162 research outputs found

    HIV-Untested Men who have Sex with Men in South Africa: The perception of not being at risk and fear of being tested.

    Get PDF
    A community-based needs assessment among men who have sex with men (MSM) in South Africa found that 27 % (n = 280/1,045) of MSM had never been tested for HIV. The most frequently reported reasons for not having been tested were the perception of not being at risk (57 %) and fear of being tested (52 %). This article explores factors associated with these two reasons among the untested MSM. In multiple logistic regressions, the perception of not being at risk of HIV infection was negatively associated with being black, coloured or Indian, being sexually active, knowing people living with HIV, and a history of sexually transmitted infections (STIs) in the past 24 months (adj. OR = .24, .32, .38, and .22, respectively). Fear of being tested for HIV was positively associated with being black, coloured or Indian, preferred gender expression as feminine, being sexually active, a history of STIs, and experience of victimization on the basis of sexual orientation (adj. OR = 2.90, 4.07, 4.62, 5.05, and 2.34, respectively). Results suggest that HIV prevention programs directed at South African MSM will be more effective if testing and treatment of STIs are better integrated into HIV testing systems. Finally, social exclusion on the basis of race and sexual orientation ought to be addressed in order to reach hidden, at-risk, populations of MSM.College of Human Science

    Region-Wide Ecological Responses of Arid Wyoming Big Sagebrush Communities to Fuel Treatments

    Get PDF
    If arid sagebrush ecosystems lack resilience to disturbances or resistance to annual invasives, then alternative successional states dominated by annual invasives, especially cheatgrass (Bromus tectorum L.), are likely after fuel treatments. We identified six Wyoming big sagebrush (Artemisia tridentata ssp. wyomingensis Beetle & Young) locations (152–381 mm precipitation) that we believed had sufficient resilience and resistance for recovery. We examined impacts of woody fuel reduction (fire, mowing, the herbicide tebuthiuron, and untreated controls, all with and without the herbicide imazapic) on short-term dominance of plant groups and on important land health parameters with the use of analysis of variance (ANOVA). Fire and mowing reduced woody biomass at least 85% for 3 yr, but herbaceous fuels were reduced only by fire (72%) and only in the first year. Herbaceous fuels produced at least 36% more biomass with mowing than untreated areas during posttreatment years. Imazapic only reduced herbaceous biomass after fires (34%). Tebuthiuron never affected herbaceous biomass. Perennial tall grass cover was reduced by 59% relative to untreated controls in the first year after fire, but it recovered by the second year. Cover of all remaining herbaceous groups was not changed by woody fuel treatments. Only imazapic reduced significantly herbaceous cover. Cheatgrass cover was reduced at least 63% with imazapic for 3 yr. Imazapic reduced annual forb cover by at least 45%, and unexpectedly, perennial grass cover by 49% (combination of tall grasses and Sandberg bluegrass [Poa secunda J. Presl.]). Fire reduced density of Sandberg bluegrass between 40% and 58%, decreased lichen and moss cover between 69% and 80%, and consequently increased bare ground between 21% and 34% and proportion of gaps among perennial plants &spigt; 2 m (at least 28% during the 3 yr). Fire, mowing, and imazapic may be effective in reducing fuels for 3 yr, but each has potentially undesirable consequences on plant communities

    Reduction of Murine Colon Tumorigenesis Driven by Enterotoxigenic Bacteroides fragilis Using Cefoxitin Treatment

    Get PDF
    BACKGROUND: Chronic inflammation and composition of the colon microbiota have been associated with colorectal cancer in humans. The human commensal enterotoxigenic Bacteroides fragilis (ETBF) is linked to both inflammatory bowel disease and colorectal cancer and, in our murine model, causes interleukin 17A (IL-17A)-dependent colon tumors. In these studies, we hypothesized that persistent colonization by ETBF is required for tumorigenesis. METHODS: We established a method for clearing ETBF in mice, using the antibiotic cefoxitin. Multiple intestinal neoplasia mice were colonized with ETBF for the experiment duration or were cleared of infection after 5 or 14 days. Gross tumors and/or microadenomas were then evaluated. In parallel, IL-17A expression was evaluated in wild-type littermates. RESULTS: Cefoxitin treatment resulted in complete and durable clearance of ETBF colonization. We observed a stepwise increase in median colon tumor numbers as the duration of ETBF colonization increased before cefoxitin treatment. ETBF eradication also significantly decreased mucosal IL-17A expression. CONCLUSIONS: The timing of ETBF clearance profoundly influences colon adenoma formation, defining a period during which the colon is susceptible to IL-17A-dependent tumorigenesis in this murine model. This model system can be used to study the microbiota-dependent and molecular mechanisms contributing to IL-17A-dependent colon tumor initiation

