bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving Pre-emptive Prescribing to Relieve Patient Discomfort Occurring Out of Hours
Authors: Williams Rhys , Herbert Fiona , Orme Amy , Casswell Georgina
Published: February 2016

Junior doctors are commonly asked to prescribe simple medications for symptom relief for patients out of hours. Unfortunately, time constraints and other pressures may lead to delays before the medications are prescribed. A quality improvement project was conducted at a large university teaching hospital to establish the extent of the problem, with the aim of finding measures to improve preemptive prescribing for patients. Baseline data was gathered over three busy wards to calculate the total of new prescriptions made over the course of a weekend. There were 24 new prescriptions required over the weekend, a percentage increase of 14.9% compared to the existing prescriptions on a Friday. Following the first intervention this decreased to 10.2%, and by the second intervention the rate was 4.9%. Data collected several months later confirmed that the interventions remained successful, and preemptive prescribing continued. Overall, our interventions have shown that the number of new prescriptions required out of hours can be reduced by educating junior doctors on preemptive prescribing.
Enabling digital pathology in the diagnostic setting: navigating through the implementation journey in an academic medical centre
Authors: Cheng Chee Leong , Azhar Rafay , Sng Shi Hui Adeline , Chua Yong Quan , Hwang Jacqueline Siok Gek , Chin Jennifer Poi Fun , Seah Waih Khuen , Loke Janel Chui Ling , Ang Roy Hang Leng , Tan Puay Hoon
Published: February 2016

Aims

As digital pathology (DP) and whole slide imaging (WSI) technology advance and mature, there is an increasing drive to incorporate DP into the diagnostic environment. However, integration of DP into the diagnostic laboratory is a non-trivial task and filled with unexpected challenges unlike standalone implementations. We share our journey of implementing DP in the diagnostic laboratory setting, highlighting seven key guiding principles that drive the progression through implementation into deployment and beyond.

Methods

The DP implementation with laboratory information system integration was completed in 8 months, including validation of the solution for diagnostic use in accordance with College of American Pathologists guidelines. We also conducted prospective validation via paired delivery of glass slides and WSI to our pathologists postdeployment.

Results

Common themes in our guiding principles included emphasis on workflow and being comprehensive in the approach, looking beyond pathologist user champions and expanding into an extended project team involving laboratory technicians, clerical/data room staff and archival staff. Concordance between glass slides and WSI ranged from 93% to 100% among various applications on validation. We also provided equal opportunities for every pathologist throughout the department to be competent and confident with DP through prospective validation, with overall concordance of 96% compared with glass slides, allowing appreciation of the advantages and limitations of WSI, hence enabling the use of DP as a useful diagnostic modality.

Conclusions

Smooth integration of DP into the diagnostic laboratory is possible with careful planning, discipline and a systematic approach adhering to our guiding principles.
Estimating the burden of heat illness in England during the 2013 summer heatwave using syndromic surveillance
Authors: Smith Sue , Elliot Alex J , Hajat Shakoor , Bone Angie , Smith Gillian E , Kovats Sari
Published: February 2016

Background

The burden of heat illness on health systems is not well described in the UK. Although the UK generally experiences mild summers, the frequency and intensity of hot weather is likely to increase due to climate change, particularly in Southern England. We investigated the impact of the moderate heatwave in 2013 on primary care and emergency department (ED) visits using syndromic surveillance data in England.

Methods

General practitioner in hours (GPIH), GP out of hours (GPOOH) and ED syndromic surveillance systems were used to monitor the health impact of heat/sun stroke symptoms (heat illness). Data were stratified by age group and compared between heatwave and non-heatwave years. Incidence rate ratios were calculated for GPIH heat illness consultations.

Results

GP consultations and ED attendances for heat illness increased during the heatwave period; GPIH consultations increased across all age groups, but the highest rates were in school children and those aged ≥75 years, with the latter persisting beyond the end of the heatwave. Extrapolating to the English population, we estimated that the number of GPIH consultations for heat illness during the whole summer (May to September) 2013 was 1166 (95% CI 1064 to 1268). This was double the rate observed during non-heatwave years.

Conclusions

These findings support the monitoring of heat illness (symptoms of heat/sun stroke) as part of the Heatwave Plan for England, but also suggest that specifically monitoring heat illness in children, especially those of school age, would provide additional early warning of, and situation awareness during heatwaves.
From cradle to grave: tracking socioeconomic inequalities in mortality in a cohort of 11 868 men and women born in Uppsala, Sweden, 1915–1929
Authors: Juárez Sol P , Goodman Anna , Koupil Ilona
Published: February 2016

Background

Ample evidence has shown that early-life social conditions are associated with mortality later in life. However, little attention has been given to the strength of these effects across specific age intervals from birth to old age. In this paper, we study the effect of the family's socioeconomic position and mother's marital status at birth on all-cause mortality at different age intervals in a Swedish cohort of 11 868 individuals followed across their lifespan.

Methods

Using the Uppsala Birth Cohort Multigenerational Study, we fitted Cox regression models to estimate age-varying HRs of all-cause mortality according to mother's marital status and family's socioeconomic position.

