bluuebunny/crossref_metadata_2025 huggingface dataset:
Wake Recovery Performance Benefit in a High-Speed Axial Compressor
Authors: Van Zante Dale E. , Adamczyk John J. , Strazisar Anthony J. , Okiishi Theodore H.
Published: December 2014

This paper addresses the significant differences in compressor rotor wake mixing loss which exist in a stage environment relative to a rotor in isolation. The wake decay for a rotor in isolation is due solely to viscous dissipation which is an irreversible process and thus leads to a loss in both total pressure and efficiency. Rotor wake decay in the stage environment is due to both viscous mixing and the inviscid strain imposed on the wake fluid particles by the stator velocity field. This straining process, referred to by Smith (1993) as recovery, is reversible and for a 2D rotor wake leads to an inviscid reduction of the velocity deficit of the wake. It will be shown that for the rotor/stator spacing typical of core compressors, wake stretching is the dominant wake decay process within the stator with viscous mixing playing a secondary role.

A model for the rotor wake decay process is developed and used to quantify the viscous dissipation effects relative to those of inviscid wake stretching. The model is verified using laser anemometer measurements acquired in the wake of a transonic rotor operated in isolation and in a stage configuration at near peak efficiency and near stall operating conditions. Additional insight is provided by a time-accurate 3D Navier Stokes simulation of the compressor stator flow field at the corresponding stage loading levels. Results from the wake decay model exhibit good agreement with the experimental data. Data from the model, laser anemometer measurements, and simulations indicate that wake straining (stretching) is the primary decay process in the stator passage. The implications of these results on compressor stage design are discussed.
Recurrent epimutation ofSDHCin gastrointestinal stromal tumors
Authors: Killian J. Keith , Miettinen Markku , Walker Robert L. , Wang Yonghong , Zhu Yuelin Jack , Waterfall Joshua J. , Noyes Natalia , Retnakumar Parvathy , Yang Zhiming , Smith William I. , Killian M. Scott , Lau C. Christopher , Pineda Marbin , Walling Jennifer , Stevenson Holly , Smith Carly , Wang Zengfeng , Lasota Jerzy , Kim Su Young , Boikos Sosipatros A. , Helman Lee J. , Meltzer Paul S.
Published: December 2014

Methylation of theSDHgene explains the loss ofSDHgene expression in SDH wild-type gastrointestinal stromal tumors.
Muscles Protect the Kidneys
Authors: Chitalia Vipul
Published: December 2014

Skeletal muscles halt the progression of kidney failure through the kinase Akt1.
Protein Clearance Ain’t What It Used to Be
Authors: Musiek Erik S.
Published: December 2014

A glial system for flushing waste proteins from the brain declines with age, revealing a possible mechanistic link between aging and protein aggregation.
A Ralstonia solanacearum Type III Effector Directs the Production of the Plant Signal Metabolite Trehalose-6-Phosphate
Authors: Poueymiro M. , Cazalé A. C. , François J. M. , Parrou J. L. , Peeters N. , Genin S.
Published: December 2014

The plant pathogen
Ralstonia solanacearum
possesses two genes encoding a trehalose-6-phosphate synthase (TPS), an enzyme of the trehalose biosynthetic pathway. One of these genes, named
ripTPS
, was found to encode a protein with an additional N-terminal domain which directs its translocation into host plant cells through the type 3 secretion system. RipTPS is a conserved effector in the
R. solanacearum
species complex, and homologues were also detected in other bacterial plant pathogens. Functional analysis of RipTPS demonstrated that this type 3 effector synthesizes trehalose-6-phosphate and identified residues essential for this enzymatic activity. Although trehalose-6-phosphate is a key signal molecule in plants that regulates sugar status and carbon assimilation, the disruption of
ripTPS
did not alter the virulence of
R. solanacearum
on plants. However, heterologous expression assays showed that this effector specifically elicits a hypersensitive-like response on tobacco that is independent of its enzymatic activity and is triggered by the C-terminal half of the protein. Recognition of this effector by the plant immune system is suggestive of a role during the infectious process.

IMPORTANCE
Ralstonia solanacearum
, the causal agent of bacterial wilt disease, infects more than two hundred plant species, including economically important crops. The type III secretion system plays a major role in the pathogenicity of this bacterium, and approximately 70 effector proteins have been shown to be translocated into host plant cells. This study provides the first description of a type III effector endowed with a trehalose-6-phosphate synthase enzymatic activity and illustrates a new mechanism by which the bacteria may manipulate the plant metabolism upon infection. In recent years, trehalose-6-phosphate has emerged as an essential signal molecule in plants, connecting plant metabolism and development. The finding that a bacterial pathogen could induce the production of trehalose-6-phosphate in plant cells further highlights the importance of this metabolite in multiple aspects of the molecular physiology of plants.
ADP-Ribosylation of NLRP3 by Mycoplasma pneumoniae CARDS Toxin Regulates Inflammasome Activity
Authors: Bose Santanu , Segovia Jesus A. , Somarajan Sudha R. , Chang Te-Hung , Kannan T. R. , Baseman Joel B.
Published: December 2014

