SCOTS PINE (PINUS SYLVESTRIS L.) RESPONSE TO CLIMATE CHANGES AND THINNING ACTIVITIES: A TREE-RING STUDY FROM SOUTH-EAST RILA MOUNTAIN, BULGARIA

Abstract As a result of the study, the Scots pine (Pinus sylvestris L.) local chronology in 'Vasil Serafimov' Ecological Station (Southeast Rila Mountains, Bulgaria) was extended with 21 years, till 2008. A significant relationship (α < 0.01) was ascertained between tree-growth indices (ITR) of the Scots pine and precipitation indices (IP), temperature indices (IT) and presence of Norway spruce (Picea abies (L.) Karst) understorey (SU). Initially, pine decreased its radial growth rate as a consequence of the drought started in 1993. Removal of Spruce understorey in the middle of the dry period (1995), however, positively influenced Scots pine radial growth since 1997. The cooler and wetter years from 2001 to the end of the studied period resulted in increased growth rate for the pine

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Impact of Diabetes Mellitus and Chronic Kidney Disease on Cardiovascular Outcomes and Platelet P2Y(12) Receptor Antagonist Effects in Patients With Acute Coronary Syndromes : Insights From the PLATO Trial

Background-There are limited data on how the combination of diabetes mellitus (DM) and chronic kidney disease (CKD) affects cardiovascular outcomes as well as response to different P2Y(12) receptor antagonists, which represented the aim of the present investigation. Methods and Results-In this post hoc analysis of the PLATO (Platelet Inhibition and Patient Outcomes) trial, which randomized acute coronary syndrome patients to ticagrelor versus clopidogrel, patients (n=15 108) with available DM and CKD status were classified into 4 groups: DM+/CKD+ (n=1058), DM+/CKD- (n=2748), DM-/CKD+ (n=2160), and DM-/CKD- (n=9142). The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or stroke at 12 months. The primary safety end point was PLATO major bleeding. DM+/CKD+ patients had a higher incidence of the primary end point compared with DM-/CKD- patients (23.3% versus 7.1%; adjusted hazard ratio 2.22; 95% CI 1.88-2.63; P Conclusions-In acute coronary syndrome patients, a gradient of risk was observed according to the presence or absence of DM and CKD, with patients having both risk factors at the highest risk. Although the ischemic benefit of ticagrelor over clopidogrel was consistent in all subgroups, the absolute risk reduction was greatest in patients with both DM and CKD.Peer reviewe

Comparative study on the oxidative stress of commercially important fish species from localities with different ecological conditions along the Bulgarian Black Sea coast

The aim of the present study was to perform a pilot assessment and analysis of the oxidative stress (OS) level in four commercially important fish species (round goby, red mullet, sprat and horse mackerel) from different localities of the Bulgarian Black Sea coast. The fish were sampled during trawl selectivity experiments. The OS level in the fish was assessed by measuring lipid peroxidation (LPO), glutathione concentration (GSH), activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST), as well as acetylcholine esterase (AChE) in gills and liver. Round goby and red mullet caught in the Nessebar Bay showed clear signs of OS with the highest levels of LPO and GST activities, accompanied by the lowest AChE activities in both liver and gills. On the contrary, round goby caught near Maslen Nos (a region with good ecological conditions) were least affected by OS with low LPO and high GSH concentrations and SOD activity. There were no significant differences in the OS bioindicators of horse mackerel from the different localities. Sprat caught in Nessebar Bay, compared to those caught from the other localities, showed presence of OS indicated by lower GSH levels and relatively higher CAT, GPx and GST activities, accompanied by low AChE activity in gills. It can be concluded that round goby and red mullet were more vulnerable to OS induced by marine environmental factors than the horse mackerel and sprat. However, their antioxidant defense system allows them to tolerate and adapt to the environment of their habitats. Further studies are needed for the assessment of OS in important fish species in the Bulgarian part of the Black Sea

Ticagrelor Versus Clopidogrel in Patients With Acute Coronary Syndromes and a History of Stroke or Transient Ischemic Attack

