bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protective influence of rosiglitazone against time‐dependent deterioration of boar spermatozoa preserved at 17°C
Authors: Wang Na , Yang Kang , Guo Hai‐Tao , Wang Jing‐Ran , Sun Huan‐Huan , Wang Shun‐Wei , Sun Meng , Sun Liang‐Zheng , Yue Shun‐Li , Zhou Jia‐Bo 
Published: May 2019

AbstractSpermatozoa are highly specialized cells, and energy metabolism plays an important role in modulating sperm viability and function. Rosiglitazone is an antidiabetic drug in the thiazolidinedione class that regulates metabolic flexibility and glucose uptake in various cell types, but its effects on boar sperm metabolism are unknown. In this study, we investigated the potential effect of rosiglitazone against time‐dependent deterioration of boar spermatozoa during liquid preservation at 17°C. Freshly ejaculated semen was diluted with Beltsville Thawing Solution (BTS) containing different concentrations of rosiglitazone, and the motility, membrane and acrosome integrity of sperm were detected. Besides, we measured glucose uptake capacity, l‐lactate production level, mitochondrial membrane potential, adenosine triphosphate (ATP) content and mitochondrial reactive oxygen species (mROS) production of sperm after boar semen had been incubated with or without rosiglitazone, iodoacetate (glycolysis inhibitor) and rotenone (electron transport chain inhibitor) for 5 days. The addition of rosiglitazone significantly enhanced sperm quality and had a strong protective effect on the sperm membrane and acrosome integrity during storage. BTS containing 50 μM rosiglitazone maintained the total motility of liquid‐preserved sperm above 60% for 7 days. Rosiglitazone improved sperm quality by regulating energy metabolism manner of preserved sperm, protected the sperm mitochondrial membrane potential, enhanced sperm ATP production and in the meanwhile reduced mROS through enhancing glycolysis but not oxidative phosphorylation. The data suggested the practical feasibility of using rosiglitazone for improving boar spermatozoa quality during semen preservation.
Oral and dental management of people with myelodysplastic syndromes and acute myeloid leukemia: A systematic search and evidence‐based clinical guidance
Authors: Abed Hassan , Alhabshi Manaf , Alkhayal Zikra , Burke Mary , Nizarali Najla 
Published: May 2019

AbstractAimsTo systematically search all studies that discussed dental procedures in patients diagnosed with myelodysplastic syndromes (MDS) and/or acute myeloid leukemia (AML) and to provide an evidence‐based clinical guidance on oral and dental management of people with MDS and/or AML.MethodsThe systematic search followed the Preferred Reporting Item for Systematic Review and Meta‐analyses Protocols (PRISMA‐P) guideline. Two databases systems were used (MEDLINE and EMBASE). PROSPERO was searched for ongoing or recently completed systematic reviews. The International Clinical Trials Registry Platform Search was searched for ongoing or recently completed trials. Level of evidence was evaluated based on the Oxford Level of Evidence. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to summarize the evidence.ResultsOnly 18 articles were selected and included in data synthesis and analysis. The level of evidence and recommendation ranged from 1 to 5 and A to D, respectively.ConclusionsAll the included studies in the data synthesis (n = 18) showed no specific guidelines were followed; however, all reflected the importance of liaison with the patient's hematoncologist at all stages of MDS and/or AML therapy.RecommendationsOral and dental assessment is crucial prior to MDS therapy to help reduce anticipated complications. Dental treatment prior to hematopoietic stem cell transplantation and/or active stage of MDS therapy is tricky and always required liaison with the hematoncologist. MDS can progress to AML; hence, dental care providers are in a good position to spot any changes and refer early to the hematoncologist for further assessment.
Risk factors of stress fractures due to the female athlete triad: Differences in teens and twenties
Authors: Nose‐Ogura Sayaka , Yoshino Osamu , Dohi Michiko , Kigawa Mika , Harada Miyuki , Hiraike Osamu , Onda Takashi , Osuga Yutaka , Fujii Tomoyuki , Saito Shigeru 
Published: May 2019

