bluuebunny/crossref_metadata_2025_split huggingface dataset:
Akt1 Regulates Vascular Smooth Muscle Cell Apoptosis Through FoxO3a and Apaf1 and Protects Against Arterial Remodeling and Atherosclerosis
Authors: Tucka Joanna , Yu Haixiang , Gray Kelly , Figg Nichola , Maguire Janet , Lam Brian , Bennett Martin , Littlewood Trevor 
Published: September 2014

Objective—
Vascular smooth muscle cell (VSMC) apoptosis occurs at low levels in atherosclerotic plaques and in vessel remodeling; however, the consequences and mediators of these levels are not known. Akt1 protects against VSMC apoptosis largely through inactivating target proteins such as forkhead class O transcription factor 3a (FoxO3a), but Akt1 signaling is reduced and FoxO3a activity is increased in human atherosclerosis. We therefore sought to determine whether inhibition of VSMC apoptosis via Akt1 activation regulates vessel remodeling and atherogenesis and to identify FoxO3a target proteins that mediate VSMC apoptosis.

Approach and Results—
We generated mice that express an Akt1 protein that can be activated specifically in arterial VSMCs. Akt1 activation did not affect normal arteries, but inhibited VSMC apoptosis and negative remodeling after carotid ligation, indicating that VSMC apoptosis is a major determinant of vessel caliber after changes in flow. Akt1 activation inhibited VSMC apoptosis during atherogenesis and increased relative fibrous cap area in plaques. Microarray studies identified multiple FoxO3a-regulated genes involved in VSMC apoptosis, including apoptotic protease activating factor 1 as a novel target. Apoptotic protease activating factor 1 mediated the proapoptotic activity of FoxO3a, was increased in human atherosclerosis, but reduced by Akt1 activity in vivo.

Conclusions—
Akt1 is a major regulator of VSMC survival in vivo during vessel remodeling and atherogenesis, mediated in large part through inhibition of FoxO3a and its downstream genes, including apoptotic protease activating factor 1. Our data suggest that even the low-level VSMC apoptosis seen during changes in flow determines vessel wall structure and promotes fibrous cap thinning during atherogenesis.
Multidisciplinary Group Clinic Appointments
Authors: Smith Carol E. , Piamjariyakul Ubolrat , Wick Jo A. , Spertus John A. , Russell Christy , Dalton Kathleen M. , Elyachar Andrea , Vacek James L. , Reeder Katherine M. , Nazir Niaman , Ellerbeck Edward F. 
Published: September 2014

Background—
This trial tested the effects of multidisciplinary group clinic appointments on the primary outcome of time to first heart failure (HF) rehospitalization or death.

Methods and Results—

HF patients (n=198) were randomly assigned to standard care or standard care plus multidisciplinary group clinics. The group intervention consisted of 4 weekly clinic appointments and 1 booster clinic at month 6, where multidisciplinary professionals engaged patients in HF self-management skills. Data were collected prospectively for 12 months beginning after completion of the first 4 group clinic appointments (2 months post randomization). The intervention was associated with greater adherence to recommended vasodilators (
P
=0.04). The primary outcome (first HF-related hospitalization or death) was experienced by 22 (24%) in the intervention group and 30 (28%) in standard care. The total HF-related hospitalizations, including repeat hospitalizations after the first time, were 28 in the intervention group and 45 among those receiving standard care. The effects of treatment on rehospitalization varied significantly over time. From 2 to 7 months post randomization, there was a significantly longer hospitalization-free time in the intervention group (Cox proportional hazard ratio=0.45 (95% confidence interval, 0.21–0.98;
P
=0.04). No significant difference between groups was found from month 8 to 12 (hazard ratio=1.7; 95% confidence interval, 0.7–4.1).

Conclusions—
Multidisciplinary group clinic appointments were associated with greater adherence to selected HF medications and longer hospitalization-free survival during the time that the intervention was underway. Larger studies will be needed to confirm the benefits seen in this trial and identify methods to sustain these benefits.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00439842.
Relationship Between Physical Activity and Heart Failure Risk in Women
Authors: Rahman Iffat , Bellavia Andrea , Wolk Alicja 
Published: September 2014

Background—
Physical activity is a modifiable health-related behavior shown to be associated with reduced risk of coronary heart disease and stroke. There is some evidence that this could also be the case for heart failure. We investigated whether total physical activity, as well as different domains of physical activity, was associated with heart failure risk.