Results

Mother's marital status and family's socioeconomic position at birth were associated with higher mortality rates throughout life (HR 1.18 (95% CI 1.12 to 1.26) for unmarried mothers; 1.19 (95% CI 1.12 to 1.25) for low socioeconomic position). While the effect of family's socioeconomic position showed little variation across different age groups, the effect of marital status was stronger for infant mortality (HR 1.47 (95% CI 1.23 to 1.76); p=0.04 for heterogeneity). The results remained robust when early life and adult mediator variables were included.

Conclusions

Family's socioeconomic position and mother's marital status involve different dimensions of social stratification with independent effects on mortality throughout life. Our findings support the importance of improving early-life conditions in order to enhance healthy ageing.
The impact of SASA!, a community mobilisation intervention, on women's experiences of intimate partner violence: secondary findings from a cluster randomised trial in Kampala, Uganda
Authors: Abramsky Tanya , Devries Karen M , Michau Lori , Nakuti Janet , Musuya Tina , Kyegombe Nambusi , Watts Charlotte
Published: February 2016

Background

Intimate partner violence (IPV) is a global public health and human rights concern, though there is limited evidence on how to prevent it. This secondary analysis of data from the SASA! Study assesses the potential of a community mobilisation IPV prevention intervention to reduce overall prevalence of IPV, new onset of abuse (primary prevention) and continuation of prior abuse (secondary prevention).

Methods

A pair-matched cluster randomised controlled trial was conducted in 8 communities (4 intervention, 4 control) in Kampala, Uganda (2007–2012). Cross-sectional surveys of community members, 18–49 years old, were undertaken at baseline (n=1583) and 4 years postintervention implementation (n=2532). Outcomes relate to women's past year experiences of physical and sexual IPV, emotional aggression, controlling behaviours and fear of partner. An adjusted cluster-level intention-to-treat analysis compared outcomes in intervention and control communities at follow-up.

Results

At follow-up, all types of IPV (including severe forms of each) were lower in intervention communities compared with control communities. SASA! was associated with lower onset of abuse and lower continuation of prior abuse. Statistically significant effects were observed for continued physical IPV (adjusted risk ratio 0.42, 95% CI 0.18 to 0.96); continued sexual IPV (0.68, 0.53 to 0.87); continued emotional aggression (0.68, 0.52 to 0.89); continued fear of partner (0.67, 0.51 to 0.89); and new onset of controlling behaviours (0.38, 0.23 to 0.62).

Conclusions

Community mobilisation is an effective means for both primary and secondary prevention of IPV. Further support should be given to the replication and scale up of SASA! and other similar interventions.

Trial registration number

NCT00790959
Challenges in reproducing results from publicly available data: an example of sexual orientation and cardiovascular disease risk
Authors: Austin Nichole , Harper Sam , Kaufman Jay S , Hamra Ghassan B
Published: February 2016

Background

Replication is a vital part of the research process and has recently received considerable attention. Analyses using publicly available data should, if adequately described, be reproducible without assistance from the original investigators. Using data from the US National Health and Nutrition Examination Survey (NHANES), a recent study reported a statistically significant difference in cardiovascular disease risk comparing subgroups of sexual minority men. We attempted to reproduce these findings and assessed whether the results were robust to alternative analytic strategies and assumptions.

Methods

We used the exclusion criteria and coding strategy described in the original paper to construct our analytical data set. Sampling weights were constructed in accordance with NHANES analytical guidelines. We estimated crude and covariate-adjusted associations between sexual orientation and vascular age using the regression models specified in the original report. We also conducted a series of sensitivity analyses to improve on the original findings.

Results

Our replication attempt was partially successful: we replicated the general trends reported in the original analysis, but not identical effect estimates. Importantly, we identified a potential misapplication of the Framingham Risk Score; correcting for this increased the probability that the reported null hypothesis test was a type I error.

Conclusions

This paper supports the recent calls for greater transparency and improved reporting in research. Even with a publicly available and well-documented data source, we were unable to exactly replicate another study's original findings. Our sensitivity analyses revealed key issues in the original analysis and demonstrate the scientific importance of research replication.
I and Thou: learning the ‘human’ side of medicine
Authors: Messinger Atara , Chin-Yee Benjamin
Published: February 2016

This essay is a reflection on the doctor–patient relationship from the perspective of two medical students, which draws on the ideas of 20th-century philosopher Martin Buber. Although Buber never wrote about medicine directly, his ‘philosophy of dialogue’ raises fundamental questions about how human beings relate to one another, and can thus offer valuable insights into the nature of the clinical encounter. We argue that Buber's basic word pairs, ‘I–You’ and ‘I–It’, provide a useful heuristic for understanding different modes of caring for patients, which we illustrate using examples of illness narratives from two literary works: Tolstoy'sIvan Ilychand Margaret Edson'sWit. Our essay demonstrates how the humanities in general and philosophy in particular can inform a more humanistic practice for healthcare trainees and practicing clinicians alike.
A time-series study of percutaneous closure of patent foramen ovale: premature adoption?
Authors: Lew Kian Nian , Angelini Gianni D , Hollingworth William
Published: February 2016

Objectives

To evaluate the impact of National Institute for Health and Care Excellence (NICE) guidance in January 2005 and subsequent trial evidence on the adoption of percutaneous closure of patent foramen ovale (PCPFO).

