bluuebunny/crossref_metadata_2025 huggingface dataset:
The developmental regulator MtrA binds GlnR boxes and represses nitrogen metabolism genes inStreptomyces coelicolor
Authors: Zhu Yanping , Zhang Peipei , Zhang Jing , Xu Wenhao , Wang Xinyuan , Wu Lili , Sheng Duohong , Ma Wei , Cao Guangxiang , Chen Xiu‐lan , Lu Yinhua , Zhang Yu‐Zhong , Pang Xiuhua
Published: March 2019

InStreptomyces, GlnR is an activator protein that activates nitrogen‐assimilation genes under nitrogen‐limiting conditions. However, less is known regarding the regulation of these genes under nitrogen‐rich conditions. We determined that the developmental regulator MtrA represses nitrogen‐assimilation genes in nitrogen‐rich media and that it competes with GlnR for binding to GlnR boxes. The GlnR boxes upstream of multiple nitrogen genes, such asamtB, were confirmed as MtrA binding sitesin vitroby electrophoretic mobility shift assays andin vivoby ChIP‐qPCR analysis. Transcriptional analysis indicated that, on nutrient‐rich medium, MtrA profoundly repressed expression of nitrogen‐associated genes, indicating opposing roles for MtrA and GlnR in the control of nitrogen metabolism. Usingin vitroandin vivoanalysis, we also showed thatglnRis itself a direct target of MtrA and that MtrA repressesglnRtranscription. We further demonstrated functional conservation of MtrA homologues in the recognition of GlnR boxes upstream of nitrogen genes from different actinobacterial species. AsmtrAandglnRare widespread among actinomycetes, this mechanism of potential competitive control over nitrogen metabolism genes may be common in this group, adding a major new layer of complexity to the known regulatory network for nitrogen metabolism inStreptomycesand related species.
Electrophysiological evidence of sustained spatial attention effects over anterior cortex: Possible contribution of the anterior insula
Authors: Berchicci Marika , Ten Brink Antonia Francisca , Quinzi Federico , Perri Rinaldo Livio , Spinelli Donatella , Di Russo Francesco
Published: March 2019

Spatial attention can improve performance in terms of speed and accuracy; this advantage may be mediated by brain processes at both poststimulus (reactive) and prestimulus (proactive) stages. Here, we studied how visuospatial attention affects both proactive and reactive brain functions using event‐related potentials (ERPs). At reactive stage, effects of attention on parietal‐occipital components are well documented; little data are available on anterior components. Seventeen participants performed simple and discriminative response tasks, while voluntarily and steadily attending either the left or right visual hemifield throughout one block. Response speed was faster for the attended side. At ERP level, attending to one hemifield did not produce lateralization of proactive components—that is, the BP and the pN. As for poststimulus components, we confirmed the well‐known amplitude effects on the P1, N1, and P3. More interesting are results for the prefrontal components previously neglected in tasks modulating spatial attention. Previous studies suggest that these components reflect perceptual and sensory‐motor awareness (pN1 and pP1 components), and stimulus‐response mapping (pP2 component) associated to anterior insular activity. Spatial attention enhanced the pN1 and the pP1 amplitude but had no effect on the pP2. Overall, results extend knowledge on spatial attention, showing that sustained spatial attention affects the activity of anterior areas, such as the anterior insula, in addition to the known influence on occipital‐parietal areas. Top‐down spatial attention is likely mediated by increased sensory and sensory‐motor awareness for attended events; this effect is evident in reactive, not proactive, brain activity.
Quantitative micro‐X‐ray fluorescence scanning spectroscopy of wet sediment based on the X‐ray absorption and emission theories: Its application to freshwater lake sedimentary sequences
Authors: Katsuta Nagayoshi , Takano Masao , Sano Naomi , Tani Yukinori , Ochiai Shinya , Naito Sayuri , Murakami Takuma , Niwa Masakazu , Kawakami Shin‐ichi
Published: March 2019

Micro‐X‐ray fluorescence scanning spectroscopy of marine and lake sedimentary sequences can provide detailed palaeoenvironmental records through element intensity proxy data. However, problems with the effects of interstitial pore water on the micro‐X‐ray fluorescence intensities have been pointed out. This is because the X‐ray fluorescence intensities are measured directly at the surfaces of split wet sediment core samples. This study developed a new method for correcting X‐ray fluorescence data to compensate for the effects of pore water using a scanning X‐ray analytical microscope. This involved simultaneous use of micro‐X‐ray fluorescence scanning spectroscopy and an X‐ray transmission detector. To evaluate the interstitial pore water content from the X‐ray transmission intensities, a fine‐grained sediment core retrieved from Lake Baikal (VER99‐G12) was used to prepare resin‐embedded samples with smooth surfaces and uniform thickness. Simple linear regression between the linear absorption coefficients of the samples and their porosity, based on the Lambert–Beer law, enabled calculation of the interstitial pore spaces and their resin content with high reproducibility. The X‐ray fluorescence intensities of resin‐embedded samples were reduced compared with those of dry sediment samples because of: (i) the X‐ray fluorescence absorption of resin within sediment; and (ii) the sediment dilution effects by resin. An improved micro‐X‐ray fluorescence correction equation based on X‐ray fluorescence emission theory considers the instrument's sensitivity to each element, which provides a reasonable explanation of these two effects. The resin‐corrected X‐ray fluorescence intensity was then successfully converted to elemental concentrations using simple linear regression between the data from micro‐X‐ray fluorescence scanning spectroscopy and from the conventional analyzer. In particular, the calculated concentration of SiO2 over the depth of the core, reflecting diatom/biogenic silica concentration, was significantly changed by the calibrations, from a progressively decreasing trend to an increasing trend towards the top of the core.
High rates of indeterminate interferon‐gamma release assays for the diagnosis of latent tuberculosis infection in liver transplantation candidates
Authors: Wigg Alan J. , Narayana Sumudu K. , Anwar Shahzaib , Ramachandran Jeyamani , Muller Kate , Chen John W. , John Libby , Hissaria Pravin , Kaambwa Billingsley , Woodman Richard J.
Published: March 2019

