bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nova Scotia pharmacists' knowledge of, experiences with and perception of factors interfering with their ability to provide emergency contraceptive pill consultations
Authors: Whelan Anne Marie , Langille Donald B , Hurst Eileen 
Published: January 2013

Abstract

Objective
The objective of this research was to explore pharmacists' knowledge of, experiences with and perception of factors interfering with their ability to provide non-prescription emergency contraceptive pill consultations in the Canadian province of Nova Scotia.

Methods
A self-administered paper questionnaire was mailed, using Dillman's tailored design method, to all pharmacists (n = 1123) registered with the Nova Scotia College of Pharmacists.

Key findings
The response rate was 53.0% (595/1123), with 451 respondents working in community practice. Most respondents reported that they had provided consultations for the emergency contraceptive product Plan B since it became available without a prescription (93.6%), and that Plan B is kept behind the pharmacy counter (83.6%). Pharmacists most frequently (47.8%) reported spending 6–10 min providing Plan B consultations. Respondents were generally knowledgeable about Plan B; however, only 39.2% knew that it can be effective for up to 5 days and 69.3% knew that the incidence of vomiting is less than 50%. The factors interfering the most with providing Plan B consultations were lack of privacy (46.1%) and lack of staff to cover during the consultation (50.9%).

Conclusions
In general, Nova Scotia pharmacists are knowledgeable about emergency contraceptive pills; however, education regarding effective timing for use of such pills would be helpful. Private areas for counselling and consideration of pharmacy staffing schedules in community pharmacies may help address pharmacist concerns regarding their ability to provide Plan B consultations.
Segmental dosimetry, toxicity and long‐term outcome in patients with prostate cancer treated with permanent seed implants
Authors: Meyer Andreas , Wassermann Julia , Warszawski‐Baumann Antje , Baumann Rolf , Machtens Stefan , Karstens Johann H. , Christiansen Hans , Merseburger Axel , Kuczyk Markus A. , von Klot Christoph 
Published: January 2013

What's known on the subject? and What does the study add?
The development of side effects characteristic for the different treatment methods with impact on the patients' quality of life plays a growing role for individual patients with early stage prostate cancer. Using permanent brachytherapy a high dose to the prostate can be applied with a steep dose gradient to the normal tissue. However, small partial volumes of normal tissue may be exposed to high doses inducing special side effects including lower urinary tract symptoms and/or erectile dysfunction. In the literature there are only few publications so far regarding segmental dosimetry and its influence on side effects and the results are conflicting.
We could not identify any dosimetric parameter in segmental dosimetry that may have an influence at certain time intervals on the development of side effects such as lower urinary tract symptoms or erectile dysfunction. However, we could state clearly that the preoperative situation is the most important factor for postoperative outcome.
Objective
To report on the side effects of patients with low to low–intermediate risk prostate cancer treated with permanent interstitial brachytherapy with special emphasis on segmental dosimetry.
Patients and Methods
A series of 186 consecutive patients treated for early stage prostate cancer receiving definitive I‐125 brachytherapy (permanent seed implantation) between November 2001 and April 2005 at our institution were examined for the development of side effects.
Morbidity was assessed prospectively using the International Prostate Symptom Score (IPSS) and the International Index of Erectile Function (IIEF‐5) in a mean follow‐up interval of 30 months.
The scores were correlated with segmental dosimetry performed 6 weeks after the implantation.
Results
The mean postoperative dose to 90% of the prostate volume (D90) was 180.2 Gy, the mean preoperative IPSS 7.2 and the mean IIEF‐5 14.35, with all scores showing a maximum deterioration after 6 weeks with normalization after 24 months.
After correlating the segmental dosimetry and the scores at different time intervals, only the baseline scores remained statistically significant in multivariate regression analysis at all time intervals (P < 0.00).
Conclusions
We could not demonstrate a correlation of segmental dosimetry with induction of side effects.
There is no relationship between dose exposure of partial volumes and the development of radiation‐induced toxicities.
The preoperative situation regarding lower urinary tract symptoms and erectile function are the most important factors for postoperative outcome.
Acquired resistance to sunitinib in human renal cell carcinoma cells is mediated by constitutive activation of signal transduction pathways associated with tumour cell proliferation
Authors: Sakai Iori , Miyake Hideaki , Fujisawa Masato 
Published: January 2013

