bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognosis of Individuals With Asymptomatic Left Ventricular Systolic Dysfunction in the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Yeboah Joseph , Rodriguez Carlos J. , Stacey Brandon , Lima Joao A. , Liu Songtao , Carr J. Jeffrey , Hundley W. Gregory , Herrington David M. 
Published: November 2012

Background—
Limited data exist on the prevalence, associations, and prognosis of individuals with asymptomatic left ventricular systolic dysfunction (ALVSD), especially in populations without previous clinical cardiovascular disease (CVD).

Methods and Results—

Kaplan-Meier and Cox proportional hazard analyses were used to assess the association between ALVSD, defined as left ventricular ejection fraction <50%, and adjudicated incident congestive heart failure (CHF), all-cause mortality, and CVD events. Of 5004 participants, 112 participants had CHF, 321 had a CVD event, and 278 died after 9 years of follow-up. The overall prevalence of ALVSD was 1.7%, with a higher prevalence in blacks (2.6%). ALVSD had a worse cardiovascular risk profile and was also associated with increased risk in unadjusted and adjusted models for incident CHF (HR [hazard ratio] [95% CI {confidence interval}]: 12.0 [7.04–20.3],
P
<0.0001 and 8.69 [4.89–15.45],
P
<0.001 respectively), CVD (HR [95% CI]: 3.32 [1.98–5.58],
P
<0.001 and 2.21 [1.30–3.73],
P
=0.003 respectively), and all-cause mortality (HR [95% CI]: 3.47 [2.03–5.94],
P
<0.0001 and 2.00 [1.13–3.54],
P
=0.017, respectively). A 10% decrement in left ventricular ejection fraction at baseline was associated with an increase in risk in unadjusted and adjusted models for clinical CHF (HR [95% CI]: 2.17 [1.82–2.63],
P
<0.0001 and 2.13 [1.73–2.51],
P
<0.001, respectively) and all-cause mortality (HR [95% CI]: 1.22 [1.05–1.41],
P
=0.009 and 1.17 [1.00–1.36],
P
=0.047, respectively). Among the subset of participants with ALVSD, the left ventricular mass index was particularly informative about risk for incident CHF (c-index=0.74).

Conclusions—
ALVSD is uncommon in individuals without previous clinical CVD, but it is associated with high risk for CHF, CVD, and all-cause mortality. The left ventricular mass index had good discrimination for incident CHF in Multi-Ethnic Study of Atherosclerosis (MESA) participants with ALVSD.
Fetal Heart Rate Predictors of Long QT Syndrome
Authors: Mitchell Jason L. , Cuneo Bettina F. , Etheridge Susan P. , Horigome Hitoshi , Weng Hsin-Yi , Benson D. Woodrow 
Published: November 2012

Background—
Fetal long QT syndrome (LQTS) is associated with complex arrhythmias including torsades de pointes and 2° atrioventricular block. Sinus bradycardia has also been associated with fetal LQTS, but little is known of this rhythm manifestation. Our purpose was to characterize the fetal heart rate (FHR)/gestational age (GA) profile of fetal LQTS.

Methods and Results—

We ascertained fetal LQTS subjects by family history (Group 1) or fetal arrhythmia referral (Group 2). We compared FHR in LQTS subjects versus normal fetuses. To identify FHR predictors of LQTS, we calculated a bradycardia index as % of LQTS FHR recordings either ≤110 beats per minute (obstetric standard) or ≤3
rd
percentile for GA. Among 42 LQTS subjects, 26 were in Group 1 and 16 in Group 2. There were 536 normal fetuses. The bradycardia index was only 15% for FHR ≤110 beats per minute, but 66% for FHR ≤3rd percentile for GA. Ten fetuses with complex arrhythmias also had severe and sustained sinus bradycardia throughout gestation. Identifying a fetal proband in Group 2 resulted in LQTS diagnosis in 9 unsuspected members of 6 families.

Conclusions—

FHR varies by GA in both normal and LQTS fetuses. Postnatal evaluation of neonates with FHR ≤3
rd
percentile for GA may improve ascertainment of LQTS in fetuses, neonates, and undiagnosed family members.
Secondary Intracerebral Hemorrhage Due to Early Initiation of Oral Anticoagulation After Ischemic Stroke
Authors: Gliem Michael , Hermsen Derik , van Rooijen Nico , Hartung Hans-Peter , Jander Sebastian 
Published: November 2012

Background and Purpose—
The uncertain risk of secondary intracerebral hemorrhage (sICH) frequently keeps clinicians from initiating oral anticoagulation (OAC) early after ischemic cardioembolic stroke. The goal of this experimental study was to determine the risk of sICH depending on the timing of OAC initiation relative to stroke onset and to address the role of hematogenous macrophages for repair processes preventing OAC-associated sICH.