Background and aims

Screening for latent tuberculosis infection (LTBI) is recommended prior to solid organ transplantation. Interferon‐gamma release assays (IGRAs) are the most widely used test for LTBI screening; however, assessment of IGRA performance in patients with end‐stage liver disease is limited. The purpose of this study was to evaluate the prevalence and predictors of indeterminate (INDT) IGRA results in liver transplantation candidates.

Methods

Between March 2011 and May 2018, we retrospectively analyzed 155 patients undergoing liver transplantation assessment, who underwent IGRA testing (Quantiferon‐TB Gold, QFT‐G) to exclude LTBI. Characteristics of patients, including age, gender, etiology of liver disease, MELD score, and absolute lymphocyte counts, were compared by QFT‐G result (determinate vs INDT).

Results

Of the 155 patients screened, the rate of positive, negative, and INDT results were 5.2%, 69.8%, and 25%, respectively. The only variable independently associated with an indeterminate test on multivariate analysis was MELD score (odds ratio = 1.07, 95% CI = 1.01‐1.14 per unit increase; P = 0.014). In 95% of INDT tests, both TB antigen tube and the positive control tube were negative and repeat testing gave the same indeterminate result, suggestive of anergy rather than laboratory error.

Conclusions

Our study suggests a high rate of INDT IGRA results during screening of liver transplant candidates for LTBI, associated with severity of liver disease and anergy. Because of the high rate of INDT QFT‐G testing in this setting, individualized risk assessment is required including a thorough assessment of clinical risk factors and knowledge of local TB prevalence.
Using natural variation to achieve a whole‐plant functional understanding of the responses mediated by jasmonate signaling
Authors: Ray Rishav , Li Dapeng , Halitschke Rayko , Gase Klaus , Baldwin Ian T.
Published: March 2019

The dramatic advances in our understanding of the molecular biology and biochemistry of jasmonate (JA) signaling have been the subject of several excellent recent reviews that have highlighted the phytohormonal function of this signaling pathway. Here, we focus on the responses mediated by JA signaling which have consequences for a plant's Darwinian fitness, i.e. the organism‐level function of JA signaling. The most diverse module in the signaling cascade, the JAZ proteins, and their interactions with other proteins and transcription factors, allow this canonical signaling cascade to mediate a bewildering array of traits in different tissues at different times; the functional coherence of these diverse responses are best appreciated in an organismal/ecological context. From published work, it appears that jasmonates can function as the ‘Swiss Army knife’ of plant signaling, mediating many different biotic and abiotic stress and developmental responses that allow plants to contextualize their responses to their frequently changing local environments and optimize their fitness. We propose that a deeper analysis of the natural variation in both within‐plant and within‐population JA signaling components is a profitable means of attaining a coherent whole‐plant functional perspective of this signaling cascade, and provide examples of this approach from the Nicotiana attenuata system.
Putting financialisation in its financial context: Transformations in local government‐led urban development in post‐financial crisis England
Authors: Christophers Brett
Published: March 2019

The burgeoning geographical literature on the financialisation of urban development has focused predominantly on the growing importance within this sphere of financial markets, motives, and institutions. This article starts from the observation that in examining such financialisation, scholars have paid insufficient attention to the details of the financial contexts within which it takes place. Through a consideration of certain high‐profile ongoing transformations in the property strategies of English local authorities, the article argues that we need to put urban financialisation – in this case, state‐led variants thereof – in its financial context: it needs to be understood as a response, at least in part, to specific financial conjunctures. After several decades of effective withdrawal, many local authorities have assumed a resurgent role in urban property ownership and development in recent years, and especially since the global financial crisis. This resurgence is apparent, albeit selectively, in regard to both commercial and residential property. On the one hand, local authorities have been rebuilding portfolios of investment (i.e., non‐operational) commercial property; on the other hand, they have been building new homes, typically not for social rent, through arms‐length housing companies. I argue that understanding these trends requires appreciation of local authorities’ particular financial circumstances in the “post‐crisis” era – their operation at the intersection of devolved austerity, reformed housing finance, and unconventional monetary policy – and of the constraints and opportunities that these circumstances shape.
The influence of acute hyperglycaemia on brachial artery flow‐mediated dilatation in the early and late follicular phases of the menstrual cycle
Authors: Williams Jennifer S. , Stimpson Taylor V. , Tremblay Joshua C. , Fenuta Alyssa M. , Pyke Kyra E.
Published: March 2019

New Findings

What is the central question of the study?

