bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein disulphide-isomerase A2 regulated intracellular tissue factor mobilisation in migrating human vascular smooth muscle cells
Authors: Peña Esther , Arderiu Gemma , Badimon Lina 
Published: January 2015

SummaryProtein-disulphide isomerase family (PDI) are an ER-stress protein that controls TF-procoagulant activity but its role in HVSMC migration and coronary artery disease remains to be elucidated. We aimed to investigate whether in human coronary smooth muscle cells (HVSMC) the ER-stress protein-disulphide isomerase family A member 2 (PDIA2) regulates tissue factor (TF) polarisation during migration and atherosclerotic remodeling. PDIA2 and TF were analysed by confocal microscopy, silenced by small interfering RNAs (siRNA) and their function analysed by transwell and migration assays in vitro and in vivo. PDIA2and TF co-localise in the front edge of motile HVSMC. Silencing PDIA2, as well as silencing TF, reduces migration. PDIA2 silenced cells show increased TF-rich microparticle shedding. In vivo cell-loaded plug implants in nude mice of PDIA2 silenced HVSMC together with microvascular endothelial cells showed a significant impairment in mature microvessel formation. PDIA2 and TF are found in remodelled atherosclerotic plaques but not in healthy coronaries. In conclusion, we demonstrate that TF is chaperoned by PDIA2 to the HVSMC membrane and to the cell migratory front. Absence of PDIA2 impairs TF intracellular trafficking to its membrane docking favoring its uncontrolled release in microparticles. TF-regulated HVSMC migration and microvessel formation is under the control of the ER-protein PDIA2.
Altered FoF1 ATP synthase and susceptibility to mitochondrial permeability transition pore during ischaemia and reperfusion in aging cardiomyocytes
Authors: Fernandez-Sanz Celia , Castellano José , Miro-Casas Elisabet , Nuñez Estefanía , Inserte Javier , Vázquez Jesús , Garcia-Dorado David , Ruiz-Meana Marisol 
Published: January 2015

SummaryAging is a major determinant of the incidence and severity of ischaemic heart disease. Preclinical information suggests the existence of intrinsic cellular alterations that contribute to ischaemic susceptibility in senescent myocardium, by mechanisms not well established. We investigated the role of altered mitochondrial function in the adverse effect of aging. Isolated perfused hearts from old mice (> 20 months) displayed increased ischaemia-reperfusion injury as compared to hearts from adult mice (6 months) despite delayed onset of ischaemic rigor contracture. In cardiomyocytes from aging hearts there was a more rapid decline of mitochondrial membrane potential (ΔΨm) as compared to young ones, but ischaemic rigor shortening was also delayed. Transient recovery of ΔΨm observed during ischaemia, secondary to the reversal of mitochondrial FoF1 ATP synthase to ATPase mode, was markedly reduced in aging cardiomyocytes. Proteomic analysis demonstrated increased oxidation of different subunits of ATP synthase. Altered bionergetics in aging cells was associated with reduced mitochondrial calcium uptake and more severe cytosolic calcium overload during ischaemia-reperfusion. Despite attenuated ROS burst and mitochondrial calcium overload, mitochondrial permeability transition pore (mPTP) opening and cell death was increased in reperfused aged cells. In vitro studies demonstrated a significantly reduced calcium retention capacity in interfibrillar mitochondria from aging hearts. Our results identify altered FoF1 ATP synthase and increased sensitivity of mitochondria to undergo mPTP opening as important determinants of the reduced tolerance to ischaemia-reperfusion in aging hearts. Because ATP synthase has been proposed to conform mPTP, it is tempting to hypothesise that oxidation of ATP synthase underlie both phenomena.
Exome Sequencing in Suspected Monogenic Dyslipidemias
Authors: Stitziel Nathan O. , Peloso Gina M. , Abifadel Marianne , Cefalu Angelo B. , Fouchier Sigrid , Motazacker M. Mahdi , Tada Hayato , Larach Daniel B. , Awan Zuhier , Haller Jorge F. , Pullinger Clive R. , Varret Mathilde , Rabès Jean-Pierre , Noto Davide , Tarugi Patrizia , Kawashiri Masa-aki , Nohara Atsushi , Yamagishi Masakazu , Risman Marjorie , Deo Rahul , Ruel Isabelle , Shendure Jay , Nickerson Deborah A. , Wilson James G. , Rich Stephen S. , Gupta Namrata , Farlow Deborah N. ,   NHLBI Grand Opportunity Exome Sequencing Project Family Studies Project Team, Neale Benjamin M. , Daly Mark J. , Kane John P. , Freeman Mason W. , Genest Jacques , Rader Daniel J. , Mabuchi Hiroshi , Kastelein John J.P. , Hovingh G. Kees , Averna Maurizio R. , Gabriel Stacey , Boileau Catherine , Kathiresan Sekar 
Published: January 2015