Methods

A retrospective time series study was conducted using the Inpatient Hospital Episode Statistics (HES) England. A total of 3801 patients, aged ≥18 and ≤60 years, who had PCPFO from 1 April 2006 to 31 March 2012 in England. Percentage change annualised (PCA) in PCPFO procedure rates between initial NICE guidance and publication of trial results was analysed.

Results

Between Quarter 2, 2006 and Quarter 4, 2009, 2163 PCPFO procedures were performed, with an increasing PCA of 48.4%. The procedure rate peaked before the presentation of equivocal results from the first randomised controlled trial (RCT) in late 2010, and declined between Quarter 4, 2009 and Quarter 4, 2011 (PCA=−15.3%). Of more than 2300 patients recruited to three RCTs, only 71 were recruited in English hospitals.

Conclusions

PCPFO was rapidly adopted after the publication of initial NICE guidance despite the absence of RCT evidence of efficacy. Very few English patients participated in international RCTs of PCPFO, suggesting that NICE recommendations also failed to encourage the generation of RCT evidence.
Association of ambulatory heart rate and atherosclerosis risk factors with blood pressure in young non-hypertensive adults
Authors: Cheng Cynthia , Daskalakis Constantine
Published: February 2016

Objective

The study objective was to assess the association between 24 h ambulatory heart rate (HR), atherosclerosis risk factors and blood pressure (BP) in young non-hypertensive patients.

Methods

We recruited 186 participants aged 18–45 years from a large urban academic Family Medicine outpatient practice, serving 40 000 individuals for this observational study. The main analyses were based on multiple linear regression, with mean 24 h BP (systolic BP (SBP) or diastolic BP (DBP)) as the outcomes, mean 24 h HR as the main predictor of interest, and controlling for age, gender, race, insulin sensitivity/resistance and endothelial function measured by strain gauge venous occlusion plethysmography.

Results

HR was independently associated with mean 24 h SBP and DBP (SBP and DBP: p=0.042 and 0.001, respectively). In our analyses, associations were markedly stronger for ambulatory compared with office BP measurements. Endothelial dysfunction was associated with higher SBP (p=0.013); plasminogen activator inhibitor-1 was significantly associated with both SBP and DBP (p=0.041 and 0.015, respectively), while insulin resistance was not associated with either SBP or DBP. Insulin resistance and C reactive protein were significant predictors of HR (p=0.013 and 0.007, respectively).

Conclusions

These findings suggest that HR may be a potential marker of elevated cardiovascular risk in young asymptomatic individuals, prior to the development of clinical hypertension or cardiovascular disease.
Serological diagnosis of Leptospirosis in bovine serum samples using a microsphere immunoassay
Authors: Wynwood S. J. , Burns M. A. , Graham G. C. , Weier S. L. , McKay D. B. , Craig S. B.
Published: February 2016

Leptospirosis causes significant economic loss within the cattle industry worldwide. Current diagnostic methods are generally inadequate for dealing with large numbers of samples, are outdated, and provide little useful diagnostic and epidemiological information. This aim of this study was to apply a microsphere immunoassay (MIA), utilising Luminex xMap technology, to 200 bovine serum samples to determine this method's usefulness in leptospirosis diagnosis in comparison with the current gold standard, the microscopic agglutination test (MAT). Although MAT is the most widely used laboratory test for the diagnosis of leptospirosis, its reliance on live cultures, subjective interpretation of results and an inability to differentiate between antibody classes, suggest MAT is no longer the best method for the diagnosis of leptospirosis. The results presented in this paper show that MIA was able to determine reactive from non‐reactive samples when compared with MAT, and was able to differentiate IgG and IgM classes of antibody. The results suggest increased sensitivity in MIA and the ability to multiplex up to 500 antigens at one time allows for significant improvements in cost‐effectiveness as well as a reduced dependency on live cultures. The relatively low cost, high throughput platform and differentiation of antibody class, as shown in previous research, make this assay worthy of consideration for the diagnosis of leptospirosis in small‐scale or large‐scale bovine populations.
CBIR Based Testing Oracles: An Experimental Evaluation of Similarity Functions
Authors: Nunes Fátima L. S. , Delamaro Márcio Eduardo , Gonçalves Vagner Mendonça , Lauretto Marcelo De Souza
Published: February 2016

Content-Based Image Retrieval (CBIR) systems constitute an innovative approach to store, to compare and to query images in a database. Visual aspects such as color, texture or shape are used to perform such operations. Recently, CBIR concepts were applied to build testing oracles for image processing programs, where test verdicts (approval/disapproval) are based on similarity measures between images produced by the program and reference images. However, the results of a CBIR system may vary depending on the components employed in the system (feature extractors and similarity functions), and few studies assessing this influence have been found in the literature. Our aim is to present an empirical analysis of ten similarity functions in CBIR systems within the context of software testing with graphic outputs. A case study with images obtained from a computer-aided diagnosis system in mammography indicated some variability among image test verdicts (approval/disapproval) according to the similarity function choice. The case study also indicates the existence of some clusters of similarity functions with high correlation coefficients.
Autonomic modification of intestinal smooth muscle contractility
Authors: Montgomery Laura E. A. , Tansey Etain A. , Johnson Chris D. , Roe Sean M. , Quinn Joe G.
Published: February 2016

