bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyclooxygenase 2 (COX2) expression and prostaglandin synthesis in neonatal rat testicular germ cells: Effects of acetaminophen and ibuprofen
Authors: Manku Gurpreet , Papadopoulos Philippos , Boisvert Annie , Culty Martine 
Published: November 2019

AbstractBackgroundIn infants, fever is often treated with acetaminophen or ibuprofen, two antipyretic and analgesic drugs inhibiting cyclooxygenases (COXs), enzymes catalyzing prostaglandin production. Infancy represents a critical developmental period when neonatal germ cells/gonocytes differentiate to spermatogonial stem cells required for spermatogenesis.Objectives(a) Determine the expression of Cox2 and associated genes in postnatal day (PND)3 rat gonocytes compared to spermatogonia. (b) Examine whether acetaminophen or ibuprofen disrupts neonatal gonocyte functions. (c) Determine whether neonatal gonocytes produce prostaglandins and whether this process is altered by acetaminophen and ibuprofen.Materials and methodsThe expression of Cox2 and related genes was determined by gene arrays and qPCR. Cox2 protein levels were determined by immunocyto/histochemistry and immunoblots. The effects of acetaminophen and ibuprofen on PND3 gonocyte viability, apoptosis, proliferation, and differentiation were examined alone and with a proliferation cocktail or differentiation factor. Prostaglandins were examined by immunocyto/histochemistry and LC‐MS.ResultsCox2 and related genes are highly expressed in gonocytes and spermatogonia. Acetaminophen and ibuprofen did not affect gonocyte survival or apoptosis, but they increased gonocyte proliferation. Ibuprofen significantly reduced RA‐induced Stra8 expression, indicating an inhibitory effect on differentiation. Ibuprofen combined with RA decreased Cox2 mRNA and protein expression. PGE2 and PGF2α were produced by neonatal gonocytes and decreased by acetaminophen and ibuprofen.DiscussionThe concomitant decrease of Stra8 expression, Cox2 expression, and PGE2 and PGF2a production in gonocytes co‐treated with RA suggests that Cox2 plays a role in PND3 gonocyte differentiation. The effects of acetaminophen and ibuprofen on proliferation suggest a negative relationship between Cox2 and proliferation. Treating neonates with acetaminophen or ibuprofen could disrupt gonocyte development, leading to adverse reproductive effects.ConclusionUnderstanding COX2 role in neonatal gonocytes and the potential risk of acetaminophen and ibuprofen treatment of infants may help prevent male reproductive pathologies.
Complete histologic normalisation is associated with reduced risk of relapse among patients with ulcerative colitis in complete endoscopic remission
Authors: Cushing Kelly C. , Tan William , Alpers David H. , Deshpande Vikram , Ananthakrishnan Ashwin N. 
Published: November 2019

SummaryBackgroundClinical and endoscopic remission are treatment targets in ulcerative colitis (UC). The value of histologic healing in altering clinical outcomes among patients with complete endoscopic healing is not well established.AimTo quantify the association between histologic activity and clinical relapse among patients with UC who were in complete endoscopic remission.MethodsThis study included patients with UC from a prospective registry who were in complete endoscopic remission. Histologic activity was quantified by a senior gastrointestinal pathologist. Histologic activity was defined as lack of normalisation (Geboes score > 0) as well as histologically active disease (Geboes score ≥2.1 and ≥3.1). The primary outcome was clinical relapse within 2 years. Multivariable regression adjusting for potential confounders examined the independent predictive value of histologic changes.ResultsThe study included 83 patients (51% women) (median age 44 years; median disease duration 11 years). Forty‐one (49%) had complete histologic normalisation. Within two years, 26 (31%) experienced clinical relapse. Patients with complete histologic normalisation were less likely to experience relapse (5/41, 12%) compared to those without normalisation (21/42, 50%, P < 0.001) (multivariable OR 7.22, 95% confidence interval (CI) 2.48‐24.70) by the Geboes score. The individual components of the Geboes score predictive of relapse were architectural changes (P = 0.03) and increased chronic inflammatory infiltrate (P < 0.001).ConclusionsComplete histologic healing using the Geboes score was associated with reduced rates of clinical relapse among patients with UC in endoscopic remission.
Histochemical and immunohistochemical adaptations on the gastroesophageal tube of the blue‐fronted parrot (Amazona aestiva Linnaeus, 1758)
Authors: da Silva Macêdo Jaqueline , Machado-santos Clarice , Ferreira Ildemar 
Published: November 2019

