bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Renin–Angiotensin System, Not the Kinin–Kallikrein System, Affects Post-Exercise Proteinuria
Authors: Koçer Günnur , Basralı Filiz , Kuru Oktay , Şentürk Ümit Kemal 
Published: May 2018

<b><i>Background/Aims:</i></b> Temporary proteinuria post-exercise is common and is caused predominantly by renal haemodynamic alterations. One reason is up-regulation of angiotensin II (Ang II) due to the reducing effect of angiotensin-converting enzyme (ACE) inhibitors. However, another, ignored, reason could be the kininase effect of ACE inhibition. This study investigated how ACE inhibition reduces post-exercise proteinuria: by either Ang II up-regulation inhibition or bradykinin elevation due to kininase activity inhibition. <b><i>Methods:</i></b> Our study included 10 volunteers, who completed 3 high-intensity exercise protocols involving cycling at 1-week intervals. The first protocol was a control arm, the second evaluated the effect of ACE inhibition and the third examined the effect of angiotensin type 1 receptor blockade. Upon application, both agents reduced systolic and diastolic blood pressure; however, there were no statistically significant ­differences. In addition, total protein, microalbumin and ­β<sub>2</sub>-microglobulin excretion levels in urine specimens were analysed before, 30 min after and 120 min after the exercise protocols. <b><i>Results:</i></b> Total protein levels in urine samples were elevated in all 3 protocols after 30 min of high-intensity exercise, compared to baseline levels. However, both ACE inhibition and angiotensin type 1 receptor blockade suppressed total protein in the 30th min. In each protocol, total protein levels returned to the baseline after 120 min. Urinary microalbumin and β<sub>2</sub>-microglobulin levels during the control protocol were significantly higher 30 min post-exercise; however, only angiotensin type 1 receptor blockade suppressed microalbumin levels. <b><i>Conclusion:</i></b> The results indicated Ang II up-regulation, not bradykinin elevation, plays a role in post-exercise proteinuria.
nSMase2 (Type 2-Neutral Sphingomyelinase) Deficiency or Inhibition by GW4869 Reduces Inflammation and Atherosclerosis in Apoe
−/−
Mice
Authors: Lallemand Tom , Rouahi Myriam , Swiader Audrey , Grazide Marie-Hélène , Geoffre Nancy , Alayrac Paul , Recazens Emeline , Coste Agnès , Salvayre Robert , Nègre-Salvayre Anne , Augé Nathalie 
Published: May 2018

Objective—
Atherosclerosis is a chronic multifactorial and inflammatory disease of large and medium arteries and the leading cause of cardiovascular diseases worldwide. The aim of this study was to investigate whether and how the nSMase2 (type 2-neutral sphingomyelinase), a key enzyme of sphingolipid metabolism, may contribute to the development of atherosclerotic lesions.

Approach and Results—

The role of nSMase2 in atherosclerosis was investigated in
Apoe
−/−
;Smpd3

fro/fro

mice, mutant for nSMase2, and in
Apoe
−/−
;Smpd3
+/+
mice intraperitoneally injected with GW4869, a pharmacological nSMase2 inhibitor. The defect or inhibition of nSMase2 resulted in a reduction of atherosclerotic lesions and a decrease in macrophage infiltration and lipid deposition, although cholesterolemia remained unchanged. nSMase2 inhibition decreased the inflammatory response of murine endothelial cells to oxLDL (oxidized low-density lipoprotein), as assessed by the significant reduction of MCP-1 (monocyte chemoattractant protein 1), ICAM-1 (intercellular adhesion molecule-1), and VCAM-1 (vascular cell adhesion molecule-1) mRNA expressions and macrophage recruitment. Likewise, in RAW264.7 or in macrophages isolated from
Apoe
−/−
/Smpd3

fro/fro

or
Apoe
−/−
/Smpd3
+/+
mice stimulated by lipopolysaccharides, nSMase2 inhibition resulted in a decrease in the expression of inflammatory molecules. Mechanistically, the anti-inflammatory response resulting from nSMase2 inhibition involves Nrf2 (nuclear factor [erythroid-derived 2]-like 2 or NF-E2–related factor-2) activation in both endothelial cells and macrophages, as assessed by the lack of protective effect of GW4869 in endothelial cells silenced for Nrf2 by small interfering RNAs, and in lipopolysaccharide-stimulated macrophages issued from Nrf2-KO mice.

