bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Acamprosate on Attentional Set‐Shifting and Cellular Function in the Prefrontal Cortex of Chronic Alcohol‐Exposed Mice
Authors: Hu Wei , Morris Brett , Carrasco Angelique , Kroener Sven 
Published: April 2015

BackgroundThe medial prefrontal cortex (mPFC) inhibits impulsive and compulsive behaviors that characterize drug abuse and dependence. Acamprosate is the leading medication approved for the maintenance of abstinence, shown to reduce craving and relapse in animal models and human alcoholics. Whether acamprosate can modulate executive functions that are impaired by chronic ethanol (EtOH) exposure is unknown. Here we explored the effects of acamprosate on an attentional set‐shifting task and tested whether these behavioral effects are correlated with modulation of glutamatergic synaptic transmission and intrinsic excitability of mPFC neurons.MethodsWe induced alcohol dependence in mice via chronic intermittent EtOH (CIE) exposure in vapor chambers and measured changes in alcohol consumption in a limited access 2‐bottle choice paradigm. Impairments of executive function were assessed in an attentional set‐shifting task. Acamprosate was applied subchronically for 2 days during withdrawal before the final behavioral test. Alcohol‐induced changes in cellular function of layer 5/6 pyramidal neurons, and the potential modulation of these changes by acamprosate, were measured using patch clamp recordings in brain slices.ResultsChronic EtOH exposure impaired cognitive flexibility in the attentional set‐shifting task. Acamprosate improved overall performance and reduced perseveration. Recordings of mPFC neurons showed that chronic EtOH exposure increased use‐dependent presynaptic transmitter release and enhanced postsynaptic N‐methyl‐d‐aspartate receptor function. Moreover, CIE treatment lowered input resistance, and decreased the threshold and the after hyperpolarization of action potentials, suggesting chronic EtOH exposure also impacted membrane excitability of mPFC neurons. However, acamprosate treatment did not reverse these EtOH‐induced changes cellular function.ConclusionsAcamprosate improved attentional control of EtOH exposed animals, but did not alter the concurrent changes in synaptic transmission or membrane excitability of mPFC neurons, indicating that these changes are not the pharmacological targets of acamprosate in the recovery of mPFC functions affected by chronic EtOH exposure.
Mechanoreceptors in the Anterior Horn of the Equine Medial Meniscus: an Immunohistochemical Approach
Authors: Nemery E. , Gabriel A. , Grulke S. , Piret J. , Toppets V. , Antoine N. 
Published: April 2015

SummaryLameness due to stifle and especially meniscal lesions is frequent in equine species. In humans, mechanoreceptors involved in proprioceptive function are well studied. Given the high incidence of meniscal injuries in horses, and the lack of information concerning them in equine menisci, our objective was to study these corpuscles in six healthy anterior horns of the equine medial meniscus, which is the most common localisation reported for equine meniscal injuries. Immunohistochemical stainings were performed using antibodies against high molecular weight neurofilaments and glial fibrillary acidic proteins. From a purely fundamental point of view, our work highlights for the first time the presence of Ruffini, Pacini and Golgi corpuscles in equine meniscus. They were found, isolated or in clusters and always located at the vicinity of blood vessels, at the level of the anterior horn of the equine medial meniscus. This morphological approach could serve as a basis for clinical studies, to evaluate the impact of these corpuscles on the poor sportive prognosis in equine meniscal tears.
A New Correction for Multiple Testing in Gene–Gene Interaction Studies
Authors: Babron Marie‐Claude , Etcheto Adrien , Dizier Marie‐Helene 
Published: April 2015