AbstractAmazona aestiva Linnaeus, 1758 is known as the blue‐fronted parrot. These animals are considered seed dispersion, contributing to ecological balance. Despite its ecological importance, A. aestiva is listed as an imminent danger of becoming extinct, as it is one of the most illegally traded native species in Brazil, besides losing its habitat due to deforestation and forest fires. The cranial oesophagus mucosa is lined with a non‐keratinized stratified squamous epithelium, and the basal layer presents melanocyte accumulation. No mucous glands were observed in the lamina propria/submucosa. The ingluvium two different muscular layer patterns were observed, one internal and circular and one very thick, external and longitudinal. The proventriculum submucosa consists of polygonal proventricular glands and contents into a broad central duct lined with simple columnar epithelium Periodic acid‐reactive Schiff positive (PAS+) and Alcian blue positive (AB+). The 5‐HT cells are dispersed in the proventricular glands located at base and apex. The ventricle mucous layer contains numerous branched folds lined by a simple columnar epithelium. The epithelium was negative reaction for PAS and positive for AB only on the fold surfaces. The 5‐HT cells were scarce and observed only at the base of the ventricular gland, as well as in the adjacent connective tissue.
Development of body knowledge as measured by arm differentiation in infants: From global to local?
Authors: Jacquey Lisa , Popescu Sergiu Tcaci , Vergne Judith , Fagard Jacqueline , Esseily Rana , O’Regan Kevin 
Published: November 2019

The ability to sense and use the body parts in an organized and differentiated manner is a precursor of body knowledge in infancy. To acquire this ability, the infant's brain might explore the perceptual consequences of its bodily actions. Undifferentiated body movements would gradually be replaced by more precise actions. Only a very few studies have tested this ‘global‐to‐local’ hypothesis, and none of them have so far been replicated. In this study, we assessed arm differentiation in 4‐, 6‐, and 8‐month‐old infants using a new contingency detection task in which infants have to detect a contingency between one of their arms’ activity and an audiovisual stimulus on a screen. We found that 4‐ to 8‐month‐old infants seem to be able to use their arms in a differentiated manner. However, surprisingly, we were not able to show a developmental trend in arm differentiation between 4 and 8 months of age.
Statement of contribution

What is already known on this subject?

Foetuses and infants possess coarse control of their body and may be sensitive to sensory feedback caused by their own movements.

Body knowledge might develop during the first year of life in what can be called a ‘global‐to‐local’ manner. Nevertheless, the precise age at which infants come to possess well‐differentiated local body knowledge requires further investigation.

What the present study adds?

4‐ to 8‐month‐old infants seem able to use their arms in a differentiated manner when exposed to an audiovisual stimulation contingent on movements of one of their arms.

However, we found no developmental trend in arm differentiation between 4 and 8 months of age.

We hypothesize that infants' sensitivity to sensorimotor contingencies and their ability to narrow down contingencies to a specific limb might evolve with age as a function of the infant's current sensorimotor interests.
Prenatal and postnatal alcohol exposure increases vulnerability to cocaine addiction in adult mice
Authors: Cantacorps Lídia , Montagud‐Romero Sandra , Luján Miguel Ángel , Valverde Olga 
Published: November 2019

Background and PurposeAlcohol exposure in utero may lead to a wide range of long‐lasting morphological and behavioural deficiencies known as fetal alcohol spectrum disorders (FASD), associated with a higher risk of later developing neuropsychiatric disorders. However, little is known about the long‐term consequences of cocaine use and abuse in individuals with FASD. This study aimed to investigate the effects of maternal binge alcohol drinking during prenatal and postnatal periods on cocaine reward‐related behaviours in adult offspring.Experimental ApproachPregnant C57BL/6 female mice were exposed to an experimental protocol of binge alcohol consumption (drinking‐in‐the‐dark test) from gestation to weaning. Male offspring were subsequently left undisturbed until reaching adulthood and were tested for cocaine‐induced motivational responses (conditioned place preference, behavioural sensitization and operant self‐administration). Protein expression of dopamine‐ and glutamate‐related molecules was assessed following cocaine‐induced reinstatement.Key ResultsThe results show that prenatal and postnatal alcohol exposure enhanced the preference for the cocaine‐paired chamber in the conditioned place preference test. Furthermore, early alcohol‐exposed mice displayed attenuated cocaine‐induced behavioural sensitization but also higher cocaine self‐administration. Furthermore, alterations in glutamatergic excitability (GluA1/GluA2 ratio) and ΔFosB expression were found in the prefrontal cortex and the striatum of alcohol‐exposed mice after cocaine‐primed reinstatement.Conclusion and ImplicationsOur findings demonstrate that maternal binge‐like alcohol consumption during gestation and lactation alters sensitivity to the reinforcing effects of cocaine in adult offspring mice. Together, such data suggest that prenatal and postnatal alcohol exposure may underlie an enhanced susceptibility of alcohol‐exposed offspring to develop drug addiction later in adulthood.
FK506 regulates Ca2+ release evoked by inositol 1,4,5‐trisphosphate independently of FK‐binding protein in endothelial cells
Authors: Buckley Charlotte , Wilson Calum , McCarron John G. 
Published: November 2019