The inflammasome is a major regulator of inflammation through its activation of procaspase-1, which cleaves prointerleukin-1β (pro-IL-1β) into its mature form. IL-1β is a critical proinflammatory cytokine that dictates the severity of inflammation associated with a wide spectrum of inflammatory diseases. NLRP3 is a key component of the inflammasome complex, and multiple signals and stimuli trigger formation of the NLRP3 inflammasome complex. In the current study, we uncovered a yet unknown mechanism of NLRP3 inflammasome activation by a pathogen-derived factor. We show that the unique bacterial ADP-ribosylating and vacuolating toxin produced by
Mycoplasma pneumoniae
and designated community-acquired respiratory distress syndrome (CARDS) toxin activates the NLRP3 inflammasome by colocalizing with the NLRP3 inflammasome and catalyzing the ADP-ribosylation of NLRP3. Mutant full-length CARDS toxin lacking ADP-ribosyltransferase (ADPRT) activity and truncated CARDS toxins unable to bind to macrophages and be internalized failed to activate the NLRP3 inflammasome. These studies demonstrate that CARDS toxin-mediated ADP-ribosylation constitutes an important posttranslational modification of NLRP3, that ADPRT activity of CARDS toxin is essential for NLRP3 inflammasome activation, and that posttranslational ADPRT-mediated modification of the inflammasome is a newly discovered mechanism for inflammasome activation with subsequent release of IL-1β and associated pathologies.

IMPORTANCE
Inflammation is a fundamental innate immune response to environmental factors, including infections. The inflammasome represents a multiprotein complex that regulates inflammation via its ability to activate specific proinflammatory cytokines, resulting in an effective host protective response. However, excessive release of proinflammatory cytokines can occur following infection that skews the host response to “hyperinflammation” with exaggerated tissue damage.
Mycoplasma pneumoniae
, a common bacterial airway pathogen, possesses a unique protein toxin with ADP-ribosyltransferase and vacuolating properties capable of reproducing the robust inflammation and cytopathology associated with mycoplasma infection. Here, we show that the toxin uniquely activates the NLRP3 inflammasome by colocalizing with and ADP-ribosylating NLRP3, possibly leading to “hyperinflammation” and thus uncovering a novel target for therapeutic intervention.
The Vibrio cholerae VprA-VprB Two-Component System Controls Virulence through Endotoxin Modification
Authors: Herrera Carmen M. , Crofts Alexander A. , Henderson Jeremy C. , Pingali S. Cassandra , Davies Bryan W. , Trent M. Stephen
Published: December 2014

The bacterial cell surface is the first structure the host immune system targets to prevent infection. Cationic antimicrobial peptides of the innate immune system bind to the membrane of Gram-negative pathogens via conserved, surface-exposed lipopolysaccharide (LPS) molecules. We recently reported that modern strains of the global intestinal pathogen
Vibrio cholerae
modify the anionic lipid A domain of LPS with a novel moiety, amino acids. Remarkably, glycine or diglycine addition to lipid A alters the surface charge of the bacteria to help evade the cationic antimicrobial peptide polymyxin. However, the regulatory mechanisms of lipid A modification in
V. cholerae
are unknown. Here, we identify a novel two-component system that regulates lipid A glycine modification by responding to important biological cues associated with pathogenesis, including bile, mildly acidic pH, and cationic antimicrobial peptides. The histidine kinase Vc1319 (VprB) and the response regulator Vc1320 (VprA) respond to these signals and are required for the expression of the
almEFG
operon that encodes the genes essential for glycine modification of lipid A. Importantly, both the newly identified two-component system and the lipid A modification machinery are required for colonization of the mammalian host. This study demonstrates how
V. cholerae
uses a previously unknown regulatory network, independent of well-studied
V. cholerae
virulence factors and regulators, to respond to the host environment and cause infection.

IMPORTANCE
Vibrio cholerae
, the etiological agent of cholera disease, infects millions of people every year.
V. cholerae
El Tor and classical biotypes have been responsible for all cholera pandemics. The El Tor biotype responsible for the current seventh pandemic has displaced the classical biotype worldwide and is highly resistant to cationic antimicrobial peptides, like polymyxin B. This resistance arises from the attachment of one or two glycine residues to the lipid A domain of lipopolysaccharide, a major surface component of Gram-negative bacteria. Here, we identify the VprAB two-component system that regulates the charge of the bacterial surface by directly controlling the expression of genes required for glycine addition to lipid A. The VprAB-dependent lipid A modification confers polymyxin B resistance and contributes significantly to pathogenesis. This finding is relevant for understanding how
Vibrio cholerae
has evolved mechanisms to facilitate the evasion of the host immune system and increase bacterial fitness.
An Observational Study on the Costs and Consequences of Acupuncture for the Management of Chronic Low Back Pain in Korean Patients
Authors: Kim Song-Yi , Lee Hyejung , Lee Hyangsook , Park Ji-Yeun , Park Sang Kyun , Park Hi-Joon
Published: December 2014

Objectives

To investigate the consequences and costs of acupuncture in general medical practice for patients with chronic low back pain (CLBP) in Korea.

Methods

A multicentre observational study was performed. Outpatients with CLBP who received at least one acupuncture session in a Korean Medicine clinic during the study period were included and followed up for 3 months. All patients received regular acupuncture treatments in accordance with the doctors’ discretion. The consequences in terms of effects included condition-specific outcomes and preference-based outcome. For cost analysis, the cumulative resource use for direct medical costs at each research clinic during the study period and direct patient data using the self-reported healthcare utilisation questionnaires were used.

Results

A total of 157 patients were eligible to participate and 105 were finally included. Significant improvements in condition-specific and preference-based measures were observed after acupuncture treatment. An average of approximately $146 (£93) per patient was reported for direct medical costs in each clinic for 1 month and $231 (£148) for 3 months. Other medical expenses related to CLBP were reduced during this period.

