Action versus Result-Oriented Schemes in a Grassland Agroecosystem: A Dynamic Modelling Approach

Effects of agri-environment schemes (AES) on biodiversity remain controversial. While most AES are action-oriented, result-oriented and habitat-oriented schemes have recently been proposed as a solution to improve AES efficiency. The objective of this study was to compare action-oriented, habitat-oriented and result-oriented schemes in terms of ecological and productive performance as well as in terms of management flexibility. We developed a dynamic modelling approach based on the viable control framework to carry out a long term assessment of the three schemes in a grassland agroecosystem. The model explicitly links grazed grassland dynamics to bird population dynamics. It is applied to lapwing conservation in wet grasslands in France. We ran the model to assess the three AES scenarios. The model revealed the grazing strategies respecting ecological and productive constraints specific to each scheme. Grazing strategies were assessed by both their ecological and productive performance. The viable control approach made it possible to obtain the whole set of viable grazing strategies and therefore to quantify the management flexibility of the grassland agroecosystem. Our results showed that habitat and result-oriented scenarios led to much higher ecological performance than the action-oriented one. Differences in both ecological and productive performance between the habitat and result-oriented scenarios were limited. Flexibility of the grassland agroecosystem in the result-oriented scenario was much higher than in that of habitat-oriented scenario. Our model confirms the higher flexibility as well as the better ecological and productive performance of result-oriented schemes. A larger use of result-oriented schemes in conservation may also allow farmers to adapt their management to local conditions and to climatic variations

Home-based isometric exercise training induced reductions resting blood pressure

Purpose: Isometric exercise training (IET) reduces resting blood pressure (BP). Most previous protocols impose exercise barriers which undermine its effectiveness as a potential physical therapy for altering BP. An inexpensive, home-based programme would promote IET as a valuable tool in the fight against hypertension. The aims of this study were: (a) to investigate whether home-based wall squat training could successfully reduce resting BP, and (b) to explore the physiological variables that might mediate a change in resting BP. Methods: Twenty-eight healthy normotensive males were randomly assigned to a control and a 4 week home-based IET intervention using a crossover design with a 4 week ‘washout’ period in-between. Wall squat training was completed 3x weekly over 4 weeks with 48 hours between sessions. Each session comprised 4x 2 minute bouts of wall squat exercise performed at a participant-specific knee joint angle relative to a target HR of 95% HRpeak, with 2 minutes rest between bouts. Resting heart rate, BP, cardiac output, total peripheral resistance and stroke volume were taken at baseline and post each condition. Results: Resting BP (systolic = -4 ± 5, diastolic = -3 ± 3 and mean arterial = -3 ± 3 mmHg), cardiac output (-0.54 ± 0.66 L∙min-1) and heart rate (-5 ± 7 beats∙min-1) were all reduced following IET, with no change in total peripheral resistance or stroke volume compared to the control. Conclusion: These findings suggest the wall squat provides an effective method for reducing resting BP in the home resulting primarily from a reduction in resting heart rate

Research into the effect Of SGLT2 inhibition on left ventricular remodelling in patients with heart failure and diabetes mellitus (REFORM) trial rationale and design