Background and PurposeFK506 and rapamycin are modulators of FK‐binding proteins (FKBP) that are used to suppress immune function after organ and hematopoietic stem cell transplantations. The drugs share the unwanted side‐effect of evoking hypertension that is associated with reduced endothelial function and nitric oxide production. The underlying mechanisms are not understood. FKBP may regulate IP3 receptors (IP3R) and ryanodine receptors (RyR) to alter Ca2+ signalling in endothelial cells.Experimental ApproachWe investigated the effects of FK506 and rapamycin on Ca2+ release via IP3R and RyR in hundreds of endothelial cells, using the indicator Cal‐520, in intact mesenteric arteries from male Sprague‐Dawley rats. IP3Rs were activated by acetylcholine or localised photo‐uncaging of IP3, and RyR by caffeine.Key ResultsWhile FKBPs were present, FKBP modulation with rapamycin did not alter IP3‐evoked Ca2+ release. Conversely, FK506, which modulates FKBP and blocks calcineurin, increased IP3‐evoked Ca2+ release. Inhibition of calcineurin (okadiac acid or cypermethrin) also increased IP3‐evoked Ca2+ release and blocked FK506 effects. When calcineurin was inhibited, FK506 reduced IP3‐evoked Ca2+ release. These findings suggest that IP3‐evoked Ca2+ release is not modulated by FKBP, but by FK506‐mediated calcineurin inhibition. The RyR modulators caffeine and ryanodine failed to alter Ca2+ signalling suggesting that RyR is not functional in native endothelium.Conclusion and ImplicationsThe hypertensive effects of the immunosuppressant drugs FK506 and rapamycin, while mediated by endothelial cells, do not appear to be exerted at the documented cellular targets of Ca2+ release and altered FKBP binding to IP3 and RyR.
Osteosarcoma‐initiating cells show high aerobic glycolysis and attenuation of oxidative phosphorylation mediated by LIN28B
Authors: Mizushima Emi , Tsukahara Tomohide , Emori Makoto , Murata Kenji , Akamatsu Asuka , Shibayama Yuji , Hamada Shuto , Watanabe Yuto , Kaya Mitsunori , Hirohashi Yoshihiko , Kanaseki Takayuki , Nakatsugawa Munehide , Kubo Terufumi , Yamashita Toshihiko , Sato Noriyuki , Torigoe Toshihiko 
Published: November 2019

AbstractOsteosarcoma (OS) is a highly malignant bone tumor and the prognosis for non‐responders to chemotherapy remains poor. Previous studies have shown that human sarcomas contain sarcoma‐initiating cells (SIC), which have the characteristics of high tumorigenesis and resistance to chemotherapy. In the present study, we characterized SIC of a novel OS cell line, screened for SIC‐related genes, and tried to regulate the proliferation of OS by metabolic interference. Initially, we established a new human OS cell line (OS13) and isolated clones showing higher tumorigenesis as SIC (OSHIGH) and counterpart clones. OSHIGH cells showed chemoresistance and their metabolism highly depended on aerobic glycolysis and suppressed oxidative phosphorylation. Using RNA‐sequencing, we identified LIN28B as a SIC‐related gene highly expressed in OSHIGH cells. mRNA of LIN28B was expressed in sarcoma cell lines including OS13, but its expression was not detectable in normal organs other than the testis and placenta. LIN28B protein was also detected in various sarcoma tissues. Knockdown of LIN28B in OS13 cells reduced tumorigenesis, decreased chemoresistance, and reversed oxidative phosphorylation function. Combination therapy consisting of a glycolysis inhibitor and low‐dose chemotherapy had antitumor effects. In conclusion, manipulation of glycolysis combined with chemotherapy might be a good adjuvant treatment for OS. Development of immunotherapy targeting LIN28B, a so‐called cancer/testis antigen, might be a good approach.
Basal serum luteinising hormone cut‐off, and its utility and cost‐effectiveness for aiding the diagnosis of the onset of puberty in girls with early stages of breast development
Authors: Wankanit Somboon , Mahachoklertwattana Pat , Pattanaprateep Oraluck , Poomthavorn Preamrudee 
Published: November 2019

