bluuebunny/crossref_metadata_2025 huggingface dataset:
Impaired Brachial Flow-Mediated Dilation Is a Predictor of a New-Onset Vascular Event after Stroke
Authors: Santos-García Diego , Blanco Miguel , Serena Joaquín , Rodríguez-Yáñez Manuel , Leira Rogelio , Castillo José
Published: July 2011

Background and Objective: Brachial arterial flow-mediated dilation (FMD) is associated with an increased risk of vascular events. Our aim was to investigate the relationship between FMD measured in the acute phase of ischemic stroke and a new major adverse vascular event in a consecutive cohort of patients followed up for 48 months after an acute first-ever stroke. Methods: We measured FMD in 120 consecutive patients with acute ischemic stroke using high-resolution ultrasonography. FMD was calculated as the relationship between the basal diameter of the brachial artery before and after transient vascular occlusion. Intima-media thickness, extracranial carotid atherosclerosis, stroke severity National Institute of Health Stroke Scale, and modified Rankin Scale at 3 months were also evaluated. A vascular event was defined as any of the following: vascular disease (VD) death, nonfatal myocardial infarction (MI), nonfatal recurrent stroke (RS), claudication or peripheral arterial thrombosis (PVD), angioplasty or cardiac bypass graft surgery. Results: There were 34 new major adverse vascular events in 32 of 120 patients (26.7%): 21 (61.8%) RS, 5 (14.7%) VD death, 5 (14.7%) MI, and 3 (8.8%) PVD. The presence of carotid artery plaque (81.3 vs. 46%; p < 0.0001), atrial fibrillation (37.5 vs. 14.8%; p = 0.007) and FMD (5.30 ± 7.48 vs. 10.54 ± 7.02; p = 0.001) were associated with new-onset vascular events. FMD ≤4.5% was an independent predictor of new-onset vascular events (hazards ratio 3.48; 95% confidence interval 1.26–9.63; p = 0.01). Conclusions: FMD is an independent predictor for a new-onset vascular event after first-ever ischemic stroke.
HIV-1 Gag-Virus-Like Particles Induce Natural Killer Cell Immune Responses via Activation and Maturation of Dendritic Cells
Authors: Chang Myint Oo , Suzuki Tomoyuki , Suzuki Hitoshi , Takaku Hiroshi
Published: July 2011

Despite the extensive efforts that have been made to combat acquired immune deficiency syndrome (AIDS), the number of people infected each year with human immunodeficiency virus type 1 (HIV-1) is still increasing worldwide, and a safe and effective vaccine to control HIV infection is urgently needed. Recently, the natural killer (NK) cell-mediated innate immune response, which represents the first line of defense against infections, has attracted attention for its role in combating HIV infection and disease progression. In the present study, we investigated the immunogenic ability of HIV-1 Gag-virus-like particles (Gag-VLPs) to induce NK cell immune responses in vitro and in vivo. Gag-VLPs efficiently activated human monocyte-derived dendritic cells (MDDCs), eliciting MDDC maturation with an associated increase in the surface expression of CD80, CD86 and MHC classes I and II, MDDC proliferation and proinflammatory cytokine production. Gag-VLP-treated MDDCs subsequently activated autologous NK cells, leading to their proliferation and production of interferon-γ and to the upregulation of NK cell cytotoxicity against YAC-1 cells and HIV-1-infected CD4+ T cells. In addition, we introduced a 2-phase immunization strategy in BALB/c mice to assess the role of DCs in the induction of NK cell immune responses by Gag-VLPs in vivo. Our findings reveal that Gag-VLPs efficiently activate DCs, which in turn induce innate and Gag-specific immune responses in NK cells.
Comparison of Steroids and Angiotensin Receptor Blockers for Patients with Advanced IgA Nephropathy and Impaired Renal Function
Authors: Moriyama Takahito , Amemiya Nobuyuki , Ochi Ayami , Tsuruta Yuki , Shimizu Ari , Itabashi Mitsuyo , Takei Takashi , Uchida Keiko , Nitta Kosaku
Published: July 2011

Background/Aims: The therapeutic strategy for advanced IgA nephropathy patients with impaired renal function is still controversial. Patients and Methods: We divided 44 IgA nephropathy patients with an estimated glomerular filtration rate (eGFR) of less than 60 ml/min/1.76 m2 and proteinuria greater than 0.5 g/g · creatinine into two groups: the angiotensin receptor blocker (ARB) group (n = 22), treated with ARBs, and the steroid group (n = 22), treated with corticosteroid. We analyzed the clinical and histological background, renal survival rate until progression to end-stage renal disease (ESRD), and the risk factors for progression. Results: The clinical and histological backgrounds were not significantly different between the groups. At 1 and 2 years after treatment, proteinuria tended to be decreased from baseline in both groups, but not significantly, and urinary red blood cells were significantly decreased in the steroid groups (p < 0.001), but not in the ARB group. The eGFR tended to be increased in the steroid group and decreased in the ARB group. However, the renal survival rate until ESRD was not significantly different between the groups. There were no significant independent risk factors for progression. Conclusion: The beneficial effect of ARBs on renal survival of advanced IgA nephropathy with impaired renal function is equal to that with steroids.
Constitutive Androstane Receptor Activation Decreases Plasma Apolipoprotein B–Containing Lipoproteins and Atherosclerosis in Low-Density Lipoprotein Receptor–Deficient Mice
Authors: Sberna Anne-Laure , Assem Mahfoud , Xiao Rui , Ayers Steve , Gautier Thomas , Guiu Boris , Deckert Valérie , Chevriaux Angélique , Grober Jacques , Le Guern Naig , Pais de Barros Jean-Paul , Moore David D. , Lagrost Laurent , Masson David
Published: July 2011

Objective—

The goal of this study was to determine the impact of the nuclear receptor constitutive androstane receptor (CAR) on lipoprotein metabolism and atherosclerosis in hyperlipidemic mice.

