bluuebunny/crossref_metadata_2025_split huggingface dataset:
AVE 0991, a non‐peptide Mas‐receptor agonist, facilitates penile erection
Authors: da Costa Gonçalves Andrey C. , Fraga‐Silva Rodrigo A. , Leite Romulo , Santos Robson A. S. 
Published: October 2012

New findings
What is the central question of this study?The renin–angiotensin system plays a crucial role in erectile function. While angiotensin II contributes to the development of erectile dysfunction, angiotensin‐(1–7) mediates penile erection by activation of the Mas receptor. However, because of its peptidic nature, angiotensin‐(1–7) is not resistant to proteolytic enzymes, thus limiting its clinical applications. In this study, we have hypothesized that the synthetic non‐peptide Mas agonist, AVE 0991, would potentiate the penile erectile function.
What is the main finding and its importanceWe demonstrated that AVE 0991 potentiates the rat penile erectile response through Mas in a nitric oxide‐dependent manner; therefore, our results suggest Mas agonists as potential targets for the treatment of erectile dysfunction.
The renin–angiotensin system plays a crucial role in erectile function. It has been shown that elevated levels of angiotensin II contribute to the development of erectile dysfunction both in humans and in aminals. On the contrary, the heptapeptide angiotensin‐(1–7) appears to mediate penile erection by activation of the Mas receptor. Recently, we have shown that the erectile function of Mas gene‐deleted mice was substantially reduced, which was associated with a marked increase in fibrous tissue in the corpus cavernosum. We have hypothesized that the synthetic non‐peptide Mas agonist, AVE 0991, would potentiate penile erectile function. We showed that intracavernosal injection of AVE 0991 potentiated the erectile response of anaesthetized Wistar rats, measured as the ratio between corpus cavernosum pressure and mean arterial pressure, upon electrical stimulation of the major pelvic ganglion. The facilitatory effect of AVE 0991 on erectile function was dose dependent and completely blunted by the nitric oxide synthesis inhibitor, l‐NAME. Importantly, concomitant intracavernosal infusion of the specific Mas receptor blocker, A‐779, abolished the effect of AVE 0991. We demonstrated that AVE 0991 potentiates the penile erectile response through Mas in an NO‐dependent manner. Importantly, these results suggest that Mas agonists, such as AVE 0991, might have significant therapeutic benefits for the treatment of erectile dysfunction.
Overexpression of peroxisome proliferator‐activated receptor α in pancreatic β‐cells improves glucose tolerance in diet‐induced obese mice
Authors: Hogh K‐Lynn N. , Uy Christopher E. , Asadi Ali , Baker Robert K. , Riedel Michael J. , Gray Sarah L. 
Published: October 2012

New findings
What is the central question of this study?Does overexpression of peroxisome proliferator‐activated receptor α (PPARα) specifically in pancreatic β‐cells of diet‐induced obese mice preserve pancreatic β‐cell function and delay the onset of obesity‐induced diabetes?
What is the main finding and its importance?This study reports the phenotype of the first in vivo model of β‐cell‐specific PPARα overexpression in a murine model of diet‐induced obesity. We show that pancreatic β‐cell‐specific overexpression of PPARα significantly improves glucose tolerance in diet‐induced obese mice. These results suggest that activation of β‐cell PPARα may be an appropriate target to preserve β‐cell function in obesity‐induced diabetes.
Lipotoxicity is implicated in pancreatic β‐cell dysfunction in obesity‐induced type 2 diabetes. In vitro, activation of peroxisome proliferator‐activated receptor α (PPARα) has been shown to protect pancreatic β‐cells from the lipotoxic effects of palmitate, thereby preserving insulin secretion. Utilizing an adeno‐associated virus (dsAAV8), overexpression of PPARα was induced specifically in pancreatic β‐cells of adult, C57Bl/6 mice fed a high‐fat diet for 20 weeks and carbohydrate metabolism and β‐cell mass assessed. We show that overexpression of PPARα in pancreatic β‐cells in vivo preserves β‐cell function in obesity, and this improves glucose tolerance by preserving insulin secretion in comparison to control mice with diet‐induced obesity. No changes in β‐cell mass were observed in PPARα‐overexpressing mice compared with diet‐induced obese control animals. This model of β‐cell‐specific PPARα overexpression provides a useful in vivo model for elucidating the mechanisms underlying β‐cell lipotoxicity in obesity‐induced type 2 diabetes.
Multiresistant Uropathogenic Escherichia coli from a Region in India Where Urinary Tract Infections Are Endemic: Genotypic and Phenotypic Characteristics of Sequence Type 131 Isolates of the CTX-M-15 Extended-Spectrum-β-Lactamase-Producing Lineage
Authors: Hussain Arif , Ewers Christa , Nandanwar Nishant , Guenther Sebastian , Jadhav Savita , Wieler Lothar H. , Ahmed Niyaz 
Published: October 2012