Background Heart failure (HF) and diabetes (DM) are a lethal combination. The current armamentarium of anti-diabetic agents has been shown to be less efficacious and sometimes even harmful in diabetic patients with concomitant cardiovascular disease, especially HF. Sodium glucose linked co-transporter type 2 (SGLT2) inhibitors are a new class of anti-diabetic agent that has shown potentially beneficial cardiovascular effects such as pre-load and after load reduction through osmotic diuresis, blood pressure reduction, reduced arterial stiffness and weight loss. This has been supported by the recently published EMPA-REG trial which showed a striking 38 and 35 % reduction in cardiovascular death and HF hospitalisation respectively. Methods The REFORM trial is a novel, phase IV randomised, double blind, placebo controlled clinical trial that has been ongoing since March 2015. It is designed specifically to test the safety and efficacy of the SLGT2 inhibitor, dapagliflozin, on diabetic patients with known HF. We utilise cardiac-MRI, cardio-pulmonary exercise testing, body composition analysis and other tests to quantify the cardiovascular and systemic effects of dapagliflozin 10 mg once daily against standard of care over a 1 year observation period. The primary outcome is to detect the change in left ventricular (LV) end systolic and LV end diastolic volumes. The secondary outcome measures include LV ejection fraction, LV mass index, exercise tolerance, fluid status, quality of life measures and others. Conclusions This trial will be able to determine if SGLT2 inhibitor therapy produces potentially beneficial effects in patients with DM and HF, thereby replacing current medications as the drug of choice when treating patients with both DM and HF

Effect of increased convective clearance by on-line hemodiafiltration on all cause and cardiovascular mortality in chronic hemodialysis patients – the Dutch CONvective TRAnsport STudy (CONTRAST): rationale and design of a randomised controlled trial [ISRCTN38365125]

BACKGROUND: The high incidence of cardiovascular disease in patients with end stage renal disease (ESRD) is related to the accumulation of uremic toxins in the middle and large-middle molecular weight range. As online hemodiafiltration (HDF) removes these molecules more effectively than standard hemodialysis (HD), it has been suggested that online HDF improves survival and cardiovascular outcome. Thus far, no conclusive data of HDF on target organ damage and cardiovascular morbidity and mortality are available. Therefore, the CONvective TRAnsport STudy (CONTRAST) has been initiated. METHODS: CONTRAST is a Dutch multi-center randomised controlled trial. In this trial, approximately 800 chronic hemodialysis patients will be randomised between online HDF and low-flux HD, and followed for three years. The primary endpoint is all cause mortality. The main secondary outcome variables are fatal and non-fatal cardiovascular events. CONCLUSION: The study is designed to provide conclusive evidence whether online HDF leads to a lower mortality and less cardiovascular events as compared to standard HD

Tissue Doppler Imaging can be useful to distinguish pathological from physiological left ventricular hypertrophy: a study in master athletes and mild hypertensive subjects

<p>Abstract</p> <p>Background</p> <p>Transthoracic echocardiography left ventricular wall thickness is often increased in master athletes and it results by intense physical training. Left Ventricular Hypertrophy can also be due to a constant pressure overload. Conventional Pulsed Wave (PW) Doppler analysis of diastolic function sometimes fails to distinguish physiological from pathological LVH.</p> <p>The aim of this study is to evaluate the role of Pulsed Wave Tissue Doppler Imaging in differentiating pathological from physiological LVH in the middle-aged population.</p> <p>Methods</p> <p>we selected a group of 80 master athletes, a group of 80 sedentary subjects with essential hypertension and an apparent normal diastolic function at standard PW Doppler analysis. The two groups were comparable for increased left ventricular wall thickness and mass index (134.4 ± 19.7 vs 134.5 ± 22.1 gr/m2; p > .05). Diastolic function indexes using the PW technique were in the normal range for both.</p> <p>Results</p> <p>Pulsed Wave TDI study of diastolic function immediately distinguished the two groups. While in master athletes the diastolic TDI-derived parameters remained within normal range (E' 9.4 ± 3.1 cm/sec; E/E' 7.8 ± 2.1), in the hypertensive group these parameters were found to be constantly altered, with mean values and variation ranges always outside normal validated limits (E' 7.2 ± 2.4 cm/sec; E/E' 10.6 ± 3.2), and with E' and E/E' statistically different in the two groups (p < .001).</p> <p>Conclusion</p> <p>Our study showed that the TDI technique can be an easy and validated method to assess diastolic function in differentiating normal from pseudonormal diastolic patterns and it can distinguish physiological from pathological LVH emphasizing the eligibility certification required by legal medical legislation as in Italy.</p

