bluuebunny/crossref_metadata_2025_split huggingface dataset:
Guava leaf extracts promote glucose metabolism in SHRSP.Z-Leprfa/Izm rats by improving insulin resistance in skeletal muscle
Authors: Guo Xiangyu , Yoshitomi Hisae , Gao Ming , Qin Lingling , Duan Ying , Sun Wen , Xu Tunhai , Xie Peifeng , Zhou Jingxin , Huang Liansha , Liu Tonghua 
Published: March 2013

Abstract

Background
Metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM) have been associated with insulin-resistance; however, the effective therapies in improving insulin sensitivity are limited. This study is aimed at investigating the effect of Guava Leaf (GL) extracts on glucose tolerance and insulin resistance in SHRSP.Z-Leprfa/Izm rats (SHRSP/ZF), a model of spontaneously metabolic syndrome.

Methods
Male rats at 7 weeks of age were administered with vehicle water or treated by gavage with 2 g/kg GL extracts daily for six weeks, and their body weights, water and food consumption, glucose tolerance, and insulin resistance were measured.

Results
Compared with the controls, treatment with GL extracts did not modulate the amounts of water and food consumption, but significantly reduced the body weights at six weeks post treatment. Treatment with GL extracts did not alter the levels of fasting plasma glucose and insulin, but significantly reduced the levels of plasma glucose at 60 and 120 min post glucose challenge, also reduced the values of AUC and quantitative insulin sensitivity check index (QUICKI) at 42 days post treatment. Furthermore, treatment with GL extracts promoted IRS-1, AKT, PI3Kp85 expression, then IRS-1, AMKP, and AKT308, but not AKT473, phosphorylation, accompanied by increasing the ratios of membrane to total Glut 4 expression and adiponectin receptor 1 transcription in the skeletal muscles.

Conclusions
These data indicated that GL extracts improved glucose metabolism and insulin sensitivity in the skeletal muscles of rats by modulating the insulin-related signaling.
Characterizing microclimate in urban malaria transmission settings: a case study from Chennai, India
Authors: Cator Lauren J , Thomas Shalu , Paaijmans Krijn P , Ravishankaran Sangamithra , Justin Johnson A , Mathai Manu T , Read Andrew F , Thomas Matthew B , Eapen Alex 
Published: March 2013

Abstract

Background
Environmental temperature is an important driver of malaria transmission dynamics. Both the parasite and vector are sensitive to mean ambient temperatures and daily temperature variation. To understand transmission ecology, therefore, it is important to determine the range of microclimatic temperatures experienced by malaria vectors in the field.

Methods
A pilot study was conducted in the Indian city of Chennai to determine the temperature variation in urban microclimates and characterize the thermal ecology of the local transmission setting. Temperatures were measured in a range of probable indoor and outdoor resting habitats of Anopheles stephensi in two urban slum malaria sites. Mean temperatures and daily temperature fluctuations in local transmission sites were compared with standard temperature measures from the local weather station. The biological implications of the different temperatures were explored using temperature-dependent parasite development models to provide estimates of the extrinsic incubation period (EIP) of Plasmodium vivax and Plasmodium falciparum.

Results
Mean daily temperatures within the urban transmission sites were generally warmer than those recorded at the local weather station. The main reason was that night-time temperatures were higher (and hence diurnal temperature ranges smaller) in the urban settings. Mean temperatures and temperature variation also differed between specific resting sites within the transmission environments. Most differences were of the order of 1-3°C but were sufficient to lead to important variation in predicted EIPs and hence, variation in estimates of transmission intensity.

Conclusions
Standard estimates of environmental temperature derived from local weather stations do not necessarily provide realistic measures of temperatures within actual transmission environments. Even the small differences in mean temperatures or diurnal temperature ranges reported in this study can lead to large variations in key mosquito and/or parasite life history traits that determine transmission intensity. Greater effort should be directed at quantifying adult mosquito resting behaviour and determining the temperatures actually experienced by mosquitoes and parasites in local transmission environments. In the absence of such highly resolved data, the approach used in the current study provides a framework for improved thermal characterization of transmission settings.
Combination treatment with ABT-737 and chloroquine in preclinical models of small cell lung cancer
Authors: Zinn Rebekah L , Gardner Eric E , Dobromilskaya Irina , Murphy Sara , Marchionni Luigi , Hann Christine L , Rudin Charles M 
Published: March 2013

Abstract

Background
New therapies are urgently needed for patients with small cell lung cancer (SCLC). Chemotherapy and targeted therapies, including the Bcl-2 inhibitor ABT-737, may induce tumor cell autophagy. Autophagy can promote survival of cancer cells under stress and comprise a pathway of escape from cytotoxic therapies.