Methods and Results—

Low-density lipoprotein receptor–deficient (Ldlr
−/−
) and apolipoprotein E–deficient (ApoE
−/−
) mice fed a Western-type diet were treated weekly with the Car agonist 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) or the vehicle only for 8 weeks. In Ldlr
−/−
mice, treatment with TCPOBOP induced a decrease in plasma triglyceride and intermediate-density lipoprotein/low-density lipoprotein cholesterol levels (≈30% decrease in both cases after 2 months,
P
<0.01). These mice also showed a significant reduction in the production of very-low-density lipoproteins associated with a decrease in hepatic triglyceride content and the repression of several genes involved in lipogenesis. TCPOBOP treatment also induced a marked increase in the very-low-density lipoprotein receptor in the liver, which probably contributed to the decrease in intermediate-density lipoprotein/low-density lipoprotein levels. Atherosclerotic lesions in the aortic valves of TCPOBOP-treated Ldlr
−/−
mice were also reduced (−60%,
P
<0.001). In ApoE
−/−
mice, which lack the physiological apoE ligand for the very-low-density lipoprotein receptor, the effect of TCPOBOP on plasma cholesterol levels and the development of atherosclerotic lesions was markedly attenuated.

Conclusion—

CAR is a potential target in the prevention and treatment of hypercholesterolemia and atherosclerosis.
Dual Metabolic Defects Are Required to Produce Hypertriglyceridemia in Obese Subjects
Authors: Taskinen Marja-Riitta , Adiels Martin , Westerbacka Jukka , Söderlund Sanni , Kahri Juhani , Lundbom Nina , Lundbom Jesper , Hakkarainen Antti , Olofsson Sven-Olof , Orho-Melander Marju , Borén Jan
Published: July 2011

Objective—

Obesity increases the risk of cardiovascular disease and premature death. However, not all obese subjects develop the metabolic abnormalities associated with obesity. The aim of this study was to clarify the mechanisms that induce dyslipidemia in obese subjects.

Methods and Results—

Stable isotope tracers were used to elucidate the pathophysiology of the dyslipidemia in hypertriglyceridemic (
n
=14) and normotriglyceridemic (
n
=14) obese men (with comparable body mass index and visceral fat volume) and in normotriglyceridemic nonobese men (
n
=10). Liver fat was determined using proton magnetic resonance spectroscopy, and subcutaneous abdominal and visceral fat were measured by magnetic resonance imaging. Serum triglycerides in obese subjects were increased by the combination of increased secretion and severely impaired clearance of triglyceride-rich very-low-density lipoprotein
1
particles. Furthermore, increased liver and subcutaneous abdominal fat were linked to increased secretion of very-low-density lipoprotein 1 particles, whereas increased plasma levels of apolipoprotein C-III were associated with impaired clearance in obese hypertriglyceridemic subjects.

Conclusion—

Dual metabolic defects are required to produce hypertriglyceridemia in obese subjects with similar levels of visceral adiposity. The results emphasize the clinical importance of assessing hypertriglyceridemic waist in obese subjects to identify subjects at high cardiometabolic risk.
Premature Senescence in Cells From Patients With Autosomal Recessive Hypercholesterolemia (ARH)
Authors: Sun Xi-Ming , Patel Dilip D. , Acosta Juan-Carlos , Gil Jesùs , Soutar Anne K.
Published: July 2011

Objective—

The defective gene causing autosomal recessive hypercholesterolemia (ARH) encodes ARH, a clathrin-associated adaptor protein required for low-density-lipoprotein receptor endocytosis in most cells but not in skin fibroblasts. The aim here was to elucidate why ARH fibroblasts grow slowly and undergo premature senescence.

Methods and Results—

Knockdown of ARH by RNA interference in IMR90 cells produces the same phenotype, indicated by increased p16 expression, γ-H2AX-positive foci, and enlarged flattened morphology. We showed that ARH contributes to several aspects of mitosis: it localizes to mitotic microtubules, with lamin B1 on the nuclear envelope and spindle matrix, and with clathrin heavy chain on mitotic spindles. Second, ARH is phosphorylated in G
2
/M phase by a roscovitine-sensitive kinase, probably cdc2. Third, cells lacking ARH show disfigured nuclei and defective mitotic spindles. Defects are most marked in ARH W22X cells, where translation starts at Met46, so the protein lacks a phosphorylation site at Ser14, identified by mass spectrometry of wild-type ARH.

Conclusion—

The ARH protein is involved in cell cycle progression, possibly by affecting nuclear membrane formation through interaction with lamin B1 or other mitotic proteins, and its absence affects cell proliferation and induces premature senescence, which may play a role in the development of atherosclerosis in ARH.
Repression of P66Shc Expression by SIRT1 Contributes to the Prevention of Hyperglycemia-Induced Endothelial Dysfunction
Authors: Zhou Shuang , Chen Hou-Zao , Wan Yan-zhen , Zhang Qing-Jun , Wei Yu-Sheng , Huang Shuai , Liu Jin-Jing , Lu Yun-Biao , Zhang Zhu-Qin , Yang Rui-Feng , Zhang Ran , Cai Hua , Liu De-Pei , Liang Chih-Chuan
Published: July 2011

Rationale:

Inactivation of the p66Shc adaptor protein confers resistance to oxidative stress and protects mice from aging-associated vascular diseases. However, there is limited information about the negative regulating mechanisms of p66Shc expression in the vascular system.

