bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two Master Switch Regulators Trigger A40926 Biosynthesis in Nonomuraea sp. Strain ATCC 39727
Authors: Lo Grasso Letizia , Maffioli Sonia , Sosio Margherita , Bibb Mervyn , Puglia Anna Maria , Alduina Rosa 
Published: May 2015

ABSTRACT

The actinomycete
Nonomuraea
sp. strain ATCC 39727 produces the glycopeptide A40926, the precursor of dalbavancin. Biosynthesis of A40926 is encoded by the
dbv
gene cluster, which contains 37 protein-coding sequences that participate in antibiotic biosynthesis, regulation, immunity, and export. In addition to the positive regulatory protein Dbv4, the A40926-biosynthetic gene cluster encodes two additional putative regulators, Dbv3 and Dbv6. Independent mutations in these genes, combined with bioassays and liquid chromatography-mass spectrometry (LC-MS) analyses, demonstrated that Dbv3 and Dbv4 are both required for antibiotic production, while inactivation of
dbv6
had no effect. In addition, overexpression of
dbv3
led to higher levels of A40926 production. Transcriptional and quantitative reverse transcription (RT)-PCR analyses showed that Dbv4 is essential for the transcription of two operons,
dbv14-dbv8
and
dbv30-dbv35
, while Dbv3 positively controls the expression of four monocistronic transcription units (
dbv4
,
dbv29
,
dbv36
, and
dbv37
) and of six operons (
dbv2-dbv1
,
dbv14-dbv8
,
dbv17-dbv15
,
dbv21-dbv20
,
dbv24-dbv28
, and
dbv30-dbv35
). We propose a complex and coordinated model of regulation in which Dbv3 directly or indirectly activates transcription of
dbv4
and controls biosynthesis of 4-hydroxyphenylglycine and the heptapeptide backbone, A40926 export, and some tailoring reactions (mannosylation and hexose oxidation), while Dbv4 directly regulates biosynthesis of 3,5-dihydroxyphenylglycine and other tailoring reactions, including the four cross-links, halogenation, glycosylation, and acylation.

IMPORTANCE
This report expands knowledge of the regulatory mechanisms used to control the biosynthesis of the glycopeptide antibiotic A40926 in the actinomycete
Nonomuraea
sp. strain ATCC 39727. A40926 is the precursor of dalbavancin, approved for treatment of skin infections by Gram-positive bacteria. Therefore, understanding the regulation of its biosynthesis is also of industrial importance. So far, the regulatory mechanisms used to control two other similar glycopeptides (balhimycin and teicoplanin) have been elucidated, and beyond a common step, different clusters seem to have devised different strategies to control glycopeptide production. Thus, our work provides one more example of the pitfalls of deducing regulatory roles from bioinformatic analyses only, even when analyzing gene clusters directing the synthesis of structurally related compounds.
Effects of Acupuncture at St25 on Inflammatory Mediators and Nuclear Factor κB Activation in a Rat Model of Severe Acute Pancreatitis
Authors: Xue Qi-Ming , Pan Hui , Huang Lu , Li Ning 
Published: May 2015

Objective To observe the effect of electroacupuncture (EA) and manual acupuncture (MA) at ST25 on inflammatory mediators and nuclear factor κ-B (NF-κB) activation in rats with sodium taurocholate-induced severe acute pancreatitis (SAP). Methods Eighty-eight male Sprague–Dawley rats were randomly divided into four groups: control (sham-operated), SAP, SAP+EA and SAP+MA (n=22 each). A SAP model was established by injecting 3.5% sodium taurocholate 1 mL/kg into the pancreatic duct. In each group, animals were killed at t=3 h (n=7), 6 h (n=7) and 12 h (n=8) after the procedure. Pancreatic expression of NF-κB was examined by immunohistochemical staining. The levels of tumour necrosis factor α (TNF-α) and interleukin 6 (IL-6) in serum were determined by ELISA. Pathological changes in the pancreas were examined microscopically. Results Serum levels of TNF-α and IL-6 increased and morphological changes consistent with tissue damage were observed in the pancreas of SAP rats. NF-κB p65 expression was significantly higher in the SAP group than in the sham-operated group (p<0.05). Treatment with acupuncture at ST25 attenuated morphological damage and reduced levels of TNF-α and IL-6 in serum. NF-κB p65 expression was also significantly reduced by acupuncture at ST25 in the pancreas at 6 and 12 h after the procedure (p<0.05). There were no significant differences between the SAP+EA and SAP+MA groups. Conclusions Acupuncture at ST25 might have a therapeutic effect on rats with SAP through inhibition of NF-κB expression and a reduction in the release of pro-inflammatory cytokines.
Electroacupuncture Attenuates Collagen-Induced Arthritis in Rats through Vasoactive Intestinal Peptide Signalling-Dependent Re-Establishment of the Regulatory T Cell/T-Helper 17 Cell Balance
Authors: Zhu Jun , Chen Xiao-Yi , Li Lian-Bo , Yu Xin-Tong , Zhou Yin , Yang Wen-Jia , Liu Zhen , Zhao Na , Fu Cong , Zhang Shu-Hui , Chen Yun-Fei 
Published: May 2015

