bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of the GLP‐1 Agonist Exendin‐4 on Intravenous Ethanol Self‐Administration in Mice
Authors: Sørensen Gunnar , Caine S. Barak , Thomsen Morgane 
Published: August 2016

BackgroundGlucagon‐like peptide 1 (GLP‐1) receptor agonists have been shown to decrease ethanol (EtOH) drinking in rodent assays. The GLP‐1 system also powerfully modulates food and fluid intake, gastrointestinal functions, and metabolism. To begin to understand the neurobiological mechanisms by which GLP‐1 receptor ligands may be able to control EtOH intake, it is important to ascertain whether they can modulate the direct reinforcing effects of EtOH, without the confound of effects on ingestive behaviors generally.MethodsWe trained experimentally naïve, free‐fed C57BL/6J mice to self‐administer EtOH intravenously. Once stable EtOH intake was acquired, we tested the effect of acute pretreatment with the GLP‐1 receptor agonist Exendin‐4. Effect of Exendin‐4 on operant behavior reinforced by a palatable liquid food was similarly evaluated as a control.ResultsIntravenous EtOH functioned as a positive reinforcer in over half the mice tested. In mice that acquired self‐administration, EtOH intake was high, indeed, reaching toxic doses; 3.2 μg/kg Exendin‐4 decreased intravenous EtOH intake by at least 70%, but had no significant effect on food‐maintained operant responding.ConclusionsThis experiment produced 2 main conclusions. First, although technically challenging and yielding only moderate throughput, the intravenous self‐administration procedure in mice is feasible, and sensitive to pharmacological manipulations. Second, GLP‐1 receptor agonists can powerfully attenuate voluntary EtOH intake by directly modulating the reinforcing effects of EtOH. These findings support the potential usefulness of GLP‐1 receptor ligands in the treatment of alcohol use disorder.
D1, but not D2, receptor blockade within the infralimbic and medial orbitofrontal cortex impairs cocaine seeking in a region‐specific manner
Authors: Cosme Caitlin V. , Gutman Andrea L. , Worth Wensday R. , LaLumiere Ryan T. 
Published: August 2016

AbstractEvidence suggests that the infralimbic cortex (IL), a subregion of the ventromedial prefrontal cortex (vmPFC), suppresses cocaine‐seeking behavior in a self‐administration paradigm, whereas the more anterior vmPFC subregion, the medial orbitofrontal cortex (mOFC), has received very little attention in this regard. Despite the established dopaminergic innervation of the vmPFC, whether dopamine receptor blockade in each subregion alters the reinstatement of cocaine seeking is unclear. To address this issue, male Sprague–Dawley rats underwent 2 weeks of cocaine self‐administration, followed by extinction training and reinstatement testing. Immediately prior to each reinstatement test, rats received microinjections of the D1 receptor antagonist SCH 23390, the D2 receptor antagonist sulpiride or their respective vehicles. D1 receptor blockade in the IL reduced cued reinstatement but had no effect on cocaine prime and cue + cocaine‐prime reinstatement, whereas D2 receptor blockade in the IL had no effect on reinstatement. For the mOFC, however, D1 receptor blockade reduced cocaine seeking in all reinstatement types, whereas blocking D2 receptors in the mOFC had no effect on any form of cocaine seeking. These findings suggest different roles for D1 receptors in the IL versus the mOFC in regulating cocaine‐seeking behavior. Moreover, even as previous work indicates that IL inactivation does not affect reinstatement but, rather, induces cocaine seeking during extinction, the present findings suggest that dopamine receptor activation in the IL is necessary for cocaine seeking under some circumstances.
Behavioral and transcriptional patterns of protracted opioid self‐administration in mice
Authors: Skupio Urszula , Sikora Magdalena , Korostynski Michal , Wawrzczak‐Bargiela Agnieszka , Piechota Marcin , Ficek Joanna , Przewlocki Ryszard 
Published: August 2016