SummaryA major problem in gene–gene interaction studies in large marker panels is how to correct for multiple testing while accounting for the dependence between marker pairs due to the presence of linkage disequilibrium. The “gold standard” approach is to perform permutations of case/control labels. However, this is often not feasible in practice, due to computational demands. Here, we propose a correction based on the effective number of independent tests of interaction between marker pairs. This number depends on the effective number of independent single‐marker tests. We tested its validity using simulated samples, as well as that of another correction of marker pair tests. We showed that our approach was valid while the other correction strongly underestimated the effective number of independent tests. Our method provides estimates of the effective number of independent tests close to those reported in the literature for a Genome‐Wide Interaction Study on a 550K chip. Our correction method is quick and simple, and can be applied whatever the marker panel and the underlying linkage disequilibrium pattern.
Joint Effect of Unlinked Genotypes: Application to Type 2 Diabetes in the EPIC‐Potsdam Case‐Cohort Study
Authors: Knüppel Sven , Meidtner Karina , Arregui Maria , Holzhütter Hermann‐Georg , Boeing Heiner 
Published: April 2015

SummaryAnalyzing multiple single nucleotide polymorphisms (SNPs) is a promising approach to finding genetic effects beyond single‐locus associations. We proposed the use of multilocus stepwise regression (MSR) to screen for allele combinations as a method to model joint effects, and compared the results with the often used genetic risk score (GRS), conventional stepwise selection, and the shrinkage method LASSO. In contrast to MSR, the GRS, conventional stepwise selection, and LASSO model each genotype by the risk allele doses. We reanalyzed 20 unlinked SNPs related to type 2 diabetes (T2D) in the EPIC‐Potsdam case‐cohort study (760 cases, 2193 noncases). No SNP–SNP interactions and no nonlinear effects were found. Two SNP combinations selected by MSR (Nagelkerke's R² = 0.050 and 0.048) included eight SNPs with mean allele combination frequency of 2%. GRS and stepwise selection selected nearly the same SNP combinations consisting of 12 and 13 SNPs (Nagelkerke's R² ranged from 0.020 to 0.029). LASSO showed similar results. The MSR method showed the best model fit measured by Nagelkerke's R² suggesting that further improvement may render this method a useful tool in genetic research. However, our comparison suggests that the GRS is a simple way to model genetic effects since it does not consider linkage, SNP–SNP interactions, and no non‐linear effects.
Predictors of depression outcomes among abstinent methamphetamine‐dependent individuals exposed to an exercise intervention
Authors: Haglund Margaret , Ang Alfonso , Mooney Larissa , Gonzales Rachel , Chudzynski Joy , Cooper Christopher B. , Dolezal Brett A. , Gitlin Michael , Rawson Richard A. 
Published: April 2015

Background and ObjectivesThis paper expands on a study investigating depression outcomes in response to an 8‐week exercise intervention among methamphetamine (MA) dependent individuals in early recovery.MethodsA total of 135 MA‐dependent individuals enrolled in residential treatment were randomly assigned to either a structured exercise intervention or a structured health education control group. Both groups were similar in format: 60‐minute sessions, offered three times a week over an 8‐week study period.ResultsResults showed that at the 8‐week trial endpoint, participants randomized to the exercise intervention showed significantly greater reduction in depression symptom scores than participants randomized to the health education group, and that participants who attended the greatest number of exercise sessions derived the greatest benefit. This paper further analyzes study data to uncover individual predictors of depression response to exercise and finds that among participants randomized to exercise treatment, individuals with the most severe medical, psychiatric, and addiction disease burden at baseline showed the most significant improvement in depressive symptoms by study endpoint.ConclusionsOur findings suggest that exercise in moderate dose is effective at treating depressive symptoms in individuals in early recovery from addiction, and furthermore, that treatment with exercise appears to be particularly beneficial to individuals who suffer from severe medical, psychiatric, and addictive disorders. (Am J Addict 2015;24:246–251)
Baseline characteristics of patients predicting suitability for rapid naltrexone induction
Authors: Mogali Shanthi , Khan Nabil A. , Drill Esther S. , Pavlicova Martina , Sullivan Maria A. , Nunes Edward , Bisaga Adam 
Published: April 2015