Background—
Exome sequencing is a promising tool for gene mapping in Mendelian disorders. We used this technique in an attempt to identify novel genes underlying monogenic dyslipidemias.

Methods and Results—

We performed exome sequencing on 213 selected family members from 41 kindreds with suspected Mendelian inheritance of extreme levels of low-density lipoprotein cholesterol (after candidate gene sequencing excluded known genetic causes for high low-density lipoprotein cholesterol families) or high-density lipoprotein cholesterol. We used standard analytic approaches to identify candidate variants and also assigned a polygenic score to each individual to account for their burden of common genetic variants known to influence lipid levels. In 9 families, we identified likely pathogenic variants in known lipid genes (
ABCA1
,
APOB
,
APOE
,
LDLR, LIPA
, and
PCSK9
); however, we were unable to identify obvious genetic etiologies in the remaining 32 families, despite follow-up analyses. We identified 3 factors that limited novel gene discovery: (1) imperfect sequencing coverage across the exome hid potentially causal variants; (2) large numbers of shared rare alleles within families obfuscated causal variant identification; and (3) individuals from 15% of families carried a significant burden of common lipid-related alleles, suggesting complex inheritance can masquerade as monogenic disease.

Conclusions—
We identified the genetic basis of disease in 9 of 41 families; however, none of these represented novel gene discoveries. Our results highlight the promise and limitations of exome sequencing as a discovery technique in suspected monogenic dyslipidemias. Considering the confounders identified may inform the design of future exome sequencing studies.
Vitamin D Depletion Aggravates Hypertension and Target‐Organ Damage
Authors: Andersen Louise Bjørkholt , Przybyl Lukasz , Haase Nadine , von Versen‐Höynck Frauke , Qadri Fatimunnisa , Jørgensen Jan Stener , Sorensen Grith Lykke , Fruekilde Palle , Poglitsch Marko , Szijarto István , Gollasch Maik , Peters Joerg , Muller Dominik N. , Christesen Henrik Thybo , Dechend Ralf 
Published: January 2015

Background
We tested the controversial hypothesis that vitamin D depletion aggravates hypertension and target‐organ damage by influencing renin.

Methods and Results

Four‐week‐old double‐transgenic rats (
dTGR
) with excess angiotensin (Ang)
II
production due to overexpression of the human renin (

hREN

) and angiotensinogen (

hAGT

) genes received vitamin D‐depleted (n=18) or standard chow (n=15) for 3 weeks. The depleted group had very low serum 25‐hydroxyvitamin D levels (mean±
SEM
; 3.8±0.29 versus 40.6±1.19 nmol/L) and had higher mean systolic
BP
at week 5 (158±3.5 versus 134.6±3.7 mm Hg,
P
<0.001), week 6 (176.6±3.3 versus 162.3±3.8 mm Hg,
P
<0.01), and week 7 (171.6±5.1 versus 155.9±4.3 mm Hg,
P
<0.05). Vitamin D depletion led to increased relative heart weights and increased serum creatinine concentrations. Furthermore, the
mRNA
s of natriuretic peptides, neutrophil gelatinase‐associated lipocalin,

hREN
,

and

rR
en

were increased by vitamin D depletion. Regulatory T cells in the spleen and in the circulation were not affected. Ang metabolites, including Ang
II
and the counter‐regulatory breakdown product Ang 1 to 7, were significantly up‐regulated in the vitamin D‐depleted groups, while
ACE
‐1 and
ACE
‐2 activities were not affected.

