bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations between circulating sex steroid hormones and leukocyte telomere length in men in the National Health and Nutrition Examination Survey
Authors: Coburn S. B. , Graubard B. I. , Trabert B. , McGlynn K. A. , Cook M. B. 
Published: May 2018

SummaryPreliminary evidence suggests that sex steroid hormones, such as danazol (a synthetic sex steroid hormone), may be involved in enhancing telomerase activity. Elucidating underlying mechanisms of telomerase activity may further therapeutic options for individuals with telomeropathies and potentially avert certain age‐related conditions. Therefore, we conducted a cross‐sectional study to investigate the relationship between circulating sex steroid hormones and SHBG with leukocyte telomere length among 499 males in NHANES (1999–2002 surveys). Sample‐weighted linear regression analyses were conducted to assess age‐adjusted and multivariable‐adjusted estimates of associations. Estimates were rescaled to represent telomere length change in base pairs per half the value of the interquartile range of the independent variable. Estradiol and free estradiol were significantly inversely associated with leukocyte telomere length (βcontinuous per § IQR = −61, p = 0.04; free estradiol βcontinuous per § IQR = −67, p = 0.03). Testosterone, free testosterone, androstanediol glucuronide, and SHBG were not associated with leukocyte telomere length. The inverse association seen in this study indicates that a danazol‐induced hypoestrogenic state could partly underlie the previously observed association between danazol therapy and increased leukocyte telomere length.
Study of Ras/MAPK pathway gene variants in Chilean patients with Cryptorchidism
Authors: Rodríguez F. , Vallejos C. , Ponce D. , Unanue N. , Hernández M. I. , Célis S. , Arcos K. , Belmar F. , López M. T. , Cassorla F. 
Published: May 2018

SummaryCryptorchidism is one of the most common congenital disorders in boys, and several genetic, hormonal, and environmental factors have been proposed as possible causes for this genitourinary defect. Genetic factors have been intensively searched, but relatively few pathogenic variants have been described. Cryptorchidism is a frequent finding in patients with RASopathies, a group of syndrome caused by mutations in genes of the Ras/MAPK pathway. Our aim was to determine whether patients with isolated cryptorchidism (IC) exhibit Ras/MAPK pathway gene variants associated with RASopathies. Two hundred thirty‐nine patients with IC were recruited after orchidopexy. Determination of Ras/MAPK pathway gene variants was performed by high‐resolution melting (HRM) analysis followed by sequencing. Restriction or allele‐specific amplification assay was applied to (i) variant confirmation; (ii) search in healthy controls; and (iii) segregation analysis. Controls correspond to 100 healthy Chilean adults without a history of cryptorchidism. Molecular analysis showed one synonymous substitution (BRAF_p.Q456Q) in two patients and four missense substitutions (SOS1_ p.R497Q, BRAF_ p.F595L, NRAS_ p.T50I, and MAP2K2_ p.Y134C) in five patients. Our results suggest that some patients with isolated cryptorchidism, but with no evidence of dysmorphic features suggestive of RASopathies, may harbor Ras/MAPK pathway gene alterations.
Antenatal risk factors associated with neonatal morbidity in large‐for‐gestational‐age infants: an international prospective cohort study
Authors: Vieira Matias C. , McCowan Lesley M.E. , North Robyn A. , Myers Jenny E. , Walker James J. , Baker Philip N. , Dekker Gustaaf A. , Kenny Louise C. , Poston Lucilla , Pasupathy Dharmintra ,   the SCOPE consortium
Published: May 2018