Methods and Results—
The Swedish Mammography Cohort was used in which 27 895 women were followed up from 1997 to 2011. First event of heart failure was ascertained through the Swedish National Patient Register and Cause of Death Register. Cox proportional hazards regression analyses were conducted to estimate multivariable-adjusted hazard ratios and 95% confidence intervals. We also analyzed survival percentiles by applying Laplace regression. During an average follow-up time of 13 years (369 207 person-years), we ascertained 2402 first events of heart failure hospitalizations and deaths. We found that moderate to high levels of total physical activity were associated with a reduced risk of future heart failure. When looking into different domains of physical activity, walking/bicycling >20 minutes/d was associated with 29% lower risk of heart failure (95% confidence interval, −36% to −21%), when investigating survival percentiles this could be translated into 18 months longer heart failure–free survival.

Conclusions—
Our study shows that physical activity could protect against heart failure in women. When looking closer into different domains of physical activity, walking or biking ≥20 minutes every day was associated with the largest risk reduction of heart failure.
Energy Metabolic Reprogramming in the Hypertrophied and Early Stage Failing Heart
Authors: Lai Ling , Leone Teresa C. , Keller Mark P. , Martin Ola J. , Broman Aimee T. , Nigro Jessica , Kapoor Kapil , Koves Timothy R. , Stevens Robert , Ilkayeva Olga R. , Vega Rick B. , Attie Alan D. , Muoio Deborah M. , Kelly Daniel P. 
Published: September 2014

Background—
An unbiased systems approach was used to define energy metabolic events that occur during the pathological cardiac remodeling en route to heart failure (HF).

Methods and Results—
Combined myocardial transcriptomic and metabolomic profiling were conducted in a well-defined mouse model of HF that allows comparative assessment of compensated and decompensated (HF) forms of cardiac hypertrophy because of pressure overload. The pressure overload data sets were also compared with the myocardial transcriptome and metabolome for an adaptive (physiological) form of cardiac hypertrophy because of endurance exercise training. Comparative analysis of the data sets led to the following conclusions: (1) expression of most genes involved in mitochondrial energy transduction were not significantly changed in the hypertrophied or failing heart, with the notable exception of a progressive downregulation of transcripts encoding proteins and enzymes involved in myocyte fatty acid transport and oxidation during the development of HF; (2) tissue metabolite profiles were more broadly regulated than corresponding metabolic gene regulatory changes, suggesting significant regulation at the post-transcriptional level; (3) metabolomic signatures distinguished pathological and physiological forms of cardiac hypertrophy and served as robust markers for the onset of HF; and (4) the pattern of metabolite derangements in the failing heart suggests bottlenecks of carbon substrate flux into the Krebs cycle.

Conclusions—
Mitochondrial energy metabolic derangements that occur during the early development of pressure overload–induced HF involve both transcriptional and post-transcriptional events. A subset of the myocardial metabolomic profile robustly distinguished pathological and physiological cardiac remodeling.
Novel Role of Kallistatin in Vascular Repair by Promoting Mobility, Viability, and Function of Endothelial Progenitor Cells
Authors: Gao Lin , Li Pengfei , Zhang Jingmei , Hagiwara Makoto , Shen Bo , Bledsoe Grant , Chang Eugene , Chao Lee , Chao Julie 
Published: September 2014

Background
Kallistatin exerts pleiotropic activities in inhibiting inflammation, apoptosis, and oxidative stress in endothelial cells. Because endothelial progenitor cells (EPCs) play a significant role in vascular repair, we investigated whether kallistatin contributes to vascular regeneration by enhancing EPC migration and function.

Methods and Results

We examined the effect of endogenous kallistatin on circulating EPCs in a rat model of vascular injury and the mechanisms of kallistatin on EPC mobility and function in vitro. In deoxycorticosterone acetate–salt hypertensive rats, we found that kallistatin depletion augmented glomerular endothelial cell loss and diminished circulating EPC number, whereas kallistatin gene delivery increased EPC levels. In cultured EPCs, kallistatin significantly reduced tumor necrosis factor‐α–induced apoptosis and caspase‐3 activity, but kallistatin's effects were blocked by phosphoinositide 3‐kinase inhibitor (LY294002) and nitric oxide (NO) synthase inhibitor (
l
‐NAME). Kallistatin stimulated the proliferation, migration, adhesion and tube formation of EPCs; however, kallistatin's actions were abolished by LY294002,
l
‐NAME, endothelial NO synthase–small interfering RNA, constitutively active glycogen synthase kinase‐3β, or vascular endothelial growth factor antibody. Kallistatin also increased Akt, glycogen synthase kinase‐3β, and endothelial NO synthase phosphorylation; endothelial NO synthase, vascular endothelial growth factor, and matrix metalloproteinase‐2 synthesis and activity; and NO and vascular endothelial growth factor levels. Kallistatin's actions on phosphoinositide 3‐kinase–Akt signaling were blocked by LY294002,
l
‐NAME, and anti–vascular endothelial growth factor antibody.

