bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concentrations of indomethacin and its metabolite desmethylindomethacin in plasma and urine after repeated indomethacin topical application to Thoroughbreds
Authors: Kusano K. , Minamijima Y. , Mashita S. , Kunii H. , Yamashita S. , Nagata S. 
Published: November 2018

SummaryBackgroundRepeated topical application of indomethacin is common in Japanese racehorses, despite the lack of pharmacokinetic data.ObjectivesTo determine the concentrations of indomethacin and its metabolite, desmethylindomethacin, in plasma and urine of Thoroughbreds topically treated repeatedly with indomethacin.Study designIn vivo experimental.MethodsSeven female Thoroughbreds were topically treated with 50 g of 1% indomethacin cream per horse to the back and hips (500 mg of indomethacin/head/2400 cm2, 0.21 g/cm2) for 3 consecutive days. Samples were pretreated by protein precipitation for plasma and liquid‐liquid extraction with ethyl acetate after hydrolysis with hydrochloric acid for urine. The concentrations of indomethacin and desmethylindomethacin in plasma and urine were measured by liquid chromatography‐mass spectrometry.ResultsIndomethacin was quantifiable in plasma up to 48–72 h and in urine up to 96 h after the final application. Desmethylindomethacin was quantifiable in plasma up to 48 h and in urine up to 72–96 h after the final application.Main limitationsThe relationship between the local and systemic indomethacin concentrations after the topical application was not clarified.ConclusionsPharmacokinetic data were acquired for repeated topical administration of 1% indomethacin cream to Thoroughbreds. Hydrolysing urine samples with hydrochloric acid was effective for the analysis of indomethacin and its metabolite, and indomethacin may be an excellent marker analyte for doping tests. The estimated withdrawal time based on the limit of detection was 342 h.
The relationship between sagittal hoof conformation and hindlimb lameness in the horse
Authors: Pezzanite L. , Bass L. , Kawcak C. , Goodrich L. , Moorman V. 
Published: November 2018

SummaryBackgroundLameness can be multifactorial and may result from the accumulation of multiple seemingly unrelated causes. The identification of factors associated with lameness could be one method to decrease incidence of lameness and prolong the equine athlete's competitive life.ObjectivesTo determine if there is an association between hoof balance in the sagittal plane and hindlimb lameness.Study designCase‐control study.MethodsEighty client‐owned horses with hindlimb lameness (cases) and 80 horses with no detectable hindlimb lameness (controls) were prospectively enroled following lameness evaluation as either cases (lameness localised with regional anaesthesia) or controls (no hindlimb lameness). Lameness cases were divided based on location (stifle, tarsus, proximal metatarsus and other sites). Lateromedial radiographs were performed on hind hooves and plantar angle of the distal phalanx (PADP) was determined. The prevalence of negative/neutralPADPand medianPADPs were calculated. Conditional logistic regression and Wilcoxon signed rank tests were used to analysePADPs, and odds ratios were calculated. Significance was set at P<0.05.ResultsThe meanPADPwas significantly smaller in cases compared to controls. The meanPADPwas significantly smaller in horses with lameness localised to tarsus and proximal suspensory, but not the stifle. Lameness in horses was associated with a negative/neutralPADP(Odds ratio [OR] 3.87, 95% confidence interval [95%CI] 1.97–7.61, P<0.01), with lameness localised to the tarsus (OR4.98, 95%CI1.34–18.54, P = 0.01) and proximal suspensory (OR5.16, 95%CI1.11–23.89, P = 0.03) being associated with a negative/neutralPADP.Main limitationsIt is unknown whether the negative/neutralPADPcontributed to lameness or lameness resulted in lowerPADP.ConclusionsHorses with hindlimb lameness localised to the distal tarsus and proximal metatarsus, but not the stifle, were more likely to have negative/neutralPADPs. Corrective farriery to improvePADPmay be investigated further as one component in the treatment of hindlimb lameness localised to regions proximal to the foot.The Summary is available in Portuguese – see Supporting Information
Heritability of metabolic traits associated with equine metabolic syndrome in Welsh ponies and Morgan horses
Authors: Norton E. M. , Schultz N. E. , Rendahl A. K. , Mcfarlane D. , Geor R. J. , Mickelson J. R. , McCue M. E. 
Published: November 2018

