bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced Atherosclerosis in apoE-inhibitory FcγRIIb–Deficient Mice Is Associated With Increased Anti-Inflammatory Responses by T Cells and Macrophages
Authors: Ng Hang Pong , Zhu Xinmei , Harmon Erin Y. , Lennartz Michelle R. , Nagarajan Shanmugam 
Published: March 2015

Objective—
Fcγ receptors (FcγRs) are classified as activating (FcγRI, III, and IV) and inhibitory (FcγRII) receptors. We have reported that deletion of activating FcγRs in apolipoprotein E (apoE) single knockout mice attenuated atherosclerosis. In this report, we investigated the hypothesis that deficiency of inhibitory FcγRIIb exacerbates atherosclerosis.

Approach and Results—

ApoE-FcγRIIb double knockout mice, congenic to the C57BL/6 (apoE-FcγRIIb
B6
−/−
), were generated and atherosclerotic lesions were assessed. In contrary to our hypothesis, when compared with apoE single knockout mice, arterial lesions were significantly decreased in apoE-FcγRIIb
B6
−/−
male and female mice fed chow or high-fat diets. Chimeric mice generated by transplanting apoE-FcγRIIb
B6
−/−
marrow into apoE single knockout mice also developed reduced lesions. CD4
+
T cells from apoE-FcγRIIb
B6
−/−
mice produced higher levels of interleukin-10 and transforming growth factor-β than their apoE single knockout counterparts. As our findings conflict with a previous report using apoE-FcγRIIb
129/B6
−/−
mice on a mixed genetic background, we investigated whether strain differences contributed to the anti-inflammatory response. Macrophages from FcγRIIb
129/B6
−/−
mice on a mixed genetic background produced more interleukin-1β and MCP-1 (monocyte chemoattractant protein-1) in response to immune complexes, whereas congenic FcγRIIb
B6
−/−
mice generated more interleukin-10 and significantly less interleukin-1β. Interestingly, the expression of lupus-associated slam genes, located in proximity to
fcgr2b
in mouse chromosome 1, is upregulated only in mixed FcγRIIb
129/B6
−/−
mice.

Conclusions—

Our findings demonstrate a detrimental role for FcγRIIb signaling in atherosclerosis and the contribution of anti-inflammatory cytokine responses in the attenuated lesions observed in apoE-FcγRIIb
B6
−/−
mice. As 129/sv genome–derived lupus-associated genes have been implicated in lupus phenotype in FcγRIIb
129/B6
−/−
mice, our findings suggest possible epistatic mechanism contributing to the decreased lesions.
Resolvin E1 (RvE1) Attenuates Atherosclerotic Plaque Formation in Diet and Inflammation-Induced Atherogenesis
Authors: Hasturk Hatice , Abdallah Rima , Kantarci Alpdogan , Nguyen Daniel , Giordano Nicholas , Hamilton James , Van Dyke Thomas E. 
Published: March 2015

Objective—
Epidemiological and recent clinical studies implicate periodontitis as an independent risk factor for cardiovascular disease. Previously, we demonstrated that rabbits with experimental periodontitis and cholesterol diet exhibit more aortic plaque compared with diet alone. We also showed that a proresolution mediator, Resolvin E1 (RvE1), reverses the experimental periodontitis. Here, we determined whether oral/topical application of RvE1 attenuates aortic atherosclerosis induced by both diet and periodontal inflammation.

Approach and Results—

Thirty-nine rabbits on a 13-week regimen of 0.5% cholesterol diet were included. Periodontitis was induced by Porphyromonas
gingivalis
in 24 rabbits and 15 rabbits were placed in no-periodontitis groups. Interventions were no-treatment, vehicle, and RvE1 treatment (4 μg/site or 0.4 μg/site) topically applied 3× per week. At 13 weeks, both periodontitis and atherosclerosis were quantified. Atherosclerotic plaques were assessed by Sudan IV staining, histology, and ex vivo MRI. Serum levels of C-reactive protein were evaluated as a measure of systemic inflammation. RvE1, used as an oral/topical agent, significantly diminished atherogenesis and prevented periodontitis (
P
<0.05). In the absence of periodontal inflammation, oral/topical application of RvE1 resulted in significantly less arterial plaque, a lower intima/media ratio, and decreased inflammatory cell infiltration compared with no-treatment (
P
<0.001). Local oral RvE1 application significantly reduced systemic levels of C-reactive protein (
P
<0.05).