Conclusions
Endogenous kallistatin plays a novel role in protection against vascular injury in hypertensive rats by promoting the mobility, viability, and vasculogenic capacity of EPCs via enhancing NO and vascular endothelial growth factor levels through activation of phosphoinositide 3‐kinase–Akt signaling. Kallistatin therapy may be a promising approach in the treatment of vascular diseases.
Racial/ethnic differences in HIV-related knowledge among young men who have sex with men and their association with condom errors
Authors: Garofalo Robert , Gayles Travis , Bottone Paul Devine , Ryan Dan , Kuhns Lisa M , Mustanski Brian 
Published: September 2014

Objective: HIV disproportionately affects young men who have sex with men, and knowledge about HIV transmission is one factor that may play a role in high rate of infections for this population. This study examined racial/ethnic differences in HIV knowledge among young men who have sex with men in the USA and their correlation to condom usage errors. Design: Participants included an ethnically diverse sample of 344 young men who have sex with men screened from an ongoing longitudinal cohort study. Eligible participants were between the ages of 16 and 20 years, born male and had previously had at least one sexual encounter with a man and/or identify as gay or bisexual. This analysis is based on cross-sectional data collected at the baseline interview using computer-assisted self-interviewing (CASI) software. Setting: Chicago, IL, USA Method: We utilised descriptive and inferential statistics, including analysis of variance (ANOVA) and Tukey’s post hoc analysis to assess differences in HIV knowledge by level of education and race/ethnicity, and negative binomial regression to determine whether HIV knowledge was associated with condom errors while controlling for age, education and race/ethnicity. Results: The study found that Black men who have sex with men scored significantly lower (average score = 67%; p < .05) than their White counterparts (average score = 83%) on a measure of HIV knowledge (mean difference = 16.1%, p < .001). Participants with less than a high school diploma and those with a high school diploma/general education diploma (GED) only had lower knowledge scores, on average (66.4% and 69.9%, respectively) than participants who had obtained post-high school education (78.1%; mean difference = 11.7% and 8.2%, respectively, ps < .05). In addition, controlling for age, race and level of education, higher HIV knowledge scores were associated with fewer condom errors (Exp B = .995, confidence interval [CI] = 0.992–0.999, p < .05). Conclusion: Findings stress the need for increased attention to HIV transmission–related educational activities targeting the social realities and unique risk mechanisms of young men who have sex with men.
Effects of cannabidiol in the treatment of patients with Parkinson’s disease: An exploratory double-blind trial
Authors: Chagas Marcos Hortes N , Zuardi Antonio W , Tumas Vitor , Pena-Pereira Márcio Alexandre , Sobreira Emmanuelle T , Bergamaschi Mateus M , dos Santos Antonio Carlos , Teixeira Antonio Lucio , Hallak Jaime EC , Crippa José Alexandre S 
Published: September 2014

Introduction: Parkinson’s disease (PD) has a progressive course and is characterized by the degeneration of dopaminergic neurons. Although no neuroprotective treatments for PD have been found to date, the endocannabinoid system has emerged as a promising target. Methods: From a sample of 119 patients consecutively evaluated in a specialized movement disorders outpatient clinic, we selected 21 PD patients without dementia or comorbid psychiatric conditions. Participants were assigned to three groups of seven subjects each who were treated with placebo, cannabidiol (CBD) 75 mg/day or CBD 300 mg/day. One week before the trial and in the last week of treatment participants were assessed in respect to (i) motor and general symptoms score (UPDRS); (ii) well-being and quality of life (PDQ-39); and (iii) possible neuroprotective effects (BDNF and H1-MRS). Results: We found no statistically significant differences in UPDRS scores, plasma BDNF levels or H1-MRS measures. However, the groups treated with placebo and CBD 300 mg/day had significantly different mean total scores in the PDQ-39 ( p = 0.05). Conclusions: Our findings point to a possible effect of CBD in improving quality of life measures in PD patients with no psychiatric comorbidities; however, studies with larger samples and specific objectives are required before definitive conclusions can be drawn.
The Effect of Rosuvastatin on Low-Density Lipoprotein Subfractions in Patients With Impaired Fasting Glucose
Authors: Rizos Christos V. , Kostapanos Michael S. , Rizos Evangelos C. , Tselepis Alexandros D. , Elisaf Moses S. 
Published: September 2014

