bluuebunny/crossref_metadata_2025_split huggingface dataset:
Corticosteroids and β2‐agonists upregulate mitogen‐activated protein kinase phosphatase 1: in vitro mechanisms
Authors: Manetsch M , Ramsay EE , King EM , Seidel P , Che W , Ge Q , Hibbs DE , Newton R , Ammit AJ 
Published: February 2012

BACKGROUND AND PURPOSEAirway remodelling is a consequence of long‐term inflammation and MAPKs are key signalling molecules that drive pro‐inflammatory pathways. The endogenous MAPK deactivator – MAPK phosphatase 1 (MKP‐1) – is a critical negative regulator of the myriad pro‐inflammatory pathways activated by MAPKs in the airway.EXPERIMENTAL APPROACHHerein we investigated the molecular mechanisms responsible for the upregulation of MKP‐1 in airway smooth muscle (ASM) by the corticosteroid dexamethasone and the β2‐agonist formoterol, added alone and in combination.KEY RESULTSMKP‐1 is a corticosteroid‐inducible gene whose expression is enhanced by long‐acting β2‐agonists in an additive manner. Formoterol induced MKP‐1 expression via the β2‐adrenoceptor and we provide the first direct evidence (utilizing overexpression of PKIα, a highly selective PKA inhibitor) to show that PKA mediates β2‐agonist‐induced MKP‐1 upregulation. Dexamethasone activated MKP‐1 transcription in ASM cells via a cis‐acting corticosteroid‐responsive region located between −1380 and −1266 bp of the MKP‐1 promoter. While the 3′‐untranslated region of MKP‐1 contains adenylate + uridylate elements responsible for regulation at the post‐transcriptional level, actinomycin D chase experiments revealed that there was no increase in MKP‐1 mRNA stability in the presence of dexamethasone, formoterol, alone or in combination. Rather, there was an additive effect of the asthma therapeutics on MKP‐1 transcription.CONCLUSIONS AND IMPLICATIONSTaken together, these studies allow us a greater understanding of the molecular basis of MKP‐1 regulation by corticosteroids and β2‐agonists and this new knowledge may lead to elucidation of optimized corticosteroid‐sparing therapies in the future.
Chemical genetics and its potential in cardiac stem cell therapy
Authors: Vieira Joaquim M , Riley Paul R 
Published: March 2012

Over the last decade or so, intensive research in cardiac stem cell biology has led to significant discoveries towards a potential therapy for cardiovascular disease; the main cause of morbidity and mortality in humans. The major goal within the field of cardiovascular regenerative medicine is to replace lost or damaged cardiac muscle and coronaries following ischaemic disease. At present, de novo cardiomyocytes can be generated either in vitro, for cell transplantation or disease modelling using directed differentiation of embryonic stem cells or induced pluripotent stem cells, or in vivo via direct reprogramming of resident adult cardiac fibroblast or ectopic stimulation of resident cardiac stem or progenitor cells. A major bottleneck with all of these approaches is the low efficiency of cardiomyocyte differentiation alongside their relative functional immaturity. Chemical genetics, and the application of phenotypic screening with small molecule libraries, represent a means to enhance understanding of the molecular pathways controlling cardiovascular cell differentiation and, moreover, offer the potential for discovery of new drugs to invoke heart repair and regeneration. Here, we review the potential of chemical genetics in cardiac stem cell therapy, highlighting not only the major contributions to the field so far, but also the future challenges.LINKED ARTICLES This article is part of a themed section on Regenerative Medicine and Pharmacology: A Look to the Future. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue‐2
Detection of Alcohol Use in the Second Trimester Among Low‐Income Pregnant Women in the Prenatal Care Settings in Jefferson County, Alabama
Authors: Li Qing , Hankin Janet , Wilsnack Sharon C. , Abel Ernest L. , Kirby Russell S. , Keith Louis G. , Obican Sarah G. 
Published: February 2012