Objective:

In this study, we investigated the role of SIRT1, a class III histone deacetylase, in the regulation of p66Shc expression and hyperglycemia-induced endothelial dysfunction.

Methods and Results:

Expressions of p66Shc gene transcript and protein were significantly increased by different kinds of class III histone deacetylase (sirtuin) inhibitors in human umbilical vein endothelial cells and 293A cells. Adenoviral overexpression of SIRT1 inhibited high-glucose–induced p66Shc upregulation in human umbilical vein endothelial cells. Knockdown of SIRT1 increased p66Shc expression and also increased the expression levels of plasminogen activator inhibitor-1 expression, but decreased manganese superoxide dismutase expression in high-glucose conditions. However, knockdown of p66Shc significantly reversed the effects of SIRT1 knockdown. In addition, p66Shc overexpression significantly decreased manganese superoxide dismutase expression and increased plasminogen activator inhibitor-1 expression in high-glucose conditions, which were recovered by SIRT1 overexpression. Moreover, compared to streptozotocin-induced wild-type diabetic mice, endothelium-specific SIRT1 transgenic diabetic mice had decreased p66Shc expression at both the mRNA and the protein levels, improved endothelial function, and reduced accumulation of nitrotyrosine and 8-OHdG (markers of oxidative stress). We further found that SIRT1 was able to bind to the p66Shc promoter (−508 bp to −250 bp), resulting in a decrease in the acetylation of histone H3 bound to the p66Shc promoter region.

Conclusion:

Our findings indicate that repression of p66Shc expression by SIRT1 contributes to the protection of hyperglycemia-induced endothelial dysfunction.
miR-15 Family Regulates Postnatal Mitotic Arrest of Cardiomyocytes
Authors: Porrello Enzo R. , Johnson Brett A. , Aurora Arin B. , Simpson Emma , Nam Young-Jae , Matkovich Scot J. , Dorn Gerald W. , van Rooij Eva , Olson Eric N.
Published: July 2011

Rationale:

Mammalian cardiomyocytes withdraw from the cell cycle during early postnatal development, which significantly limits the capacity of the adult mammalian heart to regenerate after injury. The regulatory mechanisms that govern cardiomyocyte cell cycle withdrawal and binucleation are poorly understood.

Objective:

Given the potential of microRNAs (miRNAs) to influence large gene networks and modify complex developmental and disease phenotypes, we searched for miRNAs that were regulated during the postnatal switch to terminal differentiation.

Methods and Results:

Microarray analysis revealed subsets of miRNAs that were upregulated or downregulated in cardiac ventricles from mice at 1 and 10 days of age (P1 and P10). Interestingly, miR-195 (a member of the miR-15 family) was the most highly upregulated miRNA during this period, with expression levels almost 6-fold higher in P10 ventricles relative to P1. Precocious overexpression of miR-195 in the embryonic heart was associated with ventricular hypoplasia and ventricular septal defects in β-myosin heavy chain–miR-195 transgenic mice. Using global gene profiling and argonaute-2 immunoprecipitation approaches, we showed that miR-195 regulates the expression of a number of cell cycle genes, including checkpoint kinase 1 (Chek1), which we identified as a highly conserved direct target of miR-195. Finally, we demonstrated that knockdown of the miR-15 family in neonatal mice with locked nucleic acid–modified anti-miRNAs was associated with an increased number of mitotic cardiomyocytes and derepression of Chek1.

Conclusions:

These findings suggest that upregulation of the miR-15 family during the neonatal period may be an important regulatory mechanism governing cardiomyocyte cell cycle withdrawal and binucleation.
Outcomes of Intravenous Thrombolysis in Posterior Versus Anterior Circulation Stroke
Authors: Sarikaya Hakan , Arnold Marcel , Engelter Stefan T. , Lyrer Philippe A. , Mattle Heinrich P. , Georgiadis Dimitrios , Bonati Leo H. , Fluri Felix , Fischer Urs , Findling Oliver , Ballinari Pietro , Baumgartner Ralf W.
Published: July 2011

Background and Purpose—

Intravenous thrombolysis is an approved treatment for anterior (ACS) and posterior (PCS) circulation stroke. However, no randomized controlled trial has investigated safety and efficacy of intravenous thrombolysis according to stroke territory, although PCS is assumed to differ from ACS in many ways. We aimed to compare the safety and clinical outcome of intravenous thrombolysis applied to patients with PCS and ACS.

Methods—

Prospectively collected data of 883 consecutive patients with acute ischemic stroke (788 ACS, 95 PCS) treated with intravenous thrombolysis in 3 Swiss stroke centers were analyzed. Presenting characteristics, symptomatic intracranial hemorrhage, mortality, and favorable outcome (modified Rankin scale 0 or 1) at 3 months were compared between patients with PCS and ACS.

