bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nalmefene is effective at reducing alcohol seeking, treating alcohol‐cocaine interactions and reducing alcohol‐induced histone deacetylases gene expression in blood
Authors: Calleja‐Conde Javier , Echeverry‐Alzate Victor , Giné Elena , Bühler Kora‐Mareen , Nadal Roser , Maldonado Rafael , Rodríguez de Fonseca Fernando , Gual Antoni , López‐Moreno Jose Antonio 
Published: May 2016

AbstractBackground and PurposeThe opioid antagonist nalmefene (selincro®) was approved for alcohol‐related disorders by the European Medicines Agency in 2013. However, there have been no studies regarding the effectiveness of nalmefene when alcohol is used in combination with cocaine.Experimental ApproachUsing operant alcohol self‐administration in Wistar rats and qRT‐PCR, we evaluated (i) the dose–response curve for s.c. and p.o. nalmefene; (ii) the effects of nalmefene with increasing concentrations of alcohol; (iii) the efficacy of nalmefene on cocaine‐potentiated alcohol responding; and (iv) the gene expression profiles of histone deacetylases (Hdac1–11) in peripheral blood in vivo and in the prefrontal cortex, heart, liver and kidney post mortem.Key ResultsS.c. (0.01, 0.05, 0.1 mg·kg−1) and p.o. (10, 20, 40 mg·kg−1) nalmefene dose‐dependently reduced alcohol‐reinforced responding by up to 50.3%. This effect of nalmefene was not dependent on alcohol concentration (10, 15, 20%). Cocaine potentiated alcohol responding by approximately 40% and nalmefene (0.05 mg·kg−1) reversed this effect of cocaine. Alcohol increased Hdac gene expression in blood and nalmefene prevented the increases in Hdacs 3, 8, 5, 7, 9, 6 and 10. In the other tissues, alcohol and nalmefene either did not alter the gene expression of Hdacs, as in the prefrontal cortex, or a tissue‐Hdac‐specific effect was observed.Conclusions and ImplicationsNalmefene might be effective as a treatment for alcohol‐dependent patients who also use cocaine. Also, the expression of Hdacs in peripheral blood might be useful as a biomarker of alcohol use and drug response.
The α7 nicotinic receptor dual allosteric agonist and positive allosteric modulator GAT107 reverses nociception in mouse models of inflammatory and neuropathic pain
Authors: Bagdas Deniz , Wilkerson Jenny L , Kulkarni Abhijit , Toma Wisam , AlSharari Shakir , Gul Zulfiye , Lichtman Aron H , Papke Roger L , Thakur Ganesh A , Damaj M Imad 
Published: May 2016

Background and PurposeOrthosteric agonists and positive allosteric modulators (PAMs) of the α7 nicotinic ACh receptor (nAChR) represent novel therapeutic approaches for pain modulation. Moreover, compounds with dual function as allosteric agonists and PAMs, known as ago‐PAMs, add further regulation of receptor function.Experimental ApproachInitial studies examined the α7 ago‐PAM, GAT107, in the formalin, complete Freund's adjuvant (CFA), LPS inflammatory pain models, the chronic constriction injury neuropathic pain model and the tail flick and hot plate acute thermal nociceptive assays. Additional studies examined the locus of action of GAT107 and immunohistochemical markers in the dorsal horn of the spinal cord in the CFA model.Key ResultsComplementary pharmacological and genetic approaches confirmed that the dose‐dependent antinociceptive effects of GAT107 were mediated through α7 nAChR. However, GAT107 was inactive in the tail flick and hot plate assays. In addition, GAT107 blocked conditioned place aversion elicited by acetic acid injection. Furthermore, intrathecal, but not intraplantar, injections of GAT107 reversed nociception in the CFA model, suggesting a spinal component of action. Immunohistochemical evaluation revealed an increase in the expression of astrocyte‐specific glial fibrillary acidic protein and phosphorylated p38MAPK within the spinal cords of mice treated with CFA, which was attenuated by intrathecal GAT107 treatment. Importantly, GAT107 did not elicit motor impairment and continued to produce antinociceptive effects after subchronic administration in both phases of the formalin test.Conclusions and ImplicationsCollectively, these results provide the first proof of principle that α7 ago‐PAMs represent an effective pharmacological strategy for treating inflammatory and neuropathic pain.
Maternal age and asthma in Latino populations
Authors: Abid Z. , Oh S. S. , Hu D. , Sen S. , Huntsman S. , Eng C. , Farber H. J. , Rodriguez‐Cintron W. , Rodriguez‐Santana J. R. , Serebrisky D. , Avila P. C. , Thyne S. M. , Kim K.‐Y. A. , Borrell L. N. , Williams L. K. , Seibold M. A. , Burchard E. G. , Kumar R. 
Published: May 2016