AbstractIntroductionLarge‐for‐gestational‐age infants are associated with increased risk of neonatal morbidity and mortality. However, most of them will not have adverse outcomes. Our aim was to identify antenatal clinical factors associated with neonatal morbidity in large‐for‐gestational‐age infants.Material and methodsNulliparous women from the Screening for Pregnancy Endpoints (SCOPE) study were included. We compared maternal and fetal factors between large‐for‐gestational‐age infants (birthweight >90th customized centile) with and without neonatal morbidity, defined as admission to a neonatal intensive care unit or severe neonatal morbidity. Factors were selected based on a priori hypotheses of association and included maternal demography, anthropometric measures and self‐reported physical activity (15 and 20 weeks), fetal biometry (20 weeks), and clinical information. Multivariable logistic regression was used to identify risk factors. Stratified analyses were performed by maternal obesity and physical activity.ResultsAmong term pregnancies, prevalence of large‐for‐gestational‐age infants was 9.3% (491/5255), with 11.8% (58/491) prevalence of neonatal morbidity. Random glucose at 20 weeks (odds ratio 1.52; 95% confidence interval 1.17–1.97, per 1 mmol/L increase) and no regular physical activity at 20 weeks (odds ratio 3.93; 95% confidence interval 1.75–8.83) were associated with increased risk of neonatal morbidity after adjustment for birthweight, gestational age at delivery and gestational diabetes. The increased risk associated with higher glucose levels was not evident in women with regular physical activity or without obesity.ConclusionsRegular physical activity in mid‐pregnancy is associated with lower risk for neonatal morbidity in large‐for‐gestational‐age infants and seems to offer protection against the increased risk associated with higher maternal glucose levels.
Maternal diabetes alters the development of ductus venosus shunting in the fetus
Authors: Lund Agnethe , Ebbing Cathrine , Rasmussen Svein , Kiserud Torvid , Kessler Jörg 
Published: May 2018

AbstractIntroductionDespite adequate glycemic control, the risks of fetal macrosomia and perinatal complications are increased in diabetic pregnancies. Adjustments of the umbilical venous distribution, including increased ductus venosus shunting, can be important fetal compensatory mechanisms, but the impact of pregestational diabetes on umbilical venous and ductus venosus flow is not known.Material and methodsIn this prospective study, 49 women with pregestational diabetes mellitus underwent monthly ultrasound examinations from gestational week 20 to 36. The blood velocity and the mean diameters of the umbilical vein and ductus venosus were used for calculating blood flow volumes. The development of the umbilical venous flow, ductus venosus flow and ductus venosus shunt fraction (% of umbilical venous blood shunted through the ductus venosus) was compared with a reference population, and the effect of HbA1c on the ductus venosus flow was assessed.ResultsThe umbilical venous flow was larger in pregnancies with pregestational diabetes mellitus than in low‐risk pregnancies (p < 0.001) but smaller when normalized for fetal weight (p = 0.036). The distributional pattern of the ductus venosus flow developed differently in diabetic pregnancies, particularly during the third trimester, being smaller (p = 0.007), also when normalized for fetal weight (p < 0.001). Correspondingly, the ductus venosus shunt fraction was reduced (p < 0.0001), most prominently at 36 weeks. There were negative relations between the maternal HbA1c and the ductus venosus flow velocity, flow volume and shunt fraction.ConclusionsIn pregnancies with pregestational diabetes mellitus, prioritized umbilical venous distribution to the fetal liver and lower ductus venosus shunt capacity reduce the compensatory capability of the fetus and may represent an augmented risk during hypoxic challenges during late pregnancy and birth.
Endometriosis and adenomyosis are associated with increased risk of preterm delivery and a small‐for‐gestational‐age child: a systematic review and meta‐analysis
Authors: Bruun Mette R. , Arendt Linn H. , Forman Axel , Ramlau‐Hansen Cecilia H. 
Published: May 2018

AbstractIntroductionThe objective of this systematic review and meta‐analysis was to evaluate the risk of preterm delivery and having a small‐for‐gestational‐age (SGA) child in women with endometriosis and adenomyosis compared with women without these two diseases.Material and methodsStudies on endometriosis or adenomyosis and risk of preterm delivery and/or SGA infant were included. The systematic search was conducted for all published articles in PubMed and Embase published from 1950 to 2017 using specific search terms. After duplicates were removed, two authors independently reviewed all studies, initially based on title and subsequently based on abstract. Studies considered relevant were read in full text by both reviewers to identify if studies met the inclusion criteria.ResultsThe search found 21 studies on a total of 2 517 516 women meeting the inclusion criteria. Women with endometriosis had an increased odds of preterm delivery [odds ratio (OR) 1.47, 95% CI 1.28–1.69] and SGA infant (OR 1.26, 95% CI 1.04–1.549). Compared with endometriosis, adenomyosis implied an even higher odds of both preterm delivery (OR 3.09, 95% CI 1.88–5.09) and SGA infant (OR 3.23, 95% CI 1.71–6.09) as well.ConclusionsWomen with endometriosis or adenomyosis had a higher odds of preterm delivery and having a child that was SGA compared with women without endometriosis or adenomyosis. The odds of both adverse birth outcomes was highest among women with adenomyosis. The results suggest a closer prenatal monitoring among pregnant women with endometriosis or adenomyosis.
National treatment guidelines decreased the use of racemic adrenaline for bronchiolitis in four Finnish university hospitals
Authors: Palmu Sauli , Mecklin Minna , Heikkilä Paula , Backman Katri , Peltola Ville , Renko Marjo , Korppi Matti 
Published: May 2018

