bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vacuum‐assisted deliveries and the risk of obstetric anal sphincter injuries—a retrospective register‐based study in Finland
Authors: Räisänen S , Vehviläinen‐Julkunen K , Cartwright R , Gissler M , Heinonen S 
Published: August 2012

Please cite this paper as: Räisänen S, Vehviläinen‐Julkunen K, Cartwright R, Gissler M, Heinonen S. Vacuum‐assisted deliveries and the risk of obstetric anal sphincter injuries—a retrospective register‐based study in Finland. BJOG 2012;119:1370–1378.Objectives  To identify and quantify the risks of obstetric anal sphincter injury (OASIS) separately in nulliparae, including women admitted for a first vaginal delivery after a previous caesarean section for their first birth, and multiparae delivered by vacuum extraction in Finland where the type of episiotomy is exclusively lateral.Design  A retrospective population‐based register study.Methods  Nulliparous and multiparous women with OASIS were compared separately with women without OASIS using stepwise logistic regression analysis.Main outcome measures  Risk of OASIS.Results  Among a sample of 16 802 women whose infants were delivered by vacuum extraction between 2004 and 2007, the incidence of OASIS was significantly higher among nulliparous women (475 of 13 981, 3.4%) than multiparous women (40 of 2821, 1.4%), with adjusted odds ratio 2.44 (95% CI 1.77–3.39). Lateral episiotomy was associated with 46% decreased incidence of OASIS (adjusted odds ratio 0.54, 95% CI 0.42–0.70) in nulliparae delivered by vacuum extraction. There was no statistically significant association for multiparous women. An increase of 1000 g in birthweight increased the OASIS incidence 2.10‐fold for nulliparae and 2.83‐fold for multiparae.Conclusions  Nulliparous women with infants delivered by vacuum extraction had an increased risk of OASIS compared with multiparous women. Lateral episiotomy was associated with a decreased incidence of OASIS, especially in women with large babies and long second stage. These results support liberal use of lateral episiotomy at vacuum extraction for nulliparous women at high risk of OASIS, but the role of episiotomy should be re‐investigated in interventional randomised trials.
Inhibition of Yersinia pestisDNA adenine methyltransferase in vitro by a stibonic acid compound: identification of a potential novel class of antimicrobial agents
Authors: McKelvie JC , Richards MI , Harmer JE , Milne TS , Roach PL , Oyston PCF 
Published: August 2012

Background and PurposeMultiple antibiotic resistant strains of plague are emerging, driving a need for the development of novel antibiotics effective against Yersinia pestis. DNA adenine methylation regulates numerous fundamental processes in bacteria and alteration of DNA adenine methlytransferase (Dam) expression is attenuating for several pathogens, including Y. pestis. The lack of a functionally similar enzyme in humans makes Dam a suitable target for development of novel therapeutics for plague.Experimental ApproachCompounds were evaluated for their ability to inhibit Dam activity in a high‐throughput screening assay. DNA was isolated from Yersinia grown in the presence of lead compounds and restricted to determine the effect of inhibitors on DNA methylation. Transcriptional analysis was undertaken to determine the effect of an active inhibitor on virulence‐associated phenotypes.Key ResultsWe have identified a series of aryl stibonic acids which inhibit Dam in vitro. The most active, 4‐stibonobenzenesulfonic acid, exhibited a competitive mode of inhibition with respect to DNA and a Ki of 6.46 nM. One compound was found to inhibit DNA methylation in cultured Y. pestis. The effects of this inhibition on the physiology of the cell were widespread, and included altered expression of known virulence traits, including iron acquisition and Type III secretion.Conclusions and ImplicationsWe have identified a novel class of potent Dam inhibitors. Treatment of bacterial cell cultures with these inhibitors resulted in a decrease in DNA methylation. Expression of virulence factors was affected, suggesting these inhibitors may attenuate bacterial infectivity and function as antibiotics.
Exacerbation of DSS‐induced colitis in mice lacking kinin B1 receptors through compensatory up‐regulation of kinin B2 receptors: the role of tight junctions and intestinal homeostasis
Authors: Marcon R , Claudino RF , Dutra RC , Bento AF , Schmidt EC , Bouzon ZL , Sordi R , Morais RLT , Pesquero JB , Calixto JB 
Published: August 2012

