bluuebunny/crossref_metadata_2025_split huggingface dataset:
Orexin‐mediated restoration of hippocampal synaptic potentiation in mice with established cocaine‐conditioned place preference
Authors: Lu Guan‐Ling , Lee Ming Tatt , Chiou Lih‐Chu 
Published: October 2018

AbstractOrexins (also called hypocretins) are implicated in reward and addiction, but little is known about their role(s) in the association between hippocampal synaptic plasticity and drug preference. Previously, we found that exogenous orexin via OX1 and OX2 receptors can impair low frequency stimulation‐induced depotentiation, i.e. restoring potentiation of excitatory synaptic transmission (re‐potentiation) in mouse hippocampal slices. Here, we found this re‐potentiation in hippocampal slices from mice that had acquired conditioned place preference (CPP) to cocaine. Both 10 and 20 mg/kg of cocaine induced similar magnitudes of CPP in mice and re‐potentiation in their hippocampal slices, but differed in their susceptibility to TCS1102, a dual (OX1 and OX2) orexin receptor antagonist. TCS1102 significantly attenuated CPP and hippocampal re‐potentiation induced by cocaine at 10 mg/kg but not at 20 mg/kg. Nonetheless, SCH23390, an antagonist of dopamine D1‐like receptors (D1‐likeRs), inhibited the effects induced by both doses of cocaine. SKF38393, a D1‐likeR‐selective agonist, also induced hippocampal re‐potentiation in vitro. Interestingly, this effect was attenuated by TCS1102. Conversely, SCH23390 prevented orexin A‐induced hippocampal re‐potentiation. These results suggest that endogenous orexins are released in mice during cocaine‐CPP acquisition, which sustains potentiated hippocampal transmission via OX1/OX2 receptors and may contribute to the addiction memory of cocaine. This effect of endogenous orexins, however, may be substituted by dopamine that may dominate hippocampal re‐potentiation and CPP via D1‐likeRs when the reinforcing effect of cocaine is high.
Cytisine versus varenicline for smoking cessation for Māori (the indigenous people of New Zealand) and their extended family: protocol for a randomized non‐inferiority trial
Authors: Walker Natalie , Smith Barry , Barnes Joanne , Verbiest Marjolein , Kurdziel Tomasz , Parag Varsha , Pokhrel Subhash , Bullen Chris 
Published: October 2018

AbstractBackground and aimsCytisine, a nicotinic acetylcholine receptor partial agonist (like varenicline) found in some plants, is a low‐cost, effective smoking cessation medication that may appeal to Māori [the indigenous people of New Zealand (NZ)]. The RAUORA trial aims to determine the effectiveness, safety and cost‐effectiveness of cytisine (Tabex®) versus varenicline (Champix®) for smoking cessation in Māori and thewhānau(extended family) of Māori.DesignPragmatic, community‐based, open‐label randomized non‐inferiority trial.SettingLakes District Health Board region, NZ.ParticipantsDaily smokers (n = 2140) who self‐identify as Māori orwhānauof Māori, and are: aged ≥ 18 years, motivated to quit smoking in the next 2 weeks, eligible for subsidized varenicline, able to provide verbal consent and have daily access to a mobile phone/internet. Recruitment uses multi‐media advertising.Intervention and comparatorParticipants are randomized (1 : 1 ratio) to receive a prescription for 12 weeks of cytisine tablets [following the manufacturer's dosing regimen for 25 days, then one 1.5‐mg tablet every 6 hours (two per day) until 12 weeks] or varenicline tablets (following the manufacturer's dosing regimen). Both groups receive brief stop‐smoking advice from the prescribing doctor and withdrawal‐orientated behavioural support via community‐based stop‐smoking counselling services (frequency, duration and mode of delivery tailored for participants) or a research assistant (six weekly 10–15‐minute calls). Participants are advised to reduce their smoking over the first 4 days of treatment, with day 5 as their designated quit‐date.MeasurementsThe primary outcome is carbon monoxide‐verified continuous abstinence at 6 months post‐quit date. Secondary outcomes at 1, 3, 6 and 12 months post‐quit date include: self‐reported continuous abstinence, 7‐day point prevalence abstinence, cigarettes per day, time to (re)lapse, adverse events, treatment adherence/compliance, treatment acceptability, nicotine withdrawal/urge to smoke and health‐care utilization/health‐related quality of life.CommentsThis trial compares cytisine and varenicline when used by the indigenous people of NZ and their extended family for smoking cessation.
Does the nicotine metabolite ratio moderate smoking cessation treatment outcomes in real‐world settings? A prospective study
Authors: Shahab Lion , Bauld Linda , McNeill Ann , Tyndale Rachel F. 
Published: October 2018

