bluuebunny/crossref_metadata_2025_split huggingface dataset:
Highly Potent Activation of Nrf2 by Topical Tricyclic Bis(Cyano Enone): Implications for Protection against UV Radiation during Thiopurine Therapy
Authors: Kalra Sukirti , Knatko Elena V. , Zhang Ying , Honda Tadashi , Yamamoto Masayuki , Dinkova-Kostova Albena T. 
Published: June 2012

Abstract
Chronic treatment with azathioprine, a highly effective anti-inflammatory and immunosuppressive agent, profoundly increases the risk for development of unusually aggressive cutaneous squamous cell carcinoma. Its ultimate metabolite, 6-thioguanine (6-TG) nucleotide, is incorporated in DNA of skin cells, and upon exposure to UVA radiation, causes oxidative stress, followed by damage of DNA and associated proteins. The acetylenic tricyclic bis(cyano enone) TBE-31 is a strong inhibitor of inflammation and a potent inducer of the Keap1/Nrf2/ARE pathway, which orchestrates the expression of a large network of cytoprotective genes. We now report that long-term (five days per week for four weeks) topical daily applications of small (200 nmol) quantities of TBE-31 cause a robust systemic induction of the Keap1/Nrf2/ARE pathway and decreases the 6-TG incorporation in DNA of skin, blood, and liver of azathioprine-treated mice, indicating extraordinary bioavailability and efficacy. In addition, TBE-31, at nanomolar concentrations, protects cells with 6-TG in their genomic DNA against oxidative stress caused by UVA radiation through induction of the Keap1/Nrf2/ARE pathway. At the same 6-TG DNA levels, Keap1-knockout cells, in which the pathway is constitutively upregulated, are highly resistant to UVA radiation–induced oxidative stress. The protective effects of both the Keap1-knockout genotype and TBE-31 are completely lost in the absence of transcription factor Nrf2. Our findings suggest that compounds of this kind are excellent candidates for mechanism-based chemoprotective agents against conditions in which oxidative stress and inflammation underlie disease pathogenesis. Moreover, their potential skin patch incorporation for transdermal delivery is an exciting possibility. Cancer Prev Res; 5(7); 973–81. ©2012 AACR.
Common Variation in Fatty Acid Genes and Resuscitation From Sudden Cardiac Arrest
Authors: Johnson Catherine O. , Lemaitre Rozenn N. , Fahrenbruch Carol E. , Hesselson Stephanie , Sotoodehnia Nona , McKnight Barbara , Rice Kenneth M. , Kwok Pui-Yan , Siscovick David S. , Rea Thomas D. 
Published: June 2012

Background—
Fatty acids provide energy and structural substrates for the heart and brain and may influence resuscitation from sudden cardiac arrest (SCA). We investigated whether genetic variation in fatty acid metabolism pathways was associated with SCA survival.

Methods and Results—

Subjects (mean age, 67 years; 80% male, white) were out-of-hospital SCA patients found in ventricular fibrillation in King County, WA. We compared subjects who survived to hospital admission (n=664) with those who did not (n=689), and subjects who survived to hospital discharge (n=334) with those who did not (n=1019). Associations between survival and genetic variants were assessed using logistic regression adjusting for age, sex, location, time to arrival of paramedics, whether the event was witnessed, and receipt of bystander cardiopulmonary resuscitation. Within-gene permutation tests were used to correct for multiple comparisons. Variants in 5 genes were significantly associated with SCA survival. After correction for multiple comparisons, single-nucleotide polymorphisms in
ACSL1
and
ACSL3
were significantly associated with survival to hospital admission. Single-nucleotide polymorphisms in
ACSL3, AGPAT3, MLYCD,
and
SLC27A6
were significantly associated with survival to hospital discharge.

Conclusions—
Our findings indicate that variants in genes important in fatty acid metabolism are associated with SCA survival in this population.
Cardiovascular Remodeling in Response to Long-Term Exposure to Fine Particulate Matter Air Pollution
Authors: Wold Loren E. , Ying Zhekang , Hutchinson Kirk R. , Velten Markus , Gorr Matthew W. , Velten Christina , Youtz Dane J. , Wang Aixia , Lucchesi Pamela A. , Sun Qinghua , Rajagopalan Sanjay 
Published: June 2012

Background—
Air pollution is a pervasive environmental health hazard that occurs over a lifetime of exposure in individuals from many industrialized societies. However, studies have focused primarily on exposure durations that correspond to only a portion of the lifespan. We therefore tested the hypothesis that exposure over a considerable portion of the lifespan would induce maladaptive cardiovascular responses.