Methods
We explored the combination of ABT-737 and chloroquine, an inhibitor of autophagy, in preclinical models of SCLC. These included cell culture analyses of viability and of autophagic and apoptotic pathway induction, as well as in vivo analyses of efficacy in multiple xenograft models.

Results
Combination treatment of SCLC lines with ABT-737 and chloroquine decreased viability and increased caspase-3 activation over treatment with either single agent. ABT-737 induced several hallmarks of autophagy. However, knockdown of beclin-1, a key regulator of entry into autophagy, diminished the efficacy of ABT-737, suggesting either that the effects of chloroquine were nonspecific or that induction but not completion of autophagy is necessary for the combined effect of ABT-737 and chloroquine. ABT-737 and chloroquine in SCLC cell lines downregulated Mcl-1 and upregulated NOXA, both of which may promote apoptosis. Treatment of tumor-bearing mice demonstrated that chloroquine could enhance ABT-737-mediated tumor growth inhibition against NCI-H209 xenografts, but did not alter ABT-737 response in three primary patient-derived xenograft models.

Conclusion
These data suggest that although ABT-737 can induce autophagy in SCLC, autophagic inhibition by choroquine does not markedly alter in vivo response to ABT-737 in relevant preclinical models, arguing against this as a treatment strategy for SCLC.
Organic electrochemical transistors based on a dielectrophoretically aligned nanowire array
Authors: Choi WooSeok , An Taechang , Lim Geunbae 
Published: March 2013

AbstractIn this study, we synthesized an organic electrochemical transistor (OECT) using dielectrophoresis of a carbon nanotube-Nafion (CNT-Nafion) suspension. Dielectrophoretically aligned nanowires formed a one-dimensional submicron bundle between triangular electrodes. The CNT-Nafion composite nanowire bundles showed p-type semiconductor characteristics. The drain-source current decreased with increasing gate voltage. The nanowire bundles showed potential as pH sensor because the drain-source current ratio varied linearly according to the gate voltage in pH buffers.
Hydroxychloroquine effectiveness in reducing symptoms of hand osteoarthritis (HERO): study protocol for a randomized controlled trial
Authors: Kingsbury Sarah R , Tharmanathan Puvan , Adamson Joy , Arden Nigel K , Birrell Fraser , Cockayne Sarah , Dickson John , Doherty Michael , Dziedzic Krysia S , Grainger Andrew , Hewitt Catherine E , O’Neill Terence W , Scott David L , Vincent Tonia L , Wakefield Richard J , Watt Fiona E , Torgerson David J , Conaghan Philip G 
Published: March 2013

Abstract

Background
Osteoarthritis (OA) is the most common type of arthritis, causing significant joint pain and disability. It is already a major cause of healthcare expenditure and its incidence will further increase with the ageing population. Current treatments for OA have major limitations and new analgesic treatments are needed. Synovitis is prevalent in OA and is associated with pain. Hydroxychloroquine is used in routine practice for treating synovitis in inflammatory arthritides, such as rheumatoid arthritis. We propose that treating patients with symptomatic hand OA with hydroxychloroquine will be a practical and safe treatment to reduce synovitis and pain.

Methods/design
HERO is an investigator-initiated, multicentre, randomized, double-blind, placebo-controlled trial. A total of 252 subjects with symptomatic hand OA will be recruited across primary and secondary care sites in the UK and randomized on a 1:1 basis to active treatment or placebo for 12 months. Daily medication dose will range from 200 to 400 mg according to ideal body weight. The primary endpoint is change in average hand pain during the previous two weeks (measured on a numerical rating scale (NRS)) between baseline and six months. Secondary endpoints include other self-reported pain, function and quality-of-life measures and radiographic structural change at 12 months. A health economics analysis will also be performed. An ultrasound substudy will be conducted to examine baseline levels of synovitis. Linear and logistic regression will be used to compare changes between groups using univariable and multivariable modelling analyses. All analyses will be conducted on an intention-to-treat basis.