Background-Patients with acute coronary syndromes and history of stroke or transient ischemic attack (TIA) have an increased rate of recurrent cardiac events and intracranial hemorrhages. Methods and Results-We evaluated treatment effects of ticagrelor versus clopidogrel in patients with acute coronary syndrome with and without a history of prior stroke or TIA in the PLATelet inhibition and patient Outcomes (PLATO) trial. Of the 18 624 randomized patients, 1152 (6.2%) had a history of stroke or TIA. Such patients had higher rates of myocardial infarction (11.5% versus 6.0%), death (10.5% versus 4.9%), stroke (3.4% versus 1.2%), and intracranial bleeding (0.8% versus 0.2%) than patients without prior stroke or TIA. Among patients with a history of stroke or TIA, the reduction of the primary composite outcome and total mortality at 1 year with ticagrelor versus clopidogrel was consistent with the overall trial results: 19.0% versus 20.8% (hazard ratio, 0.87; 95% confidence interval, 0.66-1.13; interaction P=0.84) and 7.9% versus 13.0% (hazard ratio, 0.62; 95% confidence interval, 0.42-0.91). The overall PLATO-defined bleeding rates were similar: 14.6% versus 14.9% (hazard ratio, 0.99; 95% confidence interval, 0.71-1.37), and intracranial bleeding occurred infrequently (4 versus 4 cases, respectively). Conclusions-Patients with acute coronary syndrome with a prior history of ischemic stroke or TIA had higher rates of clinical outcomes than patients without prior stroke or TIA. However, the efficacy and bleeding results of ticagrelor in these high-risk patients were consistent with the overall trial population, with a favorable clinical net benefit and associated impact on mortality.AstraZenecaAstraZenecaEli LillyEli LillyMerckMerckBristolMyers SquibbBristol-Myers SquibbEli Lilly/Daiichi SankyoEli Lilly/Daiichi SankyoAccumetricsAccumetricsDynabyteDynabyteNovartisNovartisEisaiEisaiBayerBayerBoehringer IngelheimBoehringer IngelheimGlaxoSmithKlineGlaxoSmithKlineJohnson and JohnsonJohnson and JohnsonOrtho/McNeillOrtho/McNeillSanofi-aventisSanofiAventisDaiichi SankyoDaiichi SankyoPortola PharmaceuticalsPortola PharmaceuticalsPozenPozenRegado BiosciencesRegado BiosciencesMedicines CompanyMedicines CompanyMSDMSDJaba RecordatiJaba RecordatiPfizerPfize

Effects of anthropogenic and environmental stressors on the current status of red mullet (Mullus barbatus L., 1758) populations inhabiting the Bulgarian Black Sea waters

The red mullet (Mullus barbatus Linnaeus, 1758) is a keynote species for the Bulgarian Black Sea ecosystem and fisheries; nevertheless, existing knowledge on population status is very scarce. The present study was intended to assess the health status and adaptive potential of M. barbatus populations inhabiting the Bulgarian waters of the Black Sea. Our findings revealed that populations of M. barbatus are exposed to a variety of anthropogenic and environmental stressors. The species’ status was assessed using representative genetic, morphological, biochemical and chemical biomarkers from specimens obtained in the research area’s northern and southern regions. Based on mtDNA markers, genetic analysis revealed low haplotype and nucleotide diversity, typically observed in overexploited or “threatened” populations. Examining the morphology of the specimens revealed no discernible pattern of differentiation. Except for aluminium and chrome, metal and PAH concentrations in fish were below the regulatory thresholds. The specimens from the southern region ingested more microplastics than those from the northern region. The majority of specimens collected from the southern region also exhibited elevated levels of oxidative stress and decreased antioxidant defence, which can be interpreted as an early indication that they had reached the limits of their adaptive potential. Further research on the composite effects of the stressogenic environment on the Black Sea biota are critically needed, as well as the introduction of new indicators and thresholds at molecular and cellular levels for adequate monitoring of both the ecological state of the marine environment and its biota

Comparison of Dabigatran Plus a P2Y(12) Inhibitor With Warfarin-Based Triple Therapy Across Body Mass Index in RE-DUAL PCI

