bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biodistribution of Evans blue in an orthotopic AY‐27 rat bladder urothelial cell carcinoma model: implication for the improved diagnosis of non‐muscle‐invasive bladder cancer (NMIBC) using dye‐guided white‐light cystoscopy
Authors: Elsen Sanne , Lerut Evelyne , Van Cleynenbreugel Ben , van der Aa Frank , van Poppel Hein , de Witte Peter A. 
Published: March 2015

ObjectivesTo investigate the possibility of using Evans blue (EB) as a novel diagnostic tool to detect bladder tumours with white‐light (WL) cystoscopy, in this preclinical study we examine the biodistribution of EB in the different layers (urothelium, submucosa, muscle) of a normal rat bladder and a rat bladder bearing a malignant urothelium composed of syngeneic AY‐27 tumour cells.Materials and MethodsEB was instilled into both normal as well as tumour‐bearing rat bladders. After instillation, bladders were removed and snap frozen in liquid nitrogen. The distribution of EB in the different layers was quantified using fluorescence microscopy. To gain more insight into the mechanism underlying the selective accumulation of EB in tumour tissue, bladder sections were prepared for ultrastructural investigations by means of transmission electron microscopy (TEM). In addition, we also examined the expression of E‐cadherin, claudin‐1 and desmoglein‐1 by immunohistochemistry to study the integrity of the bladder wall, as these molecules are key constituents of adherens junctions, tight junctions and desmosomes, respectively.ResultsIn most cases, the accumulation of EB in malignant bladders was substantially higher than in healthy bladders, at least when 1 mm EB instillations were used. In case of a 1 mm EB instillation for 2 h, the EB‐associated fluorescence in malignant urothelial tissue was 55‐times higher than the fluorescence found in normal urothelium. Ultrastructurally, malignant tissue displayed wider intercellular spaces and a decreased number of cell junction components compared with normal tissue, pointing to defects in the urothelial barrier. There were no differences in the expression of E‐cadherin, whereas desmoglein‐1 staining was stronger in the membranes of healthy bladder urothelium compared with tumour tissue. Claudin‐1 expression was negative in all samples tested.ConclusionEB is selectively taken up by tumour tissue after intravesical instillations in rats bearing bladder tumours. The lower expression of desmoglein‐1 in tumour samples, together with the reduced presence of desmosomes seen with TEM, likely imply that desmosomes play an important role in the ultrastructural differences between healthy rat urothelium and tumour tissue, and secondary to that, to the differential uptake of EB in both tissues. We consider that our findings could be useful for future clinical developments in the field of diagnostics for bladder cancer.
Role of aldehyde dehydrogenase in hypoxic vasodilator effects of nitrite in rats and humans
Authors: Arif Sayqa , Borgognone Alessandra , Lin Erica Lai‐Sze , O'Sullivan Aine G , Sharma Vishal , Drury Nigel E , Menon Ashvini , Nightingale Peter , Mascaro Jorge , Bonser Robert S , Horowitz John D , Feelisch Martin , Frenneaux Michael P , Madhani Melanie 
Published: March 2015

Background and PurposeHypoxic conditions favour the reduction of nitrite to nitric oxide (NO) to elicit vasodilatation, but the mechanism(s) responsible for bioconversion remains ill defined. In the present study, we assess the role of aldehyde dehydrogenase 2 (ALDH2) in nitrite bioactivation under normoxia and hypoxia in the rat and human vasculature.Experimental ApproachThe role of ALDH2 in vascular responses to nitrite was studied using rat thoracic aorta and gluteal subcutaneous fat resistance vessels from patients with heart failure (HF; 16 patients) in vitro and by measurement of changes in forearm blood flow (FBF) during intra‐arterial nitrite infusion (21 patients) in vivo. Specifically, we investigated the effects of (i) ALDH2 inhibition by cyanamide or propionaldehyde and the (ii) tolerance‐independent inactivation of ALDH2 by glyceryl trinitrate (GTN) on the vasodilator activity of nitrite. In each setting, nitrite effects were measured via evaluation of the concentration–response relationship under normoxic and hypoxic conditions in the absence or presence of ALDH2 inhibitors.Key ResultsBoth in rat aorta and human resistance vessels, dilatation to nitrite was diminished following ALDH2 inhibition, in particular under hypoxia. In humans there was a non‐significant trend towards attenuation of nitrite‐mediated increases in FBF.Conclusions and ImplicationsIn human and rat vascular tissue in vitro, hypoxic nitrite‐mediated vasodilatation involves ALDH2. In patients with HF in vivo, the role of this enzyme in nitrite bioactivation is at the most, modest, suggesting the involvement of other more important mechanisms.
Supraspinal actions of nociceptin/orphanin FQ, morphine and substance P in regulating pain and itch in non‐human primates
Authors: Ding H , Hayashida K , Suto T , Sukhtankar D D , Kimura M , Mendenhall V , Ko M C 
Published: March 2015