Objective Imbalance between T-helper 17 (Th17) cells and regulatory T (Treg) cells is causally linked to the development of rheumatoid arthritis (RA). In this study, we tested the hypothesis that electroacupuncture (EA) confers therapeutic benefits in RA through activation of vasoactive intestinal peptide (VIP)-dependent signalling and restoration of the Th17/Treg cell balance. Materials and Methods A collagen-induced arthritis (CIA) model was induced in Sprague–Dawley rats by injection of bovine type II collagen in incomplete Freund's adjuvant on day 0 and day 7. Three days after the second injection, EA was given at acupuncture points GB39 and ST36 three times per week for 4 weeks. To block VIP signalling, [D-P-Cl-Phe(6)-Leu(17)]-VIP, a VIP receptor antagonist, was administered intraperitoneally 30 min before EA. Inflammatory and pathological responses in the joint were assessed. Synovial VIP receptor mRNA levels and Treg and Th17 cell frequencies in the spleen were determined. Results EA significantly reduced the severity of CIA, as evidenced by reduced paw volumes, arthritis scores and inflammation scores. EA significantly increased mRNA expression of the VIP receptor VPAC1 and led to an elevation in CD4+FOXP3+ Treg cell frequency and a reduction in CD4+IL17+ Th17 cell frequency. Pre-injection of a VIP receptor antagonist significantly reversed EA-induced expansion of Treg cells, but did not alter the frequencies of Th17 cells. Conclusions EA exerts anti-inflammatory effects in a collagen-induced rat model of arthritis. These effects appear to be mediated through activation of VIP signalling and re-establishment of the Th17/Treg cell balance.
Isometric exercise induces analgesia and reduces inhibition in patellar tendinopathy
Authors: Rio Ebonie , Kidgell Dawson , Purdam Craig , Gaida Jamie , Moseley G Lorimer , Pearce Alan J , Cook Jill 
Published: May 2015

BackgroundFew interventions reduce patellar tendinopathy (PT) pain in the short term. Eccentric exercises are painful and have limited effectiveness during the competitive season. Isometric and isotonic muscle contractions may have an immediate effect on PT pain.MethodsThis single-blinded, randomised cross-over study compared immediate and 45 min effects following a bout of isometric and isotonic muscle contractions. Outcome measures were PT pain during the single-leg decline squat (SLDS, 0–10), quadriceps strength on maximal voluntary isometric contraction (MVIC), and measures of corticospinal excitability and inhibition. Data were analysed using a split-plot in time-repeated measures analysis of variance (ANOVA).Results6 volleyball players with PT participated. Condition effects were detected with greater pain relief immediately from isometric contractions: isometric contractions reduced SLDS (mean±SD) from 7.0±2.04 to 0.17±0.41, and isotonic contractions reduced SLDS (mean±SD) from 6.33±2.80 to 3.75±3.28 (p<0.001). Isometric contractions released cortical inhibition (ratio mean±SD) from 27.53%±8.30 to 54.95%±5.47, but isotonic contractions had no significant effect on inhibition (pre 30.26±3.89, post 31.92±4.67; p=0.004). Condition by time analysis showed pain reduction was sustained at 45 min postisometric but not isotonic condition (p<0.001). The mean reduction in pain scores postisometric was 6.8/10 compared with 2.6/10 postisotonic. MVIC increased significantly following the isometric condition by 18.7±7.8%, and was significantly higher than baseline (p<0.001) and isotonic condition (p<0.001), and at 45 min (p<0.001).ConclusionsA single resistance training bout of isometric contractions reduced tendon pain immediately for at least 45 min postintervention and increased MVIC. The reduction in pain was paralleled by a reduction in cortical inhibition, providing insight into potential mechanisms. Isometric contractions can be completed without pain for people with PT. The clinical implications are that isometric muscle contractions may be used to reduce pain in people with PT without a reduction in muscle strength.
Do solar cycles influence giant cell arteritis and rheumatoid arthritis incidence?
Authors: Wing Simon , Rider Lisa G , Johnson Jay R , Miller Federick W , Matteson Eric L , Crowson Cynthia S , Gabriel Sherine E 
Published: May 2015

