Mitochondrial encephalomyopathies are a heterogenous group of disorders with various biochemical defects of the respiratory chain (RC). Due to the considerable phenotypic diversity of the RC ...encephalomyopathies, they are included in the differential diagnosis of many cases of multisystem disease. Aside from clinical evaluation and family history, diagnosis can be supported by many other sources. The complexity of diagnostic information can make it difficult for the clinician to establish the level of certainty at which a RC cytopathy is diagnosed in atypical cases. We review the parameters (clinical, pathological, biochemical and molecular) which are used to aid diagnosis of RC encephalomyopathy and identify levels of abnormality in each that strongly or less strongly support the diagnosis. A system is developed that allows classification of the diagnosis in possible, probable and definite categories of certainty, which will be of value to the clinician.
Interferential current (IFC) was suggested to improve the skin manifestations of psoriasis vulgaris, possibly by enhancing the intracellular concentration of cyclic AMP. We assessed the efficacy of ...IFC on psoriatic arthritis (PsA). Nine consecutive patients were analyzed at baseline and after 16 weeks of IFC therapy. Bipolar IFC was applied twice daily to hands, feet plus all affected joints. IFC improved SF-36 assessed body pain, but not other SF-36 subscales. Morning stiffness, tender joint counts, and physician assessed disease activity improved. In contrast, visual analogue scale assessed pain, CRP and ESR measurements were unchanged. MRI of the most affected hand or foot documented a tendency towards worsened tendinitis, soft tissue swelling, and new joint space narrowing and erosions. Bone scintigraphy showed a trend towards deterioration. New joints became inflamed within treated sites. Thus IFC has analgesic effects in PsA, but does not have a satisfactory disease modifying effect.
To define the specificity and extent of duplex sonography (DS) findings suggestive of vessel wall inflammation in patients with giant cell arteritis (GCA).
Patients admitted between December 2006 and ...April 2009 to the University Hospital Basel with a suspicion of GCA were eligible for the study. DS of 2x11 arterial regions was performed in all study participants, and American College of Rheumatology criteria were applied to classify patients into GCA or non-GCA groups.
GCA was diagnosed in 38 of the 72 participants (53%). A DS pattern suggestive of vessel wall inflammation was not observed in any of the patients in the non-GCA group but, in 21 of the 38 patients with GCA (55%), DS signs suggestive of vessel wall inflammation of > or =1 vessel region were detected. In 12 of the 38 patients with GCA (32%), DS signs of large vessel vasculitis (LVV) were found in > or =1 vessel region(s) of both upper and lower limb vessels. Follow-up DS was performed 6 months after the baseline examination in 9 of the 12 patients with LVV and showed the persistence of most findings despite normalised signs of systemic inflammation.
DS detects changes in the vessel wall that appear to be specific for GCA; they can be present in upper and lower limb arteries of patients with GCA. Surprisingly, DS-detectable LVV and signs of systemic inflammation are largely dissociated.
OBJECTIVE Recent genome-wide association studies have revealed loci associated with glucose and insulin-related traits. We aimed to characterize 19 such loci using detailed measures of insulin ...processing, secretion, and sensitivity to help elucidate their role in regulation of glucose control, insulin secretion and/or action. RESEARCH DESIGN AND METHODS We investigated associations of loci identified by the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) with circulating proinsulin, measures of insulin secretion and sensitivity from oral glucose tolerance tests (OGTTs), euglycemic clamps, insulin suppression tests, or frequently sampled intravenous glucose tolerance tests in nondiabetic humans (n = 29,084). RESULTS The glucose-raising allele in MADD was associated with abnormal insulin processing (a dramatic effect on higher proinsulin levels, but no association with insulinogenic index) at extremely persuasive levels of statistical significance (P = 2.1 x 10(-71)). Defects in insulin processing and insulin secretion were seen in glucose-raising allele carriers at TCF7L2, SCL30A8, GIPR, and C2CD4B. Abnormalities in early insulin secretion were suggested in glucose-raising allele carriers at MTNR1B, GCK, FADS1, DGKB, and PROX1 (lower insulinogenic index; no association with proinsulin or insulin sensitivity). Two loci previously associated with fasting insulin (GCKR and IGF1) were associated with OGTT-derived insulin sensitivity indices in a consistent direction. CONCLUSIONS Genetic loci identified through their effect on hyperglycemia and/or hyperinsulinemia demonstrate considerable heterogeneity in associations with measures of insulin processing, secretion, and sensitivity. Our findings emphasize the importance of detailed physiological characterization of such loci for improved understanding of pathways associated with alterations in glucose homeostasis and eventually type 2 diabetes.
