bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of anxiety sensitivity on alcohol problems: evaluating chained mediation through generalized anxiety, depression and drinking motives
Authors: Allan Nicholas P. , Albanese Brian J. , Norr Aaron M. , Zvolensky Michael J. , Schmidt Norman B. 
Published: September 2014

AbstractAimsTo test whether the relations between anxiety sensitivity (AS), a transdiagnostic risk factor, and alcohol problems are explained by chained mediation models, from AS through anxiety or depressive symptoms then drinking motives in an at‐risk sample. It was hypothesized that AS would influence alcohol problems through generalized anxiety or depression symptoms and then through negatively reinforced drinking motives (i.e. drinking to cope with negative affect and drinking to conform).DesignCross‐sectional single‐ and chained‐mediation models were tested.SettingSelf‐report measures were completed in clinics at Florida State University and the University of Vermont, USA.ParticipantsParticipants consisted of 523 adult daily cigarette smokers [mean age = 37.23, standard deviation (SD) = 13.53; 48.6% female].MeasurementsAs part of a larger battery of self‐report measures, participants completed self‐report measures of AS, generalized anxiety, depression, drinking motives and alcohol problems.FindingsChained mediation was found from AS to alcohol problems through generalized anxiety then through drinking to cope with negative affect [B = 0.04, 90% confidence interval (CI) = 0.004, 0.10)]. Chained mediation was also found from AS to alcohol problems through depression then through drinking to cope with negative affect (B = 0.11, 90% CI = 0.05, 0.21) and, separately, through socially motivated drinking (B = 0.05, 90% CI = 0.003, 0.11).ConclusionsAnxiety sensitivity and alcohol problems are indirectly related through several intervening variables, such as through generalized anxiety or depression and then through drinking to cope with negative affect.
High‐frequency drug purity and price series as tools for explaining drug trends and harms in Victoria, Australia
Authors: Scott Nick , Caulkins Jonathan P , Ritter Alison , Quinn Catherine , Dietze Paul 
Published: September 2014

AbstractAimsMethamphetamine‐related harms in Victoria have increased recently in the context of stable or declining use prevalence. We determine how changes in price and purity of methamphetamine compared to other drugs such as heroin may, in part, explain these divergent patterns.MethodsDetailed methamphetamine and heroin purchase price data from 2152 participant interviews from the Melbourne Injecting Drug User cohort study were used to generate drug price series for the period January 2009–June 2013. Data on drug purity from 8818 seizures made within Victoria were used to generate drug purity series during the same period. Purity‐adjusted price data for methamphetamine and heroin were obtained for the period 2009–13 by combining the two data sets.ResultsWhile the average purity of heroin seizures remained consistent and low, the average purity of powder and of crystal methamphetamine seizures increased from 12% [95% confidence interval (CI) = 10–14%] to 37% (95% CI = 20–54%) and 21% (95% CI = 18–23%) to 64% (95% CI = 60–68%), respectively. Crystal methamphetamine purity was bimodal, with observations generally less than 20% or greater than 70%. The average unadjusted price per gram for heroin decreased from $374 (95% CI = $367–381) to $294 (95% CI = $280–308), powder methamphetamine did not change significantly from $252 (95% CI = $233–271), and crystal methamphetamine increased substantially from $464 (95% CI = $416–511) in 2009 to $795 (95% CI = $737–853) in 2011. This increase was offset by an even greater increase in purity, meaning the average purity‐adjusted price per gram declined. Furthermore, pure prices of both methamphetamine forms were similar, whereas their unadjusted prices were not. The pure price of heroin fluctuated with no ongoing trends.ConclusionsDecreases in methamphetamine purity‐adjusted price along with the bimodality of crystal methamphetamine purity may account for some of the recent increase in methamphetamine‐related harm. For a given amount spent, methamphetamine purchase power has increased and the presence of extreme purity variations may challenge individuals' control of consumption.
The association between family affluence and smoking among 15‐year‐old adolescents in 33 European countries, Israel and Canada: the role of national wealth
Authors: Pförtner Timo‐Kolja , Moor Irene , Rathmann Katharina , Hublet Anne , Molcho Michal , Kunst Anton E. , Richter Matthias 
Published: September 2014