Conclusions

The use of acupuncture to manage CLBP in general clinical practice in Korea inexpensively improved pain, functional disability and quality of life. The study results are meaningful and consistent with the results of previous trials performed in other European countries but the power of the study is not strong, having major design weaknesses. A large-scale cohort or registry based on practice may be helpful to strengthen the evidence of the cost-effectiveness of acupuncture.
Supporting colleagues to improve care: educating for quality improvement
Authors: Runnacles Jane , Roueché Alice
Published: December 2014

Clinicians at the front line of healthcare delivery are very well positioned to identify and improve the system in which they work. Training curricula, however, have not always equipped them with the skills or knowledge to implement change. This article looks at educational approaches to support clinicians to be actively involved with quality improvement (QI). It looks at the role of doctors in postgraduate training (DrPGT) and their educational supervisors and builds on the topics discussed throughout the ‘EQUIPPED’ article series. Factors for success of a QI education programme and practical ideas for overcoming barriers to supporting clinicians in QI are discussed. We present examples of educational initiatives and a framework for evaluating such programmes, and we examine the role of faculty development to help inspire and support colleagues to improve care.
Reptile-associated salmonellosis in children aged under 5 years in South West England
Authors: Murphy Dan , Oshin Femi
Published: December 2014

Objective

To determine the proportion of Salmonella cases in children aged <5 years that were reptile-associated salmonellosis (RAS) and to compare the severity of illness.

Design

To analyse all cases of salmonellosis reported to public health authorities in children aged under 5 years in the South West of the UK from January 2010 to December 2013 for reptile exposure, age, serotype, hospitalisation and invasive disease.

Results

48 of 175 (27%) Salmonella cases had exposure to reptiles. The median age of RAS cases was significantly lower than non-RAS cases (0.5 vs 1.0 year). RAS cases were 2.5 times more likely to be hospitalised (23/48) compared with non-RAS cases (25/127; p=0.0002). This trend continued in cases aged under 12 months, with significantly more RAS cases hospitalised (19/38) than non-RAS cases (8/42; p=0.003). Significantly more RAS cases had invasive disease (8/48: 5 bacteraemia, 2 meningitis, 1 colitis) than non-RAS cases (4/127: 3 bacteraemia, 1 meningitis).

Conclusions

Reptile exposure was found in over a quarter of all reported Salmonella cases in children under 5 years of age. RAS is associated with young age, hospitalisation and invasive disease.
An unusual cause for a relatively common radiographic abnormality
Authors: Odedra Anand , Farrugia Mark , Babiker Zahir
Published: December 2014

A 59-year-old Indian woman presented to the respiratory clinic with chest pains, long-standing swallowing difficulties and a chest radiograph, which was reported as showing a shadow in the right paratracheal region. A CT scan was obtained and was reported as demonstrating a right-sided paratracheal lymph node and varicosities adjacent to the inferior vena cava. Histology from an endobronchial ultrasound-guided biopsy revealed a heavily blood-stained sample but showed no evidence of granulomas or malignancy. Subsequently, the images were reviewed, with the conclusion that they were actually of an engorged azygos vein compressing the oesophagus. MRI confirmed the absence of mediastinal lymphadenopathy and the presence of a prominent hemiazygos vein compressing the oesophagus. This case highlights the importance of including anatomical abnormalities in the differential diagnosis and reassessing patients when the history and investigations do not correlate.
A diagnosis of haemolytic-uraemic syndrome blurred by alcohol abuse
Authors: Killian Martin , Bruel Tronchon Noémie , Maillard Nicolas , Tardy Bernard
Published: December 2014

A 60-year-old man with a history of alcohol abuse was admitted to the intensive care unit (ICU) for status epilepticus. At first, laboratory and imagery findings were almost normal, and the symptoms were attributed to severe alcohol withdrawal due to a history of gastroenteritis reported by his family. But, during the following days, haemolytic anaemia, thrombocytopenia, acute renal failure, and ischaemic and haemorrhagic lesions seen on a cerebral CT scan led to the diagnosis of haemolytic-uraemic syndrome (HUS). Despite these severe complications, the patient made a good recovery following ICU and plasma exchange with fresh frozen plasma (FFP), but cognitive deficit still existed after 1 month. It is important to know that neurological manifestations can precede typical biological and radiological signs in HUS, and to not be misled in the diagnosis process, especially when a more common differential diagnosis is possible.
Recurrent clot anuria following laparoscopic pyeloplasty in a solitary functioning kidney: managing with double guide wire technique
Authors: Kumar Santosh , Singh Shivanshu , Parmar Kalpesh Mahesh , Garg Nitin
Published: December 2014

Clot anuria in a solitary functioning kidney is an emergency situation. Haematuria with clot anuria in an early postoperative period represents a challenge, as treatment options are limited. Manipulation of the anastomotic site may lead to anastomotic disruption and urinoma while use of thrombolytic therapy poses the danger of increasing haematuria. We report a case of anuria due to clot retention in the upper tract following laparoscopic dismembered pyeloplasty in a solitary functioning kidney, managed successfully with double guide wire technique.
Expanding the indications: distal femoral osteotomy used successfully to treat recurrent knee effusion
Authors: Elson David William , Malpas Claire-Marie Catherine , Wilson Christopher
Published: December 2014

