bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retrospective Analysis of Mini-Open Repair Versus Open Repair for Acute Achilles Tendon Ruptures
Authors: Klein Erin E. , Weil Lowell , Baker Jeffrey R. , Weil Lowell Scott , Sung Wenjay , Knight Jessica 
Published: October 2012

Purpose: Debate exists over optimal treatment for acute Achilles tendon ruptures. Recent literature suggests the mini-open technique may provide the reliability of the open repair with the decreased complication rate of non-operative treatment. This retrospective review compares acute tendon ruptures treated with one of two techniques: open repair (TO) or mini-open repair (MOA). Methods & Results: Records were reviewed and 34 patients were found to meet the inclusion criteria for open or mini-open repair of an acute Achilles tendon rupture with follow up of at least 12 months. TO (n=16) and MOA (n=18) had no statistically significant differences in age at time of injury [TO: 41 + 2.5 years (range 20 – 68); MOA: 46 + 2.5 years (range 33 – 73)] or time between injury and surgical repair [TO: 15 + 2 days (range 2 – 30); MOA: 15 + 2 days (range 2 – 30)]. Post-operative VISA-A scores were 82 + 10 (range 42 – 98) and 92 + 5 (range 66 – 100) for TO and MOA, respectively. Significant differences were found in the time between surgical intervention and beginning of rehabilitation [TO: Post op day 37 + 5 (range 21 – 46); MOA: Post op day 19 + 2 (range 7 – 32)] and the time between surgical intervention and full return to activity [TO: Post op month 7 + 1 (range 4 – 11); MOA: Post op month 5 + 0.6 (range 4 – 11)]. Conclusion: These results suggest that the mini-open repair provides acceptable surgical outcomes while optimizing patient function after Achilles tendon repair. Level of Evidence: Therapeutic, Level III: Retrospective Comparative
Criterion-Related Validity of the Foot Health Status Questionnaire Regarding Strength and Plantar Pressure Measurements in Elderly People
Authors: Cuesta-Vargas Antonio I. , Galan-Mercant Alejandro , Martín-Borras Maria Carmen , González-Sánchez Manuel 
Published: October 2012

Background. Criterion-related validity of a self-administered questionnaire listed as gold standard requires objective testing. The aim of this study was to analyze the Foot Health Status Questionnaire (FHSQ) using functional variable measures (dynamic plantar pressure and foot strength). Materials and methods. A total of 22 elderly healthy participants (13 women and 9 men) were screened by interview and physical examination for foot or gait abnormalities. Foot strength, footprint pressure, and foot health status were measured. Results. All the items of the FHSQ show significant correlation with functional variables, but general foot health shows the highest correlation with the 4 physical variables related to plantar pressure (R2 = 0.741), followed by foot pain (R2 = 0.652). Conclusion. A set of different, directly measured physical variables related to foot strength and plantar pressure significantly correlate with the FHSQ dimensions. Level of Evidence: Cross-sectional trial
Return to Play in Athletes Following Ankle Injuries
Authors: Clanton Thomas O. , Matheny Lauren M. , Jarvis Hannah C. , Jeronimus Anastasia B. 
Published: October 2012

Background: The decision to return to play following an ankle injury is a multifactorial process involving both physical and psychological parameters. The current body of literature lacks evidence-based guidelines to assist in the decision. Objective: This article reviews the evidence to support such testing: the dorsiflexion lunge test, star excursion balance test, agility T-test, and sargent/vertical jump test. The importance of psychological factors is also highlighted. Evidence Acquisition: The primary literature search was conducted using PubMed ( http://www.ncbi.nlm.nih.gov/pubmed/ ) with the search terms “ankle AND injury” and the following limits activated: English language. A secondary search was then conducted with the search terms “return to play” and “sport injuries and return to play.” Results: Various functional tests have been used to determine whether a patient is able to return to play following an ankle injury. This study documented four tests that have been used to assess range of motion, balance and proprioception, agility and strength and the reasoning as to why these tests are used. Conclusions: Functional testing provides objective measures for gauging an athlete’s progression through the rehabilitation process. Testing balance and proprioception, strength, range of motion, and agility coupled with psychological assessment evaluates readiness for return to play.
Subcapsular sinus macrophages promote NK cell accumulation and activation in response to lymph-borne viral particles
Authors: Garcia Zacarias , Lemaître Fabrice , van Rooijen Nico , Albert Matthew L. , Levy Yves , Schwartz Olivier , Bousso Philippe 
Published: October 2012