This is the first study to examine the impact of acute hyperglycaemia on endothelial function [flow‐mediated dilatation (FMD)] in premenopausal women across the early and late follicular (EF and LF) phases of the menstrual cycle.

What is the main finding and its importance?

Flow‐mediated dilatation was impaired 90 min after glucose ingestion, with no significant difference between phases. This indicates that women are susceptible to acute hyperglycaemia‐induced endothelial dysfunction in both the EF and LF phases of the menstrual cycle, despite potentially vasoprotective elevations in estradiol levels during the LF phase.

Acute hyperglycaemia transiently impairs endothelial function in healthy men when assessed via flow‐mediated dilatation (FMD). However, research in female participants is lacking, and the impact of menstrual phase [early follicular (EF) and late follicular (LF)] on vulnerability to acute hyperglycaemia‐induced endothelial dysfunction is unknown. Seventeen healthy, naturally menstruating women [21 ± 1 years old (mean ± SD)] participated in three visits. During two visits (EFGlucose and LFGlucose), brachial artery FMD was assessed before and 60, 90 and 120 min after an oral glucose challenge (75 g glucose). During an additional EF visit, participants ingested 300 ml of water (EFTimeControl). Blood glucose and insulin increased 30 min after glucose ingestion (P < 0.001), with no difference between phases. Flow‐mediated dilatation did not change in EFTimeControl (P = 0.748) but was reduced 90 min after glucose ingestion (Pre, 8.5 ± 2.5%; Post90, 6.6 ± 2.4%, P = 0.001; Cohen's d = 0.82), with no difference between phases (main effect of phase, P = 0.506; phase by time interaction, P = 0.391). To account for individual variability in the time course of the impact of hyperglycaemia, the maximal hyperglycaemia‐induced impairment in FMD was determined in each participant and compared between phases, revealing no significant phase differences (EFGlucose, −3.1 ± 2.8%; LFGlucose, −2.4 ± 2.1%, P = 0.181; d = 0.34). These results indicate that, similar to findings in men, acute hyperglycaemia results in FMD impairment in young women. We did not detect significant protection from acute hyperglycaemia‐induced endothelial dysfunction in the LF ‘high‐oestrogen’ phase in this sample, and further research is needed to examine the potential for a protective effect of oestrogen exposure, including oral contraceptive pills and hormone replacement therapy.
A voltage‐dependent depolarization induced by low external glucose in neurons of the nucleus of the tractus solitarius: interaction with KATP channels
Authors: De Bernardis Murat Cahuê , Leão Ricardo Mauricio
Published: March 2019

Key points

Neurons from the brainstem nucleus of the tractus solitarius (NTS) participate in the counter‐regulatory mechanisms in response to hypoglycaemia.

ATP‐sensitive potassium (KATP) channels are expressed in NTS neurons, and are partially open at rest in normoglycaemic 5 mM glucose.

In normoglycaemic conditions, most NTS neurons depolarize in response to low external glucose (0.5 mM), via a voltage‐dependent mechanism.

Conversely, most NTS neurons incubated in hyperglycaemic 10 mM glucose do not respond to low glucose due to a more positive resting membrane potential caused by the closure of KATP channels following increased intracellular metabolic ATP.

Our findings show that in hyperglycaemic conditions, NTS neurons failed to sense rapid changes in external glucose, which could be related to hypoglycaemia‐associated autonomic failure.

The nucleus of the tractus solitarius (NTS) is an integrative centre for autonomic counter‐regulatory responses to hypoglycaemia. KATP channels link the metabolic status of the neuron to its excitability. Here we investigated the influence of KATP channels on the membrane potential of NTS neurons in normo‐ and hyperglycaemic external glucose concentrations, and after switching to a hypoglycaemic concentration, using in vitro electrophysiological recordings in brainstem slices. We found that in normoglycaemic (5 mM) glucose, tolbutamide, a KATP channel antagonist, depolarized the membrane of most neurons, and this effect was observed in more hyperpolarized neurons. All neurons hyperpolarized after pharmacological activation of KATP channels. Most NTS neurons depolarized in the presence of low glucose (0.5 mM), and this effect was only seen in hyperpolarized neurons. The effect of glucose was caused by a cationic current with a reversal potential around −50 mV. In the presence of hyperglycaemic glucose (10 mM), neurons were more depolarized, and fewer neurons responded to KATP blockage. Application of 0.5 mM glucose solution to these neurons depolarized the membrane only in more hyperpolarized neurons. We conclude that NTS neurons present with KATP channels open at rest in normoglycaemic conditions, and their membrane potential is affected by extracellular glucose. Moreover, NTS neurons depolarize the membrane in response to the application of a low glucose solution, but this effect is occluded by membrane depolarization triggered by KATP blockage. Our data suggest a homeostatic regulation of the membrane potential by external glucose, and a possible mechanism related to the hypoglycaemia‐associated autonomic failure.
Three-Dimensional Thermo-Elasto-Hydrodynamic Computational Fluid Dynamics Model of a Tilting Pad Journal Bearing—Part II: Dynamic Response
Authors: Yang Jongin , Palazzolo Alan
Published: March 2019