Results—

As compared with patients with ACS, those with PCS were younger (mean age, 63 versus 67 years,
P
=0.012) and had a lower mean baseline National Institutes of Health Stroke Scale score (9 versus 12,
P
<0.001). Patients with PCS less often had symptomatic intracranial hemorrhage (0% versus 5%,
P
=0.026) and had more often a favorable outcome (66% versus 47%,
P
<0.001). Mortality was similar in the 2 groups (PCS, 9%; ACS, 13%;
P
=0.243). After multivariable adjustment, PCS was an independent predictor of lower symptomatic intracranial hemorrhage frequency (
P
=0.001), whereas stroke territory was not associated either with favorable outcome (
P
=0.177) or with mortality (
P
=0.251).

Conclusions—

Our study suggests that PCS is associated with a lower risk of symptomatic intracranial hemorrhage after intravenous thrombolysis as compared with ACS, whereas favorable outcome and mortality were similar in the 2 stroke territories.
Vertebral Artery Ostium Atherosclerotic Plaque as a Potential Source of Posterior Circulation Ischemic Stroke
Authors: Al-Ali Firas , Barrow Tom , Duan Li , Jefferson Anne , Louis Susan , Luke Kim , Major Kevin , Smoker Sandy , Walker Sarah , Yacobozzi Margaret
Published: July 2011

Background and Purpose—

Although atherosclerotic plaque in the carotid and coronary arteries is accepted as a cause of ischemia, vertebral artery ostium (VAO) atherosclerotic plaque is not widely recognized as a source of ischemic stroke. We seek to demonstrate its implication in some posterior circulation ischemia.

Methods—

This is a nonrandomized, prospective, single-center registry on consecutive patients presenting with posterior circulation ischemia who underwent VAO stenting for significant atherosclerotic stenosis. Diagnostic evaluation and imaging studies determined the likelihood of this lesion as the symptom source (highly likely, probable, or highly unlikely). Patients were divided into 4 groups in decreasing order of severity of clinical presentation (ischemic stroke, TIA then stroke, TIA, asymptomatic), which were compared with the morphological and hemodynamic characteristics of the VAO plaque. Clinical follow-up 1 year after stenting assessed symptom recurrence.

Results—

One hundred fourteen patients underwent stenting of 127 lesions; 35% of the lesions were highly likely the source of symptoms, 53% were probable, and 12% were highly unlikely. Clinical presentation correlated directly with plaque irregularity and presence of clot at the VAO, as did bilateral lesions and presence of tandem lesions. Symptom recurrence at 1 year was 2%.

Conclusions—

Thirty-five percent of the lesions were highly likely the source of the symptoms. A direct relationship between some morphological/hemodynamic characteristics and the severity of clinical presentation was also found. Finally, patients had a very low rate of symptom recurrence after treatment. These 3 observations point strongly to VAO plaque as a potential source of some posterior circulation stroke.
Incidence and Risk Factors of Recurrence After Endovascular Treatment of Intracranial Vertebrobasilar Dissecting Aneurysms
Authors: Kim Byung Moon , Shin Yong Sam , Kim Se-Hyuk , Suh Sang Hyun , Ihn Yon-Kwon , Kim Dong Ik , Kim Dong Joon , Park Sung Il
Published: July 2011

Background and Purpose—

The incidence and risk factors for recurrence after endovascular treatment of intracranial vertebrobasilar dissecting aneurysms (VBDAs) have not been studied. We aimed to evaluate the incidence and risk factors for recurrence after endovascular treatment of VBDAs.

Methods—

A total of 111 patients (mean age, 45±10 years) underwent endovascular treatment for 119 VBDAs (ruptured/unruptured=73:46). Incidence and risk factors for recurrence were retrospectively evaluated.

Results—

Sixty-two VBDAs were treated by a reconstructive technique by using 1 to 3 overlapping stents with or without coiling, and 57 VBDAs were treated by a deconstructive technique by using proximal occlusion or internal trapping at the dissected segment of the parent artery. Follow-up angiography was available for 97 VBDAs (81.5%) in 89 patients at 3 days to 48 months (median, 13 months) after treatment. There were 13 recurrences: 6 had rebleeding but 7 had no rebleeding. All 6 hemorrhagic recurrences had initially presented with a ruptured form. Ten recurrences were confirmed by angiography, but 3 recurrences with rebleeding did not receive follow-up angiography. The rate of post-treatment recurrence did not differ between reconstructive and deconstructive treatments. Involvement of the posterior inferior cerebellar artery origin (odds ratio=8.026; 95% confidence interval, 1.561 to 41.259;
P
=0.013) was the only independent risk factor for recurrence.

Conclusions—

There was a 13% recurrence after endovascular treatment of VBDAs. Posterior inferior cerebellar artery origin involvement was the only independent risk factor for recurrence after endovascular treatment of VBDAs.
An Extension of Smith’s Linear Theory of Orographic Precipitation: Introduction of Vertical Layers*
Authors: Barstad Idar , Schüller Felix
Published: July 2011

This paper proposes an extension of a linear theory of orographic precipitation (OP). In the original theory, cloud water is produced by forced lifting over mountains, moderated by airflow dynamics. Controlled by a time delay τc, the cloud water converts into hydrometeors, which drift and fall out as precipitation. This drift is controlled by another time delay τf. The new extension proposed here introduces vertical layers, limited to two in this study. In this way, a more realistic vertical structure is permitted. Wind and stability may change with height and different microphysical properties may be assigned to the layers. For instance, a long fallout delay in the upper layer may represent snow that, after falling through a melting layer, turns into rain that has a short delay in the lower model layer. The sensitivity to microphysical delay and wind speed has been addressed for various interface heights separating the two layers. This layered approach allows adjustment of the water vapor influx and truncation of dry descent above a crest line, which, in the context of the existing linear theory, otherwise could cancel cloud water in lower layers. The introduction of layers requires more information in the vertical, but this may be derived, to some extent, from surface information.
Toward a Global Climatology of Severe Hailstorms as Estimated by Satellite Passive Microwave Imagers
Authors: Cecil Daniel J. , Blankenship Clay B.
Published: July 2011

