bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Non-SUMOylated Tax Protein Is Still Functional for NF-κB Pathway Activation
Authors: Pène Sabrina , Waast Laetitia , Bonnet Amandine , Bénit Laurence , Pique Claudine 
Published: July 2014

ABSTRACT
Whether NF-κB promoter transactivation by the human T-cell leukemia virus type 1 (HTLV-1) Tax protein requires Tax SUMOylation is still a matter of debate. In this study, we revisited the role of Tax SUMOylation using a strategy based on the targeting of Ubc9, the unique E2 SUMO-conjugating enzyme. We show that either a catalytically inactive form of Ubc9 (Ubc9-C93S) or Ubc9 small interfering RNA (siRNA) dramatically reduces Tax conjugation to endogenous SUMO-1 or SUMO-2/3, demonstrating that as expected, Tax SUMOylation is under the control of the catalytic activity of Ubc9. We further report that a non-SUMOylated Tax protein produced in 293T cells is still able to activate either a transfected or an integrated NF-κB reporter promoter and to induce expression of an NF-κB-regulated endogenous gene. Importantly, blocking Ubc9 activity in T cells also results in the production of a non-SUMOylated Tax that is still fully functional for the activation of a NF-κB promoter. These results provide the definitive evidence that Tax SUMOylation is not required for NF-κB-driven gene induction.

IMPORTANCE
Human T-cell leukemia virus type 1 is able to transform CD4
+
T lymphocytes. The viral oncoprotein Tax plays a key role in this process by promoting cell proliferation and survival, mainly through permanent activation of the NF-κB pathway. Elucidating the molecular mechanisms involved in NF-κB pathway activation by Tax is therefore a key issue to understand HTLV-1-mediated transformation. Tax SUMOylation was initially proposed to be critical for Tax-induced NF-κB promoter activation, which was challenged by our later observation that a low-level-SUMOylated Tax mutant was still functional for activation of NF-κB promoters. To clarify the role of Tax SUMOylation, we set up a new approach based on the inhibition of the SUMOylation machinery in Tax-expressing cells. We show that blocking the SUMO-conjugating enzyme Ubc9 abolishes Tax SUMOylation and that a non-SUMOylated Tax still activates NF-κB promoters in either adherent cells or T cells.
A Feasibility Study to Examine the Role of Acupuncture to Reduce Symptoms of Lymphoedema after Breast Cancer: A Randomised Controlled Trial
Authors: Smith Caroline A , Pirotta Marie , Kilbreath Sharon 
Published: July 2014

Objective To determine the feasibility, acceptability and safety of using acupuncture to treat arm lymphoedema in women following treatment for breast cancer. Methods We conducted a randomised controlled trial of acupuncture compared with treatment as usual. Twenty women with stable unilateral intransient lymphoedema present for at least 6 months were recruited from Sydney, Australia. The women received 12 acupuncture treatments administered to body and arm points on the non-lymphoedematous limb over 8 weeks, twice weekly for 4 weeks then once weekly for 4 weeks. Outcome measures included an assessment of interest to participate in the trial, identification of successful recruitment strategies, the appropriateness of eligibility criteria and compliance with treatment attendance. Clinical outcomes were assessed at baseline and 8 weeks and included extracellular fluid, lymphoedema symptoms, well-being and safety. Results Acupuncture was an acceptable intervention in women with upper limb lymphoedema. Compliance with the treatment protocol was high, with nine women completing all 12 treatments. Outcome forms were completed by 17 women at 8 weeks. No major adverse occurrences, as defined by the study protocol, were reported from the acupuncture group although one woman found the needling uncomfortable, and no study participant experienced an increase in swelling of >10%. There was no change in extracellular fluid or any patient-reported outcome measurement. Conclusions Lymphoedema is a persistent symptom experienced by women recovering from breast cancer. Our study suggests that acupuncture may stabilise symptoms and no major safety concerns were identified, so further research is needed. Trial Registration Number Australian New Zealand Clinical Trials Registry, http://www.anzctr.org.au ACTRN12612000607875.
Understanding how self-management interventions work for disadvantaged populations living with chronic conditions: protocol for a realist synthesis
Authors: Mills Susan L , Pumarino Javiera , Clark Nancy , Carroll Simon , Dennis Sarah , Koehn Sharon , Yu Tricia , Davis Connie , Fong Maylene 
Published: July 2014