Conclusions

Short‐term severe vitamin D depletion aggravated hypertension and target‐organ damage in
dTGR
. Our data suggest that even short‐term severe vitamin D deficiency may directly promote hypertension and impacts on renin‐angiotensin system components that could contribute to target‐organ damage. The findings add to the evidence that vitamin D deficiency could also affect human hypertension.
The Timing of Anterior Temporal Lobe Involvement in Semantic Processing
Authors: Jackson Rebecca L. , Lambon Ralph Matthew A. , Pobric Gorana 
Published: January 2015

Abstract
Despite indications that regions within the anterior temporal lobe (ATL) might make a crucial contribution to pan-modal semantic representation, to date there have been no investigations of when during semantic processing the ATL plays a critical role. To test the timing of the ATL involvement in semantic processing, we studied the effect of double-pulse TMS on behavioral responses in semantic and difficulty-matched control tasks. Chronometric TMS was delivered over the left ATL (10 mm from the tip of the temporal pole along the middle temporal gyrus). During each trial, two pulses of TMS (40 msec apart) were delivered either at baseline (before stimulus presentation) or at one of the experimental time points 100, 250, 400, and 800 msec poststimulus onset. A significant disruption to performance was identified from 400 msec on the semantic task but not on the control assessment. Our results not only reinforce the key role of the left ATL in semantic representation but also indicate that its contribution is especially important around 400 msec poststimulus onset. Together, these facts suggest that the ATL may be one of the neural sources of the N400 ERP component.
Complications and early results after operative fixation of 68 pilon fractures of the distal tibia
Authors: Lomax Adam , Singh Anjani , Jane Madeley N , Senthil Kumar C 
Published: January 2015

Background and aims In this cohort study, we present comprehensive injury specific and surgical outcome data from one of the largest reported series of pilon fractures of the distal tibia treated in a UK tertiary referral centre. Methods and results A series of 68 closed pilon fractures were retrospectively reviewed from case notes, plain radiographs and computed tomography imaging. Patient demographics, injury and fracture patterns, methods and timing of fixation and clinical and radiological outcomes were assessed over a mean follow-up period of 7.7 months (1.5–30). Overall, deep infection occurred in 1.6% with superficial infection and wound breakdown occurring in 6.3% of cases. Rates of nonunion and malunion were 7.8%. Radiological posttraumatic arthritis was present in 26.6%, which was symptomatic and requiring orthopaedic management in 9.4%. Further surgery for all causes occurred in 26.6% of cases. Conclusion Fixation of these complex fractures in subspecialist units can achieve overall low rates of wound complications, with definitive fixation of selected fractures within 48 h of initial presentation achieving comparable results to those fixed in a delayed fashion. However, this injury continues to have a significant overall complication rate with a high chance of developing early posttraumatic arthritis and of requiring further surgery.
Weight Gain after Adenotonsillectomy
Authors: Lewis Travis L. , Johnson Romaine F. , Choi Jonathan , Mitchell Ron B. 
Published: January 2015

ObjectiveTo study the association between adenotonsillectomy (T&A) and weight gain in children.Study DesignRetrospective case‐control series.SettingTertiary academic children’s medical center.Subjects and MethodsA total of 154 children who underwent T&A at a tertiary care children’s hospital between December 2010 and March 2011 were included. They were compared with 182 children with similar demographics who were seen in primary care clinics at the same institution (control group). Height and weight were compared at 6‐month intervals over a 24‐month period. Patients were divided into normal weight, overweight, and obese. A multilevel mixed‐effects regression model was used for analysis. Significance was set at P ≤. 05.ResultsChildren who underwent T&A gained more weight than controls at every interval. At 24 months, they gained an additional 2.6 kg (confidence interval [CI], 0.9‐3.9) but were an additional 1.8 cm (CI, 0.1‐3.5) taller. There was no difference in weight gain at 6 months for obese children. At 12, 18, and 24 months, the obese group outgained the control group. At 24 months, the obese T&A group had gained an average of 14.3 kg, while the control had gained 10.1 kg, for a difference of 4.2 kg (CI, 1.3‐6.1) with no difference in height changes. There were no differences in weight or height changes for the normal‐weight and overweight groups at the conclusion of the study.ConclusionsT&A leads to a significant increase in weight in obese but not normal‐weight or overweight children. Efforts should be made to provide weight reduction counseling prior to T&A in obese children.
Testing feasibility and reliability of a set of quality indicators to evaluate the organization of palliative care across Europe: A pilot study in 25 countries
Authors: Woitha Kathrin , Hasselaar Jeroen , van Beek Karen , Ahmed Nisar , Jaspers Birgit , Hendriks Jan CM , Radbruch Lukas , Vissers Kris , Engels Yvonne 
Published: January 2015

