hepatitis C virus (HCV) transmission among people who inject drugs (PWID). Phylogenetic clustering and associated factors were evaluated among PWID in Vancouver, Canada. Data were derived from the Vancouver Injection Drug Users Study. Participants who were HCV antibody-positive at enrolment and those with HCV antibody seroconversion during follow-up (1996 to 2012) were tested for HCV RNA and sequenced (Core-E2 region). Phylogenetic trees were inferred using maximum likelihood analysis and clusters were identified using ClusterPicker (90% bootstrap threshold, 0.05 genetic distance threshold). Factors associated with clustering were assessed using logistic regression. Among 655 eligible participants, HCV genotype prevalence was: G1a: 48% (n=313), G1b: 6% (n=41), G2a: 3% (n=20), G2b: 7% (n=46), G3a: 33% (n=213), G4a: <1% (n=4), G6a: 1% (n=8), G6e: <1% (n=1), and unclassifiable: 1% (n=9). The mean age was 36 years, 162 (25%) were female, and 164 (25%) were HIV+. Among 501 participants with HCV G1a and G3a, 31% (n=156) were in a pair/cluster. Factors independently associated with phylogenetic clustering included: age <40 (versus age≥40, adjusted odds ratio [AOR]=1.64; 95% confidence interval [CI] 1.03, 2.63), human immunodeficiency virus (HIV) infection (AOR=1.82; 95% CI 1.18, 2.81), HCV seroconversion (AOR=3.05; 95% CI 1.40, 6.66), and recent syringe borrowing (AOR 1.59; 95% CI 1.07, 2.36). CONCLUSION: In this sample of PWID, one-third demonstrated phylogenetic clustering. Factors independently associated with phylogenetic clustering included younger age, recent HCV seroconversion, prevalent HIV infection, and recent syringe borrowing. Strategies to enhance the delivery of prevention and/or treatment strategies to those with HIV and recent HCV seroconversion should be explored, given an increased likelihood of HCV transmission in these subpopulations.

The agricultural mechanization controversy.

Attorneys of California Rural Legal Assistance are suing the University of California on behalf of 19 farm workers, alleging that publicly funded mechanization research displaces farm workers, eliminates small farmers, hurts consumers, impairs the quality of rural life, and impedes collective bargaining. This article reviews the evidence and finds that it does not support the charges. The mechanization lawsuit is important because applied research by universities is often authorized by legislation stipulating multiple goals, leaving researchers and universities vulnerable to lawsuits alleging that only some of the legislative goals are being pursued.

Low exposure concentration effects of methoprene on endocrine-regulated processes in the crustacean Daphnia magna.

Methoprene is a growth-regulating insecticide that manifests its toxicity to target organisms by acting as a juvenile hormone agonist. Methoprene similarly may exert toxicity to crustaceans by mimicking or interfering with methyl farnesoate, a crustacean juvenoid. We hypothesized that methoprene interferes with endocrine-regulated processes in crustaceans by several mechanisms involving agonism or antagonism of juvenoid receptor complexes. In the present study, we evaluated this hypothesis, in part, by characterizing and comparing the concentration-response curves for methoprene and several endpoints related to development and reproduction of the crustacean Daphnia magna. Our results demonstrate that methoprene has multiple mechanisms of toxicity and low-exposure concentration effects. Methoprene reduced the growth rate of daphnids with evidence of only a single concentration-response line, having a threshold of 12.6 nM. Molt frequency was reduced by methoprene in a concentration-dependent manner, with a response curve corresponding to a 2-segmented line and thresholds at 4.2 and 0.21 nM. An endpoint related to reproductive maturation, the time of first brood deposition, was also affected by methoprene, with a clear concentration-dependent response and a NOEC of 32 nM. Methoprene reduced fecundity according to a 2-segmented line, with thresholds of 24 and < or =0.18 nM. These results demonstrate that methoprene elicits significant toxicity to endocrine-related processes in the 5-50 nM concentration range. Furthermore, molting and reproduction were impacted at significantly lower methoprene concentrations, with a distinct concentration response and a threshold of < or =0.2 nM. The different concentration-dependent response from that of methoprene could involve agonism or antagonism of various juvenoid receptor configurations.

Sex-specific gonadal and gene expression changes throughout development in fathead minnow.

Although fathead minnows (Pimephales promelas) are commonly used as a model fish in endocrine disruption studies, past studies have not characterized sex-specific baseline expression of genes involved in sex differentiation during development in this species. Using a sex-linked DNA marker to verify gender, we evaluated the expression over time of genes involved in sex differentiation (dmrt1, cyp19a, cyp17, star, esr1, ar) in developing fathead minnows (10-45 days post hatch). Evaluation of these molecular markers in combination with gender identification help us to better understand the mechanisms regulating sex differentiation in fathead minnows and how endocrine-disrupting chemicals may alter these processes.