Background and PurposeKinins are pro‐inflammatory peptides that are released during tissue injury, including that caused by inflammatory bowel disease. Herein, we assessed the role and underlying mechanisms through which the absence of kinin B1 receptors exacerbates the development of dextran sulfate sodium (DSS)‐induced colitis in mice.Experimental ApproachB1 and B2 receptor antagonists and B1 receptor knockout mice (B1−/−) were used to assess the involvement of B1 and B2 receptor signalling in a DSS‐colitis. B1 receptor, B2 receptor, occludin and claudin‐4 expression, cytokine levels and cell permeability were evaluated in colon from wild‐type (WT) and B1−/− mice.Key ResultsDSS‐induced colitis was significantly exacerbated in B1−/− compared with WT mice. IL‐1β, IFN‐γ, keratinocyte‐derived chemokine and macrophage inflammatory protein‐2 were markedly increased in the colon from DSS‐treated B1−/− compared with DSS‐treated WT mice. Treatment of WT mice with a selective B1 receptor antagonist, DALBK or SSR240612, had no effect on DSS‐induced colitis. Of note, B2 receptor mRNA expression was significantly up‐regulated in colonic tissue from the B1−/− mice after DSS administration. Moreover, treatment with a selective B2 receptor antagonist prevented the exacerbation of colitis in B1−/− mice following DSS administration. The water‐ or DSS‐treated B1−/− mice showed a decrease in occludin gene expression, which was partially prevented by the B2 receptor antagonist.Conclusions and ImplicationsA loss of B1 receptors markedly exacerbates the severity of DSS‐induced colitis in mice. The increased susceptibility of B1−/− may be associated with compensatory overexpression of B2 receptors, which, in turn, modulates tight junction expression.
Pharmacological effects of 3‐iodothyronamine (T1AM) in mice include facilitation of memory acquisition and retention and reduction of pain threshold
Authors: Manni Maria Elena , De Siena Gaetano , Saba Alessandro , Marchini Maja , Landucci Elisa , Gerace Elisabetta , Zazzeri Marina , Musilli Claudia , Pellegrini‐Giampietro Domenico , Matucci Rosanna , Zucchi Riccardo , Raimondi Laura 
Published: August 2012

Background and Purpose3‐Iodothyronamine (T1AM), an endogenous derivative of thyroid hormones, is regarded as a rapid modulator of behaviour and metabolism. To determine whether brain thyroid hormone levels contribute to these effects, we investigated the effect of central administration of T1AM on learning and pain threshold of mice either untreated or pretreated with clorgyline (2.5 mg·kg−1, i.p.), an inhibitor of amine oxidative metabolism.Experimental ApproachT1AM (0.13, 0.4, 1.32 and 4 μg·kg−1) or vehicle was injected i.c.v. into male mice, and after 30 min their effects on memory acquisition capacity, pain threshold and curiosity were evaluated by the following tests: passive avoidance, licking latency on the hot plate and movements on the hole‐board platform. Plasma glycaemia was measured using a glucorefractometer. Brain levels of triiodothyroxine (T3), thyroxine (T4) and T1AM were measured by HPLC coupled to tandem MS. ERK1/2 activation and c‐fos expression in different brain regions were evaluated by Western blot analysis.ResultsT1AM improved learning capacity, decreased pain threshold to hot stimuli, enhanced curiosity and raised plasma glycaemia in a dose‐dependent way, without modifying T3 and T4 brain concentrations. T1AM effects on learning and pain were abolished or significantly affected by clorgyline, suggesting a role for some metabolite(s), or that T1AM interacts at the rapid desensitizing target(s). T1AM activated ERK in different brain areas at lower doses than those effective on behaviour.Conclusions And ImplicationsT1AM is a novel memory enhancer. This feature might have important implications for the treatment of endocrine and neurodegenerative‐induced memory disorders.
Carbamazepine directly inhibits adipocyte differentiation through activation of the ERK 1/2 pathway
Authors: Turpin E , Muscat A , Vatier C , Chetrite G , Corruble E , Moldes M , Fève B 
Published: August 2012