AbstractChronic exposure to opioids induces adaptations in brain function that lead to the formation of the behavioral and physiological symptoms of drug dependence and addiction. Animal models commonly used to test these symptoms typically last less than two weeks, which is presumably too short to observe the alterations in the brain that accompany drug addiction. Here, we analyzed the phenotypic and molecular effects of nearly lifelong morphine or saccharin intake in C57BL/6J mice. We used multiple paradigms to evaluate the symptoms of compulsive drug intake: a progressive ratio schedule, intermittent access and a schedule involving a risk of punishment were programmed into an automated IntelliCage system. Gene expression profiles were evaluated in the striatum using whole‐genome microarrays and further validated using quantitative polymerase chain reaction in the striatum and the prefrontal cortex. Mice voluntary self‐administering morphine showed addiction‐related behavioral pattern that included: higher motivation to work for a drug reward, increased reward seeking and increased craving. The analysis of molecular changes revealed a tolerance effect in the transcriptional response to morphine injection (20 mg/kg, ip), as well as some long‐lasting alterations in gene expression profiles between the analyzed groups of animals. Interestingly, among the morphine‐drinking animals, certain transcriptional profiles were found to be associated with alterations in behavior. In conclusion, our model represents a novel approach for investigating the behavioral and molecular mechanisms underlying opioid addiction. Prolonged morphine intake caused adaptive processes in the brain that manifested as altered behavior and transcriptional sensitivity to opioids.
Of feathers and fur: Differential pollinator roles of birds and small mammals in the grassland succulent Aloe peglerae
Authors: Payne Stephanie L. , Symes Craig T. , Witkowski Ed T.F. 
Published: August 2016

AbstractThe pollination syndrome of the genus Aloe, with gaudy inflorescences and orange–red flowers, suggests bird pollination. However, the diversity of flowering phenologies and structures suggests that generalizations within the group are currently uninformative because few studies have addressed the role of multiple pollinator guilds, especially mammals. Aloe peglerae, endemic to montane grassland of the Magaliesberg Mountains, South Africa, is primarily bird pollinated, although small mammals are recorded nocturnal visitors. We compared the independent contributions of diurnal and nocturnal visitors, i.e. birds and small mammals respectively, to reproductive success by assigning 12 flowering A. peglerae plants to each of four pollinator selective exclusion treatments: (i) no‐visitors; (ii) nocturnal‐visitors; (iii) diurnal‐visitors; and (iv) all‐visitors (control). Birds alone contributed more to fruit set (1.2–2.6 times), average seed/fruit (1.0–1.8 times) and total seed production (1.1–2.8 times) than both the all visitors (birds and small mammals combined) and the small mammal visitors respectively. The exclusion of all visitors resulted in no fruit set, suggesting that A. peglerae requires pollinators to set seed. Germination trials over six weeks and viability testing with tetrazolium staining identified no significant differences among the three treatments that produced fruit and seed. Germination success was 90–97%, indicating that seed quality of small‐mammal and bird‐pollinated plants are similar. Aloe peglerae inflorescences were visited continuously throughout the day and night, with the Cape rock‐thrush (Monticola rupestris) and dark‐capped bulbul (Pycnonotus tricolor) being the most abundant pollinators, accounting for 68.2% and 13.7% of all visits respectively in the control treatment. Small mammals, i.e. Namaqua rock mouse (Micaelamys namaquensis) and eastern rock sengi (Elephantulus myurus), while not increasing reproductive success in the absence of birds, are suitable alternative pollinators. The presence of diurnal bird and nocturnal small mammal visitors provides a diversity of pollinators in this resilient pollination syndrome.
Area‐based study identifies risk factors associated with missed antenatal corticosteroid prophylaxis in women delivering preterm infants
Authors: Gagliardi Luigi , Amador Carolina , Puglia Monia , Mecacci Federico , Pratesi Simone , Sigali Emilio , Tomasini Barbara , Rusconi Franca ,   TIN Toscane on‐line Group
Published: August 2016

AbstractAimAll women delivering a preterm infant should receive antenatal corticosteroid prophylaxis, but many miss this opportunity. We determined the risk factors associated with missed prophylaxis in a geographically defined area of Italy.MethodsWe prospectively studied all mothers who delivered babies between 24 and 31 completed weeks of gestation, from 2009 to 2013, in all maternity units in Tuscany.ResultsOf 1232 mothers, 186 (15.1%) did not receive prophylaxis. The risk was higher in migrant mothers, with an adjusted risk ratio (RR) of 1.28 and 95% confidence interval (95% CI) of 1.04–1.56, and in mothers hospitalised for less than 24 hours (RR 4.09, 95% CI: 2.90–5.78). Preterm prelabour rupture of membranes (RR 0.63, 95% CI: 0.41–0.96) and maternal antepartum transfer (RR 0.24, 95% CI: 0.18–0.32) were protective. Hospital level at birth and gestational age did not influence the prophylaxis rate. The population‐attributable fractions were 50.4% for late hospital admissions and 10.2% for migrant status.ConclusionIn a highly organised network of hospitals, neither level of care nor gestational age influenced prophylaxis. Timely arrival of women in hospital, better recognition of the imminence of delivery and tighter steroids administration guidelines are the most relevant targets to further increase prophylaxis.
Clinical trials for authorized biosimilars in the European Union: a systematic review
Authors: Mielke Johanna , Jilma Bernd , Koenig Franz , Jones Byron 
Published: August 2016

