Pauci-immune glomerulonephritis in individuals with disease associated with levamisole-adulterated cocaine: a series of 4 cases.

Exposure to levamisole-adulterated cocaine can induce a distinct clinical syndrome characterized by retiform purpura and/or agranulocytosis accompanied by an unusual constellation of serologic abnormalities including antiphospholipid antibodies, lupus anticoagulants, and very high titers of antineutrophil cytoplasmic antibodies. Two recent case reports suggest that levamisole-adulterated cocaine may also lead to renal disease in the form of pauci-immune glomerulonephritis. To explore this possibility, we reviewed cases of pauci-immune glomerulonephritis between 2010 and 2012 at an inner city safety net hospital where the prevalence of levamisole in the cocaine supply is known to be high. We identified 3 female patients and 1 male patient who had biopsy-proven pauci-immune glomerulonephritis, used cocaine, and had serologic abnormalities characteristic of levamisole-induced autoimmunity. Each also had some other form of clinical disease known to be associated with levamisole, either neutropenia or cutaneous manifestations. One patient had diffuse alveolar hemorrhage. Three of the 4 patients were treated with short courses of prednisone and cyclophosphamide, 2 of whom experienced stable long-term improvement in their renal function despite ongoing cocaine use. The remaining 2 patients developed end-stage renal disease and became dialysis-dependent. This report supports emerging concern of more wide spread organ toxicity associated with the use of levamisole-adulterated cocaine

Minimally invasive surgery when treating endometriosis has a positive effect on health and on quality of work life of affected women

STUDY QUESTION What is the effect of the minimally invasive surgical treatment of endometriosis on health and on quality of work life (e.g. working performance) of affected women? SUMMARY ANSWER Absence from work, performance loss and the general negative impact of endometriosis on the job are reduced significantly by the laparoscopic surgery. WHAT IS KNOWN ALREADY The benefits of surgery overall and of the laparoscopic method in particular for treating endometriosis have been described before. However, previous studies focus on medical benchmarks without including the patient's perspective in a quantitative manner. STUDY DESIGN, SIZE, DURATION A retrospective questionnaire-based survey covering 211 women with endometriosis and a history of specific laparoscopic surgery in a Swiss university hospital, tertiary care center. Data were returned anonymously and were collected from the beginning of 2012 until March 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS Women diagnosed with endometriosis and with at least one specific laparoscopic surgery in the past were enrolled in the study. The study investigated the effect of the minimally invasive surgery on health and on quality of work life of affected women. Questions used were obtained from the World Endometriosis Research Foundation (WERF) Global Study on Women's Health (GSWH) instrument. The questionnaire was shortened and adapted for the purpose of the present study. MAIN RESULTS AND THE ROLE OF CHANCE Of the 587 women invited to participate in the study, 232 (232/587 = 40%) returned the questionnaires. Twenty-one questionnaires were excluded due to incomplete data and 211 sets (211/587 = 36%) were included in the study. Our data show that 62% (n = 130) of the study population declared endometriosis as influencing the job during the period prior to surgery, compared with 28% after surgery (P < 0.001). The mean (maximal) absence from work due to endometriosis was reduced from 2.0 (4.9) to 0.5 (1.4) hours per week (P < 0.001). The mean (maximal) loss in working performance after the surgery averaged out at 5.7% (12.6%) compared with 17.5% (30.5%) before this treatment (P < 0.001). LIMITATIONS, REASONS FOR CAUTION The mediocre response rate of the study weakens the representativeness of the investigated population. Considering the anonymous setting a non-responder investigation was not performed. A bias due to selection, information and negativity effects within a retrospective survey cannot be excluded, although study-sensitive questions were provided in multiple ways. The absence of a control group (sham group; e.g. patients undergoing specific diagnostic laparoscopy without treatment) is a further limitation of the study. WIDER IMPLICATIONS OF THE FINDINGS Our study shows that indicated minimally invasive surgery has a clear positive effect on the wellbeing and working performance of women suffering from moderate to severe endometriosis. Furthermore, national net savings in indirect costs with the present number of surgeries is estimated to be €10.7 million per year. In an idealized setting (i.e. without any diagnosis delay) this figure could be more than doubled. STUDY FUNDING/COMPETING INTEREST(S) The study was performed on behalf of the University Hospital of Bern (Inselspital) as one of the leading Swiss tertiary care centers. The authors do not declare any competing interest

Molecular cloning of the cDNA encoding pp36, a tyrosine-phosphorylated adaptor protein selectively expressed by T cells and natural killer cells.

