The mechanisms of atrial fibrillation in hyperthyroidism

Atrial fibrillation (AF) is a complex condition with several possible contributing factors. The rapid and irregular heartbeat produced by AF increases the risk of blood clot formation inside the heart. These clots may eventually become dislodged, causing embolism, stroke and other disorders. AF occurs in up to 15% of patients with hyperthyroidism compared to 4% of people in the general population and is more common in men and in patients with triiodothyronine (T3) toxicosis. The incidence of AF increases with advancing age. Also, subclinical hyperthyroidism is a risk factor associated with a 3-fold increase in development of AF. Thyrotoxicosis exerts marked influences on electrical impulse generation (chronotropic effect) and conduction (dromotropic effect). Several potential mechanisms could be invoked for the effect of thyroid hormones on AF risk, including elevation of left atrial pressure secondary to increased left ventricular mass and impaired ventricular relaxation, ischemia resulting from increased resting heart rate, and increased atrial eopic activity. Reentry has been postulated as one of the main mechanisms leading to AF. AF is more likely if effective refractory periods are short and conduction is slow. Hyperthyroidism is associated with shortening of action potential duration which may also contribute to AF

Lymphatic microangiopathy of the skin in systemic sclerosis

METHODS: The cutaneous capillary lymphatic system in patients with systemic sclerosis was investigated using fluorescence microlymphography. The distal upper limbs of 16 healthy controls (mean age 62.3+/-13.1 yr) and 16 patients with systemic sclerosis (mean age 58.9+/-13.6 yr) were examined and the following parameters were evaluated: (a) single lymphatic capillaries; (b) lymphatic capillary network and cutaneous backflow; (c) extension of the stained lymphatics; (d) diameter of single lymphatic capillaries. RESULTS: At the finger level, lymphatic capillaries were lacking in five patients, while they were present in all controls (P < 0.05). Extension of the stained lymphatics was increased in 11 patients (8.1+/-6.0 mm) compared to the 16 healthy controls (2.0+/-1.2 mm) (P < 0.0001). Cutaneous backflow was observed in three patients (P < 0.05). At the hand level, lymphatic network extension was significantly different between patients (3.8+/-2.4 mm) and controls (1.2+/-0.8 mm) (P < 0.01); however, no significant differences were found at the forearm level. CONCLUSION: Lesional skin in patients with systemic sclerosis exhibits evidence of lymphatic microangiopath

Association of statin use and clinical outcomes in heart failure patients: A systematic review and meta-analysis

Background The role of statins in patients with heart failure (HF) of different levels of left ventricular ejection fraction (LVEF) remains unclear especially in the light of the absence of prospective data from randomized controlled trials (RCTs) in non-ischemic HF, and taking into account potential statins’ prosarcopenic effects. We assessed the association of statin use with clinical outcomes in patients with HF. Methods We searched PubMed, EMBASE, Scopus, Google Scholar and Cochrane Central until August 2018 for RCTs and prospective cohorts comparing clinical outcomes with statin vs non-statin use in patients with HF at different LVEF levels. We followed the guidelines of the 2009 PRISMA statement for reporting and applied independent extraction by multiple observers. Meta-analyses of hazard ratios (HRs) of effects of statins on clinical outcomes used generic inverse variance method and random model effects. Clinical outcomes were all-cause mortality, cardiovascular (CV) mortality and CV hospitalization. Results Finally we included 17 studies (n = 88,100; 2 RCTs and 15 cohorts) comparing statin vs non-statin users (mean follow-up 36 months). Compared with non-statin use, statin use was associated with lower risk of all-cause mortality (HR 0.77, 95% confidence interval [CI], 0.72–0.83, P < 0.0001, I2 = 63%), CV mortality (HR 0.82, 95% CI: 0.76–0.88, P < 0.0001, I2 = 63%), and CV hospitalization (HR 0.78, 95% CI: 0.69–0.89, P = 0.0003, I2 = 36%). All-cause mortality was reduced on statin therapy in HF with both EF < 40% and ≥ 40% (HR: 0.77, 95% Cl: 0.68–0.86, P < 0.00001, and HR 0.75, 95% CI: 0.69–0.82, P < 0.00001, respectively). Similarly, CV mortality (HR 0.86, 95% CI: 0.79–0.93, P = 0.0003, and HR 0.83, 95% CI: 0.77–0.90, P < 0.00001, respectively), and CV hospitalizations (HR 0.80 95% CI: 0.64–0.99, P = 0.04 and HR 0.76 95% CI: 0.61–0.93, P = 0.009, respectively) were reduced in these EF subgroups. Significant effects on all clinical outcomes were also found in cohort studies’ analyses; the effect was also larger and significant for lipophilic than hydrophilic statins. Conclusions In conclusion, statins may have a beneficial effect on CV outcomes irrespective of HF etiology and LVEF level. Lipophilic statins seem to be much more favorable for patients with heart failure.Revisión por pare