ABSTRACT

Escherichia coli
sequence type 131 (O25b:H4), associated with the CTX-M-15 extended-spectrum beta-lactamases (ESBLs) and linked predominantly to the community-onset antimicrobial-resistant infections, has globally emerged as a public health concern. However, scant attention is given to the understanding of the molecular epidemiology of these strains in high-burden countries such as India. Of the 100 clinical
E. coli
isolates obtained by us from a setting where urinary tract infections are endemic, 16 ST131
E. coli
isolates were identified by multilocus sequence typing (MLST). Further, genotyping and phenotyping methods were employed to characterize their virulence and drug resistance patterns. All the 16 ST131 isolates harbored the CTX-M-15 gene, and half of them also carried TEM-1; 11 of these were positive for
bla
OXA
groups 1 and 12 for
aac(6
′
)-Ib-cr
. At least 12 isolates were refractory to four non-beta-lactam antibiotics: ciprofloxacin, gentamicin, sulfamethoxazole-trimethoprim, and tetracycline. Nine isolates carried the class 1 integron. Plasmid analysis indicated a large pool of up to six plasmids per strain with a mean of approximately three plasmids. Conjugation and PCR-based replicon typing (PBRT) revealed that the spread of resistance was associated with the FIA incompatibility group of plasmids. Pulsed-field gel electrophoresis (PFGE) and genotyping of the virulence genes showed a low level of diversity among these strains. The association of ESBL-encoding plasmid with virulence was demonstrated in transconjugants by serum assay. None of the 16 ST131 ESBL-producing
E. coli
strains were known to synthesize carbapenemase enzymes. In conclusion, our study reports a snapshot of the highly virulent/multiresistant clone ST131 of uropathogenic
E. coli
from India. This study suggests that the ST131 genotypes from this region are clonally evolved and are strongly associated with the CTX-M-15 enzyme, carry a high antibiotic resistance background, and have emerged as an important cause of community-acquired urinary tract infections.
The spectrum of sleep-disordered breathing symptoms and respiratory events in infants with cleft lip and/or palate
Authors: MacLean Joanna E , Fitzsimons David , Fitzgerald Dominic A , Waters Karen A 
Published: October 2012

ObjectiveTo determine the prevalence of sleep-disordered breathing (SDB) symptoms and respiratory events during sleep in infants with cleft lip and/or palate (CL/P).DesignProspective observational study.SettingCleft palate clinic, tertiary care paediatric hospital, before palate surgery.PatientsConsecutive newborn infants with CL/P.Main outcome measuresDemographics, clinical history, sleep symptoms, facial measurement and polysomnography (PSG; sleep study) data.ResultsFifty infants completed PSG at 2.7±2.3 months; 56% were male, and 30% had a clinical diagnosis of Pierre Robin sequence (PRS) or a syndrome. The majority of infants (75%) were reported to snore frequently or constantly, while 74% were reported to have heavy or loud breathing during sleep. The frequency of parent-reported difficulty with breathing during sleep was 10% for infants with isolated CL/P, 33% for those with syndrome, and 43% for PRS (χ2 16.1, p<0.05). All infants had an Obstructive–Mixed Apnoea–Hypopnoea Index (OMAHI) >1 event/h, and 75% had an OMAHI >3 events/h. Infants with PRS had higher OMAHI (34.3±5.1) than infants with isolated CL/P (7.6±1.2) or infants with syndromes (15.6±5.7, F stat, p<0.001). Multivariate analysis showed that PRS was associated with higher OMAHI (B 0.53±0.22, p=0.022), but the majority of the variance for SDB was unexplained (constant B 1.31±0.55, p=0.024).ConclusionsThe results highlight that infants across the spectrum of CL/P have a high risk of SDB symptoms and obstructive respiratory events before palate surgery. Clinicians should enquire about symptoms of SDB and consider investigation with polysomnography in all infants with CL/P.
A cross-sectional study of the association of age, race and ethnicity, and body mass index with sex steroid hormone marker profiles among men in the National Health and Nutrition Examination Survey (NHANES III)
Authors: Ritchey Jamie , Karmaus Wilfried , Sabo-Attwood Tara , Steck Susan E , Zhang Hongmei 
Published: October 2012