Methods—
C57BL/6 mice were subjected to transient middle cerebral artery occlusion. Subgroups were treated with either the vitamin K antagonist (VKA) phenprocoumon or the direct thrombin inhibitor dabigatran etexilate. Hematogenous macrophages were depleted using intraperitoneal injections of clodronate-filled liposomes.

Results—
Time to therapeutic OAC was 48 hours with VKA and 0.5 hours with dabigatran etexilate treatment. In VKA-treated mice, the risk of sICH was high if effective OAC was already present at stroke onset or achieved within 48 hours after ischemia. With more delayed OAC, the risk of sICH rapidly decreased. Compared with VKA treatment, effective anticoagulation with dabigatran etexilate was associated with a significantly reduced extent of sICH, either if present at stroke onset or if achieved 48 hours later. Partial depletion of macrophages greatly increased the extent of OAC-associated sICH in the subacute stage of 3 to 4 days after ischemia.

Conclusions—
Our findings suggest that repair mechanisms involving hematogenous macrophages rapidly decrease the risk of OAC-associated sICH in the first days after ischemic stroke. The lower risk of sICH under dabigatran etexilate compared with VKA treatment may facilitate early initiation of OAC after cardioembolic stroke.
Pharmacotherapy of obsessive-compulsive disorder: Evidence-based treatment and beyond
Authors: Fineberg Naomi A , Reghunandanan Samar , Brown Angus , Pampaloni Ilenia 
Published: November 2012

Background: Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder associated with a significant degree of functional disability and poor quality of life. Pharmacotherapy may have a substantial impact on the course and outcome of OCD. Method: We review the evidence supporting available strategies for the pharmacological treatment of OCD. Results: Selective serotonin reuptake inhibitors (SSRIs) remain the pharmacological treatment of choice and are associated with improved health-related quality of life. Discontinuation is associated with relapse and loss of quality of life, implying treatment should continue long-term. A substantial minority of patients who fail to respond to SSRI may benefit from dose elevation or adjunctive antipsychotics, though long-term trials validating the effectiveness and tolerability of these strategies are relatively lacking. Conclusion: The pharmacological evidence-base for the treatment of OCD is becoming increasingly robust. Treatment with SSRIs and clomipramine remains uncontroversial and improvements are sustained over time. Newer compounds targeting serotonin receptor subtypes and other neurotransmitter systems are undergoing evaluation.
Evaluation of Expression Profiles of Hematopoietic Stem Cell, Endothelial Cell, and Myeloid Cell Antigens in Spontaneous and Chemically Induced Hemangiosarcomas and Hemangiomas in Mice
Authors: Kakiuchi-Kiyota Satoko , Crabbs Torrie A. , Arnold Lora L. , Pennington Karen L. , Cook Jon C. , Malarkey David E. , Cohen Samuel M. 
Published: November 2012

It is unclear whether the process of spontaneous and chemically induced hemangiosarcoma and hemangioma formation in mice involves the transformation of differentiated endothelial cells (ECs) or recruitment of multipotential bone marrow–derived hematopoietic stem cells or endothelial progenitor cells (EPCs), which show some degree of endothelial differentiation. In the present study, immunohistochemical staining for hematopoietic stem cell markers (CD45 and CD34), EC markers (vascular endothelial growth factor receptor 2 [VEGFR2], CD31, and factor VIII–related antigen), and a myeloid lineage marker (CD14) was employed to better define the origin of hemangiosarcomas and hemangiomas in mice. Staining was negative for CD45, factor VIII–related antigen, and CD14 and positive for CD34, VEGFR2, and CD31, indicating that mouse hemangiosarcomas and hemangiomas are composed of cells derived from EPCs expressing CD34, VEGFR2, and CD31 but not factor VIII–related antigen. The lack of CD45 expression suggests that mouse vascular tumors may arise from EPCs that are at a stage later than hematopoietic stem cells. Since factor VIII–related antigen expression is known to occur later than CD31 expression in EPCs, our observations may indicate that these tumor cells are arrested at a stage prior to complete differentiation. In addition, myeloid lineage cells do not appear to contribute to hemangiosarcoma and hemangioma formation in mice.
Adult Recurrent Respirator Papillomatosis
Authors: Suter‐Montano Teresita , Montaño Efraim , Martínez Carmen , Plascencia Teresita , Sepulveda Mayra T. , Rodríguez Miguel 
Published: November 2012