Background and ObjectivesExtended‐release (XR) injection naltrexone has proved promising in the treatment of opioid dependence. Induction onto naltrexone is often accomplished with a procedure known as rapid naltrexone induction. The purpose of this study was to evaluate pre‐treatment patient characteristics as predictors of successful completion of a rapid naltrexone induction procedure prior to XR naltrexone treatment.MethodsA chart review of 150 consecutive research participants (N = 84 completers and N = 66 non‐completers) undergoing a rapid naltrexone induction with the buprenorphone‐clonidine procedure were compared on a number of baseline demographic, clinical and psychosocial factors. Logistic regression was used to identify client characteristics that may predict successful initiation of naltrexone after a rapid induction‐detoxification.ResultsPatients who failed to successfully initiate naltrexone were younger (AOR: 1.040, CI: 1.006, 1.075), and using 10 or more bags of heroin (or equivalent) per day (AOR: 0.881, CI: 0.820, 0.946). Drug use other than opioids was also predictive of failure to initiate naltrexone in simple bivariate analyses, but was no longer significant when controlling for age and opioid use level.ConclusionsYounger age, and indicators of greater substance dependence severity (more current opioid use, other substance use) predict difficulty completing a rapid naltrexone induction procedure. Such patients might require a longer period of stabilization and/or more gradual detoxification prior to initiating naltrexone.Scientific SignificanceOur study findings identify specific characteristics of patients who responded positively to rapid naltrexone induction. (Am J Addict 2015;24:258–264)
Neurotoxicity of intrathecal 6% hydroxyethyl starch 130/0.4 injection in a rat model
Authors: Vassal O. , Del Carmine P. , Beuriat P.‐A. , Desgranges F.‐P. , Gadot N. , Allaouchiche B. , Timour‐Chah Q. , Stewart A. , Chassard D. 
Published: April 2015

SummaryEpidural blood patch is the gold standard treatment for post‐dural puncture headache, although hydroxyethyl starch may be a useful alternative to blood if the latter is contraindicated. The aim of this experimental study was to assess whether hydroxyethyl starch given via an indwelling intrathecal catheter resulted in clinical or histopathological changes suggestive of neurotoxicity. The study was conducted in rats that were randomly allocated to receive three 10‐μl injections on consecutive days of either saline or hydroxyethyl starch administered via the intrathecal catheter. Eight rats were given injections of saline 0.9% and 11 were given 6% hydroxyethyl starch 130/0.4 derived from thin boiling waxy corn starch in 0.9% sodium chloride (Voluven®). Daily clinical evaluation, activity measured by actimetry and neuropathological analysis of the spinal cord were subsequently performed to assess for signs of neurotoxicity. No clinical or actimetric changes were observed in either group following intrathecal saline or hydroxyethyl starch administration. Histopathological examination showed non‐specific changes with no differences between the two groups. This experimental study in the rat suggests that repeated intrathecal injection of hydroxyethyl starch is not associated with neurotoxicity.
Refinements and restoring contour in head and neck reconstruction
Authors: Sofiadellis Foti , Grinsell Damien 
Published: April 2015

AbstractBackgroundTo date head and neck reconstructions of oncological defects have concentrated on primarily filling the defect to achieve primary wound healing, secondly restore function and lastly cosmesis. This paper describes a refinement of existing free tissue transfer techniques for improvement of contour, function and aesthetics.MethodsA retrospective review of 38 patients operated on by one surgeon at St Vincent's, Royal Melbourne and Western Hospitals over a 3‐year period was conducted. Data were collected on patient demographics, tumour details, nature of the defect, type of reconstructive procedure, nature of additional tissue used, radiotherapy, complications and outcome.ResultsWe present refinements in using de‐epithelialized skin paddles, flexor hallucis longus, and rectus and vastus lateralis muscle in order to achieve optimal reconstruction. Free tissue transfer refinements are discussed in anterolateral thigh, fibula, rectus and anteromedial thigh free flaps. The average defect size and volume of neck dissection prior to reconstruction is presented. A variation of radical, modified radical and selective neck dissections were required for oncological staging and clearance. Rare and minor associated complications are discussed. Post‐operative radiotherapy treatment was used in the majority of patients with preoperative adjuvant therapy required in some salvage cases. All patients achieved primary wound healing post‐operatively with no salivary leaks, flap failures or exposure of neck vessels.ConclusionsSupplementary microsurgical tissue transfer of de‐epithelialized skin, vastus lateralis, flexor hallucis longus and rectus muscles is a valuable option for restoring contour, aesthetics and vessel protection post‐radiotherapy.
Role of general surgeons in acute urinary obstruction
Authors: Rizvi Syed Ali Abbas , Leung Amy , Pretorius Casper Francois 
Published: April 2015