ABSTRACTAimsTo examine the role of national wealth in the association between family affluence and adolescent weekly smoking, early smoking behaviour and weekly smoking among former experimenters.Design and ParticipantsData were used from the Health Behaviour in School‐aged Children (HBSC) study conducted in 2005/2006 in 35 countries from Europe and North America that comprises 60 490 students aged 15 years. Multi‐level logistic regression was conducted using Markov chain Monte Carlo methods (MCMC) to explore whether associations between family affluence and smoking outcomes were dependent upon national wealth.MeasurementFamily Affluence Scale (FAS) as an indicator for the socio‐economic position of students. Current weekly smoking behaviour is defined as at least weekly smoking (dichotomous). Early smoking behaviour is measured by smoking more than a first puff before age 13 years (dichotomous). Weekly smoking among former experimenters is restricted to those who had tried a first puff in the past.FindingsThe logistic multi‐level models indicated an association of family affluence with current weekly smoking [odds ratio (OR) = 1.088; 95% credible interval (CrI) = 1.055–1.121, P < 0.001], early smoking behaviour (OR = 1.066; CrI = 1.028–1.104, P < 0.001) and smoking among former experimenters (OR = 1.100; CrI = 1.071–1.130; P < 0.001). Gross domestic product (GDP) per capita was associated positively and significantly with the relationship between family affluence and current weekly smoking (OR = 1.005; CrI = 1.003–1.007; P < 0.001), early smoking behaviour (OR = 1.003; CrI = 1.000–1.005; P = 0.012) and smoking among former experimenters (OR = 1.004; CrI = 1.002–1.006; P < 0.001). The association of family affluence and smoking outcomes was significantly stronger for girls.ConclusionsThe difference in smoking prevalence between rich and poor is greater in more affluent countries.
Increased Circulating Th1/Th2 Ratios But Not Other Lymphocyte Subsets During Controlled Ovarian Stimulation are Linked to Subsequent Implantation Failure after Transfer of In Vitro Fertilized Embryos
Authors: Liang Pei‐Yan , Yin Biao , Cai Jing , Hu Xiao‐Dong , Song Cheng , Wu Tong‐Hua , Zhao Jing , Li Guan‐Gui , Zeng Yong 
Published: September 2014

ProblemTo investigate alterations of circulating lymphocyte subsets in women undergoing controlled ovarian stimulation (COS) and survey their relations with pregnancy outcome.Method of StudyFifty‐one women were included in this study, of which 24 women were successfully pregnant in the index IVF cycle (the successful pregnancy group, sPG) and 27 women failed to get pregnant (the non‐pregnancy group, nPG). Peripheral blood was collected at three time points during COS: on the day before the first GnRHa administration (GnRHa day), on the day before the first Gn administration (Gn day), and on the day before HCG administration (HCG day). The intracellular Th1(IFN‐γ and TNF‐α)/Th2(IL‐10) ratios in circulating Th cells after in vitro phorbol‐12‐myristate‐13‐acetate stimulation, the NK cytotoxicity, and the percentage of T, B and NK cell subsets were assessed by flow cytometer. A third group consisting of patients with recurrent implantation failure (RIF group, n = 18) was also enrolled, and the intracellular Th1/Th2 ratios were assessed at HCG day.ResultsIntergroup comparison: The ratios of IFN‐γ/IL‐10 and TNF‐α/IL‐10 at HCG day were significantly higher (P < 0.05) in nPG than those in sPG, while no change at GnRHa day or Gn day. Higher (P < 0.05) ratios of IFN‐γ/IL‐10 and TNF‐α/IL‐10 at HCG day were also observed in RIF group compared to those in sPG. No significant change (P > 0.05) was found in other assessed lymphocyte subsets or in the concentrations of progesterone, estradiol, luteinizing hormone, or follicle‐stimulating hormone between the sPG and nPG at the three time points. Intragroup comparison: The ratios of IFN‐γ/IL‐10 and TNF‐α/IL‐10 at HCG day were significantly (P < 0.05) lower than those at GnRHa day in sPG, but not in nPG. No significant (P > 0.05) difference was found in other assessed parameters or at other time points.ConclusionsThe ratios of Th1/Th2 were fluctuated during COS, and they might affect the pregnancy outcome of IVF. The circulating NK cytotoxicity and percentage of lymphocyte subsets were relatively stable during the COS.
The serotonin transporter genotype modulates the relationship between early stress and adult suicidality in bipolar disorder
Authors: Benedetti Francesco , Riccaboni Roberta , Poletti Sara , Radaelli Daniele , Locatelli Clara , Lorenzi Cristina , Pirovano Adele , Smeraldi Enrico , Colombo Cristina 
Published: September 2014