BackgroundThe female athlete triad (Triad), defined by the American College of Sports Medicine as low energy availability (LEA) with or without disordered eating, menstrual dysfunction, and low bone mineral density (BMD), is associated with stress fractures and athletes aged 16‐17 years are most susceptible.PurposeTo examine whether the Triad increases the risk of stress fractures, athletes were assigned to a “teenage” group and a “20s” group.MethodsThis prospective study enrolled 390 elite female athletes and was conducted from 2012 to 2016 at Japan Institute of Sports Sciences. Blood concentrations of various hormones were examined, and BMD was measured at the lumbar spine and throughout the whole body using dual‐energy X‐ray absorptiometry. LEA was defined as body weight ≤85% of the ideal body weight for teenage athletes, or BMI ≤17.5 for athletes in their 20s. Low BMD was defined as a BMD Z‐score of <−1.0 in the lumbar spine and the whole body.ResultsAmong 390 athletes enrolled, 36 developed new stress fractures within 3 months of registration. The risk for stress fractures due to the Triad in teenage athletes was higher than for athletes in their 20s. In teenage female athletes, secondary amenorrhea, low BMD for the whole body, and a low ratio of actual body weight to ideal body weight increased the risk for stress fractures by 12.9 times, 4.5 times, and 1.1 times, respectively.ConclusionTo prevent stress fractures in female athletes with the Triad, age of athletes should be taken into consideration.
Influence of E‐cadherin genetic variation in canine mammary tumour risk, clinicopathological features and prognosis
Authors: Canadas Ana , Santos Marta , Medeiros Rui , Dias‐Pereira Patrícia 
Published: May 2019

AbstractE‐cadherin is a cell adhesion molecule that participates in several cellular processes that guarantee the maintenance of structural and functional integrity of epithelial tissues. E‐cadherin plays an important role in mammary carcinogenesis, and various studies have demonstrated the effect of CDH1 genetic variation in risk, progression and biological behaviour of human breast cancer. Although there are some recognized genetic variations in canine CDH1 gene, their influence in canine mammary tumour development and progression has not been previously evaluated. In this study, we aim to assess the influence of CDH1 SNPs rs850805755, rs852280880 and rs852639930 in the risk, clinicopathological features and clinical outcome of canine mammary tumours. A case‐control study was conducted involving 206 bitches with mammary tumours and 161 bitches free of mammary neoplasia. CDH1 SNPs rs850805755 and rs852280880 were associated with a decreased risk and a later onset of mammary tumour development. Furthermore, these SNPs were related to the development of small size carcinomas, of low histological grade and low nuclear pleomorphism. SNP rs852639930 was associated with the development of small size tumours with a non‐infiltrative, non‐invasive growth pattern. Data from the present investigation demonstrate that these CDH1 genetic variants could have a protective role in canine mammary tumours, by being associated with low risk of tumour development, delayed onset of the disease and less aggressive clinicopathological features.
Impact of a mobile application for heart rate assessment in simulated neonatal resuscitation: a randomised controlled cross-over study
Authors: Cavallin Francesco , Binotti Marco , Ingrassia Pierluigi L , Genoni Giulia , Rizzollo Stefano , Monzani Alice , Trevisanuto Daniele 
Published: May 2019

BackgroundClinical assessment of newborn heart rate (HR) at birth has been reported to be inaccurate. NeoTapAdvancedSupport (NeoTapAS) is a free-of-charge mobile application that showed good accuracy in HR estimation. This study aimed to evaluate the impact of NeoTapAS on timing of HR communication and resuscitation interventions.MethodsThis was a randomised controlled cross-over (AB/BA) study evaluating HR assessment using auscultation plus NeoTapAS compared with auscultation plus mental computation in a high-fidelity simulated newborn resuscitation scenario. Twenty teams each including three paediatric residents were randomly assigned to AB or BA arms. The primary outcome was the timing of the first HR communication. Secondary outcomes included the timing of the following four HR communications and the timing of resuscitation interventions (positive pressure ventilation, chest compressions, intubation and administration of first dose of epinephrine).ResultsNeoTapAS reduced the time to the first HR communication (mean difference −13 s, 95% CI −23 to −4; p=0.009), and the time of initiation of chest compressions (mean difference −68 s, 95% CI −116 to −18; p=0.01) and administration of epinephrine (mean difference −76 s, 95% CI −115 to −37; p=0.0004) compared with mental computation.ConclusionsIn a neonatal resuscitation simulated scenario, NeoTapAS reduced the time to the first HR communication and the time of initiation of chest compressions and administration of epinephrine compared with mental computation. This app can be especially useful in settings with limited availability of monitoring equipment, but further studies in clinical scenarios are warranted.Trial registration numberNCT03730025.
P90 Neuropsychiatric disorder and Montelukast: a case report and VigiBase® analysis
Authors: Scholz I , Banholzer S , Haschke M 
Published: May 2019