Background and PurposeCarbamazepine (CBZ), known for its anti‐epileptic, analgesic and mood‐stabilizing properties, is also known to induce weight gain but the pathophysiology of this adverse effect is still largely unknown. We tested the hypothesis that CBZ could have a direct effect on adipocyte development and metabolism.Experimental ResearchWe studied the effects of CBZ on morphological biochemical and molecular markers of adipogenesis, using several pre‐adipocyte murine cell lines (3T3‐L1, 3T3‐F442A and T37i cells) and primary cultures of human pre‐adipocytes. To delineate the mechanisms underlying the effect of CBZ, clonal expansion of pre‐adipocytes, pro‐adipogenic transcription factors, glucose uptake and lipolysis were also examined.Key ResultsCBZ strongly inhibited pre‐adipocyte differentiation and triglyceride accumulation in a time‐ and dose‐dependent manner in all models. Pleiotropic mechanisms were at the basis of the inhibitory effects of CBZ on adipogenesis and cell lipid accumulation. They included suppression of both clonal expansion and major adipogenic transcription factors such as PPAR‐γ and CCAAT/enhancer binding protein‐α, activation of basal lipolysis and decrease in insulin‐stimulated glucose transport.Conclusions and ImplicationsThe effect of CBZ on adipogenesis involves activation of the ERK1/2 pathway. Our results show that CBZ acts directly on pre‐adipocytes and adipocytes to alter adipose tissue development and metabolism.
Use and Misuse of Multivariable Approaches in Interventional Cardiology Studies on Drug‐Eluting Stents: A Systematic Review
Authors: D’ASCENZO FABRIZIO , CAVALLERO ERIKA , BIONDI‐ZOCCAI GIUSEPPE , MORETTI CLAUDIO , OMEDÈ PIERLUIGI , BOLLATI MARIO , CASTAGNO DAVIDE , MODENA MARIA GRAZIA , GAITA FIORENZO , SHEIBAN IMAD 
Published: August 2012

Aims:
Randomized clinical trials (RCTs) are the most reliable evidence, even if they require important resource and logistic efforts. Large, cost‐free and real‐world datasets may be easily accessed yielding to observational studies, but such analyses often lead to problematic results in the absence of careful methods, especially from a statistic point of view. We aimed to appraise the performance of current multivariable approaches in the estimation of causal treatment and effects in studies focusing on drug‐eluting stents (DES).
Methods and Results:
Pertinent studies published in the literature were searched, selected, abstracted, and appraised for quality and validity features. Six studies with a logistic regression were included, all of them reporting more than 10 events for covariates and different length of follow‐up, with an overall low risk of bias. Most of the 15 studies with a Cox proportional hazard analysis had a different follow‐up, with less than 10 events for covariates, yielding an overall low or moderate risk of bias. Sixteen studies with propensity score were included: the most frequent method for variable selection was logistic regression, with underlying differences in follow‐up and less than 10 events for covariate in most of them. Most frequently, calibration appraisal was not reported in the studies, on the contrary of discrimination appraisal, which was more frequently performed. In seventeen studies with propensity and matching, the latter was most commonly performed with a nearest neighbor‐matching algorithm yet without appraisal in most of the studies of calibration or discrimination. Balance was evaluated in 46% of the studies, being obtained for all variables in 48% of them.
Conclusions:
Better exploitation and methodological appraisal of multivariable analysis is needed to improve the clinical and research impact and reliability of nonrandomized studies. (J Interven Cardiol 2012;25:611–621)
Measure of the QT–RR Dynamic Coupling in Patients with the Long QT Syndrome
Authors: Halamek Josef , Couderc Jean‐Philippe , Jurak Pavel , Vondra Vlastimil , Zareba Wojciech , Viscor Ivo , Leinveber, M.Sc. Pavel 
Published: August 2012

Background: The patients with the long QT syndrome type‐1 (LQT‐1) have an impaired adaptation of the QT interval to heart rate changes. Yet, the description of the dynamic QT–RR coupling in genotyped LQT‐1 has never been thoroughly investigated.Method: We propose a method to model the dynamic QT–RR coupling by defining a transfer function characterizing the relationship between a QT interval and its previous RR intervals measured from ambulatory Holter recordings. Three parameters are used to characterize the QT–RR coupling: a fast gain (GainF), a slow gain (GainL), and a time constant (τ). We investigated the values of these parameters across genders, and in genotyped LQT‐1 patients with normal QTc interval duration (QTc  <  470 ms).Results: The QT–RR dynamic profiles are significantly different between LQT‐1 patients (97) and controls (154): LQT‐1 have longer QTc interval (453  ± 35 vs. 384  ± 26 ms, P  <  0.0001), and an increased dependency of the QT interval to previous RR changes revealed by a larger GainL (0.22  ± 0.06 vs. 0.18  ± 0.07, P  <  0.0001) and GainF (0.05  ± 0.02 vs. 0.03  ± 0.01, P  <  0.0001). Importantly, LQT‐1 patients have a faster QT dynamic response to previous RR changes described by τ: 122  ± 44 vs. 172  ± 92 beats (P  <  0.0001). This faster QT dynamic response of the QT–RR dynamic coupling remained in LQT‐1 patients with QTc in a normal range (<430 ms).Conclusions: The measurement of QT–RR dynamic coupling could be used in patients suspected to carry a concealed form of the LQT‐1 syndrome, or to provide insights into the types of arrhythmogenic triggers a patient may be prone to.
Recovery of Heart Rate Variability and Ventricular Repolarization Indices Following Exercise
Authors: Lahiri Marc K. , Chicos Alexandru , Bergner Dan , Ng Jason , Banthia Smirti , Wang Norman C. , Subačius Haris , Kadish Alan H. , Goldberger Jeffrey J. 
Published: August 2012