Temporal and quantitative changes in sexual reproductive cycling of the cladoceran Daphnia magna by a juvenile hormone analog.

Cyclic parthenogens, such as the cladoceran, Daphnia magna, utilize both asexual (parthenogenetic) and sexual reproduction in order to maximize population fitness in variable environments. Parthenogenetic reproduction is the default strategy among D. magna, while various environmental cues trigger cycles of sexual reproduction. Experiments were conducted with the juvenile hormone analog methoprene to test the hypothesis that members of the insect juvenile hormone/vertebrate retinoic acid family of transcription factors are involved in the regulation of sexual reproduction in daphnids. Neither methoprene, food reduction, or crowding independently stimulated entry into the sexual reproductive phase of the daphnids. However, the combination of food deprivation and crowding stimulated entry into the sexual reproductive phase characterized by an initial high production of males and the subsequent intermittent production of haploid egg-containing ephippia. Exposure to 160 nM methoprene along with food deprivation and crowding caused a significant reduction in the percentage of males produced during the early phase of the sexual cycle and significantly increased the percentage of males produced during the later stages of the cycle. Methoprene concentrations as low as 6.4 nM significantly reduced the number of resting eggs produced and proportionately increased the production of parthenogenetically-produced neonates. These experiments demonstrate that methoprene uncouples the coordinate production of males and resting eggs during the sexual reproductive period of D. magna. Methoprene stimulates male offspring production and defers their production to latter stages of the sexual reproductive period, while inhibiting the production of resting eggs and promoting the continuance of parthenogenetic reproduction. J. Exp. Zool. 290:148-155, 2001.

Urticating histiocytosis: a mast cell-rich variant of histiocytosis X.

Histiocytosis X and mastocytosis are proliferative processes that may have similar cutaneous manifestations. However, a positive Darier's sign (urtication on stroking of the lesion) is thought to reliably distinguish between these two diseases. We recently studied a 13-year-old girl with a 2-year history of extensive skin lesions and a positive Darier's sign. Routine histopathologic studies revealed a polymorphous cutaneous infiltrate composed of histiocytes, mast cells, eosinophils, and lymphoid cells. Electron microscopic studies demonstrated Langerhans granules in some of the histiocytes, and immunologic studies of frozen tissue showed that a significant subpopulation of the histiocytes marked as Langerhans cells. Giemsa staining of specimens from eight other cases of cutaneous histiocytosis X from our files revealed mast cells in all of the lesions, although none showed the abundance of mast cells present in the case with urtication. Our studies emphasize the often polymorphous nature of the cell population in cutaneous histiocytosis X and demonstrate that confusing clinical findings can result when the mast cell population in histiocytosis X produces urtication.

Immune complexes in the pathogenesis of hypergammaglobulinemic purpura.

Direct immunofluorescence (DIF) was performed and circulating immune complex (CIC) levels evaluated in three patients with hypergammaglobulinemia purpura (HGP) of Waldenström. The Raji cell immunoradiometric assay was used to detect complexes of both IgG and IgM type. IgM and C3 were detected in blood vessel walls of all three patients. Elevated levels of IgG complexes were detected in two patients, and elevated levels of IgM complexes were detected in all three patients. Clinical improvement after plasmapheresis was noted in one patient. A cause-and-effect relationship between CIC and the inflammation of the superficial dermal blood vessels is postulated.

Cardiac troponin I in canine patients with lymphoma and osteosarcoma receiving doxorubicin: comparison with clinical heart disease in a retrospective analysis.

The cumulative cardiotoxicity that occurs as a result of doxorubicin chemotherapy is irreversible and can affect both quality and quantity of life for the cancer patient. Cardiac troponin I (cTnI) is a sensitive and specific marker of cardiomyocyte death. The purpose of this retrospective study was to evaluate serum concentrations of cTnI in dogs with lymphoma or osteosarcoma given doxorubicin chemotherapy, and with known cardiac outcome, based on a minimum assessment by physical examination and thoracic radiography. Serum samples were also available for cTnI measurement from seven healthy dogs given intracoronary doxorubicin. Serial serum samples obtained before, during and after doxorubicin chemotherapy showed increased cTnI concentrations in some clinical patients following chemotherapy (P = 0.0083 compared to baseline), but this did not correlate with clinical signs of cardiomyopathy. In dogs that subsequently developed cardiomyopathy however, serum cTnI concentrations were elevated before clinical signs became evident (confirmed with echocardiography).