Distal femoral osteotomy (DFO) is successful in treating painful valgus arthritis of the knee. We present a case where painless recurrent knee effusion was attributed to constitutional valgus. The absence of pain made the indication for surgery atypical so DFO was carefully considered and planned. A small correction was performed, bringing alignment closer to neutral with complete resolution of the recurrent effusion. We suggest that the indications for knee osteotomy can be expanded to include recurrent joint effusion in carefully selected patients.
Idiopathic aneurysmal giant right atrial enlargement with thrombus formation
Authors: Khare Rashi , Chandra Sharad , Agarwal Vikas , Dwivedi Sudhanshu
Published: December 2014

A 12-year-old boy presented to our outpatient department with progressive dyspnoea and palpitations of 6-month duration. Cardiovascular system examination revealed a short ejection systolic murmur at the left lateral heart border. Chest X-ray showed gross cardiomegaly. Two-dimensional ECHO revealed massive aneurysmal right atrial (RA) enlargement, low-pressure tricuspid regurgitation and dysplastic tricuspid valve with compression of the left atrium (LA) and left ventricle (LV). Cardiac CT showed grossly enlarged RA compressing the LA, LV, right pulmonary artery and right upper lobe pulmonary vein. Initially, the patient refused surgery. On follow-up, a thrombus was seen in the giant RA and the patient agreed to and underwent successful surgery. Absence of pericardium was specifically excluded on cardiac MRI and on surgery. Resected atrial tissue showed wall thinning and focal fibrosis establishing idiopathic dilation of the RA. The patient is on regular follow-up.
Awareness and control of hypertension in Bangladesh: follow-up of a hypertensive cohort
Authors: Alam Dewan Shamsul , Chowdhury Muhammad Ashique Haider , Siddiquee Ali Tanweer , Ahmed Shyfuddin , Niessen Louis Wilhelmus
Published: December 2014

Objectives

To assess the effect of awareness and advice to seek care on blood pressure (BP) control among patients with hypertension in Bangladesh.

Design

Longitudinal study.

Setting

The study was carried out in icddr,b surveillance sites at rural Matlab in Chandpur district and semi-urban Kamalapur in Dhaka, Bangladesh.

Participants

Randomly selected men and non-pregnant women aged 20 years or older without any acute illness or history of any vascular events such as stroke or acute myocardial infarction.

Main outcome measure

Hypertension was defined as systolic BP (SBP) ≥140 and/or diastolic BP (DBP) ≥90 mm Hg or as self-reported hypertension under medication. We advised patients to seek care from a qualified provider and to adopt a healthy lifestyle. We compared changes in BP from baseline to follow-up at around 6 months.

Results

Overall, 17.1% (n=287) of participants had hypertension at baseline with significantly higher prevalence in the semi-urban than in the rural population (23.6% vs 10.8%; p<0.001); half were unaware of their condition. At follow-up, 83% (n=204) reported a visit to any healthcare provider. In the semi-urban area, a higher proportion of patients visited medically qualified practitioners than in the rural area (76.7% vs 36.6%, p<0.000). SBP (−3.3±20.7 mm Hg; p<0.01) and DBP (−2.0±13.0 mm Hg; p<0.02) were lower at follow-up. Those who visited medically qualified practitioners had significant SBP (−3.9±22.4 mm Hg; p<0.03) and DBP (−2.7±14.1 mm Hg; p<0.02) reduction. BP reduction did not reach statistical significance among those visiting a pharmacist or their village doctors. Overall, half of the patients with hypertension achieved the BP control goal (BP<140/90 mm Hg).

Conclusions

Awareness and simple health messages increase provider visit, reduce blood pressure and improve BP control in hypertensive Bangladeshis. Longer-term follow-up is required to verify the sustainability.
Safety and effectiveness of dipeptidyl peptidase-4 inhibitors versus intermediate-acting insulin or placebo for patients with type 2 diabetes failing two oral antihyperglycaemic agents: a systematic review and network meta-analysis
Authors: Tricco Andrea C , Antony Jesmin , Khan Paul A , Ghassemi Marco , Hamid Jemila S , Ashoor Huda , Blondal Erik , Soobiah Charlene , Yu Catherine H , Hutton Brian , Hemmelgarn Brenda R , Moher David , Majumdar Sumit R , Straus Sharon E
Published: December 2014

Objective

To evaluate the effectiveness and safety of dipeptidyl peptidase-4 (DPP-4) inhibitors versus intermediate-acting insulin for adults with type 2 diabetes mellitus (T2DM) and poor glycaemic control despite treatment with two oral agents.

Setting

Studies were multicentre and multinational.

Participants

Ten studies including 2967 patients with T2DM.

Interventions

Studies that examined DPP-4 inhibitors compared with each other, intermediate-acting insulin, no treatment or placebo in patients with T2DM.

Primary and secondary outcome measures

Primary outcome was glycosylated haemoglobin (HbA1c). Secondary outcomes were healthcare utilisation, body weight, fractures, quality of life, microvascular complications, macrovascular complications, all-cause mortality, harms, cost and cost-effectiveness.

Results

10 randomised clinical trials with 2967 patients were included after screening 5831 titles and abstracts, and 180 full-text articles. DPP-4 inhibitors significantly reduced HbA1c versus placebo in network meta-analysis (NMA; mean difference (MD) −0.62%, 95% CI −0.93% to −0.33%) and meta-analysis (MD −0.61%, 95% CI −0.81% to −0.41%), respectively. Significant differences in HbA1c were not observed for neutral protamine Hagedorn (NPH) insulin versus placebo and DPP-4 inhibitors versus NPH insulin in NMA. In meta-analysis, no significant differences were observed between DPP-4 inhibitors and placebo for severe hypoglycaemia, weight gain, cardiovascular disease, overall harms, treatment-related harms and mortality, although patients receiving DPP-4 inhibitors experienced less infections (relative risk 0.72, 95% CI 0.57 to 0.91).

