bluuebunny/crossref_metadata_2025_split huggingface dataset:
Barriers and enablers to applying for the Dietitians Association of Australia Advanced Accredited Practising Dietitian credential: A qualitative analysis
Authors: Gifford Janelle , Snell Robynne 
Published: November 2014

AbstractAimThe present study aimed to identify barriers and enablers to applying for the Advanced Accredited Practising Dietitian (AdvAPD) credential as well as problems with the application process.MethodsEleven Accredited Practising Dietitians (APDs) and nine AdvAPDs were recruited to participate by telephone in focus groups or in one‐on‐one interviews via the weekly national Dietitians Association of Australia (DAA) e‐alert and advertisement at the 2012 National Conference. Semistructured interview schedules were used to guide the groups and interviews which were recorded via the DAA conferencing facility and subsequently transcribed verbatim. Themes were identified using qualitative analysis software.ResultsBarriers to applying for the AdvAPD credential included the onerousness of the process, busy‐ness/finding the time, and having competing priorities, while working with colleagues, receiving recognition and having an AdvAPD mentor were predominant enablers. Problems identified with the application process included the difficulty in completing specific parts of the application, particularly the research and management/supervision components, and the assessment/definition of advanced practice itself. Suggested improvements included the use of technology in submission, and provision of a range of examples for reference.ConclusionsAPDs wishing to apply for the AdvAPD credential are encouraged to apply key findings such as engaging a mentor, working with colleagues and seeking successful application examples as strategies within their plan. The broader results will inform the review of the performance criteria and evidence examples currently available to AdvAPD applicants and support development of additional tools to assist the application process.
Increase of peripheral T regulatory cells during remission induction with cyclophosphamide in active systemic lupus erythematosus
Authors: Tselios Konstantinos , Sarantopoulos Alexandros , Gkougkourelas Ioannis , Papagianni Aikaterini , Boura Panagiota 
Published: November 2014

AbstractBackgroundCyclophosphamide efficacy in lupus nephritis (LN) and neuropsychiatric systemic lupus erythematosus (NPSLE) is probably mediated by a non‐specific ablation of reactive lymphocytes. However, little is known in regard to its effect on T regulatory cells (Tregs) in such patients, which was the aim of this study.Patients and MethodsTen Caucasian lupus patients were included, six with LN classes IV–V (mean age 33.8 ± 8.8 years) and four with NPSLE (mean age 35.5 ± 8.8 years, clinical manifestations: 1/4 acute confusional state, 1/4 psychosis, 2/4 refractory seizures). Cyclophosphamide was administered at monthly pulses (500 mg/m2/month for 6 months); doses of other administered drugs, including steroids, remained stable or lower. CD4+CD25highFOXP3+ Tregs were assessed by flow‐cytometry at baseline and before every subsequent pulse and 3–6 months after the final pulse. Disease activity was assessed by SLE Disease Activity Index (SLEDAI).ResultsIn LN patients, Tregs were significantly increased even after the fourth pulse (0.54 ± 0.20% vs. 1.24 ± 0.29%, P < 0.001). Likewise, in NPSLE, Tregs were significantly expanded after the fourth pulse (0.57 ± 0.23% vs. 1.41 ± 0.28%, P < 0.001). SLEDAI was significantly reduced in all patients.ConclusionsCyclophosphamide pulse therapy was associated with a significant increase of the CD4+CD25highFOXP3+ Tregs in patients with active LN and NPSLE. This effect is probably indirect and may partially explain the beneficial role of cyclophosphamide in such cases.
Prognostic impact of the TP53 rs1625895 polymorphism in DLBCL patients
Authors: Voropaeva Elena N. , Voevoda Mikhail I. , Pospelova Tatiana I. , Maksimov Vladimir N. 
Published: November 2014

SummaryThis study aimed to clarify the association between the TP53 rs1625895 polymorphism and the efficiency of R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) therapy in 106 patients with diffuse large B cell lymphoma (DLBCL). All patients received six to eight courses of R‐CHOP therapy as a first‐line treatment. The rs1625895 polymorphism was genotyped by polymerase chain reaction with restriction fragment length polymorphism assay. The G/G genotype of the TP53 rs1625895 polymorphism was shown to be associated with a high probability of R‐CHOP therapy failure in DLBCL patients according to the probability of remission as well as 5‐year overall and relapse‐free survivals.
Absorption of the Wolffian duct and duplicated ureter by the urogenital sinus: morphological study using human fetuses and embryos
Authors: Naito Michiko , Hinata Nobuyuki , Rodriguez‐Vazquez Jose Francisco , Murakami Gen , Aizawa Shin , Fujisawa Masato 
Published: November 2014