Background and PurposeNociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor agonists display a promising analgesic profile in preclinical studies. However, supraspinal N/OFQ produced hyperalgesia in rodents and such effects have not been addressed in primates. Thus, the aim of this study was to investigate the effects of centrally administered ligands on regulating pain and itch in non‐human primates. In particular, nociceptive thresholds affected by intracisternal N/OFQ were compared with those of morphine and substance P, known to provide analgesia and mediate hyperalgesia, respectively, in humans.Experimental ApproachIntrathecal catheters were installed to allow intracisternal and lumbar intrathecal administration in awake and unanaesthetized rhesus monkeys. Nociceptive responses were measured using the warm water tail‐withdrawal assay. Itch scratching responses were scored from videotapes recording behavioural activities of monkeys in their home cages. Antagonist studies were conducted to validate the receptor mechanisms underlying intracisternally elicited behavioural responses.Key ResultsIntracisternal morphine (100 nmol) elicited more head scratches than those after intrathecal morphine. Distinct dermatomal scratching locations between the two routes suggest a corresponding activation of supraspinal and spinal μ receptors. Unlike intracisternal substance P, which induced hyperalgesia, intracisternal N/OFQ (100 nmol) produced antinociceptive effects mediated by NOP receptors. Neither peptide increased scratching responses.Conclusions and ImplicationsTaken together, these results demonstrated differential actions of ligands in the primate supraspinal region in regulating pain and itch. This study not only improves scientific understanding of the N/OFQ‐NOP receptor system in pain processing but also supports the therapeutic potential of NOP‐related ligands as analgesics.
α‐Galactosylceramide suppresses murine eosinophil production through interferon‐γ‐dependent induction ofNOsynthase andCD95
Authors: Gaspar‐Elsas Maria Ignez , Queto Túlio , Masid‐de‐Brito Daniela , Vieira Bruno Marques , de Luca Bianca , Cunha Fernando Queiroz , Xavier‐Elsas Pedro 
Published: March 2015

Background and Purposeα‐Galactosylceramide (α‐GalCer), a pleiotropic immunomodulator with therapeutic potential in neoplastic, autoimmune and allergic diseases, activates invariant natural killerT‐cells throughCD1‐restricted receptors for α‐GalCer on antigen‐presenting cells, inducing cytokine secretion. However the haemopoietic effects of α‐GalCerremain little explored.Experimental Approachα‐GalCer‐induced modulation of eosinophil production inIL‐5‐stimulated bone marrow cultures was examined in wild‐type (BALB/c,C57BL/6) mice and their mutants lackingCD1, inducibleNOS(iNOS),CD95 andIFN‐γ, along with the effects of lymphocytes;IFN‐γ; caspase andiNOSinhibitors; non‐steroidal anti‐inflammatory drugs (NSAIDs) andLTD4; and dexamethasone.Key Resultsα‐GalCer (10−6–10−8M) suppressedIL‐5‐stimulated eosinopoiesis by inducing apoptosis. α‐GalCer pretreatmentin vivo(100 μg·kg−1, i.v.) suppressed colony formation byGM‐CSF‐stimulated bone marrow progenitors in semi‐solid cultures. α‐GalCerand dexamethasone synergistically promoted eosinophil maturation. Suppression of eosinophil production by α‐GalCerwas prevented by aminoguanidine and was undetectable in bone marrow lackingiNOS,CD95,CD28; orCD1d. Separation on Percoll gradients and depletion ofCD3+ cells made bone marrow precursors unresponsive to α‐GalCer. Responsiveness was restored with splenic lymphocytes. Experiments with (i)IFN‐γ‐deficient bone marrow, alone or co‐cultured with spleenT‐cells from wild‐type, but not fromCD1d‐deficient, donors; (ii)IFN‐γ neutralization; and (iii) recombinantIFN‐γ, showed that these effects of α‐GalCer were mediated by IFN‐γ. Effects of α‐GalCeron eosinophil production were blocked byLTD4andNSAIDs.Conclusions and Implicationsα‐GalCeractivation ofIFN‐γ‐secreting,CD1d‐restricted lymphocytes inducediNOS‐CD95‐dependent apoptosis in developing eosinophils. This pathway is initiated by endogenous regulatory lymphocytes, antagonised byLTD4,NSAIDsand aminoguanidine, and modified by dexamethasone.
Contextual and individual determinants of dental pain in preschool children
Authors: Ferreira‐Júnior Osmar Martins , Freire Maria do Carmo Matias , Moreira Rafael da Silveira , Costa Luciane Rezende 
Published: March 2015