An 8-yr climatology of storms producing large hail is estimated from satellite measurements using Advanced Microwave Scanning Radiometer for Earth Observing System (AMSR-E). This allows a unique, consistent comparison between regions that cannot be consistently compared using ground-based records because of varying data collection standards. Severe hailstorms are indicated most often in a broad region of northern Argentina and southern Paraguay and a smaller region in Bangladesh and eastern India. Numerous hailstorms are also estimated in the central and southeastern United States, northern Pakistan and northwestern India, central and western Africa, and southeastern Africa (and adjacent waters). Fewer hailstorms are estimated for other regions over land and scattered across subtropical oceans. Very few are estimated in the deep tropics other than in Africa. Most continental regions show seasonality with hailstorms peaking in late spring or summer. The South Asian monsoon alters the hailstorm climatology around the Indian subcontinent. About 75% of the hailstorms on the eastern side (around Bangladesh) occur from April through June, generally before monsoon onset. Activity shifts northwest to northern India in late June and July. An arc along the foothills in northern Pakistan becomes particularly active from mid-June through mid-August. The AMSR-E measurements are limited to early afternoon and late night. Tropical Rainfall Measuring Mission (TRMM) measurements are used to investigate diurnal variability in the tropics and subtropics. All of the prominent regions have hailstorm peaks in late afternoon and early evening. The United States and central Africa have the fewest overnight and early morning storms, while subtropical South America and Bangladesh have the most.
Climatological Diurnal Cycles in Clear-Sky Brightness Temperatures from the High-Resolution Infrared Radiation Sounder (HIRS)
Authors: Lindfors Anders V. , Mackenzie Ian A. , Tett Simon F. B. , Shi Lei
Published: July 2011

A climatology of the diurnal cycles of HIRS clear-sky brightness temperatures was developed based on measurements over the period 2002–07. This was done by fitting a Fourier series to monthly gridded brightness temperatures of HIRS channels 1–12. The results show a strong land–sea contrast with stronger diurnal cycles over land, and extending from the surface up to HIRS channel 6 or 5, with regional maxima over the subtropics. Over seas, the diurnal cycles are generally small and therefore challenging to detect. A Monte Carlo uncertainty analysis showed that more robust results are reached by aggregating the data zonally before applying the fit. The zonal fits indicate that small diurnal cycles do exist over sea. The results imply that for a long-lived satellite such as NOAA-14, drift in the overpass time can cause a diurnal sampling bias of more than 5 K for channel 8 (surface and lower troposphere).
Mortality of Patients With Respiratory Insufficiency and Adult Respiratory Distress Syndrome After Surgery
Authors: Memtsoudis Stavros G. , Bombardieri Anna Maria , Ma Yan , Walz J. Matthias , Chiu Ya Lin , Mazumdar Madhu
Published: July 2011

Introduction:

Obesity has long been considered a risk factor for the development of various pathologies, yet evidence supporting increased risk of perioperative mortality in obese individuals developing postoperative complications is limited. Therefore, we sought to characterize the demographics of obese and nonobese individuals developing postoperative respiratory insufficiency (RI)/adult respiratory distress syndrome (ARDS) and to quantify the impact of obesity on in-hospital mortality among this patient population utilizing data collected for the Nationwide Inpatient Sample (NIS).

Methods:

Nationwide Inpatient Sample data for each year between 1998 and 2007 were accessed. Entries were included if they underwent a surgical procedure and had a diagnosis of RI/ARDS following surgery. Patients fulfilling entry criteria were divided into those with and without obesity. In-hospital mortality was the primary outcome. A logistic regression model was fitted to elucidate if obesity was associated with increased odds for the outcome while controlling for age, gender, admission and procedure type, and comorbidity burden.

Results:

We identified 9 149 030 admissions that underwent the included surgical procedures between 1998 and 2007. Of those, 5.48% had a diagnosis of obesity. The incidence of RI/ARDS was 1.82% among obese and 2.01% among nonobese patients. Obese patients whose postoperative course was complicated by RI/ARDS had a significantly lower incidence of the need for mechanical ventilation (50% vs 55%). In-hospital mortality was significantly lower compared to nonobese patients (5.45% vs 18.72%). For those patients with RI/ARDS requiring intubation, the in-hospital mortality rate was 11% for obese and 25% for nonobese patients. In the multivariate regression analysis, obesity was associated with a 69% reduction in the odds of in-hospital mortality in postoperative patients with RI/ARDS.