ObjectiveTo determine a new therapeutic approach using granulocyte monocyte–colony‐stimulating factor (GM‐CSF) and pegylated interferon alpha 2a (Peg‐IFNα‐2a) as adjuvant therapy in patients with adult recurrent respiratory papillomatosis.Study DesignDescriptive observational clinical trial.SettingDepartments of Otolaryngology and Immunology.MethodsFourteen patients with adult recurrent respiratory papillomatosis were examined regarding medical history and number of operations before and after treatment. Voice disorder and glottal stop were evaluated using the Voice‐Related Quality‐of‐Life instrument. Papilloma staging was determined using the Coltera/Derkay diagram. The patients received Peg‐IFNα‐2a at 180 mcg weekly for 6 months. In the third month, the patients began GM‐CSF treatment at 400 mcg weekly for 2 months. The patients were observed for 12 months after treatment ended.ResultsEleven patients met the study criteria; 3 patients had tracheotomies before treatment, and they were decannulated after treatment. Before treatment, the scale of voice quality ranged from 34 to 45 points (mean, 38.31). After treatment, the range was 12 to 35 points (mean, 21.09; P <. 001). Prior to therapy, the glottal stop ranged from 50% to 90% (average, 62.27%). After therapy, the range decreased to 0% to 15% (mean, 4.63%; P <. 001). The number of surgical interventions decreased. Two patients each had 1 surgical intervention after treatment began.ConclusionA new adjuvant treatment based on immunogenetic mechanisms against human laryngeal papilloma virus, with expectations of reducing disease aggressiveness and the number of operations, avoids the risks of surgery.Implication for PracticePeg‐IFNα‐2a and GM‐CSF is an adjuvant therapy for treating adult recurrent respiratory papillomatosis.
Out of the darkness: the impact of a mood disorder over time
Authors: Parker Gordon , Paterson Amelia , Fletcher Kathryn , Hyett Matthew , Blanch Bianca 
Published: November 2012

Objective: Being diagnosed with depression or bipolar disorder has a significant impact on an individual’s life. This paper reports data examining how patients view having had such a condition. Method: Patients attending the Black Dog Institute Depression Clinic were asked to complete questionnaires examining the impact of being diagnosed with a mood disorder and dealing with that condition over time. Results: Patient responses were analysed qualitatively (in terms of positive, negative and neutral responses) and their quantitative distribution was examined. Themes were relatively consistent across unipolar and bipolar patients. Negative themes included family and work consequences, social impairment and a loss of self-confidence. Positive themes included the development of stronger familial bonds, the provision of relief and hope, positive treatment outcomes and the explanatory benefits of receiving a diagnosis. Conclusions: Findings indicate quite contrasting courses reported by patients with mood disorders (irrespective of polarity), ranging from negative to very positive evaluations.
Sesamin stimulates osteoblast differentiation through p38 and ERK1/2 MAPK signaling pathways
Authors: Wanachewin Orawan , Boonmaleerat Kanchanit , Pothacharoen Peraphan , Reutrakul Vichai , Kongtawelert Prachya 
Published: November 2012

Abstract

Background
Osteoporosis is a worldwide health problem predominantly affecting post-menopausal women. Therapies aimed at increasing bone mass in osteoporetic patients lag behind comparable investigation of therapeutic strategies focusing on the bone resorption process. Sesamin, a major lignan compound found in Sesamun indicum Linn., has a variety of pharmacological effects, though its activity on bone cell function is unclear. Herein we examine the effect of this lignan on osteoblast differentiation and function.

Method
Cell cytotoxicity and proliferative in hFOB1.19 were examined by MTT and alamar blue assay up to 96 h of treatment. Gene expression of COL1, ALP, BMP-2, Runx2, OC, RANKL and OPG were detected after 24 h of sesamin treatment. ALP activity was measured at day 7, 14 and 21 of cultured. For mineralized assay, ADSCs were cultured in the presence of osteogenic media supplement with or without sesamin for 21 days and then stained with Alizarin Red S. MAPK signaling pathway activation was observed by using western blotting.

Results
Sesamin promoted the gene expression of COL1, ALP, OCN, BMP-2 and Runx2 in hFOB1.19. On the other hand, sesamin was able to up-regulate OPG and down-regulate RANKL gene expression. ALP activity also significantly increased after sesamin treatment. Interestingly, sesamin induced formation of mineralized nodules in adipose derived stem cells (ADSCs) as observed by Alizarin Red S staining; this implies that sesamin has anabolic effects both on progenitor and committed cell stages of osteoblasts. Western blotting data showed that sesamin activated phosphorylation of p38 and ERK1/2 in hFOB1.19.