Background: There is a heightened risk of sudden cardiac death related to exercise and the postexercise recovery period, but the precise mechanism is unknown. We have demonstrated that sympathoexcitation persists for ≥45 minutes after exercise in normals and subjects with coronary artery disease (CAD). The purpose of this study is to determine whether this persistent sympathoexcitation is associated with persistent heart rate variability (HRV) and ventricular repolarization changes in the postexercise recovery period.Methods and Results: Twenty control subjects (age 50.7 ± 1.4 years), 68 subjects (age 58.2 ± 1.5 years) with CAD and preserved left ventricular ejection fraction (LVEF), and 18 subjects (age 57.6 ± 2.4 years) with CAD and depressed LVEF underwent a 16‐minute submaximal bicycle exercise protocol with continuous ECG monitoring. QT and RR intervals were measured in recovery to calculate the time dependent corrected QT intervals (QTc), the QT–RR relationship, and HRV. QTc was dependent on the choice of rate correction formula. There were no differences in QT–RR slopes among the three groups in early recovery. HRV recovered quickly in controls, more slowly in those with CAD‐preserved LVEF, and to a lesser extent in those with CAD‐depressed LVEF.Conclusion: Despite persistent sympathoexcitation for the 45‐minute recovery period, ventricular repolarization changes do not persist for that long and HRV changes differ by group. Additional understanding of the dynamic changes in cardiac parameters after exercise is needed to explore the mechanism of increased sudden cardiac death risk at this time.
Prognostic Significance of T‐Wave Amplitude in Lead aVR on the Admission Electrocardiography in Patients with Anterior Wall ST‐Elevation Myocardial Infarction Treated by Primary Percutaneous Intervention
Authors: Ayhan Erkan , Isık Turgay , Uyarel Huseyin , Ergelen Mehmet , Cicek Gokhan , Ghannadian Bahman , Eren Mehmet 
Published: August 2012

Background: T‐wave positivity in aVR lead patients with heart failure and anterior wall old ST‐segment elevation myocardial infarction (STEMI) are shown to have a higher frequency of cardiovascular mortality, although the effects on patients with STEMI treated with primary percutaneous coronary intervention (PCI) has not been investigated. In this study, we sought to determine the prognostic value of T wave in lead aVR on admission electrocardiography (ECG) for in‐hospital mortality in patients with anterior wall STEMI treated with primary PCI.Methods: After exclusion, 169 consecutive patients with anterior wall STEMI (mean age: 55 ± 12.9 years; 145 men) undergoing primary PCI were prospectively enrolled in this study. Patients were classified as a T‐wave positive (n = 53, group 1) or T‐wave negative (n = 116, group 2) in aVR based upon the admission ECG. All patients were evaluated with respect to clinical features, primary PCI findings, and in‐hospital clinical results.Results: T‐wave positive patients who received primary PCI were older, multivessel disease was significantly more frequent and the duration of the patient's hospital stay was longer than T‐wave negative patients. In‐hospital mortality tended to be higher in the group 1 when compared with group 2 (7.5% vs 1.7% respectively, P = 0.05). After adjusting the baseline characteristics, positive T wave remained an independent predictor of in hospital mortality (odds ratio: 4.41; 95% confidence interval 1.2–22.1, P = 0.05).Conclusions: T‐wave positivity in lead aVR among patients with an anterior wall STEMI treated with primary PCI is associated with an increase in hospital cardiovascular mortality.
QT Interval and Long‐Term Mortality Risk in the Framingham Heart Study
Authors: Noseworthy Peter A. , Peloso Gina M. , Hwang Shih‐Jen , Larson Martin G. , Levy Daniel , O’Donnell Christopher J. , Newton‐Cheh Christopher 
Published: August 2012