ObjectivesTo describe the embryological origin of the duplicated ureter and to investigate whether the urogenital sinus absorbs not only the Wolffian duct (WD) but also the ureter.Materials and MethodsDuring studies using sections of human fetuses (45 specimens), we incidentally found a specific type of ureteric duplication (at ~7 weeks) in which two unilateral ureters joined at the vesico‐ureteric junction, apparently representing a morphology arising at an intermediate stage between complete and partial ureteric duplication. The existing literature lacks any photographic representation of early development of the vesico‐ureteric junction, and we therefore studied horizontal sections of 10 human embryos (at ~5–6 weeks' gestation) in which the ureter did not join the urogenital sinus (future bladder) but instead joined the WD (future vas deferens).ResultsThe sinus consistently showed a reversed Y‐shape, the arms of which extended posteriorly to receive the WD. When absorption of the duct into the sinus wall reached the distal end of the ureter, the arm‐like parts appeared to enlarge posteriorly for further involvement of the duct, with little or no incorporation of the ureter; therefore, the future trigone of the bladder might develop from these arm‐like parts of the sinus posterior wall. Consequently, in the case of ureteric duplication included in the present study, it is considered that the ureters would probably have merged with the WD at closely adjacent sites.ConclusionThe present study represents the first photographic illustration of the early development of the human vesico‐ureteric junction.
Gut T cell receptor-γδ+ intraepithelial lymphocytes are activated selectively by cholera toxin to break oral tolerance in mice
Authors: Frossard C P , Asigbetse K E , Burger D , Eigenmann P A 
Published: November 2014

SummaryThe gut immune system is usually tolerant to harmless foreign antigens such as food proteins. However, tolerance breakdown may occur and lead to food allergy. To study mechanisms underlying food allergy, animal models have been developed in mice by using cholera toxin (CT) to break tolerance. In this study, we identify T cell receptor (TCR)-γδ+ intraepithelial lymphocytes (IELs) as major targets of CT to break tolerance to food allergens. TCR-γδ+ IEL-enriched cell populations isolated from mice fed with CT and transferred to naive mice hamper tolerization to the food allergen β-lactoglobulin (BLG) in recipient mice which produce anti-BLG immunoglobulin (Ig)G1 antibodies. Furthermore, adoptive transfer of TCR-γδ+ cells from CT-fed mice triggers the production of anti-CT IgG1 antibodies in recipient mice that were never exposed to CT, suggesting antigen-presenting cell (APC)-like functions of TCR-γδ+ IELs. In contrast to TCR-αβ+ cells, TCR-γδ+ IELs bind and internalize CT both in vitro and in vivo. CT-activated TCR-γδ+ IELs express major histocompatibility complex (MHC) class II molecules, CD80 and CD86 demonstrating an APC phenotype. CT-activated TCR-γδ+ IELs migrate to the lamina propria, where they produce interleukin (IL)-10 and IL-17. These results provide in-vivo evidence for a major role of TCR-γδ+ IELs in the modulation of oral tolerance in the pathogenesis of food allergy.
Pleiotropic Role of PPARγ in Intracerebral Hemorrhage: An Intricate System Involving Nrf2, RXR, and NF‐κB
Authors: Zhao Xiu‐Rong , Gonzales Nicole , Aronowski Jaroslaw 
Published: November 2014

SummaryIntracerebral hemorrhage (ICH) is a subtype of stroke involving formation of hematoma within brain parenchyma, which accounts for 8–15% of all strokes in Western societies and 20–30% among Asian populations, and has a 1‐year mortality rate >50%. The high mortality and severe morbidity make ICH a major public health problem. Only a few evidence‐based targeted treatments are used for ICH management, and interventions focus primarily on supportive care and comorbidity prevention. Even in patients who survive the ictus, extravasated blood (including plasma components) and subsequent intrahematoma hemolytic products trigger a series of adverse events within the brain parenchyma, leading to secondary brain injury, edema and severe neurological deficits or death. Although the hematoma in humans gradually resolves within months, full restoration of neurological function can be slow and often incomplete, leaving survivors with devastating neurological deficits. During past years, peroxisome proliferator‐activated receptor gamma (PPARγ) transcription factor and its agonists received recognition as important players in regulating not only glucose and lipid metabolism (which underlies its therapeutic effect in type 2 diabetes mellitus), and more recently, as an instrumental pleiotropic regulator of antiinflammation, antioxidative regulation, and phagocyte‐mediated cleanup processes. PPARγ agonists have emerged as potential therapeutic target for stroke. The use of PPARγ as a therapeutic target appears to have particularly strong compatibility toward pathogenic components of ICH. In addition to its direct genomic effect, PPARγ may interact with transcription factor, NF‐κB, which may underlie many aspects of the antiinflammatory effect of PPARγ. Furthermore, PPARγ appears to regulate expression of Nrf2, another transcription factor and master regulator of detoxification and antioxidative regulation. Finally, the synergistic costimulation of PPARγ and retinoid X receptor, RXR, may play an additional role in the therapeutic modulation of PPARγ function. In this article, we outline the main components of the role of PPARγ in ICH pathogenesis.
Elevated immune monitoring early after cardiac transplantation is associated with increased plaque progression by intravascular ultrasound
Authors: Cheng Richard , Azarbal Babak , Yung Aaron , Chang David H. , Patel Jignesh K. , Kobashigawa Jon A. 
Published: November 2014