Learning objectiveRecognize neuropsychiatric symptoms as possible adverse drug reactions (ADR) associated with the leukotriene receptor antagonist Montelukast in childrenClinical CaseAn 11-year-old boy suffering from asthma presented to his pediatrician with an acute onset of nervousness, restlessness and irritability. The teacher noticed a decline in school performance with a reduced attention span. The patient had been treated with Salbutamol (Ventolin®) and Salmeterol/Fluticasone (Seretide®) for the last few years. A treatment with Montelukast chewable tablets was started four months ago. The ADR was reported to the Regional Pharmacovigilance Centre (RPVC) Bern. The termination of the therapy with Montelukast lead to an amelioration of the symptoms. According to the WHO-UMC Causality Categories,1 the causality of Montelukast and the described symptoms was classified as ‘probable’. The causality of the comedication was considered ‘unlikely’ as it had been used for several years without complications. After work-up at the RPVC, the case was reported anonymously to the National Pharmacovigilance Center of the Swiss Agency for Therapeutic Products Swissmedic.DiscussionMontelukast is a cysteinyl-leukotriene type 1-receptor antagonist used in the treatment of bronchial asthma in adults and children. Psychiatric disorders such as agitation, psychomotor hyperactivity (including irritability and restlessness), disorders of attention and memory impairment (and others) are listed as known ADRs of Montelukast.2 3 The WHO pharmacovigilance database VigiBase® lists a total of 20’897 ADR reports for Montelukast, of which 4’705 (22.5%) refer to nervous system disorders and 6’828 (32.7%) to psychiatric disorders. Within the group of nervous system disorders 256 (5.4%) reports of psychomotor hyperactivity, 232 (4.9%) reports of disturbance in attention and 91 (1.9%) reports of memory impairment were recorded.4 The most common symptoms in the group of psychiatric disorders are depression (1’311, 19.2%) and aggressive behavior (1’175, 17.2%). If psychiatric ADRs occur, the risks and benefits of Montelukast should be reassessed.ReferencesThe use of the WHO-UMC system for standardised case causality assessment. Available from:https://www.who.int/medicines/areas/quality_safety/safety_efficacy/WHOcausality_assessment.pdfMarchand MS, Jonville-Bera AP, Autret-Leca E, [Psychiatric disorders associated with montelukast: data from the National Pharmacovigilance Database]. Arch Pediatr 2013;20(3):269–73.Aldea Perona A, Garcia-Saiz M, Sanz Alvarez E. Psychiatric disorders and montelukast in children: A disproportionality analysis of the vigibase((R)). Drug Saf 2016;9(1):69–78.Disclosure(s)Nothing to disclose
P07 Roxithromycin in early pregnancy and the risk of major congenital malformation: a register based nationwide cohort study
Authors: Olsen RH , Poulsen HE , Andersen JT 
Published: May 2019

BackgroundMedicine use during pregnancy often causes concern for fetal harm. Roxithromycin, a macrolide antibiotic, is regarded as inadvisable to use during pregnancy due to lack of safety data. However, alternative macrolides have been associated with adverse outcomes in pregnancy. We conducted a register-based nationwide cohort study testing the hypothesis that use of roxithromycin in the first trimester is associated with major congenital malformations.MethodsWe included all Danish women giving live birth from 1997 to 2012. Women with at least one redeemed receipt of roxithromycin during first trimester were regarded as exposed. Multivariable logistic regression adjusting for maternal age, multiple birth, parity, year of conception, smoking, educational length, and household income was performed, supplemented by sensitivity analyses comparing unexposed with exposure to increasing accumulated doses of roxithromycin.ResultsThe study included 966,372 pregnancies of which 2,430 children were born to an exposed mother, 78 (3.34%) of the exposed children were diagnosed with a major congenital malformation compared with 33,609 (3.49%) among children born to unexposed mothers. The odds ratio for the occurrence of a major congenital malformation after exposure to roxithromycin was 0.96 (95% CI 0.76–1.20) and multifactorially adjusted 0.94 (0.74–1.18). Sensitivity analyses comparing unexposed with exposure to increasing accumulated doses of roxithromycin showed no dose response relationship. Further, no differences in the type of major malformation according to the EUROCAT subgrouping system were seen.ConclusionsWe found no association between exposure to roxithromycin in the first trimester of pregnancy and major congenital malformations.Disclosure(s)Nothing to disclose
P31 No interaction between doxapram and caffeine for the treatment of preterm neonates with apnea
Authors: Engbers A , Dia N , Völler S , Knibbe CAJ , Reiss IKM , Koch BCP , Flint RB , Simons SHP 
Published: May 2019