Conclusions

DPP-4 inhibitors were superior to placebo in reducing HbA1c levels in adults with T2DM taking at least two oral agents. Compared with placebo, no safety signals were detected with DPP-4 inhibitors and there was a reduced risk of infection. There was no significant difference in HbA1c observed between NPH and placebo or NPH and DPP-4 inhibitors.

Trial registration number

PROSPERO # CRD42013003624.
Acupuncture atHouxi(SI 3) acupoint for acute neck pain caused by stiff neck: study protocol for a pilot randomised controlled trial
Authors: Sun Zhong-ren , Yue Jin-huan , Tian Hong-zhao , Zhang Qin-hong
Published: December 2014

Introduction

The use of acupuncture has been suggested for the treatment of acute neck pain caused by stiff neck in China. However, current evidence is insufficient to draw any conclusions about its efficacy. Therefore this pilot study was designed to evaluate the feasibility and efficacy of acupuncture at theHouxi(SI3) acupoint for treatment of acute neck pain.

Methods/analysis

This pilot study will be a two-parallel-group, assessor-blinded, randomised controlled trial. Thirty-six stiff neck participants with acute neck pain will be recruited and randomly divided into two groups in a 1:1 ratio. Participants in the control group will receive massage on the local neck region (5 min each session, three times a day for 3 days). In addition to massage, patients in the treatment group will receive acupuncture (one session a day for 3 days). Measures will be taken at 0, 3 and 15 days. The primary outcome is the Northwick Park Neck Pain Questionnaire (NPQ). The secondary outcome is the Short Form of the McGill Pain Questionnaire (SF-MPQ).

Ethics/dissemination

The protocol for this pilot randomised clinical trial has undergone ethics scrutiny and been approved by the ethics review boards of the First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine (Permission number: HZYLL201303502). The findings of this study will provide important clinical evidence on the feasibility and efficacy of acupuncture treatment for stiff neck patients with acute neck pain. In addition, it will explore the feasibility of further acupuncture research.

Trial registration number

ChiCTR-TRC-13003911.
A Frailty Instrument for primary care for those aged 75 years or more: findings from the Survey of Health, Ageing and Retirement in Europe, a longitudinal population-based cohort study (SHARE-FI75+)
Authors: Romero-Ortuno Roman , Soraghan Christopher
Published: December 2014

Objective

To create and validate a frailty assessment tool for community-dwelling adults aged ≥75 years.

Design

Longitudinal, population-based study.

Setting

The Survey of Health, Ageing and Retirement in Europe (SHARE).

Participants

4001 women and 3057 men aged ≥75 years from the second wave of SHARE. 3325 women and 2587 men had complete information for the frailty indicators: fatigue, low appetite, weakness, observed gait (walking without help, walking with help, chairbound/bedbound, unobserved) and low physical activity.

Main outcome measures

The internal validity of the frailty indicators was tested with latent class analysis, by modelling an underlying variable with three ordered categories. The predictive validity of the frailty classification was tested against 2-year mortality and 4-year disability. The mortality prediction of SHARE-FI75+ was compared with that of previously operationalised frailty scales in SHARE (SHARE-FI, 70-item index, phenotype, FRAIL).

Results

In both genders, all frailty indicators significantly aggregated into a three-category ordinal latent variable. After adjusting for baseline age, comorbidity and basic activities of daily living (BADL) disability, the frail had an OR for 2-year mortality of 2.2 (95% CI 1.2 to 3.8) in women and 4.2 (2.6 to 6.8) in men. The mortality prediction of SHARE-FI75+ was similar to that of the other SHARE frailty scales. By wave 4, 49% of frail women (78 of 159) had at least one more limitation with BADL (compared with 18% of non-frail, 125 of 684; p<0.001); in men, these proportions were 39% (26 of 66) and 18% (110 of 621), respectively (p<0.001). A calculator is supplied for point-of-care use, which automatically replicates the frailty classification for any given measurements.

Conclusions

SHARE-FI75+ could help frailty case finding in primary care and provide a focus for personalised community interventions. Further validation in trials and clinical programmes is needed.
Acupuncture for postoperative pain in laparoscopic surgery: a systematic review protocol
Authors: Lee Seunghoon , Park Jimin , Kim Jihye , Kang Jung Won , Choi Do-Young , Park Sun Jin , Nam Dongwoo , Lee Jae-Dong
Published: December 2014

Introduction

This review aims to evaluate the effectiveness and safety of acupuncture for patients with postoperative pain after laparoscopic surgery.

Methods and analysis

We will search the following databases from their inception to October 2014: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Allied and Complementary Medicine Database (AMED), three Chinese databases (China National Knowledge Infrastructure (CNKI), the Chongqing VIP Chinese Science and Technology Periodical Database (VIP) and the Wanfang database), one Japanese database (Japan Science and Technology Information Aggregator, Electronic (J-STAGE)) and eight Korean databases (Korean Association of Medical Journal Edition, Korean Medical Database, Korean Studies Information Service System, National Discovery for Science Leaders, Database Periodical Information Academic, Korean National Assembly Digital Library, Oriental Medicine Advanced Searching Integrated System and Korean Traditional Knowledge Portal). All randomised controlled trials of acupuncture for postoperative pain after laparoscopic surgery will be considered for inclusion. The risk of bias and reporting quality will be assessed using the Cochrane risk of bias tool, the Consolidated Standards of Reporting Trials (CONSORT) and the revised STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA). The risk ratio for dichotomous data and mean difference or standard mean difference for continuous data will be calculated with 95% CIs.