Background: Systemic sclerosis (SSc) is a multisystem autoimmune disease, which is classified into a diffuse cutaneous (dcSSc) and a limited cutaneous (lcSSc) subset according to the skin ...involvement. In order to better understand the vascular, immunological and fibrotic processes of SSc and to guide its treatment, the EULAR Scleroderma Trials And Research (EUSTAR) group was formed in June 2004. Aims and methods: EUSTAR collects prospectively the Minimal Essential Data Set (MEDS) on all sequential patients fulfilling the American College of Rheumatology diagnostic criteria in participating centres. We aimed to characterise demographic, clinical and laboratory characteristics of disease presentation in SSc and analysed EUSTAR baseline visits. Results: In April 2006, a total of 3656 patients (1349 with dcSSc and 2101 with lcSSc) were enrolled in 102 centres and 30 countries. 1330 individuals had autoantibodies against Scl70 and 1106 against anticentromere antibodies. 87% of patients were women. On multivariate analysis, scleroderma subsets (dcSSc vs lcSSc), antibody status and age at onset of Raynaud’s phenomenon, but not gender, were found to be independently associated with the prevalence of organ manifestations. Autoantibody status in this analysis was more closely associated with clinical manifestations than were SSc subsets. Conclusion: dcSSc and lcSSc subsets are associated with particular organ manifestations, but in this analysis the clinical distinction seemed to be superseded by an antibody-based classification in predicting some scleroderma complications. The EUSTAR MEDS database facilitates the analysis of clinical patterns in SSc, and contributes to the standardised assessment and monitoring of SSc internationally.
Coronagraphs are highly sensitive to wavefront errors, with performance degrading rapidly in the presence of low-order aberrations. Correcting these aberrations at the coronagraphic focal plane is ...key to optimal performance. We present two new methods based on the sequential phase diversity approach of the "Fast and Furious" algorithm that can correct low-order aberrations through a coronagraph. The first, called "2 Fast 2 Furious," is an extension of Fast and Furious to all coronagraphs with even symmetry. The second, "Tokyo Drift," uses a deep learning approach and works with general coronagraphic systems, including those with complex phase masks. Both algorithms have 100% science uptime and require effectively no diversity frames or additional hardware beyond the deformable mirror and science camera, making them suitable for many high contrast imaging systems. We present theory, simulations, and preliminary lab results demonstrating their performance.
On 2008 March 19, one of the brightest gamma-ray bursts (GRBs) ever recorded was detected by several ground-and space-based instruments spanning the electromagnetic spectrum from radio to gamma rays. ...With a peak visual magnitude of 5.3, GRB 080319B was dubbed the "naked-eye" GRB, as an observer under dark skies could have seen the burst without the aid of an instrument. Presented here are results from observations of the prompt phase of GRB 080319B taken with the Milagro TeV observatory. The burst was observed at an elevation angle of 47degrees Analysis of the data is performed using both the standard air shower method and the scaler or single-particle technique, which results in a sensitive energy range that extends from ~5 GeV to > 20 TeV. These observations provide the only direct constraints on the properties of the high-energy gamma-ray emission from GRB 080319B at these energies. No evidence for emission is found in the Milagro data, and upper limits on the gamma-ray flux above 10 GeV are derived. The limits on emission between ~25 and 200 GeV are incompatible with the synchrotron self-Compton model of gamma-ray production and disfavor a corresponding range (2 eV-16 eV) of assumed synchrotron peak energies. This indicates that the optical photons and soft (~650 keV) gamma rays may not be produced by the same electron population.
Fibromyalgia (FM) is a disorder characterised by diffuse widespread musculoskeletal aching and stiffness and multiple tender points 1. Its pathophysiology is poorly understood. The influence of ...aerobic endurance exercise on pain in patients with FM was investigated. Twenty-seven patients (25 female, 2 male) participated in a controlled clinical study and performed 12 weeks of jogging, walking, cycling or swimming following a given schedule. Twelve sedentary FM patients (11 female, 1 male) served as controls. Before and after training both the study and the control groups were evaluated spiroergometrically. Tender point pain was quantified by dolorimetry. The painful body surface was estimated by a pain body diagram, and its intensity by a visual analogue scale and a ranking scale. Patients trained for an average of 25 min two to three times a week, with an average intensity of 50% of maximal oxygen uptake (VO2max). Unlike the control group, the training group exhibited a decrease in heart rate and VO2 and an increase in respiratory quotient during submaximal workload. Maximal performance capacity and VO2max remained unchanged, whereas the wattpulse (watt/heart rate) improved at maximal workload. Pain parameters remained unchanged in the control group, but in the training group the mean number of positive tender points (15.4/12.7), the mean pain threshold of the gluteal tender point (2.89 kp/3.50 kp) and the painful body surface (18%/15% body surface) decreased significantly. Subjective general pain condition deteriorated in two patients but improved in 17. Our results suggest a positive effect of aerobic endurance exercise on fitness and well-being in patients with FM.
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