Reactivity of pulmonary circulation and right ventricle function to inhaled nitric oxide in systemic sclerosis patients

Systemic sclerosis (SSc) is complicated by pulmonary hypertension and right ventricle (RV) failure in approximately 10% of the patients. Factors influencing the reactivity of pulmonary circulation to vasodilators are not established, while the examination of vasoreactivity is important in determining the treatment, because systemic administration of oral vasodilators can induce severe adverse events in nonresponders. The mechanism of RV failure in SSc is unclear and may result either from increased RV afterload or intrinsic myocardial disease. The aim of the study was to assess the reactivity of pulmonary circulation to inhaled nitric oxide (iNO) and to evaluate its influence on RV function in SSc patients with elevated right ventricle systolic pressure (RVSP). In 60 SSc patients aged 24–73 (58 females, two males; 33 patients with limited SSc and 27 with diffuse SSc), echocardiographic examination with tissue Doppler echocardiography (TDE) was performed. RV function was measured by systolic (S) and early diastolic (E) velocity of tricuspid annulus by TDE. In patients with RVSP >45 mmHg, the reactivity of pulmonary circulation was assessed by iNO test. High-resolution computerized tomography (HRCT) was performed to assess the extent of pulmonary fibrosis. Of 14 SSc subjects with elevated RVSP (13 females, one male; RVSP 47–62 mmHg), positive reaction to iNO was observed in five (RVSP decreased from 51.6 ± 3.7 to 32.24 ± 2.3 mmHg); nine patients were not reactive (RVSP 53.5 ± 5.7 mmHg before iNO vs. 49.6 ± 6.7 mmHg). RV systolic function was decreased in patients with elevated RVSP as compared to the patients with normal pulmonary pressure (S velocity 13.2 ± 1.3 vs. 14.4 ± 1.6 cm/s, respectively, p < 0.05). Significant increase of RV systolic function during iNO test was found in reactive patients only (S velocity before iNO 12.8 ± 1.2 cm/s, during iNO 14.5 ± 1.5 cm/s, p < 0.01). RVSP decrease strongly correlated with S velocity increase (r = 0.95, p < 0.0001). Response to iNO was found only in limited form of SSc; diffuse SSc patients showed no response. Pulmonary fibrosis on HRCT was more frequent in subjects nonreactive to iNO (67% of patients) than in the reactive group (40% of patients). The reactivity of pulmonary circulation to iNO in SSc patients with elevated RVSP was found predominantly in limited form of the disease. Pulmonary fibrosis typical for diffuse SSc was more frequent in nonreactive subjects. Elevated pulmonary pressure plays an important role in RV systolic dysfunction. Pulmonary pressure decrease during iNO test leads to the improvement of RV systolic function. Therapy for right-heart failure in reactive SSc patients should be directed, if possible, at the decrease in pulmonary resistance

An integrated Pan-European perspective on coastal Lagoons management through a mosaic-DPSIR approach

© The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 6 (2016): 19400, doi:10.1038/srep19400.A decision support framework for the management of lagoon ecosystems was tested using four European Lagoons: Ria de Aveiro (Portugal), Mar Menor (Spain), Tyligulskyi Liman (Ukraine) and Vistula Lagoon (Poland/Russia). Our aim was to formulate integrated management recommendations for European lagoons. To achieve this we followed a DPSIR (Drivers-Pressures-State Change-Impacts-Responses) approach, with focus on integrating aspects of human wellbeing, welfare and ecosystem sustainability. The most important drivers in each lagoon were identified, based on information gathered from the lagoons’ stakeholders, complemented by scientific knowledge on each lagoon as seen from a land-sea perspective. The DPSIR cycles for each driver were combined into a mosaic-DPSIR conceptual model to examine the interdependency between the multiple and interacting uses of the lagoon. This framework emphasizes the common links, but also the specificities of responses to drivers and the ecosystem services provided. The information collected was used to formulate recommendations for the sustainable management of lagoons within a Pan-European context. Several common management recommendations were proposed, but specificities were also identified. The study synthesizes the present conditions for the management of lagoons, thus analysing and examining the activities that might be developed in different scenarios, scenarios which facilitate ecosystem protection without compromising future generations.This study was supported by the European Commission, under the 7th Framework Programme, through the collaborative research project LAGOONS (contract n° 283157); by European funds through COMPETE and by Portuguese funds through the national Foundation for Science and Technology – FCT (PEst-C/MAR/LA0017/2013). The post-Doc grant SFRH/BPD/41117/2007 (M Dolbeth) and the PhD grant SFRH/BD/79170/2011 (LP Sousa) supported by FCT are also acknowledged

Systemic sclerosis-associated pulmonary hypertension: why disease-specific composite endpoints are needed