Dissemination

The results of this review will be disseminated through peer-reviewed publication or conference presentation. Our findings will summarise the current evidence of acupuncture to treat postoperative pain after laparoscopic surgery, and may provide important guidance for acupuncture usage after laparoscopic surgery for clinicians and patients.

Trial registration number

PROSPERO 2014: CRD42014010825.
Childhood adversities predict strongly the use of psychotropic drugs in adulthood: a population-based cohort study of 24 284 Finns
Authors: Koskenvuo Karoliina , Koskenvuo Markku
Published: December 2014

Background

Exposure to adverse childhood experiences has been shown to be associated with negative health outcomes including mental health problems, but only a few studies with register-based data have used psychotropic drugs as an outcome variable. The purpose of this study is to examine whether adverse emotional childhood experiences, such as serious conflicts in the family and frequent fear of a family member, predict the use of psychotropic drugs in adulthood. In addition, the association of a child–parent relationship during childhood with the use of psychotropic drugs is studied.

Methods

The participants of the population-based Health and Social Support Study (24 284 working aged Finns) were followed up for 9 years. The information on childhood experiences and child–parent relationships was obtained from the questionnaires in 1998 and 2003. The number of psychotropic purchases (antipsychotics, drugs for bipolar disorder, antidepressants, anxiolytics, hypnotics and sedatives) was obtained from the National-Drug-Prescription-Register. Logistic and multinomial regression models were used.

Results

A graded association between childhood adversities and the use of psychotropic drugs was found, even after adjustments for occupational training, work status, recent life events and health behaviour. Frequent fear of a family member showed the strongest association: the OR for multiple use of antidepressants was 3.08 (95% CI 2.72 to 3.49) and 2.69 (2.27 to 3.20) for multiple use of anxiolytics. Use of psychotropic drugs was clearly increased among those with poor child–parent relationship and multiple childhood adversities.

Conclusions

The results highlight the effect of environmental factors during childhood on mental health and the need for early recognition of families at risk.
Formation of multi-armed spiral waves in neuronal network induced by adjusting ion channel conductance
Authors: Wang Chunni , Ma Jun , Hu Bolin , Jin Wuyin
Published: December 2014

The Hodgkin–Huxley neuron model is used to describe the local dynamics of nodes in a two-dimensional regular network with nearest-neighbor connections. Multi-armed spiral waves emerge when a group of spiral waves rotate the same core synchronously. Here we have numerically investigated how multi-armed spiral waves are formed in such a system. Under the appropriate conditions, multi-armed spiral waves were able to develop as a result of adjusting the conductance of ion channels of particular neurons in the network. In a realistic neuron model, it can be practiced by blocking potassium of ion channels embedded in the membrane of neurons. For example, decreasing the potassium channel conductance in some neurons with a certain transient period can lead to the development of a group of double spirals in a localized area of the network. Furthermore, decreasing the excitability and the external forcing current to zero led to the growth of these double spirals and the formation of a stable multi-armed spiral wave that occupied the network under inhomogeneity.
Water Drop Algorithms
Authors: Siddique Nazmul , Adeli Hojjat
Published: December 2014

This article presents a review of a novel nature-inspired adaptive optimization algorithm known as Water Drop Algorithm (WDA) which imitates the dynamics of river systems and the behavior of water drops when they are moving in a river system such as the variation of velocity, the change of sediment/soil in the river bed, the change of direction of the flow, and so on. Recent improved, modified, and adaptive WDAs are examined in this paper. Various applications of WDA are described briefly including the vehicle routing problem, economic load dispatch problem, economic and emission dispatch problem, optimal data aggregation tree in wireless networks, reactive power dispatch problem service selection, and reservoir operation.
Mitochondria-derived ROS bursts disturb Ca2+ cycling and induce abnormal automaticity in guinea pig cardiomyocytes: a theoretical study
Authors: Li Qince , Su Di , O'Rourke Brian , Pogwizd Steven M. , Zhou Lufang
Published: December 2014

Mitochondria are in close proximity to the redox-sensitive sarcoplasmic reticulum (SR) Ca2+ release [ryanodine receptors (RyRs)] and uptake [Ca2+-ATPase (SERCA)] channels. Thus mitochondria-derived reactive oxygen species (mdROS) could play a crucial role in modulating Ca2+ cycling in the cardiomyocytes. However, whether mdROS-mediated Ca2+ dysregulation translates to abnormal electrical activities under pathological conditions, and if yes what are the underlying ionic mechanisms, have not been fully elucidated. We hypothesize that pathological mdROS induce Ca2+ elevation by modulating SR Ca2+ handling, which activates other Ca2+ channels and further exacerbates Ca2+ dysregulation, leading to abnormal action potential (AP). We also propose that the morphologies of elicited AP abnormality rely on the time of mdROS induction, interaction between mitochondria and SR, and intensity of mitochondrial oxidative stress. To test the hypotheses, we developed a multiscale guinea pig cardiomyocyte model that incorporates excitation-contraction coupling, local Ca2+ control, mitochondrial energetics, and ROS-induced ROS release. This model, for the first time, includes mitochondria-SR microdomain and modulations of mdROS on RyR and SERCA activities. Simulations show that mdROS bursts increase cytosolic Ca2+ by stimulating RyRs and inhibiting SERCA, which activates the Na+/Ca2+ exchanger, Ca2+-sensitive nonspecific cationic channels, and Ca2+-induced Ca2+ release, eliciting abnormal AP. The morphologies of AP abnormality are largely influenced by the time interval among mdROS burst induction and AP firing, dosage and diffusion of mdROS, and SR-mitochondria distance. This study defines the role of mdROS in Ca2+ overload-mediated cardiac arrhythmogenesis and underscores the importance of considering mitochondrial targets in designing new antiarrhythmic therapies.
Muscle metaboreflex activation during dynamic exercise evokes epinephrine release resulting in β2-mediated vasodilation
Authors: Kaur Jasdeep , Spranger Marty D. , Hammond Robert L. , Krishnan Abhinav C. , Alvarez Alberto , Augustyniak Robert A. , O'Leary Donal S.
Published: December 2014