AbstractObjectiveTo determine basal and gonadotrophin‐releasing hormone analogue (GnRHa)‐stimulated peak luteinising hormone (LH) cut‐offs to diagnose onset of early or normal puberty in girls with each Tanner stage of breast (II and III).Design, Patients and MeasurementsA retrospective study of 601 girls with breast onset before 8 years of age who underwent GnRHa test was conducted. Patients were categorized as CPP and premature thelarche. Each group was divided into two subgroups; Tanner II and III. Cost‐effectiveness analysis was performed.ResultsIn comparison with basal LH cut‐off of 0.3 IU/L, basal LH cut‐off of 0.2 IU/L had comparable specificity (Tanner II: 98.0% vs 94.8%, Tanner III: 98.8% vs 93.8%), but greater sensitivity (Tanner II: 28.3% vs 41.7%, Tanner III: 45.2% vs 59.3%). Specificity of basal LH cut‐off of 0.2 IU/L was not inferior to that of the traditionally used peak LH of 5 IU/L. Using basal LH cut‐off of 0.2 IU/L followed by GnRHa test in girls with negative basal LH was more cost‐saving when compared with using the cut‐off of 0.3 IU/L. Moreover, using basal LH cut‐off of 0.2 IU/L followed by GnRHa test provided a cost reduction when compared with performing GnRHa test in all patients.ConclusionsBasal serum LH cut‐off of 0.2 IU/L could be a simple and cost‐saving tool for initial diagnosis of onset of early or normal puberty in girls with Tanner II and III before proceeding to GnRH testing.
Investigating the social environment of the A‐not‐B search task
Authors: Dunn Kirsty , Bremner James Gavin 
Published: November 2019

AbstractControversy exists concerning the origins of object permanence, with different measures suggesting different conclusions. Looking measures have been interpreted as evidence for early understanding (Baillargeon, 1987, Developmental Psychology, 23:655), while Piaget (The construction of reality in the child, 1954) interpreted perseverative reaching behaviour on his AB search task to be indicative of limited understanding. However, looking measures are often reported to be an unreliable index of infant expectation (Haith, 1998, Infant Behaviour and Development, 21:167) and reaching behaviour has been explained by many alternative processes (e.g. Smith et al., 1999, Psychological Review, 106:235; Topál et al., 2008, Science, 321:1831). We aimed to investigate whether social looking (Dunn & Bremner, 2017, Developmental Science, 20:e12452; Walden et al., 2007, Developmental Science, 10:654) can be used as a valid measure of infant expectation of object location during the Piagetian AB search task. Furthermore, we aimed to test the social accounts of perseverative reaching by investigating how the direction of experimenter gaze would affect infant search and social behaviour. Infant search and social behaviour was compared on B trials across three different conditions, namely experimenter gaze to midline, location A and location B. Search performance significantly improved when the experimenter looked to location B. Infant social looking indicated that infants expect the object to be found in the location in which they search and are actively seeking information about object location from the experimenter. We conclude that social looking is a valid index of infant expectation that has provided support for the importance of the social environment on the AB search task. This casts doubt on the potential for this task to provide information related to the development of object permanence in infancy.
Elevated fasting vs post‐load glucose levels and pregnancy outcomes in gestational diabetes: a population‐based study
Authors: Ryan E. A. , Savu A. , Yeung R. O. , Moore L. E. , Bowker S. L. , Kaul P. 
Published: November 2019