ObjectiveBipolar disorder (BD) is associated with a higher risk of suicide and with worse early life stress. A serotonin (5‐hydroxytryptamine; 5‐HT) transporter‐linked polymorphic region (5‐HTTLPR) has been shown to influence the relationship between stress and the risk of attempting suicide in the general population, but has not been investigated in BD.MethodsWe studied 136 inpatients (93 females, 43 males) with a major depressive episode in the course of BD. Early and recent stressful life events were scored on the Social Readjustment Rating Scale (SRRS). Regional gray matter (GM) volumes were analyzed, acquiring T1‐weighted images on a 3.0 Tesla scanner.ResultsHomozygote l/l patients attempted suicide in a higher proportion than *s carriers. A separate‐slopes logistic regression showed a significant effect of 5‐HTTLPR on the relationship between stress, depression, and suicide among *s carriers, but not among l/l homozygotes, early stress associated with worse probability of attempting suicide and with earlier age at onset of BD. Exposure to early stress correlated with GM volumes in the right prefrontal cortex (Brodmann area 46) – again, in *s carriers only.Conclusions5‐HTTLPR modulated the relationship between early life stress and the core features of bipolar illness. 5‐HTTLPR*s carriers showed a higher sensitivity to the effects of stress; when exposed to low levels of early stress, they were protected against suicide in respect to l/l, but higher levels of stress progressively increased their risk of suicide and reduced the age at onset of illness.
Electrophysiological (EEG) evidence for reduced performance monitoring in euthymic bipolar disorder
Authors: Morsel Anne M , Morrens Manuel , Temmerman Anke , Sabbe Bernard , de Bruijn Ellen RA 
Published: September 2014

ObjectivesApart from mood episodes, many cognitive deficits are present in bipolar disorder (BD). Performance monitoring is an important aspect of executive functioning and involves continuous monitoring of behavior and making subsequent changes when an error is made. On a neurophysiological level, the error‐related negativity (ERN), an event‐related brain potential (ERP) generated in the anterior cingulate cortex (ACC), reflects this process of performance monitoring. Abnormal ERN amplitudes have been observed in many major psychiatric disorders. However, despite conflicting evidence regarding the role of the ACC in BD, no studies to date have investigated performance monitoring as reflected in the ERN in BD.MethodsSixteen patients with BD in a euthymic state and 14 matched healthy controls performed a speeded two‐choice reaction‐time paradigm (Flankers Task) while electroencephalogram (EEG) measures were obtained. Behavioral and ERP measurements were analyzed for the two groups.ResultsThe patients with BD, although euthymic, scored higher on depressive symptoms than healthy controls. While no behavioral group differences were found, patients with BD displayed lower ERN amplitudes than healthy controls when controlling for effects of residual mood.ConclusionsThe lower ERN amplitudes in the BD group reflect reduced performance monitoring and extend current knowledge of executive functioning in BD. Importantly, these findings go a long way to resolving the contradictory results regarding ACC involvement in BD by showing that taking into account residual mood may greatly influence error‐related ACC activations and is critically important in understanding cognitive deficits in BD.
Simultaneous Variable Selection for Joint Models of Longitudinal and Survival Outcomes
Authors: He Zangdong , Tu Wanzhu , Wang Sijian , Fu Haoda , Yu Zhangsheng 
Published: September 2014