BackgroundPrenatal alcohol use, a leading preventable cause of birth defects and developmental disabilities, remains a prevalent public health concern in the United States. This study aims to detect the proportion and correlates of prenatal alcohol use in the prenatal care settings in Alabama. Prenatal care settings were chosen because of their potential as stable locations to screen for and to reduce prenatal alcohol use within a community.MethodsWe conducted a cross‐sectional study of 3,046 women in the 22 and 23 weeks of gestation who sought prenatal care in 8 community‐based public clinics and participated in the Perinatal Emphasis Research Center project in Jefferson County, Alabama, from 1997 to 2001. Frequency and quantity of alcohol use in the past 3 months were assessed by research nurses during face‐to‐face interviews. We conducted logistic regression analyses to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of correlates of prenatal alcohol use.ResultsParticipants were predominantly young, African American, and unmarried, 86.5% on Medicaid. The proportion of alcohol use in the second trimester of pregnancy was 5.1%; 0.3% of women reported 4 or more drinks on a drinking day to research nurses. Older maternal age (OR = 1.11; 95% CI = 1.08 to 1.15), use of welfare (OR = 1.43; 95% CI = 1.02 to 2.02), and male partner–perpetrated violence (OR = 2.96; 95% CI = 1.92 to 4.56) were positively associated with elevated risk of prenatal alcohol use. Protective factors included higher levels of self‐esteem (OR = 0.94; 95% CI = 0.89 to 0.98) and more years of education (OR = 0.88; 95% CI = 0.78 to 0.98).ConclusionsPrenatal alcohol use remains a public health issue among low‐income pregnant women in Jefferson County, Alabama. Research nurses detected it in the second trimester. Future studies need to encourage screening for prenatal alcohol use in the prenatal care settings by obstetrician‐gynecologists, family physicians, nurses, and midwives. Combined interventions to educate and empower women and strengthen families are needed.
Binge Alcohol–Induced Microvesicular Liver Steatosis and Injury are Associated with Down‐Regulation of Hepatic Hdac1, 7, 9, 10, 11 and Up‐Regulation of Hdac3
Authors: Kirpich Irina , Ghare Smita , Zhang Jingwen , Gobejishvili Leila , Kharebava Giorgi , Barve Swati Joshi , Barker David , Moghe Akshata , McClain Craig J. , Barve Shirish 
Published: February 2012

BackgroundBinge, as well as chronic, alcohol consumption affects global histone acetylation leading to changes in gene expression. It is becoming increasingly evident that these histone‐associated epigenetic modifications play an important role in the development of alcohol‐mediated hepatic injury.MethodsC57BL/6 mice were gavaged 3 times (12‐hour intervals) with ethanol (EtOH; 4.5 g/kg). Hepatic histone deacetylase (Hdac) mRNAs were assessed by qRT‐PCR. Total HDAC activity was estimated by a colorimetric HDAC activity/inhibition assay. Histone acetylation levels were evaluated by Western blot. Liver steatosis and injury were evaluated by histopathology, plasma aminotransferase (ALT) activity, and liver triglyceride accumulation. Expression of fatty acid synthase (Fas) and carnitine palmitoyl transferase 1a (Cpt1a) was also examined. HDAC 9 association with Fas promoter was analyzed.ResultsBinge alcohol exposure resulted in alterations of hepatic Hdac mRNA levels. Down‐regulation of HDAC Class I (Hdac 1), Class II (Hdac 7, 9, 10), and Class IV (Hdac 11) and up‐regulation of HDAC Class I (Hdac 3) gene expression were observed. Correspondent to the decrease in HDAC activity, an increase in hepatic histone acetylation was observed. These molecular events were associated with microvesicular hepatic steatosis and injury characterized by increased hepatic triglycerides (48.02 ± 3.83 vs. 19.90 ± 3.48 mg/g liver, p < 0.05) and elevated plasma ALT activity (51.98 ± 6.91 vs. 20.8 ± 0.62 U/l, p < 0.05). Hepatic steatosis was associated with an increase in FAS and a decrease in CPT1a mRNA and protein expression. Fas promoter analysis revealed that binge EtOH treatment decreased HDAC 9 occupancy at the Fas promoter resulting in its transcriptional activation.ConclusionsDeregulation of hepatic Hdac expression likely plays a major role in the binge alcohol‐induced hepatic steatosis and liver injury by affecting lipogenesis and fatty acid β‐oxidation.
Predictors of Atrio‐Ventricular Conduction Disease, Long‐Term Outcomes in Patients with Myotonic Dystrophy Types I and II
Authors: HA ANDREW H. , TARNOPOLSKY MARK A. , BERGSTRA T. GRAHAM , NAIR GIRISH M. , AL‐QUBBANY ATIF , HEALEY JEFF S. 
Published: March 2012