SummaryBackgroundEquine metabolic syndrome (EMS) is a complex clinical disorder with both environmental and genetic factors contributing to EMS phenotypes. Estimates of heritability determine the proportion of variation in a trait that is attributable to genetics.ObjectivesTo provide heritability estimates for nine metabolic traits associated with EMS in two high‐risk breeds.Study designRetrospective cohort study.MethodsHigh‐density single‐nucleotide polymorphism (SNP) genotype data was used to estimate the heritability (h2SNP) of nine metabolic traits relevant to EMS in a cohort of 264 Welsh ponies and 286 Morgan horses. Traits included measurements of insulin, glucose, non‐esterified fatty acids (NEFA), triglycerides, leptin, adiponectin, ACTH, and glucose (GLU‐OST) and insulin (INS‐OST) following an oral sugar challenge.ResultsIn Welsh ponies, seven of the nine traits had statistically significant h2SNP estimates that were considered moderately to highly heritable (h2SNP>0.20) including: triglycerides (0.313; s.e. = 0.146), glucose (0.408; s.e. = 0.135), NEFA (0.434; s.e. = 0.136), INS‐OST (0.440; s.e. = 0.148), adiponectin (0.488; s.e. = 0.143), leptin (0.554; s.e. = 0.132) and insulin (0.808; s.e. = 0.108). In Morgans, six of the nine traits had statistically significant h2SNP estimates that were also determined to be moderately to highly heritable including: INS‐OST (0.359; s.e. = 0.185), leptin (0.486; s.e. = 0.177), GLU‐OST (0.566 s.e. = 0.175), insulin (0.592; s.e. = 0.195), NEFA (0.684; s.e. = 0.164), and adiponectin (0.913; s.e. = 0.181).Main limitationsInsufficient population size may have limited power to obtain statistically significant h2SNP estimates for ACTH (both breeds), glucose and triglycerides in Morgans and GLU‐OST in Welsh ponies.ConclusionsThis study provides the first concrete evidence of a genetic contribution to key phenotypes associated with EMS. Eight of these nine traits had moderate to high h2SNP estimates in this cohort. These data demonstrate that continued research for identification of the genetic risk factors for EMS phenotypes within and across breeds is warranted.
Respect, trust and continuity: A qualitative study exploring service users’ experience of involvement at a Healthy Life Centre in Norway
Authors: Sagsveen Espen , Rise Marit B. , Grønning Kjersti , Westerlund Heidi , Bratås Ola 
Published: November 2018

AbstractBackgroundTo meet the challenges caused by non‐communicable diseases, Norway has established Healthy Life Centres within primary care to encourage a healthy lifestyle. To promote people's health and ensure high‐quality services, user involvement in contemporary health care is regarded as essential.ObjectiveTo explore the experience of user involvement among Healthy Life Centre users participating in individual health consultations, followed by physical activity groups and/or diet courses.MethodsThis was a qualitative study based on twenty semi‐structured individual interviews conducted between September 2015 and May 2016 at a Healthy Life Centre in Norway. Data were analysed using systematic text condensation.ResultsBeing respected and having a trustworthy relationship with the professionals were found to be essential for the service users’ involvement. Building a trustworthy relationship was disrupted for some service users by a lack of relational continuity. This lack of continuity jeopardized the continuation of professionals’ awareness of the service users’ challenges and personal goals. The service users’ preferred levels of user involvement varied. Some service users did not always want to play an active part and instead wanted the professionals, as “experts,” to decide.ConclusionsThe findings imply that the professionals need to assess each service user's desires for involvement and consider how these can be met. Thus, user involvement cannot be understood without considering the particular setting and each individual service user's preferences for involvement. Relational continuity is needed to maintain the service users’ challenges and goals throughout the services and to promote health behaviour changes.
Neutrophils mitigate the systemic host response during endotoxemia in mice
Authors: van der Meer Anne Jan , Ding Chao , Hoogendijk Arie Johan , de Vos Alex F. , Boon Louis , Zeerleder Sacha S. , van der Poll Tom 
Published: November 2018

SummaryRecent studies have suggested that neutrophils can exert anti‐inflammatory effects. To determine the role of neutrophils in the acute response to lipopolysaccharide (LPS), a component of the Gram‐negative bacterial cell wall, we challenged neutrophil‐depleted and control mice with LPS and analyzed the plasma concentrations of biomarkers indicative of the cytokine and chemokine network, activation of coagulation and the vascular endothelium, and cellular injury. We here show that neutrophils serve an anti‐inflammatory role upon LPS administration, as reflected by sustained elevations of multiple cytokines and chemokines, and enhanced release of nucleosomes in mice depleted of neutrophils, compared with control mice.
Interleukin‐17/interleukin‐17 receptor axis elicits intestinal neutrophil migration, restrains gut dysbiosis and lipopolysaccharide translocation in high‐fat diet‐induced metabolic syndrome model
Authors: Pérez Malena M. , Martins Larissa M. S. , Dias Murilo S. , Pereira Camila A. , Leite Jefferson A. , Gonçalves Enrico C. S. , de Almeida Paula Z. , de Freitas Emanuelle N. , Tostes Rita C. , Ramos Simone G. , de Zoete Marcel R. , Ryffel Bernhard , Silva João S. , Carlos Daniela 
Published: November 2018