Conclusions—

The genetic deficiency or inhibition of nSMase2 strongly decreases the development of atherosclerotic lesions in
Apoe
−/−
mice, by reducing inflammatory responses through a mechanism involving the Nrf2 pathway. Inhibitors of nSMase2 may, therefore, constitute a novel approach to slow down atherosclerosis progression.
Periprocedural Outcomes of Direct Oral Anticoagulants Versus Warfarin in Nonvalvular Atrial Fibrillation
Authors: Nazha Bassel , Pandya Bhavi , Cohen Jessica , Zhang Meng , Lopes Renato D. , Garcia David A. , Sherwood Matthew W. , Spyropoulos Alex C. 
Published: May 2018

Background:
Direct oral anticoagulants (DOACs) are surpassing warfarin as the anticoagulant of choice for stroke prevention in nonvalvular atrial fibrillation. DOAC outcomes in elective periprocedural settings have not been well elucidated and remain a source of concern for clinicians. The aim of this meta-analysis was to evaluate the periprocedural safety and efficacy of DOACs versus warfarin in patients with nonvalvular atrial fibrillation.

Methods:

We reviewed the literature for data from phase III randomized controlled trials comparing DOACs with warfarin in the periprocedural period among patients with nonvalvular atrial fibrillation. Substudies from 4 trials (RE-LY [Randomized Evaluation of Long-Term Anticoagulation Therapy], ROCKET AF [Rivaroxaban Once Daily Oral Direct Factor Xa Inhibitor Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation], ARISTOTLE [Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation], and ENGAGE-AF [Effective Anticoagulation With Factor xA Next Generation in Atrial Fibrillation]) were included in the meta-analysis. DOACs as a group and warfarin were compared in terms of the 30-day pooled risk for stroke/systemic embolism, major bleeding, and death, according to whether the study drug was interrupted or not periprocedurally. The overall relative risk (RR) was estimated with a random-effects model. The
I
2
test was used to assess heterogeneity in RR among the studies.

Results:

In the uninterrupted anticoagulant strategy, there were no differences in the rates of stroke/systemic embolism (pooled risk, 0.6% [29 events/4519 procedures] versus 1.1% [31/2971]; RR, 0.70; 95% confidence interval [CI], 0.41–1.18) and death (1.4% versus 1.8%; RR, 0.77; 95% CI, 0.53–1.12) between DOACs and warfarin and significantly fewer major bleeding events (2.0% versus 3.3%; RR, 0.62; 95% CI, 0.47–0.82) with DOACs compared to warfarin. Under an interrupted strategy, there was no significant difference between DOACs versus warfarin for stroke/systemic embolism (0.4% [41/9260] versus 0.5% [31/7168]; RR, 0.95; 95% CI, 0.59–1.55), major bleeding (2.1% versus 2.0%; RR, 1.05; 95% CI, 0.85–1.30), and death (0.7% versus 0.6%; RR, 1.24; 95% CI, 0.76–2.04). The studies were homogeneous (
I
2
=0.0%) for all calculated pooled associations except for the RR of death in the interrupted strategy (
I
2
=26.3%).

Conclusions:
The short-term safety and efficacy of DOACs and warfarin are not different in patients with nonvalvular atrial fibrillation periprocedurally. Under an uninterrupted anticoagulation strategy, DOACs are associated with a 38% lower risk of major bleeding compared with warfarin.
Referential complementarity in traditional Negev Arabic
Authors: Cerqueglini Letizia , Henkin Roni 
Published: May 2018