Conclusions
The data suggest that sesamin has the ability to trigger osteoblast differentiation by activation of the p38 and ERK MAPK signaling pathway and possibly indirectly regulate osteoclast development via the expression of OPG and RANKL in osteoblasts. Therefore, sesamin may be a promising phytochemical that could be developed for supplementation of osteoporotic therapy.
Modulation of endogenous pathways enhances bioethanol yield and productivity in Escherichia coli
Authors: Munjal Neha , Mattam AnuJose , Pramanik Dibyajyoti , Srivastava PremShankar , Yazdani Syed Shams 
Published: November 2012

Abstract

Background

E. coli is a robust host for various genetic manipulations and has been used commonly for bioconversion of hexose and pentose sugars into valuable products. One of the products that E. coli make under fermentative condition is ethanol. However, availability of limited reducing equivalence and generation of competing co-products undermine ethanol yield and productivity. Here, we have constructed an E. coli strain to produce high yield of ethanol from hexose and pentose sugars by modulating the expression of pyruvate dehydrogenase and acetate kinase and by deleting pathways for competing co-products.

Results
The availability of reducing equivalence in E. coli was increased by inducing the expression of the pyruvate dehydrogenase (PDH) operon under anaerobic condition after replacement of its promoter with the promoters of ldhA, frdA, pflB, adhE and gapA. The SSY05 strain, where PDH operon was expressed under gapA promoter, demonstrated highest PDH activity and maximum improvement in ethanol yield. Deletion of genes responsible for competing products, such as lactate (ldhA), succinate (frdA), acetate (ack) and formate (pflB), led to significant reduction in growth rate under anaerobic condition. Modulation of acetate kinase expression in SSY09 strain regained cell growth rate and ethanol was produced at the maximum rate of 12 mmol/l/h from glucose. The resultant SSY09(pZSack) strain efficiently fermented xylose under microaerobic condition and produced 25 g/l ethanol at the maximum rate of 6.84 mmol/l/h with 97% of the theoretical yield. More importantly, fermentation of mixture of glucose and xylose was achieved by SSY09(pZSack) strain under microaerobic condition and ethanol was produced at the maximum rate of 0.7 g/l/h (15 mmol/l/h), respectively, with greater than 85% of theoretical yield.

Conclusions
The E. coli strain SSY09(pZSack) constructed via endogenous pathway engineering fermented glucose and xylose to ethanol with high yield and productivity. This strain lacking any foreign gene for ethanol fermentation is likely to be genetically more stable and therefore should be tested further for the fermentation of lignocellulosic hydrolysate at higher scale.
Left ventricular twist is load-dependent as shown in a large animal model with controlled cardiac load
Authors: A’roch Roman , Gustafsson Ulf , Poelaert Jan , Johansson Göran , Haney Michael 
Published: November 2012

Abstract

Background
Left ventricular rotation and twist can be assessed noninvasively by speckle tracking echocardiography. We sought to characterize the effects of acute load change and change in inotropic state on rotation parameters as a measure of left ventricular (LV) contractility.

Methods
Seven anesthetised juvenile pigs were studied, using direct measurement of left ventricular pressure and volume and simultaneous transthoracic echocardiography. Transient inflation of an inferior vena cava balloon (IVCB) catheter produced controlled load reduction. First and last beats in the sequence of eight were analysed with speckle tracking (STE) during the load alteration and analysed for change in rotation/twist during controlled load alteration at same contractile status. Two pharmacological inotropic interventions were also included to examine the same hypothesis in additionally conditions of increased and decreased myocardial contractility in each animal. Paired comparisons were made for different load states using the Wilcoxon’s Signed Rank test.

Results
The inferior vena cava balloon occlusion (IVCBO) load change compared for first to last beat resulted in LV twist increase (11.67° ±2.65° vs. 16.17° ±3.56° respectively, p < 0.004) during the load alteration and under adrenaline stimulation LV twist increase 12.56° ±5.1° vs. 16.57° ±4.6° (p < 0.013), and though increased, didn’t reach significance in negative inotropic condition. Untwisting rate increased significantly at baseline from −41.7°/s ±41.6°/s vs.−122.6°/s ±55.8°/s (P < 0.039) and under adrenaline stimulation untwisting rate increased (−55.3°/s ±3.8°/s vs.−111.4°/s ±24.0°/s (p < 0.05), but did not systematically changed in negative inotropic condition.