What's known on the subject? and What does the study add?
Although there have been a few studies investigating the molecular mechanism mediating the acquisition of resistance to molecular‐targeted agents, including sunitinib, by renal cell carcinoma (RCC) cells, this mechanism remains largely unclear.
The maintenance of protein kinase activation during sunitinib treatment may be involved in the acquisition of a phenotype resistant to sunitinib in RCC, and additional treatment with agents targeting activated protein kinases could be a promising approach for overcoming resistance to sunitinib in RCC.
Objective
To characterise the mechanism involved in the acquired resistance to sunitinib, a potential inhibitor of multiple receptor tyrosine kinases (RTKs), in renal cell carcinoma (RCC).
Materials and Methods
A parental human RCC cell line, ACHN (ACHN/P), was continuously exposed to increasing doses of sunitinib, and a cell line resistant to sunitinib (ACHN/R), showing an ≈5‐fold higher IC50 (concentration that reduces the effect by 50%) than that of ACHN/P, was developed.
Results
ACHN/R appeared to acquire significant cross resistance to sorafenib; however, there were no significant differences in sensitivities to the Mammalian target of rapamycin inhibitors, temsirolimus and everolimus, between ACHN/P and ACHN/R.
After sunitinib treatment, the expression levels of phosphorylated Akt and p44/42 mitogen‐activated protein kinase in ACHN/P, but not those in ACHN/R, were significantly inhibited.
RTK assay showed that treatment of ACHN/P with sunitinib resulted in the marked downregulation of several phosphorylated RTKs compared with that of ACHN/R.
Additional treatment with a specific inhibitor of Akt significantly increased the sensitivity of ACHN/R to sunitinib, but not that of ACHN/P.
There were no significant differences between in vivo growth patterns of ACHN/P and ACHN/R in mice before and after the administration of sunitinib; however, the proportion of cells positive for TUNEL (terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labelling) staining in ACHN/P tumour was significantly greater than that in ACHN/R tumour in mice treated with sunitinib.
Conclusion
The maintenance of protein kinase activation during sunitinib treatment may be involved in the acquisition of resistant phenotype to sunitinib in RCC cells.
Dielectric and Magnetic Properties of Sr(Fe1/2Ta1/2)O3 Complex Perovskite Ceramics
Authors: Lv Xin , Liu Xiao Qiang , Zhao Hong Jian , Yang Wen Zhi , Chen Xiang Ming 
Published: January 2013

The dielectric and magnetic properties of Sr(Fe1/2Ta1/2)O3 complex perovskite ceramics were systematically investigated together with the structure. The X‐ray powder diffraction analysis confirmed a B‐site disordered orthorhombic structure in space group Pbnm. Only one broadened dielectric peak with strong frequency dispersion was observed in the present ceramics, which was significantly different from that for the analogue Ba(Fe1/2Nb1/2)O3 and Ba(Fe1/2Ta1/2)O3. The strong dependence of sample thickness and electrode material indicated that the dielectric relaxation behavior at lower frequency was due to the interface effects. The present ceramics were spin glass state with slight ferromagnetic behavior below the Néel temperature (20 K). The co‐presence of Fe3+ and Fe2+ was confirmed by the μeff value.
Patients With Hypertensive Crises Who Are Admitted to a Coronary Care Unit: Clinical Characteristics and Outcomes
Authors: Pacheco Héctor González , Victorino Neisser Morales , Urquiza Juan Pablo Núñez , Castillo Alfredo Altamirano , Herrera Ursulo Juárez , Mendoza Alexandra Arias , Manzur Francisco Azar , de la Cruz Jose Luis Briseño , Sánchez Carlos Martínez 
Published: January 2013

