Exaggerated Waiting Impulsivity Associated with Human Binge Drinking,and High Alcohol Consumption in Mice

There are well-established links between impulsivity and alcohol use in humans and animal models; however, whether exaggerated impulsivity is a premorbid risk factor or a consequence of alcohol intake remains unclear. In a first approach, human young (18–25 years) social binge and non-binge drinkers were tested for motor impulsivity and attentional abilities in a human version of the Five-Choice Serial Reaction Time Task (Sx-5CSRTT), modeled on the rodent 5CSRTT. Participants completed four variants of the Sx-5CSRT, in addition to being screened for impulsive traits (BIS-11 questionnaire) and impulsive behavior (by means of the Delay Discounting Questionnaire, Two-Choice Impulsivity Paradigm (TCIP), Stop Signal Reaction Time, and Time Estimation Task). Using a second approach, we compared one of these impulsivity measures, 5CSRTT performance, in two inbred strains of mice known to differ in alcohol intake. Compared with non-bingers (NBD; n=22), binge drinkers (BD, n=22) showed robust impairments in attention and premature responding when evaluated under increased attentional load, in addition to presenting deficits in decision making using the TCIP. The best predictors for high binge drinking score were premature responding in the Sx-5CSRTT, trait impulsivity in the BIS-11, and decision making in the TCIP. Alcohol-naïve C57BL/6J (B6) mice (alcohol preferring) were more impulsive in the 5CSRTT than DBA2/J (D2) mice (alcohol averse); the degree of impulsivity correlated with subsequent alcohol consumption. Homologous measures in animal and human studies indicate increased premature responding in young social BD and in the ethanol-preferring B6 strain of mice.Impulsivity has been consistently implicated as both a determinant and a consequence of alcohol abuse. Binge patterns of alcohol consumption, in particular, have been associated with impaired attentional function and executive function (Scaife and Duka, 2009; Townshend and Duka, 2005), and increased impulsive behavior in both humans and rodent models (Bell et al, 2013; Duka et al, 2003; Stephens and Duka, 2008). However, it is unclear whether high levels of impulsivity are a cause or consequence of alcohol intake.Given the prevalence of binge drinking in adolescence (Healey et al, 2014), the first aim of our study was to examine the relationship of binge drinking to measures of waiting impulsivity and attentional abilities in human adolescents (18–25 years old) and in rodents, which consume alcohol. Taking the rodent 5CSRTT (Robbins, 2002) as a model, we developed a novel, iPad-based task (Sussex 5CSRTT; Sx-5CSRTT), to assess both attentional performance and anticipatory behavior in humans. BD were also characterized in four additional measures of impulsivity, based on different operational definitions of the construct. The Stop Signal Task, used to assess ability to inhibit a prepotent response (Logan, 1994), served as an additional measure of ‘motoric impulsivity''. The Delay Discounting Questionnaire measured preference for immediate over-delayed rewards (Petry, 2001) and, combined with the Two-Choice Impulsivity paradigm (Dougherty et al, 2005), provided an index of ‘choice'' impulsivity or decision making; the fourth behavioral measure used was the Time Estimation Task. Although each of these five measures has been used in the clinical context as an index of impulsive behavior, the sensitivity of each task to characterize impulsive phenotype in young social BD, and their relationship to one another has not been explored. We anticipated binge drinking might be differentially associated with different aspects of impulsive behavior, but generally that high binge drinking scores would be associated with high levels of trait and behavioral motor impulsivity and aversion to delay.The role of premorbid impulsivity as a predictor of elevated alcohol intake cannot be easily disentangled in human studies, as impulsivity measures are almost inevitably assessed after a period of alcohol use. Animal models are more powerful tools in this respect as they allow the exclusion of alcohol experience as a potential contributor to impulsivity. Therefore, having established that 5CSRTT waiting impulsivity was associated with human binge drinking, we asked whether waiting impulsivity in alcohol-naïve mice predicted alcohol drinking in two widely used B6 and D2 inbred strains, that also differ in alcohol consumption (Crabbe et al, 1994). We have previously reported (Walker et al, 2011) that prior exposure to high alcohol concentrations over several weeks in adulthood has only transitory effects in increasing impulsivity in B6 mice. We predicted greater impulsivity in the high-ethanol-preferring mice indicating a potential causal relationship between waiting impulsivity and high alcohol consumption.Using homologous measures of impulsivity in mouse and humans, we provide evidence that waiting impulsivity is associated with binge drinking in young adult humans, and predicts alcohol consumption in mice.     