Muscle metaboreflex-induced increases in mean arterial pressure (MAP) during submaximal dynamic exercise are mediated principally by increases in cardiac output. To what extent, if any, the peripheral vasculature contributes to this rise in MAP is debatable. In several studies, we observed that in response to muscle metaboreflex activation (MMA; induced by partial hindlimb ischemia) a small but significant increase in vascular conductance occurred within the nonischemic areas (calculated as cardiac output minus hindlimb blood flow and termed nonischemic vascular conductance; NIVC). We hypothesized that these increases in NIVC may stem from a metaboreflex-induced release of epinephrine, resulting in β2-mediated dilation. We measured NIVC and arterial plasma epinephrine levels in chronically instrumented dogs during rest, mild exercise (3.2 km/h), and MMA before and after β-blockade (propranolol; 2 mg/kg), α1-blockade (prazosin; 50 μg/kg), and α1 + β-blockade. Both epinephrine and NIVC increased significantly from exercise to MMA: 81.9 ± 18.6 to 141.3 ± 22.8 pg/ml and 33.8 ± 1.5 to 37.6 ± 1.6 ml·min−1·mmHg−1, respectively. These metaboreflex-induced increases in NIVC were abolished after β-blockade (27.6 ± 1.8 to 27.5 ± 1.7 ml·min−1·mmHg−1) and potentiated after α1-blockade (36.6 ± 2.0 to 49.7 ± 2.9 ml·min−1·mmHg−1), while α1 + β-blockade also abolished any vasodilation (33.7 ± 2.9 to 30.4 ± 1.9 ml·min−1·mmHg−1). We conclude that MMA during mild dynamic exercise induces epinephrine release causing β2-mediated vasodilation.
Chemokine receptor Cxcr4 contributes to kidney fibrosis via multiple effectors
Authors: Yuan Amy , Lee Yashang , Choi Uimook , Moeckel Gilbert , Karihaloo Anil
Published: December 2014

Kidney fibrosis is the final common pathway for virtually every type of chronic kidney disease and is a consequence of a prolonged healing response that follows tissue inflammation. Chronic kidney inflammation ultimately leads to progressive tissue injury and scarring/fibrosis. Several pathways have been implicated in the progression of kidney fibrosis. In the present study, we demonstrate that G protein-coupled chemokine (C-X-C motif) receptor (CXCR)4 was significantly upregulated after renal injury and that sustained activation of Cxcr4 expression augmented the fibrotic response. We demonstrate that after unilateral ureteral obstruction (UUO), both gene and protein expression of Cxcr4 were highly upregulated in tubular cells of the nephron. The increased Cxcr4 expression in tubules correlated with their increased dedifferentiated state, leading to increased mRNA expression of platelet-derived growth factor (PDGF)-α, transforming growth factor (TGF)-β1, and concurrent loss of bone morphogenetic protein 7 (Bmp7). Ablation of tubular Cxcr4 attenuated UUO-mediated fibrotic responses, which correlated with a significant reduction in PDGF-α and TGF-β1levels and preservation of Bmp7 expression after UUO. Furthermore, Cxcr4+immune cells infiltrated the obstructed kidney and further upregulate their Cxcr4 expression. Genetic ablation of Cxcr4 from macrophages was protective against UUO-induced fibrosis. There was also reduced total kidney TGF-β1, which correlated with reduced Smad activation and α-smooth muscle actin levels. We conclude that chronic high Cxcr4 expression in multiple effector cell types can contribute to the pathogenesis of renal fibrosis by altering their biological profile. This study uncovered a novel cross-talk between Cxcr4-TGF-β1and Bmp7 pathways and may provide novel targets for interrupting the progression of fibrosis.
Respiratory cortical processing to inspiratory resistances during wakefulness in children with the obstructive sleep apnea syndrome
Authors: Tapia Ignacio E. , McDonough Joseph M. , Huang Jingtao , Marcus Carole L. , Gallagher Paul R. , Shults Justine , Davenport Paul W.
Published: December 2014