Background:
Patients with myotonic dystrophy (DM) have an annual mortality of approximately 3.5%, one‐third of which is sudden cardiac death. The predictors of cardiac conduction disease in these patients are incompletely defined.
Methods:
A single‐center cohort study included 211 patients with DM type 1 (DM1) and 25 DM type 2 (DM2). A severe electrocardiogram (ECG) abnormality was defined as a PR interval of ≥240 ms or QRS duration of ≥120 ms.
Results:
A severe ECG abnormality was found in 24% of DM1 patients and 17% of DM2 patients. Among DM1 patients, those with a severe ECG abnormality were older (41.6 ± 14.6 vs 35.4 ± 12.6 years) and more likely to have hypertension (13.2% vs 4.2%, P = 0.038), heart failure (4.4% vs 0%, P = 0.056), atrial arrhythmias (6.6% vs 0.7%, P < 0.001), a higher number of trinucleotide repeats (689 ± 451 vs 474 ± 322, P = 0.01), and a family history of sudden cardiac death (26.7% vs 5.6%, P < 0.001) or pacemaker implantation (20% vs 0.7%, P < 0.001). Pacemakers or defibrillators were implanted in 14% of all patients, including 65% of patients with severe ECG abnormalities. During 57 ± 46 months, 13 patients died (1.16% per year), including three patients who died suddenly, two of whom had normally functioning pacemakers.
Conclusion:
In DM1, atrio‐ventricular conduction disease is associated with increasing age, concomitant cardiovascular disease, nucleotide repeat length, and family history. The systematic identification of conduction disease and aggressive use of prophylactic pacemakers is associated with low rate of sudden cardiac death. (PACE 2012; 35:1262–1269)
On the Varieties and Particularities of Cultural Experience
Authors: Hollan Douglas 
Published: February 2012

AbstractI argue that certain varieties of psychoanalysis and cultural phenomenology are not antithetical, and that indeed, their respective foci and methodologies each have strengths that balance out the other's limitations. Put more strongly, the two perspectives need one another. Experience should not be reduced to solipsism, nor should specific individuals, each marked by their own “pinch of destiny” and experiential heaviness, be lost in the haze of ever receding future horizons. The unfolding of self‐awareness and experience is indeed an autopoietic, recursive process whose complexities surely escape any single perspective. [cultural phenomenology, psychoanalysis, pinch of destiny, varieties of cultural experience, subjectivity]
On Inaccessibility and Vulnerability: Some Horizons of Compatibility between Phenomenology and Psychoanalysis
Authors: Throop C. Jason 
Published: February 2012

AbstractIn this article I examine the relationship between psychodynamic and phenomenological accounts of subjective experience. In so doing, my goal is not to displace the integrity of either phenomenology or psychoanalysis as historically, theoretically, and practically unique traditions in the human sciences and philosophy. It is instead to propose that a distinctly anthropological application and extension of phenomenology articulated in the context of the ethnographic encounter may reveal new points of contact between them. [ethnographic epoché, experience, intersubjectivity, phenomenology, psychoanalysis]
Commentary: Interdisciplinary Dialogue: A Site of Estrangement
Authors: Corin Ellen 
Published: February 2012

AbstractIn this article I address two broad questions: how can we best imagine a dialogue between psychoanalysis and anthropology in relation to subjectivity? And which are key elements of a psychoanalytic approach that have the potential to challenge anthropology and open interesting avenues of collaboration? In relation to the first question, I contend that dialogue has to take place not at border zones but between the most specific and conceptually advanced topics in each discipline. Building on French psychoanalysis, I emphasize several points: a dynamic notion of the Unconscious conceived as a field of struggle among competing forces, implying that the Subject is divided and nontransparent; the notion of Kulturarbeit conceived by Freud as a work of transformation of basic human drives that operates together at the individual and at the collective levels, inviting a revision of the status of culture in psychoanalysis; and an interpretative stance that builds on free associations and floating attention and operates in decomposing the apparent coherence and rationality of discourse. I present anthropology and psychoanalysis as sharing an interest in the “site of the stranger” and in the destabilizing power of Otherness. Their dialogue reveals additional textures both in ethnography and in psychoanalytic concepts. [psychoanalysis, Otherness, Kulturarbeit, interpretation, interdisciplinarity]
Solid and Liquid Phase Sintering of Submicrometer Carbides with Different Cobalt Contents
Authors: Soares Eduardo , Malheiros Luis F. , Sacramento Joaquim , Valente Manuel A. , Oliveira Filipe J. 
Published: March 2012