Conclusions—
The results suggest that oral/topical RvE1 attenuates enhanced atherogenesis induced by periodontitis and prevents vascular inflammation and atherogenesis in the absence of periodontitis. The inhibition of vascular inflammation with endogenous mediators of resolution of inflammation provides a novel approach in the prevention of atherogenic events.
Prospective Randomized Trial of Moderately Strenuous Aerobic Exercise After an Implantable Cardioverter Defibrillator
Authors: Dougherty Cynthia M. , Glenny Robb W. , Burr Robert L. , Flo Gayle L. , Kudenchuk Peter J. 
Published: March 2015

Background—
Despite its salutary effects on health, aerobic exercise is often avoided after receipt of an implantable cardioverter defibrillator (ICD) because of fears that exercise may provoke acute arrhythmias. We prospectively evaluated the effects of a home aerobic exercise training and maintenance program (EX) on aerobic performance, ICD shocks, and hospitalizations exclusively in ICD recipients.

Methods and Results—

A total of 160 patients (124 men and 36 women) were randomly assigned who had an ICD for primary (43%) or secondary (57%) prevention to EX or usual care (UC). The primary outcome was peak oxygen consumption, measured with cardiopulmonary exercise testing at baseline and 8 and 24 weeks. EX consisted of 8 weeks of home walking for 1 h/d, 5 d/wk at 60% to 80% of heart rate reserve, followed by 16 weeks of maintenance home walking for 150 min/wk. Adherence to EX was determined from exercise logs, ambulatory heart rate recordings of exercise, and weekly telephone contacts. Patients assigned to UC received no exercise directives and were monitored by monthly telephone contact. Adverse events were identified by ICD interrogations, patient reports, and medical charts. ICD recipients averaged 55±12 years and mean ejection fraction of 40.6±15.7; all were taking β-blocker medications. EX significantly increased peak oxygen consumption (EX, 26.7±7.0 mL/kg per minute; UC, 23.9±6.6 mL/kg per minute;
P
=0.002) at 8 weeks, which persisted during maintenance exercise at 24 weeks (EX, 26.9±7.7 mL/kg per minute; UC, 23.4±6.0 mL/kg per minute;
P
<0.001). ICD shocks were infrequent (EX=4 versus UC=8), with no differences in hospitalizations or deaths between groups.

Conclusions—
Prescribed home exercise is safe and significantly improves cardiovascular performance in ICD recipients without causing shocks or hospitalizations.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00522340.
Physical Activity Measured by Accelerometry and its Associations With Cardiac Structure and Vascular Function in Young and Middle‐Aged Adults
Authors: Andersson Charlotte , Lyass Asya , Larson Martin G. , Spartano Nicole L. , Vita Joseph A. , Benjamin Emelia J. , Murabito Joanne M. , Esliger Dale W. , Blease Susan J. , Hamburg Naomi M. , Mitchell Gary F. , Vasan Ramachandran S. 
Published: March 2015

Background
Physical activity is associated with several health benefits, including lower cardiovascular disease risk. The independent influence of physical activity on cardiac and vascular function in the community, however, has been sparsely investigated.

Measures and Results

We related objective measures of moderate‐ to vigorous‐intensity physical activity (
MVPA
, assessed by accelerometry) to cardiac and vascular indices in 2376 participants of the Framingham Heart Study third generation cohort (54% women, mean age 47 years). Using multivariable regression models, we related
MVPA
to the following echocardiographic and vascular measures: left ventricular mass, left atrial and aortic root sizes, carotid–femoral pulse wave velocity, augmentation index, and forward pressure wave. Men and women engaged in
MVPA
29.9±21.4 and 25.5±19.4 min/day, respectively. Higher values of
MVPA
(per 10‐minute increment) were associated with lower carotid–femoral pulse wave velocity (estimate −0.53 ms/m;
P
=0.006) and lower forward pressure wave (estimate −0.23 mm Hg;
P
=0.03) but were not associated with augmentation index (estimate 0.13%;
P
=0.25).
MVPA
was associated positively with log
e
left ventricular mass (estimate 0.006 log
e
[g/m
2
];
P
=0.0003), left ventricular wall thickness (estimate 0.07 mm;
P
=0.0001), and left atrial dimension (estimate 0.10 mm;
P
=0.01).
MVPA
also tended to be positively associated with aortic root dimension (estimate 0.05 mm;
P
=0.052). Associations of
MVPA
with cardiovascular measures were similar, in general, for bouts lasting <10 versus ≥10 minutes.