Intestinal smooth muscle contracts rhythmically in the absence of nerve and hormonal stimulation because of the activity of pacemaker cells between and within the muscle layers. This means that the autonomic nervous system modifies rather than initiates intestinal contractions. The practical described here gives students an opportunity to observe this spontaneous activity and its modification by agents associated with parasympathetic and sympathetic nerve activity. A section of the rabbit small intestine is suspended in an organ bath, and the use of a pressure transducer and data-acquisition software allows the measurement of tension generated by the smooth muscle of intestinal walls. The application of the parasympathetic neurotransmitter ACh at varying concentrations allows students to observe an increase in intestinal smooth muscle tone with increasing concentrations of this muscarinic receptor agonist. Construction of a concentration-effect curve allows students to calculate an EC50value for ACh and consider some basic concepts surrounding receptor occupancy and activation. Application of the hormone epinephrine to the precontracted intestine allows students to observe the inhibitory effects associated with sympathetic nerve activation. Introduction of the drug atropine to the preparation before a maximal concentration of ACh is applied allows students to observe the inhibitory effect of a competitive antagonist on the physiological response to a receptor agonist. The final experiment involves the observation of the depolarizing effect of K+on smooth muscle. Students are also invited to consider why the drugs atropine, codeine, loperamide, and botulinum toxin have medicinal uses in the management of gastrointestinal problems.
Assessment and comparison of student engagement in a variety of physiology courses
Authors: Hopper Mari K.
Published: February 2016

Calls for reform in science education have promoted active learning as a means to improve student engagement (SENG). SENG is generally acknowledged to have a positive effect on student learning, satisfaction, and retention. A validated 14-question survey was used to assess SENG in a variety of upper- and lower-level physiology courses, including 100-level Anatomy and Physiology 1, 300-level Animal Physiology, 400-level Advanced Physiology, and 500-level Medical Physiology courses. The results indicated that SENG did not vary consistently by course level, format, or curriculum. The highest levels of SENG were found in the Advanced Physiology course, which included SENG as a primary objective of the course. Physiology student SENG scores were compared with National Survey of Student Engagement (NSSE) scores. The results demonstrated that physiology students enrolled in the Anatomy and Physiology 1 course reported lower levels of SENG than first-year students that completed the NSSE. Students enrolled in the Advanced Physiology course reported higher levels of SENG than fourth-year students that completed the NSSE. Assessment of SENG offers insights as to how engaged students are, identifies where efforts may best be applied to enhance SENG, and provides a baseline measure for future comparisons after targeted course modifications.
Using paper presentation breaks during didactic lectures improves learning of physiology in undergraduate students
Authors: Ghorbani Ahmad , Ghazvini Kiarash
Published: February 2016

Many studies have emphasized the incorporation of active learning into classrooms to reinforce didactic lectures for physiology courses. This work aimed to determine if presenting classic papers during didactic lectures improves the learning of physiology among undergraduate students. Twenty-two students of health information technology were randomly divided into the following two groups: 1) didactic lecture only (control group) and 2) didactic lecture plus paper presentation breaks (DLPP group). In the control group, main topics of gastrointestinal and endocrine physiology were taught using only the didactic lecture technique. In the DLPP group, some topics were presented by the didactic lecture method (similar to the control group) and some topics were taught by the DLPP technique (first, concepts were covered briefly in a didactic format and then reinforced with presentation of a related classic paper). The combination of didactic lecture and paper breaks significantly improved learning so that students in the DLPP group showed higher scores on related topics compared with those in the control group ( P < 0.001). Comparison of the scores of topics taught by only the didactic lecture and those using both the didactic lecture and paper breaks showed significant improvement only in the DLPP group ( P < 0.001). Data obtained from the final exam showed that in the DLPP group, the mean score of the topics taught by the combination of didactic lecture and paper breaks was significantly higher than those taught by only didactic lecture ( P < 0.05). In conclusion, the combination of paper presentation breaks and didactic lectures improves the learning of physiology.
2015 Meeting of the National Directors of Graduate Studies in Pharmacology and Physiology
Authors: McFalls Ashley J. , Barnett Joey V. , Karpa Kelly D.
Published: February 2016

Researchers trained in pharmacology and physiology must possess not only a comprehensive knowledge of chemistry and the nature of compounds but also a deep understanding of physiology and predict how these compounds function in a system or organism. However, graduate programs in pharmacology and physiology have increasingly begun to focus on more reductionist approaches to basic science, neglecting training in integrative/systems physiology. In response to a decline in the competency of recent pharmacology and physiology graduates, a biennial meeting, National Directors of Graduate Studies (NDOGS) in pharmacology and physiology, was conceived to address these concerns and improve the quality of graduate education. NDOGS functions as a forum for directors of pharmacology and physiology programs to exchange ideas and tackle the challenges facing graduate education. The 2015 meeting was held on the campus of the University of Cincinnati, and each day of the meeting was allocated for discussion of a broad topic. On Friday, talks were aimed at “enhancing the professional pipeline.” On Saturday, the theme of “fitting training to emerging needs” tackled ways that universities can respond to the emerging needs of a changing society. Sunday morning updated graduate program directors about changes to National Institutes of Health T32 Training Grant applications and provided a forum for program directors to share their experiences and concerns. Throughout the meeting, presentations and discussions highlighted challenges and opportunities that apply broadly to PhD training in the biomedical sciences and revealed best practices to improve training and career preparation of PhD trainees.
GPER activation ameliorates aortic remodeling induced by salt-sensitive hypertension
Authors: Liu Liu , Kashyap Shreya , Murphy Brennah , Hutson Dillion D. , Budish Rebecca A. , Trimmer Emma H. , Zimmerman Margaret A. , Trask Aaron J. , Miller Kristin S. , Chappell Mark C. , Lindsey Sarah H.
Published: February 2016