ObjectivesSince sex hormone markers are metabolically linked, examining sex steroid hormones singly may account for inconsistent findings by age, race/ethnicity and body mass index (BMI) across studies. First, these markers were statistically combined into profiles to account for the metabolic relationship between markers. Then, the relationships between sex steroid hormone profiles and age, race/ethnicity and BMI were explored in multinomial logistic regression models.DesignCross-sectional survey.SettingThe US Third National Health and Nutrition Examination Survey (NHANES III).Participants1538 Men, >17 years.Primary outcome measureSex hormone profiles.ResultsCluster analysis was used to identify four statistically determined profiles with Blom-transformed T, E, sex hormone binding globulin (SHBG), and 3-α diol G. We used these four profiles with multinomial logistic regression models to examine differences by race/ethnicity, age and BMI. Mexican American men >50 years were associated with the profile that had lowest T, E and 3-α diol G levels compared to other profiles (p<0.05). Non-Hispanic Black, overweight (25–29.9 kg/m2) and obese (>30 kg/m2) men were most likely to be associated with the cluster with the lowest SHBG (p<0.05).ConclusionThe associations of sex steroid hormone profiles by race/ethnicity are novel, while the findings by age and BMI groups are largely consistent with observations from single hormone studies. Future studies should validate these hormone profile groups and investigate these profiles in relation to chronic diseases and certain cancers.
Coronary and mortality risk of novel oral antithrombotic agents: a meta-analysis of large randomised trials
Authors: Mak Koon-Hou 
Published: October 2012

ObjectiveOral direct thrombin and anti-Xa inhibitors have been shown to be efficacious in the prevention and treatment of venous thromboembolism, and prevention of embolic events in atrial fibrillation. Recent studies showed that dabigatran may be associated with increased rates of myocardial infarction (MI). Coronary risk for the other agents was unclear. The aim of the study is to determine the coronary risk among four novel antithrombotic agents.DesignMixed treatment comparison meta-analysis.Data sources and study selectionRandomised controlled trials (RCTs) on ximelagatran, dabigatran, rivaroxaban and apixaban were obtained from PubMed search (February 2012) and major scientific meeting in 2011. The random-effects model was used to evaluate the effect of these agents on MI or acute coronary syndrome (MI/ACS), major bleeding complication and all-cause mortality.ResultsFrom 28 RCTs (n=138 948), the risk for MI/ACS was higher for dabigatran (OR 1.30; 95% CI 1.04 to 1.63; p=0.021) but lower for rivaroxaban (OR 0.78; 95% CI 0.69 to 0.89; p<0.001). Ximelagatran showed a higher risk for MI/ACS, which was not statistically significant, while apixaban demonstrated a non-significant lower likelihood. Among the RCTs for MI/ACS among the four agents, only those pertaining to ximelagatran showed heterogeneity. Major bleeding complication rates varied considerably among different agents. Importantly, these agents were associated with a lower all-cause mortality, without heterogeneity among the studies.ConclusionsThe risk for coronary events was significantly higher for dabigatran but not significantly higher for ximelagatran. Conversely, this risk was lower among anti-Xa inhibitors. All-cause mortality was lower among those receiving novel antithrombotic agents. This information may be useful in selecting agents for specific subsets of patients requiring anticoagulation.
Effects of a free school breakfast programme on children's attendance, academic achievement and short-term hunger: results from a stepped-wedge, cluster randomised controlled trial
Authors: Mhurchu Cliona Ni , Gorton Delvina , Turley Maria , Jiang Yannan , Michie Jo , Maddison Ralph , Hattie John 
Published: October 2012