BackgroundIn preterm neonates with apneas, co-administration with doxapram is often initiated in case of inadequate response to caffeine alone. While doxapram is exclusively registered for adults, there is limited information on its use in preterm infants. To examine whether the observed effects of doxapram are actually due to doxapram itself, and not a pharmacokinetic interaction between both respiratory stimulants, we studied the pharmacokinetics (PK) of caffeine in a population of preterm neonates receiving both caffeine and doxapram.MethodsCaffeine concentrations from patients in the DINO study (NCT02421068) who received both caffeine and doxapram were analyzed using NONMEM V7.3. A PK model of caffeine in preterm neonates was used as a basis to estimate the PK parameters of caffeine when co-administered with doxapram with F fixed to 1 and ka fixed to 1.48 h-1.1 The results of the current study were compared to those of the reference population published by Charles et al.1ResultsIn 15 preterm infants 58 samples were collected in which caffeine plasma levels were determined. Median gestational age (GA) was 26.3 (range 24–28) weeks, postnatal age (PNA) was 25 (0–63) days and current weight was 1100 (600–2140) grams. Caffeine CL and Vd for an individual with a PNA of 12 days were estimated 0.2 L/h/70kg (RSE 28%) and 68.2 L/70kg (RSE 73%), respectively. Maturation of CL was best described by a power function with an exponent of 0.404 (RSE 89%). These results seem in good agreement with the reference population of preterm neonates receiving caffeine without doxapram with values of 0.167 L/kg/70 kg, 58.6 L/70kg and 0.358.1ConclusionIn this pharmacokinetic study in preterm neonates receiving both caffeine and doxapram, we found similar values for CL, Vd and maturation of CL with PNA compared to literature values obtained in preterm neonates receiving caffeine alone.ReferencesBG C. et al. Caffeine citrate treatment for extremely premature infants with apnea: population pharmacokinetics, absolute bioavailability, and implications for therapeutic drug monitoring. Ther. Drug Monit 2008;30:709–716.Disclosure(s)Nothing to disclose
P35 Aprepitant in the prevention of cardiotoxic adverse effects of Doxorubicin in the paediatric population – a systematic literature investigation
Authors: Feickert M , Burckhardt BB 
Published: May 2019

BackgroundIn cell line experiments, the selective NK-1-receptor antagonist Aprepitant was able to inhibit the cardiotoxic adverse effects of Doxorubicin,1 a common cytostatic used in paediatric cancer therapies. Cytostatic therapy is one of the principal reasons for toxic cardiomyopathy in children, resulting in dilated cardiomyopathy and consequently leading to heart failure. However, Aprepitant is currently licenced for adults and children and is indicated amongst others in the antiemetic supportive therapy of Doxorubicin regimes. To address the hypothesis of any indication of Aprepitant in preventing cardiotoxic adverse effects of Doxorubicin, systematic literature research is needed.MethodsSystematic literature research was examined using PubMed in January 2019. Selected inclusion criteria were: ‘Substance P’ or ‘Aprepitant’ and ‘Doxorubicin’/’cardiac inflammation’/’cardiomyopathy’ or ‘Aprepitant’ and ‘paediatrics’/’neonates’/’children’. The use of Aprepitant in adults and children as an antiemetic agent and the involvement of Substance P in (neurogenic) inflammation, cardiac infarction or diabetes led to the exclusion of publications.ResultsThe PubMed search resulted in 220 identified publications whereby 33 were relevant concerning the potential use of Aprepitant in the prevention of cardiotoxic adverse effects of Doxorubicin. It emphasises the potential use of Aprepitant in the prevention of toxic cardiomyopathy by antagonizing the inflammatory effects of the endogenous NK-1-agonist Substance P regarding cell and animal models.1 2 Based on these models, Substance P is associated with adverse cardiac remodelling and cardiac inflammation. However, in children, Aprepitant was only used as an antiemetic agent and no off-label indication was described.ConclusionSince toxic cardiomyopathy is a severe adverse effect in the Doxorubicin therapy in children, the evaluation of the role of Substance P is a promising and worthy approach to condense the knowledge about a potential use of Aprepitant in preventing paediatric toxic cardiomyopathy.ReferencesRobinson P, Kasembeli M, Bharadwaj U, et al. Substance P receptor signaling mediates doxorubicin-induced cardiomyocyte apoptosis and triple-negative breast cancer chemoresistance. Biomed Res Int2016; 2016. doi:10.1155/2016/1959270Levick SP, Soto-Pantoja DR, Bi J, et al. Doxorubicin-induced myocardial fibrosis involves the neurokinin-1 receptor and direct effects on cardiac fibroblasts. Heart Lung Circ. Published Online First: September 2018. doi:10.1016/j.hlc.2018.08.003Disclosure(s)Martin Feickert and Bjoern B. Burckhardt declare that there is no conflict of interest. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Increasing incidence of colorectal cancer in young adults in Europe over the last 25 years
Authors: Vuik Fanny ER , Nieuwenburg Stella AV , Bardou Marc , Lansdorp-Vogelaar Iris , Dinis-Ribeiro Mário , Bento Maria J , Zadnik Vesna , Pellisé María , Esteban Laura , Kaminski Michal F , Suchanek Stepan , Ngo Ondřej , Májek Ondřej , Leja Marcis , Kuipers Ernst J , Spaander Manon CW 
Published: May 2019

