bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiviral Effects of Artesunate on Polyomavirus BK Replication in Primary Human Kidney Cells
Authors: Sharma Biswa Nath , Marschall Manfred , Henriksen Stian , Rinaldo Christine Hanssen 
Published: October 2013

ABSTRACT

Polyomavirus BK (BKV) causes polyomavirus-associated nephropathy (PyVAN) and hemorrhagic cystitis (PyVHC) in renal and bone marrow transplant patients, respectively. Antiviral drugs with targeted activity against BKV are lacking. Since the antimalarial drug artesunate was recently demonstrated to have antiviral activity, the possible effects of artesunate on BKV replication in human primary renal proximal tubular epithelial cells (RPTECs), the host cells in PyVAN, were explored. At 2 h postinfection (hpi), RPTECs were treated with artesunate at concentrations ranging from 0.3 to 80 μM. After one viral replication cycle (approximately 72 hpi), the loads of extracellular BKV DNA, reflecting viral progeny production, were reduced in a concentration-dependent manner. Artesunate at 10 μM reduced the extracellular BKV load by 65%; early large T antigen mRNA and protein expression by 30% and 75%, respectively; DNA replication by 73%; and late VP1 mRNA and protein expression by 47% and 64%, respectively. Importantly, the proliferation of RPTECs was also inhibited in a concentration-dependent manner. At 72 hpi, artesunate at 10 μM reduced cellular DNA replication by 68% and total metabolic activity by 47%. Cell impedance and lactate dehydrogenase measurements indicated a cytostatic but not a cytotoxic mechanism. Flow cytometry and 5-ethynyl-2′-deoxyuridine incorporation revealed a decreased number of cells in S phase and suggested cell cycle arrest in G
0
or G
2
phase. Both the antiproliferative and antiviral effects of artesunate at 10 μM were reversible. Thus, artesunate inhibits BKV replication in RPTECs in a concentration-dependent manner by inhibiting BKV gene expression and genome replication. The antiviral mechanism appears to be closely connected to cytostatic effects on the host cell, underscoring the dependence of BKV on host cell proliferative functions.
Sensory and motor deficits exist on the non-injured side of patients with unilateral tendon pain and disability—implications for central nervous system involvement: a systematic review with meta-analysis
Authors: Heales L J , Lim E C W , Hodges P W , Vicenzino B 
Published: October 2013

IntroductionTendinopathy manifests as activity-related tendon pain with associated motor and sensory impairments. Tendon tissue changes in animals present in injured as well as contralateral non-injured tendon. This review investigated evidence for bilateral sensory and motor system involvement in unilateral tendinopathy in humans.MethodsA comprehensive search of electronic databases, and reference lists using keywords relating to bilateral outcomes in unilateral tendinopathy was undertaken. Study quality was rated with the Epidemiological Appraisal Instrument and meta-analyses carried out where appropriate. Analysis focused on comparison of measures in the non-symptomatic side of patients against pain-free controls.ResultsThe search revealed 5791 studies, of which 20 were included (117 detailed reviews, 25 met criteria). There were 17 studies of lateral epicondylalgia (LE) and one each for patellar, Achilles and rotator cuff tendinopathy. Studies of LE were available for meta-analysis revealing the following weighted pooled mean deficits: pressure pain thresholds (−144.3 kPa; 95% CI −169.2 to −119.2 p<0.001), heat pain thresholds (−1.2°C; 95% CI −2.1 to −0.2, p<0.001), cold pain thresholds (3.1°C; 95% CI 1.8 to 4.4, p<0.001) and reaction time (37.8 ms; 95% CI 24.8 to 50.7, p<0.001).DiscussionDeficits in sensory and motor systems present bilaterally in unilateral tendinopathy. This implies potential central nervous system involvement. This indicates that rehabilitation should consider the contralateral side of patients. Research of unilateral tendinopathy needs to consider comparison against pain-free controls in addition to the contralateral side to gain a complete understanding of sensory and motor features.
Clinical Outcomes of Surgical Pulmonary Valve Replacement After Repair of Tetralogy of Fallot and Potential Prognostic Value of Preoperative Cardiopulmonary Exercise Testing
Authors: Babu-Narayan Sonya V. , Diller Gerhard-Paul , Gheta Radu R. , Bastin Anthony J. , Karonis Theodoros , Li Wei , Pennell Dudley J. , Uemura Hideki , Sethia Babulal , Gatzoulis Michael A. , Shore Darryl F. 
Published: October 2013

Background—
Indications for surgical pulmonary valve replacement (PVR) after repair of tetralogy of Fallot have recently been broadened to include asymptomatic patients.