AbstractBackgroundImmune monitoring (IM) has not been shown to be associated with cardiac allograft vasculopathy (CAV).MethodsMaximal intimal area, average percent stenosis, plaque volume, and maximal intimal thickness (MIT) were measured for matched baseline and one‐yr IVUS segments in a blinded fashion. Patients were divided into quartiles by IM scores and outcomes compared. Optimal IM cutoff was determined.ResultsIM assays were measured at 63.7 ± 16.4 d after transplantation in fifty patients. Progression of maximal intimal area (p = 0.005), average percent stenosis (p < 0.001), plaque volume (p = 0.005), and MIT (p = 0.001) were increased across the quartiles. An optimal IM assay cutoff of 406.0 ng ATP/mL demonstrated a sensitivity of 66.7% and specificity of 94.3% for predicting rapid progression of MIT ≥ 0.5 mm. Mean IM scores for Group 1 vs. Group 2 were 176.4 ± 102.2 and 616.3 ± 239.5 ngATP/mL, respectively. Rapid progression of MIT ≥ 0.5 mm occurred in 5/38 patients (13.2%) in Group 1 vs. 10/12 patients (83.3%) in Group 2 (p < 0.001). The risk ratio for rapid progression with elevated IM was 11.7 (p < 0.001).ConclusionElevated early IM scores are associated with progression of CAV by IVUS. These findings suggest the potential of IM for tailoring of immunosuppressive regimens to minimize the progression of CAV in high‐risk patients.
Treatment of antibody‐mediated rejection in renal transplant patients: a clinical practice survey
Authors: Burton Stephanie A. , Amir Naaseha , Asbury Alaina , Lange Alex , Hardinger Karen L. 
Published: November 2014

AbstractIntroductionPreferences for the testing and treatment of antibody‐mediated rejection (AMR) in renal transplant patients vary among programs and individual practitioners. The description of these preferences and identification of commonalities can contribute to creating a standard of care.MethodsA survey was distributed through the Transplant Listserv of the American College of Clinical Pharmacy (ACCP) and via email to members of the American Society of Transplantation Community of Pharmacy (AST CoP), collected, and analyzed.ResultsMost clinicians (26/28) test for donor‐specific antibodies (DSAs) when evaluating a patient with possible AMR. Treatments for AMR varied widely among responding clinicians and included intravenous immune globulin (IVIG, n = 25), plasmapheresis (n = 24), rituximab (n = 8), bortezomib (n = 4), rabbit antithymocyte globulin (n = 2), and eculizumab (n = 1). Weight‐based dosing of IVIG averaged 1.8 g/kg total dose. Six centers use rituximab as initial therapy, while two use rituximab if other therapy fails. Four centers use bortezomib as initial therapy, while two centers use it for severe/persistent AMR. One center uses eculizumab as initial therapy and one center uses it for severe AMR.ConclusionMethods for the detection of AMR are similar, yet treatment of AMR varies widely. Most centers utilize DSA for detection and a combination of IVIG and plasmapheresis for treatment.
Stress and inflammatory biomarkers and symptoms are associated with bioimpedance measures
Authors: Tsigos Constantine , Stefanaki Charikleia , Lambrou George I. , Boschiero Dario , Chrousos George P. 
Published: November 2014