AbstractAimsTo examine the relative association between fasting plasma glucose vs post‐load (1‐h and 2‐h) glucose levels based on the oral glucose tolerance test in pregnancy and large‐for‐gestational‐age and hypertensive disorders of pregnancy outcomes.MethodsAll live singleton births between October 2008 and December 2014 in Alberta, Canada were included. Gestational diabetes mellitus was diagnosed using Diabetes Canada criteria. Logistic regression models were used to examine the association between fasting plasma glucose vs post‐load values and large‐for‐gestational‐age infants and hypertensive disorders of pregnancy after adjusting for maternal characteristics and pharmaceutical intervention in gestational diabetes pregnancies.ResultsAmong 257 547 pregnancies, 208 344 (80.9%) had negative 50‐g glucose challenge tests, 36 261 (14.1%) had negative 75‐g oral glucose tolerance tests, and 12 942 (5.0%) had gestational diabetes based on either elevated fasting plasma glucose (n=4130, 1.6%) or elevated 1‐h and/or 2‐h oral glucose tolerance test values (n=8812, 3.4%). Large‐for‐gestational‐age and hypertensive disorders of pregnancy rates were 8.1% and 5.1% in negative glucose challenge test pregnancies, 11.0% and 7.0% in negative oral glucose tolerance test pregnancies, 22.4% and 11.9% in gestational diabetes pregnancies with elevated fasting plasma glucose, and 9.1% and 8% in gestational diabetes pregnancies with elevated post‐load levels, respectively. Among gestational diabetes pregnancies, those with elevated fasting plasma glucose were at higher risk of large‐for‐gestational age (adjusted odds ratio 2.66, 95% CI 2.39–2.96) and hypertensive disorders of pregnancy (adjusted odds ratio 1.51, 95% CI 1.33–1.72) outcomes relative to pregnancies with post‐load glucose elevations only. Fasting plasma glucose remained significantly associated with adverse outcomes in gestational diabetes pregnancies with and without pharmacological intervention.ConclusionsElevated fasting plasma glucose in women with gestational diabetes is a stronger predictor of large‐for‐gestational‐age and hypertensive disorders of pregnancy outcomes than elevated post‐load glucose.
β‐Cell and renal transplantation options for diabetes
Authors: Flatt A. J. S. , Bennett D. , Counter C. , Brown A. L. , White S. A. , Shaw J. A. M. 
Published: November 2019

AbstractDespite major advances in structured education, insulin delivery and glucose monitoring, diabetes self‐management remains an unremitting challenge. Insulin therapy is inextricably linked to risk of dangerous hypoglycaemia and sustained hyperglycaemia remains a leading cause of renal failure. This review sets out to demystify transplantation for diabetes multidisciplinary teams, facilitating consideration and incorporation within holistic overall person‐centred management. Deceased and living donor kidney, whole pancreas and isolated islet transplant procedures, indications and potential benefits are described, in addition to outcomes within the integratedUKtransplant programme.
Insulin degludec/liraglutide (IDegLira) maintains glycaemic control and improves clinical outcomes, regardless of pre‐trial insulin dose, in people with type 2 diabetes that is uncontrolled on basal insulin
Authors: Meneghini L. , Doshi A. , Gouet D. , Vilsbøll T. , Begtrup K. , Őrsy P. , Ranthe M. F. , Lingvay I. 
Published: November 2019

AbstractAimsTo assess whether people with type 2 diabetes transferring from higher basal insulin doses (> 20 units) to a starting dose of 16 units of insulin degludec/liraglutide (IDegLira) benefit from IDegLira with/without transient loss of glycaemic control.MethodsPost hoc analysis of DUAL V and VII assessed fasting self‐measured blood glucose (SMBG) over weeks 1–8, changes in HbA1c, body weight and mean insulin dose over 26 weeks, and percentage of participants achieving HbA1c < 53 mmol/mol (7.0%) by end of trial in participants with type 2 diabetes uncontrolled with basal insulin. IDegLira was compared with continued up‐titration of insulin glargine (IGlar U100) in DUAL V, or switching to basal–bolus therapy in DUAL VII (IGlar U100 and insulin aspart), across pre‐trial insulin dose groups (20–29, 30–39 and 40–50 units/day).ResultsIn all subgroups, participants treated with IDegLira experienced significant improvements in HbA1c by end of trial, which were greater than with IGlar U100 up‐titration (estimated treatment difference –5.86, –6.59 and –6.91 mmol/mol for pre‐trial insulin doses of 20–29, 30–39 and 40–50 units/day, respectively) and similar to basal–bolus therapy (estimated treatment difference –0.16, –1.0 and –0.01 mmol/mol for pre‐trial insulin doses of 20–29, 30–39 and 40–50 units/day, respectively). Compared with IGlar U100 and basal–bolus therapy, IDegLira participants experienced weight loss vs. weight gain, lower rates of hypoglycaemia and a lower mean end of trial total daily insulin dose. In both trials, mean fasting SMBG decreased from weeks 1 to 8 across all subgroups, despite a temporary increase in mean fasting SMBG in the 40–50 units pre‐trial insulin dose group during week 1 [mean increase (sd) +1.1 (2.0) mmol/l for DUAL V and +1.1 (2.1) mmol/l for DUAL VII], which reverted to baseline by week 4.ConclusionsRegardless of pre‐trial insulin dose, IDegLira resulted in improved clinical outcomes, even in participants transferring from 40–50 units of basal insulin, despite a transient (< 4 weeks), clinically non‐relevant, elevation in pre‐breakfast SMBG. (Clinical Trial Registry Number NCT01952145 and NCT02420262).