Conclusions
In our community‐based sample, greater physical activity was associated with lower vascular stiffness but with higher echocardiographic left ventricular mass and left atrial size. These findings suggest complex relations of usual levels of physical activity and cardiovascular remodeling.
Angiotensin‐Converting Enzyme‐2 Overexpression Improves Atrial Remodeling and Function in a Canine Model of Atrial Fibrillation
Authors: Zhou Tingquan , Wang Zhenglong , Fan Jinqi , Chen Shaojie , Tan Zhen , Yang Hanxuan , Yin Yuehui 
Published: March 2015

Background

Atrial fibrosis is an important factor in initiating and maintaining atrial fibrillation. The purpose of this study was to test the hypothesis that atrial angiotensin‐converting enzyme‐2 (
ACE
2) overexpression might inhibit atrial collagen accumulation and improve atrial remodeling in a canine atrial pacing model.

Methods and Results

Thirty‐two mongrel dogs of both genders were divided randomly into 4 groups: sham‐operated, control, gene therapy with adenovirus‐enhanced green fluorescent protein (Ad‐
EGFP
), and gene therapy with Ad‐
ACE
2. All of the dogs in the control, Ad‐
EGFP
, and Ad‐
ACE
2 groups were paced at 450 bpm for a period of 14 days. The dogs in the sham group were instrumented without pacing. After 2 weeks, all of the dogs underwent a thoracotomy operation and received epicardial gene painting. On post–gene transfer day 21, the animals underwent electrophysiology, histology, and molecular studies. The percentage of fibrosis in the Ad‐
ACE
2 group was markedly lower than the percentage in the control and Ad‐
EGFP
groups. Compared with the other groups,
ACE
2 expression was increased significantly in the Ad‐
ACE
2 group. Compared with the sham and Ad‐
ACE
2 groups, the expression levels of transforming growth factor‐β1 and Smad3 were significantly higher in the Ad‐
EGFP
and control groups; however, the expression levels of Smad7 were lower in the atrial tissue as detected by Western blot and reverse transcription polymerase chain reaction.

Conclusions

Our results demonstrate that the overexpression of
ACE
2 inhibits atrial collagen accumulation and improves left atrial remodeling and function in a canine model of atrial fibrillation. Thus, targeted gene
ACE
2 therapy provides a promising approach for the treatment of atrial fibrillation.
Renal Tubule Angiotensin II Type 1 Receptor–Associated Protein Promotes Natriuresis and Inhibits Salt‐Sensitive Blood Pressure Elevation
Authors: Wakui Hiromichi , Uneda Kazushi , Tamura Kouichi , Ohsawa Masato , Azushima Kengo , Kobayashi Ryu , Ohki Kohji , Dejima Toru , Kanaoka Tomohiko , Tsurumi‐Ikeya Yuko , Matsuda Miyuki , Haruhara Kotaro , Nishiyama Akira , Yabana Machiko , Fujikawa Tetsuya , Yamashita Akio , Umemura Satoshi 
Published: March 2015

Background

Angiotensin
II
type 1 receptor (
AT
1R)–associated protein (
ATRAP;
Agtrap
gene) promotes
AT
1R internalization along with suppression of pathological
AT
1R activation. In this study, we examined whether enhancement of
ATRAP
in the renal distal tubules affects sodium handling and blood pressure regulation in response to high salt (
HS
) loading, using
ATRAP
transgenic mice on a salt‐sensitive C57
BL
/6J background.

Methods and Results

Renal
ATRAP
transgenic (
rATRAP
‐Tg) mice, which exhibit renal tubule–dominant
ATRAP
enhancement, and their wild‐type littermate C57
BL
/6J mice on a normal salt diet (0.3% NaCl) at baseline were subjected to dietary
HS
loading (4% NaCl) for 7 days. In
rATRAP
‐Tg mice, the dietary
HS
loading–mediated blood pressure elevation was suppressed compared with wild‐type mice, despite similar baseline blood pressure. Although renal angiotensin
II
level was comparable in
rATRAP
‐Tg and wild‐type mice with and without
HS
loading, urinary sodium excretion in response to
HS
loading was significantly enhanced in the
rATRAP
‐Tg mice. In addition, functional transport activity of the amiloride‐sensitive epithelial Na
+
channel was significantly decreased under saline volume–expanded conditions in
rATRAP
‐Tg mice compared with wild‐type mice, without any evident change in epithelial Na
+
channel protein expression. Plasma membrane
AT
1R expression in the kidney of
rATRAP
‐Tg mice was decreased compared with wild‐type mice.