AbstractBackgroundThis large cross‐sectional, multi‐centre study evaluated the association of body composition measurements by a novel dual frequency bioimpedance device (BIA‐ACC) with chronic stress/inflammation biomarkers and the presence of medically unexplained symptoms (MUS).Materials and methodsParticipants were adult Caucasians of both sexes and included 10 416 lean subjects with no MUS (Group A), 58 710 lean subjects with MUS (Group B) and 30 445 overweight/obese subjects with no MUS and excessive fat mass (FM) (Group C).ResultsTotal body extracellular water (ECW) was higher, while intracellular water (ICW) was lower in Group B than both other groups (P < 0·01). Group A had significantly lower FM and higher skeletal mass (SK) and phase angle (PA) than Group B and lower circulating high sensitivity (hs) CRP levels than both other groups. hsCRP was higher in Group C than Group A though (P < 0·01). Salivary cortisol in Group B was lower in the morning and higher in the evening than both other groups (P < 0·001), indicating circadian rhythm obliteration or reversal in this group. ECW correlated positively with serum hsCRP and 8 p.m. salivary cortisol, but negatively with 8 a.m. salivary cortisol, while PA correlated positively with 8 a.m. and negatively with 8 p.m. salivary cortisol and serum hsCRP. Both 8 a.m. and 8 p.m. salivary cortisol and serum hsCRP were associated with the presence of MUS and BIA‐ACC measurements, including ECW, ICW, FM, SK and PA.ConclusionsMUS is an index of chronic stress and inflammation and BIA‐ACC may provide a useful, bloodless and rapid tool in the clinical setting, distinguishing patients with chronic stress/inflammation from healthy subjects and monitoring their response to treatment.
An electronic oral health record to document, plan and educate
Authors: Wagner I‐V. , Lex MacNeil M. A. J. , Esteves A. , MacEntee M. I. 
Published: November 2014

AbstractThe University of British Columbia (UBC) in collaboration with a software developer (Planmeca Oy, Finland) created an electronic oral health record based on the principles of cognitive ergonomics rooted in the European research and development project ‘ORQUEST’ to guide students through medical, dental, social histories, examinations, treatment planning and progress notes. Clinicians in each dental specialty of the Faculty of Dentistry and software engineers cooperated to define the clinical content and workflow of clinical procedures in three phases: (i) development of a radiographic module, (ii) development of medical, dental, social and family histories, intra‐ and extra‐oral examinations, progress notes and treatment planning and (iii) development of the orthodontic section accompanied by an optimisation phase to correct technical problems and clinical content issues. From a practical perspective, this EOHR enhances the clinical performance of students and the quality assurance capacity of the institution. It facilitates audits of clinical productivity and research, and it can be modified with relative ease to suit similar educational and clinical environments in either public or private healthcare settings.
RAGE mediates the inactivation of nAChRs in sympathetic neurons under high glucose conditions
Authors: Chandna Andrew R. , Nair Manoj , Chang Christine , Pennington Paul R. , Yamamoto Yasuhiko , Mousseau Darrell D. , Campanucci Verónica A. 
Published: November 2014

AbstractAutonomic dysfunction is a serious complication of diabetes and can lead to cardiovascular abnormalities and premature death. It was recently proposed that autonomic dysfunction is triggered by oxidation‐mediated inactivation of neuronal nicotinic acetylcholine receptors (nAChRs), impairing synaptic transmission in sympathetic ganglia and resulting in autonomic failure. We investigated whether the receptor for advanced glycation end products (RAGE) and its role in the generation of reactive oxygen species (ROS) could be contributing to the events that initiate sympathetic malfunction under high glucose conditions. Using biochemical, live imaging and electrophysiological tools we demonstrated that exposure of sympathetic neurons to high glucose increases RAGE expression and oxidative markers, and that incubation with RAGE ligands (e.g. AGEs, S100 and HMGB1) mimics both ROS elevation and nAChR inactivation. In contrast, co‐treatment with either antioxidants or an anti‐RAGE IgG prevented the inactivation of nAChRs. Lastly, a role for RAGE in this context was corroborated by the lack of sensitivity of sympathetic neurons from RAGE knock‐out mice to high glucose. These data define a pivotal role for RAGE in initiating the events associated with exposure of sympathetic neurons to high glucose, and strongly support RAGE signaling as a potential therapeutic target in the autonomic complications associated with diabetes.
The course of childhood‐onset epilepsy over the first two decades: A prospective, longitudinal study
Authors: Berg Anne T. , Rychlik Karen 
Published: November 2014