SummarySound evidence supports a role for interleukin‐17 (IL‐17) ‐producing γδ T cells and IL‐17‐producing helper T (Th17) cells in intestinal homeostasis, especially in intestinal barrier integrity. In the present study, we aimed to evaluate the role of IL‐17 cytokine in the regulation of intestinal immunity and obesity‐induced metabolic syndrome (MetS) in an experimental murine model. C57BL/6 wild‐type (WT) mice and mice lacking the IL‐17 cytokine receptor (IL‐17RA−/−) were fed either a control diet (CD) or a high‐fat diet (HFD) for 9 weeks. Our data demonstrate that IL‐17RA−/− mice are protected against obesity, but develop hyperglycemia, hyperinsulinemia and insulin resistance. In parallel, HFD‐fed IL‐17RA−/− mice display intense inflammation in the ileum compared with WT mice on the HFD. IL‐17RA−/− mice fed the HFD exhibit impaired neutrophil migration to the intestinal mucosa and reduced gene expression of the CXCL‐1 chemokine and CXCR‐2 receptor in the ileum. Interestingly, the populations of neutrophils (CD11b+ Ly6G+) and anti‐inflammatory macrophages (CD11b+ CX3CR1+) are increased in the mesenteric lymph nodes of these mice. IL‐17RA−/− mice on the HFD also display increased commensal bacterial translocation into the bloodstream and elevated lipopolysaccharide (LPS) levels in the visceral adipose tissue (VAT). Metagenomic analysis of bacterial 16S gene revealed increased Proteobacteria and Bacteroidetes phyla, the main representatives of Gram‐negative bacteria, and reduced Akkermansia muciniphila in the fecal samples of IL‐17RA−/− mice fed the HFD. Together, these data indicate that the IL‐17/IL‐17R axis drives intestinal neutrophil migration, limits gut dysbiosis and attenuates LPS translocation to VAT, resulting in protection to MetS.
Phase transition, microstructure and electrical properties of K1‐xNaxNbO3‐based ceramic sintered in reducing atmosphere
Authors: Cen Zhenyong , Zhen Yichao , Feng Wei , Chen Lingling , Zhao Peiyao , Yu Yan , Xiao Mengjian , Li Longtu , Wang Xiaohui 
Published: November 2018

AbstractLead‐free 0.955K1‐xNaxNbO3‐0.045Bi0.5Na0.5ZrO3+0.4% mol MnO ceramics (Abbreviated as K1‐xNxN‐0.045BNZ+0.4Mn) were prepared by a conventional solid‐state sintering method in a reducing atmosphere (oxygen partial pressure : 1 × 10−11 MPa). All K1‐xNxN‐0.045BNZ+0.4Mn samples show a pure perovskite structure with a polymorphic phase boundary (PPB) composed of rhombohedral (R) and tetragonal (T) phases. A high Na/K ratio and a low Na/K ratio can both induce an increase in the rhombohedral phase. The reverse piezoelectric coefficient and its temperature stability in K1‐xNxN‐0.045BNZ+0.4Mn ceramics can be improved by controlling the Na/K ratio. The increase in the Na/K ratio from x = 0.46 to x = 0.56 can decrease the A‐site cation vacancies. The activation energy of the grain is higher than that of the grain boundary due to the accumulation of oxygen vacancies at the grain boundary. K1‐xNxN‐0.045BNZ+0.4Mn ceramics with excellent piezoelectric properties (quasi‐static piezoelectric coefficient d33 = 326 pC/N, and = 472 pm/V at Emax = 25 kV/cm) were obtained at x = 0.52.
Therapeutic effects of lentinan on inflammatory bowel disease and colitis‐associated cancer
Authors: Liu Yanrong , Zhao Jianmin , Zhao Yali , Zong Shumin , Tian Yixuan , Chen Shuang , Li Meng , Liu Huijuan , Zhang Qiang , Jing Xueshuang , Sun Bo , Wang Hongzhi , Sun Tao , Yang Cheng 
Published: November 2018