AbstractObjectivesDespite growing interest on dental pain in children, there are very few studies on its prevalence and determinants among preschool children. The objective of this study was to assess prevalence of dental pain and associated individual and contextual factors in 5 year‐old Brazilian children.MethodsThis cross‐sectional study used primary data from the 2010 National Survey of Oral Health, carried out in capital cities and a sample of country towns. Participants were 7280 5‐year‐olds, who were examined in their homes and whose parents answered a questionnaire. Dependent variable was report of dental pain in the last 6 months. Independent variables were contextual (city level) socioeconomic factors, and individual (child) sociodemographic and oral health‐related variables. Data analysis included hierarchized Poisson regression models, using a multilevel approach and prevalence rate (PR) estimates.ResultsThe prevalence of dental pain was 22.0% (95% CI 19.1–25.2). It was higher among those living in cities with lower human development index (PR 0.07; 95% CI 0.02–0.22) and with a higher percentage of their population with an incomplete primary education (PR 1.03; 95% CI 1.01–1.06). Indigenous children had prevalence of dental pain 1.97 times higher (95% CI 1.19–3.26) than those of white colour. Families with monthly incomes of U$ 218.00 or less and between U$ 219.00 and U$ 656.00 had, respectively, a prevalence of dental pain 2.67 (95% CI 1.33–5.32) and 2.11 (95% CI 1.03–4.32) times higher than families with highest income level. For each unit increase in the number of dwellers per bedroom, there was a 14% increase in the probability of having pain. Children with caries experience had a 3.45 (95% CI 2.58–4.62) higher prevalence of pain than caries‐free individuals.ConclusionDental pain prevalence in Brazilian preschool children was high and influenced by contextual and individual factors.
Toll‐like receptor‐4 knockout mice are more resistant to optic nerve crush damage than wild‐type mice
Authors: Morzaev Dana , Nicholson James D , Caspi Tomm , Weiss Shirel , Hochhauser Edith , Goldenberg‐Cohen Nitza 
Published: March 2015

AbstractBackgroundThis study aims to investigate the role of the inflammatory response following optic nerve crush (ONC) in knockout mice for the toll‐like receptor‐4 gene (TLR4−/−) compared to wild‐type (WT) mice.MethodsONC was induced in TLR4−/− and C57BL6 WT mice. Histological sections of the retina and optic nerve were analysed on days 1, 3 or 21 after injury. Molecular analysis with real‐time quantitative polymerase chain reaction was used to study the expression of CD45, tumour necrosis‐alpha (TNF‐α) and glial fibrillary acidic protein, as well as retinal ganglion cell (RGC) markers THY‐1 and Brn3b.ResultsThere was a 25.5% and 38% loss in the RGC layer of the ONC‐injured eyes of the TLR4−/− and the WT mice, respectively (with 27% and 9% of the remaining cells positive for Brn3a, respectively). Mean levels of Thy‐1 and Brn3b were higher in the TLR4−/− mice. CD45 and Iba1 staining revealed infiltration of inflammatory cells into the injured nerve and retina in both groups. Molecular analysis of the optic nerve on day 1 showed increased TNF‐α expression and reduced CD45 and GFAP expression; on day 3, CD45 reverted to baseline but GFAP remained low; on day 21, all 3 markers were at baseline in the TLR4−/− group and decreased in the WT group.ConclusionInflammation plays a major role in the response to ONC injury. Reduced levels of inflammation are associated with improved RGC preservation. The increase in TNF‐α and reduction in CD45 in both TLR4−/− and WT mice may indicate the presence of an alternative pathway for induction of RGC death.
Conditioned medium from fresh and demineralized bone enhances osteoclastogenesis in murine bone marrow cultures
Authors: Caballé‐Serrano Jordi , Schuldt Filho Guenther , Bosshardt Dieter D. , Gargallo‐Albiol Jordi , Buser Daniel , Gruber Reinhard 
Published: March 2015