Conclusion:

In our analysis, obesity was associated with a decreased incidence and adjusted odds for in-hospital mortality after surgery. Our results support the emerging concept of the “obesity paradox.”
An examination of current adapted physical activity provision in primary and special schools in Ireland
Authors: Crawford Susan
Published: July 2011

The Disability in Sport Taskforce report examining adapted physical activity (APA) in the Irish context (Department of Education and Science, 1999) found that teachers involved in primary mainstream and specialist settings expressed a grave lack of self-confidence, due to lack of training, in the delivery of APA programmes to children with special educational needs (SEN). A further study by Meegan and MacPhail (2006) indicated the need to promote positive attitudes among Irish physical educators toward teaching students with SEN as well as improving initial teacher training and postgraduate training for SEN in physical education (PE). The aim of this study was to examine the current status of APA in primary and special school settings in Ireland, by postal questionnaire. The overall response rate was 42% (n = 171). Key findings indicated that respondents (100%) wished to participate in further specific training in APA leading to a formal qualification. Respondents expressed dissatisfaction with initial teacher training (60%), minimal ongoing in-service provision (70%) and limited teaching resources (68%) for the provision of quality APA to children with SEN.
‘Making space, pushing time’: A Sudanese hip-hop group and their wardrobe-recording studio
Authors: Wilson Michael John
Published: July 2011

This article explores the appropriation of an everyday domestic space by a group of young Sudanese men living in Western Sydney, Australia. The participants’ construction of a do-it-yourself (DIY) wardrobe-recording studio acts as a starting point from which to investigate the transnational reproduction of spatial and material practices of resourcefulness in the context of resettlement. Concepts of space, appropriation and emplacement are employed to critically examine the pragmatic, inventive and resourceful use of an ordinary bedroom space. I ague that the ongoing project has solidified a common purpose among the participants, providing them with a material and symbolic platform from which to engage Sudanese and other migrant youth, as well as a creative means of avoiding the potentially negative effects of idle time. The article concludes that longer-term settlement strategies need to be put in place, which address the secondary settlement challenges of monitoring and needs assessment, and customized support for self-funded, youth-based projects.
Two concepts of culture in the early Nietzsche
Authors: Church Jeffrey
Published: July 2011

Culture remains a divisive issue in liberal democracies, and this article argues Nietzsche offers a principled middle ground between the conservative and progressive camps of recent and ongoing ‘culture wars’. Hence, this article challenges the ‘aristocratic’ versus ‘democratic’ Nietzsche debate by making the case that Nietzsche defended two opposed notions of culture in his early period work: a national or group culture and a cosmopolitan culture. This opposition is salutary, however, in that each form of culture moderates the excesses of the other so that both jointly can aim to perfect what Nietzsche claims is our bifurcated human nature.
Rousseau on needs, language and pity: The limits of ‘public reason’
Authors: James David
Published: July 2011

The idea of ‘public reason’ has recently been associated with Rousseau’s views on the formation of a general will. Advocates of this idea in the Kantian tradition tend to emphasize reflective acts of rational deliberation which, I suggest, are more suited to written than to spoken language. Rousseau’s accounts of the role of spoken language as a means of expressing human needs and the role of pity in the development of a moral form of reasoning, which allows one properly to take into account the interests of others, show that he cannot be so easily interpreted as an advocate of the idea of public reason. This is because his views on the importance of spoken language in democratic politics and the essential part played by the sentiment of pity in the development of moral reasoning imply the legitimacy of modes of expression in the formation of a general will that are not, in any obvious sense, compatible with the demands of public reason.
Luck, institutions, and global distributive justice: A defence of global luck egalitarianism
Authors: Tan Kok-Chor
Published: July 2011

Luck egalitarianism provides one powerful way of defending global egalitarianism. The basic luck egalitarian idea that persons ought not to be disadvantaged compared to others on account of his or her bad luck seems to extend naturally to the global arena, where random factors such as persons’ place of birth and the natural distribution of the world’s resources do affect differentially their life chances. Yet luck egalitarianism as an ideal, as well as its global application, has come under severe criticisms in recent debate. My aim in this article is to restore plausibility to the luck egalitarian idea, and to suggest how it could then provide a plausible grounding for global egalitarianism. To do this, I will propose a more modest but also more defensible conception of luck egalitarianism that can also strengthen the case for global distributive justice.
External Cueing Improves Motor Imagery Quality in Patients With Parkinson Disease
Authors: Heremans Elke , Nieuwboer Alice , Feys Peter , Vercruysse Sarah , Vandenberghe Wim , Sharma Nikhil , Helsen Werner F.
Published: July 2011

Background. Patients with Parkinson disease (PD) are often profoundly slow in their performance of physical tasks, as well as in motor imagery (MI). This may limit the implementation and potential benefits of MI practice during rehabilitation. Objective. The authors investigated whether the quality of MI could be improved by external cueing. Methods. Fourteen patients with PD and 14 healthy controls physically executed and visually imagined a goal-directed aiming task and a box-and-block task, both in the presence and absence of visual and auditory cues. Mental chronometry and eye movement recording allowed objective evaluation of the temporal and spatial characteristics of MI when compared with physical execution. Visual analogue scales were used to assess imagery vividness. Results. The presence of visual cues significantly reduced the patients’ bradykinesia during MI and increased their imagery vividness. Conclusions. Visual cueing optimizes MI quality for PD patients and is a potential tool to increase the efficacy of MI practice in PD rehabilitation.
Deflecting the CNN effect: public opinion polling and Livingstonian outcomes
Authors: Kogen Lauren , Price Monroe E
Published: July 2011

Can the analysis and dissemination of public opinion polling be organized in such a way as to shift public debate and help reframe an issue that has been strongly influenced by CNN-like mediated activities? Drawing upon polling experience in Darfur, the authors examine this question in the highly disputed context of international conflicts, an area where CNN effects are manifest. They argue that government-sponsored polls can become part of official reactions to the CNN effect in three primary ways: first, deflecting the CNN effect by re-framing narratives and policy options; second, trumping the CNN effect by returning to a form of evidence-based policy making in which research, rather than media pressure, dictates decision making; and third, circumventing the CNN effect by engaging in improved approaches to conflict resolution.
Decreases in IL-7 levels during antiretroviral treatment of HIV infection suggest a primary mechanism of receptor-mediated clearance
Authors: Hodge Jessica N. , Srinivasula Sharat , Hu Zonghui , Read Sarah W. , Porter Brian O. , Kim Insook , Mican JoAnn M. , Paik Chang , DeGrange Paula , Di Mascio Michele , Sereti Irini
Published: July 2011

