bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antimicrobial tolerance and the significance of persister cells in recalcitrant chronic wound biofilms
Authors: Percival Steven L. , Hill Katja E. , Malic Sladjana , Thomas David W. , Williams David W. 
Published: January 2011

ABSTRACTThe application of antimicrobials in the management of wounds is a complex procedure requiring appropriate clinical decision making, judgment and a thorough understanding of antimicrobial therapies, together with their potential disadvantages. There is considerable direct and indirect evidence for the presence of bacterial biofilms in the chronic wound bed, and it has been demonstrated that bacteria within these biofilms may exhibit both specific and nonspecific antimicrobial tolerance. The antimicrobial tolerance of biofilms is a major concern in the treatment of both infected and nonhealing chronic wounds and an understanding of the mechanisms involved is of fundamental importance in managing wound infections and developing future wound management strategies. The aim of this review is therefore to provide an overview of our current understanding of the mechanisms by which bacteria in wound biofilms can resist conventional antibiotic and antibacterial therapies which is very important to wound healing.
Young Adult Couples’ Decision Making Regarding Emergency Contraceptive Pills
Authors: Beaulieu Richard , Kools Susan M. , Kennedy Holly Powell , Humphreys Janice 
Published: January 2011

Abstract Purpose: Unintended pregnancy is a significant public health problem among young people worldwide. The purpose of this study was to explore and better understand the reasons for the apparent underuse of emergency contraceptive pills (ECP) in young people in coupled relationships. Theoretical Rational: In postmodern explications of grounded theory, social construction of realities and the influence of subjectivities on the meanings of experiences lead to the development of partial truths that may change with time, context, and situation. Methods: Grounded theory methods guided semi‐structured face‐to‐face interviews and data analysis. Twenty‐two couples aged 18 to 25 years old were recruited through public notices. Findings: Four salient and interrelated conditions were constructed to help explain the complexities involved in young couples decision making regarding ECP use: (a) the shifting locus of responsibility for contraceptive decision making: in a perfect world versus biological reality; (b) relationship power: control‐vulnerability continuum; (c) a woman's autonomy over her own body; and (d) conflicting views on ECP. Conclusions: Healthcare professionals whose practice includes young people need to be aware of possible couple dynamics when discussing contraception. Clients in supportive relationships should be encouraged to engage in open communication with their partners about their contraception needs, including possible ECP use. Clinical Relevance: The results of this study contribute to the body of knowledge with regard to decision making related to ECP use in young adults.
Randomized, Double-Blinded, Placebo-Controlled Crossover Trial of Treating Erectile Dysfunction with Sildenafil After Radiotherapy and Short-Term Androgen Deprivation Therapy: Results of RTOG 0215
Authors: Watkins Bruner Deborah , James Jennifer L. , Bryan Charlene J. , Pisansky Thomas M. , Rotman Marvin , Corbett Thomas , Speight Joycelyn , Byhardt Roger , Sandler Howard , Bentzen Søren , Kachnic Lisa , Berk Lawrence 
Published: January 2011

ABSTRACT

Introduction
Erectile dysfunction (ED) may be the most commonly observed adverse event (AE) associated with the combination of radiation therapy (RT) and androgen deprivation therapy (ADT). A significant number of men are trying phosphodiesterase type 5 inhibitors (PDE5s) such as sildenafil to treat ED, yet sildenafil studies to date shed little light on the response to ED after ADT.

Aim
The purpose of this trial was to evaluate sildenafil in the treatment of ED in prostate cancer patients previously treated with external beam RT and neoadjuvant and concurrent ADT.

Methods
In this randomized, double-blinded crossover trial, eligible patients received RT/ADT for intermediate risk prostate cancer and currently had ED as defined by the International Index of Erectile Function (IIEF). Patients were randomized to 12 weeks of sildenafil or placebo followed by 1 week of no treatment then 12 weeks of the alternative. Treatment differences were evaluated using a marginal model for binary crossover data.

Main Outcome Measures
The primary end point was improved erectile function, as measured by the IIEF.