AbstractBackgroundAn emergency JJ stent is occasionally required to manage a patient with obstructive uropathy. In regional centres where there is no emergency urology service available, general surgeons are required to perform ureteric stent insertions. The aim of our study is to assess the efficacy of general surgeons in ureteric stent insertion.MethodsWe retrospectively analysed the ureteric stent registry data from 1 January 2010 to 31 July 2014.ResultsA total of 185 ureteric stents were inserted between 1 January 2010 and 31 July 2014. Of these, 132 were for emergency cases. General surgeons performed 65 of the emergency stents. There were no complications associated with ureteric stent insertion.ConclusionUreteric stent insertion can be safely performed by general surgeons if adequately trained. Surgical trainees intending to work at the regional centres should be trained in ureteric stent insertions to prevent unnecessary hospital transfers.
Operative intervention rates for acute diverticulitis: a multicentre state‐wide study
Authors: Hong Michael K.‐Y. , Tomlin Andrew M. , Hayes Ian P. , Skandarajah Anita R. 
Published: April 2015

AbstractBackgroundAcute colonic diverticulitis is placing an increasing strain on our health care resources. Measurement of the problem is difficult at a regional level, yet essential to improve and optimize treatment of this condition. Therefore, we aimed to use Australian state‐level administrative data to determine the current practice and outcomes in major metropolitan hospitals.MethodsCoding algorithms designed to increase the yield and accuracy of administrative data were used to find emergency admissions from the Victorian Admitted Episodes Dataset. Eight tertiary referral centres with specialist colorectal services from 2009 to 2013 were studied. Key metrics including the operative intervention rate were measured.ResultsThere were 2829 emergency admissions for acute diverticulitis across 4 years in eight hospitals, with 724 being complicated. The emergency operative intervention rate was 10.4%, with a third of admissions for complicated diverticulitis having an operation. Hartmann's procedure was the most commonly performed emergency operation, accounting for 72% of resections. Patient characteristics were consistent across the hospitals, including a median length of stay of 3 and 6 days for uncomplicated and complicated diverticulitis, respectively.ConclusionHartmann's procedure is currently the most common emergency operation for acute complicated diverticulitis in Victorian metropolitan hospitals. Our practice and outcomes can be measured meaningfully using administrative data.
Four Ways Life Extension will Change Our Relationship with Death
Authors: Davis John K. 
Published: April 2015

AbstractDiscussions of life extension ethics have focused mainly on whether an extended life would be desirable to have, and on the social consequences of widely available life extension. I want to explore a different range of issues: four ways in which the advent of life extension will change our relationship with death, not only for those who live extended lives, but also for those who cannot or choose not to. Although I believe that, on balance, the reasons in favor of developing life extension outweigh the reasons against doing so (something I won't argue for here), most of these changes probably count as reasons against doing so.First, the advent of life extension will alter the human condition for those who live extended lives, and not merely by postponing death. Second, it will make death worse for those who lack access to life extension, even if those people live just as long as they do now. Third, for those who have access to life extension but prefer to live a normal lifespan because they think that has advantages, the advent of life extension will somewhat reduce some of those advantages, even if they never use life extension. Fourth, refusing life extension turns out to be a form of suicide, and this will force those who have access to life extension but turn it down to choose between an extended life they don't want and a form of suicide they may (probably mistakenly) consider immoral.
In Favour of Medical Dissensus: Why We Should Agree to Disagree About End‐of‐Life Decisions
Authors: Wilkinson Dominic , Truog Robert , Savulescu Julian 
Published: April 2015