Hardmetal wear tools industry has observed a consistent increase in new applications and market interest for submicrometer carbides, despite the fabrication issues related with powder processing and sintering that subsist on these new materials. New technologies with lower temperature exposure and high heating rates or optimizing the current sintering process are imperative to improve their quality and consistency. As the new sintering technologies in study are costly for industrial use and still limited in terms of flexibility, we studied and developed in this work a combined sintering approach to maximize the densification of submicrometer grades (WC 0.6 μm and WC 0.4 μm) with 3.5 and 12 wt% Co while controlling the deleterious grain growth. Sintering at solid and liquid phase was performed with vacuum sintering and post‐sintering performed using Hot‐Isostatic‐Pressing. Thermal cycles were designed based on thermal analyses experiments performed to the powders allowing to design a densification process at lower temperatures to maximize microstructural homogeneity, densification, and reduce grain growth using current industrial technologies, reflected in high hardness and mechanical strength obtained.
Neuropsychological correlates of insight in obsessive–compulsive disorder
Authors: Kashyap H. , Kumar J. K. , Kandavel T. , Reddy Y. C. J. 
Published: February 2012

Kashyap H, Kumar JK, Kandavel T, Reddy YCJ. Neuropsychological correlates of insight in obsessive–compulsive disorder.Objective:  There are limited data on neuropsychological correlates of poor insight in obsessive–compulsive disorder (OCD). We hypothesize that poor insight may be associated with greater impairment in tasks of conflict resolution/response inhibition and possibly impairment in a task of verbal learning and memory.Method:  Insight and neuropsychological functions were assessed in 150 subjects with DSM‐IV OCD. The neuropsychological data of 177 healthy control subjects were used for comparison.Results:  Insight score correlated significantly with the Stroop Interference Test for conflict resolution/response inhibition (P = 0.002), and showed trends for significance with the Controlled Oral Word Association (COWA) average for verbal fluency (P = 0.021) and delayed recall on the Auditory Verbal Learning Test (AVLT) for verbal memory (P = 0.015). On regression analysis, the AVLT delayed recall, the COWA average, the Matrix score, the Yale‐Brown Obsessive–Compulsive Scale total score, and current antipsychotic use emerged as significant predictors of poorer insight.Conclusion:  Poor insight is associated with greater impairments in conflict resolution/response inhibition, verbal memory, and fluency. Individuals with poorer insight may have difficulty in appropriately processing conflicting information, updating their memory with corrective information, and then accessing this corrective information to modify their irrational beliefs.
Antisocial behavioral syndromes and 3‐year quality‐of‐life outcomes in United States adults
Authors: Goldstein R. B. , Dawson D. A. , Smith S. M. , Grant B. F. 
Published: February 2012

Goldstein RB, Dawson DA, Smith SM, Grant BF. Antisocial behavioral syndromes and 3‐year quality‐of‐life outcomes in United States adults.Objective:  To examine 3‐year quality‐of‐life (QOL) outcomes among United States adults with Diagnostic and Statistical Manual of Mental Disorders – Fourth Edition (DSM‐IV) antisocial personality disorder (ASPD), syndromal adult antisocial behavior without conduct disorder (CD) before age 15 [adulthood antisocial behavioral syndrome (AABS), not a DSM‐IV diagnosis], or no antisocial behavioral syndrome at baseline.Method:  Face‐to‐face interviews (n = 34 653). Psychiatric disorders were assessed using the Alcohol Use Disorder and Associated Disabilities Interview Schedule – DSM‐IV Version. Health‐related QOL was assessed using the Short‐Form 12‐Item Health Survey, version 2 (SF‐12v2). Other outcomes included past‐year Perceived Stress Scale‐4 (PSS‐4) scores, employment, receipt of Supplemental Security Income (SSI), welfare, and food stamps, and participation in social relationships.Results:  Antisocial personality disorder and AABS predicted poorer employment, financial dependency, social relationship, and physical health outcomes. Relationships of antisociality to SSI and food stamp receipt and physical health scales were modified by baseline age. Both antisocial syndromes predicted higher PSS‐4, AABS predicted lower SF‐12v2 Vitality, and ASPD predicted lower SF‐12v2 Social Functioning scores in women.Conclusion:  Similar prediction of QOL by ASPD and AABS suggests limited utility of requiring CD before age 15 to diagnose ASPD. Findings underscore the need to improve prevention and treatment of antisocial syndromes.
Assessing cognitive changes in the elderly: Reliable Change Indices for the Mini‐Mental State Examination
Authors: Stein J. , Luppa M. , Maier W. , Wagner M. , Wolfsgruber S. , Scherer M. , Köhler M. , Eisele M. , Weyerer S. , Werle J. , Bickel H. , Mösch E. , Wiese B. , Prokein J. , Pentzek M. , Fuchs A. , Leicht H. , König H.‐H. , Riedel‐Heller S. G. ,   for the AgeCoDe Study Group
Published: February 2012