Discussion
The HERO trial is designed to examine whether hydroxychloroquine is an effective analgesic treatment for OA and whether it provides any long-term structural benefit. The ultrasound substudy will address whether baseline synovitis is a predictor of therapeutic response. This will potentially provide a new treatment for OA, which could be of particular use in the primary care setting.

Trial registration

ISRCTN91859104.
Outcome of surgical treatment for proximal long segment post intubation tracheal stenosis
Authors: Bagheri Reza , Majidi Mohammadreza , Khadivi Ehsan , attar Alireza Sharifian , Tabari Azadeh 
Published: March 2013

Abstract

Background
Post intubation long segment tracheal stenosis is a serious problem which usually requires multiple methods of treatment. The aim of this study was to evaluate the results of surgical treatment in long segment post intubation tracheal stenosis.

Methods
Between 2004 to 2008, 20 patients with proximal long segment tracheal stenosis and resection of over 40% of tracheal length, were analyzed in terms of age, sex, clinical symptoms, etiology of stenosis, length of stenosis and resection, role of suprahyoeid release with bilateral hyoeid bone cutting maneuver, post operative complications and life quality 3 year after surgery.

Results
M/F was 2/5, with the average age of 23.5 ± 0.5 years. Average length of stenosis was 4.2 ± 0.4 cm and the average length of resected segment was 5.2 ± 0.4 cm. Early postoperative complications occurred in 4 patients (20%), 5 patients (25%) had late stenosis and 4 of them were treated with multiple dilation and one patient needed tracheostomy and prolonged T. tube. We didn’t have any mortality. 80% of patients had excellent surgical results in follow up period.

Conclusion
Surgery is the best method of treatment in long and multi segment tracheal stenosis.
Incidence and pattern of technical complications in balloon-guided osteoplasty for depressed tibial plateau fractures: a pilot study in 20 consecutive patients
Authors: Mauffrey Cyril , Fader Ryan , Hammerberg E Mark , Hak David J , Stahel Philip F 
Published: March 2013

Abstract

Background
Inflation bone tamps are becoming increasingly popular as a reduction tool for depressed tibial plateau fractures. A number of recent publications have addressed the technical aspects of balloon inflation osteoplasty. However, no study has yet been published to describe the technical limitations, intraoperative complications, and surgical bailout strategies for this new technology.

Methods
Observational retrospective study of all patients managed with inflatable bone tamps for depressed tibial plateau fractures between October 1, 2010 and December 1, 2012. The primary outcome parameter was the rate of complications, which were stratified into “minor” and “major” depending on the necessity for altering the surgical plan intraoperatively, and based on the risk for patient harm. This study was approved by the Institutional Review Board of the State of Colorado.

Results
A consecutive series of 20 patients were managed by balloon inflation osteoplasty for depressed tibial plateau fractures during the 15 months study period. The mean age was 42.8 years (range 20–79), with 9 females and 11 males. A total of 13 patients sustained an adverse intraoperative event (65%), with three patients sustaining multiple technical complications. Minor events (n = 8) included the burst of a balloon with extrusion of contrast dye, and the unintentional posterior wall displacement during balloon inflation. Major events (n = 5) included the intra-articular injection of calcium phosphate in the knee joint, and the inability to elevate the depressed articular fragment with the inflatable bone tamp.

Conclusion
The observed intraoperative complication rate of 65% reflects a steep learning curve for the use of inflation bone tamps to reduce depressed tibial plateau fractures. Specific surgical bailout options are provided in this article, based on our early anecdotal experience in a pilot series of 20 consecutive cases. Patients should be advised on the benefits and risks of this new technology as part of the shared decision-making process during the informed consent.
Evaluation of reference genes for reverse transcription quantitative PCR analyses of fish-pathogenic Francisella strains exposed to different growth conditions
Authors: Brudal Espen , Winther-Larsen Hanne Cecilie , Colquhoun Duncan John , Duodu Samuel 
Published: March 2013

Abstract

Background
Reverse transcription quantitative PCR has become a powerful technique to monitor mRNA transcription in response to different environmental conditions in many bacterial species. However, correct evaluation of data requires accurate and reliable use of reference genes whose transcription does not change during the course of the experiment. In the present study exposure to different growth conditions was used to validate the transcription stability of eight reference gene candidates in three strains from two subspecies of Francisella noatunensis, a pathogen causing disease in both warm and cold water fish species.