ObjectiveTo examine the influence of solar cycle and geomagnetic effects on the incidence of giant cell arteritis (GCA) and rheumatoid arthritis (RA).MethodsWe used data from patients with GCA (1950–2004) and RA (1955–2007) obtained from population-based cohorts. Yearly trends in age-adjusted and sex-adjusted incidence were correlated with the F10.7 index (solar radiation at 10.7 cm wavelength, a proxy for the solar extreme ultraviolet radiation) and AL index (a proxy for the westward auroral electrojet and a measure of geomagnetic activity). Fourier analysis was performed on AL, F10.7, and GCA and RA incidence rates.ResultsThe correlation of GCA incidence with AL is highly significant: GCA incidence peaks 0–1 year after the AL reaches its minimum (ie, auroral electrojet reaches a maximum). The correlation of RA incidence with AL is also highly significant. RA incidence rates are lowest 5–7 years after AL reaches maximum. AL, GCA and RA incidence power spectra are similar: they have a main peak (periodicity) at about 10 years and a minor peak at 4–5 years. However, the RA incidence power spectrum main peak is broader (8–11 years), which partly explains the lower correlation between RA onset and AL. The auroral electrojets may be linked to the decline of RA incidence more strongly than the onset of RA. The incidences of RA and GCA are aligned in geomagnetic latitude.ConclusionsAL and the incidences of GCA and RA all have a major periodicity of about 10 years and a secondary periodicity at 4–5 years. Geomagnetic activity may explain the temporal and spatial variations, including east-west skewness in geographic coordinates, in GCA and RA incidence, although the mechanism is unknown. The link with solar, geospace and atmospheric parameters need to be investigated. These novel findings warrant examination in other populations and with other autoimmune diseases.
Intravenous thrombolysis guided by a telemedicine consultation system for acute ischaemic stroke patients in China: the protocol of a multicentre historically controlled study
Authors: Yuan Ziwen , Wang Bo , Li Feijiang , Wang Jing , Zhi Jin , Luo Erping , Liu Zhirong , Zhao Gang 
Published: May 2015

IntroductionThe rate of intravenous thrombolysis with tissue-type plasminogen activator or urokinase for stroke patients is extremely low in China. It has been demonstrated that a telestroke service may help to increase the rate of intravenous thrombolysis and improve stroke care quality in local hospitals. The aim of this study, also called the Acute Stroke Advancing Program, is to evaluate the effectiveness and safety of decision-making concerning intravenous thrombolysis via a telemedicine consultation system for acute ischaemic stroke patients in China.Methods and analysisThis is a multicentre historically controlled study with a planned enrolment of 300 participants in each of two groups. The telestroke network consists of one hub hospital and 14 spoke hospitals in underserved regions of China. The usual stroke care quality in the spoke hospitals without guidance from the hub hospital will be used as the historical control. The telemedicine consultation system is an interactive, two-way, wireless, audiovisual system accessed on portable devices. The primary outcome is the percentage of patients treated with intravenous thrombolysis within 4.5 h of stroke onset.Ethics and disseminationThe project has been approved by the Institutional Review Board of Xijing Hospital. The results will be published in scientific journals and presented to local government and relevant institutes.Trial registration numberNCT02088346 (12 March 2014).
High-intensity statin therapy in patients with chronic kidney disease: a systematic review and meta-analysis
Authors: Yan Yu-Ling , Qiu Bo , Wang Jing , Deng Song-Bai , Wu Ling , Jing Xiao-Dong , Du Jian-Lin , Liu Ya-Jie , She Qiang 
Published: May 2015