IL-7 is essential for T-cell homeostasis. Elevated serum IL-7 levels in lymphopenic states, including HIV infection, are thought to be due to increased production by homeostatic feedback, decreased receptor-mediated clearance, or both. The goal of this study was to understand how immune reconstitution through antiretroviral therapy (ART) in HIV+ patients affects IL-7 serum levels, expression of the IL-7 receptor (CD127), and T-cell cycling. Immunophenotypic analysis of T cells from 29 HIV− controls and 43 untreated HIV+ patients (30 of whom were followed longitudinally for ≤ 24 months on ART) was performed. Restoration of both CD4+ and CD8+ T cells was driven by increases in CD127+ naive and central memory T cells. CD4+ T-cell subsets were not fully restored after 2 years of ART, whereas serum IL-7 levels normalized by 1 year of ART. Mathematical modeling indicated that changes in serum IL-7 levels could be accounted for by changes in the receptor concentration. These data suggest that T-cell restoration after ART in HIV infection is driven predominantly by CD127+ cells and that decreases of serum IL-7 can be largely explained by improved CD127-mediated clearance.
Pericytes promote endothelial cell survival through induction of autocrine VEGF-A signaling and Bcl-w expression
Authors: Franco Marcela , Roswall Pernilla , Cortez Eliane , Hanahan Douglas , Pietras Kristian
Published: July 2011

Endothelial cells (ECs) in blood vessels under formation are stabilized by the recruitment of pericytes, both in normal tissues and during angiogenesis in pathologic situations, including neoplasia. In the tumor vasculature, besides supporting the functionality of blood flow, pericytes protect ECs from antiangiogenic therapies, and have thus been implicated in clinical resistance to vascular targeting drugs. However, the molecular nature of the crosstalk between pericytes and ECs is largely unchartered. Herein, we identified pericyte-induced survival signals in ECs by isolation of vascular fragments derived from tumors that had been genetically or pharmacologically engineered to be either pericyte-rich or pericyte-poor. Pericytes induced the antiapoptotic protein Bcl-w in tumor ECs both in vivo and in vitro, thereby conveying protection from cytotoxic damage. The pericyte-dependent survival signaling in ECs was consequential to enforcement of an autocrine loop involving VEGF-A expression in ECs. Through molecular and functional studies, we delineated a signal transduction pathway in ECs downstream of integrin αv involving activation of NF-κB as the initiating event of the protective crosstalk from pericytes. Our elucidation of pericyte-derived pro-survival signaling in tumor ECs has potentially important implications for clinical development of antiangiogenic drugs, and suggests new therapeutic targets for rational multitargeting of cancer.
Human regulatory T cells in allogeneic stem cell transplantation
Authors: Ukena Sya N. , Velaga Sarvari , Geffers Robert , Grosse Jens , Baron Udo , Buchholz Stefanie , Stadler Michael , Bruder Dunja , Ganser Arnold , Franzke Anke
Published: July 2011

GVHD is still one of the major complications after allogeneic stem cell transplantation. Whereas murine data have clearly shown the beneficial effects of regulatory T cells (Tregs) on the prevention of GVHD, data from the human system are rare. Here, we present a comparative dynamic analysis of CD4+CD25hiCD127lo/− Tregs from patients with and without GVHD analyzing the whole genome profile over the first 6 months after stem cell transplantation, representing the most sensitive time window for tolerance induction. The Treg transcriptome showed a high stability. However, the comparison of Treg transcriptomes from patients with and without GVHD uncovered regulated gene transcripts highly relevant for Treg cell function. The confirmative protein analyses demonstrated a significantly higher expression of granzyme A, CXCR3, and CCR5 in Tregs of immune tolerant patients. These results point to a reduced suppressive function of Tregs from GVHD patients with diminished migration capacity to the target organs.
Serum CC chemokine ligand-18 predicts lung disease worsening in systemic sclerosis
Authors: Tiev K.P. , Hua-Huy T. , Kettaneh A. , Gain M. , Duong-Quy S. , Tolédano C. , Cabane J. , Dinh-Xuan A.T.
Published: July 2011

Elevated serum CC chemokine ligand (CCL)18 reflects lung fibrosis activity in systemic sclerosis (SSc) and could be an early marker of lung function worsening. Therefore, we sought to evaluate whether serum CCL18 levels at baseline could predict worsening of lung disease in SSc.

In this prospective study, 83 SSc patients were analysed longitudinally over a 4-yr observation period for the risk of occurrence of combined deleterious events, defined as a 10% decrease from baseline of total lung capacity or forced vital capacity % predicted, or death, according to serum CCL18 at inclusion. Receiver operating characteristic (ROC) curve analysis was performed for prediction of events during the first year after inclusion.

The best cut-off level of serum CCL18 for prediction of a combined event within the follow-up period was 187 ng·mL−1, with 53% sensitivity and 96% specificity (area under the ROC curve 0.86; p<0.001). After a mean±sdfollow-up of 33.7±10.8 months, a higher rate of disease progression occurred in the group with serum CCL18 levels >187 ng·mL−1. The adjusted hazard ratio was 5.36 (95% CI 2.44–11.75; p<0.001).