Part II presents a novel approach for predicting dynamic coefficients for a tilting pad journal bearing (TPJB) using computational fluid dynamics (CFD) and finite element method (FEM), including fully coupled elastic deflection, heat transfer, and fluid dynamics. Part I presented a similarly novel, high fidelity approach for TPJB static response prediction which is a prerequisite for the dynamic characteristic determination. The static response establishes the equilibrium operating point values for eccentricity, attitude angle, deflections, temperatures, pressures, etc. The stiffness and damping coefficients are obtained by perturbing the pad and journal motions about this operating point to determine changes in forces and moments. The stiffness and damping coefficients are presented in “synchronously reduced form” as required by American Petroleum Institute (API) vibration standards. Similar to Part I, an advanced three-dimensional thermal—Reynolds equation code validates the CFD code for the special case when flow Between Pad (BP) regions is ignored, and the CFD and Reynolds pad boundary conditions are made identical. The results show excellent agreement for this validation case. Similar to the static response case, the dynamic characteristics from the Reynolds model show large discrepancies compared with the CFD results, depending on the Reynolds mixing coefficient (MC). The discrepancies are a concern given the key role that stiffness and damping coefficients serve instability and response predictions in rotordynamics software. The uncertainty of the MC and its significant influence on static and dynamic response predictions emphasizes a need to utilize the CFD approach for TPJB simulation in critical machines.
A Semianalytical Vibration Analysis of Partially Wet Square Cantilever Plate With Numerical and Experimental Verification: Partially Wet Modeshapes
Authors: Verma Y. , Datta N. , Praharaj R.
Published: March 2019

A semianalytical study of a uniform homogenous partially submerged square cantilever plate vibration is presented. The structure is assumed to be a Kirchhoff's plate, clamped on one edge and free on the other edges. The lengthwise section of the plate is a cantilever clamped-free (CF) beam, while the widthwise section is a free-free (FF) beam. The plate modeshape is a weighted superposition of the product of the beam modeshapes, with unknown weights. The CF beam has only flexural modes. The FF beam has two rigid-body modes, i.e., translational and rotational modes. Rayleigh–Ritz method (RRM) is used to set up the free vibration eigenvalue problem. The eigenvector gives the unknown weights. The modeshapes generated are further used in the boundary element method (BEM) to calculate the fluid inertia, which participates in the vibration and leads to a consistent drop in frequencies. The dependence of this reduction on the submergence level is studied for the first six frequencies of the plate. The frequencies are also experimentally generated by the impact hammer test, both in the dry state, and under three distinct levels of submergence: 25%, 50%, and 75% from the free edge opposite to the clamped edge. The frequencies and modeshapes are also verified through numerical analysis using the commercial code ansys 16.0. Conclusions are drawn regarding the influence of fluid inertia distribution on the final plate modeshape, leading to insights into sound structural designs.
BordetellaFilamentous Hemagglutinin, a Model for the Two-Partner Secretion Pathway
Authors: Nash Zachary M. , Cotter Peggy A.
Published: March 2019

Bacteria use a variety of mechanisms to translocate proteins from the cytoplasm, where they are synthesized, to the cell surface or extracellular environment or directly into other cells, where they perform their ultimate functions. Type V secretion systems (T5SS) use β-barrel transporter domains to export passenger domains across the outer membranes of Gram-negative bacteria. Distinct among T5SS are type Vb or two-partner secretion (TPS) systems in which the transporter and passenger are separate proteins, necessitating a mechanism for passenger-translocator recognition in the periplasm and providing the potential for reuse of the translocator. This review describes current knowledge of the TPS translocation mechanism, usingBordetellafilamentous hemagglutinin (FHA) and its transporter FhaC as a model. We present the hypothesis that the TPS pathway may be a general mechanism for contact-dependent delivery of toxins to target cells.
Global, regional and national burden of emergency medical diseases using specific emergency disease indicators: analysis of the 2015 Global Burden of Disease Study
Authors: Razzak Junaid , Usmani Mohammad Farooq , Bhutta Zulfiqar A
Published: March 2019

Objective

There are currently no metrics for measuring population-level burden of emergency medical diseases (EMDs). This study presents an analysis of the burden of EMDs using two metrics: the emergency disease mortality rate (EDMR) and the emergency disease burden (EDB) per 1000 population at the national, regional and global levels.

Methods

We used the 1990 and 2015 Global Burden of Disease Study for morbidity and mortality data on 249 medical conditions in 195 countries. Thirty-one diseases were classified as ‘emergency medical diseases’ based on earlier published work. We developed two indicators, one focused on mortality (EDMR) and the other on burden (EDB). We compared the EDMR and EDB across countries, regions and income groups and compared these metrics from 1990 to 2015.

Results

In 2015, globally, there were 28.3 million deaths due to EMDs. EMDs contributed to 50.7% of mortality and 41.5% of all burden of diseases. The EDB in low-income countries is 4.4 times that of high-income countries. The EDB in the African region is 273 disability-adjusted life years (DALYs) per 1000 compared with 100 DALYs per 1000 in the European region. There has been a 6% increase in overall mortality due to EMDs from 1990 to 2015. Globally, injuries (22%), ischaemic heart disease (17%), lower respiratory infections (11%) and haemorrhagic strokes (7%) made up about 60% of EMDs in 2015.