ObjectiveTo evaluate the efficacy and safety of high-intensity statin therapy in patients with chronic kidney disease (CKD).DesignA systematic review and meta-analysis.Data sourcesRandomised controlled trials (RCTs) comparing high-intensity statin therapy (atorvastatin 80 mg or rosuvastatin 20/40 mg) with moderate/mild statin treatment or placebo were derived from the databases (PubMed, Embase, Ovid, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, and ISI Web of Knowledge).Outcome measurePrimary end points: clinical events (all-cause mortality, stroke, myocardial infarction and heart failure); secondary end points: serum lipid, renal function changes and adverse events.ResultsA total of six RCTs with 10 993 adult patients with CKD were included. A significant decrease in stroke was observed in the high-intensity statin therapy group (RR 0.69, 95% CI 0.56 to 0.85). However, the roles of high-intensity statin in decreasing all-cause mortality (RR 0.85, 95% CI 0.67 to 1.09), myocardial infarction (RR 0.69, 95% CI 0.40 to 1.18) and heart failure (RR 0.73, 95% CI 0.48 to 1.13) remain unclear with low evidence. High-intensity statin also had obvious effects on lowering the LDL-C level but no clear effects on renal protection. Although pooled results showed no significant difference between the intervention and control groups in adverse event occurrences, it was still insufficient to put off the doubts that high-intensity statin might increase adverse events because of limited data sources and low quality evidences.ConclusionsHigh-intensity statin therapy could effectively reduce the risk of stroke in patients with CKD. However, its effects on all-cause mortality, myocardial infarction, heart failure and renal protection remain unclear. Moreover, it is hard to draw conclusions on the safety assessment of intensive statin treatment in this particular population. More studies are needed to credibly evaluate the effects of high-intensity statin therapy in patients with CKD.
Intrauterine insemination: a UK survey on the adherence to NICE clinical guidelines by fertility clinics
Authors: Kim Dongah , Child Tim , Farquhar Cynthia 
Published: May 2015

ObjectiveTo evaluate the awareness and response of fertility clinics in the UK to the National Institute for Health and Care Excellence (NICE) guideline recommendation that intrauterine insemination (IUI) should not be offered routinely, in order to report on current practice in the UK.DesignOnline questionnaire survey of fertility clinics in the UK regarding their current clinical practice of IUI, formal discussion of the guideline recommendations, and any alterations made since the recommendations.Setting66 UK fertility clinics licensed to provide IUI.Participants46 fertility clinics, including 6 clinic groups which represent 70% of all clinics and clinic groups licensed to provide IUI in April 2014 when the survey email was sent.ResultsOf the 46 clinics that responded, 96% (44/46) of clinics continue to offer IUI. 98% (43/44) of those offering IUI also use ovarian stimulation. The most commonly used medications for ovarian stimulation are gonadotrophins (95%), followed by clomiphene citrate (49%) and letrozole (19%). 78% (36/46) of clinics had formally discussed NICE guideline recommendations. 17 clinics (37%) had made some changes to their practices; as a result, four clinics reported a reduction in the number of IUI cycles, six clinics had restricted the indications for IUI, and five clinics had begun informing patients of the guideline recommendations, while two did not specify.ConclusionsThe majority of clinics were aware of the guideline recommendations. However, only a small proportion of clinics had made significant changes to their practice by reducing the number of IUI cycles or restricting the clinical indications for IUI. The availability of further evidence will assist NICE and clinicians in making recommendations on the use of IUI. There is a need to further explore the reasons for the lack of adherence to the recommendations.
Fructosamine measurement for diabetes mellitus diagnosis and monitoring: a systematic review and meta-analysis protocol
Authors: Nansseu Jobert Richie N , Fokom-Domgue Joël , Noubiap Jean Jacques N , Balti Eric V , Sobngwi Eugène , Kengne André Pascal 
Published: May 2015