Stein J, Luppa M, Maier W, Wagner M, Wolfsgruber S, Scherer M, Köhler M, Eisele M, Weyerer S, Werle J, Bickel H, Mösch E, Wiese B, Prokein J, Pentzek M, Fuchs A, Leicht H, König H‐H, Riedel‐Heller SG for the AgeCoDe Study Group. Assessing cognitive changes in the elderly: Reliable Change Indices for the Mini‐Mental State Examination.Objective:  The diagnosis of dementia includes evidence of decline in cognitive functioning over time measured by objective cognitive tasks. Normative data for changes adjusted for the impact of socio‐demographic factors on cognitive test performance are lacking to interpret changes in Mini‐Mental State Examination (MMSE) test scores.Method:  As part of the German Study on Ageing, Cognition and Dementia in Primary Care Patients (AgeCoDe Study), a sample of 1090 cognitively healthy individuals, aged 75 years and older, was assessed at 1.5‐year intervals over a period of 4.5 years using the MMSE. Age‐ and education‐specific Reliable Change Indices (RCIs) were computed.Results:  Age and education were significantly associated with MMSE test performance, and gender indicated no impact. Across different age and education subgroups, changes from at least 2 up to 3 points indicated significant (i.e., reliable) changes in MMSE test scores at the 90% confidence level. Furthermore, the calculation of RCIs for individual patients is demonstrated.Conclusion:  This study provides age‐ and education‐specific MMSE norms based upon RCI methods to interpret cognitive changes in older age groups. The computation of RCI scores improves the interpretation of changes in MMSE test scores by controlling for measurement error, practice effects, or regression to the mean.
Chlorhexidine decreases the risk of ventilator‐associated pneumonia in intensive care unit patients: a randomized clinical trial
Authors: Özçaka Ö. , Başoğlu Ö. K. , Buduneli N. , Taşbakan M. S. , Bacakoğlu F. , Kinane D. F. 
Published: February 2012

Özçaka Ö, Başoğlu ÖK, Buduneli N, Taşbakan MS, Bacakoğlu F, Kinane DF. Chlorhexidine decreases the risk of ventilator‐associated pneumonia in intensive care unit patients: a randomized clinical trial. J Periodont Res 2012; 47: 584–592. © 2012 John Wiley & Sons A/SBackground and Objective:  The aim was to evaluate whether oral swabbing with 0.2% chlorhexidine gluconate (CHX) decreases the risk of ventilator‐associated pneumonia (VAP) in intensive care unit (ICU) patients.Material and Methods:  Sixty‐one dentate patients scheduled for invasive mechanical ventilation for at least 48 h were included in this randomized, double‐blind, controlled study. As these patients were variably incapacitated, oral care was provided by swabbing the oral mucosa four times/d with CHX in the CHX group (29 patients) and with saline in the control group (32 patients). Clinical periodontal measurements were recorded, and lower‐respiratory‐tract specimens were obtained for microbiological analysis on admission and when VAP was suspected. Pathogens were identified by quantifying colonies using standard culture techniques.Results:  Ventilator‐associated pneumonia developed in 34/61 patients (55.7%) within 6.8 d. The VAP development rate was significantly higher in the control group than in the CHX group (68.8% vs. 41.4%, respectively; p = 0.03) with an odds ratio of 3.12 (95% confidence interval = 1.09–8.91). Acinetobacter baumannii was the most common pathogen (64.7%) of all species identified. There were no significant differences between the two groups in clinical periodontal measurements, VAP development time, pathogens detected or mortality rate.Conclusion:  The finding of the present study, that oral care with CHX swabbing reduces the risk of VAP development in mechanically ventilated patients, strongly supports its use in ICUs and indeed the importance of adequate oral hygiene in preventing medical complications.