Results
The study accrued 115 patients and 61 (55%) completed all three IIEF assessments. Sildenafil effect was significant (P = 0.009) with a difference in probabilities of erectile response of 0.17 (95% confidence interval: 0.06, 0.29), and 0.21 (0.06, 0.38) for patients receiving ≤120 days of ADT. However, as few as 21% of patients had a treatment-specific response, only improving during sildenafil but not during the placebo phase.

Conclusions
This is the first controlled trial to suggest a positive sildenafil response for ED treatment in patients previously treated with RT/ADT, however, only a minority of patients responded to treatment. ADT duration may be associated with response and requires further study. The overall low response rate suggests the need for study of additional or preventative strategies for ED after RT/ADT for prostate cancer.
Pedophilic Behavior from Brain Disease
Authors: Mendez Mario , Shapira Jill S. 
Published: January 2011

ABSTRACT

Introduction
Child molestation or other pedophilic behavior may result as a consequence of a brain disorder.

Aim
To characterize the mechanisms of pedophilic behavior associated with neurological diseases.

Methods
We report eight patients with pedophilic behavior as a manifestation of their brain disorder and review the literature.

Main Outcome Measures
The sexual, neuropsychiatric, and neurological aspects of a series of patients.

Results
All eight developed sexual behavior toward prepubescent children in mid- to late-life coincident with the development of a neurological disorder. Five had limited insight, anxiety, or concern for their behavior and tended to have frontal lobe executive deficits. Most of this group had frontally predominant disorders. Two others retained insight and concern in the context of marked hypersexuality. This second group had treated Parkinson’s disease and resembled reports of pedophilic behavior from subcortical lesions. The further presence of right temporal lobe-amygdala involvement may have predisposed to specific sexual preoccupation in some patients.

Conclusions
Brain disorders may release a predisposition to sexual attraction for children through disinhibition with frontal disease, sexual preoccupation with right temporal disease, or hypersexuality with subcortical disease in non-motor basal ganglia, hypothalamus, or septal nuclei. Differentiating these mechanisms of pedophilic behavior from brain disease could facilitate targeted interventions.
Does Metabolic Syndrome Impair Sexual Function in Middle- to Old-Aged Women?
Authors: Kim Yun Hwan , Kim Sun Mie , Kim Jin Ju , Cho In Seong , Jeon Myung Jae 
Published: January 2011

ABSTRACT

Introduction
To date, there are few studies dealing with the impact of metabolic syndrome (MS) on female sexual function, and the association between MS and female sexual dysfunction (FSD) in middle- to old-aged women remains unclear.

Aim
To evaluate the impact of MS on sexual function in middle- to old-aged women.

Methods
From May 2009 to January 2010, we performed a cross-sectional study of sexually active women (≥40 years old) who visited a health-screening clinic. Comprehensive history taking, anthropometric measurement, laboratory testing, and questionnaire administration were performed for each of the total 773 women enrolled.

Main Outcome Measures
The Female Sexual Function Index (FSFI) was used to assess the key dimensions of female sexual function.

Results
The median age of enrolled subjects was 48 (40–65) years, and the rates of MS and FSD were 12.2% (94/773) and 54.7% (423/773), respectively. We found that the demographics of women with and without MS (P &lt; 0.05) differed significantly from one another in terms of age, menopausal status, body mass index, educational status, household income, and urinary incontinence (UI) symptoms, although their frequency of FSD was similar (52.1% vs. 55.1%). After adjusting clinical confounders, we found that only the pain domain score was significantly different between women with MS and without MS, while the total FSFI score and other constituent domain scores showed little difference between the two groups. However, in the multivariate logistic regression model, MS and most of its components were not associated with FSD; only age, menopausal status, smoking, depression, and symptomatic UI proved to be independent risk factors for FSD (P &lt; 0.05).

Conclusions
Our study suggests that MS may have little impact on sexual function in middle- to old-aged women. Further studies with population-based and longitudinal design should be conducted to confirm this finding.
The Effect of Prolapse Surgery on Vaginal Sensibility
Authors: Lakeman Mariëlle M.E. , van der Vaart C. Huub , Laan Ellen , Roovers Jan-Paul W.R. 
Published: January 2011

ABSTRACT

Introduction
Prolapse surgery has been shown to have major impact on sexual function. Since prolapse surgery not only influences psychological factors but might also influence physiological conditions such as vaginal innervation, there is a need for objective outcome measurements to better understand the effects of prolapse surgery on sexual function.