IntroductionFructosamine is a marker of glucose control reflecting the average glycaemic level over the preceding 2–3 weeks. Fructosamine has not gained as much popularity as glycated haemoglobin (HbA1c) for diabetes mellitus (DM) control monitoring, and the related underlying reasons remain unclear. We aim to search for and summarise available evidence on the accuracy of fructosamine measurements to diagnose and monitor DM.Methods and analysisThis systematic review will include randomised control trials, controlled before-and-after studies, time series designs, cohort studies, case–control studies and cross-sectional surveys reporting the diagnosis and/or monitoring of DM (type 1 DM, type 2 DM and gestational DM) with fructosamine compared with other measures of glycaemia (fasting glucose, oral glucose tolerance test, random glucose, HbA1c), without any language restriction. We will perform electronic searches in PubMed, Scopus and other databases, supplemented with manual searches. Articles published from 1 January 1980 to 30 June 2015 will be eligible for inclusion in this review. Two authors will independently screen, select studies, extract data and assess the risk of bias with discrepancies resolved by consensus. We will assess clinical heterogeneity by examining the types of interventions and outcomes in each study, and pool studies judged to be clinically homogeneous. We will also assess statistical heterogeneity using the χ2test of homogeneity and quantify it using the I2statistic. Absolute accuracy measures (sensitivity, specificity) will be pooled in a bivariate random-effects model, allowing for intersetting variability. Negative and positive predictive values will be computed for fructosamine, compared with another measure of glycaemia from the pooled estimates of sensitivity and specificity, using Bayes’ theorem.Ethics and disseminationThis systematic review will use data from published studies and does not require ethics approval. Findings will be published in a peer-reviewed journal and presented at scientific conferences.Trial registration numberPROSPERO (ID=CRD42015015930).
Protocol for the CHEST Australia Trial: a phase II randomised controlled trial of an intervention to reduce time-to-consult with symptoms of lung cancer
Authors: Murray Sonya R , Murchie Peter , Campbell Neil , Walter Fiona M , Mazza Danielle , Habgood Emily , Kutzer Yvonne , Martin Andrew , Goodall Stephen , Barnes David J , Emery Jon D 
Published: May 2015

IntroductionLung cancer is the most common cancer worldwide, with 1.3 million new cases diagnosed every year. It has one of the lowest survival outcomes of any cancer because over two-thirds of patients are diagnosed when curative treatment is not possible. International research has focused on screening and community interventions to promote earlier presentation to a healthcare provider to improve early lung cancer detection. This paper describes the protocol for a phase II, multisite, randomised controlled trial, for patients at increased risk of lung cancer in the primary care setting, to facilitate early presentation with symptoms of lung cancer.Methods/analysisThe intervention is based on a previous Scottish CHEST Trial that comprised of a primary-care nurse consultation to discuss and implement a self-help manual, followed by self-monitoring reminders to improve symptom appraisal and encourage help-seeking in patients at increased risk of lung cancer. We aim to recruit 550 patients from two Australian states: Western Australia and Victoria. Patients will be randomised to the Intervention (a health consultation involving a self-help manual, monthly prompts and spirometry) or Control (spirometry followed by usual care). Eligible participants are long-term smokers with at least 20 pack years, aged 55 and over, including ex-smokers if their cessation date was less than 15 years ago. The primary outcome is consultation rate for respiratory symptoms.Ethics and disseminationEthical approval has been obtained from The University of Western Australia's Human Research Ethics Committee (RA/4/1/6018) and The University of Melbourne Human Research Committee (1 441 433). A summary of the results will be disseminated to participants and we plan to publish the main trial outcomes in a single paper. Further publications are anticipated after further data analysis. Findings will be presented at national and international conferences from late 2016.Trial registration numberAustralian New Zealand Clinical Trial Registry ACTRN 1261300039 3752.
Improving the care of patients with a hip fracture: a quality improvement report
Authors: Hawkes David , Baxter Jonathan , Bailey Claire , Holland Gemma , Ruddlesdin Jennifer , Wall Alun , Wykes Philip 
Published: May 2015

IntroductionHip fractures are associated with high rates of morbidity and mortality and their incidence is set to increase. The National Hip Fracture Database and the Best Practice Tariff were introduced with the aim of improving patient care. This complete audit cycle charts the substantial clinical improvements that were achieved in a busy district general hospital.MethodsThe first audit cycle comprised 379 patients who were admitted between May 2012 and April 2013. The primary audit criterion was operative intervention within 36 h of admission. Variation according to the day of the week of admission was assessed to evaluate specific deficiencies in local service provision. The principle audit intervention was the introduction of two additional morning trauma lists. A re-audit of 162 patients was conducted prospectively between January 2014 and June 2014.ResultsMean time to theatre was 49±39 h during the first audit cycle compared with 27±19 h (p<0.0001) during the second. Consequently, the proportion of patients undergoing operative intervention within 36 h of admission improved from 41% to 78% (p<0.0001). Overall achievement of Best Practice Tariff was significantly higher during the second cycle: 28% vs 73% (p<0.0001).ConclusionsSignificant improvements in the quality of hip fracture care were achieved following this audit. These were accomplished by rigorously analysing the variation in Best Practice Tariff achievement according to the day of the week on which patients were admitted. Targeted interventions could therefore be introduced that addressed specific problems in local service provision.