SummaryBackgroundYounger maternal age at birth is associated with increased risk of asthma in offspring in European descent populations, but has not been studied in Latino populations.ObjectivesWe sought to examine the relationship between maternal age at birth and prevalence of asthma in a nationwide study of Latino children.MethodsWe included 3473 Latino children aged 8–21 years (1696 subjects with physician‐diagnosed asthma and 1777 healthy controls) from five US centres and Puerto Rico recruited from July 2008 through November 2011. We used multiple logistic regression models to examine the effect of maternal age at birth on asthma in offspring overall and in analyses stratified by ethnic subgroup (Mexican American, Puerto Rican and other Latino). Secondary analyses evaluated the effects of siblings, acculturation and income on this relationship.ResultsMaternal age < 20 years was significantly associated with decreased odds of asthma in offspring, independent of other risk factors (OR = 0.73, 95% CI: 0.57–0.93). In subgroup analyses, the protective effect of younger maternal age was observed only in Mexican Americans (OR = 0.53, 95% CI: 0.36, 0.79). In Puerto Ricans, older maternal age was associated with decreased odds of asthma (OR = 0.65, 95% CI: 0.44–0.97). In further stratified models, the protective effect of younger maternal age in Mexican Americans was seen only in children without older siblings (OR = 0.44, 95% CI: 0.23–0.81).Conclusion and Clinical RelevanceIn contrast to European descent populations, younger maternal age was associated with decreased odds of asthma in offspring in Mexican American women. Asthma is common in urban minority populations but the factors underlying the varying prevalence among different Latino ethnicities in the United States is not well understood. Maternal age represents one factor that may help to explain this variability.
Long‐term Evaluation of Peri‐implant Bone Level after Reconstruction of Severely Atrophic Edentulous Maxilla via Vertical and Horizontal Guided Bone Regeneration in Combination with Sinus Augmentation: A Case Series with 1 to 15 Years of Loading
Authors: Urban Istvan A. , Monje Alberto , Lozada Jaime L. , Wang Hom‐Lay 
Published: May 2016

AbstractBackgroundTo the best of the authors' knowledge, there is very limited clinical data on the outcomes of simultaneous guided bone regeneration (GBR) for horizontal and/or vertical bone gain for the reconstruction of severely atrophic edentulous maxilla. Therefore, the purpose of the clinical series presented herein was to clinically evaluate long‐term horizontal and vertical bone gain, as well as implant survival rate after reconstruction of severely atrophic edentulous maxillary ridges.Material and MethodsSixteen patients (mean age: 64.6 ± 14.6 years of age) were consecutively treated for vertical and/or horizontal bone augmentation via GBR in combination with bilateral sinus augmentation utilizing a mixture of autologous and anorganic bovine bone. Implant survival, bone gain, intraoperative/postoperative complications and peri‐implant bone loss were calculated up to the last follow‐up exam.ResultsOverall, 122 dental implants were placed into augmented sites and have been followed from 12 to 180 months (mean: 76.5 months). Implant survival was 100% (satisfactory survival rate of 97.5%). Mean bone gain was 5.6 mm (max: 9 mm; min: 3 mm) While vertical bone gain was 5.1 ± 1.8 mm; horizontal bone gain was 7.0 ± 1.5 mm. No intraoperative/postoperative complications were noted. Mean peri‐implant bone loss values were consistent within the standards for implant success (1.4 ± 1.0 mm). At patient‐level, only one patient who had three implants presented with severe peri‐implant bone loss.ConclusionComplete reconstruction of an atrophied maxilla can be successfully achieved by means of guided bone regeneration for horizontal and/or vertical bone gain including bilateral sinus augmentation using a mixture of anorganic bovine bone and autologous bone.
Gene expression profiles in guided bone regeneration using combinations of different biomaterials: a pilot animal study
Authors: Suleimenova Dina , Hashimi Saeed M. , Li Ma , Ivanovski Saso , Mattheos Nikos 
Published: May 2016