The mRen2 female rat is an estrogen- and salt-sensitive model of hypertension that reflects the higher pressure and salt sensitivity associated with menopause. We previously showed that the G protein-coupled estrogen receptor (GPER) mediates estrogenic effects in this model. The current study hypothesized that GPER protects against vascular injury during salt loading. Intact mRen2 female rats were fed a normal (NS; 0.5% Na+) or high-salt diet (HS; 4% Na+) for 10 wk, which significantly increased systolic blood pressure (149 ± 5 vs. 224 ± 8 mmHg; P < 0.001). Treatment with the selective GPER agonist G-1 for 2 wk did not alter salt-sensitive hypertension (216 ± 4 mmHg; P > 0.05) or ex vivo vascular responses to angiotensin II or phenylephrine ( P > 0.05). However, G-1 significantly attenuated salt-induced aortic remodeling assessed by media-to-lumen ratio (NS: 0.43; HS+veh: 0.89; HS+G-1: 0.61; P < 0.05). Aortic thickening was not accompanied by changes in collagen, elastin, or medial proliferation. However, HS induced increases in medial layer glycosaminoglycans (0.07 vs. 0.42 mm2; P < 0.001) and lipid peroxidation (0.11 vs. 0.51 mm2; P < 0.01), both of which were reduced by G-1 (0.20 mm2 and 0.23 mm2; both P < 0.05). We conclude that GPER's beneficial actions in the aorta of salt-loaded mRen2 females occur independently of changes in blood pressure and vasoreactivity. GPER-induced attenuation of aortic remodeling was associated with a reduction in oxidative stress and decreased accumulation of glycosaminoglycans. Endogenous activation of GPER may protect females from salt- and pressure-induced vascular damage.
Cardiac Sirt1 mediates the cardioprotective effect of caloric restriction by suppressing local complement system activation after ischemia-reperfusion
Authors: Yamamoto Tsunehisa , Tamaki Kayoko , Shirakawa Kohsuke , Ito Kentaro , Yan Xiaoxiang , Katsumata Yoshinori , Anzai Atsushi , Matsuhashi Tomohiro , Endo Jin , Inaba Takaaki , Tsubota Kazuo , Sano Motoaki , Fukuda Keiichi , Shinmura Ken
Published: February 2016

Caloric restriction (CR) confers cardioprotection against ischemia-reperfusion (I/R) injury. We previously found the essential roles of endothelial nitric oxide synthase in the development of CR-induced cardioprotection and Sirt1 activation during CR (Shinmura K, Tamaki K, Ito K, Yan X, Yamamoto T, Katsumata Y, Matsuhashi T, Sano M, Fukuda K, Suematsu M, Ishii I. Indispensable role of endothelial nitric oxide synthase in caloric restriction-induced cardioprotection against ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 308: H894–H903, 2015). However, the exact mechanism by which Sirt1 in cardiomyocytes mediates the cardioprotective effect of CR remains undetermined. We subjected cardiomyocyte-specific Sirt1 knockout (CM- Sirt1 −/−) mice and the corresponding control mice to either 3-mo ad libitum feeding or CR (−40%). Isolated perfused hearts were subjected to 25-min global ischemia, followed by 60-min reperfusion. The recovery of left ventricle function after I/R was improved, and total lactate dehydrogenase release into the perfusate during reperfusion was attenuated in the control mice treated with CR, but a similar cardioprotective effect of CR was not observed in the CM- Sirt1 −/− mice. The expression levels of cardiac complement component 3 (C3) at baseline and the accumulation of C3 and its fragments in the ischemia-reperfused myocardium were attenuated by CR in the control mice, but not in the CM- Sirt1 −/− mice. Resveratrol treatment also attenuated the expression levels of C3 protein in cultured neonatal rat ventricular cardiomyocytes. Moreover, the degree of myocardial I/R injury in conventional C3 knockout ( C3 −/−) mice treated with CR was similar to that in the ad libitum-fed C3 −/− mice, although the expression levels of Sirt1 were enhanced by CR. These results demonstrate that cardiac Sirt1 plays an essential role in CR-induced cardioprotection against I/R injury by suppressing cardiac C3 expression. This is the first report suggesting that cardiac Sirt1 regulates the local complement system during CR.
BMP type I receptor ALK2 is required for angiotensin II-induced cardiac hypertrophy
Authors: Shahid Mohd , Spagnolli Ester , Ernande Laura , Thoonen Robrecht , Kolodziej Starsha A. , Leyton Patricio A. , Cheng Juan , Tainsh Robert E. T. , Mayeur Claire , Rhee David K. , Wu Mei. X. , Scherrer-Crosbie Marielle , Buys Emmanuel S. , Zapol Warren M. , Bloch Kenneth D. , Bloch Donald B.
Published: February 2016