Activation of T and natural killer (NK) cells leads to the tyrosine phosphorylation of pp36 and to its association with several signaling molecules, including phospholipase Cgamma-1 and Grb2. Microsequencing of peptides derived from purified rat pp36 protein led to the cloning, in rat and man, of cDNA encoding a T- and NK cell-specific protein with several putative Src homology 2 domain-binding motifs. A rabbit antiserum directed against a peptide sequence from the cloned rat molecule recognized tyrosine phosphorylated pp36 from pervanadate-treated rat thymocytes. When expressed in 293T human fibroblast cells and tyrosine-phosphorylated, pp36 associated with phospholipase Cgamma-1 and Grb2. Studies with GST-Grb2 fusion proteins demonstrated that the association was specific for the Src homology 2 domain of Grb-2. Molecular cloning of the gene encoding pp36 should facilitate studies examining the role of this adaptor protein in proximal signaling events during T and NK cell activation

Splotch: Visualizing Cosmological Simulations

We present a light and fast, public available, ray-tracer {\tt Splotch} software tool which supports the effective visualization of cosmological simulations data. We describe the algorithm it relies on, which is designed in order to deal with point-like data, optimizing the ray-tracing calculation by ordering the particles as a function of their ``depth'' defined as a function of one of the coordinates or other associated parameter. Realistic three-dimensional impressions are reached through a composition of the final color in each pixel properly calculating emission and absorption of individual volume elements. We describe several scientific as well as public applications realized with {\tt Splotch}. We emphasize how different datasets and configurations lead to remarkable different results in terms of the images and animations. A few of these results are available online.Comment: 19 Pages, 8 Figures, to appear in New Journal of Physics, Focus Issue on "Visualisation in Physics", edited by B. Sanders, T. Senden and V. Springe

Clinical Perspectives on Incorporating Cardiorespiratory Fitness in Clinical Practice

Cardiorespiratory fitness (CRF) has been documented as a strong, independent predictor of non-communicable disease and mortality in both clinical and apparently healthy populations. This well-established relationship has impelled organizations, including the American Heart Association, to release scientific statements highlighting the importance of accurate quantification of CRF. Current knowledge of the relationship between CRF and mortality is predominantly based on estimated CRF obtained from varying indirect methods. Cardiopulmonary exercise testing (CPX), the gold standard method of CRF measurement, provides a more accurate and reliable quantification of CRF compared to estimated methods. This review provides support for the diagnostic and prognostic use of CRF based on the current literature and makes a case for the use of CPX when available, as well as the need for standardization of normative values defining CRF levels to increase the efficacy of the risk assessment. Further, clinical applications of CPX-derived CRF are discussed, providing clinicians with recommendations on how to use and interpret this measure in practice to guide clinical decisions and improve patient outcomes

Development and Validity of a Workplace Health Promotion Best Practices Assessment

Objective: To explore the factor structure of the HERO Health and Well-being Best Practices Scorecard in Collaboration with Mercer (HERO Scorecard) to develop a reduced version and examine the reliability and validity of that version. Methods: A reduced version of the HERO Scorecard was developed through formal statistical analyses on data collected from 845 organizations that completed the original HERO Scorecard. Results: The final factors in the reduced Scorecard represented content pertaining to organizational and leadership support, program comprehensiveness, program integration, and incentives. All four implemented practices were found to have a strong, statistically significant effect on perceived effectiveness. Organizational and leadership support had the strongest effect (β = 0.56), followed by incentives (β = 0.23). Conclusion: The condensed version of the HERO Scorecard has the potential to be a promising tool for future research on the extent to which employers are adopting best practices in their health and well-being (HWB) initiatives

