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

Rheostatic Control of ABA Signaling through HOS15-Mediated OST1 Degradation

Dehydrating stresses trigger the accumulation of abscisic acid (ABA), a key plant stress-signaling hormone that activates Snf1-Related Kinases (SnRK2s) to mount adaptive responses. However, the regulatory circuits that terminate the SnRK2s signal relay after acclimation or post-stress conditions remain to be defined. Here, we show that the desensitization of the ABA signal is achieved by the regulation of OST1 (SnRK2.6) protein stability via the E3-ubiquitin ligase HOS15. Upon ABA signal, HOS15-induced degradation of OST1 is inhibited and stabilized OST1 promotes the stress response. When the ABA signal terminates, protein phosphatases ABI1/2 promote rapid degradation of OST1 via HOS15. Notably, we found that even in the presence of ABA, OST1 levels are also depleted within hours of ABA signal onset. The unexpected dynamics of OST1 abundance are then resolved by systematic mathematical modeling, demonstrating a desensitizing feedback loop by which OST1-induced upregulation of ABI1/2 leads to the degradation of OST1. This model illustrates the complex rheostat dynamics underlying the ABA-induced stress response and desensitization.This work demonstrates that HOS15 negatively regulates ABA signaling by interacting with and affecting OST1 protein stability, which leads to controlled turnover of ABA signaling and drought-stress response

Palynology and correlation of the Upper Pennsylvanian Tobra Formation from Zaluch Nala, Salt Range, Pakistan

Samples from the upper 84 m of a 125 m thick section of the Tobra Formation at Zaluch Nala, western Salt Range, Pakistan yielded palynomorph taxa including the spores Horriditriletes sp. and Microbaculispora tentula, abundant monosaccate pollen including Barakarites cf. rotatus, Cannanoropollis janakii and Plicatipollenites malabarensis, and rare taeniate and non-taeniate bisaccate pollen. Converrucosisporites grandegranulatus, Cycadopites cymbatus, Horriditriletes ramosus, Horriditriletes tereteangulatus and Microbaculispora tentula indicate the South Oman 2165B Biozone (Late Pennsylvanian), suggesting that the Tobra Formation in Zaluch Nala is equivalent to the middle part of the Al Khlata Formation of South Oman (Petroleum Development Oman (PDO) Al Khlata production unit AK P5). Brevitriletes leptoacaina, Brevitriletes parmatus, Horriditriletes ramosus and Microbaculispora tentula indicate the lower part of the Oman and Saudi Arabia Palynological Zone 2 (OSPZ2). The Tobra Formation assemblages are also correlated with those from Stage 2 and the eastern Australian Microbaculispora tentula Oppel-zone, based on the occurrence of Brevitriletes cornutus, Brevitriletes parmatus, Cycadopites cymbatus, Horriditriletes ramosus, Horriditriletes tereteangulatus and Microbaculispora tentula. The Tobra Formation in Zaluch Nala lacks the deglaciation sequence that is present in several other palaeogeographically nearby basins such as those of south Arabia and Western Australia. This is an indication of either non-deposition during the deglaciation period or erosion associated with the unconformity between the Tobra Formation and the overlying Warchha Formation