IntroductionSelf-management programmes are complex interventions aimed at improving the way individuals self-manage chronic conditions, but there are questions about the overall impact of these programmes on disadvantaged populations, in terms of their capacity to engage with and receive the benefits from these initiatives. Given the increased resources being directed towards self-management initiatives, clinicians and policy makers need knowledge on how self-management interventions work for these populations. Most systematic reviews of self-management interventions do not consider the complex interactions between implementation contexts, intervention strategies, and mechanisms that influence how self-management interventions work in real life for disadvantaged groups.MethodsTo address the need for better understanding of these mechanisms and to create context-relevant knowledge, we are conducting a realist synthesis of evidence on self-management interventions for disadvantaged populations living with chronic conditions. The primary research question is: What are the key mechanisms operating in chronic condition self-management interventions among disadvantaged populations? In this protocol, we outline the steps we will take to identify the programme theory for self-management interventions and candidate middle-range theories; to search for evidence in academic and grey literature; to appraise and extract the collected evidence; to synthesise and interpret the findings to generate key context-mechanism-outcome configurations and to disseminate results to relevant stakeholder and to peer-review publications.DisseminationUnderstandings of how chronic conditions self-management interventions work among disadvantaged populations is essential knowledge for clinicians and other decision makers who need to know which programmes they should implement for which groups. Results will also benefit medical researchers who want to direct effort towards current gaps in knowledge in order to advance the self-management field. In addition, the study will make a contribution to the evolving body of knowledge on the realist synthesis method and, in particular, to its application to behaviour change interventions for disadvantaged populations.
Alfaxalone as an induction agent for anaesthesia in terrapins and tortoises
Authors: Knotek Z. 
Published: July 2014

The aim of this study was to evaluate short‐term intravenous anaesthesia with alfaxalone in chelonians. In the first part of the study, alfaxalone at a dose rate of 5 mg/kg was administered intravenously to 10 adult female red‐eared terrapins (Trachemys scripta elegans) following 24 hours of fasting. The induction time, tracheal tube insertion time, surgical plane of anaesthesia interval, and full recovery time were recorded. The head, neck and leg withdrawal reflex was lost within 21.09±8.07 seconds. The mean tracheal tube insertion time, the time of surgical plane of anaesthesia and full recovery time were 27.50±12.96 seconds, 26.40±4.72 minutes and 33.70±4.76 minutes, respectively. In the second part of the study, 50 chelonians (20 red‐eared terrapins, 10 Hermann's tortoises, eight spur‐thighed tortoises, six marginated tortoises and six Russian tortoises) were treated intravenously with 5 mg/kg alfaxalone after administration of 1 mg/kg meloxicam and 2 mg/kg butorphanol intramuscularly. The head, neck and leg withdrawal reflex was lost within 21.52±6.57 seconds, the endotracheal tube could be inserted within 25.76±8.24 seconds, and the time to deep pain sensation loss was 29.46±9.67 seconds. Intravenous use of alfaxalone proved to be a suitable method of induction for inhalation anaesthesia in terrapins and tortoises.
Effect of oxygen vacancy on the improved photocatalytic activity of Cr-doped TiO2
Authors: Khan Matiullah , Li Jing , Cao Wenbin , Mansoor Bilal , Rehman Fida 
Published: July 2014

We employed ab initio calculations to study the effect of various defects on the structural, electronic and optical properties of anatase TiO 2. Single Cr doping at Ti sites introduced isolated Cr 3d states in the band gap of TiO 2. Charge compensated Cr doped model was introduced by simultaneously doping two Cr atoms at Ti sites along with one oxygen vacancy ( Ti 14 O 31 Cr 2). It has been found that Ti 14 O 31 Cr 2 can narrow the band gap significantly and passivate gap states. Removal of the isolated Cr 3d states from the band gap and improved visible light absorption would effectively enhance the photocatalytic activity of Cr doped TiO 2. Our calculations provide reasonable explanation for the previously reported experimental findings.
Combined hormonal contraception and risk of venous thromboembolism within the first year following pregnancy
Authors: Bergholt Thomas , Nielsen Anne Kristine , Paidas Michael J. , Løkkegaard Ellen Christine L. , Petersen Jesper Friis 
Published: July 2014

