Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Photon beam asymmetry Sigma for eta and eta ' photoproduction from the proton

Measurements of the linearly-polarized photon beam asymmetry $\Sigma$ for photoproduction from the proton of $\eta$ and $\eta^\prime$ mesons are reported. A linearly-polarized tagged photon beam produced by coherent bremsstrahlung was incident on a cryogenic hydrogen target within the CEBAF Large Acceptance Spectrometer. Results are presented for the $\gamma p \to \eta p$ reaction for incident photon energies from 1.070 to 1.876 GeV, and from 1.516 to 1.836 GeV for the $\gamma p \to \eta^\prime p$ reaction. For $\gamma p \to \eta p$, the data reported here considerably extend the range of measurements to higher energies, and are consistent with the few previously published measurements for this observable near threshold. For $\gamma p \to \eta^\prime p$, the results obtained are consistent with the few previously published measurements for this observable near threshold, but also greatly expand the incident photon energy coverage for that reaction. Initial analysis of the data reported here with the Bonn-Gatchina model strengthens the evidence for four nucleon resonances -- the $N(1895)1/2^-$, $N(1900)3/2^+$, $N(2100)1/2^+$ and $N(2120)3/2^-$ resonances -- which presently lack the "four-star" status in the current Particle Data Group compilation, providing examples of how these new measurements help refine models of the photoproduction process.Comment: 10 pages, 3 figure

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Effects of anthocyanidins on myogenic differentiation and antioxidant defense in primary myogenic cells isolated from rainbow trout (Oncorhynchus mykiss)

There is increasing interest in using plant-derived extracts to promote growth and health in finfish species in recent years. Elucidating the effects of plant secondary metabolites on skeletal muscle growth signaling will contribute to an improved understanding of the effects of feeding carnivorous fish diets supplemented with plant extracts on fish somatic growth. Dietary intake of anthocyanins, a type of flavonoid widely distributed in plants, has long been associated with beneficial effects in both human and animal health; however, their effects in finfish are largely unknown. We conducted an experiment to test the effect of three doses (treatments A, B and C; 1. ×, 2.5. × and 10. ×, respectively) of a mixture of three types of anthocyanidins (peonidin, cyanidin and pelargonidin chloride) on the expression of several genes in primary myogenic cells isolated from the skeletal muscle of rainbow trout (Oncorhynchus mykiss) after 24. h of treatment. The genes of interest analyzed are involved in myogenic programing (pax7, myoD and myogenin), Notch signaling (her6 and hey2) and antioxidant enzymes (sod1, cat and gpx1). Significantly greater expression of pax7 in cells under treatment B compared with the untreated cells was detected. Although no differences in expression of myogenic regulatory factors, myoD and myogenin between test groups or the control were detected, a trend toward significantly lower expression in all groups tested compared with the control group was observed. Moreover, significantly higher expression levels of her6 and hey2 in cells under treatments A and B compared with untreated cells were detected. Although no significant differences in the expression of cat and sod1, significantly greater expression in gpx1 in all treated groups compared with the control group was detected. Collectively, we demonstrated that anthocyanidins enhance the expression of gpx1 in primary myogenic cells, thereby contributing to skeletal muscle tissue defense against oxidative stress in finfish species. Further, anthocyanidins appear to delay myogenic differentiation in primary myogenic cells by up-regulating the expression of pax7 while decreasing myogenic regulatory factors in a Notch signaling-dependent interaction. Whether this effect results a reduced growth performance and/or an increase in feed conversion ratio in fish fed diets supplemented with plant extracts rich in anthocyanins or anthocyanidins needs further study, and the need to better define the potential effects of different polyphenol classes in myogenic differentiation on primary myogenic cells from carnivorous fish is warranted. Statement of relevance: The study contributes to increase our understanding regarding the effect of plant-derived secondary metabolites such as anthocyanidins on myogenic program and antioxidant enzyme defense in differentiating myogenic cells from carnivorous fish. We have demonstrated that anthocyanidins may delay the progress of the myogenic differentiation process and promote antioxidant defense expression in myogenic cells. © 2015 Elsevier B.V

Clinical features, molecular heterogeneity, and prognostic implications in <em>YARS2</em>-related mitochondrial myopathy.

Importance: YARS2 mutations have been associated with a clinical triad of myopathy, lactic acidosis, and sideroblastic anemia in predominantly Middle Eastern populations. However, the identification of new patients expands the clinical and molecular spectrum of mitochondrial disorders. Objectives: To review the clinical, molecular, and genetic features of YARS2-related mitochondrial disease and to demonstrate a new Scottish founder variant. Design, Setting, and Participants: An observational case series study was conducted at a national diagnostic center for mitochondrial disease in Newcastle upon Tyne, England, and review of cases published in the literature. Six adults in a well-defined mitochondrial disease cohort and 11 additional cases described in the literature were identified with YARS2 variants between January 1, 2000, and January 31, 2015. Main Outcome and Measures: The spectrum of clinical features and disease progression in unreported and reported patients with pathogenic YARS2 variants. Results: Seventeen patients (median [interquartile range] age at onset, 1.5 [9.8] years) with YARS2-related mitochondrial myopathy were identified. Fifteen individuals (88%) exhibited an elevated blood lactate level accompanied by generalized myopathy; only 12 patients (71%) manifested with sideroblastic anemia. Hypertrophic cardiomyopathy (9 [53%]) and respiratory insufficiency (8 [47%]) were also prominent clinical features. Central nervous system involvement was rare. Muscle studies showed global cytochrome-c oxidase deficiency in all patients tested and severe, combined respiratory chain complex activity deficiencies. Microsatellite genotyping demonstrated a common founder effect shared between 3 Scottish patients with a p.Leu392Ser variant. Immunoblotting from fibroblasts and myoblasts of an affected Scottish patient showed normal YARS2 protein levels and mild respiratory chain complex defects. Yeast modeling of novel missense YARS2 variants closely correlated with the severity of clinical phenotypes. Conclusions and Relevance: The p.Leu392Ser variant is likely a newly identified founder YARS2 mutation. Testing for pathogenic YARS2 variants should be considered in patients presenting with mitochondrial myopathy, characterized by exercise intolerance and muscle weakness even in the absence of sideroblastic anemia irrespective of ethnicity. Regular surveillance and early treatment for cardiomyopathy and respiratory muscle weakness is advocated because early treatment may mitigate the significant morbidity and mortality associated with this genetic disorder