Patients with hypertensive crises, especially hypertensive emergencies, require immediate admittance to an intensive care unit for rapid blood pressure (BP) control. The authors analyzed the prevalence of hypertensive crisis, the clinical characteristics, and the evolution of patients with hypertensive emergencies and urgencies. Patients were divided into 3 groups according to their BP values: group I, predominant systolic hypertension (≥180/≤119 mm Hg); group II, severe systolic and diastolic hypertension (≥180/≥120 mm Hg); and group III, predominant diastolic hypertension (≤179/≥120 mm Hg). Of all of the patients admitted to a coronary care unit, 538 experienced a hypertensive crisis, which represented 5.08% of all admissions. Hypertensive emergency was predominant in 76.6% of the cases, which corresponded to acute coronary syndrome and acute decompensated heart failure in 59.5% and 25.2% of the cases, respectively. A pattern of predominant systolic hypertension (≥180/≤119 mm Hg) was most commonly observed in the hypertensive crisis group (71.4%) and the hypertensive emergency group (72.1%). The medications that were most commonly used at onset included intravenous vasodilators (nitroglycerin in 63.4% and sodium nitroprusside in 16.4% of the patients). The overall mortality rate was 3.7%. The mortality rate was 4.6% for hypertensive emergency cases and 0.8% for hypertensive urgencies cases.
Interconnections between apoptotic, autophagic and necrotic pathways: implications for cancer therapy development
Authors: Jain Mayur V. , Paczulla Anna M. , Klonisch Thomas , Dimgba Florence N. , Rao Sahana B. , Roberg Karin , Schweizer Frank , Lengerke Claudia , Davoodpour Padideh , Palicharla Vivek R. , Maddika Subbareddy , Łos Marek 
Published: January 2013

SummaryThe rapid accumulation of knowledge on apoptosis regulation in the 1990s was followed by the development of several experimental anticancer‐ and anti‐ischaemia (stroke or myocardial infarction) drugs. Activation of apoptotic pathways or the removal of cellular apoptotic inhibitors has been suggested to aid cancer therapy and the inhibition of apoptosis was thought to limit ischaemia‐induced damage. However, initial clinical studies on apoptosis‐modulating drugs led to unexpected results in different clinical conditions and this may have been due to co‐effects on non‐apoptotic interconnected cell death mechanisms and the ‘yin‐yang’ role of autophagy in survival versus cell death. In this review, we extend the analysis of cell death beyond apoptosis. Upon introduction of molecular pathways governing autophagy and necrosis (also called necroptosis or programmed necrosis), we focus on the interconnected character of cell death signals and on the shared cell death processes involving mitochondria (e.g. mitophagy and mitoptosis) and molecular signals playing prominent roles in multiple pathways (e.g. Bcl2‐family members and p53). We also briefly highlight stress‐induced cell senescence that plays a role not only in organismal ageing but also offers the development of novel anticancer strategies. Finally, we briefly illustrate the interconnected character of cell death forms in clinical settings while discussing irradiation‐induced mitotic catastrophe. The signalling pathways are discussed in their relation to cancer biology and treatment approaches.
Hypoxia‐inducing factors as master regulators of stemness properties and altered metabolism of cancer‐ and metastasis‐initiating cells
Authors: Mimeault Murielle , Batra Surinder K. 
Published: January 2013

AbstractAccumulating lines of experimental evidence have revealed that hypoxia‐inducible factors, HIF‐1α and HIF‐2α, are key regulators of the adaptation of cancer‐ and metastasis‐initiating cells and their differentiated progenies to oxygen and nutrient deprivation during cancer progression under normoxic and hypoxic conditions. Particularly, the sustained stimulation of epidermal growth factor receptor (EGFR), insulin‐like growth factor‐1 receptor (IGF‐1R), stem cell factor (SCF) receptor KIT, transforming growth factor‐β receptors (TGF‐βRs) and Notch and their downstream signalling elements such as phosphatidylinositol 3′‐kinase (PI3K)/Akt/molecular target of rapamycin (mTOR) may lead to an enhanced activity of HIFs. Moreover, the up‐regulation of HIFs in cancer cells may also occur in the hypoxic intratumoral regions formed within primary and secondary neoplasms as well as in leukaemic cells and metastatic prostate and breast cancer cells homing in the hypoxic endosteal niche of bone marrow. The activated HIFs may induce the expression of numerous gene products such as induced pluripotency‐associated transcription factors (Oct‐3/4, Nanog and Sox‐2), glycolysis‐ and epithelial‐mesenchymal transition (EMT) programme‐associated molecules, including CXC chemokine receptor 4 (CXCR4), snail and twist, microRNAs and angiogenic factors such as vascular endothelial growth factor (VEGF). These gene products in turn can play critical roles for high self‐renewal ability, survival, altered energy metabolism, invasion and metastases of cancer cells, angiogenic switch and treatment resistance. Consequently, the targeting of HIF signalling network and altered metabolic pathways represents new promising strategies to eradicate the total mass of cancer cells and improve the efficacy of current therapies against aggressive and metastatic cancers and prevent disease relapse.
Bone marrow mesenchymal stem cells increase motility of prostate cancer cells via production of stromal cell‐derived factor‐1α
Authors: Mognetti Barbara , Montagna Giuseppe La , Perrelli Maria Giulia , Pagliaro Pasquale , Penna Claudia 
Published: January 2013