The Association between the Change in Directly Measured Cardiorespiratory Fitness across Time and Mortality Risk

Background The relationship between cardiorespiratory fitness (CRF) and mortality risk has typically been assessed using a single measurement, though some evidence suggests the change in CRF over time influences risk. This evidence is predominantly based on studies using estimated CRF (CRFe). The strength of this relationship using change in directly measured CRF over time in apparently healthy men and women is not well understood. Purpose To examine the association of change in CRF over time, measured using cardiopulmonary exercise testing (CPX), with all-cause and disease-specific mortality and to compare baseline and subsequent CRF measurements as predictors of all-cause mortality. Methods Participants included 833 apparently healthy men and women (42.9 ± 10.8 years) who underwent two maximal CPXs, the second CPX being ≥1 year following the baseline assessment (mean 8.6 years, range 1.0 to 40.3 years). Participants were followed for up to 17.7 (SD 11.8) years for all-cause-, cardiovascular disease- (CVD), and cancer mortality. Cox-proportional hazard models were performed to determine the association between the change in CRF, computed as visit 1 (CPX1) peak oxygen consumption (VO2peak [mL·kg−1·min−1]) – visit 2 (CPX2) VO2peak, and mortality outcomes. A Wald-Chi square test of equality was used to compare the strength of CPX1 to CPX2 VO2peak in predicting mortality. Results During follow-up, 172 participants died. Overall, the change in CPX-CRF was inversely related to all-cause, CVD, and cancer mortality (p < 0.05). Each 1 mL·kg−1·min−1 increase was associated with a ~11, 15, and 16% (all p < 0.001) reduction in all-cause, CVD, and cancer mortality, respectively. The inverse relationship between CRF and all-cause mortality was significant (p < 0.05) when men and women were examined independently, after adjusting for years since first CPX, baseline VO2peak, and age. Further, the Wald Chi-square test of equality found CPX2 VO2peak to be a significantly stronger predictor of all-cause mortality than CPX1 VO2peak (p < 0.05). Conclusion The change in CRF over time was inversely related to mortality outcomes, and mortality was better predicted by CRF measured at subsequent test than CPX1 CRF. These findings emphasize the importance of adopting lifestyle behaviors that promote CRF, as well as support the need for routine assessment of CRF in clinical practice to better assess risk

The Influence of Change in Cardiorespiratory Fitness With Short-Term Exercise Training on Mortality Risk From The Ball State Adult Fitness Longitudinal Lifestyle Study

Objective To assess the influence of changes in cardiorespiratory fitness (CRF) after exercise training on mortality risk in a cohort of self-referred, apparently healthy adults. Patients and Methods A total of 683 participants (404 men, 279 women; mean age: 42.7±11.0 y) underwent two maximal cardiopulmonary exercise tests (CPX) between March 20, 1970, and December 11, 2012, to assess CRF at baseline (CPX1) and post-exercise training (CPX2). Participants were followed for an average of 29.8±10.7 years after their CPX2. Cox proportional hazards models were performed to determine the relationship of CRF change with mortality, with change in CRF as a continuous variable, as well as a categorical variable. A Wald chi-square test was used to compare the coefficients estimating the relationship of peak oxygen consumption (VO2peak) at CPX1 with VO2peak measured at CPX2 with time until death for all-cause mortality. Results During the follow-up period there were 180 deaths. When assessed independently, there were 20% (95% CI, 10–49%) and 38% (95% CI, 7–66%) lower mortality risks per 1 metabolic equivalent improvement in CRF (P\u3c.01) in men and women, respectively, after multivariable adjustment. Those that remained unfit had ∼2-fold higher risk for all-cause mortality compared with those that remained fit and CRF at CPX2 was a stronger predictor of all-cause mortality than at CPX1 (P=.02). Conclusion Improving CRF through exercise training lowers mortality risk. Clinicians should encourage individuals to participate in exercise training to improve CRF to lower risk of mortality