AbstractNatural killer (NK) cells become activated during viral infection in response to cytokines or to engagement of NK cell activating receptors. However, the identity of cells sensing viral particles and mediating NK cell activation has not been defined. Here, we show that local administration of a modified vaccinia virus Ankara vaccine in mice results in the accumulation of NK cells in the subcapsular area of the draining lymph node and their activation, a process that is strictly dependent on type I IFN signaling. NK cells located in the subcapsular area exhibited reduced motility and were found associated with CD169+-positive subcapsular sinus (SCS) macrophages and collagen fibers. Moreover, depletion of SCS macrophages using clodronate liposomes abolished NK cell accumulation and activation. Our results identify SCS macrophages as primary mediators of NK cell activation in response to lymph-borne viral particles suggesting that they act as early sensors of local infection or delivery of viral-based vaccines.
Inhibitory effect of HIV-specific neutralizing IgA on mucosal transmission of HIV in humanized mice
Authors: Hur Eun Mi , Patel Sonal N. , Shimizu Saki , Rao Dinesh S. , Gnanapragasam Priyanthi N. P. , An Dong Sung , Yang Lili , Baltimore David 
Published: October 2012

Abstract
HIV-1 infections are generally initiated at mucosal sites. Thus, IgA antibody, which plays pivotal roles in mucosal immunity, might efficiently prevent HIV infection. However, mounting a highly effective HIV-specific mucosal IgA response by conventional immunization has been challenging and the potency of HIV-specific IgA against infection needs to be addressed in vivo. Here we show that the polymeric IgA form of anti-HIV antibody inhibits HIV mucosal transmission more effectively than the monomeric IgA or IgG1 form in a comparable range of concentrations in humanized mice. To deliver anti-HIV IgA in a continual manner, we devised a hematopoietic stem/progenitor cell (HSPC)–based genetic approach using an IgA gene. We transplanted human HSPCs transduced with a lentiviral construct encoding a class-switched anti-HIV IgA (b12-IgA) into the humanized bone marrow-liver-thymus (BLT) mice. The transgene was expressed specifically in B cells and plasma cells in lymphoid organs and mucosal sites. After vaginal HIV-1 challenge, mucosal CD4+ T cells in the b12-IgA–producing mice were protected from virus-mediated depletion. Similar results were also obtained in a second humanized model, “human immune system mice.” Our study demonstrates the potential of anti-HIV IgA in immunoprophylaxis in vivo, emphasizing the importance of the mucosal IgA response in defense against HIV/AIDS.
The vitamin K–dependent anticoagulant factor, protein S, inhibits multiple VEGF-A–induced angiogenesis events in a Mer- and SHP2-dependent manner
Authors: Fraineau Sylvain , Monvoisin Arnaud , Clarhaut Jonathan , Talbot Julie , Simonneau Claire , Kanthou Chryso , Kanse Sandip M. , Philippe Michel , Benzakour Omar 
Published: October 2012

Abstract
Protein S is a vitamin K–dependent glycoprotein, which, besides its anticoagulant function, acts as an agonist for the tyrosine kinase receptors Tyro3, Axl, and Mer. The endothelium expresses Tyro3, Axl, and Mer and produces protein S. The interaction of protein S with endothelial cells and particularly its effects on angiogenesis have not yet been analyzed. Here we show that human protein S, at circulating concentrations, inhibited vascular endothelial growth factor (VEGF) receptor 2–dependent vascularization of Matrigel plugs in vivo and the capacity of endothelial cells to form capillary-like networks in vitro as well as VEGF-A–induced endothelial migration and proliferation. Furthermore, protein S inhibited VEGF-A–induced endothelial VEGFR2 phosphorylation and activation of mitogen-activated kinase-Erk1/2 and Akt. Protein S activated the tyrosine phosphatase SHP2, and the SHP2 inhibitor NSC 87877 reversed the observed inhibition of VEGF-A–induced endothelial proliferation. Using siRNA directed against Tyro3, Axl, and Mer, we demonstrate that protein S-mediated SHP2 activation and inhibition of VEGF-A–stimulated proliferation were mediated by Mer. Our report provides the first evidence for the existence of a protein S/Mer/SHP2 axis, which inhibits VEGFR2 signaling, regulates endothelial function, and points to a role for protein S as an endogenous angiogenesis inhibitor.
Shared monocyte subset phenotypes in HIV-1 infection and in uninfected subjects with acute coronary syndrome
Authors: Funderburg Nicholas T. , Zidar David A. , Shive Carey , Lioi Anthony , Mudd Joseph , Musselwhite Laura W. , Simon Daniel I. , Costa Marco A. , Rodriguez Benigno , Sieg Scott F. , Lederman Michael M. 
Published: October 2012