Methods and Results—

C57BL/6 male mice were exposed to concentrated ambient particles <2.5
µ
m (particulate matter, PM or PM
2.5
) or filtered air (FA), 6 h/d, 5 d/wk, for 9 months. Assessment of cardiac contractile function, coronary arterial flow reserve, isolated cardiomyocyte function, expression of hypertrophic markers, calcium handling proteins, and cardiac fibrosis were then performed. Mean daily concentrations of PM
2.5
in the exposure chamber versus ambient daily PM
2.5
concentration at the study site were 85.3 versus 10.6
µ
g/m

3

(7.8-fold concentration), respectively. PM
2.5
exposure resulted in increased hypertrophic markers leading to adverse ventricular remodeling characterized by myosin heavy chain (MHC) isoform switch and fibrosis, decreased fractional shortening (39.8 ± 1.4 FA versus 27.9 ± 1.3 PM, FS%), and mitral inflow patterns consistent with diastolic dysfunction (1.95 ± 0.05 FA versus 1.52 ± 0.07 PM, E/A ratio). Contractile reserve to dobutamine was depressed (62.3 ± 0.9 FA versus 49.2 ± 1.5 PM, FS%) in response to PM
2.5
without significant alterations in maximal vasodilator flow reserve. In vitro cardiomyocyte function revealed depressed peak shortening (8.7 ± 0.6 FA versus 7.0 ± 0.4 PM, %PS) and increased time-to-90% shortening (72.5 ± 3.2 FA versus 82.8 ± 3.2 PM, ms) and relengthening (253.1 ± 7.9 FA versus 282.8 ± 9.3 PM, ms), which were associated with upregulation of profibrotic markers and decreased total antioxidant capacity. Whole-heart SERCA2a levels and the ratio of
α
/
β
-MHC were both significantly decreased (
P
<0.05) in PM
2.5
-exposed animals, suggesting a switch to fetal programming.

Conclusions—

Long-term exposure to environmentally relevant concentrations of PM
2.5
resulted in a cardiac phenotype consistent with incipient heart failure.
Mechanistic Evaluation of Echocardiographic Dyssynchrony Indices
Authors: Lumens Joost , Leenders Geert E. , Cramer Maarten J. , De Boeck Bart W. L. , Doevendans Pieter A. , Prinzen Frits W. , Delhaas Tammo 
Published: June 2012

Background—
The power of echocardiographic dyssynchrony indices to predict response to cardiac resynchronization therapy (CRT) appears to vary between indices and between studies. We investigated whether the variability of predictive power between the dyssynchrony indices can be explained by differences in their operational definitions.

Methods and Results—

In 132 CRT-candidates (left ventricular [LV] ejection fraction, 19 ± 6%; QRS width, 170 ± 22 ms), 4 mechanical dyssynchrony indices (septal systolic rebound stretch [SRSsept], interventricular mechanical dyssynchrony [IVMD], septal-to-lateral peak shortening delay [Strain-SL], and septal-to-posterior wall motion delay [SPWMD]) were quantified at baseline. CRT response was quantified as 6-month percent change of LV end-systolic volume. Multiscale computer simulations of cardiac mechanics and hemodynamics were used to assess the relationships between dyssynchrony indices and CRT response within wide ranges of dyssynchrony of LV activation and reduced contractility. In patients, SRSsept showed best correlation with CRT response followed by IVMD, Strain-SL, and SPWMD (
R
=−0.56, −0.50, −0.48, and −0.39, respectively; all
P
<0.01). In patients and simulations, SRSsept and IVMD showed a continuous linear relationship with CRT response, whereas Strain-SL and SPWMD showed discontinuous relationships characterized by data clusters. Model simulations revealed that this data clustering originated from the complex multipeak pattern of septal strain and motion. In patients and simulations with (simulated) LV scar, SRSsept and IVMD retained their linear relationship with CRT response, whereas Strain-SL and SPWMD did not.