Background: A well-organized palliative care service is a prerequisite for offering good palliative care. Reliable and feasible quality indicators are needed to monitor the quality of their organization. Aim: To test feasibility and reliability of a previously developed set of quality indicators in settings and services that provide palliative care across Europe. Methods: A total of 38 quality indicators, applicable in all types of settings, rated in a RAND Delphi process, and operationalized into 38 yes/no questions, were used. Descriptives statistics, factor and reliability analyses, analysis of variance, and chi-square analyses were used. Design: Cross-sectional online survey. Setting/participants: Questionnaires were sent to representatives of 217 palliative care settings in 25 countries. Included settings were hospices, inpatient dedicated palliative care beds, palliative care outpatient clinics, palliative care units, day care centers for palliative care, palliative care home support teams, inpatient palliative care support teams, care homes, and nursing homes. Results: All invited 25 European Association of Palliative Care countries took part. In total, 107 out of 217 participants responded (57%). The quality indicators were reduced to four coherent sub-scales, being “equipment and continuity of care,” “structured documentation of essential palliative care elements in the medical record,” “training and appraisal of personnel,” and “availability of controlled drugs.” No significant differences in quality criteria between the different types of settings and services were identified. Conclusion: The set of quality indicators appeared to measure four reliable domains that assess the organization of different palliative care settings. It can be used as a starting point for quality improvement activities.
Outcome of posterior cruciate ligament reconstruction using the single- versus double bundle technique: A meta-analysis
Authors: Zhao Jing-xin , Zhang Li-hai , Mao Zhi , Zhang Li-cheng , Zhao Zhe , Su Xiu-yun , Zhang Li-ning , Gao Yuan , Sun Yong , Tang Pei-fu 
Published: January 2015

Objective To test the hypothesis that double bundle posterior cruciate ligament (PCL) reconstruction yields better improvement in stability and functional recovery of the knee than the single bundle technique. Methods PubMed®, Embase®, the Cochrane Library, CNKI, Wanfang and CBM disc databases were searched for comparative trials of PCL reconstruction using the single- versus double bundle technique. Data were extracted and meta-analysis was performed for stability improvement and functional recovery. Results The meta-analysis included 435 patients in three randomized controlled trials (RCTs) and eight non-RCTs. Double bundle reconstruction provided significantly better 90° posterior stability than the single bundle technique (weighted mean difference 0.81, 95% confidence interval, [CI] 0.2, 1.42). Double bundle reconstruction resulted in a significantly higher likelihood of International Knee Documentation Committee (IKDC) examination grade A than the single bundle technique (odds ratio 0.41, 95% CI 0.24, 0.72). Conclusions The small amount of data available indicates that double bundle reconstruction is superior to the single bundle technique after isolated PCL injury. These findings should be interpreted with caution due to the low quality and limited sample size of the studies concerned.
Does Primary Hip Arthroscopy Result in Improved Clinical Outcomes?
Authors: Gupta Asheesh , Redmond John M. , Stake Christine E. , Dunne Kevin F. , Domb Benjamin G. 
Published: January 2015