BackgroundFree school breakfast programmes (SBPs) exist in a number of high-income countries, but their effects on educational outcomes have rarely been evaluated in randomised controlled trials.MethodsA 1-year stepped-wedge, cluster randomised controlled trial was undertaken in 14 New Zealand schools in low socioeconomic resource areas. Participants were 424 children, mean age 9±2 years, 53% female. The intervention was a free daily SBP. The primary outcome was children's school attendance. Secondary outcomes were academic achievement, self-reported grades, sense of belonging at school, behaviour, short-term hunger, breakfast habits and food security.ResultsThere was no statistically significant effect of the breakfast programme on children's school attendance. The odds of children achieving an attendance rate <95% was 0.76 (95% CI 0.56 to 1.02) during the intervention phase and 0.93 (95% CI 0.67 to 1.31) during the control phase, giving an OR of 0.81 (95% CI 0.59 to 1.11), p=0.19. There was a significant decrease in children's self-reported short-term hunger during the intervention phase compared with the control phase, demonstrated by an increase of 8.6 units on the Freddy satiety scale (95% CI 3.4 to 13.7, p=0.001). There were no effects of the intervention on any other outcome.ConclusionsA free SBP did not have a significant effect on children's school attendance or academic achievement but had significant positive effects on children's short-term satiety ratings. More frequent programme attendance may be required to influence school attendance and academic achievement.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR)—ACTRN12609000854235.
Improvements in recanalization with modern stroke therapy: a review of prospective ischemic stroke trials during the last two decades
Authors: Fargen Kyle M , Meyers Philip M , Khatri Pooja , Mocco J 
Published: October 2012

IntroductionA number of recent trials evaluating intra-arterial therapies for acute ischemic stroke have been completed. We present a review of prospective acute ischemic stroke trials reported in a peer-reviewed forum during the last 20 years to provide insight into the general direction of this rapidly evolving field.MethodsProspective trials evaluating acute stroke intra-arterial therapies since 1999 were included, with the National Institute of Neurological Disorders and Stroke rtPA trial published in 1995 as a baseline comparator. Patient presenting factors and outcome data were analyzed based on year of publication and best-fit lines and linear regression analyses were generated.ResultsThirteen prospective trials were included. Regression analyses demonstrated no appreciable change in the median NIH Stroke Scale score of subjects at the time of enrollment since 1995 (p=0.44) and no appreciable improvements in good outcome based on a modified Rankin score of 0–2 at 90 days (p=0.66) or mortality at 90 days (p=0.55). A significant increase in time from onset of symptoms to treatment among enrolled patients was noted from 1995 to 2012 (p=0.03). In addition, a significant improvement in recanalization/reperfusion was noted over the last two decades (p=0.02).ConclusionsThis review of prospective acute ischemic stroke trials since 1999 indicates a substantial improvement in revascularization in the setting of a significant increase in time to therapy onset, but no appreciable change in good functional outcome.
Statin-induced lung injury: diagnostic clue and outcome
Authors: Huang Li-Kuo , Tsai Ming-Ji , Tsai Han-Chen , Chao Heng-Sheng , Lin Fang-Chi , Chang Shi-Chuan 
Published: October 2012

Abstract

Background
Statin-induced lung injury (SILI) is an uncommon but serious complication of statins. The clinical features and outcome of patients with SILI vary widely. Clinical data relevant to diagnosis and outcome of patients with SILI were investigated in this study.

Method
Four cases of SILI diagnosed at our institute and 12 cases reported in the English literature from 1995 to 2010 were studied. The patients were further divided into favourable and unfavourable outcome groups and compared.

Results
Compared with the 12 previously reported cases, fever (p=0.008) and consolidation (p=0.027) were more common and duration of statin treatment was significantly shorter (p=0.030) in our patients. Foamy alveolar macrophages in bronchoalveolar lavage fluid (BALF) were found in our four patients. Patients with cough (p=0.024), fever (p=0.026) and alveolar infiltrates (p=0.036), especially ground-glass opacity (GGO) (p=0.001) shown on thoracic high-resolution CT (HRCT), had a favourable outcome. Conversely, those with fibrosis shown on HRCT (p=0.008) had an unfavourable outcome. Stepwise logistic regression analysis demonstrated that cough (p=0.011), fever (p=0.005), and alveolar infiltrates (p=0.017), GGO (p&lt;0.001) and fibrosis (p=0.002) shown on thoracic HRCT were independent factors affecting the outcome of SILI.

Conclusions
For patients with SILI, pulmonary phospholipidosis, as shown by foamy alveolar macrophages in BALF, may be valuable in diagnosis, and clinical symptoms and thoracic HRCT findings are of value in predicting the outcome.
Health-related quality of life among patients with symptomatic carotid disease
Authors: Vlajinac Hristina , Marinkovic Jelena , Maksimovic Milos , Kocev Nikola , Vasiljevic Nadja , Backovic Dusan , Radak Djordje 
Published: October 2012

Abstract

Objectives
To evaluate health-related quality of life (HRQoL) in patients with symptomatic carotid disease (amaurosis fugax, transient ischaemic attack, stroke); to compare it with that of the general population; to explore whether HRQoL depends on the severity of the disease and to investigate the possible association between some demographic and clinical characteristics of patients and HRQoL.