AbstractBackground and aimsIn smoking treatment trials comparing varenicline with transdermal nicotine replacement therapy (NRT), stratified by nicotine metabolite (3‐hydroxycotinine/cotinine) ratio (NMR), the relative benefit of varenicline is greater among normal rather than slow metabolizers. This study tested if the relative effectiveness of varenicline and NRT is associated with NMR status in a natural treatment setting. A secondary aim was to test if this relationship is moderated by behavioural support.DesignProspective observational multi‐centre study with 4‐week and 52‐week follow‐up.SettingNine English Stop Smoking Services (SSS).ParticipantsData came from 1556 smokers (aged ≥ 16 years) attending SSS between March 2012 and March 2013.InterventionsParticipants received pharmacotherapy together with behavioural support.MeasurementsThe primary outcome was carbon monoxide‐verified continuous abstinence at both follow‐up times. Main explanatory variables were (1) NMR status [slow (NMR < 0.31, n = 451) versus normal (NMR ≥ 0.31, n = 1105) metabolizers]; (2) pharmacotherapy (varenicline versus NRT) and (3) behavioural support (individual versus group‐based treatment). Analyses adjusted for baseline socio‐demographic, SSS, mental/physical health and smoking characteristics.FindingsOf participants, 44.2% [95% confidence interval (CI) = 41.7–46.6%] and 8.0% (95% CI = 6.8–9.5%) were continuously abstinent at 4 and 52 weeks. Varenicline was more effective than NRT at 4 weeks (P < 0.001) but only marginally so at 52 weeks (P = 0.061). There was no or inclusive evidence that NMR status moderated relative efficacy of varenicline and NRT at 4‐ [P = 0.60, Bayes factor (BF) = 0.25] or 52‐week follow‐ups (P = 0.74, BF = 0.73). However, this relationship was moderated by behavioural support (p = 0.012): the relative benefit of varenicline over NRT at 52‐week follow‐up was greater in slow, not normal, metabolizers receiving group rather than individual support (P = 0.012).ConclusionsIn a real‐world setting, the nicotine metabolite ratio status of treatment‐seeking smokers does not appear to contribute substantially to the differential effectiveness of varenicline and nicotine replacement therapy in Stop Smoking Services, when both pharmacotherapy and behavioural support are self‐selected.
Iatrogenic subcutaneous facial emphysema secondary to a Class V dental restoration: a case report
Authors: Chien PY‐H 
Published: October 2018

AbstractSubcutaneous facial emphysema (SFE) following routine dental operative procedure is an uncommon but potentially life‐threatening complication. The present case details a Class V restoration where air was introduced into the fascial tissue planes via the gingival sulcus from the use of an air‐driven dental handpiece. Although the SFE is usually self‐limiting within 3–10 days, such instances should be regarded as a medical emergency as in severe cases, the air may spread to the neck, mediastinum and thorax to result in cervicofacial emphysema with potential pneumomediastinum and pneumothorax.
A frameshift variant in the EDA gene in Dachshunds with X‐linked hypohidrotic ectodermal dysplasia
Authors: Hadji Rasouliha S. , Bauer A. , Dettwiler M. , Welle M. M. , Leeb T. 
Published: October 2018

SummaryX‐linked hypohidrotic ectodermal dysplasia (XLHED) is a genetic disease characterized by hypoplasia or absence of hair, teeth and sweat glands. The EDA gene, located on the X chromosome, encodes the type II transmembrane protein ectodysplasin A. Variants in the EDA gene can lead to XLHED in humans, mice, cattle and dogs. In the present study, we investigated a litter of Dachshund puppies, of which four male puppies showed clinical signs of XLHED. We performed a candidate gene analysis in one affected puppy and several non‐affected relatives. This analysis revealed a single base‐pair deletion in the coding sequence of the EDA gene in the affected puppy (NM_001014770.2:c.842delT). The deletion is predicted to cause a frameshift, NP_001014770.1:p.(Leu281HisfsTer22), leading to a premature stop codon which truncates more than one quarter of the EDA protein. Sanger sequencing results confirmed that this variant was inherited from the dam. Based on knowledge about the functional impact of EDA variants in dogs and other species, c.842delT is a convincing candidate causative variant for the observed XLHED in the male puppies.
When does curatively treated colorectal cancer recur? An Australian perspective
Authors: Reece Mifanwy M. , Chapuis Pierre H. , Keshava Anil , Stewart Peter , Suen Michael , Rickard Matthew J. F. X. 
Published: October 2018