Background: Prediabetes substantially increases cardiovascular risk. We examined the effect of rosuvastatin on the quantity and quality of low-density lipoprotein cholesterol (LDL-C) in patients with dyslipidemia having impaired fasting glucose (IFG) compared to normoglycemic patients with dyslipidemia. Methods: This was a prospective observational study including patients with dyslipidemia and IFG (IFG group, n = 49) matched with normoglycemic patients with dyslipidemia (control group, n = 64). Study participants, following dietary intervention, were prescribed rosuvastatin 10 or 20 mg/d to achieve LDL-C goals. Baseline as well as 24 weeks posttreatment changes in the serum lipid profile were evaluated. Moreover, analysis of the LDL subfraction profile was conducted using a polyacrylamide tube gel electrophoresis method. Results: Similar effects were observed in lipid profile in both treatment groups. Patients with IFG experienced a greater decrease in the cholesterol concentration of small dense LDL particles (−65.7%, P < .001 vs baseline) compared to controls (−38.5%, P < .001 vs baseline; P = .018 vs patients with IFG). There was no significant difference in the changes of cholesterol concentration of large and buoyant LDL particles in the IFG group when compared to the control group. A greater increase in the mean LDL particle size (+1.5%, P < .001 vs baseline) was noted in the IFG group compared to the control group at 24 weeks (+0.4%, P = .028 vs baseline; P = .008 vs IFG group). Conclusion: Targeting dyslipidemia with rosuvastatin was associated with more favorable changes in the LDL subfraction profile in patients with IFG compared to normoglycemic ones.
Plasma renin level and aldosterone to renin ratio are associated with presence of carotid plaques in patients with stable coronary artery disease
Authors: Lee Min-Yi , Lai Wen-Ter 
Published: September 2014

Introduction: We aimed to determine the association between plasma aldosterone and renin levels as well as their ratios with carotid plaques in patients with coronary artery disease (CAD). Materials and methods: Carotid intima-media thickness (IMT) and plaque score were evaluated in 111 patients with stable CAD. Plasma renin and aldosterone levels were measured in all patients. Aldosterone to renin ratio (ARR) was calculated. All patients were categorized into: Group 1 (normal coronary angiography), Group 2 (patients had CAD but without carotid plaque) and Group 3 (patients had CAD and at least one carotid plaque). Results: Renin levels are significantly higher in Group 3 than in Group 1 and 2. ARR was significantly lower in Group 3 than in Group 1 and 2. Renin levels were found to be positively correlated with carotid IMT and plaque score but ARR was inversely associated with carotid IMT and plaque score. Renin levels and ARR are independently associated with presence of carotid plaque in CAD patients (OR 1.124, CI 1.021–1.237, p = 0.017 and OR 0.906, CI 0.839–0.978, p = 0.011, adjusted for age, respectively). Conclusions: Plasma renin and ARR but not aldosterone are independently associated with presence of carotid plaques in CAD patients. Hence, the linkage between aldosterone and renin plays a more important role than aldosterone alone in carotid atherosclerosis.
Health-related quality of life and long-term morbidity and mortality in patients hospitalised with systolic heart failure
Authors: Berg Jenny , Lindgren Peter , Kahan Thomas , Schill Owe , Persson Hans , Edner Magnus , Mejhert Märit 
Published: September 2014