Background: Hip arthroscopy has gained increasing popularity over the past decade. The need to develop metrics to evaluate success and complications in primary hip arthroscopy is an important goal. Purpose: To evaluate 2-year patient-related outcome (PRO) scores and patient satisfaction scores for a single surgeon at a high-volume referral center for all primary hip arthroscopy procedures performed. Study Design: Case series; Level of evidence, 4. Methods: During the study period between April 2008 and October 2011, data were collected on all patients who underwent primary hip arthroscopy. All patients were assessed pre- and postoperatively with 4 PRO measures: the modified Harris Hip Score (mHHS), Non-Arthritic Hip Score (NAHS), Hip Outcome Score–Activities of Daily Living (HOS-ADL), and Hip Outcome Score–Sport-Specific Subscale (HOS-SSS). Pain was estimated on the visual analog scale (VAS), and satisfaction was measured on a scale from 0 to 10. The number of patients who underwent revision arthroscopy, total hip arthroplasty (THA), or a resurfacing procedure during the study period was also reported. Results: A total of 595 patients were included in the study. The score improvement from preoperative to 2-year follow-up was 61.29 to 82.02 for mHHS, 62.79 to 83.05 for HOS-ADL, 40.96 to 70.07 for HOS-SSS, 57.97 to 80.41 for NAHS, and 5.86 to 2.97 for VAS. All scores were statistically significantly different ( P < .0001). Overall patient satisfaction was 7.86 ± 2.3 (range, 1-10). Forty-seven (7.7%) patients underwent revision hip arthroscopy, and 54 (9.1%) patients underwent either THA or the hip resurfacing procedure during the study period. The multivariate regression analysis showed that increased age at time of surgery was a significant risk factor for conversion to THA, revision arthroscopy, and change in NAHS <10 points. Acute injury, acetabuloplasty, iliopsoas release, and patient sex were significant for 2 of these 3 types of failure. Conclusion: Primary hip arthroscopy for all procedures performed in aggregate had excellent clinical outcomes and patient satisfaction scores at short-term follow-up in this study. More studies must be conducted to determine the definition of a successful outcome. There was a 6.1% minor complication rate, which was consistent with previous studies. Patients should be counseled regarding the potential progression of degenerative change leading to arthroplasty as well as the potential for revision surgery.
On-Site Treatment of Exertional Heat Stroke
Authors: Sloan Brian K. , Kraft Emily M. , Clark Dave , Schmeissing Scott W. , Byrne Brian C. , Rusyniak Daniel E. 
Published: January 2015

Background: Exertional heat stroke is a devastating condition that can cause significant morbidity and mortality. Rapid cooling is the most effective means of treating heat stroke, but little is published on the safety and logistics of cooling patients on site at a major sporting event. Purpose: To describe an on-site exertional heat stroke treatment protocol and to compare the outcomes of patients treated on site to those transferred to hospitals. Study Design: Descriptive epidemiological study. Methods: Using race-day medical records and ambulance run sheets, patients who developed exertional heat stroke at the Indianapolis half-marathon from 2005 to 2012 were identified. Exertional heat stroke was defined as runners with a core temperature measured with a rectal thermometer greater than 102°F and altered mental status. Clinical information and patient outcomes were abstracted from the race medical tent and hospital charts by 3 separate trained reviewers using structured methods and a data collection form. Two reviewers, using a RedCAP database and dual-data entry, abstracted records for each patient. A third arbitrated all discrepancies between reviewers. Clinical signs, treatments, and outcomes were calculated using descriptive statistics, and data were grouped and compared for patients treated on site or transferred to local hospitals for treatment. Results: Over 235,000 athletes participated in the event over the 8-year period, with 696 seeking medical care. A total of 32 heat stroke victims were identified during the study period; of these, 22 were treated on site. Of these, 68% were treated with cold-water immersion and 59% were discharged home from the race. Ten exertional heat stroke patients were transported from the race course to local hospitals. None of them underwent cold-water immersion, and 40% of them were subsequently discharged home. No patients in the study died. Conclusion: On-site treatment of athletes who develop exertional heat stroke appears to be both safe and effective. On-site treatment may decrease the local burden of critically ill patients to emergency departments during large athletic events.
Theatre of Emotion: A Nepalese Dramatic Art Form
Authors: Toffin Gérard 
Published: January 2015

AbstractEvery year, traditional Balami woodcutters, living on the edge of the Katmandu valley, in Nepal, offer ritual dramatic performances to the people of the surrounding villages. Among these, the small town of Pharping. These performances stage traditional royal sequences. Over the years, changes took place in the plot. Comic dimension fits alongside the more dramatic aspects of these stories. Emotions expressed by the comedians play a critical role in the drama, particularly when it comes to the tears wept by the princesses who witness their husbands’ death. The play is highly structured and codified; religious beliefs are embedded in it. These pieces end with animal sacrifices that took place on stage. Derived from the classical Newar theatre of the Malla era (17th-18th centuries), they are the product of a persistent combination of popular traditions with learned literature.