BackgroundWhile most colorectal cancer (CRC) recurrences reportedly occur within 3 years following curative treatment, many studies are limited by short‐term follow‐up. This study examines the time to recurrence of CRC in a large Australian cohort with a long follow‐up period and assesses whether time to recurrence has changed over time.MethodsA comprehensive prospective database of patients undergoing resection for CRC is maintained at Concord Hospital, Sydney. Demographic and time to recurrence data were extracted for patients who developed a recurrence following potentially curative resection for colon cancer from 1995 to 2010 and rectal cancer from 1971 to 2010. Non‐deceased patients had a minimum of 5 years follow‐up.ResultsBetween 1995 and 2010, 2575 patients with CRC underwent surgery. After exclusions, 386 had recurrence following potentially curative resection, ranging from 1 to 172.5 months (median 20.3) after treatment. Within 1 year, 27.5% recurred, 57.5% by 2 years, 74.6% by 3 years, 85.5% by 4 years and 89.6% by 5 years. There was no difference in time to recurrence between colon and rectal cancers (P = 0.674). Among patients having a potentially curative resection for rectal cancer between 1971 and 2010, 386 recurred. There was no difference in time to recurrence by decade (P = 0.863).ConclusionThe majority of recurrences occurred within 3 years of curative treatment. Had surveillance been limited to 5 years, detection of more than 10% of recurrences would have been delayed. Time to recurrence for rectal cancer has not changed in over 40 years, despite treatment advances.
Snus users had high levels of nicotine, cotinine and 3‐hydroxycotinine in their breastmilk, and the clearance was slower than in smoking mothers
Authors: Nordenstam Felicia , Lundell Bo , Edstedt Bonamy Anna‐Karin , Raaschou Pauline , Wickström Ronny 
Published: October 2018

AbstractAimUsing snus, an oral moist tobacco, has increased among pregnant women in Sweden, the only European Union country where sales are legal. This study evaluated whether snus generated similar concentrations of nicotine and its metabolites in breastmilk to cigarette smoking.MethodsWe analysed 49 breastmilk samples from 33 nursing mother – 13 snus users, six cigarette smokers and 14 controls – for concentrations of nicotine, cotinine and 3‐hydroxycotinine. The mothers were recruited at antenatal clinics in Sweden from 2007 to 2012.ResultsThe median nicotine concentration in breastmilk of the snus users was 38.7 ng/mL (0–137) versus 24.0 ng/mL (0–56) in smokers, with median cotinine levels of 327.6 ng/mL (37–958) versus 164.4 ng/mL and median 3‐hydroxycotinine levels of 202.7 ng/mL (28–452) versus 112.4 (0–231), respectively. Nicotine was still detected in the breastmilk of eight of the 13 snus users after abstaining from tobacco for a median duration of 11 hours (0.6–12.5), while the breastmilk of the smokers was nicotine‐free after four hours’ abstinence.ConclusionSnus users had high levels of nicotine and metabolites in their breastmilk and nicotine was found even after 12.5 hours of abstinence.
Bitterless guaifenesin prodrugs—design, synthesis, characterization, in vitro kinetics, and bitterness studies
Authors: Thawabteh Amin , Lelario Filomena , Scrano Laura , Bufo Sabino A. , Nowak Stefanie , Behrens Maik , Di Pizio Antonella , Niv Masha Y. , Karaman Rafik 
Published: October 2018