AbstractProstate cancer frequently metastasizes to the bone, and the interaction between cancer cells and bone microenvironment has proven to be crucial in the establishment of new metastases. Bone marrow mesenchymal stem cells (BM‐MSCs) secrete various cytokines that can regulate the behaviour of neighbouring cell. However, little is known about the role of BM‐MSCs in influencing the migration and the invasion of prostate cancer cells. We hypothesize that the stromal cell‐derived factor‐1α released by BM‐MSCs may play a pivotal role in these processes. To study the interaction between factors secreted by BM‐MSCs and prostate cancer cells we established an in vitro model of transwell co‐culture of BM‐MSCs and prostate cancer cells DU145. Using this model, we have shown that BM‐MSCs produce soluble factors which increase the motility of prostate cancer cells DU145. Neutralization of stromal cell‐derived factor‐1α (SDF1α) via a blocking antibody significantly limits the chemoattractive effect of bone marrow MSCs. Moreover, soluble factors produced by BM‐MSCs greatly activate prosurvival kinases, namely AKT and ERK 1/2. We provide further evidence that SDF1α is involved in the interaction between prostate cancer cells and BM‐MSCs. Such interaction may play an important role in the migration and the invasion of prostate cancer cells within bone.
Molecular microarray analysis reveals allergen‐ and exotoxin‐specific IgE repertoires in children with atopic dermatitis
Authors: Ott H. , Weißmantel S. , Kennes L.N. , Merk H.F. , Baron J.M. , Fölster‐Holst R. 
Published: January 2013

AbstractBackgroundChildren suffering from atopic dermatitis frequently show allergen‐specific sensitization. However, the corresponding IgE‐recognition patterns have not yet been extensively characterized using multiallergen microarrays.ObjectiveTo provide comprehensive, molecular IgE repertoires in paediatric patients with atopic dermatitis using microarray technology.MethodsSera of 140 affected children were screened with a protein microarray containing a panel of 95 inhalant, food and staphylococcal antigen components. In addition, total serum IgE levels and further clinical parameters were recorded.ResultsAt a mean total IgE level of 1528 kU/L, the number of sensitizations varied from 0 to 32 per patient, and regression analysis revealed a significant association between total IgE and the quantity of recognized antigens. A total of 78 single allergen and microbial components elicited at least one IgE response, while 11 plant and 13 non‐plant molecules were recognized by more than 10% of patients. Specific IgE against Staphylococcus aureus could be detected in 14% of children. Sensitization rates against the studied allergen molecules differed significantly when stratified by age. Whereas reactivity against inhalant allergens and SEC was lowest in the youngest group (<24 months) reaching highest values in children ≥72 months, IgE responses against food allergen components peaked in younger age groups (0–48 months) and clearly declined in patients of higher age. The large amount of microarray data could be aggregated by centroid cluster analysis revealing valid allergen clusters possibly linked with higher disease severity as determined by multivariate analysis of covariance.ConclusionAllergenic molecule microarray analysis can be regarded as a suitable research tool for large‐scale IgE screening in infants and children with atopic dermatitis (AD). Still, further studies in well‐defined populations are needed to exactly identify its tangible benefits in the diagnostic and therapeutic management of affected patients in daily clinical practice.
Tacrolimus abrogates TGF‐β1‐induced type I collagen production in normal human fibroblasts through suppressing p38MAPK signalling pathway: implications on treatment of chronic atopic dermatitis lesions
Authors: Lan C.‐C.E. , Fang A.‐H. , Wu P.‐H. , Wu C.‐S. 
Published: January 2013