AbstractIn this study, we investigated the therapeutic potential of lentinan in mouse models of inflammatory bowel disease (IBD) and colitis‐associated cancer (CAC). Lentinan decreased the disease activity index and macroscopic and microscopic colon tissue damage in dextran sulphate sodium (DSS)‐induced or TNBS‐induced models of colitis. High‐dose lentinan was more effective than salicylazosulfapyridine in the mouse models of colitis. Lentinan decreased the number of tumours, inflammatory cell infiltration, atypical hyperplasia and nuclear atypia in azoxymethane/DSS‐induced CAC model. It also decreased the expression of pro‐inflammatory cytokines, such as IL‐13 and CD30L, in IBD and CAC model mice possibly by inhibiting Toll‐like receptor 4 (TLR4)/NF‐κB signalling and the expression of colon cancer markers, such as carcinoembryonic antigen, cytokeratin 8, CK18 and p53, in CAC model mice. In addition, lentinan restored the intestinal bacterial microbiotal community structure in IBD model mice. Thus, it shows therapeutic potential in IBD and CAC model mice possibly by inhibiting TLR4/NF‐κB signalling‐mediated inflammatory responses and disruption of the intestinal microbiotal structure.
Managing adverse effects by dose reduction during routine treatment of locally advanced basal cell carcinoma with the hedgehog inhibitor vismodegib: a single centre experience
Authors: Woltsche N. , Pichler N. , Wolf I. , Di Meo N. , Zalaudek I. 
Published: November 2018

Linked article: This article is commented on by M. Scalvenzi et al., pp. e146–e147 in this issue. To view this article visit https://doi.org/10.1111/jdv.15469.
Calcipotriol plus betamethasone dipropionate aerosol foam vs. apremilast, methotrexate, acitretin or fumaric acid esters for the treatment of plaque psoriasis: a matching‐adjusted indirect comparison
Authors: Bewley A.P. , Shear N.H. , Calzavara‐Pinton P.G. , Hansen J.B. , Nyeland M.E. , Signorovitch J. 
Published: November 2018

AbstractBackgroundPlaque psoriasis has significant impact on patients’ quality of life. Topical therapy is considered the treatment mainstay for mild‐to‐moderate disease according to guidelines. Calcipotriol/betamethasone dipropionate (Cal/BD) [0.005%/0.05%] aerosol foam is indicated for psoriasis vulgaris treatment in adults. Cal/BD foam trials demonstrated improved efficacy and similar safety in this population. Psoriasis treatment is complicated by the broad range of disease presentation, variability and therapeutic options; particularly decisions on transition from topical to non‐biologic systemic treatment are difficult. Assessing comparative effectiveness of treatment options provides meaningful value to treatment decisions.ObjectiveTo compare efficacy of Cal/BD foam individual patient data from pooled trials with efficacy of non‐biologic systemic treatments based on aggregated patient characteristics and treatment outcomes.MethodsIndividual data from four Cal/BD foam trials in 749 psoriasis patients were pooled to conduct matching‐adjusted indirect comparisons. Literature review identified non‐biologic systemic treatment trials where methods, populations and outcomes align with Cal/BD foam trials. Of 3090 screened publications, four studies of apremilast, methotrexate, acitretin or fumaric acid esters (FAE) were included.ResultsAfter baseline matching, patients treated with 4 weeks of Cal/BD foam had greater Physician's Global Assessment 0/1 response compared to those treated with 16 weeks of apremilast (52.7% vs. 30.4%; P < 0.001). Patients treated with Cal/BD foam had significantly greater Psoriasis Area and Severity Index (PASI) 75 response at Week 4 compared to 16 weeks of apremilast treatment (51.1% vs. 21.6%; P < 0.001). Cal/BD foam patients demonstrated significantly greater PASI 75 response improvements at Week 4 vs. 12 weeks of methotrexate (50.8% vs. 33.5%; P < 0.001) or acitretin (50.9% vs. 31.7%; P = 0.009), and comparable response to FAE (42.4% vs. 47.0%; P = 0.451).ConclusionsDespite recent treatment advances, unmet needs for psoriasis patients remain. Cal/BD foam offers improved efficacy in baseline matched psoriasis patients compared to apremilast, methotrexate or acitretin, and comparable efficacy to FAE.
Frontal fibrosing alopecia: a case series of 65 patients seen in a single Italian centre
Authors: Starace M. , Brandi N. , Alessandrini A. , Bruni F. , Piraccini B.M. 
Published: November 2018