Conclusions—
The power to predict CRT response differs between indices of mechanical dyssynchrony. SRSsept and IVMD better represent LV dyssynchrony amenable to CRT and better predict CRT response than the indices assessing time-to-peak deformation or motion.
Endothelial Cell–Specific FGD5 Involvement in Vascular Pruning Defines Neovessel Fate in Mice
Authors: Cheng Caroline , Haasdijk Remco , Tempel Dennie , van de Kamp Esther H. M. , Herpers Robert , Bos Frank , Den Dekker Wijnand K. , Blonden Lau A.J. , de Jong Renate , Bürgisser Petra E. , Chrifi Ihsan , Biessen Erik A.L. , Dimmeler Stefanie , Schulte-Merker Stefan , Duckers Henricus J. 
Published: June 2012

Background—
New vessel formation contributes to organ development during embryogenesis and tissue repair in response to mechanical damage, inflammation, and ischemia in adult organisms. Early angiogenesis includes formation of an excessive primitive network that needs to be reorganized into a secondary vascular network with higher hierarchical structure. Vascular pruning, the removal of aberrant neovessels by apoptosis, is a vital step in this process. Although multiple molecular pathways for early angiogenesis have been identified, little is known about the genetic regulators of secondary network development.

Methods and Results—

Using a transcriptomics approach, we identified a new endothelial specific gene named FYVE, RhoGEF, and PH domain–containing 5 (FGD5) that plays a crucial role in vascular pruning. Loss- and gain-of-function studies demonstrate that FGD5 inhibits neovascularization, indicated by in vitro tube-formation, aortic-ring, and coated-bead assays and by in vivo coated-bead plug assays and studies in the murine retina model. FGD5 promotes apoptosis-induced vaso-obliteration via induction of the hey1-p53 pathway by direct binding and activation of cdc42. Indeed, FGD5 correlates with apoptosis in endothelial cells during vascular remodeling and was linked to rising p21
CIP1
levels in aging mice.

Conclusion—
We have identified FGD5 as a novel genetic regulator of vascular pruning by activation of endothelial cell–targeted apoptosis.
Maternal Experience of Interactions With Providers Among Mothers With Milk Supply Concern
Authors: Flaherman Valerie J. , Hicks Katherine G. , Cabana Michael D. , Lee Kathryn A. 
Published: June 2012

Background. Milk supply concern is the most common reason given by mothers for discontinuing breastfeeding. Objectives. To describe maternal experiences of interactions with health care providers related to milk supply. Patients and methods. Ten focus groups (N = 56 participants) were conducted among mothers who had had milk supply concern in the first month after birth. Group sessions were audio-recorded, transcribed, coded, and analyzed to identify themes. Results. Interactions regarding milk supply concern evoked strong emotions, including gratitude, guilt, disappointment, and fear, and measurement of infant weight was frequently reported as a trigger for these emotions. Some mothers reported that experiencing “pressure” and “guilt” when providers emphasized exclusive breastfeeding led to suboptimal breastfeeding choices. Conclusions. Interactions with providers about milk supply concern evoke strong emotions among mothers. Providers should be aware that how they communicate routine advice regarding infant weight and formula may have unintended consequences, including discontinuation of breastfeeding.
The Capability of Static and Dynamic Features to Distinguish Competent From Genuinely Expert Practitioners in Pediatric Diagnosis
Authors: Loveday Thomas , Wiggins Mark W. , Searle Ben J. , Festa Marino , Schell David 
Published: June 2012

Children’s Hospital at Westmead, Sydney, Australia Objective: The authors describe the development of a new, more objective method of distinguishing experienced competent nonexpert from expert practitioners within pediatric intensive care. Background: Expert performance involves the acquisition and use of refined feature-event associations (cues) in the operational environment. Competent nonexperts, although experienced, possess rudimentary cue associations in memory. Thus, they cannot respond as efficiently or as reliably as their expert counterparts, particularly when key diagnostic information is unavail- able, such as that provided by dynamic cues. Method: This study involved the application of four distinct tasks in which the use of relevant cues could be expected to increase both the accuracy and the efficiency of diagnostic performance. These tasks included both static and dynamic stimuli that were varied systematically. A total of 50 experienced pediatric intensive staff took part in the study. Results: The sample clustered into two levels across the tasks: Participants who performed at a consistently high level throughout the four tasks were labeled experts, and participants who performed at a lower level throughout the tasks were labeled competent nonexperts. The groups differed in their responses to the diagnostic scenarios presented in two of the tasks and their ability to maintain performance in the absence of dynamic features. Conclusion: Experienced pediatricians can be decomposed into two groups on the basis of their capacity to acquire and use cues; these groups differ in their diagnostic accuracy and in their ability to maintain performance in the absence of dynamic features. Application: The tasks may be used to identify practitioners who are failing to acquire expertise at a rate consistent with their experience, position, or training. This information may be used to guide targeted training efforts.
Role of vinyl thiethoxy silane grafted onto fluororubber in compatibilization of fluororubber and silicone rubber blends
Authors: Guo Jianhua , Zeng Xingrong , Li Hongqiang , Luo Quankun 
Published: June 2012