AbstractThe mechanisms responsible for increased cardiovascular risk associated with HIV-1 infection are incompletely defined. Using flow cytometry, in the present study, we examined activation phenotypes of monocyte subpopulations in patients with HIV-1 infection or acute coronary syndrome to find common cellular profiles. Nonclassic (CD14+CD16++) and intermediate (CD14++CD16+) monocytes are proportionally increased and express high levels of tissue factor and CD62P in HIV-1 infection. These proportions are related to viremia, T-cell activation, and plasma levels of IL-6. In vitro exposure of whole blood samples from uninfected control donors to lipopolysaccharide increased surface tissue factor expression on all monocyte subsets, but exposure to HIV-1 resulted in activation only of nonclassic monocytes. Remarkably, the profile of monocyte activation in uncontrolled HIV-1 disease mirrors that of acute coronary syndrome in uninfected persons. Therefore, drivers of immune activation and inflammation in HIV-1 disease may alter monocyte subpopulations and activation phenotype, contributing to a pro-atherothrombotic state that may drive cardiovascular risk in HIV-1 infection.
Characteristics and outcome of patients with second primary lung cancer
Authors: Reinmuth Niels , Stumpf Andreas , Stumpf Patrick , Muley Thomas , Kobinger Sonja , Hoffmann Hans , Herth Felix J.F. , Schnabel Philipp A. , Warth Arne , Bischoff Helge , Thomas Michael 
Published: October 2012

Patients with lung cancer are at risk of developing a second primary lung cancer (SPLC). However, the characteristics of patients at risk remain largely speculative.We reviewed 2816 lung cancer patients from our institution for the occurrence of SPLC. Any SPLC was categorised as synchronous when diagnosed within 2 years of the first primary lung cancer (FPLC) and after direct histological comparison of both tumours. All other SPLCs were considered as metachronous.139 patients developed a second malignancy including 69 nonsmall cell lung cancer (NSCLC) and 9 small cell lung cancer. The median interval for diagnosis of metachronous SPLC (n=59) after FPLC occurrence was 72 months. SPLC detected within 5 years of FPLC diagnosis had a more favourable stage distribution (p=0.02). After diagnosis of SPLC, patients had a superior median overall survival compared to controls (57.7versus18.1 months; p<0.0001). Interestingly, comparing only stage IV NSCLC patients, a history of FPLC was also associated with a favourable survival (median 27.4versus8.97 months; p=0.007).In summary, previous lung cancer treatment does not lead to impaired prognosis after diagnosis of SPLC. Improved surveillance programmes beyond 5 years after FPLC treatment may result in more favourable disease stages for detected SPLC.
Intrabronchial activated protein C enhances lipopolysaccharide-induced pulmonary responses
Authors: Kager Liesbeth M. , de Boer J. Daan , Bresser Paul , van der Zee Jaring S. , Zeerleder Sacha , Meijers Joost C.M. , van 't Veer Cornelis , van der Poll Tom 
Published: October 2012

Intravenous administration of activated protein C (APC) inhibits coagulation and inflammation in the lungs of humans and animals. Investigations in rodents demonstrated that direct intrapulmonary delivery of APC also exerts anticoagulant and anti-inflammatory effects. The effect of intrabronchial administration of recombinant human (rh)APC on lipopolysaccharide (LPS)-induced haemostatic and inflammatory alterations in the bronchoalveolar space of humans was studied.Eight subjects received rhAPCviaintrabronchial instillation by bronchoscope, while in a contralateral subsegment subjects received saline; all subjects were challenged bilaterally with LPS in the same lung subsegments. Four additional subjects received rhAPC (75 μg), with saline as a control in the contralateral subsegment, while they were bilaterally “challenged” with saline. After 6 h a bronchoalveolar lavage was performed and coagulation and inflammatory parameters were measured.rhAPC enhanced LPS-induced coagulation activation in the bronchoalveolar space, when compared with the control side. In addition, rhAPC amplified LPS-induced pro-inflammatory responses, as indicated by higher concentrations of cytokines and chemokines. rhAPC alone did not have procoagulant or pro-inflammatory effects.Locally administered rhAPC has unexpected procoagulant and pro-inflammatory effects in LPS-challenged lung subsegments. These data argue against a role for intrapulmonary delivery of rhAPC as a treatment strategy for lung inflammatory disorders in humans.
The use of inhaled corticosteroids and the risk of adrenal insufficiency
Authors: Lapi Francesco , Kezouh Abbas , Suissa Samy , Ernst Pierre 
Published: October 2012