    Mutant PIK3CA promotes cell growth and invasion of human cancer cells

    Get PDF
    SummaryPIK3CA is mutated in diverse human cancers, but the functional effects of these mutations have not been defined. To evaluate the consequences of PIK3CA alterations, the two most common mutations were inactivated by gene targeting in colorectal cancer (CRC) cells. Biochemical analyses of these cells showed that mutant PIK3CA selectively regulated the phosphorylation of AKT and the forkhead transcription factors FKHR and FKHRL1. PIK3CA mutations had little effect on growth under standard conditions, but reduced cellular dependence on growth factors. PIK3CA mutations resulted in attenuation of apoptosis and facilitated tumor invasion. Treatment with the PI3K inhibitor LY294002 abrogated PIK3CA signaling and preferentially inhibited growth of PIK3CA mutant cells. These data have important implications for therapy of cancers harboring PIK3CA alterations

    Short Telomeres, even in the Presence of Telomerase, Limit Tissue Renewal Capacity

    Get PDF
    Autosomal-dominant dyskeratosis congenita is associated with heterozygous mutations in telomerase. To examine the dosage effect of telomerase, we generated a line of mTR+/ÿ mice on the CAST/EiJ background, which has short telomeres. Interbreeding of heterozygotes resulted in progressive telomere shortening, indicating that limiting telomerase compromises telomere mainte- nance. In later-generation heterozygotes, we observed a decrease in tissue renewal capacity in the bone marrow, intestines, and testes that resembled defects seen in dyskeratosis congenita patients. The pro- gressive worsening of disease with decreasing telomere length suggests that short telo- meres, not telomerase level, cause stem cell failure. Further, wild-type mice derived from the late-generation heterozygous parents, termed wt*, also had short telomeres and displayed a germ cell defect, indicating that telomere length determines these phenotypes. We propose that short telomeres in mice that have normal telomerase levels can cause an occult form of genetic disease

    Heterotopic Ossifications in a Mouse Model of Albright Hereditary Osteodystrophy

    Get PDF
    Albright hereditary osteodystrophy (AHO) is characterized by short stature, brachydactyly, and often heterotopic ossifications that are typically subcutaneous. Subcutaneous ossifications (SCO) cause considerable morbidity in AHO with no effective treatment. AHO is caused by heterozygous inactivating mutations in those GNAS exons encoding the α-subunit of the stimulatory G protein (Gαs). When inherited maternally, these mutations are associated with obesity, cognitive impairment, and resistance to certain hormones that mediate their actions through G protein-coupled receptors, a condition termed pseudohypoparathyroidism type 1a (PHP1a). When inherited paternally, GNAS mutations cause only AHO but not hormonal resistance, termed pseudopseudohypoparathyroidism (PPHP). Mice with targeted disruption of exon 1 of Gnas (GnasE1−/+) replicate human PHP1a or PPHP phenotypically and hormonally. However, SCO have not yet been reported in GnasE1+/− mice, at least not those that had been analyzed by us up to 3 months of age. Here we now show that GnasE1−/+ animals develop SCO over time. The ossified lesions increase in number and size and are uniformly detected in adult mice by one year of age. They are located in both the dermis, often in perifollicular areas, and the subcutis. These lesions are particularly prominent in skin prone to injury or pressure. The SCO comprise mature bone with evidence of mineral deposition and bone marrow elements. Superficial localization was confirmed by radiographic and computerized tomographic imaging. In situ hybridization of SCO lesions were positive for both osteonectin and osteopontin. Notably, the ossifications were much more extensive in males than females. Because GnasE1−/+ mice develop SCO features that are similar to those observed in AHO patients, these animals provide a model system suitable for investigating pathogenic mechanisms involved in SCO formation and for developing novel therapeutics for heterotopic bone formation. Moreover, these mice provide a model with which to investigate the regulatory mechanisms of bone formation
    • 

    corecore