Oral cysteamine as an adjunct treatment in cystic fibrosis pulmonary exacerbations: An exploratory randomized clinical trial

Background Emerging data suggests a possible role for cysteamine as an adjunct treatment for pulmonary exacerbations of cystic fibrosis (CF) that continue to be a major clinical challenge. There are no studies investigating the use of cysteamine in pulmonary exacerbations of CF. This exploratory randomized clinical trial was conducted to answer the question: In future pivotal trials of cysteamine as an adjunct treatment in pulmonary exacerbations of CF, which candidate cysteamine dosing regimens should be tested and which are the most appropriate, clinically meaningful outcome measures to employ as endpoints? Methods and findings Multicentre double-blind randomized clinical trial. Adults experiencing a pulmonary exacerbation of CF being treated with standard care that included aminoglycoside therapy were randomized equally to a concomitant 14-day course of placebo, or one of 5 dosing regimens of cysteamine. Outcomes were recorded on days 0, 7, 14 and 21 and included sputum bacterial load and the patient reported outcome measures (PROMs): Chronic Respiratory Infection Symptom Score (CRISS), the Cystic Fibrosis Questionnaire–Revised (CFQ-R); FEV1, blood leukocyte count, and inflammatory markers. Eighty nine participants in fifteen US and EU centres were randomized, 78 completed the 14-day treatment period. Cysteamine had no significant effect on sputum bacterial load, however technical difficulties limited interpretation. The most consistent findings were for cysteamine 450mg twice daily that had effects additional to that observed with placebo, with improved symptoms, CRISS additional 9.85 points (95% CI 0.02, 19.7) p = 0.05, reduced blood leukocyte count by 2.46x109 /l (95% CI 0.11, 4.80), p = 0.041 and reduced CRP by geometric mean 2.57 nmol/l (95% CI 0.15, 0.99), p = 0.049. Conclusion In this exploratory study cysteamine appeared to be safe and well-tolerated. Future pivotal trials investigating the utility of cysteamine in pulmonary exacerbations of CF need to include the cysteamine 450mg doses and CRISS and blood leukocyte count as outcome measures. Clinical trial registration NCT03000348; www.clinicaltrials.gov

The use of the CR-10 scale to allow self-regulation of isometric exercise intensity in pre-hypertensive and hypertensive participants

Purpose: Isometric exercise (IE) has been shown to lower blood pressure (BP). Using equipment with force output displays, intensity is usually regulated at 30% maximal voluntary contraction (MVC); however, the cost of programmable equipment and their requirement for maximal contractions presents limitations. A simple, cost-effective alternative deserves investigation. The purpose of this study was (i) to explore the relationship between %MVC, change in systolic BP (ΔSBP), and perceived exertion (CR-10) and (ii) to assess the validity of self-regulation of intensity during isometric handgrip exercise. Methods: Fourteen pre-hypertensive and hypertensive adults completed eight, 2-minute isometric handgrip exercises at randomised intensities; participants estimated their perceived exertion at 30-second intervals (Estimation Task). Subsequently, on three separate occasions participants performed four 2-minute contractions at an exertion level that they perceived to be equivalent to CR-10 “Level-6” (Production Task). Results: There were significant linear relationships between the estimated exertion on the CR-10 scale, and ΔSBP (r=0.784) and %MVC (r=0.845). Level 6 was equivalent to an average ΔSBP of 38mmHg (95% CI; 44mmHg, 32mmHg) and a relative force of 33% MVC (95% CI; 36.2%, 30%). During the production task, %MVC was not significantly different between the estimation task and each production task. In at least the first two repetitions of each production task, ΔSBP was significantly lower than that observed in the estimation task. Conclusion: These findings show that CR-10 “level-6” is an appropriate method of self-regulating isometric handgrip intensity; its use offers an affordable and accessible alternative for isometric exercise prescription aimed at reducing BP