Adrenal insufficiency is a potential complication of therapy with an inhaled corticosteroid (ICS). Although prior studies found the highest risk of adrenal insufficiency with fluticasone, a more potent ICS, these results might be explained by a channelling bias and concomitant exposure to oral corticosteroids.We re-examined the relationship between the use of ICSs and adrenal insufficiency by using a cohort of patients treated for respiratory conditions during 1990–2005, identified in the healthcare databases from the province of Quebec, Canada, with follow-up until 2007. A nested case–control analysis was performed within this cohort. Cases of adrenal insufficiency were matched with up to 10 controls.392 cases were identified (incidence rate 1.1 per 10 000 person-years). Although the rate of adrenal insufficiency was not significantly higher among all current users of ICSs, patients receiving the highest dosages showed a greater risk (OR 1.84, 95% CI 1.16–2.90). Consistently, an increased risk was estimated for the highest tertile of ICS dose (OR 1.90, 95% CI 1.07–3.37) cumulated in the year before the event.ICS at high doses appear to be a significant independent risk factor for adrenal insufficiency. Physicians prescribing ICS at such dosages should be sensitive to the signs and symptoms of adrenal insufficiency in their patients.
Intermittent hypoxia-activated cyclooxygenase pathway: role in atherosclerosis
Authors: Gautier-Veyret Elodie , Arnaud Claire , Bäck Magnus , Pépin Jean-Louis , Petri Marcelo H. , Baguet Jean-Philippe , Tamisier Renaud , Lévy Patrick , Stanke-Labesque Françoise 
Published: October 2012

Intermittent hypoxia, the main stimulus of obstructive sleep apnoea (OSA), induces inflammation, leading to early atherosclerosis. Whether the cyclooxygenase (COX) pathway contributes to intermittent hypoxia-induced atherosclerosis remains to be determined.We studied the effects of 8-weeks of intermittent hypoxia exposure on COX-pathway gene expression and atherosclerosis, and the influence of COX-1 inhibition by SC-560 on atherosclerosis progression in aortas of apolipoprotein E-/-mice. Urinary 11-dehydrothromboxane B2(11-dTXB2) was assessed in 50 OSA subjects free of cardiovascular risk factor matched for age and body mass index with 25 controls, and 56 OSA with cardiovascular risk factor.Intermittent hypoxia significantly increased atherosclerotic lesion sizes, mRNA levels of COX-1 and thromboxane synthase (TXBS). Lesion sizes correlated to COX-1 (r = 0.654, p = 0.0003) and TXBS (r = 0.693, p<0.0001) mRNA levels. COX-1 inhibition reduced lesion progression in intermittent hypoxia mice only (p = 0.04). Urinary 11-dTXB2was similar in OSA subjects free of cardiovascular risk factor and controls, but was increased by 13% (p = 0.007) in OSA subjects with cardiovascular risk factor compared with those without.Although OSA itself was not associated with increased urinary 11-dTXB2concentration, the COX-1 pathway was activated in intermittent hypoxia-exposed mice and in OSA subjects presenting with cardiovascular risk factor, and may contribute to intermittent hypoxia-induced atherogenesis. COX-1 inhibition could be of clinical interest in the prevention of cardiovascular morbidity in OSA.
Identification of asthma clusters in two independent Korean adult asthma cohorts
Authors: Kim Tae-Bum , Jang An-Soo , Kwon Hyouk-Soo , Park Jong-Sook , Chang Yoon-Seok , Cho Sang-Heon , Choi Byoung Whui , Park Jung-Won , Nam Dong-Ho , Yoon Ho-Joo , Cho Young-Joo , Moon Hee-Bom , Cho You Sook , Park Choon-Sik 
Published: October 2012