Results
Relative transcription levels for genes encoding DNA gyrase (gyrA), RNA polymerase beta subunit (rpoB), DNA polymerase I (polA), cell division protein (ftsZ), outer membrane protein (fopA), riboflavin biosynthesis protein (ribC), 16S ribosomal RNA (16S rRNA) and DNA helicases (uvrD) were quantified under exponential, stationary and iron-restricted growth conditions. The suitability of selected reference genes for reliable interpretation of gene expression data was tested using the virulence-associated intracellular growth locus subunit C (iglC) gene.

Conclusion
Although the transcription stability of the reference genes was slightly different in the three strains studied, fopA, ftsZ and polA proved to be the most stable and suitable for normalization of gene transcription in Francisella noatunensis ssp.
Use of a physiologically-based pharmacokinetic model to simulate artemether dose adjustment for overcoming the drug-drug interaction with efavirenz
Authors: Siccardi Marco , Olagunju Adeniyi , Seden Kay , Ebrahimjee Farid , Rannard Steve , Back David , Owen Andrew 
Published: March 2013

Abstract
Purpose
To treat malaria, HIV-infected patients normally receive artemether (80 mg twice daily) concurrently with antiretroviral therapy and drug-drug interactions can potentially occur. Artemether is a substrate of CYP3A4 and CYP2B6, antiretrovirals such as efavirenz induce these enzymes and have the potential to reduce artemether pharmacokinetic exposure. The aim of this study was to develop an in vitro in vivo extrapolation (IVIVE) approach to model the interaction between efavirenz and artemether. Artemether dose adjustments were then simulated in order to predict optimal dosing in co-infected patients and inform future interaction study design.

Methods
In vitro data describing the chemical properties, absorption, distribution, metabolism and elimination of efavirenz and artemether were obtained from published literature and included in a physiologically based pharmacokinetic model (PBPK) to predict drug disposition simulating virtual clinical trials. Administration of efavirenz and artemether, alone or in combination, were simulated to mirror previous clinical studies and facilitate validation of the model and realistic interpretation of the simulation. Efavirenz (600 mg once daily) was administered to 50 virtual subjects for 14 days. This was followed by concomitant administration of artemether (80 mg eight hourly) for the first two doses and 80 mg (twice daily) for another two days.

Results
Simulated pharmacokinetics and the drug-drug interaction were in concordance with available clinical data. Efavirenz induced first pass metabolism and hepatic clearance, reducing artemether Cmax by 60% and AUC by 80%. Dose increases of artemether, to correct for the interaction, were simulated and a dose of 240 mg was predicted to be sufficient to overcome the interaction and allow therapeutic plasma concentrations of artemether.

Conclusions
The model presented here provides a rational platform to inform the design for a clinical drug interaction study that may save time and resource while the optimal dose is determined empirically. Wider application of IVIVE could help researchers gain a better understanding of the molecular mechanisms underpinning variability in drug disposition.
Pannexin1 hemichannels are critical for HIV infection of human primary CD4+ T lymphocytes
Authors: Orellana J A , Velasquez S , Williams D W , Sáez J C , Berman J W , Eugenin E A 
Published: March 2013

ABSTRACTHIV is a major public health issue, and infection of CD4+ T lymphocytes is one of its key features. Whereas several cellular proteins have been identified that facilitate viral infection and replication, the role of hemichannels in these processes has not been fully characterized. We now show that the HIV isolates, R5 and X4, induced a transient-early (5–30 min) and a later, persistent (48–120 h) opening of Panx1 hemichannels, which was dependent on the binding of HIV to CD4 and CCR5/CXCR4 receptors. Blocking Panx1 hemichannels by reducing their opening or protein expression inhibited HIV replication in CD4+ T lymphocytes. Thus, our findings demonstrate that Panx1 hemichannels play an essential role in HIV infection.
Dwarfism and Increased Adiposity in the gh1 Mutant Zebrafish vizzini
Authors: McMenamin Sarah K. , Minchin James E.N. , Gordon Tiffany N. , Rawls John F. , Parichy David M. 
Published: March 2013