AimIn 2006, Omnitrope (by Sandoz) was the first approved biosimilar in Europe. To date, 21 biosimilars for seven different biologics are on the market. The present study compared the clinical trials undertaken to obtain market authorization.MethodsWe summarized the findings of a comprehensive review of all clinical trials up to market authorization of approved biosimilars, using the European public assessment reports (EPARs) published by the European Medicines Agency (EMA). The features compared were, among others, the number of patients enrolled, the number of trials, the types of trial design, choice of endpoints and equivalence margins for pharmacokinetic (PK)/pharmacodynamic (PD) and phase III trials.ResultsThe variability between the clinical development strategies is high. Some differences are explainable by the characteristics of the product; if, for example, the PD marker can be assumed to predict the clinical outcome, no efficacy trials might be necessary. However, even for products with the same reference product, the sample size, endpoints and statistical models are not always the same.ConclusionsThere seems to be flexibility for sponsors regarding the decision as to how best to prove biosimilarity.
Anti‐Inflammatory Effect of Erythropoietin in the TNBS‐induced Colitis
Authors: Mateus Vanessa , Rocha João , Alves Paula , Mota‐Filipe Helder , Sepodes Bruno , Pinto Rui Manuel Amaro 
Published: August 2016

AbstractErythropoietin is a potent stimulator of erythroid progenitor cells, which is able to inhibit NF‐kB activation, due to its pleiotropic properties, thus promoting an anti‐inflammatory effect. As inflammatory bowel disease is a chronic disease with reduced quality of life, and the current pharmacotherapy only induces or maintains the patient in remission, there is a crucial need of new pharmacological approaches. The main objective of this study was to evaluate the effect of erythropoietin in the TNBS‐induced colitis model in mice with a normal intestinal flora. Mice with TNBS‐induced colitis were treated with a daily dose of erythropoietin at 500 IU/kg bw/day and 1000 IU/Kg bw/day IP during 4 days. As to clinical symptoms/signs, erythropoietin attenuated the decreased body‐weight and reduced diarrhoea and oedema of the anus registered in the non‐treated mice group in a dose‐dependent manner. The anti‐inflammatory properties of erythropoietin in the TNBS‐induced colitis were confirmed by suppression of pro‐inflammatory mediators, such as TNF‐α, IL‐1β and MPO, as well as a significant increase in the anti‐inflammatory cytokine, IL‐10, was promoted. These treated mice also presented a reduction in haemoglobin faecal and ALP, suggesting a beneficial effect of erythropoietin in the haemorrhagic focus and destruction of the enterocyte associated with the colon injury induced by TNBS, respectively. The histopathological score was reduced after treatment with erythropoietin, decreasing the severity and extension of the colitis. Furthermore, renal and hepatic biomarkers, as well as haematocrit concentration, remained stabilized after treatment. In conclusion, erythropoietin reduces the inflammatory response associated with TNBS‐induced colitis in mice.
Modulation of the immune response toMycobacterium tuberculosisduring malaria/M. tuberculosisco-infection
Authors: Chukwuanukwu R C , Onyenekwe C C , Martinez-Pomares L , Flynn R , Singh S , Amilo G I , Agbakoba N R , Okoye J O 
Published: August 2016

