Background: Hand pain with stiffness is a common clinical presentation to early arthritis clinics, with outcome varying from resolution to the development of rheumatoid arthritis. Objective: To ...assess the response and predictors of response to intramuscular methylprednisolone (MP) and hydroxychloroquine (HCQ) using a standardised treatment protocol. Methods: Patients with inflammatory hand pain (IHP), defined as predominantly hand pain and morning stiffness of at least 30 min duration, received a standardised assessment prior to receiving intramuscular MP. Response (primary outcome) at 4 weeks was a 50% improvement in symptoms as perceived by the patient; responders who relapsed received repeat intramuscular MP and HCQ. Results: 102 patients were recruited, of which 21% were rheumatoid factor (RF) positive, 23% had clinical synovitis, 25% had raised C-reactive protein level and 55% had ultrasound-detected synovitis. 73% responded, with associated significant reductions in morning stiffness, Health Assessment Questionnaire, painful and tender joint counts, and visual analogue scores (p⩽0.006 for all). Ultrasound-detected synovitis (p<0.001) and RF (p = 0.04), but not clinical synovitis (p = 0.74), were significantly associated with response to intramuscular MP. 86% who remained on HCQ long term reported a benefit. Conclusions: Patients with IHP have significant improvement in symptoms and function following intramuscular MP. Further placebo-controlled trials are required to assess the role of intramuscular MP and ultrasonography in managing this patient group.
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Exposure to certain nanoparticles can cause fibrosis and cancer as a result of unresolved inflammation. Inflammation resolution is largely mediated through specialized pro‐resolving ...mediators (SPMs). To understand the mechanism by which nanoparticle‐induced pulmonary inflammation is resolved, we analyzed and compared the inflammatory and pro‐resolving responses to fibrogenic multi‐walled carbon nanotubes (MWCNTs) and low‐toxicity fullerenes (C60F). Pharyngeal aspiration of MWCNTs at 40 μg/mouse or C60F at doses larger than 640 μg/mouse elicited pulmonary effects in B6C3F1 mice. Histopathology showed that both particles stimulated acute inflammation, predominated by neutrophils and macrophages, in the lung on day 1, which transitioned to histiocytic inflammation by day 7, and to granuloma and interstitial fibrosis by day 28 in MWCNTs, and to a much lesser extent, C60F exposed mice. Flow cytometric profiling of bronchoalveolar lavage fluid (BALF) cells revealed that neutrophil infiltration peaked at day 1 and declined to 36.6% for MWCNTs‐ and 16.8% for C60F (1,280 μg/mouse)‐treated mice by day 7, and to basal levels by day 28 in both groups, suggesting a rapid initiation phase and an extended resolution phase in both groups. Additionally, MWCNTs stimulated dynamic changes in eosinophils, bone marrow‐derived inflammatory macrophages, monocyte‐derived dendritic cells, and T lymphocytes, indicating distinctive patterns of immune cell infiltration in the BAL in response to nanoparticles. MWCNTs stimulated high levels of pro‐inflammatory lipid mediators, including leukotriene B4 (LTB4) and prostaglandin E2 (PGE2), on day 1. At the same time, MWCNTs induced high levels of SPMs, including resolvin D1 (RvD1) and E1 (RvE1) and lipoxin A4 (LXA4), on day 1, which continued to rise and peaked on day 7, creating a high RvD1/LTB4 or RvD1/PGE2 ratio. C60F stimulated a similar pattern of changes in the mediators but to a much lesser extent. Together, these findings suggest that MWCNTs at a low dose and fullerenes at a high dose induce time‐dependent progression from type 1 to type 2 inflammation with an extended resolution phase mediated through SPMs.
Support or Funding Information
This work was funded by grant 09390BN5 (DWP and QM) and grant 09390BMX (QM) from the Health Effects Laboratory Division, the Nanotechnology Research Center, and the NORA Research Program at the National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, USA.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Klotho-VS heterozygosity (KL-VS
) is associated with reduced risk of Alzheimer's disease (AD). However, whether KL-VS
is associated with lower levels of pathologic tau, i.e., the key AD pathology ...driving neurodegeneration and cognitive decline, is unknown. Here, we assessed the interaction between KL-VS
and levels of beta-amyloid, a key driver of tau pathology, on the levels of PET-assessed neurofibrillary tau in 551 controls and patients across the AD continuum. KL-VS
showed lower cross-sectional and longitudinal increase in tau-PET per unit increase in amyloid-PET when compared to that of non-carriers. This association of KL-VS
on tau-PET was stronger in Klotho mRNA-expressing brain regions mapped onto a gene expression atlas. KL-VS
was related to better memory functions in amyloid-positive participants and this association was mediated by lower tau-PET. Amyloid-PET levels did not differ between KL-VS
carriers versus non-carriers. Together, our findings provide evidence to suggest a protective role of KL-VS
against amyloid-related tau pathology and tau-related memory impairments in elderly humans at risk of AD dementia.