SummaryEstimating the risk of venous thromboembolism (VTE) associated with combined hormonal contraceptives following early terminated pregnancies or birth, a Danish nationwide retrospective cohort observing a one-year follow-up was defined using three unique registries. All Danish women with confirmed pregnancies aged 15–49 during the period of 1995–2009 were included. The main outcomes were relative and absolute risks of first time venous thromboembolism in users as well as non-users of combined hormonal contraceptives. In 985,569 person-years, 598 venous thromboembolisms were recorded. After early terminated pregnancies and births, respectively, 113 and 485 events occurred in 212,552 and 773,017 person-years. After early terminated pregnancies, the crude VTE incidence ratios were similar, and the numbers needed to harm were equal between groups that did or did not use combined hormonal contraceptives throughout the follow-up year. After childbirth, individuals that used combined hormonal contraceptives were more likely than non-users to experience VTE depicted by crude incidence ratios; however, the difference was only significant after 14 weeks. This implied that the numbers needed to harm were lower for those that used compared to those that did not use combined oral contraceptives in the initial 14 weeks postpartum. In conclusion, the use of combined hormonal contraceptives after early terminated pregnancies was not detrimental, but during the puerperal period, they should be used with caution.
L-selectin deficiency decreases aortic B1a and Breg subsets and promotes atherosclerosis
Authors: Gjurich Breanne , Taghavie-Moghadam Parésa , Ley Klaus , Galkina Elena 
Published: July 2014

SummaryThere is a significant recruitment of leucocytes into aortas during atherogenesis. L-selectin regulates leucocyte migration into secondary lymphoid and peripheral tissues and was proposed to play a role in leucocyte homing into aortas. Here, we determine the role of L-selectin in atherosclerosis. L-selectin-deficient Apoe -/- (Sell -/- Apoe -/-) mice had a 74% increase in plaque burden compared to Apoe -/- mice fed a chow diet for 50 weeks. Elevated atherosclerosis was accompanied by increased aortic leucocyte content, but a 50% reduction in aortic B cells despite elevated B cell counts in the blood. Follicular B cells represented 65%, whereas B1a and regulatory B cells (Breg) comprised 5% of aortic B cells. B1a and Breg cell subsets were reduced in Sell -/- Apoe -/- aortas with accompanied two-fold decrease in aortic T15 antibody and 1.2-fold decrease of interleukin-10 (IL-10) levels. L-selectin was required for B1 cell homing to the atherosclerotic aorta, as demonstrated by a 1.5-fold decrease in the migration of Sell -/- Apoe -/- vs Apoe -/- cells. Notably, we found a 1.6-fold increase in CD68hi macrophages in Sell -/- Apoe -/- compared to Apoe -/- aortas, despite comparable blood monocyte numbers and L-selectin-dependent aortic homing. L-selectin had no effect on neutrophil migration into aorta, but led to elevated blood neutrophil numbers, suggesting a potential involvement of neutrophils in atherogenesis of Sell -/- Apoe -/- mice. Thus, L-selectin deficiency increases peripheral blood neutrophil and lymphocyte numbers, decreases aortic B1a and Breg populations, T15 antibody and IL-10 levels, and increases aortic macrophage content of Sell -/- Apoe -/- mice. Altogether, these data provide evidence for an overall atheroprotective role of L-selectin.
Effects of thrombopoietin receptor agonists on procoagulant state in patients with immune thrombocytopenia
Authors: Álvarez Román María Teresa , Bello Ihosvany Fernández , Arias-Salgado Elena G. , Pollmar María Isabel Rivas , Yuste Víctor Jiménez , Salces Mónica Martín , Butta Nora V. 
Published: July 2014

SummaryThrombopoietin receptor agonists (TPO-RA) have recently been introduced for the treatment of immune thrombocytopenia (ITP), an antiplatelet-antibodies autoimmune disease. The observation of a low frequency of bleeding episodes despite their thrombocytopenia suggests the existence of a compensatory mechanism. This study aimed to evaluate the effect of TPO-RA treatment on platelet function and on the procoagulant state in ITP patients before (ITP-bR) and after responding (ITP-aR) to treatment. Plasma- and microparticle (MP)-associated procoagulant capacity from ITP patients was similar before and after responding to the TPO-RA regimen but higher than the healthy control values. High MP-associated procoagulant activity did not seem to be due to increased platelet activation, since platelet stimulation by agonists was reduced in ITP-bR and ITP-aR patients. It could be related to increased platelet apoptosis, evaluated in terms of surface phosphatidylserine (PS), observed in both ITP groups. In summary, TPO-RA treatment increased platelet count but did not ameliorate their function and did not change plasma- and MP-associated procoagulant state of ITP patient responders to this therapy.
Thrombin-induced platelet activation via PAR4: pivotal role for exosite II
Authors: Boknäs Niklas , Faxälv Lars , Centellas Daniel Sanchez , Wallstedt Maria , Ramström Sofia , Grenegård Magnus , Lindahl Tomas 
Published: July 2014