SummaryTuberculosis (TB) causes significant morbidity and mortality on a global scale. The African region has 24% of the world's TB cases. TB overlaps with other infectious diseases such as malaria and HIV, which are also highly prevalent in the African region. TB is a leading cause of death among HIV-positive patients and co-infection with HIV and TB has been described as a syndemic. In view of the overlapping epidemiology of these diseases, it is important to understand the dynamics of the immune response to TB in the context of co-infection. We investigated the cytokine response to purified protein derivative (PPD) in peripheral blood mononuclear cells from TB patients co-infected with HIV or malaria and compared it to that of malaria- and HIV-free TB patients. A total of 231 subjects were recruited for this study and classified into six groups; untreated TB-positive, TB positive subjects on TB drugs, TB- and HIV-positive, TB- and malaria-positive, latent TB and apparently healthy control subjects. Our results demonstrate maintenance of interferon (IFN)-γ production in HIV and malaria co-infected TB patients in spite of lower CD4 counts in the HIV-infected cohort. Malaria co-infection caused an increase in the production of the T helper type 2 (Th2)-associated cytokine interleukin (IL)-4 and the anti-inflammatory cytokine IL-10 in PPD-stimulated cultures. These results suggest that malaria co-infection diverts immune response against M. tuberculosis towards a Th-2/anti-inflammatory response which might have important consequences for disease progression.
Geographic extent of introgression in Sebastes mentella and its effect on genetic population structure
Authors: Saha Atal , Johansen Torild , Hedeholm Rasmus , Nielsen Einar E. , Westgaard Jon‐Ivar , Hauser Lorenz , Planque Benjamin , Cadrin Steven X. , Boje Jesper 
Published: August 2016

AbstractGenetic population structure is often used to identify management units in exploited species, but the extent of genetic differentiation may be inflated by geographic variation in the level of hybridization between species. We identify the genetic population structure of Sebastes mentella and investigate possible introgression within the genus by analyzing 13 microsatellites in 2,562 redfish specimens sampled throughout the North Atlantic. The data support an historical divergence between the “shallow” and “deep” groups, beyond the Irminger Sea where they were described previously. A third group, “slope,” has an extended distribution on the East Greenland Shelf, in addition to earlier findings on the Icelandic slope. Furthermore, S. mentella from the Northeast Arctic and Northwest Atlantic waters are genetically different populations. In both areas, interspecific introgression may influence allele frequency differences among populations. Evidence of introgression was found for almost all the identified Sebastes gene pools, but to a much lower extent than suggested earlier. Greenland waters appear to be a sympatric zone for many of the genetically independent Sebastes groups. This study illustrates that the identified groups maintain their genetic integrity in this region despite introgression.
The economics of land use reveals a selection bias in tree species distribution models
Authors: Ay Jean‐Sauveur , Guillemot Joannès , Martin‐StPaul Nicolas , Doyen Luc , Leadley Paul 
Published: August 2016

AbstractAimsIn human‐dominated ecosystems, the presence of a given species is the result of both the ecological suitability of the site and human impacts such as land‐use choices. The influence of land‐use choices on the predictions of species distribution models (SDMs) has, however, been often neglected. Here, we provide a theoretical analysis of the land‐use selection bias affecting classical SDMs in the case of either presence‐only or presence–absence datasets. Land‐use selection bias in the predictions of SDMs is then quantified for four widespread European tree species.LocationContinental France.MethodsWe describe a bivariate selection model (BSM) that estimates simultaneously the economics of land‐use choices and species responses to bioclimatic variables. The land‐use equation, based on an econometric model of landowner choices, is joined to an equation of species responses to bioclimatic variables.ResultsWe found a significant land‐use selection bias in all the species studied. The sign and the magnitude of the bias varied among species and were strongly related to the type of dataset used in the SDM calibration (presence‐only or presence–absence). In addition, the BSM estimates the spatial covariance between the probability of presence and the presence of compatible land use. We found that, depending on the species, sites with high ecological suitability could present a high probability of compatible land use (positive covariance) or a low probability (negative covariance).Main conclusionWe showed that the use of classical SDMs in human‐dominated areas can lead to strong miss‐estimations of actual species distributions and could therefore prevents sound projections of the effects of climate change. The proposed BSM represents a crucial step to account for the economic forces shaping species distribution in anthropized areas and paves the way for a direct assessment of trade‐offs and opportunities that may arise in a context of global change.
Depression and hospital admission in older patients with head and neck cancer: analysis of a national healthcare database
Authors: Laurence Brian , Mould‐Millman Nee‐Kofi , Nero Kenneth E. , Salter Reginald O. , Sagoo Paramjeet K. 
Published: August 2016