Abstract
Spatial Frames of Reference (FoRs) are mental coordinate systems applied to locate a Figure (F) with respect to a Ground (G). In Levinson’s theory (2003), every language selects a dominant FoR among Intrinsic, Relative and Absolute, leaving non-dominant FoRs for restricted sets of cases. Bohnemeyer (2011) enlarged this typology, describing ‘referentially promiscuous systems’, as characterized by free switch among FoRs and absence of a default strategy used by the whole community. We show here that Traditional Negev Arabic (TNA) represents a new, hitherto unknown type, which we label ‘referential complementarity’: all its speakers use all three FoRs in everyday discourse, yet not freely switching among them. Different Gs of traditional life, when observed in their traditional locations, prime specific referential strategies: inherently partitioned Gs (horse/coffee-pot) prime the binary Intrinsic FoR; those with no inherent partition (stone/tree) prime ternary Relative or Absolute FoRs, depending on their alignment vis-à-vis the Observer (O). Interestingly, culturally salient objects considered integral to the tent, such as a hosting cushion or a tent pole, absorb the tent’s Intrinsic orientation; but outside the tent these behave just like their non-tent-integral counterparts (stone/tree). In particular, the Absolute FoR is used for (i) culturally unfamiliar Gs (chair/shoe/dinosaur) and (ii) certain Gs in non-salient O-F-G alignments. We conclude that FoR selection in TNA follows culture-specific rules, paying more attention to cultural familiarity or salience than to supposedly universal metrical and formal features.
The Influence of the Lower Stratosphere on Ridging Atlantic Ocean Anticyclones over South Africa
Authors: Ndarana Thando , Bopape Mary-Jane , Waugh Darryn , Dyson Liesl 
Published: May 2018

AbstractThe link between Rossby wave breaking and ridging Atlantic Ocean anticyclones in the South African domain is examined using NCEP–DOE AMIP-II reanalysis data. A simple composite analysis, which used the duration of ridging events as a basis of averaging, reveals that ridging anticyclones are coupled with Rossby wave breaking at levels higher than the dynamical tropopause. Lower-stratospheric PV anomalies extend to the surface, thus coupling the ridging highs with the lower stratosphere. The anomaly extending from the 70-hPa level to the surface contributes to a southward extension of the surface negative anomaly over the Namibian coast, which induces a cyclonic flow, causing the ridging anticyclone to take a bean-like shape. The surface positive anomaly induces the internal anticyclonic flow within the large-scale pressure system, causing the ridging end to break off and amalgamate with the Indian Ocean high pressure system. Lower-stratospheric Rossby wave breaking lasts for as long as the ridging process, suggesting that the former is critical to the longevity of the latter by maintaining and keeping the vertical coupling intact.
An assessment of the effect of haemoglobin variants on detection by faecal immunochemical tests
Authors: Carroll Magdalen RR , John Cerin , Mantio Debbie , Djedovic Natasha K , Benton Sally C 
Published: May 2018

Background Faecal immunochemical tests (FIT) for haemoglobin (Hb) are being used in the investigation of colorectal cancer. These tests use antibodies raised to the globin moiety of human Hb. Where the globin structure is abnormal or reduced, it is possible that antibody binding, and thus Hb-detection may be affected. Methods Lysates prepared from whole blood samples of patients with known variants were diluted in manufacturer-specific buffer to 10, 100 and 500 μg Hb/g faeces. These samples were analysed on four FIT analysers and the results compared with samples with no known variant present (normal samples). Results The results from this study show that of 20 variants tested, three showed a decrease in detection by all four analysers. These were β-thalassaemia major and two fetal cord blood samples. Conclusions Of 20 common Hb variants studied, 17 did not affect detection of Hb by the FIT systems tested. Hb variants leading to a reduction in the presence of a globin chain caused a reduction in Hb detection; in such cases, cancers could be missed.
Performance and drug release studies of poly (ɛ-caprolactone)/γ-poly (glutamic acid) fibrous membranes
Authors: Zhan Henan , Liu Shan , Hu Xiyu , Jiang Dong 
Published: May 2018

Fibrous membranes of poly(ɛ-caprolactone)/γ-poly(glutamicacid) (PCL/γ-PGA) composites were successfully produced via an electrospinning process. In doing so, the water solubility of florfenicol (FF) could be enhanced and the drug release properties of FF could be controlled. The mechanical, morphologic, and thermal properties of the fibrous membranes of PCL/γ-PGA were studied by using an electronic single fiber strength machine, scanning electron microscopy, and differential scanning calorimetry. The wettability of the fibrous membranes of PCL/γ-PGA was also measured as discussed in the subsequent section. Fourier transform infrared spectroscopy was applied in the structural analysis of the PCL/γ-PGA-FF fibrous membranes. The results indicated that FF was well blended in the composite membranes of PCL/γ-PGA. In vitro dissolution tests showed that PCL/γ-PGA (85/15; 8%) as both a biodegradable and biocompatible blend may improve the solubility of FF. Therefore, fibrous membranes of PCL/γ-PGA may represent ideal materials for the controlled drug release in various clinical applications.
Increasing rates for certification of visual impairment at Royal Cornwall Hospital Trust: An audit series
Authors: Savage Nicholas St John , Claridge Kate , Green Jessica 
Published: May 2018