Conclusion

Globally, EMDs contributed to more than half of all years of life lost. There is a significant disparity between the EDMR and EDB between regions and socioeconomic groups at the global level.
Immunisation financing and programme performance in the Middle East and North Africa, 2010 to 2017
Authors: Saxenian Helen , Sadr-Azodi Nahad , Kaddar Miloud , Senouci Kamel
Published: March 2019

Immunisation is a cornerstone to primary health care and is an exceptionally good value. The 14 low-income and middle-income countries in the Middle East and North Africa region make up 88% of the region’s population and 92% of its births. Many of these countries have maintained high immunisation coverage even during periods of low or negative economic growth. However, coverage has sharply deteriorated in countries directly impacted by conflict and political unrest. Approximately 1.3 million children were not completely vaccinated in 2017, as measured by third dose of diphtheria–pertussis–tetanus vaccine. Most of the countries have been slow to adopt the newer, more expensive life-saving vaccines mainly because of financial constraints and the socioeconomic context. Apart from the three countries that have had long-standing assistance from Gavi, the Vaccine Alliance, most countries have not benefited appreciably from donor and partner activities in supporting their health sector and in achieving their national and subnational immunisation targets. Looking forward, development partners will have an important role in helping reconstruct health systems in conflict-affected countries. They can also help with generating evidence and strategic advocacy for high-priority and cost-effective services, including immunisation. Governments and ministries of health would ensure important benefits to their populations by investing further in their immunisation programmes. Where possible, the health system can create and expand fiscal space from efficiency gains in harmonising vaccine procurement mechanisms and service integration; broader revenue generation from economic growth; and reallocation of government budgets to health, and from within health, to immunization.
Risk factors for thromboembolic and bleeding events in anticoagulated patients with atrial fibrillation: the prospective, multicentre observational PREvention oF thromboembolic events - European Registry in Atrial Fibrillation (PREFER in AF)
Authors: Rohla Miklos , Weiss Thomas W , Pecen Ladislav , Patti Giuseppe , Siller-Matula Jolanta M , Schnabel Renate B , Schilling Richard , Kotecha Dipak , Lucerna Markus , Huber Kurt , De Caterina Raffaele , Kirchhof Paulus
Published: March 2019

Objectives

We identified factors associated with thromboembolic and bleeding events in two contemporary cohorts of anticoagulated patients with atrial fibrillation (AF), treated with either vitamin K antagonists (VKA) or non-VKA oral anticoagulants (NOACs).

Design

Prospective, multicentre observational study.

Setting

461 centres in seven European countries.

Participants

5310 patients receiving a VKA (PREvention oF thromboembolic events - European Registry in Atrial Fibrillation (PREFER in AF), derivation cohort) and 3156 patients receiving a NOAC (PREFER in AF Prolongation, validation cohort) for stroke prevention in AF.

Outcome measures

Risk factors for thromboembolic events (ischaemic stroke, systemic embolism) and major bleeding (gastrointestinal bleeding, intracerebral haemorrhage and other life-threatening bleeding).

Results

The mean age of patients enrolled in the PREFER in AF registry was 72±10 years, 40% were female and the mean CHA2DS2-VASc Score was 3.5±1.7. The incidence of thromboembolic and major bleeding events was 2.34% (95% CI 1.93% to 2.74%) and 2.84% (95% CI 2.41% to 3.33%) after 1-year of follow-up, respectively.

Abnormal liver function, prior stroke or transient ischaemic attack, labile international normalised ratio (INR), concomitant therapy with antiplatelet or non-steroidal anti-inflammatory drugs, heart failure and older age (≥75 years) were independently associated with both thromboembolic and major bleeding events.

With the exception of unstable INR values, these risk factors were validated in patients treated with NOACs (PREFER in AF Prolongation Study, 72±9 years, 40% female, CHA2DS2-VASc 3.3±1.6). For each single point decrease on a modifiable bleeding risk scale we observed a 30% lower risk for major bleeding events (OR 0.70, 95% CI 0.64 to 0.76, p<0.01) and a 28% lower rate of thromboembolic events (OR 0.72, 95% CI 0.66 to 0.82, p<0.01).

Conclusion

Attending to modifiable risk factors is an important treatment target in anticoagulated AF patients to reduce thromboembolic and bleeding events. Initiation of anticoagulation in those at risk of stroke should not be prevented by elevated bleeding risk scores.
Comparison of combined lumbar and sacral plexus block with sedation versus general anaesthesia on postoperative outcomes in elderly patients undergoing hip fracture surgery (CLSB-HIPELD): study protocol for a prospective, multicentre, randomised controlled trial
Authors: Zhang Junfeng , Wang Xiaofeng , Zhang Hui , Shu Zhuolin , Jiang Wei
Published: March 2019

Introduction

Hip fracture in elderly people is a global public health problem, with substantial associated mortality and disability. Nearly all patients with hip fracture undergo surgical treatment, but optimal anaesthesia for hip fracture surgery in elderly patients is still inconclusive. Ultrasound-guided combined lumbar and sacral plexus block has been widely used in hip fracture surgery in recent years, especially for some high-risk patients. However, it is not clear whether it can improve the postoperative outcomes of elderly patients with hip fracture.

