bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

ABSTRACT

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

ABSTRACT

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

ABSTRACT

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.
Reptile-associated salmonellosis in children aged under 5 years in South West England
Authors: Murphy Dan , Oshin Femi 
Published: December 2014

ObjectiveTo determine the proportion of Salmonella cases in children aged <5 years that were reptile-associated salmonellosis (RAS) and to compare the severity of illness.DesignTo 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.Results48 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).ConclusionsReptile 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.
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

ObjectivesTo assess the effect of awareness and advice to seek care on blood pressure (BP) control among patients with hypertension in Bangladesh.DesignLongitudinal study.SettingThe study was carried out in icddr,b surveillance sites at rural Matlab in Chandpur district and semi-urban Kamalapur in Dhaka, Bangladesh.ParticipantsRandomly 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 measureHypertension 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.ResultsOverall, 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).ConclusionsAwareness 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

ObjectiveTo 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.SettingStudies were multicentre and multinational.ParticipantsTen studies including 2967 patients with T2DM.InterventionsStudies that examined DPP-4 inhibitors compared with each other, intermediate-acting insulin, no treatment or placebo in patients with T2DM.Primary and secondary outcome measuresPrimary 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.Results10 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).ConclusionsDPP-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 numberPROSPERO # 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

IntroductionThe 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/analysisThis 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/disseminationThe 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 numberChiCTR-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

ObjectiveTo create and validate a frailty assessment tool for community-dwelling adults aged ≥75 years.DesignLongitudinal, population-based study.SettingThe Survey of Health, Ageing and Retirement in Europe (SHARE).Participants4001 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 measuresThe 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).ResultsIn 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.ConclusionsSHARE-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

IntroductionThis review aims to evaluate the effectiveness and safety of acupuncture for patients with postoperative pain after laparoscopic surgery.Methods and analysisWe 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.DisseminationThe 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 numberPROSPERO 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

BackgroundExposure 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.MethodsThe 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.ResultsA 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.ConclusionsThe results highlight the effect of environmental factors during childhood on mental health and the need for early recognition of families at risk.