Comparative Functional Genomics Analysis of NNK Tobacco-Carcinogen Induced Lung Adenocarcinoma Development in Gprc5a-Knockout Mice

Background: Improved understanding of lung cancer development and progression, including insights from studies of animal models, are needed to combat this fatal disease. Previously, we found that mice with a knockout (KO) of G-protein coupled receptor 5A (Gprc5a) develop lung tumors after a long latent period (12 to 24 months). Methodology/Principal Findings: To determine whether a tobacco carcinogen will enhance tumorigenesis in this model, we administered 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) i.p. to 2-months old Gprc5a-KO mice and sacrificed groups (n = 5) of mice at 6, 9, 12, and 18 months later. Compared to control Gprc5a-KO mice, NNK-treated mice developed lung tumors at least 6 months earlier, exhibited 2- to 4-fold increased tumor incidence and multiplicity, and showed a dramatic increase in lesion size. A gene expression signature, NNK-ADC, of differentially expressed genes derived by transcriptome analysis of epithelial cell lines from normal lungs of Gprc5a-KO mice and from NNK-induced adenocarcinoma was highly similar to differential expression patterns observed between normal and tumorigenic human lung cells. The NNK-ADC expression signature also separated both mouse and human adenocarcinomas from adjacent normal lung tissues based on publicly available microarray datasets. A key feature of the signature, up-regulation of Ube2c, Mcm2, and Fen1, was validated in mouse normal lung and adenocarcinoma tissues and cells by immunohistochemistry and western blotting, respectively

The Kolumbo submarine volcano of Santorini island is a large pool of bacterial strains with antimicrobial activity

Microbes in hydrothermal vents with their unique secondary metabolism may represent an untapped potential source of new natural products. In this study, samples were collected from the hydrothermal field of Kolumbo submarine volcano in the Aegean Sea, in order to isolate bacteria with antimicrobial activity. Eight hundred and thirty-two aerobic heterotrophic bacteria were isolated and then differentiated through BOX-PCR analysis at the strain level into 230 genomic fingerprints, which were screened against 13 different type strains (pathogenic and nonpathogenic) of Gram-positive, Gram-negative bacteria and fungi. Forty-two out of 176 bioactive-producing genotypes (76 %) exhibited antimicrobial activity against at least four different type strains and were selected for 16S rDNA sequencing and screening for nonribosomal peptide (NRPS) and polyketide (PKS) synthases genes. The isolates were assigned to genus Bacillus and Proteobacteria, and 20 strains harbored either NRPS, PKS type I or both genes. This is the first report on the diversity of culturable mesophilic bacteria associated with antimicrobial activity from Kolumbo area; the extremely high proportion of antimicrobial-producing strains suggested that this unique environment may represent a potential reservoir of novel bioactive compounds

The role of epigenetic dysregulation in the epidemic of allergic disease

The epidemic of allergic disease in early life is one of the clearest indicators that the developing immune system is vulnerable to modern environmental changes. A range of environmental exposures epidemiologically associated with allergic disease have been shown to have effects on the foetal immune function in pregnancy, including microbial burden, dietary changes and environmental pollutants. Preliminary studies now suggest that these early effects on immune development may be mediated epigenetically through a variety of processes that collectively modify gene expression and allergic susceptibility and that these effects are potentially heritable across generations. It is also possible that rising rates of maternal allergy, a recognised direct risk factor for infant allergic disease, may be further amplifying the effects of environmental changes. Whilst effective prevention strategies are the ultimate goal in reversing the allergy epidemic, the specific environmental drivers, target genes, and intracellular pathways and mechanisms of early life immune programming are still unclear. It is hoped that identifying genes that are differentially regulated in association with subsequent allergic disease will assist in identifying causal pathways and upstream contributing environmental factors. In this way, epigenetic paradigms are likely to provide valuable insights into how the early environment can be modified to more favourably drive immune development and reverse the allergic epidemic