AbstractSomatic growth and adipogenesis are closely associated with the development of obesity in humans. In this study, we identify a zebrafish mutant, vizzini, that exhibits both a severe defect in somatic growth and increased accumulation of adipose tissue. Positional cloning of vizzini revealed a premature stop codon in gh1. Although the effects of GH are largely through igfs in mammals, we found no decrease in the expression of igf transcripts in gh1 mutants during larval development. As development progressed, however, we found overall growth to be progressively retarded and the attainment of specific developmental stages to occur at abnormally small body sizes relative to wild type. Moreover, both subcutaneous (sc) and visceral adipose tissues underwent precocious development in vizzini mutants, and at maturity, the sizes of different fat deposits were greatly expanded relative to wild type. In vivo confocal imaging of sc adipose tissue (SAT) expansion revealed that vizzini mutants exhibit extreme enlargement of adipocyte lipid droplets without a corresponding increase in lipid droplet number. These findings suggest that GH1 signaling restricts SAT hypertrophy in zebrafish. Finally, nutrient deprivation of vizzini mutants revealed that SAT mobilization was greatly diminished during caloric restriction, further implicating GH1 signaling in adipose tissue homeostasis. Overall, the zebrafish gh1 mutant, vizzini, exhibits decreased somatic growth, increased adipose tissue accumulation, and disrupted adipose plasticity after nutrient deprivation and represents a novel model to investigate the in vivo dynamics of vertebrate obesity.
Does pre-coating total knee tibial implants affect the risk of aseptic revision?
Authors: Bini S. A. , Chen Y. , Khatod M. , Paxton E. W. 
Published: February 2013

We evaluated the impact of pre-coating the tibial component with polymethylmethacrylate (PMMA) on implant survival in a cohort of 16 548 primary NexGen total knee replacements (TKRs) in 14 113 patients. In 13 835 TKRs a pre-coated tray was used while in 2713 TKRs the non-pre-coated version of the same tray was used. All the TKRs were performed between 2001 and 2009 and were cemented. TKRs implanted with a pre-coated tibial component had a lower cumulative survival than those with a non-pre-coated tibial component (p = 0.01). After adjusting for diagnosis, age, gender, body mass index, American Society of Anesthesiologists grade, femoral coupling design, surgeon volume and hospital volume, pre-coating was an independent risk factor for all-cause aseptic revision (hazard ratio 2.75, p = 0.006). Revision for aseptic loosening was uncommon for both pre-coated and non-pre-coated trays (rates of 0.12% and 0%, respectively). Pre-coating with PMMA does not appear to be protective of revision for this tibial tray design at short-term follow-up.Cite this article: Bone Joint J 2013;95-B:367–70.
Primary total knee replacement in patients with mental disability improves their mental health and knee function
Authors: Clement N. D. , MacDonald D. , Burnett R. 
Published: February 2013

We assessed the effect of mental disability on the outcome of total knee replacement (TKR) and investigated whether mental health improves post-operatively. Outcome data were prospectively recorded over a three-year period for 962 patients undergoing primary TKR for osteoarthritis. Pre-operative and one year Short-Form (SF)-12 scores and Oxford knee scores (OKS) were obtained. The mental component of the SF-12 was stratified into four groups according to level of mental disability (none ≥ 50, mild 40 to 49, moderate 30 to 39, severe < 30). Patients with any degree of mental disability had a significantly greater subjective physical disability according to the SF-12 (p = 0.06) and OKS (p < 0.001). The improvement in the disease-specific score (OKS) was not affected by a patient’s mental health (p = 0.33). In contrast, patients with mental disability had less of an improvement in their global physical health (SF-12) (p < 0.001). However, patients with any degree of mental disability had a significant improvement in their mental health post-operatively (p < 0.001). Despite a similar improvement in their disease-specific scores and improvement in their mental health, patients with mental disability were significantly more likely to be dissatisfied with their TKR at one year (p = 0.001). Patients with poor mental health do benefit from improvements in their mental health and knee function after TKR, but also have a higher rate of dissatisfaction. Cite this article: Bone Joint J 2013;95-B:360–6.