AbstractAimInhaled racemic adrenaline was used for bronchiolitis in many hospitals in Finland prior to new national current care guidelines for bronchiolitis in 2014, which limited its recommendations to on‐demand rescue therapy. We studied the drug's use before and after the new guidelines to gauge changes in prescribing habits.MethodsThis 2012–2016 study analysed how many 0.5 mL doses of racemic adrenaline were used for children by emergency rooms, paediatric wards and paediatric intensive care units at four university hospitals and estimated drug and staff costs.ResultsThere were substantial differences in the yearly consumption of racemic adrenaline between the hospitals before and after the bronchiolitis guidelines were published, with reductions in drug costs and staff time. The overall use more than halved during the study period, particularly in two hospitals where baseline consumptions were highest, but not in a third where baseline consumption was already low. In the fourth, the baseline consumption was modest and there was a constant decrease during the study years.ConclusionThe current care guidelines for bronchiolitis had some impact on clinical practice, as the overall use of racemic adrenaline more than halved, but considerable differences remained in the four study hospitals after their publication.
Elevated anti‐tissue transglutaminase antibodies in children newly diagnosed with type 1 diabetes do not always indicate coeliac disease
Authors: Rinawi Firas , Badarneh Basel , Tanous Osama , Bashir Husam , Tennenbaum‐Rakover Yardena , Peleg Sarit 
Published: May 2018

AbstractAimElevated levels of anti‐tissue transglutaminase (anti‐tTG) antibody may spontaneously normalise in children with newly diagnosed type 1 diabetes, even if they eat gluten. The prevalence of this phenomenon and predictors of a subsequent coeliac disease (CD) diagnosis were determined.MethodsThe medical records of children diagnosed with type 1 diabetes at Ha'Emek Medical Centre, Israel, from 2007 to 2015, were retrospectively reviewed for elevated anti‐tTG antibody levels. Demographic, clinical, laboratory and histological findings were compared between CD patients and those with transient coeliac serology.ResultsOf 425 patients with new onset type 1 diabetes, 34 (8%) had elevated anti‐tTG antibodies: CD was diagnosed in 14, anti‐tTG normalisation occurred in 13 and duodenal biopsies did not suggest CD in seven without anti‐tTG antibody normalisation. Protective factors for a subsequent CD diagnosis were older age (p = 0.009) and mildly elevated anti‐tTG antibody levels at the time of the type 1 diabetes diagnosis (p = 0.007), and decreased anti‐tTG levels within six months of diagnosis (p = 0.03).ConclusionSerological follow‐up of a diet containing gluten is recommended for children who have newly diagnosed type 1 diabetes and slightly elevated anti‐tTG antibodies with no symptoms that suggest CD.
Peritoneal and Systemic Responses of Obese TypeIIDiabetic Rats to Chronic Exposure to a Hyperbranched Polyglycerol‐Based Dialysis Solution
Authors: La Han Bo , Guan Qiunong , Chafeeva Irina , Mendelson Asher A. , da Roza Gerald , Liggins Richard , Kizhakkedathu Jayachandran N. , Du Caigan 
Published: May 2018