AbstractA respected number of drugs suffer from bitter taste which results in patient incompliance. With the aim of solving the bitterness of guaifenesin, dimethyl maleate, maleate, glutarate, succinate, and dimethyl succinate prodrugs were designed and synthesized. Molecular orbital methods were utilized for the design of the ester prodrugs. The density functional theory (DFT) calculations revealed that the hydrolysis efficiency of the synthesized prodrugs is significantly sensitive to the pattern of substitution on C=C bond and distance between the nucleophile and the electrophile. The hydrolysis of the prodrugs was largely affected by the pH of the medium. The experimental t1/2 for the hydrolysis of guaifenesin dimaleate ester prodrugs in 1N HCl was the least and for guaifenesin dimethyl succinate was the highest. Functional heterologous expression of TAS2R14, a broadly tuned bitter taste receptor responding to guaifenesin, and experiments using these prodrugs revealed that, while some of the prodrugs still activated the receptor similarly or even stronger than the parent substance, succinate derivatization resulted in the complete loss of receptor responses. The predicted binding modes of guaifenesin and its prodrugs to the TAS2R14 homology model suggest that the decreased activity of the succinate derivatives may be caused by a clash with Phe247.
Statistical Learning Is Not Age‐Invariant During Childhood: Performance Improves With Age Across Modality
Authors: Shufaniya Amir , Arnon Inbal 
Published: October 2018

AbstractHumans are capable of extracting recurring patterns from their environment via statistical learning (SL), an ability thought to play an important role in language learning and learning more generally. While much work has examined statistical learning in infants and adults, less work has looked at the developmental trajectory of SL during childhood to see whether it is fully developed in infancy or improves with age, like many other cognitive abilities. A recent study showed modality‐based differences in the effect of age during childhood: While visual SL improved with age, auditory SL did not. This finding was taken as evidence for modality‐based differences in SL. However, since that study used auditory linguistic stimuli (syllables), the differential effect of age may have been driven by stimulus type (linguistic vs. non‐linguistic) rather than modality. Here, we ask whether age will affect performance similarly in the two modalities when non‐linguistic auditory stimuli are used (familiar sounds instead of syllables). We conduct a large‐scale study of children's performance on visual and non‐linguistic auditory SL during childhood (ages 5–12 years). The results show a similar effect of age in both modalities: Unlike previous findings, both visual and non‐linguistic auditory SL improved with age. These findings highlight the stimuli‐sensitive nature of SL and suggest that modality‐based differences may be stimuli‐dependent, and that age‐invariance may be limited to linguistic stimuli.
Delayed calcineurin inhibitor introduction and renal outcomes in liver transplant recipients receiving basiliximab induction
Authors: Lange Nicholas W. , Salerno David M. , Sammons Chelsea M. , Jesudian Arun B. , Verna Elizabeth C. , Brown Robert S. 
Published: October 2018

AbstractBackgroundTo investigate the impact of delayed calcineurin inhibitor (CNI) initiation in liver transplant recipients (LTR) with peri‐operative renal insufficiency receiving basiliximab induction, we compared renal outcomes of LTR stratified by the degree of achieved post‐operative renal recovery (RR) prior to CNI initiation.MethodsAll adult LTR transplanted between 01/2007 and 12/2015 who received basiliximab were included. Patients who received multi‐organ transplantations, were repeat transplant recipients, or expired prior to post‐operative day (POD) 90 were excluded. The primary outcome of our retrospective analysis was renal function at POD 90.ResultsA total of 210 patients were included in our final analysis. Most patients were Caucasian males undergoing liver transplantation for liver disease secondary to hepatitis C virus. Baseline characteristics were similar among the evaluable population. Estimated GFR was significantly higher among patients with the greatest degree of post‐operative renal recovery at POD 90; however, this difference did not persist at POD 180. There was no significant difference in incidence or severity of biopsy‐proven acute rejection (BPAR) at any measured time point.ConclusionsDelayed CNI initiation following liver transplantation in patients with post‐operative renal insufficiency who receive basiliximab induction does not adversely affect the incidence of BPAR or long‐term renal outcomes.
Neural correlates of facial emotion processing in infancy
Authors: Xie Wanze , McCormick Sarah A. , Westerlund Alissa , Bowman Lindsay C. , Nelson Charles A. 
Published: October 2018

