Characterisation of the immune response to type I collagen in scleroderma

This study was conducted to examine the frequency, phenotype, and functional profile of T lymphocytes that proliferate in response to type I collagen (CI) in patients with scleroderma (SSc). Peripheral blood mononuclear cells (PBMCs) from SSc patients, healthy controls, and rheumatoid arthritis disease controls were labeled with carboxy-fluorescein diacetate, succinimidyl ester (CFSE), cultured with or without antigen (bovine CI) for 14 days, and analysed by flow cytometry. Surface markers of proliferating cells were identified by multi-color flow cytometry. T-cell lines were derived after sorting for proliferating T cells (CFSE(low)). Cytokine expression in CI-responsive T cells was detected by intracellular staining/flow cytometry and by multiplex cytokine bead assay (Bio-Plex). A T-cell proliferative response to CI was detected in 8 of 25 (32%) SSc patients, but was infrequent in healthy or disease controls (3.6%; p = 0.009). The proliferating T cells expressed a CD4(+), activated (CD25(+)), memory (CD45RO(+)) phenotype. Proliferation to CI did not correlate with disease duration or extent of skin involvement. T-cell lines were generated using in vitro CI stimulation to study the functional profile of these cells. Following activation of CI-reactive T cells, we detected intracellular interferon (IFN)-γ but not interleukin (IL)-4 by flow cytometry. Supernatants from the T-cell lines generated in vitro contained IL-2, IFN-γ, GM-CSF (granulocyte macrophage-colony-stimulating factor), and tumour necrosis factor-α, but little or no IL-4 and IL-10, suggesting that CI-responsive T cells express a predominantly Th1 cytokine pattern. In conclusion, circulating memory CD4 T cells that proliferate to CI are present in a subset of patients with SSc, but are infrequent in healthy or disease controls

Bone mineral density and risk of heart failure in older adults: The Cardiovascular Health Study

Background Despite increasing evidence of a common link between bone and heart health, the relationship between bone mineral density ( BMD ) and heart failure ( HF ) risk remains insufficiently studied. Methods and Results We investigated whether BMD measured by dual‐energy x‐ray absorptiometry was associated with incident HF in an older cohort. Cox models were stratified by sex and interactions of BMD with race assessed. BMD was examined at the total hip and femoral neck separately, both continuously and by World Health Organization categories. Of 1250 participants, 442 (55% women) developed HF during the median follow‐up of 10.5 years. In both black and nonblack women, neither total hip nor femoral neck BMD was significantly associated with HF ; there was no significant interaction by race. In black and nonblack men, total hip, but not femoral neck, BMD was significantly associated with HF , with evidence of an interaction by race. In nonblack men, lower total hip BMD was associated with higher HF risk (hazard ratio, 1.13 [95% CI, 1.01–1.26] per 0.1 g/cm 2 decrement), whereas in black men, lower total hip BMD was associated with lower HF risk (hazard ratio, 0.74 [95% CI, 0.59–0.94]). There were no black men with total hip osteoporosis. Among nonblack men, total hip osteoporosis was associated with higher HF risk (hazard ratio, 2.83 [95% CI, 1.39–5.74]) compared with normal BMD . Conclusions Among older adults, lower total hip BMD was associated with higher HF risk in nonblack men but lower risk in black men, with no evidence of an association in women. Further research is needed to replicate these findings and to study potential underlying pathways. </jats:sec

Antiepileptic Drug Use, Falls, Fractures, and BMD in Postmenopausal Women: Findings From the Women's Health Initiative (WHI)

Antiepileptic drugs (AEDs) are used increasingly in clinical practice to treat a number of conditions. However, the relationship between the use of these medications, particularly the newer AEDs, and fracture risk has not been well characterized. We used data from the Women's Health Initiative (WHI) to determine the relationship bewteen the use of AEDs and falls, fractures, and bone mineral density (BMD) over an average of 7.7 years of follow-up. We included 138,667 women (1,385 users of AEDs and 137,282 nonusers) aged 50 to 79 years in this longitudinal cohort analyses. After adjustment for covariates, use of AEDs was positively associated with total fractures [hazard ratio (HR) = 1.44, 95% confidence interval (CI) 1.30–1.61], all site-specific fractures including the hip (HR = 1.51, 95% CI 1.05–2.17), clinical vertebral fractures (HR = 1.60, 95% CI 1.20–2.12), lower arm or wrist fractures (HR = 1.40, 95% CI 1.11–1.76), and other clinical fractures (HR = 1.46, 95% CI 1.29–1.65) and two or more falls (HR = 1.62, 95% CI 1.50–1.74) but not with baseline BMD or changes in BMD (p ≥ .064 for all sites). Use of more than one and use of enzyme-inducing AEDs were significantly associated with total fractures (HR = 1.55, 95% CI 1.15–2.09 and HR = 1.36, 95% CI 1.09–1.69, respectively). We conclude that in clinical practice, postmenopausal women who use AEDs should be considered at increased risk for fracture, and attention to fall prevention may be particularly important in these women. © 2010 American Society for Bone and Mineral Research

Urinary Tract Stones and Osteoporosis: Findings From the Women's Health Initiative

