Blood pressure changes after renal denervation at 10 European expert centers

We did a subject-level meta-analysis of the changes (Δ) in blood pressure (BP) observed 3 and 6 months after renal denervation (RDN) at 10 European centers. Recruited patients (n=109; 46.8% women; mean age 58.2 years) had essential hypertension confirmed by ambulatory BP. From baseline to 6 months, treatment score declined slightly from 4.7 to 4.4 drugs per day. Systolic/diastolic BP fell by 17.6/7.1 mm Hg for office BP, and by 5.9/3.5, 6.2/3.4, and 4.4/2.5 mm Hg for 24-h, daytime and nighttime BP (P0.03 for all). In 47 patients with 3- and 6-month ambulatory measurements, systolic BP did not change between these two time points (P0.08). Normalization was a systolic BP of <140 mm Hg on office measurement or <130 mm Hg on 24-h monitoring and improvement was a fall of 10 mm Hg, irrespective of measurement technique. For office BP, at 6 months, normalization, improvement or no decrease occurred in 22.9, 59.6 and 22.9% of patients, respectively; for 24-h BP, these proportions were 14.7, 31.2 and 34.9%, respectively. Higher baseline BP predicted greater BP fall at follow-up; higher baseline serum creatinine was associated with lower probability of improvement of 24-h BP (odds ratio for 20-μmol l(-1) increase, 0.60; P=0.05) and higher probability of experiencing no BP decrease (OR, 1.66; P=0.01). In conclusion, BP responses to RDN include regression-to-the-mean and remain to be consolidated in randomized trials based on ambulatory BP monitoring. For now, RDN should remain the last resort in patients in whom all other ways to control BP failed, and it must be cautiously used in patients with renal impairment

Body mass index related electrocardiographic findings in healthy young individuals with a normal body mass index

IntroductionAn increased body mass index (BMI) (>25 kg/m2) is associated with a wide range of electrocardiographic changes. However, the association between electrocardiographic changes and BMI in healthy young individuals with a normal BMI (18.5–25 kg/m2) is unknown. The aim of this study was to evaluate the association between BMI and electrocardiographic parameters.MethodsData from 1,290 volunteers aged 18 to 30 years collected at our centre were analysed. Only subjects considered healthy by a physician after review of collected data with a normal BMI and in sinus rhythm were included in the analysis. Subjects with a normal BMI (18.5–25 kg/m2) were divided into BMI quartiles analysis and a backward multivariate regression analysis with a normal BMI as a continuous variable was performed.ResultsMean age was 22.7 ± 3.0 years, mean BMI was 22.0, and 73.4% were male. There were significant differences between the BMI quartiles in terms of maximum P-wave duration, P-wave balance, total P-wave area in lead V1, PR-interval duration, and heart axis. In the multivariate model maximum P-wave duration (standardised coefficient (SC) = +0.112, P P-wave balance in lead V1 (SC = +0.072, P P P ConclusionIncreased BMI was related with discrete electrocardiographic alterations including an increased P-wave duration, increased P-wave balance, a leftward shift of the heart axis, and decreased Sokolow-Lyon voltage on a standard twelve lead electrocardiogram in healthy young individuals with a normal BMI.Medicinal Chemistr

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Structural, functional and mechanistic insights uncover the fundamental role of orphan connexin-62 in platelets

Connexins (Cxs) oligomerise to form hexameric hemichannels in the plasma membrane that can further dock together on adjacent cells to form gap junctions and facilitate intercellular-trafficking of molecules. In this study, we report the expression and function of an ‘orphan’ connexin, Cx62, in human and mouse (Cx57, mouse homologue) platelets. A novel mimetic peptide (62Gap27) was developed to target the second extracellular loop of Cx62 and 3D structural models predicted its interference with gap junction and hemichannel function. The ability of 62Gap27 to regulate both gap junction and hemichannel-mediated intercellular communication was observed using FRAP analysis and flow cytometry. Cx62 inhibition by 62Gap27 suppressed a range of agonist-stimulated platelet functions and impaired thrombosis and haemostasis. This was associated with elevated PKA-dependent signalling in a cyclic adenosine monophosphate-independent manner, and was not observed in Cx57 deficient mouse platelets (in which the selectivity of 62Gap27 for this connexin was also confirmed). Notably, Cx62 hemichannels were observed to function independently of Cx37 and Cx40 hemichannels. Together, our data reveal a fundamental role for a hitherto uncharacterised connexin in the regulation of the function of circulating cells

Peripheral and central arterial pressure and its relationship to vascular target organ damage in carotid artery, retina and arterial stiffness. Development and validation of a tool. The Vaso risk study