Bone morphogenetic protein (BMP) signaling contributes to the development of cardiac hypertrophy. However, the identity of the BMP type I receptor involved in cardiac hypertrophy and the underlying molecular mechanisms are poorly understood. By using quantitative PCR and immunoblotting, we demonstrated that BMP signaling increased during phenylephrine-induced hypertrophy in cultured neonatal rat cardiomyocytes (NRCs), as evidenced by increased phosphorylation of Smads 1 and 5 and induction of Id1 gene expression. Inhibition of BMP signaling with LDN193189 or noggin, and silencing of Smad 1 or 4 using small interfering RNA diminished the ability of phenylephrine to induce hypertrophy in NRCs. Conversely, activation of BMP signaling with BMP2 or BMP4 induced hypertrophy in NRCs. Luciferase reporter assay further showed that BMP2 or BMP4 treatment of NRCs repressed atrogin-1 gene expression concomitant with an increase in calcineurin protein levels and enhanced activity of nuclear factor of activated T cells, providing a mechanism by which BMP signaling contributes to cardiac hypertrophy. In a model of cardiac hypertrophy, C57BL/6 mice treated with angiotensin II (A2) had increased BMP signaling in the left ventricle. Treatment with LDN193189 attenuated A2-induced cardiac hypertrophy and collagen deposition in left ventricles. Cardiomyocyte-specific deletion of BMP type I receptor ALK2 (activin-like kinase 2), but not ALK1 or ALK3, inhibited BMP signaling and mitigated A2-induced cardiac hypertrophy and left ventricular fibrosis in mice. The results suggest that BMP signaling upregulates the calcineurin/nuclear factor of activated T cell pathway via BMP type I receptor ALK2, contributing to cardiac hypertrophy and fibrosis.
Muscle metaboreflex and cerebral blood flow regulation in humans: implications for exercise with blood flow restriction
Authors: Prodel Eliza , Balanos George M. , Braz Igor D. , Nobrega Antonio C. L. , Vianna Lauro C. , Fisher James P.
Published: February 2016

We investigated the effect of activating metabolically sensitive skeletal muscle afferents (muscle metaboreflex) on cerebral blood flow and the potentially confounding influence of concomitant changes in the partial pressure of arterial carbon dioxide. Eleven healthy males (25 ± 4 yr) performed submaximal leg cycling exercise on a semirecumbent cycle ergometer (heart rate: ∼120 beats/min), and assessments were made of the partial pressure of end-tidal carbon dioxide (PetCO2), internal carotid artery blood flow (ICAQ) and conductance (ICACVC), and middle cerebral artery mean blood velocity (MCAvm) and conductance index (MCACVCi).The muscle metaboreflex was activated during cycling with leg blood flow restriction (BFR) or isolated with postexercise ischemia (PEI). In separate trials, PetCO2was either permitted to fluctuate spontaneously (control trial) or was clamped at 1 mmHg above resting levels (PetCO2clamp trial). In the control trial, leg cycling with BFR decreased PetCO2(Δ−4.8 ± 0.9 mmHg vs. leg cycling exercise) secondary to hyperventilation, while ICAQ, ICACVC, and MCAvmwere unchanged and MCACVCidecreased. However, in the PetCO2clamp trial, leg cycling with BFR increased both MCAvm(Δ5.9 ± 1.4 cm/s) and ICAQ(Δ20.0 ± 7.8 ml/min) and attenuated the decrease in MCACVCi, while ICACVCwas unchanged. In the control trial, PEI decreased PetCO2(Δ−7.0 ± 1.3 mmHg vs. rest), MCAvmand MCACVCi, whereas ICAQand ICACVCwere unchanged. In contrast, in the PetCO2clamp trial both ICAQ(Δ18.5 ± 11.9 ml/min) and MCAvm(Δ8.8 ± 2.0 cm/s) were elevated, while ICACVCand MCACVCiwere unchanged. In conclusion, when hyperventilation-related decreases in PetCO2are prevented the activation of metabolically sensitive skeletal muscle afferent fibers increases cerebral blood flow.
Novel wave power analysis linking pressure-flow waves, wave potential, and the forward and backward components of hydraulic power
Authors: Mynard Jonathan P. , Smolich Joseph J.
Published: February 2016

Wave intensity analysis provides detailed insights into factors influencing hemodynamics. However, wave intensity is not a conserved quantity, so it is sensitive to diameter variations and is not distributed among branches of a junction. Moreover, the fundamental relation between waves and hydraulic power is unclear. We, therefore, propose an alternative to wave intensity called “wave power,” calculated via incremental changes in pressure and flow (dPdQ) and a novel time-domain separation of hydraulic pressure power and kinetic power into forward and backward wave-related components (ΠP± and ΠQ±). Wave power has several useful properties: 1) it is obtained directly from flow measurements, without requiring further calculation of velocity; 2) it is a quasi-conserved quantity that may be used to study the relative distribution of waves at junctions; and 3) it has the units of power (Watts). We also uncover a simple relationship between wave power and changes in ΠP± and show that wave reflection reduces transmitted power. Absolute values of ΠP± represent wave potential, a recently introduced concept that unifies steady and pulsatile aspects of hemodynamics. We show that wave potential represents the hydraulic energy potential stored in a compliant pressurized vessel, with spatial gradients producing waves that transfer this energy. These techniques and principles are verified numerically and also experimentally with pressure/flow measurements in all branches of a central bifurcation in sheep, under a wide range of hemodynamic conditions. The proposed “wave power analysis,” encompassing wave power, wave potential, and wave separation of hydraulic power provides a potent time-domain approach for analyzing hemodynamics.
The mitochondrial function of the cerebral vasculature in insulin-resistant Zucker obese rats
Authors: Merdzo Ivan , Rutkai Ibolya , Tokes Tunde , Sure Venkata N. L. R. , Katakam Prasad V. G. , Busija David W.
Published: February 2016