Kidney and bladder stones (urinary tract stones) and osteoporosis are prevalent, serious conditions for postmenopausal women. Men with kidney stones are at increased risk of osteoporosis; however, the relationship of urinary tract stones to osteoporosis in postmenopausal women has not been established. The purpose of this study was to determine whether urinary tract stones are an independent risk factor for changes in bone mineral density (BMD) and incident fractures in women in the Women's Health Initiative (WHI). Data were obtained from 150,689 women in the Observational Study and Clinical Trials of the WHI with information on urinary tract stones status: 9856 of these women reported urinary tract stones at baseline and/or incident urinary tract stones during follow‐up. Cox regression models were used to determine the association of urinary tract stones with incident fractures and linear mixed models were used to investigate the relationship of urinary tract stones with changes in BMD that occurred during WHI. Follow‐up was over an average of 8 years. Models were adjusted for demographic and clinical factors, medication use, and dietary histories. In unadjusted models there was a significant association of urinary tract stones with incident total fractures (HR 1.10; 95% CI, 1.04 to 1.17). However, in covariate adjusted analyses, urinary tract stones were not significantly related to changes in BMD at any skeletal site or to incident fractures. In conclusion, urinary tract stones in postmenopausal women are not an independent risk factor for osteoporosis. © 2015 American Society for Bone and Mineral Research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/115895/1/jbmr2553.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/115895/2/jbmr2553_am.pd

Detection of bcl-2 rearrangement in mucosa-associated lymphoid tissue lymphomas from patients with hepatitis C virus infection

Lette

Search for 14.4 keV solar axions from M1 transition of Fe-57 with CUORE crystals

We report the results of a search for axions from the 14.4 keV M1 transition from Fe-57 in the core of the sun using the axio-electric effect in TeO2 bolometers. The detectors are 5x5x5 cm3 crystals operated at about 10 mK in a facility used to test bolometers for the CUORE experiment at the Laboratori Nazionali del Gran Sasso in Italy. An analysis of 43.65 kg d of data was made using a newly developed low energy trigger which was optimized to reduce the detectors energy threshold. An upper limit of 0.63 c kg-1 d-1 was established at 95% C.L.. From this value, a lower bound at 95% C.L. was placed on the Peccei-Quinn energy scale of fa >= 0.76 10**6 GeV for a value of S=0.55 for the flavor-singlet axial vector matrix element. Bounds are given for the interval 0.15 < S < 0.55.Comment: 14 pages, 6 figures, submitted to JCA

Validation of techniques to mitigate copper surface contamination in CUORE

In this article we describe the background challenges for the CUORE experiment posed by surface contamination of inert detector materials such as copper, and present three techniques explored to mitigate these backgrounds. Using data from a dedicated test apparatus constructed to validate and compare these techniques we demonstrate that copper surface contamination levels better than 10E-07 - 10E-08 Bq/cm2 are achieved for 238U and 232Th. If these levels are reproduced in the final CUORE apparatus the projected 90% C.L. upper limit on the number of background counts in the region of interest is 0.02-0.03 counts/keV/kg/y depending on the adopted mitigation technique.Comment: 10 pages, 6 figures, 6 table

Fracture Risk in Men With Congestive Heart Failure Risk Reduction With Spironolactone

ObjectivesThe purpose of this study was to determine whether spironolactone use is associated with fractures in men with congestive heart failure (CHF).BackgroundIn rats with aldosteronism, spironolactone preserves skeletal strength. However, in humans, the relationship of spironolactone to fractures is not known.MethodsThe medical records of all male patients with CHF from 1999 to 2005 treated at the Veterans Affairs Medical Center, Memphis, Tennessee, were reviewed (n = 4,735). Odds ratios with 95% confidence intervals of having a fracture associated with spironolactone use were estimated using conditional logistic regression.ResultsWe identified 167 cases with a single-incident fracture and matched these by age and race to 668 control subjects without fractures. After adjustment for covariates, spironolactone use was inversely associated with total fracture (odds ratio: 0.575; 95% confidence interval: 0.346 to 0.955, p = 0.0324).ConclusionsThe use of spironolactone is inversely associated with fractures in men with CHF

Jaguar Densities across Human-Dominated Landscapes in Colombia: The Contribution of Unprotected Areas to Long Term Conservation

Large carnivores such as jaguars (Panthera onca) are species of conservation concern because they are suffering population declines and are keystone species in their ecosystems. Their large area requirements imply that unprotected and ever-increasing agricultural regions can be important habitats as they allow connectivity and dispersal among core protected areas. Yet information on jaguar densities across unprotected landscapes it is still scarce and crucially needed to assist management and range-wide conservation strategies. Our study provides the first jaguar density estimates of Colombia in agricultural regions which included cattle ranching, the main land use in the country, and oil palm cultivation, an increasing land use across the Neotropics. We used camera trapping across two agricultural landscapes located in the Magdalena River valley and in the Colombian llanos (47–53 stations respectively; >2000 trap nights at both sites) and classic and spatially explicit capture-recapture models with the sex of individuals as a covariate. Density estimates were 2.52±0.46–3.15±1.08 adults/100 km2 in the Magdalena valley, whereas 1.12±0.13–2.19±0.99 adults/100 km2 in the Colombian llanos, depending on analysis used. We suggest that jaguars are able to live across unprotected human-use areas and co-exist with agricultural landscapes including oil-palm plantations if natural areas and riparian habitats persist in the landscape and hunting of both jaguar and prey is limited. In the face of an expanding agriculture across the tropics we recommend land-use planning, adequate incentives, regulations, and good agricultural practices for range-wide jaguar connectivity and survival