AbstractObjectivesThe aim of this study was to investigate the gene expression profile related to guided bone regeneration (GBR) at the early healing stage while using combinations of different biomaterials.Materials and methodsCranial defects in 4 New Zealand rabbits were filled with A) biphasic calcium phosphate/experimental pericardium‐derived collagen membrane, B) Bio‐Oss®/Bio‐Gide®, C) biphasic calcium phosphate/strontium hydroxyapatite‐containing collagen membrane and D) Bio‐Oss®/strontium hydroxyapatite‐containing collagen membrane. Seven days after surgery, one animal was subjected to histological observation and histomorphometric analysis, and three animals to real‐time quantitative reverse transcription polymerase chain reaction (PCR). An RT2 Profiler PCR Array (PANZ‐026Z, QIAGEN, QIAGEN Sciences, Germantown, MD, USA) was conducted to observe the gene expression profile of groups A, C and D as compared with the control group B.ResultsThe analysis showed 9 of the 84 genes on the array to be significantly different in the three experimental groups (six genes in group D, four in group C and one in group A). Group D demonstrated the most changes in gene expression profile at day 7. Genes that were significantly down‐regulated (AHSG, EGF) or up‐regulated (CDH11, MMP13, GLI1 and MCSF) are responsible for early‐stage bone formation, bone remodeling and pre‐osteoclast development. The gene expression profile of this group correlated with the histological findings, as this group showed the higher formation of osteoid as compared with the other groups.ConclusionGene expression patterns at early‐stage healing of GBR‐treated defects appear to be related to the biomaterial used. The combination of Bio‐Oss® and strontium hydroxyapatite‐containing collagen membrane showed the most pro‐osteogenic gene regulation profile (group D), implying the stimulation of key transcriptional factors, which appeared to translate into the up‐regulation of the osteogenic process and earlier bone formation.
Granulomatous‐lymphocytic interstitial lung disease as the first manifestation of common variable immunodeficiency
Authors: Tashtoush Basheer , Memarpour Roya , Ramirez Jose , Bejarano Pablo , Mehta Jinesh 
Published: May 2016

AbstractCommon variable immunodeficiency (CVID) is one of the most common primary immunodeficiencies, which is characterized by reduced serum immunoglobulin levels and B‐lymphocyte dysfunction. There are many clinical manifestations of this disease, the most common of which are recurrent respiratory tract infections. Among the most recently recognized autoimmune manifestation of CVID is a disease described as granulomatous‐lymphocytic interstitial lung disease (GLILD), where CVID coexists with a small airway lymphoproliferative disorder, mimicking follicular bronchiolitis, or lymphocytic interstitial pneumonitis (LIP) on histology specimens. We herein describe the clinical and radiological features of GLILD in a 55‐year‐old woman where the diagnosis of CVID was actively pursued and eventually confirmed after her lung biopsy showed characteristic features of GLILD. The patient had dramatic response to treatment with IVIG and corticosteroids for 3 months followed by Mycophenolate mofetil for maintenance therapy.
Patterns of drug dependence in a Queensland (Australia) sample of Indigenous and non‐Indigenous people who inject drugs
Authors: Smirnov Andrew , Kemp Robert , Ward James , Henderson Suzanna , Williams Sidney , Dev Abhilash , Najman Jake M. 
Published: May 2016