AbstractBackgroundFrontal fibrosing alopecia (FFA) is increasing in prevalence worldwide and several series from different countries have been published, in order to detect possible causes of the disease outbreak.ObjectiveTo analyze the epidemiological, clinical and trichoscopic features of FFA seen in an Italian Dermatology Unit.MethodsClinical, trichoscopy, histopathology and medical details of all patients were compared with literature and general population data.ResultsFrom 2005 to 2017, we diagnosed FFA in 65 Caucasian females, with the number of diagnoses per year progressively rising. Premenopausal onset was detected in 21%. Frontal hair line recession was associated with parietal involvement in 80% of cases, occipital in 12.3% and eyebrows alopecia in 86.1%. In six cases, eyebrow alopecia preceded hair loss. Non‐inflammatory facial papules were detected in 1/3 of the patients. Itching was reported by 2/3 of the patients and was indicative of disease progression. Trichoscopy showed empty follicles/yellow dots, absence of follicular ostia, mild follicular hyperkeratosis, perifollicular erythema and ‘lonely hair’. Scalp lichen plano‐pilaris was seen in 15 patients, female pattern hair loss in 22. Therapy included short‐term treatment with systemic or intralesional corticosteroids followed by therapy with 5α‐reductase inhibitors of hydroxychloroquine and topical drugs. Arrest of FFA progression was seen in 75% of the patients, while 16 experienced worsening of the hairline despite therapy.ConclusionsFrontal fibrosing alopecia not rarely starts before menopause, loss of the eyebrows can be the first sign of the disease, about 50% of the patients have other autoimmune conditions, FFA severity is not related to its duration, itching, follicular hyperkeratosis and erythema at trichoscopy are signs of disease progression, 25% of the patients show progression of hairline recession despite therapy.
Identification of novel sRNAs involved in oxidative stress response in the fish pathogen Vibrio alginolyticus by transcriptome analysis
Authors: Peng Tao , Kan Jie , Lun Jingsheng , Hu Zhong 
Published: November 2018

AbstractVibrio alginolyticus as an important pathogen in aquaculture can encounter the oxidative stress produced by the immune system during infection. Previous studies showed that sRNAs have important functions in response to oxidative stress in bacteria; however, less of sRNAs related to oxidative stress response were identified in V. alginolyticus. In this study, a total of 749 novel sRNAs were identified by RNA sequencing; among them, 128 sRNAs were up‐ or downregulated in response to oxidative stress. In addition, 1,870 genes exhibited variation on mRNA levels in oxidative stress response. By analysing the target genes of the sRNAs, we concluded that these sRNAs could regulate expressions of genes responsible for iron transport, catalase, GSH‐dependent defence system, electron transferred and stress response. Moreover, the functions of the sRNAs are also seemed related to the pathogenicity in V. alginolyticus. Based on the results, we constructed the oxidative stress model in V. alginolyticus. This study provides us the first outlook of sRNAs function in oxidative stress response in V. alginolyticus. Furthermore, this study can help us to prevent and control this important opportunistic pathogen in aquaculture.
The evidence for the physiological effects of lactate on the cerebral microcirculation: a systematic review
Authors: Hollyer Tristan R. , Bordoni Luca , Kousholt Birgitte S. , van Luijk Judith , Ritskes‐Hoitinga Merel , Østergaard Leif 
Published: November 2018

AbstractLactate's role in the brain is understood as a contributor to brain energy metabolism, but it may also regulate the cerebral microcirculation. The purpose of this systematic review was to evaluate evidence of lactate as a physiological effector within the normal cerebral microcirculation in reports ranging from in vitro experiments to in vivo studies in animals and humans. Following pre‐registration of a review protocol, we systematically searched the PubMed, EMBASE, and Cochrane databases for literature covering themes of ‘lactate’, ‘the brain’, and ‘microcirculation’. Abstracts were screened, and data extracted independently by two individuals. We excluded studies evaluating lactate in disease models. Twenty‐eight papers were identified, 18 of which were in vivo animal experiments (65%), four on human studies (14%), and six on in vitro or ex vivo experiments (21%). Approximately half of the papers identified lactate as an augmenter of the hyperemic response to functional activation by a visual stimulus or as an instigator of hyperemia in a dose‐dependent manner, without external stimulation. The mechanisms are likely to be coupled to NAD+/NADH redox state influencing the production of nitric oxide. Unfortunately, only 38% of these studies demonstrated any control for bias, which makes reliable generalizations of the conclusions insecure. This systematic review identifies that lactate may act as a dose‐dependent regulator of cerebral microcirculation by augmenting the hyperemic response to functional activation below 5 mmol/kg, and by initiating a hyperemic response above 5 mmol/kg.Open Science BadgesThis article has received a badge for *Pre‐registration* because it made the data publicly available. The data can be accessed at www.radboudumc.nl/getmedia/53625326-d1df-432c-980f-27c7c80d1a90/THollyer_lactate_protocol.aspx. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.
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