Blastomycosis of bones and joints

A retrospective study of 45 patients hospitalized with blastomycosis of bones or joints revealed 41 cases of osteomyelitis and 12 cases of septic arthritis. The majority were men (35 [78%] patients) and non-Aboriginal (32 [71%] patients). Median time from the onset of symptoms to hospitalization was shorter in women than men (male, 48 d; female, 14 d; P < 0.02), and shorter for Aboriginals than non-Aboriginals (non-Aboriginal, 50 d; Aboriginal, 19 d; P < 0.04). Cutaneous disease was present in 33 (73%) patients, and lung involvement was present in 29 (64%) patients. The most common osseous sites of involvement were the lower limb and axial skeleton. Common orthopaedic symptoms of bone lesions included bone pain in 42 (78%) patients, swelling in 32 (59%) patients, and soft tissue abscesses in 21 (39%) patients. Joint infection (12 patients) manifested as a monoarticular arthropathy presenting with effusion in 9 (75%) patients, pain in 8 (67%) patients, and decreased range of motion in 5 (42%) patients. Osseous blastomycosis can mimic bacterial infection and should be included in the differential diagnosis of bone and joint infection in patients who have visited or who live in geographic regions where B dermatitidis is endemic.     

A Framework for the Next Generation of Risk Science

Objectives: In 2011, the U.S. Environmental Protection Agency initiated the NexGen project to develop a new paradigm for the next generation of risk science.Methods: The NexGen framework was built on three cornerstones: the availability of new data on toxicity pathways made possible by fundamental advances in basic biology and toxicological science, the incorporation of a population health perspective that recognizes that most adverse health outcomes involve multiple determinants, and a renewed focus on new risk assessment methodologies designed to better inform risk management decision making.Results: The NexGen framework has three phases. Phase I (objectives) focuses on problem formulation and scoping, taking into account the risk context and the range of available risk management decision-making options. Phase II (risk assessment) seeks to identify critical toxicity pathway perturbations using new toxicity testing tools and technologies, and to better characterize risks and uncertainties using advanced risk assessment methodologies. Phase III (risk management) involves the development of evidence-based population health risk management strategies of a regulatory, economic, advisory, community-based, or technological nature, using sound principles of risk management decision making.Conclusions: Analysis of a series of case study prototypes indicated that many aspects of the NexGen framework are already beginning to be adopted in practice.Citation: Krewski D, Westphal M, Andersen ME, Paoli GM, Chiu WA, Al-Zoughool M, Croteau MC, Burgoon LD, Cote I. 2014. A framework for the next generation of risk science. Environ Health Perspect 122:796–805; http://dx.doi.org/10.1289/ehp.1307260     

Adiposity and estrogen receptor-positive,postmenopausal breast cancer risk: Quantification of the mediating effects of fasting insulin and free estradiol

Adiposity increases estrogen receptor (ER)-positive postmenopausal breast cancer risk. While mechanisms underlying this relationship are uncertain, dysregulated sex-steroid hormone production and insulin signaling are likely pathways. Our aim was to quantify mediating effects of fasting insulin and free estradiol in the adiposity and ER-positive postmenopausal breast cancer association. We used data from a case–cohort study of sex hormones and insulin signaling nested within the Melbourne Collaborative Cohort Study. Eligible women, at baseline, were not diagnosed with cancer, were postmenopausal, did not use hormone therapy and had no history of diabetes or diabetes medication use. Women with ER-negative disease or breast cancer diagnosis within the first follow-up year were excluded. We analyzed the study as a cumulative sampling case–control study with 149 cases and 1,029 controls. Missing values for insulin and free estradiol were multiply imputed with chained equations. Interventional direct (IDE) and indirect (IIE) effects were estimated using regression-based multiple-mediator approach. For women with body mass index (BMI) >30 kg/m² compared to women with BMI 18.5–25 kg/m², the risk ratio (RR) of breast cancer was 1.75 (95% confidence interval [CI] 1.05–2.91). The estimated IDE (RR) not through the mediators was 1.03 (95% CI 0.43–2.48). Percentage mediated effect through free estradiol was 72% (IIE-RR 1.56; 95% CI 1.11–2.19). There was no evidence for an indirect effect through insulin (IIE-RR 1.12; 95% CI 0.68–1.84; 28% mediated). Our results suggest that circulating free estradiol plays an important mediating role in the adiposity–breast cancer relationship but does not explain all of the association.     

Human hair follicle bulge cells are biochemically distinct and possess an epithelial stem cell phenotype

Stem cells are vital for the homeostasis of self-renewing tissues and their manipulation may have wide ranging applications, including gene therapy, wound repair, and tissue transplantation. Although rodent hair follicle stem cells have been localized to the follicle bulge, the location of human hair follicle stem cells is less clear, and their characterization has been hampered by a lack of cellular markers for the bulge area. We demonstrate that the C8/144B monoclonal antibody, originally raised against a CD8 peptide sequence, immunostains the human hair follicle bulge. We show that this antibody recognizes cytokeratin 15 (K15) in keratinocytes, and that K15-positive bulge cells possess a stem cell phenotype characterized by their slowly cycling nature, proliferation at the onset of new hair follicle growth, and high level of beta1 integrin expression. These results localize human hair follicle stem cells to the bulge and suggest that K15 is preferentially expressed in epithelial stem cells.     

运动性心律失常

运动性心律失常是指发生于机体剧烈运动期间或之后的心律失常。临床表现不一,从心悸、头晕、晕厥、心绞痛、急性心肌梗死和充血性心力衰竭,甚至到心脏性猝死。运动性心律失常可见于心肌缺血,如患有动脉粥样硬化性心脏病以及患有原发性或继发性心肌病的患者。然而,也可能发生在似乎健康的个体。在后一组人群中,运动性心律失常可以是良性的,但也可以是获得性(如药物诱发)或先天性(如先天性长QT综合征或致心律失常性右室发育不良)心电活动或结构的异常而呈恶性。这种潜在病理生理学机制的复杂性,使运动性心律失常的诊断和治疗成为临床医学上的…