AbstractIn the present study we examined the neural correlates of facial emotion processing in the first year of life using ERP measures and cortical source analysis. EEG data were collected cross‐sectionally from 5‐ (N = 49), 7‐ (N = 50), and 12‐month‐old (N = 51) infants while they were viewing images of angry, fearful, and happy faces. The N290 component was found to be larger in amplitude in response to fearful and happy than angry faces in all posterior clusters and showed largest response to fear than the other two emotions only over the right occipital area. The P400 and Nc components were found to be larger in amplitude in response to angry than happy and fearful faces over central and frontal scalp. Cortical source analysis of the N290 component revealed greater cortical activation in the right fusiform face area in response to fearful faces. This effect started to emerge at 5 months and became well established at 7 months, but it disappeared at 12 months. The P400 and Nc components were primarily localized to the PCC/Precuneus where heightened responses to angry faces were observed. The current results suggest the detection of a fearful face in infants’ brain can happen shortly (~200–290 ms) after the stimulus onset, and this process may rely on the face network and develop substantially between 5 to 7 months of age. The current findings also suggest the differential processing of angry faces occurred later in the P400/Nc time window, which recruits the PCC/Precuneus and is associated with the allocation of infants’ attention.
Glucose metabolism dysregulation at the onset of mental illness is not limited to first episode psychosis: A systematic review and meta‐analysis
Authors: Kucukgoncu Suat , Kosir Urska , Zhou Elton , Sullivan Erin , Srihari Vinod H. , Tek Cenk 
Published: October 2018

AimTo compare the differences of glucose metabolism outcomes between treatment‐naïve, patients with first episode psychosis (FEP) and mood disorders.MethodsWe conducted a systematic review and meta‐analysis of glucose intolerance in treatment‐naïve, first episode patients with severe mental illnesses (SMIs).ResultsWe identified 31 eligible studies. Compared to healthy controls, FEP group have higher insulin and insulin resistance levels, and both groups have higher glucose tolerance test results. No significant differences were found in glucose metabolism outcomes between FEP and mood disorder groups.ConclusionsOur results highlight impaired glucose metabolism at the onset of SMIs, suggesting both patients with psychosis and mood disorders are high‐risk groups for diabetes development.
Cognitive neuroscience can support public health approaches to minimise the harm of ‘losses disguised as wins’ in multiline slot machines
Authors: Myles Dan , Carter Adrian , Yücel Murat 
Published: October 2018

AbstractVideo slot machines are associated with both accelerated transition into problematic forms of gambling, as well as psychosocial harm above and beyond other forms of gambling. A growing body of evidence is uncovering how key design features of multiline slot machines produce an inflated experience of reward, despite the fact that these features offer no overall financial benefit to the player. A pernicious example of this are ‘losses disguised as wins’ (LDWs), which occur when simultaneous bets placed on multiple lines result in a winning combination that returns an amount greater than zero, but less the total wager. These events are usually accompanied by the same celebratory sounds and animations that accompany true wins. We argue that LDWs may leverage neuropsychological phenomena that underlie reinforcement learning and contribute to extended or repetitive use and gambling‐related harm. While other characteristics of slot machine gambling have been examined by cognitive neuroscientists, this feature has not yet received attention. Neuroscientific methods can be used to assess the impact of LDWs on the human reward system, to assess the claim that these events are a reinforcing and contributing factor in the development of harmful play. Positive findings would provide further persuasive evidence in support of strategies to minimise gambling harm through the regulation of machine design.
Perceived Romantic Relationship Quality: Associations With Adolescents' Depressive Symptoms and Externalizing Behavior
Authors: Beckmeyer Jonathon J. , Coleman Marilyn , Proulx Christine M. 
Published: October 2018

ObjectiveTo understand whether 15‐year‐old adolescents' reports of positive and negative interactions in their romantic relationships are associated with their depressive symptoms and externalizing behavior.BackgroundTo ensure that relationship education programs comprehensively address adolescent romantic development, there is a need for research focused on relationship dynamics during adolescence. In particular, there is a paucity of research on the associations between romantic relationship quality and adolescent adjustment.MethodData were from adolescents in romantic relationships during the fourth wave of the NICHD Study of Early Child Care and Youth Development (N = 205). Adolescents reported the positive and negative interactions in their romantic relationships, depressive symptoms, and externalizing behavior.ResultsNegative interactions were positively associated with depressive symptoms and externalizing behavior. Positive interactions were not associated with adolescent adjustment but did moderate the associations between negative interactions and depressive symptoms. Specifically, and unexpectedly, positive interactions exacerbated the association between high (+1 SD) negative interactions and depressive symptoms.ConclusionAdolescents in romantic relationships may be at risk for depressive symptoms and externalizing behavior when they experience negative interactions with romantic partners. They do not, however, appear to benefit from positive interactions.ImplicationsA primary goal of adolescent‐specific relationship education should be to minimize negative interactions between romantic partners.