AbstractMetabolic syndrome (MetS) is commonly observed among peritoneal dialysis (PD) patients, and hyperbranched polyglycerol (HPG) is a promising glucose‐sparing osmotic agent forPD. However, the biocompatibility of aHPG‐basedPDsolution (HPG) in subjects with MetS has not been investigated. This study compared the local and systemic effects of aHPGsolution with conventional physioneal (PYS) and icodextrin (ICO)PDsolutions in rats with MetS. Obese type 2 diabeticZSF1 rats received a daily intraperitoneal injection ofPDsolutions (10 mL) for 3 months. The peritoneal membrane (PM) function was determined by ultrafiltration (UF), and the systemic responses were determined by profiling blood metabolic substances, cytokines and oxidative status. Tissue damage was assessed by histology. At the end of the 3‐month treatment withPDsolutions,PMdamage andUFloss in both thePYSandICOgroups were greater than those in theHPGgroup. Blood analyses showed that compared to the baseline control, the rats in theHPGgroup exhibited a significant decrease only in serum albumin andIL‐6 and a minor glomerular injury, whereas in both thePYSandICOgroups, there were more significant decreases in serum albumin, antioxidant activity,IL‐6,KC/GRO(CXCL1) andTNF‐α (inICOonly) as well as a more substantial glomerular injury compared to theHPGgroup. Furthermore,PYSincreased serum creatinine, serum glucose and urine production. In conclusion, compared toPYSorICOsolutions, theHPGsolution had less adverse effects locally on thePMand systemically on distant organs (e.g. kidneys) and the plasma oxidative status in rats with MetS.
Potentially Inappropriate Prescribing to Older Patients: Criteria, Prevalence and an Intervention to Reduce It: The Prescription Peer Academic Detailing (Rx‐PAD) Study – A Cluster‐Randomized, Educational Intervention in Norwegian General Practice
Authors: Rognstad Sture , Brekke Mette , Gjelstad Svein , Straand Jørund , Fetveit Arne 
Published: May 2018

AbstractPotentially inappropriate prescriptions (PIP) is drug treatment, which in general, at the group level for a median/mean patient, can be considered unfavourable meaning that the risks commonly may outweigh the benefits. This MiniReview reports and discusses the main findings in a large cluster‐randomized educational intervention in Norwegian general practice, aimed at reducing the prevalence of PIPs to patients ≥70 years (The Rx‐PAD study). Targets for the intervention were general practitioners (GPs) in continuing medical education (CME) groups receiving educational outreach visits (i.e. peer academic detailing). A Delphi consensus process, with a panel of medical experts, was undertaken to elaborate a list of explicit criteria defining PIPs for patients ≥70 years in general practice. Agreement was achieved for 36 explicit PIP criteria, the so‐called Norwegian General Practice (NorGeP) criteria. Using a selection (n = 24) of these criteria during a 1‐year baseline period on the prescribing practice of 454 GPs (i.e. those enrolled to participate in the intervention trial), we found a prevalence rate of 24.7 PIPs per 100 patients ≥70 years per year. In the Rx‐PAD study, 449 GPs completed an educational intervention (96.6% of the included GPs), 250 in the intervention group and 199 in the control arm. Following the intervention, PIPs were reduced by 13% (95% CI 8.6–17.3), and the number of patients who were no longer exposed to one or more PIPs was reduced by 1173 (8.1%). The GPs who responded most strongly to the educational intervention were the oldest GPs (57–68 years), and these were the GPs with the highest prevalence of PIPs at baseline before the intervention.
Allosteric and Orthosteric Activators of mGluR8 Differentially Affect the Chemotherapeutic‐Induced Human Neuroblastoma SH‐SY5Y Cell Damage: The Impact of Cell Differentiation State
Authors: Jantas Danuta , Grygier Beata , Zatorska Justyna , Lasoń Władysław 
Published: May 2018

AbstractThe participation of group III metabotropic glutamate receptors (mGluRs) in cancer growth and progression is still an understudied issue. Based on our recent data on high expression of mGluR8 in human neuroblastoma SH‐SY5Y cells, in this study, we evaluated the effect of an mGluR8‐specific positive allosteric modulator (PAM: AZ12216052) and orthosteric agonist [(S)‐3,4‐DCPG ((S)‐3,4‐dicarboxyphenylglycine)] on chemotherapeutic (doxorubicin, irinotecan or cisplatin)‐evoked cell damage in undifferentiated (UN‐) and retinoic acid‐differentiated (RA‐) SH‐SY5Y cells. The data showed that AZ12216052 as well as a group III mGluR antagonist (UBP1112) but not (S)‐3,4‐DCPG partially inhibited the cell damage evoked by doxorubicin, irinotecan or cisplatin in UN‐SH‐SY5Y cells. In RA‐SH‐SY5Y, we observed only a modest protective effect of mGluR8 PAM. In contrast, both types of mGluR8 activators significantly enhanced toxic effects of doxorubicin and irinotecan in RA‐SH‐SY5Y cells. These data suggest that in undifferentiated neuroblastoma malignant cells, some mGluR8 modulators can decrease cytotoxic effects of chemotherapeutics which exclude them from the group of putative anticancer agents. On the other hand, in SH‐SY5Y cells differentiated to a more mature neuron‐like phenotype, that is non‐malignant cells, the mGluR8 activators can aggravate the chemotherapeutic neurotoxicity which is a well‐known undesired effect of these drugs. Our pharmacological data add new observations to the unexplored field of research on the role of mGluR8 in cancer, pointing to complexity of response which could be mediated by particular types of mGluR8 ligands at least in neuroblastoma cells.
One‐carbon cycle support rescues sperm damage in experimentally induced varicocoele in rats
Authors: Mohammadi Parisa , Hassani‐Bafrani Hassan , Tavalaee Marziyeh , Dattilo Maurizio , Nasr‐Esfahani Mohammad H. 
Published: May 2018