ObjectiveThe incidence of colorectal cancer (CRC) declines among subjects aged 50 years and above. An opposite trend appears among younger adults. In Europe, data on CRC incidence among younger adults are lacking. We therefore aimed to analyse European trends in CRC incidence and mortality in subjects younger than 50 years.DesignData on age-related CRC incidence and mortality between 1990 and 2016 were retrieved from national and regional cancer registries. Trends were analysed by Joinpoint regression and expressed as annual percent change.ResultsWe retrieved data on 143.7 million people aged 20–49 years from 20 European countries. Of them, 187 918 (0.13%) were diagnosed with CRC. On average, CRC incidence increased with 7.9% per year among subjects aged 20–29 years from 2004 to 2016. The increase in the age group of 30–39 years was 4.9% per year from 2005 to 2016, the increase in the age group of 40–49 years was 1.6% per year from 2004 to 2016. This increase started earliest in subjects aged 20–29 years, and 10–20 years later in those aged 30–39 and 40–49 years. This is consistent with an age-cohort phenomenon. Although in most European countries the CRC incidence had risen, some heterogeneity was found between countries. CRC mortality did not significantly change among the youngest adults, but decreased with 1.1%per year between 1990 and 2016 and 2.4% per year between 1990 and 2009 among those aged 30–39 years and 40–49 years, respectively.ConclusionCRC incidence rises among young adults in Europe. The cause for this trend needs to be elucidated. Clinicians should be aware of this trend. If the trend continues, screening guidelines may need to be reconsidered.
Incidences, temporal trends and risks of hospitalisation for gastrointestinal bleeding in new or chronic low-dose aspirin users after treatment forHelicobacter pylori: a territory-wide cohort study
Authors: Guo Chuan-Guo , Cheung Ka Shing , Zhang Feifei , Chan Esther W , Chen Lijia , Wong Ian CK , Leung Wai K 
Published: May 2019

ObjectiveThe risk of GI bleeding (GIB) in aspirin users afterHelicobacter pylori(HP) eradication remains poorly defined. We characterised the incidences and temporal trends of hospitalisations for all GIB in aspirin users after HP eradication therapy.DesignBased on a territory-wide health database, we identified all patients who had received the first course of clarithromycin-based triple therapy between 2003 and 2012. Patients were divided into three cohorts according to aspirin use: new users (commenced after HP eradication), chronic users (commenced before and resumed after HP eradication) and non-users. The primary outcome was to determine the risk of hospitalisation for GIB.ResultsWe included 6985 new aspirin users, 5545 chronic users and 48 908 non-users. The age-adjusted and sex-adjusted incidence of hospitalisation for all GIB in new, chronic and non-users was 10.4, 7.2 and 4.6 per 1000 person-years, respectively. Upper and lower GIB accounted for 34.7% and 45.3% of all bleeding, respectively. Compared with chronic users, new users had a higher risk of GIB (HR with propensity score matching: 1.89; 95% CI 1.29 to 2.70). Landmark analysis showed that the increased risk in new aspirin users was only observed in the first 6 months for all GIB (HR 2.10, 95% CI 1.41 to 3.13) and upper GIB (HR 2.52, 95% CI 1.38 to 4.60), but not for lower GIB.ConclusionNew aspirin users had a higher risk of GIB than chronic aspirin users, particularly during the initial 6 months. Lower GIB is more frequent than upper GIB in aspirin users who had HP eradicated.