Methods and Results—

The outcomes of PVR in adults after repair of tetralogy of Fallot at a single tertiary center were retrospectively studied. Preoperative cardiopulmonary exercise testing was included. Mortality was the primary outcome measure. In total, 221 PVRs were performed in 220 patients (130 male patients; median age, 32 years; range, 16–64 years). Homografts were used in 117 patients, xenografts in 103 patients, and a mechanical valve in 1 patient. Early (30-day) mortality was 2%. Overall survival was 97% at 1 year, 96% at 3 years, and 92% at 10 years. Survival after PVR in the later era (2005–2010; n=156) was significantly better compared with survival in the earlier era (1993–2004; n=65; 99% versus 94% at 1 year and 98% versus 92% at 3 years, respectively;
P
=0.019). Earlier era patients were more symptomatic preoperatively (
P
=0.036) with a lower preoperative peak oxygen consumption (peak

o
2
;
P
<0.001). Freedom from redo surgical or transcatheter PVR was 98% at 5 years and 96% at 10 years for the whole cohort. Peak

o
2
, E/CO2 slope (ratio of minute ventilation to carbon dioxide production), and heart rate reserve during cardiopulmonary exercise testing predicted risk of early mortality when analyzed with logistic regression analysis; peak

o
2
emerged as the strongest predictor on multivariable analysis (odds ratio, 0.65 per 1 mL·kg
−1
·min
−1
;
P
=0.041).

Conclusions—
PVR after repair of tetralogy of Fallot has a low and improving mortality, with a low need for reintervention. Preoperative cardiopulmonary exercise testing predicts surgical outcome and should therefore be included in the routine assessment of these patients.
Operative Management of Ulnar Collateral Ligament Insufficiency in Adolescent Athletes
Authors: Jones Kristofer J. , Dines Joshua S. , Rebolledo Brian J. , Weeks Kenneth D. , Williams Riley J. , Dines David M. , Altchek David W. 
Published: October 2013

Background: The incidence of ulnar collateral ligament (UCL) injuries of the elbow has increased in adolescents over the past decade because of widespread participation in athletics and heightened awareness among physicians. Hypothesis: Ulnar collateral ligament reconstruction using the docking technique would result in a successful return to athletic activity in this age group. Study Design: Case series; Level of evidence, 4. Methods: Study participants were 55 skeletally mature adolescent athletes (mean age, 17.6 years; range, 15-18 years) who underwent UCL reconstruction between 2008 and 2010. While the majority of patients were baseball players (n = 47), there were 3 gymnasts and 5 javelin throwers included in the study. Each patient underwent UCL reconstruction utilizing the docking technique after an adequate trial of nonoperative management (mean, 5.8 months). At the latest follow-up, patients were evaluated to determine their ability to return to athletic activity. Clinical outcomes were classified using the Conway scale, the Andrews-Timmerman score, and the Kerlan-Jobe Orthopaedic Clinic (KJOC) score. Results: At a minimum 2-year follow-up, 87% (48/55) of patients had excellent results using the Conway scale. Overall, there were only 2 poor results (3.6%) that were observed in patients with concomitant osteochondritis dissecans lesions of the capitellum. There were 4 postoperative complications in 4 patients (2 gymnasts and 2 javelin throwers) who developed ulnar neuritis after UCL reconstruction. The mean Andrews-Timmerman score was 83.6 ± 7.2 (range, 30-100), and the mean KJOC score was 88.0 ± 6.0 (range, 40-100). Conclusion: The docking technique results in favorable clinical outcomes in adolescent athletes with UCL insufficiency at a minimum of 2 years postoperatively. Patients with concomitant intra-articular lesions should be cautioned preoperatively that they might experience inferior clinical outcomes. Postoperatively, adolescent gymnasts and javelin throwers may be at an increased risk for transient paresthesia of the ulnar nerve caused by increased stress on the medial elbow.
The first five years of a preventive programme for haemoglobinopathies in Northeastern Iraq
Authors: Al-Allawi Nasir AS , Jalal Sana D , Ahmed Najmaddin H , Faraj Azad H , Shalli Awaz , Hamamy Hanan 
Published: October 2013