AbstractIntroduction and AimsDespite over‐representation of Indigenous Australians in sentinel studies of injecting drug use, little is known about relevant patterns of drug use and dependence. This study compares drug dependence and possible contributing factors in Indigenous and non‐Indigenous Australians who inject drugs.Design and MethodsRespondent‐driven sampling was used in major cities and ‘peer recruitment’ in regional towns of Queensland to obtain a community sample of Indigenous (n = 282) and non‐Indigenous (n = 267) injectors. Data are cross sectional. Multinomial models were developed for each group to examine types of dependence on injected drugs (no dependence, methamphetamine‐dependent only, opioid‐dependent only, dependent on methamphetamine and opioids).ResultsAround one‐fifth of Indigenous and non‐Indigenous injectors were dependent on both methamphetamine and opioids in the previous 12 months. Psychological distress was associated with dual dependence on these drugs for Indigenous [adjusted relative risk (ARR) 4.86, 95% confidence interval (CI) 2.08–11.34] and non‐Indigenous (ARR 4.14, 95% CI 1.59–10.78) participants. Unemployment (ARR 8.98, 95% CI 2.25–35.82) and repeated (> once) incarceration as an adult (ARR 3.78, 95% CI 1.43–9.97) were associated with dual dependence for Indigenous participants only. Indigenous participants had high rates of alcohol dependence, except for those dependent on opioids only.Discussion and ConclusionsThe drug dependence patterns of Indigenous and non‐Indigenous people who inject drugs were similar, including the proportions dependent on both methamphetamine and opioids. However, for Indigenous injectors, there was a stronger association between drug dependence and contextual factors such as unemployment and incarceration. Expansion of treatment options and community‐level programs may be required. [Smirnov A, Kemp R, Ward J, Henderson S, Williams S, Dev A, Najman J M. Patterns of drug dependence in a Queensland (Australia) sample of Indigenous and non‐Indigenous people who inject drugs. Drug Alcohol Rev 2016;35:611‐619]
Death from liver disease in a cohort of injecting opioid users in a Swedish city in relation to registration for opioid substitution therapy
Authors: Jerkeman Anna , Håkansson Anders , Rylance Rebecca , Wagner Philippe , Alanko Blomé Marianne , Björkman Per 
Published: May 2016

AbstractIntroduction and AimsInjecting opioid users are at elevated risk of death. Although liver disease (especially hepatitis C) is common, its impact on mortality is low in active injectors. Because opioid substitution therapy (OST) reduces the risk of death from directly drug related causes, we hypothesised that the proportion of liver‐related deaths would increase in subjects receiving OST. We investigated liver‐related mortality in a cohort of injecting opioid users attending a needle exchange program (NEP) in a Swedish city in relation to OST exposure.Design and MethodsParticipants enrolled in the NEP between 1987 and 2011 with available national identity numbers, and registered use of opioids, were included. Linkage based on national identity numbers was performed with national registers for death, emigration and prescription of OST. Participants were categorised as non‐OST recipients until the registered date of first OST prescription, and hence as OST recipients. Hazard ratios were calculated by Cox regression for overall and liver‐related mortality in relation to OST, with OST as a time‐dependent variable.ResultsAmong 4494 NEP participants, 1488 opioid users were identified; 711/1488 had been prescribed OST. During a follow‐up period of 15 546 person‐years 368 deaths occurred. Sixteen deaths were caused by liver disease; 10 of these occurred in OST recipients. The risk of liver‐related death was significantly increased in OST receiving participants (hazard ratio 3.08, 95% confidence interval [1.09, 8.68], P = 0.03).ConclusionsLiver related mortality among opioid users was significantly elevated in OST recipients, showing the long‐term importance of chronic liver disease in this population. [Jerkeman A, Håkansson A, Rylance R, Wagner P, Alanko Blomé M, Björkman P. Death from liver disease in a cohort of injecting opioid users in a Swedish city in relation to registration for opioid substitution therapy. Drug Alcohol Rev 2017;36:424–431]
Pathophysiologische Grundlagen der Systemtherapien bei Psoriasis
Authors: Volc Sebastian , Ghoreschi Kamran 
Published: May 2016