Little is known about mitochondrial functioning in the cerebral vasculature during insulin resistance (IR). We examined mitochondrial respiration in isolated cerebral arteries of male Zucker obese (ZO) rats and phenotypically normal Zucker lean (ZL) rats using the Seahorse XFe24 analyzer. We investigated mitochondrial morphology in cerebral blood vessels as well as mitochondrial and nonmitochondrial protein expression levels in cerebral arteries and microvessels. We also measured reactive oxygen species (ROS) levels in cerebral microvessels. Under basal conditions, the mitochondrial respiration components (nonmitochondrial respiration, basal respiration, ATP production, proton leak, and spare respiratory capacity) showed similar levels among the ZL and ZO groups with the exception of maximal respiration, which was higher in the ZO group. We examined the role of nitric oxide by measuring mitochondrial respiration following inhibition of nitric oxide synthase with Nω-nitro-l-arginine methyl ester (l-NAME) and mitochondrial activation after administration of diazoxide (DZ). Both ZL and ZO groups showed similar responses to these stimuli with minor variations. l-NAME significantly increased the proton leak, and DZ decreased nonmitochondrial respiration in the ZL group. Other components were not affected. Mitochondrial morphology and distribution within vascular smooth muscle and endothelium as well as mitochondrial protein levels were similar in the arteries and microvessels of both groups. Endothelial nitric oxide synthase (eNOS) and ROS levels were increased in cerebral microvessels of the ZO. Our study suggests that mitochondrial function is not significantly altered in the cerebral vasculature of young ZO rats, but increased ROS production might be due to increased eNOS in the cerebral microcirculation during IR.
Antenatal BAY 41-2272 reduces pulmonary hypertension in the rabbit model of congenital diaphragmatic hernia
Authors: Vuckovic Aline , Herber-Jonat Susanne , Flemmer Andreas W. , Strizek Brigitte , Engels Alexander C. , Jani Jacques C.
Published: February 2016

Infants with congenital diaphragmatic hernia (CDH) fail to adapt at birth because of persistent pulmonary hypertension (PH), a condition characterized by excessive muscularization and abnormal vasoreactivity of pulmonary vessels. Activation of soluble guanylate cyclase by BAY 41-2272 prevents pulmonary vascular remodeling in neonatal rats with hypoxia-induced PH. By analogy, we hypothesized that prenatal administration of BAY 41-2272 would improve features of PH in the rabbit CDH model. Rabbit fetuses with surgically induced CDH at day 23 of gestation were randomized at day 28 for an intratracheal injection of BAY 41-2272 or vehicle. After term delivery (day 31), lung mechanics, right ventricular pressure, and serum NH2-terminal-pro-brain natriuretic peptide (NT-proBNP) levels were measured. After euthanasia, lungs were processed for biological or histological analyses. Compared with untouched fetuses, the surgical creation of CDH reduced the lung-to-body weight ratio, increased mean terminal bronchial density, and impaired lung mechanics. Typical characteristics of PH were found in the hypoplastic lungs, including increased right ventricular pressure, higher serum NT-proBNP levels, thickened adventitial and medial layers of pulmonary arteries, reduced capillary density, and lower levels of endothelial nitric oxide synthase. A single antenatal instillation of BAY 41-2272 reduced mean right ventricular pressure and medial thickness of small resistive arteries in CDH fetuses. Capillary density, endothelial cell proliferation, and transcripts of endothelial nitric oxide synthase increased, whereas airway morphometry, lung growth, and mechanics remained unchanged. These results suggest that pharmacological activation of soluble guanylate cyclase may provide a new approach to the prenatal treatment of PH associated with CDH.
The New TLC Method for Separation and Determination of Multicomponent Mixtures of Plant Extracts
Authors: Matysik Elżbieta , Woźniak Anna , Paduch Roman , Rejdak Robert , Polak Beata , Donica Helena
Published: February 2016

The new mode of two-dimensional gradient thin layer chromatography (MGD-2D TLC) has been presented. Short distance development of sample in the first dimension leads to formation of the preconcentrated narrow zones. They are consecutively separated in the second dimension with the mobile phase gradient in several steps of development until the eluent reaches the further end of the chromatographic plate. The use of the above-mentioned technique allows isolating and then identifying the compounds of various polarity from the multicomponent mixture. The practical application of two-dimensional gradient thin layer chromatography has been performed for isolation of the two plant (JuniperusandThymus) oils components as the examples of test mixtures. The experiments have been carried out with the use of silica gel plates as well as a normal phase condition. The results of solute separation with isocratic one-dimensional thin layer chromatography system have been compared with those of two-dimensional gradient system. It has been observed that application of the latter mode leads to almost triplicated number of zones in comparison with the former one. It is purposeful to apply the proposed mode to control the purity of the dominant component or components of the mixture.
Plant Responses to High Frequency Electromagnetic Fields
Authors: Vian Alain , Davies Eric , Gendraud Michel , Bonnet Pierre
Published: February 2016