AbstractObjectivesOsteoclasts rapidly form on the surface of bone chips at augmentation sites. The underlying molecular mechanism, however, is unclear. Soluble factors released from bone chips in vitro have a robust impact on mesenchymal cell differentiation. Whether these soluble factors change the differentiation of hematopoietic cells into osteoclasts remains unknown.MethodsOsteoclastogenesis, the formation of tartrate‐resistant acid phosphatase‐positive multinucleated cells, was studied with murine bone marrow cultures exposed to RANKL and M‐CSF, and conditioned medium from fresh (BCM) and demineralized bone matrix (DCM). Histochemical staining, gene and protein expression, as well as viability assays were performed.ResultsThis study shows that BCM had no impact on osteoclastogenesis. However, when BCM was heated to 85°C (BCMh), the number of tartrate‐resistant acid phosphatase‐positive multinucleated cells that developed in the presence of RANKL and M‐CSF approximately doubled. In line with the histochemical observations, there was a trend that BCMh increased expression of osteoclast marker genes, in particular the transcription factor c‐fos. The expression of c‐fos was significantly reduced by the TGF‐β receptor I antagonist SB431542. DCM significantly stimulated osteoclastogenesis, independent of thermal processing.ConclusionsThese data demonstrate that activated BCM by heat and DBM are able to stimulate osteoclastogenesis in vitro. These in vitro results support the notion that the resorption of autografts may be supported by as yet less defined paracrine mechanisms.
Acupoint herbal patching for allergic rhinitis: a systematic review and meta‐analysis of randomised controlled trials
Authors: Zhou F. , Yan L.‐J. , Yang G.‐Y. , Liu J.‐P. 
Published: March 2015

BackgroundAcupoint herbal patching (AHP) is extensively used in treatment of allergic rhinitis in China. However, existing systematic review is insufficient.Objective of reviewTo evaluate the effectiveness and safety of AHP in treating allergic rhinitis.Search strategyWe searched seven electronic databases for randomised controlled trials (RCTs) from inception until August 2014.Evaluation methodTwo authors selected studies, extracted data and evaluated risk of bias independently. The Cochrane risk of bias tool was applied to assess the methodological quality of the included trials, and RevMan 5.2 software was utilised to perform data analysis.ResultsTwenty RCTs involving 2438 participants were included. Most of them were evaluated as high risk of bias. Acupoint herbal patching significantly decreased the recurrence rate at 6 months compared with Western medicine (RR 0.52; 95% CI 0.42–0.64), and similar effect was found for AHP plus Western medicine versus Western medicine (RR 0.53; 95% CI 0.44–0.65). Acupoint herbal patching appeared to be more effective than placebo in improving total clinical symptoms and signs after treatment and at 6 months, and in improving quality of life at <3 months and over 3 months. No severe adverse effects were found in the AHP groups.ConclusionsAcupoint herbal patching alone or combined with Western medicine appears to be more effective than placebo or Western medicine, respectively. Acupoint herbal patching seems to be a safe treatment. However, the findings should be interpreted with caution. Further large‐scale, rigorously designed trials are warranted to confirm the findings.
Barriers and facilitators in the implementation of recommendations for hand eczema prevention among healthcare workers
Authors: van der Meer Esther W. C. , van der Gulden Joost W. J. , van Dongen Diana , Boot Cécile R. L. , Anema Johannes R. 
Published: March 2015