Background Health-related quality of life has been shown to impact prognosis in chronic heart failure, however with limited long-term follow-up. We analysed data spanning 8–12 years to assess the impact of health-related quality of life using the Nottingham Health Profile on first hospitalisation and mortality, for cardiovascular and all causes. Methods We included 208 patients aged ≥60 years with New York Heart Association class II–IV and left ventricular systolic dysfunction hospitalised in Stockholm during 1996–99. Data on hospital admissions, discharge diagnoses and date and cause of death were collected from administrative databases and medical records until 2007. Cox proportional hazard models were employed to analyse the time to event for mortality and hospitalisations. Results Mean age was 76 years, 58% were male and mean ejection fraction was 34%. Median survival was 4.6 years (range 6 days–11.9 years); 148 patients died. All-cause and cardiovascular mortality were determined by physical mobility (by Nottingham Health Profile), age, gender, diuretic dose and haemoglobin level. Glomerular filtration rate was significant for all-cause mortality, while atrioventricular plane displacement was predictive of cardiovascular mortality. Median time to first all-cause and cardiovascular hospitalisation was 5.7 and 11.2 months, respectively. Time to first all-cause hospitalisation was determined by physical mobility, emotional reactions, age, gender and haemoglobin level, while only physical mobility and diuretic dose predicted time to first cardiovascular hospitalisation. Conclusions In conclusion, in patients with systolic chronic heart failure, physical mobility as part of health-related quality of life is an independent prognostic marker for cardiovascular and all-cause readmissions and mortality over 12 years.
Stress and DNA repair biology of the Fanconi anemia pathway
Authors: Longerich Simonne , Li Jian , Xiong Yong , Sung Patrick , Kupfer Gary M. 
Published: September 2014

Abstract
Fanconi anemia (FA) represents a paradigm of rare genetic diseases, where the quest for cause and cure has led to seminal discoveries in cancer biology. Although a total of 16 FA genes have been identified thus far, the biochemical function of many of the FA proteins remains to be elucidated. FA is rare, yet the fact that 5 FA genes are in fact familial breast cancer genes and FA gene mutations are found frequently in sporadic cancers suggest wider applicability in hematopoiesis and oncology. Establishing the interaction network involving the FA proteins and their associated partners has revealed an intersection of FA with several DNA repair pathways, including homologous recombination, DNA mismatch repair, nucleotide excision repair, and translesion DNA synthesis. Importantly, recent studies have shown a major involvement of the FA pathway in the tolerance of reactive aldehydes. Moreover, despite improved outcomes in stem cell transplantation in the treatment of FA, many challenges remain in patient care.
Autosomal-dominant B-cell deficiency with alopecia due to a mutation in NFKB2 that results in nonprocessable p100
Authors: Lee Cindy Eunhee , Fulcher David A. , Whittle Belinda , Chand Rochna , Fewings Nicole , Field Matthew , Andrews Daniel , Goodnow Christopher C. , Cook Matthew C. 
Published: September 2014

Key Points
A novel NFKB2 mutation confers a severe B-cell deficiency, but antibody production is partially preserved. Unprocessed p100 results in an IκB-like action on the canonical nuclear factor-κB pathway.
Efficacy, safety and tolerability of linezolid for the treatment of XDR-TB: a study in China
Authors: Tang Shenjie , Yao Lan , Hao Xiaohui , Zhang Xia , Liu Gang , Liu Xin , Wu Meiying , Zen Linhai , Sun Hua , Liu Yidian , Gu Jin , Lin Feishen , Wang Xiafang , Zhang Zhanjun 
Published: September 2014

Linezolid may be effective in treating multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis. We conducted a prospective, multicentre, randomised study to further evaluate the efficacy, safety and tolerability of linezolid in patients with extensively drug-resistant tuberculosis in China.65 patients who had culture-positive sputum for extensively drug-resistant tuberculosis were randomly assigned to a linezolid therapy group or a control group. Patients in the two groups adopted a 2-year individually based chemotherapy regimen. The linezolid therapy group was given linezolid at a start dose of 1200 mg per day for a period of 4–6 weeks and this was then followed by a dose of 300–600 mg per day.The proportion of sputum culture conversions in the linezolid therapy group was 78.8% by 24 months, significantly higher than that in the control group (37.6%, p<0.001). The treatment success rate in linezolid therapy group was 69.7%, significantly higher than that in the control group (34.4%, p=0.004). 27 (81.8%) patients had clinically significant adverse events in the linezolid group, of whom 25 (93%) patients had events that were possibly or probably related to linezolid. Most adverse events resolved after reducing the dosage of linezolid or temporarily discontinuing linezolid.Linezolid containing chemotherapy for treatment of extensively drug-resistant tuberculosis may significantly promote cavity closure, increase sputum culture-conversion rate and improve treatment success rate.