High frequency nonionizing electromagnetic fields (HF-EMF) that are increasingly present in the environment constitute a genuine environmental stimulus able to evoke specific responses in plants that share many similarities with those observed after a stressful treatment. Plants constitute an outstanding model to study such interactions since their architecture (high surface area to volume ratio) optimizes their interaction with the environment. In the present review, after identifying the main exposure devices (transverse and gigahertz electromagnetic cells, wave guide, and mode stirred reverberating chamber) and general physics laws that govern EMF interactions with plants, we illustrate some of the observed responses after exposure to HF-EMF at the cellular, molecular, and whole plant scale. Indeed, numerous metabolic activities (reactive oxygen species metabolism,α- andβ-amylase, Krebs cycle, pentose phosphate pathway, chlorophyll content, terpene emission, etc.) are modified, gene expression altered (calmodulin, calcium-dependent protein kinase, and proteinase inhibitor), and growth reduced (stem elongation and dry weight) after low power (i.e., nonthermal) HF-EMF exposure. These changes occur not only in the tissues directly exposed but also systemically in distant tissues. While the long-term impact of these metabolic changes remains largely unknown, we propose to consider nonionizing HF-EMF radiation as a noninjurious, genuine environmental factor that readily evokes changes in plant metabolism.
Anger Emotional Stress Influences VEGF/VEGFR2 and Its Induced PI3K/AKT/mTOR Signaling Pathway
Authors: Sun Peng , Wei Sheng , Wei Xia , Wang Jieqiong , Zhang Yuanyuan , Qiao Mingqi , Wu Jibiao
Published: February 2016

Objective.We discuss the influence of anger emotional stress upon VEGF/VEGFR2 and its induced PI3K/AKT/mTOR signal pathway.Methods.We created a rat model of induced anger (anger-out and anger-in) emotional response using social isolation and resident-intruder paradigms and assessed changes in hippocampus’ VEGF content, neuroplasticity, and the PI3K/AKT/mTOR signaling pathway.Results.The resident-intruder method successfully generated anger-out and anger-in models that differed significantly in composite aggression score, aggression incubation, open field behavior, sucrose preference, and weight gain. Anger emotional stress decreased synaptic connections and VEGFR2 expression. Anger emotional stress led to abnormal expression of VEGF/VEGFR2 mRNA and protein and disorderly expression of key factors in the PI3K/AKT/mTOR signal pathway. Fluoxetine administration ameliorated behavioral abnormalities and damage to hippocampal neurons caused by anger emotional stress, as well as abnormal expression of some proteins in VEGF/VEGFR2 and its induced PI3K/AKT/mTOR signal pathway.Conclusion.This research provides a detailed classification of anger emotion and verifies its influence upon VEGF and the VEGF-induced signaling pathway, thus providing circumstantial evidence of mechanisms by which anger emotion damages neurogenesis. As VEGFR2 can promote neurogenesis and vasculogenesis in the hippocampus and frontal lobe, these results suggest that anger emotional stress can result in decreased neurogenesis.
A Fuzzy Based Sensor Web for Adaptive Prediction Framework to Enhance the Availability of Web Service
Authors: Ramalingam Sundharam , Mohandas Lakshmi
Published: February 2016

Present day businesses revolve around internet applications (e.g., e-commerce, e-business, and internet banking) which are primarily supported by web services . The increasing consumer reliance on these internet-based applications causes dynamic variation in the number of requests received by web services and a slowdown in response time during peak load periods. To overcome this difficulty, in this paper, we propose a fuzzy logic (FL) based prediction and replication framework to replicate the web services over distributed servers and achieve timely responses. This framework senses the proximity of future interval response time against agreed service level agreement (SLA) time using sensor web called proximity sensor service. Also, it determines the replication requirement using FL and implements the FL decision using resource control algorithm to replicate the web service on another server before the SLA time is violated or to reclaim the excess resource. We conduct appropriate test scenarios in a dedicated test environment and compare the results with existing models. The results show that our framework replicates the web service at more appropriate times than the existing models and achieves 82% prediction accuracy. Thus, our framework significantly improves the availability of web services with minimal intervention from system administrators.
A Method for Trust Quantification in Cloud Computing Environments
Authors: Li Xiaohui , He Jingsha , Zhao Bin , Fang Jing , Zhang Yixuan , Liang Hongxing
Published: February 2016

Cloud computing and Internet of Things (IoT) are emerging technologies that have experienced rapid development in recent years. While cloud computing presents a new platform over which services are offered to the user more conveniently, IoT facilitates the collection of a large amount of data via interconnected wireless sensors for event monitoring and control. In such environments, ownership and control over the data may lead to potential conflict between the protection of data and the provision of services. Thus, cloud security has received a great deal of attention in recent years. In this paper, we propose a method for trust quantification based on fuzzy comprehensive evaluation theory for cloud computing to protect user data through trust quantification of cloud services after we introduce trust ontology for cloud services and define user preference trust values. By enhancing the existing trust concept based on dynamic requirements, we introduce some cloud service attributes to study layered service representation for trust preference and then apply the fuzzy comprehensive evaluation theory to perform trust quantification. We also perform some experiment to show that the proposed method is effective and can dynamically perform trust quantification to deal with malicious acts of nonfaithful services.