SummaryThrombin-induced platelet activation via PAR1 and PAR4 is an important event in haemostasis. Although the underlying mechanisms responsible for ensuring efficient PAR1 activation by thrombin have been extensively studied, the potential involvement of recognitions sites outside the active site of the protease in thrombin-induced PAR4 activation is largely unknown. In this study, we developed a new assay to assess the importance of exosite I and II for PAR4 activation with α- and γ-thrombin. Surprisingly, we found that exosite II is critical for activation of PAR4. We also show that this dependency on exosite II likely represents a new mechanism, as it is unaffected by blockage of the previously known interaction between thrombin and glycoprotein Ibα.
Dark Chocolate Acutely Improves Walking Autonomy in Patients With Peripheral Artery Disease
Authors: Loffredo Lorenzo , Perri Ludovica , Catasca Elisa , Pignatelli Pasquale , Brancorsini Monica , Nocella Cristina , De Falco Elena , Bartimoccia Simona , Frati Giacomo , Carnevale Roberto , Violi Francesco 
Published: July 2014

Background

NOX
‐2, the catalytic subunit of
NADPH
oxidase, has a key role in the formation of reactive oxidant species and is implicated in impairing flow‐mediated dilation (
FMD
). Dark chocolate exerts artery dilatation via down‐regulating
NOX
2‐mediated oxidative stress. The aim of this study was to investigate whether dark chocolate improves walking autonomy in peripheral artery disease (
PAD
) patients via an oxidative stress‐mediated mechanism.

Methods and Results

FMD
, serum levels of isoprostanes, nitrite/nitrate (NOx) and
sNOX
2‐dp, a marker of blood
NOX
2 activity, maximal walking distance (
MWD
) and maximal walking time (
MWT
) were studied in 20
PAD
patients (14 males and 6 females, mean age: 69±9 years) randomly allocated to 40 g of dark chocolate (>85% cocoa) or 40 g of milk chocolate (≤35% cocoa) in a single blind, cross‐over design. The above variables were assessed at baseline and 2 hours after chocolate ingestion. Dark chocolate intake significantly increased
MWD
(+11%;
P
<0.001),
MWT
(+15%;
P
<0.001), serum NOx (+57%;
P
<0.001) and decreased serum isoprostanes (−23%;
P
=0.01) and
sNOX
2‐dp (−37%;
P
<0.001); no changes of the above variables were observed after milk chocolate intake. Serum epicatechin and its methylated metabolite significantly increased only after dark chocolate ingestion. Multiple linear regression analysis showed that Δ of
MWD
was independently associated with Δ of
MWT
(
P
<0.001) and Δ of NOx (
P
=0.018). In vitro study demonstrated that
HUVEC
incubated with a mixture of polyphenols significantly increased nitric oxide (
P
<0.001) and decreased E‐selectin (
P
<0.001) and
VCAM
1 (
P
<0.001).

Conclusion

In
PAD
patients dark but not milk chocolate acutely improves walking autonomy with a mechanism possibly related to an oxidative stress‐mediated mechanism involving
NOX
2 regulation.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
01947712.
Rotational and Translational Stability of Different Methods for Direct Acromioclavicular Ligament Repair in Anatomic Acromioclavicular Joint Reconstruction
Authors: Beitzel Knut , Obopilwe Elifho , Apostolakos John , Cote Mark P. , Russell Ryan P. , Charette Ryan , Singh Hardeep , Arciero Robert A. , Imhoff Andreas B. , Mazzocca Augustus D. 
Published: July 2014