Background: The association between QT interval and mortality has been demonstrated in large, prospective population‐based studies, but the strength of the association varies considerably based on the method of heart rate correction. We examined the QT‐mortality relationship in the Framingham Heart Study (FHS).Methods: Participants in the first (original cohort, n = 2,365) and second generation (offspring cohort, n = 4,530) cohorts were included in this study with a mean follow up of 27.5 years. QT interval measurements were obtained manually using a reproducible digital caliper technique.Results: Using Cox proportional hazards regression adjusting for age and sex, a 20 millisecond increase in QTc (using Bazett's correction; QT/RR1/2 interval) was associated with a modest increase in risk of all‐cause mortality (HR 1.14, 95% CI 1.10–1.18, P < 0.0001), coronary heart disease (CHD) mortality (HR 1.15, 95% CI 1.05–1.26, P = 0.003), and sudden cardiac death (SCD, HR 1.19, 95% CI 1.03–1.37, P = 0.02). However, adjustment for heart rate using RR interval in linear regression attenuated this association. The association of QT interval with all‐cause mortality persisted after adjustment for cardiovascular risk factors, but associations with CHD mortality and SCD were no longer significant.Conclusion: In FHS, there is evidence of a graded relation between QTc and all‐cause mortality, CHD death, and SCD; however, this association is attenuated by adjustment for RR interval. These data confirm that using Bazett's heart rate correction, QTc, overestimates the association with mortality. An association with all‐cause mortality persists despite a more complete adjustment for heart rate and known cardiovascular risk factors.
Determinants of survival in patients receiving dialysis in Libya
Authors: Alashek Wiam A. , McIntyre Christopher W. , Taal Maarten W. 
Published: August 2012

AbstractMaintenance dialysis is associated with reduced survival when compared with the general population. In Libya, information about outcomes on dialysis is scarce. This study, therefore, aimed to provide the first comprehensive analysis of survival in Libyan dialysis patients. This prospective multicenter study included all patients in Libya who had been receiving dialysis for >90 days in June 2009. Sociodemographic and clinical data were collected upon enrolment and survival status after 1 year was determined. Two thousand two hundred seventy‐three patients in 38 dialysis centers were followed up for 1 year. The majority were receiving hemodialysis (98.8%). Sixty‐seven patients were censored due to renal transplantation, and 46 patients were lost to follow‐up. Thus, 2159 patients were followed up for 1 year. Four hundred fifty‐eight deaths occurred, (crude annual mortality rate of 21.2%). Of these, 31% were due to ischemic heart disease, 16% cerebrovascular accidents, and 16% due to infection. Annual mortality rate was 0% to 70% in different dialysis centers. Best survival was in age group 25 to 34 years. Binary logistic regression analysis identified age at onset of dialysis, physical dependency, diabetes, and predialysis urea as independent determinants of increased mortality. Patients receiving dialysis in Libya have a crude 1‐year mortality rate similar to most developed countries, but the mean age of the dialysis population is much lower, and this outcome is thus relatively poor. As in most countries, cardiovascular disease and infection were the most common causes of death. Variation in mortality rates between different centers suggests that survival could be improved by promoting standardization of best practice.
Obstructive sleep apnea in incremental hemodialysis: Determinants, consequences, and impact on survival
Authors: Sivalingam Murugan , Chakravorty Indranil , Mouatt Sarah , Farrington Ken 
Published: August 2012

AbstractSleep disorders are common in hemodialysis patients, although causes and consequences remain unclear. We sought to establish prevalence, determinants, and outcomes of sleep disturbances in patients receiving incremental dialysis. One hundred two unselected patients undergoing incremental high‐flux hemodialysis or hemodiafiltration underwent limited overnight sleep study. Large subsets underwent echocardiography, interdialytic ambulatory blood pressure monitoring, and brain natriuretic peptide measurements. Patients were followed up to 44 months. Full sleep data were obtained in 91 patients. All had sleep disturbance as evidenced by an apnea–hypopnea index >5/min. We defined major obstructive sleep apnea (MOSA) as an apnea–hypopnea index ≥15, together with either significant oxygen desaturation or symptoms of daytime sleepiness. Forty patients met these criteria. Significant independent predictors of MOSA were age <65 years, male gender, has diabetes, and has a brain natriuretic peptide >2500 pg/mL. Mean ambulatory blood pressure and left ventricular mass index were significantly higher in these patients. In a model controlling for body mass index, high C‐reactive protein, and the presence of cancer, MOSA was associated with a twofold increased risk of mortality, although this did not reach statistical significance. MOSA was common, and was associated with hypertension and high left ventricular mass index. Whether obstructive sleep apnea contributes to the high mortality remains to be firmly established.