BACKGROUND: Body mass index (BMI) affects drug levels of nonvitamin K antagonist oral anticoagulants. We sought to assess whether BMI affected outcomes in the RE-DUAL PCI trial. METHODS: RE-DUAL PCI (NCT02164864) evaluated the safety and efficacy of a dual-antithrombotic-therapy regimen using dabigatran (110 mg or 150 mg twice daily and a P2Y12 platelet antagonist) in comparison with triple therapy of warfarin, aspirin, and a P2Y12 platelet inhibitor in 2725 patients with atrial fibrillation who had undergone percutaneous coronary intervention (PCI). We compared the risk of first International Society on Thrombosis and Haemostasis (ISTH)-defined major or clinically relevant nonmajor bleeding events (primary endpoint) and the composite of death, myocardial infarction, stroke, systemic embolism, or unplanned revascularization (main efficacy endpoint) in relation to baseline BMI. RESULTS: Median (range) BMI was 28.1 (14-66) kg/m2. Dabigatran dual therapy versus warfarin triple therapy had relevantly and similarly lower rates of bleeding at both 110 mg and 150 mg twice-daily doses, irrespective of BMI. Thromboembolic event rates appeared consistent across categories of BMI, including those <25 and ≥35 kg/m2 (P for interaction: 0.806 and 0.279, respectively). CONCLUSIONS: The reduction in bleeding with dabigatran dual therapy compared with warfarin triple therapy in patients here evaluated appears consistent across BMI categories

Antithrombotic Therapy in Patients With Atrial Fibrillation and Acute Coronary Syndrome Treated Medically or With Percutaneous Coronary Intervention or Undergoing Elective Percutaneous Coronary Intervention: Insights From the AUGUSTUS Trial.

BACKGROUND The safety and efficacy of antithrombotic regimens may differ between patients with atrial fibrillation who have acute coronary syndromes (ACS), treated medically or with percutaneous coronary intervention (PCI), and those undergoing elective PCI. METHODS Using a 2×2 factorial design, we compared apixaban with vitamin K antagonists and aspirin with placebo in patients with atrial fibrillation who had ACS or were undergoing PCI and were receiving a P2Y12 inhibitor. We explored bleeding, death and hospitalization, as well as death and ischemic events, by antithrombotic strategy in 3 prespecified subgroups: patients with ACS treated medically, patients with ACS treated with PCI, and those undergoing elective PCI. RESULTS Of 4614 patients enrolled, 1097 (23.9%) had ACS treated medically, 1714 (37.3%) had ACS treated with PCI, and 1784 (38.8%) had elective PCI. Apixaban compared with vitamin K antagonist reduced International Society on Thrombosis and Haemostasis major or clinically relevant nonmajor bleeding in patients with ACS treated medically (hazard ratio [HR], 0.44 [95% CI, 0.28-0.68]), patients with ACS treated with PCI (HR, 0.68 [95% CI, 0.52-0.89]), and patients undergoing elective PCI (HR, 0.82 [95% CI, 0.64-1.04]; Pinteraction=0.052) and reduced death or hospitalization in the ACS treated medically (HR, 0.71 [95% CI, 0.54-0.92]), ACS treated with PCI (HR, 0.88 [95% CI, 0.74-1.06]), and elective PCI (HR, 0.87 [95% CI, 0.72-1.04]; Pinteraction=0.345) groups. Compared with vitamin K antagonists, apixaban resulted in a similar effect on death and ischemic events in the ACS treated medically, ACS treated with PCI, and elective PCI groups (Pinteraction=0.356). Aspirin had a higher rate of bleeding than did placebo in patients with ACS treated medically (HR, 1.49 [95% CI, 0.98-2.26]), those with ACS treated with PCI (HR, 2.02 [95% CI, 1.53-2.67]), and those undergoing elective PCI (HR, 1.91 [95% CI, 1.48-2.47]; Pinteraction=0.479). For the same comparison, there was no difference in outcomes among the 3 groups for the composite of death or hospitalization (Pinteraction=0.787) and death and ischemic events (Pinteraction=0.710). CONCLUSIONS An antithrombotic regimen consisting of apixaban and a P2Y12 inhibitor without aspirin provides superior safety and similar efficacy in patients with atrial fibrillation who have ACS, whether managed medically or with PCI, and those undergoing elective PCI compared with regimens that include vitamin K antagonists, aspirin, or both. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT02415400