Conclusions
Peak systolic LV twist and peak early diastolic untwisting rate are load dependent. Differences in LV load should be included in the interpretation when serial measures of twist are compared.
Clinicodemographic aspect of resectable pancreatic cancer and prognostic factors for resectable cancer
Authors: Chiang Kun-Chun , Yeh Chun-Nan , Ueng Shir-Hwa , Hsu Jun-Te , Yeh Ta-Sen , Jan Yi-Yin , Hwang Tsann-Long , Chen Miin-Fu 
Published: November 2012

Abstract

Background
Pancreatic adenocarcinoma (PCA) is one of the most lethal human malignancies, and radical surgery remains the cornerstone of treatment. After resection, the overall 5-year survival rate is only 10% to 29%. At the time of presentation, however, about 40% of patients generally have distant metastases and another 40% are usually diagnosed with locally advanced cancers. The remaining 20% of patients are indicated for surgery on the basis of the results of preoperative imaging studies; however, about half of these patients are found to be unsuitable for resection during surgical exploration. In the current study, we aimed to determine the clinicopathological characteristics that predict the resectability of PCA and to conduct a prognostic analysis of PCA after resection to identify favorable survival factors.

Methods
We retrospectively reviewed the medical files of 688 patients (422 men and 266 women) who had undergone surgery for histopathologically proven PCA in the Department of Surgery at Chang Gung Memorial Hospital in Taiwan from 1981 to 2006. We compared the clinical characteristics of patients who underwent resection and patients who did not undergo resection in order to identify the predictive factors for successful resectability of PCA, and we conducted prognostic analysis for PCA after resection.

Results
A carbohydrate antigen 19–9 (CA 19–9) level of 37 U/ml or greater and a tumor size of 3 cm or more independently predicted resectability of PCA. In terms of survival after resection, PCA patients with better nutritional status (measured as having an albumin level greater than 3.5 g/dl), radical resection, early tumor stage and better-differentiated tumors were associated with favorable survival.

Conclusions
Besides traditional imaging studies, preoperative CA 19–9 levels and tumor size can also be used to determine the resectability of PCA. Better nutritional status, curative resection, early tumor stage and well-differentiated tumors predict the favorable prognosis of PCA patients after resection.
Delayed apoptosis by neutrophils from COPD patients is associated with altered bak, bcl-xl, and mcl-1 mRNA expression
Authors: Zhang Jisong , He Jian , Xia Jingwen , Chen Zhen , Chen Xiaodong 
Published: November 2012

AbstractBackgroundDelayed neutrophil apoptosis may be an important factor in the persistent inflammation associated with chronic obstructive pulmonary disease (COPD). Bcl-2 family proteins are important regulators of neutrophil apoptosis. We determined the mRNA levels of pro-apoptotic Bak and anti-aptototic Bcl-xl and Mcl-1 members of the Bcl-2 family in unstimulated peripheral blood neutrophils from patients with mild to moderate COPD and compared these to neutrophils from healthy controls.MethodsNeutrophils were isolated from peripheral blood samples of 47 COPD patients (smokers: N = 24) and 47 healthy controls (smokers: N = 24). Percentages of apoptotic cells were determined at 4, 24, and 36 h for unstimulated neutrophils culturedin vitro. Neutrophil mRNA expression of Bak, Bcl-xl, and Mcl-1 was determined by real-time polymerase chain reaction (PCR). FEV1 (% predicted) and FVC were determined by spirometry and correlations between mRNA levels and lung function parameters were determined.ResultsThe percentages of apoptotic cells among unstimulated neutrophils from COPD patients were significantly lower compared to cells from controls after 4, 24, and 36 h in culture; smoking history had only a minimal effect on these differences. Unstimulated neutrophils from COPD patients had significantly lower Bak mRNA expression and higher expressions of Bcl-xl and Mcl-1 mRNA than cells from healthy controls. Again, smoking history had only a minimal effect on these trends. Bak mRNA expression was significantly positively correlated with both % predicted FEV1 and the FEV1/FVC ratio, while Bcl-xl and Mcl-1 mRNA expressions were significantly negatively correlated with %predicted FEV1 and the FEV1/FVC ratio.ConclusionsThe genes for pro-apoptotic Bak, and anti-apoptotic Bcl-xl and Mcl-1 may be important in regulating the delayed neutrophil apoptosis observed in COPD, which may contribute to COPD pathogenesis.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1605269445677066