Method and analysis

This research project is a two-arm, parallel, multicentre, prospective randomised controlled trail. A total of 1086 patients aged 75 and older scheduled for hip fracture surgery in five clinical trial centres of China will be randomised in a 1:1 ratio to receive either combined lumbar and sacral plexus block plus sedation or general anaesthesia. The primary outcome will be the postoperative 1-year all-cause mortality. The secondary outcomes will be the incidence of postoperative complications, high-sensitivity cardiac troponin T, early mobility after surgery, postoperative Visual Analogue Scale pain scores, postoperative delirium, length of stay in intensive care unit and hospital, cost-effective outcomes, Barthel Index and incidence of adverse events after discharge. Assessments will be conducted in four steps: preoperative, intraoperative, in-hospital data collection and post-discharge telephone follow-up.

Ethics and dissemination

This study has been supported by Shanghai Municipal Commission of Health and Family Planning Foundation for Key Developing Disciplines (2015ZB0103) and approved by the Ethics Committee of Shanghai Sixth People’s Hospital [No: 2016–28-(2)]. At the time of manuscript submission, the protocol version is V.1.6 (March 2nd, 2018) with one subsequent approved amendment. Results will be disseminated via an international peer-reviewed publication.

Trial registration number

NCT03318133.
Rationale, design and study protocol of the randomised controlled trial: Diabetes Interventional Assessment of Slimming or Training tO Lessen Inconspicuous Cardiovascular Dysfunction (the DIASTOLIC study)
Authors: Gulsin Gaurav Singh , Brady Emer M , Swarbrick Daniel J , Athithan Lavanya , Henson Joseph , Baldry Emma , McAdam John , Marsh Anna-Marie , Parke Kelly S , Wormleighton Joanne V , Levelt Eylem , Yates Thomas , Bodicoat Danielle , Khunti Kamlesh , Davies Melanie J , McCann Gerry P
Published: March 2019

Introduction

Despite their young age and relatively short duration of disease, younger adults with type 2 diabetes (T2D) already have diastolic dysfunction and may be at risk of incipient heart failure. Whether weight loss or exercise training improve cardiac dysfunction in people with T2D remains to be established.

Methods and analysis

Prospective, randomised, open-label, blind endpoint trial. The primary aim of the study is to determine if diastolic function can be improved by either a meal replacement plan or a supervised exercise programme, compared with guideline-directed care. A total of 90 obese participants with T2D (aged 18–65 years), diabetes duration <12 years and not on insulin treatment will be randomised to either guideline-directed clinical care with lifestyle coaching, a low-energy meal replacement diet (average ≈810 kcal/day) or a supervised exercise programme for 12 weeks. Participants undergo glycometabolic profiling, cardiopulmonary exercise testing, echocardiography and MRI scanning to assesses cardiac structure and function and dual-energy X-ray absorptiometry scanning for body composition. Key secondary aims are to assess the effects of the interventions on glycaemic control and insulin resistance, exercise capacity, blood pressure, changes in body composition and association of favourable cardiac remodelling with improvements in weight loss, exercise capacity and glycometabolic control.

Ethics and dissemination

The study has full ethical approval, and data collection was completed in August 2018. The study results will be submitted for publication within 6 months of completion.

Trial registration number

NCT02590822; Pre-results.
Effectiveness of interventions for optimising adherence to treatments for the prevention and management of scars: protocol for a systematic review and meta-analysis
Authors: Killey Jessica , Simons Megan , Kimble Roy M , Tyack Zephanie
Published: March 2019

Introduction

Treatments used in the management of scarring following wounds of the skin can be complex and time consuming, and patients may experience difficulties adhering to these treatments. Therefore, the aim of this systematic review is to identify the types of interventions that have been used to optimise adherence to treatment for preventing or reducing skin scars in adults and children and to determine the effectiveness of these interventions.

Methods and analysis

Databases (PubMed, Embase, the Cumulative Index to Nursing and Allied Health Literature, PsycINFO, Web of Science and OTSeeker) will be searched using the developed search strategy to identify eligible randomised trials. Adults and children using scar treatments to prevent or manage scarring as a result of a dermal wound (which may occur following burn injury, surgery, lacerations, piercings, vaccinations, acne and other conditions affecting the skin) will be included. Any intervention with the potential to effect adherence will be included. Titles and abstracts located through searching will be screened by two independent reviewers. Full text of studies will also be screened to determine eligibility for final inclusion. Two reviewers will assess the quality of included studies using the Cochrane ‘risk of bias’ tool. Data extraction forms will be developed and two reviewers will extract the data. A third reviewer will be used at each stage to ensure consensus is achieved. Meta-analysis and meta-regression will be completed if appropriate, otherwise a narrative synthesis of results will be undertaken.

Ethics and dissemination

No ethical approval is necessary for this systematic review as no patients will be directly involved. Results of this systematic review will be disseminated through journal publications and relevant conference presentations.

PROSPERO registration number

CRD42018095082.
Synthesising evidence on patient portals: a protocol for an umbrella review
Authors: Petrovskaya Olga , Lau Francis , Antonio Marcy
Published: March 2019

Introduction

Over the last two decades, patient portals have emerged as a noticeable eHealth strategy. To date, research on patient portals has been rapidly increasing. Our umbrella review aims to provide a meta-level synthesis to make sense of the evidence on patient portals from published systematic reviews (SRs).