SummaryObjectivesDetermine frequency of remissions, relapses, and pharmacoresistance over two decades. Develop a composite measure of seizure control over that time.MethodsCommunity‐based cohort of children with newly diagnosed epilepsy prospectively followed for up to 21 years with frequent calls and periodic medical record review. Multiple periods of 1‐, 2‐, 3‐, and 5‐year remission with subsequent relapses were recorded. Other outcomes included pharmacoresistance (failure of two adequately used drugs), early remission and early pharmacoresistance by 2 years, and complete remission at last contact (CR‐LC, 5 years both seizure‐ and drug‐free at last contact). A composite summary of seizure course was created with eight categories ranging from early sustained remission and CR‐LC (best) to never achieving a 1‐year remission (worst).ResultsFive hundred sixteen of 613 participants were followed ≥10 years. An initial 1‐ 2‐, 3‐, and 5‐year remission occurred, respectively, in 95%, 92%, 89%, and 81%. Relapses followed in 52%, 41%, 29%, and 15%, respectively. Repeated remission after relapse was common. Up to seven 1‐year, five 2‐year and 3‐year, and two 5‐year remissions were recorded per participant. Pharmacoresistance at any time, early pharmacoresistance (<2 years), early remission, and CR‐LC occurred in 118 (22.9%), 70 (13.6%), 283 (54.8%), and 311 (60.3%). Composite outcomes were early sustained remission with CR‐LC (N = 172, 33%); later but then sustained remission with CR‐LC (N = 51, 10%); one (N = 61, 12%) or more (N = 27, 5%) remission‐relapse episodes but then CR‐LC; various non‐CR‐LC outcomes (N = 179, 35%); and never achieved 1‐year remission (N = 26, 5%). These patterns varied across groups defined by epilepsy type and presence of brain insults or neurodisability (p < 0.0001).SignificanceThe seizure prognosis of pediatric epilepsies is highly variable. Most patients follow complex courses not easily summarized by remission status at the end of a period of follow‐up. These complexities may facilitate efforts to understand the impact epilepsy has on young people entering adulthood.
Evaluation of carotenoids and reactive oxygen species in human skin after UV irradiation: a critical comparison between in vivo and ex vivo investigations
Authors: Meinke Martina C. , Müller Robert , Bechtel Anne , Haag Stefan F. , Darvin Maxim E. , Lohan Silke B. , Ismaeel Fakher , Lademann Jürgen 
Published: November 2014

AbstractUV irradiation is one of the most harmful exogenous factors for the human skin. In addition to the development of erythema, free radicals, that is reactive oxygen species (ROS), are induced under its influence and promote the development of oxidative stress in the skin. Several techniques are available for determining the effect of UV irradiation. Resonance Raman spectroscopy (RRS) measures the reduction of the carotenoid concentration, while electron paramagnetic resonance (EPR) spectroscopy enables the analysis of the production of free radicals. Depending on the method, the skin parameters are analysed in vivo or ex vivo. This study provides a critical comparison between in vivo and ex vivo investigations on the ROS formation and carotenoid depletion caused by UV irradiation in human skin. The oxygen content of tissue was also determined. It was shown that the antioxidant status measured in the skin samples in vivo and ex vivo was different. The depletion in the carotenoid concentration in vivo exceeded the value determined ex vivo by a factor of about 1.5, and the radical formation after UV irradiation was significantly greater in vivo by a factor of 3.5 than that measured in excised human skin, which can be explained by the lack of oxygen ex vivo.
A putative antipruritic mechanism of the phosphodiesterase‐4 inhibitor E6005 by attenuating capsaicin‐induced depolarization of C‐fibre nerves
Authors: Wakita Hisashi , Ohkuro Masayoshi , Ishii Naoto , Hishinuma Ieharu , Shirato Manabu 
Published: November 2014

AbstractE6005, a potent, selective phosphodiesterase (PDE) 4 inhibitor, has been developed as a novel topical agent of atopic dermatitis (AD). It has been shown to inhibit itching in patients with AD as well in mouse models. To study the mechanism underlying the anti‐pruritic effect of E6005, we examined its effect on the activation of dorsal root ganglion (DRG) neurons associated with the itch sensation. Depolarization of DRG neurons by a transient receptor potential vanilloid 1 (TRPV 1) activator, capsaicin was attenuated by E6005 as well as by a 3′,5′‐cyclic adenosine monophosphate (cAMP) elevator, forskolin. E6005 elevated intracellular levels of cAMP in DRG cells. Taken together, these results suggest that E6005 suppresses TRPV1‐mediated C‐fibre depolarization through elevation of cAMP levels, thereby exerting an anti‐pruritic effect. Thus, E6005 shows the potential to be a new agent for managing pruritus in various skin disorders, including AD.