Conclusions

These results demonstrated that distal tubule–dominant enhancement of
ATRAP
inhibits pathological renal sodium reabsorption and blood pressure elevation in response to
HS
loading. The findings suggest that
ATRAP
‐mediated modulation of sodium handling in renal distal tubules could be a target of interest in salt‐sensitive blood pressure regulation.
Magnetic Resonance Imaging in the Evaluation of Clinical Treatment of Otospongiosis
Authors: de Oliveira Vicente Andy , Chandrasekhar Sujana S. , Yamashita Helio K. , Cruz Oswaldo Laercio M. , Barros Flavia A. , Penido Norma O. 
Published: March 2015

ObjectivesTo evaluate the applicability of magnetic resonance imaging (MRI) as a method for monitoring the activity of otospongiotic lesions before and after clinical treatment.Study DesignProspective, randomized, controlled, double‐blind study.SettingOne single tertiary care institution in a large, cosmopolitan city.MethodsTwenty‐six patients (n = 42 ears) with clinical, audiometric, and tomographic diagnosis of otosclerosis were enrolled. If computed tomography (CT) demonstrated active lesions, these patients underwent MRI to detect otospongiotic foci, seen as areas of gadolinium enhancement. Patients were divided into 3 groups and received treatment with placebo, sodium alendronate, or sodium fluoride for 6 months. After this period, clinical and audiometric evaluations and a second MRI were performed. Each MRI was evaluated by both a neuroradiologist and an otolaryngologist in a subjective (visual) and objective (using specific eFilm Workstation software) manner.ResultsOtospongiosis was most predominantly identified in the region anterior to the oval window, and this site was reliable for comparing pre‐ and posttreatment scans. The patients in the alendronate and sodium fluoride groups had MRI findings that suggested a decrease in activity of otospongiotic lesions, more relevant in the alendronate group. These findings were statistically significant for both subjective and objective MRI evaluations.ConclusionsMRI shows higher sensitivity than clinical or audiometric assessment for detecting reduction in activity of otospongiosis. The objective MRI evaluation based on software analysis was the most accurate method of monitoring clinical treatment response in otospongiosis.
Sraffa’s Contributions to the Methodology of Economics
Authors: Sinha Ajit 
Published: March 2015

This article highlights some of Sraffa’s main contributions to the methodology of economics. It argues that Sraffa rejected counterfactual reasoning and hence the ‘marginal method’ of analysis. Sraffa’s theory is built solely on factual and objective information and hence it removes psychology from economics as well. Sraffa’s theory shows that considerations of demand and the condition of equilibrium of demand and supply are irrelevant to a logical theory of prices. The article goes on to show how Sraffa’s novel approach to economic theory was able to expose the logical errors of ‘marginal method’ in the Austrian and Neo-classical theories of distribution. Finally, it also raises some questions for Sraffa’s theory that need to be resolved. JEL: B2, B3, B4, B5
Methodology of the Social Sciences in the Age of Complexity: Unity, Autonomy or Integration?
Authors: Nachane Dilip M. 
Published: March 2015

The principle of ‘unity of sciences’ (comprising natural, social and human sciences) has a long history. While the term ‘unity’ lends itself to various interpretations, in recent years it is generally understood as ‘methodological unity’. In opposition to the ‘unity’ viewpoint, several social scientists have argued for the methodological autonomy of social sciences. This article attempts to analyze the reasons behind the triumph of the ‘unity’ principle around the 1960s, and how it ushered in an era of formalism in social sciences, especially economics. Dissatisfaction with formalism, in general, and Bourbakism, in particular, in recent years has prompted the search for alternative methodologies in the social sciences, with complexity theory offering much promise. JEL: A12, B41
Periaqueductal gray calcitonin gene-related peptide modulates trigeminovascular neurons
Authors: Pozo-Rosich P , Storer RJ , Charbit AR , Goadsby PJ 
Published: March 2015

Background Calcitonin gene-related peptide (CGRP) receptor antagonism is an approach to migraine therapy. The locus of action of antimigraine treatment is not resolved. The objective was to investigate CGRP receptors in the ventrolateral periaqueductal gray (vlPAG) involved in the modulation of trigeminovascular nociception by descending influences on neurotransmission. Methods The presence of calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1), which form functional CGRP receptors, was investigated. CGRP and its receptor antagonists, olcegepant and CGRP ( 8 – 37 ), were microinjected into the vlPAG while changes of neural responses in the trigeminocervical complex (TCC) were monitored. Results Immunoreactivity indicated the presence of functional CGRP receptor components in the vlPAG and adjacent mesencephalic trigeminal nucleus. Inhibition of TCC responses to stimulation of dural afferents and ophthalmic cutaneous receptive fields after microinjection of bicuculline into vlPAG indicated a connection between the vlPAG and TCC neurons. CGRP facilitated these TCC responses, whereas olcegepant and CGRP ( 8 – 37 ) decreased them. Conclusions CGRP and its receptor antagonists act on neurons in the region of vlPAG to influence nociceptive transmission in the TCC. This suggests CGRP receptor antagonists may act at loci outside of the TCC and reinforces the concept of migraine as a disorder of the brain.
Surgical Excision of Posttraumatic Ossifications at the Proximal Hamstrings in Young Athletes
Authors: Orava Sakari , Hetsroni Iftach , Marom Niv , Mann Gideon , Sarimo Janne , Ben-Zvi Ofer , Lempainen Lasse 
Published: March 2015