The audit series investigated how rates of Certification of Visual Impairment (CVI) at Royal Cornwall Hospital Trust (RCHT) performed when compared against Public Health England (PHE) indices. Our aim was to assess whether CVI rates could be improved by promoting clinician awareness. We collected CVI data for Sight Impairment (SI) and Severe Sight Impairment (SSI) from a prospective MS Excel database maintained at RCHT for all certifications between 1 August 2014 and 31 July 2016. Annual local certification rates were compared to regional and national rates using data from Public Health Outcomes Framework (PHOF) for glaucoma, age-related macular degeneration (ARMD), and diabetic eye disease. We found that overall rates of certification were above both those of the South West region and England; however, certifications for ARMD and glaucoma fell below the regional and national rates. Reasons for this may include variations in ethnicity, introduction of anti-vascular endothelial growth factor (anti-VEGF) agents, and/or the potential delay in CVI completion while under treatment for ARMD. We concluded that raising awareness among clinicians did not prove a satisfactory intervention to improve certification rates. In response to these findings, RCHT and a local charity, iSight Cornwall, have jointly funded an Eye Clinic Liaison Officer (ECLO) to enhance the certification process. This is expected to deliver immediate service improvement. Considerable overlap in dual diagnoses presents a problem in interpretation of CVI data, which could be targeted by the implementation of electronic certification.
The therapeutic potential of the mesenchymal stem cell secretome in ischaemic stroke
Authors: Cunningham Catriona J , Redondo-Castro Elena , Allan Stuart M 
Published: May 2018

Mesenchymal stem cells (MSCs) hold great potential as a regenerative therapy for stroke, leading to increased repair and functional recovery in animal models of cerebral ischaemia. While it was initially hypothesised that cell replacement was an important mechanism of action of MSCs, focus has shifted to their paracrine actions or the so called “bystander” effect. MSCs secrete a wide array of growth factors, chemokines, cytokines and extracellular vesicles, commonly referred to as the MSC secretome. There is evidence suggesting the MSC secretome can promote repair through a number of mechanisms including preventing cell apoptosis, modulating the inflammatory response and promoting endogenous repair mechanisms such as angiogenesis and neurogenesis. In this review, we will discuss the in vitro approaches currently being employed to drive the MSC secretome towards a more anti-inflammatory and regenerative phenotype. We will then examine the role of the secretome in promoting repair and improving recovery in preclinical models of cerebral ischaemia.
Increased diagnostic confidence in the diagnosis of pituitary micro-lesions with the addition of three-dimensional sampling perfection with application-optimized contrasts using different flip-angle evolutions sequences
Authors: Tang Ying , Wu Yue , Zhang Hua , Wang Jing , Yao ZhenWei 
Published: May 2018

Background Conventional magnetic resonance imaging (MRI) is adversely affected by thick slices, small intersection gaps, and the partial volume effect, leading to the missed diagnosis or misdiagnosis of pituitary micro-lesions. Purpose To evaluate the diagnostic yield of three-dimensional sampling perfection with application-optimized contrasts using different flip-angle evolutions (3D-T2 SPACE) sequences compared with a standard MRI protocol for the diagnosis of pituitary micro-lesions. Material and Methods The MRI findings of 664 patients with clinically suspected pituitary lesions were retrospectively analyzed. All patients underwent coronal 3D-T2 SPACE sequences followed by T1-weighted (T1W) imaging. Conventional scanning sequences included coronal and sagittal T1W imaging and post-contrast enhanced coronal and sagittal T1 imaging. All images were independently evaluated by two experienced neuroradiologists. The inter-observer agreement was analyzed using kappa statistics. Results Compared with conventional sequences, there was an increase in diagnostic confidence of 60.3% for the diagnosis of pituitary micro-lesions with the addition of 3D-T2 SPACE sequences. The lesion conspicuity scores of combined conventional and 3D-T2 SPACE sequences were significantly higher than those of conventional imaging (z = −6.403, P < 0.01) and 3D-T2 SPACE sequences (z = −4.243, P < 0.01). In addition, the inter-observer agreement of 3D-T2 SPACE sequences was good (κ = 0.826). Conclusion Combined with routine sequences, post-contrast enhanced 3D-T2 SPACE sequences effectively improve diagnostic confidence in the diagnosis of pituitary micro-lesions. Post-contrast enhanced 3D-T2 SPACE is suitable for detecting pico-adenomas, micro-lesions adjacent to the cavernous sinuses or sellar floor, lesions between the anterior and posterior lobes, and lesions with early phase enhancement.
Utility of a novel elastic traction system in endoscopic thyroidectomy via breast approach: initial experience with 34 patients
Authors: Lyu Yi-Jun , Shen Fang , Zhang Hai , Chen Gao-Xiang 
Published: May 2018