Methods

We will employ a modified version of the Joanna Briggs Institute umbrella review method. The search strategy encompasses multiple databases. The inclusion criterion is specific to SRs focused on patient portal. Patients or public were not involved in this work.

Analysis

Two researchers will independently screen titles/abstracts and then full-text articles against the inclusion/exclusion criteria. Methodological quality of included reviews will be assessed and data will be extracted from the final selection of reviews. These reviews will be categorised into quantitative, qualitative and/or mixed-synthesis groups based on information about the design of primary studies provided in the reviews. Correspondingly, we will create quantitative, qualitative and/or mixed-synthesis Excel data-extraction tables. Within each table, data will be extracted with the reference to primary studies as reported in the reviews, and will be synthesised into themes and then a smaller number of findings/outcomes. Modified Grading of Recommendations Assessment, Development and Evaluation (GRADE) and Confidence in the Evidence from Reviews of Qualitative research (CERQual) tools will be applied to assess the strength of evidence at the level of each finding/outcome. The output of our umbrella review will consist of summary of findings tables and evidence profile tables. A narrative meta-level synthesis will be provided. We will use the clinical adoption meta-model as an organising framework.

Ethics and dissemination

As an outcome of this review, we will create a guidance and roadmap to be used in a future Delphi study to gather feedback from Canadian eHealth stakeholders. We will also present at conferences and publish the final report. The umbrella review does not require ethical approval.

PROSPERO registration number

CRD42018096657.
Impact of red meat, processed meat and fibre intake on risk of late-onset chronic inflammatory diseases: prospective cohort study on lifestyle factors using the Danish ‘Diet, Cancer and Health’ cohort (PROCID-DCH):protocol
Authors: Rasmussen Nathalie Fogh , Rubin Katrine Hass , Stougaard Maria , Tjønneland Anne , Stenager Egon , Lund Hetland Merete , Glintborg Bente , Bygum Anette , Andersen Vibeke
Published: March 2019

Introduction

Chronic inflammatory diseases (CIDs) (Crohn’s disease, ulcerative colitis, psoriasis, psoriatic arthritis, rheumatoid arthritis and multiple sclerosis) are diseases of the immune system that have some shared genetic and environmental predisposing factors, but still few studies have investigated the effects of lifestyle on disease risk of several CIDs. The primary aim of this prospective cohort study is to investigate the impact of fibre, red meat and processed meat on risk of late-onset CID, with the perspective that results of this study can contribute in supporting future diet recommendations for effective personalised prevention.

Methods and analysis

The study will use data from 57 053 persons from the prospective Danish cohort study ‘Diet, Cancer and Health’ together with National Health Registry data. The follow-up period is from December 1993 to December 2018. Questionnaire data on diet and lifestyle were collected at entry to the Diet, Cancer and Health study. The outcome CID is defined as having a diagnosis of one of the CIDs registered in the National Patient Registry or, for multiple sclerosis, in the Danish Multiple Sclerosis Registry during follow-up and being treated with a drug used for the specific disease. The major outcome of the analyses will be to detect variability in risk of late onset of any CID and, if power allows, disease risk of late onset of each CID diagnosis between persons with different fibre and red meat, and processed meat intake. The outcome will be adjusted for age, sex, body mass index, physical activity, energy, alcohol, fermented dairy products, education, smoking status, hormone replacement therapy and comorbidity.

Ethics and dissemination

The study is approved by the Danish Data Protection Agency (2012-58-0018). The core study is an open register-based cohort study. The study does not need approval from the Ethics committee or Institutional Review Board by Danish law. Study findings will be disseminated through peer-reviewed journals, patient associations and presentations at international conferences.

Trial registration number

NCT03456206; Post-results.
The impact of decentralising colposcopy services from tertiary-level to primary-level care in inner-city Johannesburg, South Africa: a before and after study
Authors: Maimela Gloria , Nene Xolisile , Mvundla Nontuthuko , Sawry Shobna , Smith Trudy , Rees Helen , Kachingwe Elizabeth , Chersich Matthew
Published: March 2019

Objective

To assess whether decentralising colposcopy services to a primary care facility in inner-city Johannesburg, South Africa raises access to colposcopy.

Design

Before–after study comparing 2 years before and 2 years after decentralisation, using clinical records and laboratory data on cervical cytology and histology.

Primary outcome

The proportion of all women attending Hillbrow Community Health Centre (HCHC) with an abnormal Papanikolaou (Pap) smear who had a colposcopy post-decentralisation.

Setting

Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) has provided colposcopy services for several decades. HCHC, located about 3 km away, began colposcopy services in 2014.

Participants

Women, aged above 18 years, who had a colposcopy for diagnosis and treatment of precancerous cervical lesions following a Pap smear, from 2012 to 2016 at CMJAH or HCHC.