The writing committee for each performance measure set is carefully guided with respect to the methodology of development of performance measures (1). ...to avoid duplication of performance measure ...development efforts, writing committees are also instructed to evaluate existing nationally recognized performance measures using the attributes of good performance measures specified by the ACC/AHA. ...it is within the scope of the writing committee's task to comment, when appropriate, on the strengths and limitations of such external reporting for a particular cardiovascular disease state or patient population.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The positron emission tomography (PET) imaging technique, which is utilized in human behavior and psychiatric disorder research, was performed on the brains of clinically normal mixed breed dogs, 3 ...hound-type (long floppy ears) mixed breed dogs and 3 non-hound retriever-type mixed breed dogs. Glucose metabolism was obtained with F-18 fluorodeoxyglucose (FDG), and quantitative analysis was performed by standardized uptake value (SUV) measurement. Magnetic resonance (MR) images were obtained in each dog, and these images were superimposed on PET images to identify anatomical locations. The glucose metabolism in each region of interest was compared between the three hound-type dogs and 3 non-hound-type dogs. The two anatomically different types of dog were compared to assess whether breed-typical behavioral tendencies (e.g., sniffing behavior in hound-type dogs, staring and retrieving in Labrador-type dogs) are reflected in baseline brain metabolic activity. There were no significant differences between the hound-type dogs and non-hound-type dogs in cerebral SUV values. These data might serve as normal canine cerebral metabolism data for FDG PET studies in dogs and form the basis for investigations into behavioral disorders in dogs such as compulsive disorder, anxiety disorders and cognitive dysfunction.
This study examined whether training under normobaric hypoxic conditions (simulating medium level altitude) would enhance physical performance and selected muscle adaptations over and above that ...which occurs with normoxic training. Ten healthy males (19-25 yr) underwent 8 wk of unilateral cycle ergometry training so that one leg was trained while breathing an inspirate of 13.5% O2 and the other while breathing normal ambient air. Pre- and post-training measurements included single leg VO2max and time to fatigue at 95% VO2max. Needle biopsies from quadriceps were assayed for oxidative and glycolytic enzyme activity and analyzed for capillary density, fiber area, % fiber type, and mitochondrial and lipid volume density. VO2max, time to fatigue, citrate synthase (CS), succinate dehydrogenase, and phosphofructokinase activity increased significantly (P > 0.05) in both legs following training. The increase in CS activity in the hypoxically trained leg was also significantly greater than that in the normoxically trained leg. It thus appears that training under moderate normobaric hypoxic conditions enhances muscle citrate synthase activity to a greater extent than training under normoxic conditions.
Colorectal cancer is the second leading cause of cancer death in developed countries. Genome-wide association studies (GWAS) have successfully identified novel susceptibility loci for colorectal ...cancer. To follow up on these findings, and try to identify novel colorectal cancer susceptibility loci, we present results for GWAS of colorectal cancer (2,906 cases, 3,416 controls) that have not previously published main associations. Specifically, we calculated odds ratios and 95% confidence intervals using log-additive models for each study. In order to improve our power to detect novel colorectal cancer susceptibility loci, we performed a meta-analysis combining the results across studies. We selected the most statistically significant single nucleotide polymorphisms (SNPs) for replication using ten independent studies (8,161 cases and 9,101 controls). We again used a meta-analysis to summarize results for the replication studies alone, and for a combined analysis of GWAS and replication studies. We measured ten SNPs previously identified in colorectal cancer susceptibility loci and found eight to be associated with colorectal cancer (
p
value range 0.02 to 1.8 × 10
−8
). When we excluded studies that have previously published on these SNPs, five SNPs remained significant at
p
< 0.05 in the combined analysis. No novel susceptibility loci were significant in the replication study after adjustment for multiple testing, and none reached genome-wide significance from a combined analysis of GWAS and replication. We observed marginally significant evidence for a second independent SNP in the
BMP2
region at chromosomal location 20p12 (rs4813802; replication
p
value 0.03; combined
p
value 7.3 × 10
−5
). In a region on 5p33.15, which includes the coding regions of the
TERT
-
CLPTM1L
genes and has been identified in GWAS to be associated with susceptibility to at least seven other cancers, we observed a marginally significant association with rs2853668 (replication
p
value 0.03; combined
p
value 1.9 × 10
−4
). Our study suggests a complex nature of the contribution of common genetic variants to risk for colorectal cancer.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Post-traumatic stress and disability Neal, Leigh A.; Green, Gillian; Turner, Mark A.
British journal of psychiatry,
03/2004, Volume:
184, Issue:
3
Journal Article
Peer reviewed
Open access
Post-traumatic stress is thought to account for significant disability. It is also known to be highly comorbid with other psychiatric conditions such as depression and alcohol dependence.
To ...determine the relationship between post-traumatic stress, depression, alcohol dependence and disability.
Seventy armed services personnel were assessed for DSM-IV diagnoses of post-traumatic stress disorder, major depressive disorder and alcohol dependence, and with continuous measures of symptoms of post-traumatic stress, depression and alcohol dependence following a traumatic event. These variables, as predictors of disability (using the Sheehan Disability Scale), were analysed using multivariate analysis of variance, analysis of covariance and multiple regression backward elimination models.
No significant interaction was found for the diagnostic variables even after controlling for the continuous symptom measures. In the regression models, symptoms of depression were a significant predictor of total disability (R(2)=0.39). Symptoms of alcohol dependence and post-traumatic stress did not significantly predict disability.
Since post-traumatic stress was not found to be associated with disability, its clinical importance may be questionable.
The Plutonium-238 (
238
Pu) Production program at Idaho National Laboratory (INL) is actively qualifying irradiation targets containing
237
Np for the Advanced Test Reactor (ATR) to produce
238
Pu ...for future National Aeronautics and Space Administration missions. INL qualified and loaded seven targets in the ATR's south flux trap for cycle 169A, which occurred in Spring 2021. The irradiation qualification program has expanded to additional ATR irradiation positions after two baseline production targets in three positions validated significant production of
238
Pu. The validation model was followed by the PFS-1 experimental test in the ATR Critical Facility that verified
238
Pu production cross sections. This paper outlines the progress and status of the
238
Pu production program at INL. The qualification effort, safety analysis, hardware status, and future activities for qualification of an updated target design for use in the ATR are discussed.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
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