Children with the obstructive sleep apnea syndrome (OSAS) have impaired respiratory afferent cortical processing during sleep that persists after treatment of OSAS. However, it is unknown whether this impairment is present during wakefulness and, if so, whether it improves after OSAS treatment. We hypothesized that children with OSAS, during wakefulness, have abnormal cortical processing of respiratory stimuli manifested by blunted respiratory-related evoked potentials (RREP) and that this resolves after OSAS treatment. We measured RREP during wakefulness in 26 controls and 21 children with OSAS before and after treatment. Thirteen participants with OSAS repeated testing 3–6 mo after adenotonsillectomy. RREP were elicited by interruption of inspiration by total occlusion and 30 and 20 cmH2O/l per s resistances. Nf at Fz latency elicited by occlusion was longer in children with OSAS at baseline compared with controls (78.8 ± 24.8 vs. 63.9 ± 19.7 ms, P = 0.05). All other peak amplitudes and latencies were similar between the two groups. After OSAS treatment, Nf at Fz latency elicited by 30 cmH2O/l per s decreased significantly (before, 88 ± 26 vs. after, 71 ± 25 ms, P = 0.02), as did that elicited by 20 cmH2O/l per s (85 ± 27 vs. 72 ± 24 ms, P = 0.004). The amplitude of N1 at Cz elicited by occlusion increased from −3.4 ± 5.6 to −7.4 ± 3 μV ( P = 0.049) after treatment. We concluded that children with OSAS have partial delay of respiratory afferent cortical processing during wakefulness that improves after treatment.
Impaired firing properties of dentate granule neurons in an Alzheimer's disease animal model are rescued by PPARγ agonism
Authors: Nenov Miroslav N. , Tempia Filippo , Denner Larry , Dineley Kelly T. , Laezza Fernanda
Published: December 2014

Early cognitive impairment in Alzheimer's disease (AD) correlates with medial temporal lobe dysfunction, including two areas essential for memory formation: the entorhinal cortex and dentate gyrus (DG). In the Tg2576 animal model for AD amyloidosis, activation of the peroxisome proliferator-activated receptor-gamma (PPARγ) with rosiglitazone (RSG) ameliorates hippocampus-dependent cognitive impairment and restores aberrant synaptic activity at the entorhinal cortex to DG granule neuron inputs. It is unknown, however, whether intrinsic firing properties of DG granule neurons in these animals are affected by amyloid-β pathology and if they are sensitive to RSG treatment. Here, we report that granule neurons from 9-mo-old wild-type and Tg2576 animals can be segregated into two cell types with distinct firing properties and input resistance that correlate with less mature type I and more mature type II neurons. The DG type I cell population was greater than type II in wild-type littermates. In the Tg2576 animals, the type I and type II cell populations were nearly equal but could be restored to wild-type levels through cognitive enhancement with RSG. Furthermore, Tg2576 cell firing frequency and spike after depolarization were decreased in type I and increased in type II cells, both of which could also be restored to wild-type levels upon RSG treatment. That these parameters were restored by PPARγ activation emphasizes the therapeutic value of RSG against early AD cognitive impairment.
A function for binaural integration in auditory grouping and segregation in the inferior colliculus
Authors: Nakamoto Kyle T. , Shackleton Trevor M. , Magezi David A. , Palmer Alan R.
Published: December 2014

Responses of neurons to binaural, harmonic complex stimuli in urethane-anesthetized guinea pig inferior colliculus (IC) are reported. To assess the binaural integration of harmonicity cues for sound segregation and grouping, responses were measured to harmonic complexes with different fundamental frequencies presented to each ear. Simultaneously gated harmonic stimuli with fundamental frequencies of 125 Hz and 145 Hz were presented to the left and right ears, respectively, and recordings made from 96 neurons with characteristic frequencies >2 kHz in the central nucleus of the IC. Of these units, 70 responded continuously throughout the stimulus and were excited by the stimulus at the contralateral ear. The stimulus at the ipsilateral ear excited (EE: 14%; 10/70), inhibited (EI: 33%; 23/70), or had no significant effect (EO: 53%; 37/70), defined by the effect on firing rate. The neurons phase locked to the temporal envelope at each ear to varying degrees depending on signal level. Many of the cells (predominantly EO) were dominated by the response to the contralateral stimulus. Another group (predominantly EI) synchronized to the contralateral stimulus and were suppressed by the ipsilateral stimulus in a phasic manner. A third group synchronized to the stimuli at both ears (predominantly EE). Finally, a group only responded when the waveform peaks from each ear coincided. We conclude that these groups of neurons represent different “streams” of information but exhibit modifications of the response rather than encoding a feature of the stimulus, like pitch.
Temporal and spatial limits of pattern motion sensitivity in macaque MT neurons
Authors: Kumbhani Romesh D. , El-Shamayleh Yasmine , Movshon J. Anthony
Published: December 2014

Many neurons in visual cortical area MT signal the direction of motion of complex visual patterns, such as plaids composed of two superimposed drifting gratings. To compute the direction of pattern motion, MT neurons combine component motion signals over time and space. To determine the spatial and temporal limits of signal integration, we measured the responses of single MT neurons to a novel set of “pseudoplaid” stimuli in which the component gratings were alternated in time or space. As the temporal or spatial separation of the component gratings increased, neuronal selectivity for the direction of pattern motion decreased. Using descriptive models of signal integration, we inferred the temporal and spatial structure of the mechanisms that compute pattern direction selectivity. The median time constant for integration was roughly 10 ms, a timescale characteristic of integration by single cortical pyramidal neurons. The median spatial integration field was roughly one-third of the MT receptive field diameter, suggesting that the spatial limits are set by stages of processing in earlier areas of visual cortex where receptive fields are smaller than in MT. Interestingly, pattern direction-selective neurons had shorter temporal integration times than component direction-selective neurons but similar spatial integration windows. We conclude that pattern motion can only be signaled by MT neurons when the component motion signals co-occur within relatively narrow spatial and temporal limits. We interpret these results in the framework of recent hierarchical models of MT.