SummaryJoint models of longitudinal and survival outcomes have been used with increasing frequency in clinical investigations. Correct specification of fixed and random effects is essential for practical data analysis. Simultaneous selection of variables in both longitudinal and survival components functions as a necessary safeguard against model misspecification. However, variable selection in such models has not been studied. No existing computational tools, to the best of our knowledge, have been made available to practitioners. In this article, we describe a penalized likelihood method with adaptive least absolute shrinkage and selection operator (ALASSO) penalty functions for simultaneous selection of fixed and random effects in joint models. To perform selection in variance components of random effects, we reparameterize the variance components using a Cholesky decomposition; in doing so, a penalty function of group shrinkage is introduced. To reduce the estimation bias resulted from penalization, we propose a two-stage selection procedure in which the magnitude of the bias is ameliorated in the second stage. The penalized likelihood is approximated by Gaussian quadrature and optimized by an EM algorithm. Simulation study showed excellent selection results in the first stage and small estimation biases in the second stage. To illustrate, we analyzed a longitudinally observed clinical marker and patient survival in a cohort of patients with heart failure.
Remote conditioning the heart overview: translatability and mechanism
Authors: Schmidt Michael Rahbek , Redington Andrew , Bøtker Hans Erik 
Published: September 2014

Conditioning the heart to resist predictable and unpredictable ischaemia–reperfusion (IR) injury is one of the fastest growing areas of bench to bedside research within cardiology. Basic science has provided important insights into signalling pathways and protective mechanisms in the heart, and a growing number of clinical studies have, with important exceptions, shown the potential applicability and beneficial effect of various mechanical conditioning strategies achieved by intermittent short‐lasting‐induced ischaemia of the heart itself or a remote tissue. Remote ischaemic conditioning (RIC) in particular has been utilized in a number of clinical settings with promising results. However, while many novel ‘downstream’ mechanisms of RIC have been discovered, translation to pharmacological conditioning has not yet been convincingly demonstrated in clinical studies. One explanation for this apparent failure may be that most pharmacological approaches mimic a single instrument in a complex orchestra activated by mechanical conditioning. Recent studies, however, provide important insights into upstream events occurring in RIC, which may allow for development of drugs activating more complex systems of biological organ protection. With this review, we will systematically examine the first generation of pharmacological cardioprotection studies and then provide a summary of the recent discoveries in basic science that could illuminate the path towards more advanced approaches in the next generation of pharmacological agents that may work by reproducing the diverse effects of RIC, thereby providing protection against IR injury.Linked ArticlesThis article is part of a themed section on Conditioning the Heart – Pathways to Translation. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue‐8
Hydrogen peroxide stimulation of CFTR reveals an Epac‐mediated, soluble AC‐dependent cAMP amplification pathway common to GPCR signalling
Authors: Ivonnet P , Salathe M , Conner G E 
Published: September 2014

Background and PurposeH2O2 is widely understood to regulate intracellular signalling. In airway epithelia, H2O2 stimulates anion secretion primarily by activating an autocrine PGE2 signalling pathway via EP4 and EP1 receptors to initiate cytic fibrosis transmembrane regulator (CFTR)‐mediated Cl− secretion. This study investigated signalling downstream of the receptors activated by H2O2.Experimental ApproachAnion secretion by differentiated bronchial epithelial cells was measured in Ussing chambers during stimulation with H2O2, an EP4 receptor agonist or β2‐adrenoceptor agonist in the presence and absence of inhibitors of ACs and downstream effectors. Intracellular calcium ([Ca2+]I) changes were followed by microscopy using fura–2‐loaded cells and PKA activation followed by FRET microscopy.Key ResultsTransmembrane adenylyl cyclase (tmAC) and soluble AC (sAC) were both necessary for H2O2 and EP4 receptor‐mediated CFTR activation in bronchial epithelia. H2O2 and EP4 receptor agonist stimulated tmAC to increase exchange protein activated by cAMP (Epac) activity that drives PLC activation to raise [Ca2+]i via Ca2+ store release (and not entry). Increased [Ca2+]i led to sAC activation and further increases in CFTR activity. Stimulation of sAC did not depend on changes in [HCO3−]. Ca2+‐activated apical KCa1.1 channels and cAMP‐activated basolateral KV7.1 channels contributed to H2O2‐stimulated anion currents. A similar Epac‐mediated pathway was seen following β2‐adrenoceptor or forskolin stimulation.Conclusions and ImplicationsH2O2 initiated a complex signalling cascade that used direct stimulation of tmACs by Gαs followed by Epac‐mediated Ca2+ crosstalk to activate sAC. The Epac‐mediated Ca2+ signal constituted a positive feedback loop that amplified CFTR anion secretion following stimulation of tmAC by a variety of stimuli.
Ionic mechanisms underlying the negative chronotropic action of propofol on sinoatrial node automaticity in guinea pig heart
Authors: Kojima Akiko , Ito Yuki , Kitagawa Hirotoshi , Matsuura Hiroshi 
Published: September 2014