Aims
To assess the effects of prolapse surgery with or without stress incontinence surgery on vaginal sensibility and to assess the relationship between vaginal wall sensibility and sexual well-being.

Methods
This study was performed parallel to a randomized controlled trial comparing vaginal and abdominal prolapse surgery with or without incontinence surgery in women with uterine prolapse stage 2 or more.

Main Outcome Measures
Vaginal wall sensibility was defined as mean sensation threshold to electrical stimulation of the vaginal wall at four standardized places, measured before and 6 months after surgery. Higher sensation thresholds postsurgery relative to presurgery indicate diminished vaginal wall sensibility. Sexual function was assessed at the same time points using a questionnaire.

Results
Data on vaginal wall sensibility were obtained from 65 patients. The sensibility of the distal posterior (P = 0.02) and distal anterior (P = 0.10) vaginal wall decreased after vaginal surgery compared to abdominal surgery. Abdominal prolapse surgery with incontinence surgery decreased sensibility of the distal part of the anterior vaginal wall significantly more than abdominal prolapse surgery only (P = 0.01). Before surgery, vaginal wall sensibility was lower in women who reported vaginal dryness or anorgasmia. The presence of genital pain was associated with higher vaginal wall sensibility. Postoperative vaginal wall sensibility was similar in women with and without sexual problems.

Conclusion
Vaginal prolapse surgery as well as abdominal prolapse surgery with additional incontinence surgery resulted in decreased vaginal wall sensibility. This pilot study shows no influence of the decreased vaginal wall sensibility on sexual well-being. Larger studies are needed to better understand the association between changes in vaginal wall sensibility and changes in sexual well-being.
Model for Cameron-band emission in comets: a case for the EPOXI mission target comet 103P/Hartley 2
Authors: Bhardwaj Anil , Raghuram Susarla 
Published: January 2011

Abstract
The CO2 production rate has been derived in comets using Cameron-band (a3Π→X1Σ) emission of CO molecules, assuming that photodissociative excitation of CO2 is the main production mechanism of CO in the a3Π metastable state. We have developed a model for the production and loss of CO(a3Π), which has been applied to comet 103P/Hartley 2: the target of the EPOXI mission. Our model calculations show that photoelectron impact excitation of CO and dissociative excitation of CO2 can together contribute about 60–90 per cent to Cameron-band emission. The modelled brightness of (0–0) Cameron-band emission on comet Hartley 2 is consistent with Hubble Space Telescope observations for 3–5 per cent CO2 (depending on the model input solar flux) and 0.5 per cent CO relative to water, where the photoelectron impact contribution is about 50–75 per cent. We suggest that estimation of CO2 abundances on comets using Cameron-band emission may be reconsidered. We predict a height-integrated column brightness of the Cameron band of ∼1300 Rayleigh during the EPOXI mission encounter period.
Changes in immunological markers and influx of macrophages following trans‐scleral thermotherapy of uveal melanoma
Authors: Dennaoui Jihan , Bronkhorst Inge H. G. , Ly Long V. , de Wolff‐Rouendaal Didi , Keunen Jan E. E. , Schalij‐Delfos Nicoline E. , Jager Martine J. 
Published: January 2011