Background: Proximal hamstring tears can be associated with chronic disability related to the unusual formation of heterotopic ossifications. The role for operative intervention in these circumstances has not been clearly defined. Purpose/Hypothesis: The purpose of this study was to describe the surgical management of young athletes who had chronic disability related to proximal hamstring ossifications after eccentric load injuries. The hypothesis was that after surgical excision of posttraumatic heterotopic ossifications at the proximal hamstrings with concomitant repair of the tendons to the ischium, significant functional improvement with low risk of postoperative complications can be expected at minimum 2-year follow-up. Study Design: Case series; Level of evidence, 4. Methods: The cases of 11 consecutive male athletes who developed chronic disability associated with heterotopic ossifications at the proximal hamstring muscles after sports-related tears were reviewed. During surgery, the ossified mass was meticulously excised, and the tendons were debrided and fixed to the ischium. At minimum 2-year follow-up, self-reported outcome was rated as excellent, good, moderate, or poor. Operative reports and office visits were reviewed. Activity level before the injury and at latest follow-up was graded with the Tegner scale. Results: The median age at injury was 17 years (range, 13-25 years). Sports activities included ice hockey, soccer, track and field athletics, and judo. Mean interval from injury to surgery was 45 months. The smallest ossified mass was 2 × 2 × 4 cm and the largest, 3 × 4 × 9 cm. Median follow-up was 4 years (range, 2-10 years). Six patients had excellent, 1 patient had good, and 4 patients had moderate outcomes; 7 of them were able to return to preinjury activities (Tegner score, 7-10). There were 2 cases of loss of skin sensation at the posterior femoral cutaneous nerve distribution, but neither patient described this as significantly interfering with any activity. All patients had symmetric side-to-side single-legged hop test and a 5 out of 5 on hamstring muscle strength at latest follow-up. Conclusion: Heterotopic ossifications that develop at the proximal hamstrings after eccentric load injuries can be associated with significant chronic disability. These cases can be effectively treated by surgical excision of the ossified masses and concomitant debridement with suture fixation of the proximal hamstring tendons to the ischium. Return to preinjury activities is expected in the majority of these cases, with low postoperative risks.
Evaluating Eccentric Hip Torque and Trunk Endurance as Mediators of Changes in Lower Limb and Trunk Kinematics in Response to Functional Stabilization Training in Women With Patellofemoral Pain
Authors: Baldon Rodrigo de Marche , Piva Sara Regina , Scattone Silva Rodrigo , Serrão Fábio Viadanna 
Published: March 2015

Background: Altered movement patterns of the trunk and lower limbs have been associated with patellofemoral pain (PFP). It has been assumed that increasing the strength of the hip and trunk muscles would improve lower limb and trunk kinematics in these patients. However, evidence in support of that assumption is limited. Purpose: To determine whether increases in the strength of hip muscles and endurance of trunk muscles in response to functional stabilization training will mediate changes in frontal plane lower limb kinematics in patients with PFP. Study Design: Controlled laboratory study. Methods: Thirty-one female athletes were randomized to either a functional stabilization training group that emphasized strengthening of the trunk and hip muscles or a standard training group that emphasized stretching and quadriceps strengthening. Patients attended a baseline assessment session, followed by 8 weeks of intervention, and were then reassessed at the end of the intervention period. The potential mediators that were evaluated included eccentric torque of hip muscles and endurance of the trunk muscles. The outcome variables were the lower limb and trunk kinematics in the frontal plane assessed during a single-legged squat task. Results: The eccentric strength of the gluteus muscles showed a mediation effect ranging from 18% to 32% on changes to frontal plane kinematics (decreased ipsilateral trunk inclination, pelvis contralateral depression, and hip adduction excursions) observed in the functional stabilization training group after intervention. Conclusion: Although the mediation effects were small, the results suggest that improvements in the strength of the gluteus muscles can influence the frontal plane movement patterns of the lower limb and trunk in women with PFP. Clinical Relevance: Patients with PFP might benefit from strengthening of the hip muscles to improve frontal plane lower limb and trunk kinematics during functional tasks.