Asthma is a heterogeneous airway disease with various clinical phenotypes. It is crucial to clearly identify clinical phenotypes to achieve better asthma management.We used cluster analysis to classify the clinical groups of 724 asthmatic patients from the Cohort for Reality and Evolution of Adult Asthma in Korea (COREA), and in 1843 subjects from another independent Korean asthma cohort of Soonchunhyang University Asthma Genome Research Centre (SCH) (Bucheon, Republic of Korea). Hierarchical cluster analysis was performed by Ward's method, followed by κ-means cluster analysis.Cluster analysis of the COREA cohort indicated four asthma subtypes: 1) smoking asthma; 2) severe obstructive asthma; 3) early-onset atopic asthma; and 4) late-onset mild asthma. An independent cluster analysis of the SCH cohort also indicated four clusters that were similar to the COREA clusters.Our results indicate that adult Korean asthma patients can be classified into four distinct clusters.
Drug resistance beyond extensively drug-resistant tuberculosis: individual patient data meta-analysis
Authors: Migliori Giovanni Battista , Sotgiu Giovanni , Gandhi Neel R. , Falzon Dennis , DeRiemer Kathryn , Centis Rosella , Hollm-Delgado Maria-Graciela , Palmero Domingo , Pérez-Guzmán Carlos , Vargas Mario H. , D'Ambrosio Lia , Spanevello Antonio , Bauer Melissa , Chan Edward D. , Schaaf H. Simon , Keshavjee Salmaan , Holtz Timothy H. , Menzies Dick ,   The Collaborative Group for Meta-Analysis of Individual Patient Data in MDR-TB
Published: October 2012

The broadest pattern of tuberculosis (TB) drug resistance for which a consensus definition exists is extensively drug-resistant (XDR)-TB. It is not known if additional drug resistance portends worsened patient outcomes. This study compares treatment outcomes of XDR-TB patients with and without additional resistance in order to explore the need for a new definition.Individual patient data on XDR-TB outcomes were included in a meta-analysis comparing outcomes between XDR alone and three nonmutually exclusive XDR-TB patient groups: XDR plus resistance to all the second-line injectables (sli) and capreomycin and kanamycin/amikacin (XDR+2sli) XDR plus resistance to second-line injectables and to more than one group 4 drug,i.e.ethionamide/protionamide, cycloserine/terizidone or para-aminosalicylic acid (XDR+sliG4) and XDR+sliG4 plus resistance to ethambutol and/or pyrazinamide (XDR+sliG4EZ).Of 405 XDR-TB cases, 301 were XDR alone, 68 XDR+2sli, 48 XDR+sliG4 and 42 XDR+sliG4EZ. In multivariate analysis, the odds of cure were significantly lower in XDR+2sli (adjusted OR 0.4, 95% CI 0.2–0.8) compared to XDR alone, while odds of failure and death were higher in all XDR patients with additional resistance (adjusted OR 2.6–2.8).Patients with additional resistance beyond XDR-TB showed poorer outcomes. Limitations in availability, accuracy and reproducibility of current drug susceptibility testing methods preclude the adoption of a useful definition beyond the one currently used for XDR-TB.
Increased phosphorylated p38 mitogen-activated protein kinase in COPD lungs
Authors: Gaffey Kate , Reynolds Sophie , Plumb Jonathan , Kaur Manminder , Singh Dave 
Published: October 2012

The p38 mitogen-activated protein kinase (MAPK) pathway is upregulated in chronic obstructive pulmonary disease (COPD). To date, dual labelling to identify cell-type-specific presence of phosphorylated (phospho-)p38 MAPK has not been carried out.Phospho-p38 MAPK was quantified in a variety of cell types in the lung tissue of 20 COPD patients, 12 smokers and 12 nonsmokers using immunohistochemistry. Paired blood and sputum neutrophils (from seven subjects with COPD), and CD8 and epithelial cells (from three subjects with COPD) were cultured with a p38 MAPK inhibitor. Supernatant tumour necrosis factor-α and CXCL8 levels were analysed by ELISA. Sputum and blood neutrophil cytospins were analysed for phospho-p38 MAPK.Phospho-p38 MAPK was increased in bronchial epithelial cells, macrophages and CD20+ and CD8+ lymphocytes in COPD lungs. Sputum and lung tissue neutrophils were devoid of phospho-p38 in all patient groups. The p38 MAPK inhibitor SB100 attenuated pro-inflammatory mediator release in COPD lung CD8 cells and airway epithelia, but there was no effect on COPD sputum neutrophils.Our data indicate cell-specific anti-inflammatory effects of p38 MAPK inhibition in the lung.