Results

Pre-decentralisation at CMJAH, 910 women had colposcopy (2012–2014). Post-decentralisation (2014–2016), 721 had colposcopy at CMJAH and 399 at HCHC, the decentralised facility. The number who had a Pap smear at HCHC and then a colposcopy rose threefold post-decentralisation (114 vs 350). Post-decentralisation, 43 women at HCHC were referred to CMJAH for colposcopy, compared with 114 pre-decentralisation. Post-decentralisation, 47.3% of women at CMJAH waited >6 months for colposcopy, while 35.5% did at HCHC (p<0.001). Across all three groups, 26.9%–30.3% of women had cervical intraepithelial neoplasia III lesions or carcinoma on colposcopy. The proportion of invalid specimens was similar at CMJAH and HCHC (1.8%–2.8%). Of 401 women who had an abnormal Pap smear at HCHC post-decentralisation, 267 had colposcopy (66.6%).

Conclusion

Decentralisation can decrease the time to colposcopy and reduce the workload of tertiary hospitals. Overall, more women accessed services. Colposcopy coverage at HCHC is higher than other sites, but could be further improved. Decentralisation did not appear to undermine the quality of services and this model could be extended to similar settings in South Africa and elsewhere.
Comparison of three video laryngoscopes and direct laryngoscopy for emergency endotracheal intubation: a retrospective cohort study
Authors: Suzuki Kei , Kusunoki Shinji , Tanigawa Koichi , Shime Nobuaki
Published: March 2019

Objective

Video laryngoscopes are used for managing difficult airways. This study compared three video laryngoscopes’ (Pentax-Airway Scope [Pentax], King Vision[King] and McGrath MAC [McGrath]) performances with the Macintosh direct laryngoscope (Macintosh) as emergency tracheal intubations (TIs) reference.

Design

Retrospective cohort study.

Setting

The emergency department (ED) and the intensive care unit (ICU) of two Japanese tertiary-level hospitals.

Participants

All consecutive video-recorded emergency TI cases in EDs and ICUs between December 2013 and June 2015.

Primary outcome measures

The primary study endpoint was first-pass intubation success. A subgroup analysis examined the first-pass intubation success of expert versus non-expert operators. A logistic regression analysis was performed to identify the predictors of first-pass intubation success.

Results

A total of 287 emergency TIs were included. The first-pass intubation success rates were 78%, 58%, 78% and 58% for the Pentax, King, McGrath and Macintosh instruments, respectively (p=0.004, Fisher’s exact test). The non-expert operators’ success rates were significantly higher (p=0.00004, Fisher’s exact test) for the Pentax (87%) and McGrath (78%) instruments than that for the King (50%) and Macintosh (46%) instruments, unlike that of the experts (67%, 67%, 78% and 78% for Pentax, McGrath, King and Macintosh, respectively; p=0.556, Fisher’s exact test). After TI indication, difficult airway characteristics, and expert versus non-expert operator parameters adjustments, the Pentax (OR=3.422, 95% CI 1.551 to 7.550; p=0.002) and McGrath (OR= 3.758, CI 1.640 to 8.612; p=0.002) instruments showed significantly higher first-pass intubation success odds when compared with the Macintosh laryngoscope (reference, OR=1). The King instrument, however, (OR=1.056; 95% CI 0.487 to 2.289, p=0.889) failed to show any significant superiority.

Conclusion

The Pentax and McGrath laryngoscopes showed significantly higher emergency TI first-pass intubation success rates than the King laryngoscope when compared with the Macintosh laryngoscope, especially for non-expert operators.

Trial registration number

UMIN000027925; Results.
Knowledge and use of evidence-based medicine in daily practice by health professionals: a cross-sectional survey
Authors: Lafuente-Lafuente Carmelo , Leitao Catia , Kilani Insaf , Kacher Zineb , Engels Cynthia , Canouï-Poitrine Florence , Belmin Joël
Published: March 2019

Objectives

Healthcare professionals are expected to firmly ground their practice in sound evidence. That implies that they know and use evidence-based medicine (EBM). In this study, our aim was to know how often health professionals actually made use of EBM in their daily practice.

Design

A questionnaire survey of healthcare professionals.

Participants

Healthcare professionals who attended six university postgraduate courses. 226 answered the questionnaire (144 physicians, 64 nurses and 24 pharmacists; response rate 63.3%).

Setting

56.5% of respondents worked in hospitals (mostly non-teaching), 25.0% in nursing homes and 10.2% in primary care. All participants were French-speaking and lived in France or Switzerland.

Measures

Declared degree of knowledge and use of EBM, use of EBM-related information sources.

Results

Overall, 14.2% of respondents declared to use EBM regularly in their daily practice and 15.6% declared to use EBM only occasionally. The remaining respondents declared they: knew about EBM but did not use it (33.1%), had just heard about EBM (31.9%) or did not know what EBM is (4.0%). Concerning the use of EBM-related information sources, 83.4% declared to use at least monthly (or more often) clinical guidelines, 47.1% PubMed, 21.3% the Cochrane Library and 6.4% other medical databases.

Fewer pharmacists (12%) declared to use EBM in their practice than nurses (22%) or doctors (36%). No difference appeared when analysed by gender, work setting or years after graduation. The most frequent obstacles perceived for the practice of EBM were: lack of general knowledge about EBM, lack of skills for critical appraisal and lack of time.

Conclusions

Only a minority of health professionals—with differences between physicians, nurses and pharmacists—declare to regularly use EBM in their professional practice. A larger proportion appears to be interested in EBM but seems to be deterred by their lack of knowledge, skills and personal time.