Objective To evaluate the feasibility and effectiveness of a preventive programme for haemoglobinopathies in a single centre in Northeastern Iraq. Methods Premarital screening, genetic counselling and prenatal diagnosis (PND) were implemented over a 5 year period. Results Among a total of 108,264 screened individuals (54,132 couples), β-thalassaemia trait, δβ-thalassaemia trait, and sickle cell trait were diagnosed in 3.98%, 0.11% and 0.07%, respectively. Of 130 at risk couples (2.4/1000), 107 (82%) were available for follow up, with 105 couples (98.1%) proceeding with their marriage after counselling. In the 125 registered pregnancies in the latter couples, PND was performed in 85 (in 80 couples, uptake 76%). Selective termination was chosen in 10 of the 11 pregnancies with an affected fetus. Six affected babies were born among couples who declined PND. At the same time 30 already married couples with at least one thalassaemic child underwent PND, revealing three affected fetuses; all three pregnancies were terminated. Conclusion The programme revealed that most at risk couples diagnosed by premarital screening chose to proceed with their marriage, with 76% seeking PND followed by selective termination of an affected fetus. A 65% reduction in number of affected births was reported over the 5 year period. This regional programme could serve as a prototype for a national haemoglobinopathy prevention programme.
Uncontrolled confounding in studies of screening effectiveness: an example of colonoscopy
Authors: Eldridge Ronald C , Doubeni Chyke A , Fletcher Robert H , Zauber Ann G , Corley Douglas A , Doria-Rose V Paul , Goodman Michael 
Published: October 2013

Objective To estimate the expected magnitude of error produced by uncontrolled confounding from health behaviours in observational medical record-based studies evaluating effectiveness of screening colonoscopy. Methods We used data from the prospective National Institutes of Health American Association of Retired Persons (NIH-AARP) Diet and Health Study to assess the impact of health behaviour related factors (lifestyle, education, and use of non-steroidal anti-inflammatory drugs [NSAID]) on the association between colonoscopy and colorectal cancer (CRC) mortality. We first examined the difference between adjusted and unadjusted results within the cohort data, and then estimated a broader range of likely confounding errors based on the Breslow-Day approach that uses prevalence of confounders among persons with and without exposure, and the rate ratio reflecting the association between these confounders and the outcome of interest. As dietary factors and habits are often inter-correlated, we combined these variables (physical activity, body mass index, waist-to-hip ratio, alcohol consumption, and intakes of red meat, processed meat, fibre, milk, and calcium) into a “healthy lifestyle score” (HLS). Results The estimated error (a ratio of biased-to-true result) attributable to confounding by HLS was 0.959–0.997, indicating less than 5% departure from the true effect of colonoscopy on CRC mortality. The corresponding errors ranged from 0.970 to 0.996 for NSAID, and from 0.974 to 1.006 for education (all ≤3% difference). The results for other CRC screening tests were similar. Conclusion Health behaviour-related confounders, either alone or in combination, seem unlikely to strongly affect the association between colonoscopy and CRC mortality in observational studies of CRC screening.
Long-term consequences of open abdomen management
Authors: Frazee Richard C , Abernathy Stephen , Jupiter Daniel , Davis Matthew , Regner Justin , Isbell Travis , Smith Randall 
Published: October 2013

Background There is little data on the long-term results of the open abdomen technique regarding subsequent bowel obstruction, enterocutaneous fistula and ventral hernia rates. This study represents our follow-up of these complications. Methods A retrospective review of patients undergoing open abdomen management was performed. Patient demographics and development of subsequent ventral hernia, enteric fistula and/or bowel obstruction were evaluated. Results Seventy-three men and 47 women with a mean age of 51 underwent open abdomen management; 85 for inflammatory conditions and 35 for haemorrhagic conditions. Only 27 patients did not achieve definitive fascial closure and were left open for secondary closure or had a biologic mesh bridge; 13 patients had component separation to achieve fascial closure. With a mean follow-up of 21 months, 30 patients (25%) developed a ventral hernia, 13 patients (11%) experienced an enterocutaneous fistula and two patients developed bowel obstruction. Ventral hernias and enterocutaneous fistulae occurred in 78% and 41%, respectively, of patients not definitively closed compared with 10% and 2%, respectively, of patients closed primarily at initial management ( p < 0.05). Conclusions There is a high incidence of ventral hernia and enterocutaneous fistula when open abdomen management necessitates leaving the abdomen open or using a biologic mesh bridge. Strategies for primary fascia closure including component separation should be employed.
Clonal diversity of Acinetobacter baumannii clinical isolates revealed by a snapshot study
Authors: Wang Xiaohui , Qiao Fu , Yu Rujia , Gao Yanyu , Zong Zhiyong 
Published: October 2013

Abstract

Background

Acinetobacter baumannii is a notorious opportunistic pathogen mainly associated with hospital-acquired infections. Studies on the clonal relatedness of isolates could lay the foundation for effective infection control. A snapshot study was performed to investigate the clonal relatedness of A. baumannii clinical isolates in our local settings.