ZusammenfassungDas Spektrum der systemischen antipsoriatischen Therapie hat sich in den letzten 15 Jahren deutlich erweitert. Während uns bis zum Ende des letzten Jahrtausends mit Methotrexat, Ciclosporin, Acitretin und Fumarsäureester lediglich vier orale Systemtherapien zur Verfügung standen, verfügen wir heute zusätzlich über sieben verschiedene Biologika und ein neues orales Antipsoriatikum. Hinzu kommen die ersten verfügbaren Biosimilars. Sechs weitere Biologika mit neuen Zielstrukturen und mindestens vier weitere Biosimilars befinden sich aktuell in der Phase‐III‐Prüfung. Zu verdanken haben wir diese Entwicklung den neuen Erkenntnissen über die Pathogenese der Psoriasis, bei der nicht nur der Tumornekrosefaktor (TNF), sondern insbesondere die Th17‐Immunantwort mit ihren Zytokinen Interleukin 23 und 17 von zentraler Bedeutung sind. Hierauf basieren sowohl die neue Generation der Biologika als auch die neue Generation von immunmodulatorischen small molecules. Phosphodiesterase‐4‐Inhibitoren, Dimethylfumarat‐Präparate und Januskinase‐Inhibitoren interagieren alle mit der Th17‐Immunantwort. Einige dieser Substanzen befinden sich bereits in fortgeschrittener klinischer Entwicklung und wirken auch bei der Psoriasisarthritis. Somit gehören sowohl die Psoriasis als auch die Psoriasisarthritis heute zu den am besten kontrollierbaren entzündlichen Autoimmunkrankheiten. Die Dermatologie entwickelt sich zunehmend zu einer Domäne moderner zielgerichteter Immuntherapien.
Intravenous immunoglobulin in paediatric neurology: safety, adherence to guidelines, and long‐term outcome
Authors: Nosadini Margherita , Mohammad Shekeeb S , Suppiej Agnese , Sartori Stefano , Dale Russell C ,   IVIG in Neurology Study Group
Published: May 2016

AimIntravenous immunoglobulin (IVIG) is an expensive therapy used in immunodeficiency and autoimmune disorders. Increasing demands and consequent shortages result in a need for usage to conform to guidelines.MethodWe retrospectively evaluated IVIG use for neuroimmunological indications and adherence to existing guidelines in a major Australian paediatric hospital between 2000 and 2014.ResultsOne‐hundred and ninety‐six children (96 male, 100 female; mean age at disease onset 6y 5mo [range 3mo–15y 10mo], mean age at first IVIG dose 7y 2mo [range 3mo–16y 5mo]) received IVIG for neuroimmunological indications during the study period (28.1% had Guillain–Barré syndrome), representing 15.5% of all hospital indications. In total, 1669 IVIG courses were administered (total 57 221g, median 78g/patient, range 12–5748g). The highest median numbers of courses were in chronic inflammatory demyelinating polyneuropathies, opsoclonus‐myoclonus ataxia syndrome, suspected immune‐mediated epilepsies, and Rasmussen's encephalitis. Adverse reactions occurred in 25.5% of patients, but these were mostly minor. Outcome at follow‐up was best in anti‐N‐methyl‐d‐aspartate receptor (anti‐NMDAR) encephalitis, Guillain–Barré syndrome, and myasthenia gravis, and worst in Rasmussen's encephalitis and epilepsies. The total cost of IVIG was US$2 595 907 (median $3538/patient, range $544–260 766). Of patients receiving IVIG, 45.4% to 57.1% were given the therapy for ‘weak’ indications or indications ‘not listed’ in international guidelines. Some entities commonly treated with IVIG in current practice, such as anti‐NMDAR encephalitis and transverse myelitis, are not listed in most guidelines.InterpretationOur study demonstrates that IVIG is generally well tolerated but expensive, and discloses discrepancies between guidelines and clinical practice in paediatric neurology, suggesting both the need for greater adherence to current recommendations, and for recommendations to be updated to accommodate emerging indications.
Impaired Left and Right Ventricular Systolic and Diastolic Function in Response to Exercise in Patients with Diastolic Dysfunction
Authors: Narayanan Meena , Bamba Alyssa , Liu Shuang , Naqvi Tasneem Z. 
Published: May 2016