AbstractEnd‐of‐life decision‐making is controversial. There are different views about when it is appropriate to limit life‐sustaining treatment, and about what palliative options are permissible. One approach to decisions of this nature sees consensus as crucial. Decisions to limit treatment are made only if all or a majority of caregivers agree. We argue, however, that it is a mistake to require professional consensus in end‐of‐life decisions.In the first part of the article we explore practical, ethical, and legal factors that support agreement. We analyse subjective and objective accounts of moral reasoning: accord is neither necessary nor sufficient for decisions. We propose an alternative norm for decisions – that of ‘professional dissensus’.In the final part of the article we address the role of agreement in end‐of‐life policy. Such guidelines can ethically be based on dissensus rather than consensus.Disagreement is not always a bad thing.
Prescribing Posttraumatic Growth
Authors: Harbin Ami 
Published: April 2015

AbstractThis article introduces questions in psychiatric ethics regarding the substantial field of qualitative and quantitative research into ‘posttraumatic growth’, which investigates how, after devastating experiences, individuals can come to feel that they have developed warmer relationships, increased spirituality, or a clearer vision of their priorities. In one area of this research, researchers of posttraumatic growth outline strategies for clinicians interested in assisting their patients in achieving such growth. In this article, I articulate two ethical concerns about this account of posttraumatic growth and the practice of growth‐oriented therapy. The first is a concern about the status and effects of the ideal of posttraumatic health implicit in their account, and the second a concern about the ethical implications of the clinical recommendations for the post‐trauma patient. I argue for the need for more attention to the hazardous implications of relating to patients as though they are on their way to, and themselves largely in control of, their own posttraumatic growth.
The p.R1819_C1948delinsS mutation makes von Willebrand factor ADAMTS13‐resistant and reduces its collagen‐binding capacity
Authors: Daidone Viviana , Saga Giorgia , Barbon Giovanni , Pontara Elena , Cattini Maria G. , Morpurgo Margherita , Zanotti Giuseppe , Casonato Alessandra 
Published: April 2015

SummaryThis report concerns abnormal ADAMTS13 (a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13) and collagen interactions coinciding with the p.R1819_C1948delinsS von Willebrand factor (VWF) mutation associated with the deletion of the C‐terminus of the A3 domain (amino acids 1819–1947) in a patient with a history of bleeding. The von Willebrand disease (VWD) phenotype of the patient featured low plasma and platelet VWF, multimers with smears extending over the highest normal oligomers in plasma, but not platelets, and an impaired collagen‐binding capacity. In vitro full‐length p.R1819_C1948delinsS VWF expression showed impaired VWF release, increased cellular content with normally‐multimerized VWF and impaired collagen binding. The recombinant p.R1819_C1948delinsS VWF fragment, extending from domains A2 to B3 (p.R1819_C1948delinsS A2‐B3 VWF), was completely resistant to proteolysis by ADAMTS13 in the presence of 1·5 mol/l urea, unlike its normal counterpart. The defect stems from impaired ADAMTS13 binding to p.R1819_C1948delinsS A2‐B3, analysed under static conditions. Partial deletion of the C‐terminus of the A3 domain thus makes VWF resistant to ADAMTS13, interfering with ADAMTS13 binding to VWF, and impairing the collagen‐binding capacity of VWF. The p.R1819_C1948delinsS mutation has both haemorrhagic features (defective collagen binding, reduced VWF levels) and prothrombotic (ADAMTS13 resistance) features, and the latter probably mitigate the patient's bleeding symptoms.
INFORMATION AGGREGATION, GROWTH, AND FRANCHISE EXTENSION WITH APPLICATIONS TO FEMALE ENFRANCHISEMENT AND INEQUALITY
Authors: Ellis Christopher , Fender John 
Published: April 2015

ABSTRACTWe develop a model of voluntary gradual franchise extension and growth based on the idea that voting is an information aggregation mechanism. A larger number of voters means that more correct decisions are made, hence increasing output, but also implies that any incremental output must be shared among more individuals. These conflicting incentives lead to a dynamic model of franchise extensions that is consistent with several real world episodes, including female enfranchisement. The model also predicts that in certain circumstances growth and enfranchisement will be accompanied by Kuznets curve type behaviour in inequality. Contrary to the preceding literature these conclusions do not rest on incentives for strategic delegation.