ObjectivesThe aim the study was to determine whether the presence of depression was associated with an increased likelihood of hospital admission among adult patients 50 years and over diagnosed with head and neck cancer (HNC) visiting emergency departments (EDs) in the United States.BackgroundHead and neck cancer is associated with high morbidity and mortality. In patients with cancer, depression is predictive of increased mortality and the effect remains after adjusting for comorbidities. Patients with cancer who are depressed are less likely to participate in treatment decisions and to seek social support which can lead to worsening overall health outcomes among patients with HNC.Materials and MethodsWe performed secondary analysis of data from the Nationwide Emergency Department Sample (NEDS) in the United States using multivariable Poisson regression to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs). We included adults aged 50 years and older, diagnosed with HNC using International Classification of Diseases, 9th revision (ICD‐9‐CM) codes. We controlled for demographic, clinical and hospital characteristics in the multivariable models.ResultsIn the final multivariable model for adults 50 years and over, male HNC patients with depression were 28% (CI = 21–36%) more likely to be admitted following an ED visit and female HNC patients with depression were 31% (CI = 20–42%) more likely to be admitted. In stratified analysis, the association was strongest for males with specific HNC of the oral cavity who were 56% (CI = 25–94%) more likely to be admitted.ConclusionDepression is associated with hospital admission among adults aged 50 and over with HNC.
Factors related to the decision‐making for moving the older adults into long‐term care facilities in Taiwan
Authors: Hsieh Yen‐Ping , Huang Ying‐Chia , Lan Shou‐Jen , Ho Ching‐Sung 
Published: August 2016

AimTo investigate the relationships between demographic characteristics of the elderly, type of long‐term care (LTC) facilities, and the reasons for moving into LTC facilities.MethodsResearch participants included people aged over 65 years, living in LTC facilities. A total of 1280 questionnaires were distributed to 111 LTC facilities in Taiwan; 480 questionnaires were retrieved, and 232 were included in the valid sample. The study used a non‐linear canonical correlation analysis, which assesses the relationships among similar sets of categorical variables.ResultsThe results showed that the older adults in quadrant I were characterized by being involved in the decision‐making regarding the choice of LTC facilities and received economic support from their children. The older adults in quadrant II mainly lived in LTC facilities to receive medical care, whereas those in quadrant III typically included individuals with low income, who did not choose to live in LTC facilities. Furthermore, those in quadrant IV had positive cognitions associated with LTC facilities.ConclusionsWe believe that the results of the present study will facilitate policy‐making in the field of LTC, provide reference to the practitioners and the older adults, and identify the types of decisions older adults make when moving into LTC facilities, thus assisting older adults to improve their strategies regarding staying in LTC facilities. Geriatr Gerontol Int 2017; 17: 1319–1327.
Optimal frequency/time combination of whole‐body vibration training for improving muscle size and strength of people with age‐related muscle loss (sarcopenia): A randomized controlled trial
Authors: Wei Ning , Pang Marco YC , Ng Shamay SM , Ng Gabriel YF 
Published: August 2016

AbstractAimTo determine the optimal combination of frequency and exposure time of a whole‐body vibration (WBV) training program for improving muscle performance of older people with age‐related muscle loss.MethodsA total of 80 community‐dwelling older adults with age‐related muscle loss were randomly divided into four equal groups, namely, low‐frequency long duration (20 Hz × 720 s), medium‐frequency medium duration (40 Hz × 360 s), high‐frequency short duration (60 Hz × 240 s) and control (no training) for 12‐week WBV training and 12‐week follow up. Assessments were carried out at baseline, mid‐intervention, post‐intervention, mid‐follow up, follow up for the cross‐sectional area of the vastus medialis, isometric knee extension strength at 90°, and isokinetic knee extension at 60°/s and 180°/s.ResultsThere was a significant time × group interaction effect in isokinetic knee extension at 180°/s. Significant time effects were found in all muscle strength outcome variables. Group differences in percentage change from baseline were significant between medium‐frequency medium duration and control on isokinetic knee extension at 180°/s and 60°/s. No changes were found in the cross‐sectional area of the vastus medialis.ConclusionsWith the total number of vibrations controlled, the combination of 40 Hz and 360 s of WBV exercise had the best outcome among all other combinations tested. The improvements in knee extension performance can be maintained for 12 weeks after cessation of WBV training. Geriatr Gerontol Int 2017; 17: 1412–1420.