Objective To summarize our experiences in using an elastic traction, space-making technique for endoscopic thyroidectomy via breast approach in the treatment of early-stage differentiated papillary thyroid carcinoma. Methods A retrospective analysis was performed on patients who underwent endoscopic thyroidectomy via breast approach for thyroid carcinoma in our department. We used our self-developed “mini elastic traction space-maker” in a group of 34 patients; another 45 patients who underwent the procedure with the conventional CO2 insufflation method were enlisted as the control group. Results All patients had successful unilateral lobectomy and central lymph node dissection (CLND) surgeries. The adoption of the intraoperative elastic traction system increased the height of the subcutaneous working space (by 1 cm) and significantly decreased the times required for lobectomy and CLND compared with the controls (46.7 ± 4.7 min vs. 50.7 ± 4.9 min). However, there was no significant difference between the two groups in the set-up time to create the working space. Conclusions The elastic traction, space-making technique is a safe and feasible technique for endoscopic thyroidectomy via breast approach.
Drug cost avoidance in clinical trials of breast cancer
Authors: Mañes-Sevilla M , Romero-Jiménez R , Herranz-Alonso A , Sánchez-Fresneda M , Gonzalez-Haba E , Collado-Borrel R , Benedi-González J , Sanjurjo-Sáez M 
Published: May 2018

Background The objectives of this study were to determine if clinical trials in breast cancer, with an investigational drug, created direct drug cost savings for the healthcare system related to cost avoidance of the best standard of care treatments used in these studies. The aim was to quantify this potential drug cost avoidance. Methods We conducted a retrospective observational study of the drug cost avoidance during the study period (2014–2016). We included clinical trials with investigational drug, managed by pharmacy department and provided by the sponsor. The patients included had a therapeutic alternative defined as standard treatment that should have been received in case of not participating in the clinical trial. Direct cost savings, to national healthcare system, associated to clinical trials were calculated. Results Thirty-seven clinical trials with a total of 89 breast cancer patients were included in the study. A total of 62.2% were phase III and 75.7% belonged to the pharmaceutical industry. They provided a total cost avoidance of 957,246€ (1,130,028$), an average cost avoidance per patient of 10,756€ (12,697$). Conclusions Our study suggests that those clinical trials in which investigational drug are provided or refunded by the sponsor provide substantial cost savings. Due to the shortage of published articles that calculate the cost avoided in medication, we cannot compare directly the results obtained in the different institutions.
Stakeholders' resistance to telemedicine with focus on physicians: Utilizing the Delphi technique
Authors: Choi Woo Seok , Park Joowoong , Choi Jin Young Brian , Yang Jae-Suk 
Published: May 2018

Introduction Sufficient infrastructure for information and communications technology (ICT) and a well-established policy are necessary factors for smooth implementation of telemedicine. However, despite these necessary conditions being met, there are situations where telemedicine still fails to be accepted as a system due to the low receptivity of stakeholders. In this study, we analyse stakeholders' resistance to an organization's implementation of telemedicine. Focusing on the physicians' interests, we propose a strategy to minimize conflicts and improve acceptance. Methods The Delphi study involved 190 telemedicine professionals who were recommended by 485 telemedicine-related personnel in South Korea. Results Out of 190 professionals, 60% of enrolled participants completed the final questionnaires. The stakeholders were categorized into four groups: policy-making officials, physicians, patients, and industrialists. Among these, the physicians were most opposed to the adoption of telemedicine. The main causes of such opposition were found to be the lack of a medical services delivery system and the threat of disruption for primary care clinics. Very little consensus was observed among the stakeholders, except on the following points: the need for expansion of the national health insurance budget by the government, and the need for enhancement of physicians' professional autonomy to facilitate smooth agreements. Discussion Our analysis on the causes of the resistance to telemedicine, carried out with the groups mentioned above, has important implications for policy-makers deriving strategies to achieve an appropriate consensus.