Methods
This cross-sectional study involved 175 patients with symptomatic carotid atherosclerotic disease who were referred for endarterectomy between January 2011 and December 2011. HRQoL was measured using Medical Outcome Survey Short Form 36 (SF-36).

Results
In comparison to both referent populations, patients with carotid disease had significantly lower mean SF-36 scores for role-physical (41.6 vs. 61.5 and 67.8), social functioning (65.4 vs. 73.8 and 80.0), role-emotional (48.2 vs. 68.6 and 80.5) and mental health (51.5 vs. 61.9 and 66.0). The SF-36 scores were significantly lower in female patients with carotid disease than in men (for role-physical 32.3 vs. 46.5; for bodily pain 57.0 vs. 73.0; for general health 55.6 vs. 61.5; for vitality 55.4 vs. 60.1; for social functioning 57.1 vs. 69.8 and for role-emotional 37.2 vs. 54.1). Significantly lower SF-36 scores were also found in patient with comorbidity (for physical functioning 68.1 vs. 77.7; for role-physical 35.1 vs. 52.3; for bodily pain 62.6 vs. 75.4; for general health 56.8 vs. 63.8; for social functioning 61.9 vs. 71.0, for role-emotional 41.6 vs. 59.1and for mental health 52.5 vs 49.8). In a multivariable analysis, education, occupation, body mass index, metabolic syndrome and severity of the disease had a weak influence on patients' HRQoL, while age, marital status, smoking, alcohol consumption, physical activity and the degree of carotid stenosis had no effect on patients' HRQoL. The SF-36 scores did not substantially change after adjustment for confounding variables.

Conclusions
Patients with symptomatic carotid disease had poorer HRQoL, especially its mental components, than the general population. The severity of the disease was significantly associated only with the SF-36 role-physical subscale. HRQoL in patients with symptomatic carotid disease was poorer in women than in men, and was not affected by age and other demographic and clinical characteristics of patients.
Complex gynaecological and urological problems in adolescents: challenges and transition
Authors: Creighton Sarah M , Wood Dan 
Published: October 2012

Abstract
The diagnosis and early management of genitourinary disorders in children is challenging for the child, parents and carers. There have been enormous developments in paediatric care medically and surgically and as a result many patients with complex anomalies reach adult life and have a normal desire for a good quality of life. Adolescence changes the challenges faced as anatomical growth may alter the surgical outcomes both functionally and cosmetically. Emotional and psychological development also creates important challenges that all those involved have to face. These patients need expert care and advice throughout adolescence and into adult life. This should be delivered by a multidisciplinary team that includes urology, gynaecology, nephrology, endocrinology and psychology. This creates a safe clinical and supportive environment for patients and their families.
Sexually transmitted infection testing and self-reported diagnoses among a community sample of men who have sex with men, in Scotland
Authors: McDaid Lisa M , Li Jessica , Knussen Christina , Flowers Paul 
Published: October 2012

IntroductionTo examine sexually transmitted infection (STI) testing and self-reported diagnoses among men who have sex with men (MSM), in Scotland.MethodsCross-sectional survey of seven Glasgow gay bars in July 2010 (n=822, 62% response rate); 693 are included in the analyses.Results81.8% reported ever having had an STI test; 37.4% had tested in the previous 6 months; 13.2% reported having an STI in the previous 12 months. The adjusted odds of having ever tested were significantly higher for men who had 6+ sexual partners in the previous 12 months (adjusted OR=2.66), a maximum sexual health knowledge score (2.23), and had talked to an outreach worker/participated in counselling (1.96), and lower for men reporting any high-risk unprotected anal intercourse (UAI) in the previous 12 months (0.51). Adjusted odds of recent testing were higher for men who had 6+ sexual partners (2.10), talked to an outreach worker/participated in counselling (1.66), maximum sexual health knowledge (1.59), and higher condom use knowledge (1.04), and lower for men aged ≥25 years (0.46). Adjusted odds of having had an STI in the previous 12 months were higher for men who had 6+ sexual partners (3.96) and any high-risk UAI in the previous 12 months (2.24) and lower for men aged ≥25 years (0.57).ConclusionsSTI testing rates were relatively high, yet still below the minimum recommended for MSM at high risk. Consideration should be given to initiating recall systems for men who test positive for STIs, and to developing behavioural interventions which seek to address STI transmission.