In summary, serum CCL18 is an accurate predictive biomarker for the identification of patients with a higher risk of subsequent scleroderma lung disease worsening.
Nomogram to predict the presence ofEGFRactivating mutation in lung adenocarcinoma
Authors: Girard N. , Sima C.S. , Jackman D.M. , Sequist L.V. , Chen H. , Yang J.C-H. , Ji H. , Waltman B. , Rosell R. , Taron M. , Zakowski M.F. , Ladanyi M. , Riely G. , Pao W.
Published: July 2011

Epidermal growth factor receptor (EGFR) tumour genotyping is crucial to guide treatment decisions regarding the use of EGFR tyrosine kinase inhibitors in nonsmall cell lung cancer (NSCLC). However, some patients may not be able to obtain tumour testing, either because tissue is limited and/or tests are not routinely offered. Here, we aimed to build a model-based nomogram to allow for prediction of the presence ofEGFRmutations in NSCLC.

We retrospectively collected clinical and pathological data on 3,006 patients with NSCLC who had their tumours genotyped forEGFRmutations at five institutions worldwide. Variables of interest were integrated in a multivariate logistic regression model.

In the 2,392 non-Asian patients with lung adenocarcinomas, the most important predictors of harbouringEGFRmutation were: lower tobacco smoking exposure (OR 0.41, 95% CI 0.37–0.46), longer time interval between smoking cessation and diagnosis (OR 2.19, 95% CI 1.71–2.80), advanced stage (OR 1.58, 95% CI 1.18–2.13), and papillary (OR 4.57, 95% CI 3.14–6.66) or bronchioloalveolar (OR 2.84, 95% CI 1.98–4.06) histologically predominant subtype. A nomogram was established and showed excellent discriminating accuracy: the concordance index on an independent validation dataset was 0.84.

As clinical practices transition to incorporating genotyping as part of routine care, this nomogram could be highly useful to predict the presence ofEGFRmutations in lung adenocarcinoma in non-Asian patients when mutational profiling is not available or possible.
GPS-Prot: A web-based visualization platform for integrating host-pathogen interaction data
Authors: Fahey Marie E , Bennett Melanie J , Mahon Cathal , Jäger Stefanie , Pache Lars , Kumar Dhiraj , Shapiro Alex , Rao Kanury , Chanda Sumit K , Craik Charles S , Frankel Alan D , Krogan Nevan J
Published: July 2011

Background

The increasing availability of HIV-host interaction datasets, including both physical and genetic interactions, has created a need for software tools to integrate and visualize the data. Because these host-pathogen interactions are extensive and interactions between human proteins are found within many different databases, it is difficult to generate integrated HIV-human interaction networks.

Results

We have developed a web-based platform, termed GPS-Prothttp://www.gpsprot.org, that allows for facile integration of different HIV interaction data types as well as inclusion of interactions between human proteins derived from publicly-available databases, including MINT, BioGRID and HPRD. The software has the ability to group proteins into functional modules or protein complexes, generating more intuitive network representations and also allows for the uploading of user-generated data.

Conclusions

GPS-Prot is a software tool that allows users to easily create comprehensive and integrated HIV-host networks. A major advantage of this platform compared to other visualization tools is its web-based format, which requires no software installation or data downloads. GPS-Prot allows novice users to quickly generate networks that combine both genetic and protein-protein interactions between HIV and its human host into a single representation. Ultimately, the platform is extendable to other host-pathogen systems.
Cytoskeleton proteins previously considered exclusive to Ganglion Cells are transiently expressed by all retinal neuronal precursors
Authors: Gutierrez Christian , McNally Minda , Canto-Soler M Valeria
Published: July 2011

Background

Understanding the mechanisms governing cell fate specification remains one of the main challenges in the study of retinal development. In this context, molecular markers that identify specific cell types become crucial tools for the analysis and interpretation of these phenomena. In studies using the developing chick retina, expression of the mid-size neurofilament (NF-M) and a chick-specific microtubule associated protein recognized by the RA4 antibody (MAP(RA4)), have been broadly used to selectively identify ganglion cells and their committed precursors. However, observations in our laboratory suggested that the expression of these proteins may not be restricted to cells of the ganglion cell lineage. Because of its potential significance in the field, we pursued a detailed analysis of the expression of these two molecules in combination with an array of proteins that allowed precise identification of all retinal cell-type precursors throughout the development of the chick retina.

Results

Both, NF-M and MAP(RA4) proteins, showed a dynamic pattern of expression coincident with the progression of retinal cell differentiation. Both proteins were coexpressed spatially and temporally in postmitotic neuronal precursors throughout development. Expression of both proteins was seen in ganglion cell precursors and adult differentiated ganglion cells, but they were also transiently expressed by precursors of the photoreceptor, horizontal, bipolar and amacrine cell lineages.

Conclusions

We have clearly demonstrated that, contrary to the generally accepted paradigm, expression of NF-M and MAP(RA4) proteins is not exclusive to ganglion cells. Rather, both proteins are transiently expressed by all neuronal retinal progenitors in a developmentally-regulated manner. In addition, MAP(RA4) and NF-M are the first molecules so far characterized that may allow unambiguous identification of postmitotic precursors from the pool of mitotically active progenitors and/or the differentiated cell population during retinogenesis. These results are of significant impact for the field of developmental biology of the retina, since they provide novel and important information for the appropriate design and interpretation of studies on retinal cell differentiation, as well as for the reinterpretation of previously published studies.