Background: Many reconstructions of acromioclavicular (AC) joint dislocations have focused on the coracoclavicular (CC) ligaments and neglected the functional contribution of the AC ligaments and the deltotrapezial fascia. Purpose: To compare the modifications of previously published methods for direct AC reconstruction in addition to a CC reconstruction. The hypothesis was that there would be significant differences within the variations of surgical reconstructions. Study Design: Controlled laboratory study. Methods: A total of 24 cadaveric shoulders were tested with a servohydraulic testing system. Two digitizing cameras evaluated the 3-dimensional movement. All reconstructions were based on a CC reconstruction using 2 clavicle tunnels and a tendon graft. The following techniques were used to reconstruct the AC ligaments: a graft was shuttled underneath the AC joint back from anterior and again sutured to the acromial side of the joint (group 1), a graft was fixed intramedullary in the acromion and distal clavicle (group 2), a graft was passed over the acromion and into an acromial tunnel (group 3), and a FiberTape was fixed in a cruciate configuration (group 4). Anterior, posterior, and superior translation, as well as anterior and posterior rotation, were tested. Results: Group 1 showed significantly less posterior translation compared with the 3 other groups ( P < .05) but did not show significant differences compared with the native joint. Groups 3 and 4 demonstrated significantly more posterior translation than the native joint. Group 1 showed significantly less anterior translation compared with groups 2 and 3. Group 3 demonstrated significantly more anterior translation than the native joint. Group 1 demonstrated significantly less superior translation compared with the other groups and with the native joint. The AC joint of group 1 was pulled apart less compared with all other reconstructions. Only group 1 reproduced the native joint for the anterior rotation at the posterior marker. Group 4 showed significantly increased distances for all 3 measure points when the clavicle was rotated posteriorly. Conclusion: Reconstruction of the AC ligament by direct wrapping and suturing of the remaining graft around the AC joint (group 1) was the most stable method and was the only one to show anterior rotation comparable with the native joint. In contrast, the transacromial technique (group 3) showed the most translation and rotation. Clinical Relevance: An anatomic repair should address both the CC ligaments and the AC ligaments to control the optimal physiologic function (translation and rotation).
Barriers and Strategies to an Iterative Model of Advance Care Planning Communication
Authors: Ahluwalia Sangeeta C. , Bekelman David B. , Huynh Alexis K. , Prendergast Thomas J. , Shreve Scott , Lorenz Karl A. 
Published: July 2014

Background: Early and repeated patient–provider conversations about advance care planning (ACP) are now widely recommended. We sought to characterize barriers and strategies for realizing an iterative model of ACP patient–provider communication. Methods: A total of 2 multidisciplinary focus groups and 3 semistructured interviews with 20 providers at a large Veterans Affairs medical center. Thematic analysis was employed to identify salient themes. Results: Barriers included variation among providers in approaches to ACP, lack of useful information about patient values to guide decision making, and ineffective communication between providers across settings. Strategies included eliciting patient values rather than specific treatment choices and an increased role for primary care in the ACP process. Conclusions: Greater attention to connecting providers across the continuum, maximizing the potential of the electronic health record, and linking patient experiences to their values may help to connect ACP communication across the continuum.
Avoidable hospitalizations in Switzerland: a small area analysis on regional variation, density of physicians, hospital supply and rurality
Authors: Berlin Claudia , Busato André , Rosemann Thomas , Djalali Sima , Maessen Maud 
Published: July 2014

Abstract

Background
Avoidable hospitalizations (AH) are hospital admissions for diseases and conditions that could have been prevented by appropriate ambulatory care. We examine regional variation of AH in Switzerland and the factors that determine AH.

Methods
We used hospital service areas, and data from 2008–2010 hospital discharges in Switzerland to examine regional variation in AH. Age and sex standardized AH were the outcome variable, and year of admission, primary care physician density, medical specialist density, rurality, hospital bed density and type of hospital reimbursement system were explanatory variables in our multilevel poisson regression.

Results
Regional differences in AH were as high as 12-fold. Poisson regression showed significant increase of all AH over time. There was a significantly lower rate of all AH in areas with more primary care physicians. Rates increased in areas with more specialists. Rates of all AH also increased where the proportion of residences in rural communities increased. Regional hospital capacity and type of hospital reimbursement did not have significant associations. Inconsistent patterns of significant determinants were found for disease specific analyses.

Conclusion
The identification of regions with high and low AH rates is a starting point for future studies on unwarranted medical procedures, and may help to reduce their incidence. AH have complex multifactorial origins and this study demonstrates that rurality and physician density are relevant determinants. The results are helpful to improve the performance of the outpatient sector with emphasis on local context. Rural and urban differences in health care delivery remain a cause of concern in Switzerland.