Results
Among 82 non-repetitive Acinetobacter spp. clinical isolates that were recovered during a period of four days in 13 hospitals in Sichuan, Southwest China, 67 isolates were identified as A. baumannii. Half of the 67 A. baumannii isolates were non-susceptible to carbapenems. bla
OXA-23 was the only acquired carbapenemase gene detected, present in 40 isolates including five carbapenem-susceptible ones. The isolates belonged to 62 pulsotypes determined by PFGE and 31 sequence types (ST) by multi-locus sequence typing. Forty-three isolates belonged to the globally-disseminated clonal complex 92, among which ST75, ST92 and ST208 were the most common sequence types.

Conclusions
Clinical isolates of A. baumannii were diverse in clonality in this snapshot study. However, most of the isolates belonged to the globally-distributed clonal complex CC92. ST75, ST92 and ST208 were the most common types in our region. In particular, ST208 might be an emerging lineage carrying bla
OXA-23.
Proteins of novel lactic acid bacteria from Apis mellifera mellifera: an insight into the production of known extra-cellular proteins during microbial stress
Authors: Butler Èile , Alsterfjord Magnus , Olofsson Tobias C , Karlsson Christofer , Malmström Johan , Vásquez Alejandra 
Published: October 2013

Abstract

Background
Lactic acid bacteria (LAB) has been considered a beneficial bacterial group, found as part of the microbiota of diverse hosts, including humans and various animals. However, the mechanisms of how hosts and LAB interact are still poorly understood. Previous work demonstrates that 13 species of Lactobacillus and Bifidobacterium from the honey crop in bees function symbiotically with the honeybee. They protect each other, their hosts, and the surrounding environment against severe bee pathogens, bacteria, and yeasts. Therefore, we hypothesized that these LAB under stress, i.e. in their natural niche in the honey crop, are likely to produce bioactive substances with antimicrobial activity.

Results
The genomic analysis of the LAB demonstrated varying genome sizes ranging from 1.5 to 2.2 mega-base pairs (Mbps) which points out a clear difference within the protein gene content, as well as specialized functions in the honeybee microbiota and their adaptation to their host. We demonstrate a clear variation between the secreted proteins of the symbiotic LAB when subjected to microbial stressors. We have identified that 10 of the 13 LAB produced extra-cellular proteins of known or unknown function in which some are arranged in interesting putative operons that may be involved in antimicrobial action, host interaction, or biofilm formation. The most common known extra-cellular proteins secreted were enzymes, DNA chaperones, S-layer proteins, bacteriocins, and lysozymes. A new bacteriocin may have been identified in one of the LAB symbionts while many proteins with unknown functions were produced which must be investigated further.

Conclusions
The 13 LAB symbionts likely play different roles in their natural environment defending their niche and their host and participating in the honeybee’s food production. These roles are partly played through producing extracellular proteins on exposure to microbial stressors widely found in natural occurring flowers. Many of these secreted proteins may have a putative antimicrobial function. In the future, understanding these processes in this complicated environment may lead to novel applications of honey crop LAB proteins.
The study of the Oxytropis kansuensis-induced apoptotic pathway in the cerebrum of SD rats
Authors: Lu Hao , Zhang Liang , Wang Shan-shan , Wang Wen-long , Zhao Bao-yu 
Published: October 2013

Abstract

Background
Locoweeds cause significant livestock poisoning and economic loss all over the world. Animals can develop locoism, a chronic neurological disease, after grazing on locoweeds. Oxytropis kansuensis is a variety of locoweed that contains swainsonine as its main toxic ingredient. The purpose of this study was to investigate the apoptotic pathway induced in the cerebrum by swainsonine.

Results
Twenty-four Sprague-Dawley rats were randomly divided into four groups (experimental groups I, II, III and a control group) and 6 SD rats of each group were feed in 3 cages separately. Rats were penned as groups and fed with feeds containing 15% (SW content 0.03‰), 30% (SW content 0.06‰), or 45% (SW content 0.09‰) O. kansuensis for experimental groups I, II, and III, respectively, or complete feed in the case of the control group. One hundred and nineteen days after poisoning, and all rats showed neurological disorders at different degrees, which were considered to be successful established a chronic poisoning model of O. kansuensis. rats were sacrificed and the expression of Fas, FasL, Bcl-2, Bax as well as cleaved caspase-3, -8 and -9 proteins in brain tissues were detected by Western blot. The results showed that SW treatment up-regulated Fas and Fas ligand (FasL) (P < 0.05), and that there was an increase in Bax and a decrease in Bcl-2 protein (P < 0.01). Moreover, SW treatment significantly increases the activation of caspase-3, 8 and -9, the key effectors in apoptosis pathway (P < 0.01).