The blends of fluororubber (FKM) and silicone rubber (MVQ) were prepared by the incorporation of fumed silica using vinyl thiethoxy silane (VTEO) grafted onto FKM (FKM- g-VTEO) as a compatibilizer. The effect of the compatibilizer loading on the curing characteristics, mechanical properties, heat aging properties and oil resistance was investigated. Dynamic mechanical analysis indicates that FKM- g-VTEO acts as a compatibilizer in the FKM/MVQ blends. The tensile properties and oil resistance of FKM/MVQ blends increase with the increasing loading of FKM- g-VTEO up to 9 phr and the heat aging properties increase with the addition of the compatibilizer up to 6 phr. The fracture surfaces of tensile samples were observed by scanning electron microscopy (SEM). SEM of the tensile fracture surface of the blends and rubber–filler interaction studies shows that the presence of FKM- g-VTEO enhances the interfacial interaction of fumed silica and rubber matrix.
Marx, Minsky, and the Great Recession
Authors: Ivanova Maria N. 
Published: June 2012

This paper challenges prevailing accounts of the financial origins of the Great Recession by engaging two distinct theoretical perspectives originating in Karl Marx and Hyman Minsky. The paper argues that the domestic and global, financial and “real” origins of the crisis are deeply intertwined as the financialization of the U.S. economy and the globalization of production are inextricably linked. Thus, the merits of a Marxian interpretation of the crisis surpass those of the Minskyan for at least two reasons. First, the structural causes of the Great Recession lie not in the U.S. financial sector but in the system of globalized production which reflects the growing unevenness of capital accumulation on a planetary scale, manifested in the global imbalances. Second, the belief that social problems have monetary or financial origins, and could be resolved by tinkering with money and financial institutions, is fundamentally flawed, for the very recurrence of crises attests to the limits of fiscal and monetary policies as means to ensure “balanced” accumulation. JEL Codes: E40, E50, E60, F30, F40, F50
Interleukin-18, interleukin-8, and CXCR2 and the risk of silicosis
Authors: Mohebbi Iraj , Rad Isa Abdi , Bagheri Morteza 
Published: June 2012

Molecular mechanisms in the pathogenesis of silicosis are not fully understood. Exposure to crystalline silica leads to the activation of signaling pathways controlling the production and secretion of inflammatory mediators. Inflammatory cytokines are noted as important candidate genes for fibrotic lung diseases. Cytokines, chemokines, and variations of their genes have been associated with upregulation or downregulation of chronic inflammatory mediators. Variations in the interleukin (IL)-18, IL-8 and chemokine receptor CXCR2 genes are believed to influence the risk of silicosis in stone-grinding factory workers in Iran. Allele-specific oligonucleotide polymerase chain reaction (PCR) procedure was carried out for IL-18 −137 and IL-18 −607, meanwhile touchdown PCR was performed for IL-8 −251 and CXCR2 +1208 genotyping. Variation in genotypic and allelic frequencies was not statistically different among cases versus controls ( p > 0.05). These findings indicated for the first time that IL-18 −137, IL-18 −607, IL-8 −251, and CXCR2 +1208 are suggested not to influence the risk of silicosis in tested occupational group.
The protective effects of carnosine in alcohol-induced hepatic injury in rats
Authors: Baykara B , Mıcılı S Cilaker , Tugyan K , Tekmen I , Bagriyanik HA , Sonmez U , Sonmez A , Oktay G , Yener N , Ozbal S 
Published: June 2012

Consumption of alcohol leads to oxidative stress in liver by inducing lipid peroxidation. The aim of this study was to investigate the effects of carnosine (CAR) in alcohol-induced liver injury by biochemical and histomorphological evaluations. The rats were divided into four groups, namely, control group, alcohol (AL) group, CAR group and AL + CAR group. Three doses of ethanol (5 g/kg, 25% (v/v) in distilled water) were given by nasogastric catheter for twice-a-day. CAR (100 mg/kg) was given 1 h before the administration of ethanol using the same method. Levels of alanine aminotransferase, aspartate aminotransferase, myeloperoxidase and malondialdehyde were significantly increased in the AL group compared with control, CAR and AL + CAR groups. Glutathione level was significantly decreased in the AL group, while it was increased in the AL + CAR group. Immunoreactivity of caspase-3 and bax increased in the hepatocytes of AL group when compared with control and AL + CAR groups. Expression of bcl-2 was decreased in AL group than AL + CAR group. Under electron microscopy, dense mitochondria, accumulation of lipid, sinusoidal dilatation, vacuolization and decrease in the number of microvilli were observed in AL group, while these findings were markedly less in the AL + CAR group. In conclusion, pretreatment of CAR is effective for recovering biochemical alterations and morphologic damage in the liver of rats treated with ethanol.
Oxidative stress and tissue pathology caused by subacute exposure to ammonium acetate in rats and their response to treatments with alpha-ketoglutarate and N-acetyl cysteine
Authors: Satpute RM , Lomash Vinay , Hariharakrishnan J , Rao Pooja , Singh Poonam , Gujar NL , Bhattacharya Rahul 
Published: June 2012