Abstract.Purpose:  In trans‐scleral thermotherapy (TSTT), heat is applied through the sclera in order to target an intraocular uveal melanoma. Previously, it had been shown that in uveal melanoma, hyperthermia and transpupillary thermotherapy influenced expression of immunologically relevant proteins, such as S100, HLA and heat‐shock proteins (HSPs). We investigated whether TSTT induced similar changes.Methods:  Experimental TSTT was applied on eleven uveal melanomas prior to enucleation. Each tumour sample was processed for histopathological examination; immunohistochemical analysis was performed to determine expression of S100, HLA, HSPs and macrophage markers.Results:  In TSTT‐treated areas, expression of S100 and different HSPs was lost, while an upregulated expression of HSP GP96 was observed at the border of these areas. Expression levels of HLA‐A and HLA‐B varied between tumours and were not influenced by TSTT. The borders of the TSTT‐treated areas showed high numbers of infiltrating macrophages, which were predominantly of the M2 phenotype.Conclusion:  TSTT has an effect on immunological parameters with local loss of expression of HSPs and S100. The influx of M2 macrophages around the TSTT‐treated areas indicates the presence of an innate immune reaction against the induced necrosis, suggesting that TSTT‐treated tumour cells are removed by a macrophage‐mediated tissue repair mechanism.
Protein kinase A signalling is involved in the relaxant responses to the selective β-oestrogen receptor agonist diarylpropionitrile in rat aortic smooth muscle in vitro
Authors: Valero Marta S , Pereboom Desiree , Barcelo-Batllory Silvia , Brines Laia , Garay Ricardo P , Alda José O 
Published: January 2011

Abstract

Objectives
The oestrogen receptor β (ERβ) selective agonist diarylpropionitrile (DPN) relaxes endothelium-denuded rat aorta, but the signalling mechanism is unknown. The aim of this study was to assess whether protein kinase A (PKA) signalling is involved in DPN action.

Methods
cAMP was measured by radioimmunoassay, HSP20 phosphorylation by 2D gel electrophoresis with immunoblotting, and membrane potential and free cytosolic calcium by flow cytometry.

Key findings
DPN increased cAMP content and hyperpolarised cell membranes over the same range of concentrations as it relaxed phenylephrine-precontracted aortic rings (10–300 µM). DPN-induced vasorelaxation was largely reduced by the PKA inhibitors Rp-8-Br-cAMPS (8-bromoadenosine-3′, 5′-cyclic monophosphorothioate, Rp-isomer) and H-89 (N-(2-bromocynnamyl(amino)ethyl)-5-isoquinoline sulfonamide HCl) (−73%) and by the adenylate cyclase inhibitor MDL12330A (cis-N-(2-phenylcyclopentyl)-azacyclotridec-1-en-2-amine)) (−65.5%). Conversely, the PKG inhibitor Rp-8-Br-cGMP was inactive against DPN vasorelaxation. In aortic smooth muscle segments, DPN increased PKA-dependent HSP20 phosphorylation, an effect reversed by H-89. Relaxant responses to DPN were modestly antagonised (−23 to −48% reduction; n = 12 per compound) by the potassium channel inhibitors iberiotoxin, PNU-37883A, 4-aminopyridine, or BaCl2. All four potassium channel inhibitors together reduced DPN relaxation by 86 ± 9% (n = 12) and fully blocked DPN hyperpolarisation.

Conclusions
ERβ-dependent relaxation of rat aortic smooth muscle evokes an adenylate cyclase/cAMP/PKA signalling pathway, likely activating the cystic fibrosis transmembrane conductance regulator chloride channel and at least four potassium channels.
Collaboration in chronic care: unpacking the relationship of pharmacists and general medical practitioners in primary care
Authors: Dey Rosalind M , de Vries Michael J W , Bosnic-Anticevich Sinthia 
Published: January 2011

Abstract

Objectives
The objective of this research was to gain deeper understanding of the expectations, experiences and perceptions of Australian general medication practitioners (GPs) and pharmacists around collaboration in chronic illness (asthma) management in the primary care setting.

Methods
A qualitative research methodology utilising a semi-structured interview guide, based on theory and an empirical approach, was used to fulfill the objectives of this study. Face-to-face interviews with pharmacists (n = 18) and GPs (n = 7) were recorded, transcribed and coded for concepts and themes. Relationships between concepts and themes were examined and used to describe the nature of collaborative relationships in the primary care setting.

Key findings
A relationship between GPs and pharmacists currently exists although there is minimal collaboration and there are several areas of practice and patient care in which the two professional groups are mismatched. At the same time, this research uncovered key aspects of the GP–pharmacist relationship, which could be used to develop more collaborative relationships in the future. The findings from this study were evaluated in light of the Collaborative Working Relationships model and published literature.