Pulmonary arterial hypertension (PAH) is a serious complication of systemic sclerosis (SSc). In clinical trials PAH-SSc has been grouped with other forms, including idiopathic PAH. The primary endpoint for most pivotal studies was improvement in exercise capacity. However, composite clinical endpoints that better reflect long-term outcome may be more meaningful. We discuss potential endpoints and consider why the same measures may not be appropriate for both idiopathic PAH and PAH-SSc due to inherent differences in clinical outcome and management strategies of these two forms of PAH. Failure to take this into account may compromise progress in managing PAH in SSc

Comprehensive plasma proteomic profiling reveals biomarkers for active tuberculosis

BACKGROUND. Tuberculosis (TB) kills more people than any other infection, and new diagnostic tests to identify active cases are required. We aimed to discover and verify novel markers for TB in nondepleted plasma. / METHODS. We applied an optimized quantitative proteomics discovery methodology based on multidimensional and orthogonal liquid chromatographic separation combined with high-resolution mass spectrometry to study nondepleted plasma of 11 patients with active TB compared with 10 healthy controls. Prioritized candidates were verified in independent UK (n = 118) and South African cohorts (n = 203). / RESULTS. We generated the most comprehensive TB plasma proteome to date, profiling 5022 proteins spanning 11 orders-of-magnitude concentration range with diverse biochemical and molecular properties. We analyzed the predominantly low–molecular weight subproteome, identifying 46 proteins with significantly increased and 90 with decreased abundance (peptide FDR ≤ 1%, q ≤ 0.05). Verification was performed for novel candidate biomarkers (CFHR5, ILF2) in 2 independent cohorts. Receiver operating characteristics analyses using a 5-protein panel (CFHR5, LRG1, CRP, LBP, and SAA1) exhibited discriminatory power in distinguishing TB from other respiratory diseases (AUC = 0.81). / CONCLUSION. We report the most comprehensive TB plasma proteome to date, identifying novel markers with verification in 2 independent cohorts, leading to a 5-protein biosignature with potential to improve TB diagnosis. With further development, these biomarkers have potential as a diagnostic triage test. / FUNDING. Colciencias, Medical Research Council, Innovate UK, NIHR, Academy of Medical Sciences, Program for Advanced Research Capacities for AIDS, Wellcome Centre for Infectious Diseases Research

The Rise and Fall of Hypertension: Lessons Learned from Eastern Europe

Hypertension is a progressive cardiovascular syndrome that arises from many differing, but interrelated, etiologies. Hypertension is the most prevalent cardiovascular disorder, affecting 20% to 50% of the adult population in developed countries. Arterial hypertension is a major risk factor for cardiovascular diseases and death. Epidemiologic data have shown that control of hypertension is achieved in only a small percentage of hypertensive patients. Findings from the World Health Organization project Monitoring Trends and Determinants in Cardiovascular Diseases (MONICA) showed a remarkably high prevalence (about 65%) of hypertension in Eastern Europeans. There is virtually no difference however, between the success rate in controlling hypertension when comparing Eastern and Western European populations. Diagnosing hypertension depends on both population awareness of the dangers of hypertension and medical interventions aimed at the detecting elevated blood pressure, even in asymptomatic patients. Medical compliance with guidelines for the treatment of hypertension is variable throughout Eastern Europe. Prevalence of hypertension increases with age, and the management of hypertension in elderly is a significant problem. The treatment of hypertension demands a comprehensive approach to the patient with regard to cardiovascular risk and individualization of hypertensive therapy

Fluorescent RNA cytosine analogue - an internal probe for detailed structure and dynamics investigations

The bright fluorescent cytosine analogue tCO stands out among fluorescent bases due to its virtually unquenched fluorescence emission in duplex DNA. However, like most reported base analogues, it has not been thoroughly characterized in RNA. We here report on the first synthesis and RNA-incorporation of tCO, and characterize its base-mimicking and fluorescence properties in RNA. As in DNA, we find a high quantum yield inside RNA duplexes (&lt;?F&gt; = 0.22) that is virtually unaffected by the neighbouring bases (?F = 0.20-0.25), resulting in an average brightness of 1900 M-1 cm-1. The average fluorescence lifetime in RNA duplexes is 4.3 ns and generally two lifetimes are required to fit the exponential decays. Fluorescence properties in ssRNA are defined by a small increase in average quantum yield (&lt;?F &gt; = 0.24) compared to dsRNA, with a broader distribution (?F = 0.17-0.34) and slightly shorter average lifetimes. Using circular dichroism, we find that the tCO-modified RNA duplexes form regular A-form helices and in UV-melting experiments the stability of the duplexes is only slightly higher than that of the corresponding natural RNA (&lt;?T m&gt; = + 2.3 °C). These properties make tCO a highly interesting fluorescent RNA base analogue for detailed FRET-based structural measurements, as a bright internal label in microscopy, and for fluorescence anisotropy measurements of RNA dynamics