AbstractBackgroundAtopic dermatitis (AD) is a commonly encountered inflammatory skin disease. Although acute lesions of acute AD are characterized by intense inflammation, the hallmarks of chronic AD lesions include lichenified fibrosis and thickening of the upper dermis. The increased expression of transforming growth factor beta 1 (TGF‐β1), a well‐known fibrogenic cytokine, is observed in chronic AD lesions. Tacrolimus (FK506) ointment has been reported to be effective for treating AD as well as some TGF‐β1‐induced fibrotic diseases.ObjectivesTo evaluate the effect of tacrolimus on TGF‐β1‐stimulated cultured normal human dermal fibroblasts and explore the potential signalling pathways involved.MethodsFibroblasts cultured from healthy adult human foreskins were treated with TGF‐β1 with or without tacrolimus. The impact on cell viability and proliferation were assessed by [3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide] (MTT) assay and BrdU incorporation assay respectively. Reverse transcription‐polymerase chain reaction (RT‐PCR), quantitative real‐time PCR, enzyme‐linked immunosorbent assay (ELISA) and western blotting were performed to evaluate the relevant expressions of mRNA or proteins in fibroblasts.ResultsOur results revealed that the increased expressions of transforming growth factor‐β receptor I (TGF‐βRI) and TGF‐βRII in TGF‐β1‐treated fibroblasts were suppressed by tacrolimus treatment. In addition, tacrolimus significantly inhibited fibroblast proliferation enhanced by TGF‐β1. TGF‐β1 increased type I collagen production, and this enhancing effect was suppressed by tacrolimus. The down‐regulation of MMP‐1 and up‐regulation of TIMP‐1 induced by TGF‐β1 were reversed by tacrolimus. The increase in phosphorylated p38 mitogen‐activated protein kinase (p38MAPK) expression stimulated by TGF‐β1 was down‐regulated by tacrolimus. Moreover, the fibroblasts treated with p38MAPK inhibitor significantly reduced type I collagen expression induced by TGF‐β1.ConclusionsThe present results demonstrated that tacrolimus significantly inhibited physiological functions of fibroblasts enhanced by TGF‐β1 in vitro. Clinically, we propose that topical tacrolimus may not only reduce AD recurrence but also ameliorate dermal fibrosis often seen in chronic AD lesions.
Measurement of health‐related quality of life in dermatological research and practice: outcome of theEADVTaskforce on Quality of Life
Authors: Prinsen C.A.C. , de Korte J. , Augustin M. , Sampogna F. , Salek S.S. , Basra M.K.A. , Holm E.A. , Nijsten T.E.C. ,   The EADV Taskforce on Quality of Life
Published: January 2013

AbstractIn the last decade, the importance of the measurement of health‐related quality of life (HRQoL) has grown significantly. Today,HRQoL measurement is generally considered to be important in clinical trials, in the assessment of disease severity, in patient management and in the field of health economics. Therefore, a good understanding of the concept ofHRQoL and its measurement instruments is a prerequisite for both researchers and clinicians. The European Academy for Dermatology and Venereology (EADV) Taskforce on Quality of Life encourages the application ofHRQoL instruments in research and clinical practice, and with this manuscript, the Taskforce aims to contribute to the quality of this application. In dermatology, a large number ofHRQoL instruments exist and herewith, we summarize the most commonly used generic and dermatology‐specificHRQoL instruments. Information is given on the most important psychometric characteristics of these instruments, including: scale structure, reliability, validity and responsiveness. Furthermore, a flow chart is provided to support researchers and clinicians in selecting an existing instrument or, in case an appropriate instrument does not exist, in finding alternative solutions. The present manuscript is the first of a series of manuscripts to be written on behalf of theEADVTaskforce on Quality of Life, aiming to contribute to the scientific knowledge and measurement of patient reported outcomes in dermatological research and practice.