Conclusions
A model for the development of GP–pharmacist relationship has been postulated which articulates the dynamic nature of professional relationship in primary care and highlights a pathway to more collaborative practice. Future research should focus on further developing this model.
Numerous IgG4-positive plasma cells are ubiquitous in diverse localised non-specific chronic inflammatory conditions and need to be distinguished from IgG4-related systemic disorders
Authors: Strehl Johanna D , Hartmann Arndt , Agaimy Abbas 
Published: January 2011

BackgroundIgG4-related systemic fibrosclerosis is a recently defined disorder characterised by a diffuse or tumefactive inflammatory reaction rich in IgG4-positive plasma cells associated with sclerosis and obliterative phlebitis. Although characteristic histopathological features are essential for the diagnosis of these disorders, to date there exists no consensus regarding the cut-off values used to define a ‘significant IgG4-positive plasma cell count,’ and data regarding the distribution of IgG4-positive plasma cells under common (non-specific) inflammatory conditions are lacking.MethodsThe authors analysed 121 randomly selected histopathological specimens containing prominent lymphoplasmacytic infiltrates (11 obstructive sialadenitis, 27 inflammatory lesions of the oral cavity, 24 inflammatory gastrointestinal lesions, 15 rheumatoid synovitis, 15 non-specific synovitis, eight non-specific dermatitis and 21 primary carcinomas with a peritumoral inflammatory response). For comparison, seven cases of sclerosing sialadenitis (Küttner tumour) were examined.ResultsHigh counts of IgG4 plasma cells were found in sclerosing sialadenitis (mean 40/high-power field (hpf)), contrasting sharply with sialadenitis caused by sialolithiasis (mean 3/hpf). Greatly varied but generally high counts of IgG4-positive plasma cells were also seen in several of the other lesions, particularly in rheumatoid synovitis (mean 55/hpf), oral cavity lesions (mean 79/hpf) and carcinoma-associated inflammatory response (mean 24/hpf). The mean IgG4/IgG ratios for all lesions varied between 0 and 0.4.ConclusionsThe results demonstrate the ubiquitous occurrence of variably high numbers of IgG4-positive plasma cells under diverse non-specific inflammatory conditions, indicating that high IgG4-positive plasma cell counts and high IgG4/IgG ratios per se do not reliably distinguish IgG4-associated systemic disease from non-specific conditions, and that the IgG4 counts must be cautiously interpreted in the context of appropriate clinical and histopathological features.
CCT241533 Is a Potent and Selective Inhibitor of CHK2 that Potentiates the Cytotoxicity of PARP Inhibitors
Authors: Anderson Victoria E. , Walton Michael I. , Eve Paul D. , Boxall Katherine J. , Antoni Laurent , Caldwell John J. , Aherne Wynne , Pearl Laurence H. , Oliver Antony W. , Collins Ian , Garrett Michelle D. 
Published: January 2011

Abstract
CHK2 is a checkpoint kinase involved in the ATM-mediated response to double-strand DNA breaks. Its potential as a drug target is still unclear, but inhibitors of CHK2 may increase the efficacy of genotoxic cancer therapies in a p53 mutant background by eliminating one of the checkpoints or DNA repair pathways contributing to cellular resistance. We report here the identification and characterization of a novel CHK2 kinase inhibitor, CCT241533. X-ray crystallography confirmed that CCT241533 bound to CHK2 in the ATP pocket. This compound inhibits CHK2 with an IC50 of 3 nmol/L and shows minimal cross-reactivity against a panel of kinases at 1 μmol/L. CCT241533 blocked CHK2 activity in human tumor cell lines in response to DNA damage, as shown by inhibition of CHK2 autophosphorylation at S516, band shift mobility changes, and HDMX degradation. CCT241533 did not potentiate the cytotoxicity of a selection of genotoxic agents in several cell lines. However, this compound significantly potentiates the cytotoxicity of two structurally distinct PARP inhibitors. Clear induction of the pS516 CHK2 signal was seen with a PARP inhibitor alone, and this activation was abolished by CCT241533, implying that the potentiation of PARP inhibitor cell killing by CCT241533 was due to inhibition of CHK2. Consequently, our findings imply that CHK2 inhibitors may exert therapeutic activity in combination with PARP inhibitors. Cancer Res; 71(2); 463–72. ©2011 AACR.