BackgroundDiastolic dysfunction (DD) is associated with exercise intolerance. To evaluate mechanisms of exercise intolerance in patients with DD, we performed bicycle stress echocardiography.Method and ResultsDoppler measurements were performed at baseline, during exercise and recovery in 26 patients (58 ± 11 years) with DD and normal left ventricular ejection fraction and 6 normal controls (53 ± 5 years). Compared to controls, patients achieved similar target heart rates but lower METs (5.5 ± 2 vs. 9.8 ± 3, P < 0.01) and a higher peak pulmonary artery pressure (PAP) at peak exercise (50 ± 13 vs. 32 ± 7 mmHg, P < 0.01) despite similar PAP at rest and similar mean blood pressure at peak exercise (110.4 ± 18.0 vs. 106.9 ± 11.4 mmHg, P = NS). In patients versus controls, mitral E/E' was similar at baseline (10 ± 3 vs. 8 ± 1.3, P = NS) but higher at recovery (11 ± 2 vs. 7 ± 2, P < 0.05), % mitral filling time was shorter at baseline, onset, and peak exercise, whereas % LV and RV ejection time was similar to controls throughout exercise. Compared to controls, lateral mitral annular S' (11.8 ± 2.5 cm/sec vs. 14.9 ± 1.9 cm/sec, P < 0.02) and tricuspid annular S' (14.8 ± 4.1 cm/sec vs. 19.4 ± 4.0 cm/sec, P < 0.05) were lower at peak exercise in patients.ConclusionDiastolic filling time is reduced at rest and stress while LV ejection time increases normally during exercise in DD. There is a reduced systolic reserve in LV and RV during exercise in DD. These mechanisms contribute to exercise intolerance and elevation of left atrial and PAP in patients with DD.
Density‐mediated indirect interactions alter host foraging behaviour of parasitoids without altering foraging efficiency
Authors: DE RIJK MARJOLEIN , ZHANG XI , VAN DER LOO JUULTJE A. H. , ENGEL BAS , DICKE MARCEL , POELMAN ERIK H. 
Published: May 2016

1. Foraging decisions of parasitoids are influenced by host density via density‐mediated indirect interactions. However, in the parasitoid's environment, non‐suitable herbivores are also present. These non‐hosts also occur in different densities, which can affect a parasitoid's foraging behaviour.2. The influence of non‐host densities can be expressed during the first phase of the foraging process, when parasitoids use plant volatiles to locate plants infested by their host. They may also play a role during the second phase, when parasitoids use infochemicals from the host and plant to locate, recognise and accept the host.3. By using laboratory and field setups, it was studied whether the density of non‐host herbivores influences these two phases of the foraging behaviour of the parasitoid Cotesia glomerata as well as the parasitoid's efficiency to find its host, Pieris brassicae caterpillars.4. The findings show that a high non‐host density, regardless of the species used, negatively affected parasitoid preference for host‐infested plants, but that the behaviour on the plant and the total host‐finding efficiency of the parasitoids were not influenced by non‐host density.5. These results are discussed in the context of density‐mediated indirect interactions.