SummaryBackgroundEvidence‐based recommendations are available for the prevention of hand eczema among healthcare workers. However, the implementation of these recommendations is not always successful.ObjectivesTo identify barriers and facilitators in the implementation of recommendations for the prevention of hand eczema among healthcare workers alongside a randomized controlled trial.MethodsA qualitative study was performed in which 19 healthcare workers were interviewed. The interview transcripts were open coded and also coded by means of a template by two researchers to identify relevant barriers and facilitators.ResultsMost barriers and facilitators reported for the recommendations were found at the level of the innovation (e.g. the recommendations), whereas for the guideline as a whole, multiple levels (socio‐political, organization, user, and facilities) were identified.ConclusionsTo enhance the implementation of recommendations for the prevention of hand eczema in a healthcare setting, having knowledge about these recommendations seems to be an important first step. In addition, maintaining the attention of the subject, testing the products beforehand and close collaboration with the infection control department might enhance implementation. Furthermore, it is important that the recommendations fit in with the work of the healthcare workers. When the implementation of the recommendations is prepared, these points should be taken into account.
Use of clinical next‐generation sequencing to identify melanomas harboring SMARCB1 mutations
Authors: Stockman David L. , Curry Jonathan L. , Torres‐Cabala Carlos A. , Watson Ian R. , Siroy Alan E. , Bassett Roland L. , Zou Lihua , Patel Keyur P. , Luthra Rajyalakshmi , Davies Michael A. , Wargo Jennifer A. , Routbort Mark A. , Broaddus Russell R. , Prieto Victor G. , Lazar Alexander J. , Tetzlaff Michael T. 
Published: March 2015

BackgroundSMARCB1 (INI1/BAF47/SNF5) encodes a part of a multiprotein complex that regulates gene expression through chromatin remodeling. SMARCB1 expression is lost or downregulated in multiple human tumors, including epithelioid sarcoma, meningioma and rhabdoid tumors of the brain, soft tissue and kidney.MethodsA 46‐gene or 50‐gene next‐generation sequencing AmpliSeq Cancer Panel (Life Technologies; San Francisco, CA, USA) was applied to ∼1400 primary or metastatic melanoma tissues.ResultsWe identified eight cases of melanoma harboring mutations in SMARCB1. Immunohistochemistry demonstrated preservation of SMARCB1 protein expression in all cases. SMARCB1 mutations occurred together with TP53 mutations in five of the eight cases, suggesting a functional relationship between these tumor suppressors in melanoma.ConclusionsBecause single‐base substitutions in SMARCB1 occur in a small subset of melanomas and do not affect SMARCB1 protein expression, such mutations would only be discovered by sequencing approaches. Our findings highlight the potential for next‐generation sequencing platforms to identify mutations unexpected for melanoma that may contribute to its oncogenic potential. Though rare, the identification of SMARCB1 mutations adds to the growing literature regarding the role of epigenetic control mechanisms in melanoma progression and therapeutic resistance and provide a rationale for strategies targeting such alterations (via chromatin remodeling agents) in clinical trials.
Superficial fibrin thrombi … and other findings: a review of the histopathology of human scabietic infections
Authors: Elwood Hillary , Berry Ryan S. , Gardner Jerad M. , Shalin Sara C. 
Published: March 2015

BackgroundCutaneous infection with the mite Sarcoptes scabiei var. hominis is associated with epidermal and dermal changes. After noting superficial fibrin thrombi in two biopsies with scabies mites, we comprehensively reviewed the histopathologic findings in scabietic infections to determine the frequency of this finding.MethodsTwenty five biopsies of scabies infection were retrieved from the archives of our institution; only cases containing scabietic mite parts or scybala were included. The microscopic features were documented.ResultsNearly half (40%) of the cases showed fibrin thrombi within vessels of the superficial dermis. Other frequent findings included dermal eosinophils (88% of cases), epidermal spongiosis (76% of cases), lymphocyte atypia (64%), a superficial and deep infiltrate (52% of cases), dermal neutrophils (52%) and endothelial cell swelling (52%). Half of the cases contained polarizable mite elements. Less commonly encountered features included extravasated erythrocytes (44%), dermal edema (32%), pink ‘pigtails’(28%), intraepidermal pustules (24%), plasma cells (20%) and vasculitis (4%).ConclusionsThe pathologic characteristics of scabietic infection are wide‐ranging. Spongiosis, superficial and deep inflammation, and dermal eosinophils and neutrophils are seen in the majority of cases. Superficial fibrin thrombi are not uncommon in scabietic infection, and may provide a helpful diagnostic clue when mites are not visible on initial sections.