ObjectivesTo investigate whether micronutrients in support of the one‐carbon cycle and glutathione synthesis are effective in improving sperm damage after surgical varicocoele induction in rats and whether any effect is achieved without a rebound reductive stress as seen with oral antioxidants.Materials and MethodsSurgical varicocoele was induced in adult male Wistar rats and resulted in significant damage to the testis and sperm cells measured at 2 and 4 months after surgery. At 2 months after surgery, rats received a 2‐month oral supplementation in support of the one‐carbon cycle containing B vitamins (B2, B3, B6, folic acid and B12), N‐acetyl‐cysteine, zinc, small amounts of vitamin E, and a natural source of betalains and quercetine (Condensyl®; Parthenogen SAGL, Lugano, Switzerland and Nurilia SARL, Lyon, France).ResultsOne‐carbon cycle supplementation, compared to untreated controls, significantly improved the morphometric characteristics of testis (P < 0.05), sperm concentration, motility and abnormal morphology (P < 0.001), sperm chromatin condensation (aniline blue staining, P < 0.05), sperm DNA damage (acridine orange staining, P < 0.05) and sperm lipid peroxidation (BODIPY C11, P < 0.001). The improvement in both nuclear condensation and DNA damage and the lack of excessive inhibition of lipid peroxidation confirmed that no reductive stress had occurred.ConclusionsMicronutrients in support of the one‐carbon cycle are effective in the treatment of surgically induced varicocoele in rats, probably by activating natural antioxidant defences and epigenetics. These results support the idea that essential micronutrients including B vitamins may also have a positive influence in clinical varicocoele, which should be tested in prospective clinical trials.
IDH‐mutated astrocytomas with 19q‐loss constitute a subgroup that confers better prognosis
Authors: Otani Ryohei , Uzuka Takeo , Higuchi Fumi , Matsuda Hadzki , Nomura Masashi , Tanaka Shota , Mukasa Akitake , Ichimura Koichi , Kim Phyo , Ueki Keisuke 
Published: May 2018

IDH‐mutant gliomas are classified into astrocytic or oligodendroglial tumors by 1p/19q status in the WHO 2016 classification, with the latter presenting with characteristic morphology and better prognosis in general. However, the morphological and genetic features within each category are varied, and there might be distinguishable subtypes. We analyzed 170 WHO grade II‐IV gliomas resected in our institution. 1p/19q status was analyzed by microsatellite analysis, and genetic mutations were analyzed by next‐generation sequencing and Sanger sequencing. For validation, the Brain Lower Grade Glioma dataset of The Cancer Genome Atlas was analyzed. Of the 42 grade III IDH‐mutated gliomas, 12 were 1p‐intact/19q‐intact (anaplastic astrocytomas [AA]), 7 were 1p‐intact/19q‐loss (AA), and 23 showed 1p/19q‐codeletion (anaplastic oligodendrogliomas). Of the 88 IDH‐wild type glioblastomas (GBMs), 14 showed 1p‐intact/19q‐loss status. All of the seven 1p‐intact/19q‐loss AAs harbored TP53 mutation, but no TERT promotor mutation. All 19q‐loss AAs had regions presenting oligodendroglioma‐like morphology, and were associated with significantly longer overall survival compared to 19q‐intact AAs (P = .001). This tendency was observed in The Cancer Genome Atlas Lower Grade Glioma dataset. In contrast, there was no difference in overall survival between the 19q‐loss GBM and 19q‐intact GBM (P = .4). In a case of 19q‐loss AA, both oligodendroglial morphology and 19q‐loss disappeared after recurrence, possibly indicating correlation between 19q‐loss and oligodendroglial morphology. We showed that there was a subgroup, although small, of IDH‐mutated astrocytomas harboring 19q‐loss that present oligodendroglial morphology, and also were associated with significantly better prognosis compared to other 19q‐intact astrocytomas.