<p>Abstract</p> <p>Background</p> <p>Ambulatory blood pressure monitoring (ABPM) shows a better correlation to target organ damage and cardiovascular morbidity-mortality than office blood pressure. A loss of arterial elasticity and an increase in carotid artery intima-media thickness (IMT) has been associated with increased cardiovascular morbidity-mortality. Tools have been developed that allow estimation of the retinal arteriovenous index but not all studies coincide and there are contradictory results in relation to the evolution of the arteriosclerotic lesions and the caliber of the retinal vessels. The purpose of this study is to analyze the relationship between peripheral and central arterial pressure (clinic and ambulatory) and vascular structure and function as evaluated by the carotid artery intima-media thickness, retina arteriovenous index, pulse wave velocity (PWV) and ankle-brachial index in patients with and without type 2 diabetes. In turn, software is developed and validated for measuring retinal vessel thickness and automatically estimating the arteriovenous index.</p> <p>Methods/Design</p> <p>A cross-sectional study involving a control group will be made, with a posterior 4-year follow-up period in primary care. The study patients will be type 2 diabetics, with a control group of non-diabetic individuals. Consecutive sampling will be used to include 300 patients between 34-75 years of age and no previous cardiovascular disease, one-half being assigned to each group. Main measurements: age, gender, height, weight and abdominal circumference. Lipids, creatinine, microalbuminuria, blood glucose, HbA1c, blood insulin, high sensitivity C-reactive protein and endothelial dysfunction markers. Clinic and ambulatory blood pressure monitoring. Carotid ultrasound to evaluate IMT, and retinography to evaluate the arteriovenous index. ECG to assess left ventricle hypertrophy, ankle-brachial index, and pulse wave analysis (PWA) and pulse wave velocity (PWV) with the Sphigmocor System.</p> <p>Discussion</p> <p>We hope to obtain information on the correlation of different ABPM-derived parameters and PWA to organ target damage - particularly vascular structure and function evaluated from the IMT and PWV - and endothelial dysfunction in patients with and without type 2 diabetes. We also hope to demonstrate the usefulness of the instrument developed for the automated evaluation of retinal vascularization in the early detection of alterations in vascular structure and function and in the prognosis of middle-term cardiovascular morbidity.</p> <p>Trial Registration</p> <p>Clinical Trials.gov Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01325064">NCT01325064</a></p

The enigma of in vivo oxidative stress assessment: isoprostanes as an emerging target

Oxidative stress is believed to be one of the major factors behind several acute and chronic diseases, and may also be associated with ageing. Excess formation of free radicals in miscellaneous body environment may originate from endogenous response to cell injury, but also from exposure to a number of exogenous toxins. When the antioxidant defence system is overwhelmed, this leads to cell damage. However, the measurement of free radicals or their endproducts is tricky, since these compounds are reactive and short lived, and have diverse characteristics. Specific evidence for the involvement of free radicals in pathological situations has been difficult to obtain, partly owing to shortcomings in earlier described methods for the measurement of oxidative stress. Isoprostanes, which are prostaglandin-like bioactive compounds synthesized in vivo from oxidation of arachidonic acid, independently of cyclooxygenases, are involved in many human diseases, and their measurement therefore offers a way to assess oxidative stress. Elevated levels of F2-isoprostanes have also been seen in the normal human pregnancy, but their physiological role has not yet been defined. Large amounts of bioactive F2-isoprostanes are excreted in the urine in normal basal situations, with a wide interindividual variation. Their exact role in the regulation of normal physiological functions, however, needs to be explored further. Current understanding suggests that measurement of F2-isoprostanes in body fluids provides a reliable analytical tool to study oxidative stress-related diseases and experimental inflammatory conditions, and also in the evaluation of various dietary antioxidants, as well as drugs with radical-scavenging properties. However, assessment of isoprostanes in plasma or urine does not necessarily reflect any specific tissue damage, nor does it provide information on the oxidation of lipids other than arachidonic acid

Neogene Uplift and Magmatism of Anatolia: Insights from Drainage Analysis and Basaltic Geochemistry

It is generally agreed that mantle dynamics have played a significant role in generating and maintaining the elevated topography of Anatolia during Neogene times. However, there is much debate about the relative importance of subduction zone and asthenospheric processes. Key issues concern onset and cause of regional uplift, thickness of the lithospheric plate, and the presence or absence of temperature and/or compositional anomalies within the convecting mantle. Here, we tackle these interlinked issues by analyzing and modeling two disparate suites of observations. First, a drainage inventory of 1,844 longitudinal river profiles is assembled. This geomorphic database is inverted to calculate the variation of Neogene regional uplift through time and space by minimizing the misfit between observed and calculated river profiles subject to independent calibration. Our results suggest that regional uplift commenced in the east at 20 Ma and propagated westward. Secondly, we have assembled a database of geochemical analyses of basaltic rocks. Two different approaches have been used to quantitatively model this database with a view to determining the depth and degree of asthenospheric melting across Anatolia. Our results suggest that melting occurs at depths as shallow as 60 km in the presence of mantle potential temperatures as high as 1400°C. There is evidence that potential temperatures are higher in the east, consistent with the pattern of sub-plate shear wave velocity anomalies. Our combined results are consistent with isostatic and admittance analyses and suggest that elevated asthenospheric temperatures beneath thinned Anatolian lithosphere have played a first order role in generating and maintaining regional dynamic topography and basaltic magmatism

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Development and Standardisation of Banana Pseudostem Based Novel Functional Blended Ready to Drink (RTD) Beverages and Studies Nutritional Changes during Storage

Not AvailableBanana pseudostem contributes about 30% of the total plant biomass which contains significant amount of minerals. The aim of the present investigation was to study the development and standardisation of functional ready to drink (RTD) banana pseudostem beverages using ginger rhizome and nannari root extracts and study their storage stability up to 6 months under ambient temperature and 13.5°C. Ginger rhizome and nannari root extracts at the concentration of 4% were found to be appropriate for the preparation of ginger and nannari-flavoured RTD banana pseudostem beverages. Nutrients analysis revealed that the flavoured RTD banana pseudostem beverages had significant amount of nutrients, namely total sugar (10.62 to 10.83 g/100 ml), total Carbohydrate (CHO) (13.92 to 16.08 g/100 ml), vitamin ‘C’ (0.673 to 0.707 mg/100 ml), sodium (0.920% to 0.935%), potassium (8.13% to 8.30%), zinc (1.034 to 1.117 ppm), copper (0.9183 to 0.9190 ppm) and manganese (0.9544 to 1.0144 ppm). After 6 months of storage, the drink blended with ginger rhizome extract was found best in terms of nutrient retention and colour and appearance, flavour, consistency, taste and overall acceptability followed by nannari-flavoured banana pseudostem RTD beverages.Not Availabl