Conclusion
Our data suggest that SW induces apoptosis in cells of the brain through death receptor and mitochondria-mediated, caspase-dependent apoptotic pathways in the brain tissue of SD rats.
Gleaning evolutionary insights from the genome sequence of a probiotic yeast Saccharomyces boulardii
Authors: Khatri Indu , Akhtar Akil , Kaur Kamaldeep , Tomar Rajul , Prasad Gandham Satyanarayana , Ramya Thirumalai Nallan Chakravarthy , Subramanian Srikrishna 
Published: October 2013

Abstract

Background
The yeast Saccharomyces boulardii is used worldwide as a probiotic to alleviate the effects of several gastrointestinal diseases and control antibiotics-associated diarrhea. While many studies report the probiotic effects of S. boulardii, no genome information for this yeast is currently available in the public domain.

Results
We report the 11.4 Mbp draft genome of this probiotic yeast. The draft genome was obtained by assembling Roche 454 FLX + shotgun data into 194 contigs with an N50 of 251 Kbp. We compare our draft genome with all other Saccharomyces cerevisiae genomes.

Conclusions
Our analysis confirms the close similarity of S. boulardii to S. cerevisiae strains and provides a framework to understand the probiotic effects of this yeast, which exhibits unique physiological and metabolic properties.
PointBreak: A Randomized Phase III Study of Pemetrexed Plus Carboplatin and Bevacizumab Followed by Maintenance Pemetrexed and Bevacizumab Versus Paclitaxel Plus Carboplatin and Bevacizumab Followed by Maintenance Bevacizumab in Patients With Stage IIIB or IV Nonsquamous Non–Small-Cell Lung Cancer
Authors: Patel Jyoti D. , Socinski Mark A. , Garon Edward B. , Reynolds Craig H. , Spigel David R. , Olsen Mark R. , Hermann Robert C. , Jotte Robert M. , Beck Thaddeus , Richards Donald A. , Guba Susan C. , Liu Jingyi , Frimodt-Moller Bente , John William J. , Obasaju Coleman K. , Pennella Eduardo J. , Bonomi Philip , Govindan Ramaswamy 
Published: October 2013

Purpose PointBreak (A Study of Pemetrexed, Carboplatin and Bevacizumab in Patients With Nonsquamous Non-Small Cell Lung Cancer) compared the efficacy and safety of pemetrexed (Pem) plus carboplatin (C) plus bevacizumab (Bev) followed by pemetrexed plus bevacizumab (PemCBev) with paclitaxel (Pac) plus carboplatin (C) plus bevacizumab (Bev) followed by bevacizumab (PacCBev) in patients with advanced nonsquamous non–small-cell lung cancer (NSCLC). Patients and Methods Patients with previously untreated stage IIIB or IV nonsquamous NSCLC and Eastern Cooperative Oncology Group performance status of 0 to 1 were randomly assigned to receive pemetrexed 500 mg/m2 or paclitaxel 200 mg/m2 combined with carboplatin area under the curve 6 and bevacizumab 15 mg/kg every 3 weeks for up to four cycles. Eligible patients received maintenance until disease progression: pemetrexed plus bevacizumab (for the PemCBev group) or bevacizumab (for the PacCBev group). The primary end point of this superiority study was overall survival (OS). Results Patients were randomly assigned to PemCBev (n = 472) or PacCBev (n = 467). For PemCBev versus PacCBev, OS hazard ratio (HR) was 1.00 (median OS, 12.6 v 13.4 months; P = .949); progression-free survival (PFS) HR was 0.83 (median PFS, 6.0 v 5.6 months; P = .012); overall response rate was 34.1% versus 33.0%; and disease control rate was 65.9% versus 69.8%. Significantly more study drug–related grade 3 or 4 anemia (14.5% v 2.7%), thrombocytopenia (23.3% v 5.6%), and fatigue (10.9% v 5.0%) occurred with PemCBev; significantly more grade 3 or 4 neutropenia (40.6% v 25.8%), febrile neutropenia (4.1% v 1.4%), sensory neuropathy (4.1% v 0%), and alopecia (grade 1 or 2; 36.8% v 6.6%) occurred with PacCBev. Conclusion OS did not improve with the PemCBev regimen compared with the PacCBev regimen, although PFS was significantly improved with PemCBev. Toxicity profiles differed; both regimens demonstrated tolerability.