Ammonia is a widely used industrial chemical that is recognized as a potent neurotoxin and environmental pollutant. The present study addresses the oxidative stress and tissue pathology caused by 4 weeks of exposure to ammonium acetate (AMA; 100 mg/kg daily; orally) in rats, and their response to oral treatments with alpha-ketoglutarate (A-KG; 1.0 g/kg), a potential cyanide antidote, and/or N-acetyl cysteine (NAC; 10 mg/kg), an antioxidant. The organ–body weight index of brain and liver was significantly increased by AMA but kidney was unaffected. Also, plasma ammonia levels were significantly elevated without any concomitant change in blood gas status and hematology but levels of catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and reduced glutathione (GSH) in the brain and liver were diminished, accompanied by elevated levels of malondialdehyde. Levels of glutathione disulfide (GSSG) were unaffected, but the ratio of GSH:GSSG was reduced. Plasma alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase and total bilirubin were raised but urea, uric acid and creatinine levels were not altered. AMA also caused temporal, hepatic and renal pathology. However, the renal pathology was not supported by any biochemical alterations. A-KG or NAC alone afforded less protection against AMA as compared to both given together. The protective efficacy of A-KG can be ascribed to its ability to detoxify ammonia and additionally both A-KG and NAC have antioxidant properties as well. The study suggests a new therapeutic regimen for ammonia poisoning.
Role of aqueous Bryoria capillaris (Ach.) extract as a genoprotective agent on imazalil-induced genotoxicity in vitro
Authors: Turkez Hasan , Aydin Elanur , Aslan Ali 
Published: June 2012

In recent years, a number of studies have suggested that lichens might be the easily accessible sources of natural drugs that could be used as a possible food supplement. Extensive research is being carried out to explore the importance of lichen species, which are known to contain a variety of pharmacological active compounds. On the other hand, imazalil (IMA), a commonly used fungicide in both agricultural and clinical domains, is suspected to produce very serious toxic effects in vertebrates. In this context, the antigenotoxic effect of aqueous Bryoria capillaris (Ach.) extract (BCE) was studied against the genotoxic damage induced by IMA on cultured human lymphocytes using chromosomal aberrations (CA) and micronucleus (MN) as cytogenetic parameters. Human peripheral lymphocytes were treated in vitro with varying concentrations of BCE (5, 10, 25, 50 and 100 µg/mL), tested in combination with IMA (336 µg/mL). BCE alone was not genotoxic, and when combined with IMA treatment, it reduced the frequency of CAs and the rates of MN. A clear dose-dependent decrease in the genotoxic damage of IMA was observed, suggesting a genoprotective role of BCE. The results of the present study suggest that this plant extract per se do not have genotoxic potential, but can modulate the genotoxicity of IMA on peripheral human lymphocytes in vitro. In conclusion, our findings may have an important application in the protection of cultured human lymphocyte from the genetic damage and side effects induced by agricultural and medical chemicals that are hazardous to people.
Latino Values in the Context of Palliative Care
Authors: Gaudio F. Del , Hichenberg S. , Eisenberg M. , Kerr E. , Zaider T. I. , Kissane D. W. 
Published: June 2012

Background: Clinicians meet a variety of ethnicities among patients and families in hospice programs. This article focuses on Latino families. Methods: Within a controlled trial of family therapy in the context of palliative care, 17 families identified as Hispanic. Five were examined qualitatively herein. Results: A synopsis of each family’s narrative is presented here. Patterns of strong family loyalty ( Familismo), the gender roles of Machismo and Marianismo, the importance of family tradition, expectations about caregiving, and the place of faith and religion emerged as prominent and able potentially to impact on the therapy. Conclusions: Family therapists need to be thoughtful about cultural issues as they strive to support families.