Background and PurposePropofol is a widely used intravenous anaesthetic agent, but has undesirable cardiac side effects, including bradyarrhythmia and its severe form asystole. This study examined the ionic and cellular mechanisms underlying propofol‐induced bradycardia.Experimental ApproachSinoatrial node cells, isolated from guinea pig hearts, were current‐ and voltage‐clamped to record action potentials and major ionic currents involved in their spontaneous activity, such as the hyperpolarization‐activated cation current (If), T‐type and L‐type Ca2+ currents (ICa,T and ICa,L, respectively) and the rapidly and slowly activating delayed rectifier K+ currents (IKr and IKs, respectively). ECGs were recorded from Langendorff‐perfused, isolated guinea pig hearts.Key ResultsPropofol (≥5 μM) reversibly decreased the firing rate of spontaneous action potentials and their diastolic depolarization rate. Propofol impaired If activation by shifting the voltage‐dependent activation to more hyperpolarized potentials (≥1 μM), slowing the activation kinetics (≥3 μM) and decreasing the maximal conductance (≥10 μM). Propofol decreased ICa,T (≥3 μM) and ICa,L (≥1 μM). Propofol suppressed IKs (≥3 μM), but had a minimal effect on IKr. Furthermore, propofol (≥5 μM) decreased heart rates in Langendorff‐perfused hearts. The sinoatrial node cell model reasonably well reproduced the negative chronotropic action of propofol.Conclusions and ImplicationsMicromolar concentrations of propofol suppressed the slow diastolic depolarization and firing rate of sinoatrial node action potentials by impairing If activation and reducing ICa,T, ICa,L and IKs. These observations suggest that the direct inhibitory effect of propofol on sinoatrial node automaticity, mediated via multiple channel inhibition, underlies the propofol‐induced bradycardia observed in clinical settings.
The sphingosine 1‐phosphate receptor agonist FTY720 is neuroprotective after cuprizone‐induced CNS demyelination
Authors: Slowik A , Schmidt T , Beyer C , Amor S , Clarner T , Kipp M 
Published: September 2014

Background and PurposeModulation of the sphingosine 1‐phosphate receptor is an approved treatment for relapsing multiple sclerosis because of its anti‐inflammatory effect of retaining lymphocytes within the lymph nodes. Here, we evaluated the potential of an agonist at this receptor, FTY720 (fingolimod), to activate the promyelinating pathways within the brain to encourage remyelination and neuroprotection.Experimental ApproachIn this study, we used the cuprizone model in male C57BL/6 mice and tested the promyelinating and neuroprotective effects of FTY720 after acute and chronic toxin‐induced experimental demyelination. We used histological, immunohistochemical and gene expression methods.Key ResultsThe midline of the corpus callosum was severely demyelinated after acute and chronic cuprizone‐induced demyelination. Robust endogenous remyelination was evident after acute, but impaired after chronic, demyelination. FTY720 treatment modestly accelerated myelin recovery after acute but not chronic cuprizone exposure. Markers of gliosis (astrocyte and microglia activation) were not affected by FTY720 treatment. Remarkably, the accumulation of amyloid precursor protein‐positive spheroids in axons was less distinct in FTY720‐treated animals, indicating that this compound alleviated ongoing axonal damage.Conclusions and ImplicationsWe show that even during endogenous remyelination, axonal degeneration continued at a low level, accumulating over time. This continuous neurodegenerative process was ameliorated by FTY720 treatment. FTY720 preserved CNS integrity by direct interaction with brain resident cells, the actions of which are still to be defined.