Highly reactive 2-deoxy-2-iodo-d-allo and d-gulo pyranosyl sulfoxide donors ensure β-stereoselective glycosylations with steroidal aglycones

The preparation of well-defined d-xylo and d-ribo glycosides represents a synthetic challenge due to the limited configurational availability of starting materials and the laborious synthesis of homogeneous 2-deoxy-β-glycosidic linkages, in particular that of the sugar-steroid motif, which represents the “stereoselective determining step” of the overall synthesis. Herein we describe the use of 2-deoxy-2-iodo-glycopyranosyl sulfoxides accessible from widely available d-xylose and d-ribose monosaccharides as privileged glycosyl donors that permit activation at very low temperature. This ensures a precise kinetic control for a complete 1,2-trans stereoselective glycosylation of particularly challenging steroidal aglycones.

Highly stereoselective synthesis of challenging steroidal 2-deoxy-β-glycosides with d-xylo and d-ribo configurations enabled by low temperature activation of 2-deoxy-2-iodoglycopyranosyl sulfoxides.     

Impact of depression and/or anxiety on the presentation of cardiovascular events in a cohort with metabolic syndrome. StreX project: Five years of follow-up

Objectives

To determine the role of anxiety and depression on the incidence of cardiovascular events (CVE) in a Catalonian population with metabolic syndrome (MetS) over a five-year follow-up according to the number/type of MetS criteria.

Consensus document from GESITRA-SEIMC on the prevention and treatment of cytomegalovirus infection in transplanted patients

Cytomegalovirus (CMV) infection remains an important complication of transplantation. The last decade has been characterized by improvements to management that has reduced its morbidity and mortality. The advance has been particularly important in the diagnosis and prevention. Several techniques have been developed that allow the increasingly rapid and sensitive diagnosis. The different preventive strategies include use of appropriate blood products, immune globulin, and antiviral agents either as prophylaxis or pre-emptive therapy. The development of effective oral drugs as valganciclovir also represents a new advance. It is necessary to summarize these advances to facilitate the development of local policies reflecting recent changes. The Group of Study of Infections in Transplantation (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) has therefore produced actual recommendations in the management of CMV infection after transplantation.     

Comparison of the Framingham Risk Score,SCORE and WHO/ISH cardiovascular risk prediction models in an Asian population

Background

Cardiovascular risk-prediction models are used in clinical practice to identify and treat high-risk populations, and to communicate risk effectively. We assessed the validity and utility of four cardiovascular risk-prediction models in an Asian population of a middle-income country.

Methods

Data from a national population-based survey of 14,863 participants aged 40 to 65 years, with a follow-up duration of 73,277 person-years was used. The Framingham Risk Score (FRS), SCORE (Systematic COronary Risk Evaluation)-high and -low cardiovascular-risk regions and the World Health Organization/International Society of Hypertension (WHO/ISH) models were assessed. The outcome of interest was 5-year cardiovascular mortality. Discrimination was assessed for all models and calibration for the SCORE models.

Results

Cardiovascular risk factors were highly prevalent; smoking 20%, obesity 32%, hypertension 55%, diabetes mellitus 18% and hypercholesterolemia 34%. The FRS and SCORE models showed good agreement in risk stratification. The FRS, SCORE-high and -low models showed good discrimination for cardiovascular mortality, areas under the ROC curve (AUC) were 0.768, 0.774 and 0.775 respectively. The WHO/ISH model showed poor discrimination, AUC = 0.613. Calibration of the SCORE-high model was graphically and statistically acceptable for men (χ² goodness-of-fit, p = 0.097). The SCORE-low model was statistically acceptable for men (χ² goodness-of-fit, p = 0.067). Both SCORE-models underestimated risk in women (p < 0.001).

Conclusions

The FRS and SCORE-high models, but not the WHO/ISH model can be used to identify high cardiovascular risk in the Malaysian population. The SCORE-high model predicts risk accurately in men but underestimated it in women.     

The rs1333049 polymorphism on locus 9p21.3 and extreme longevity in Spanish and Japanese cohorts

GeroScience - The rs1333049 (G/C) polymorphism located on chromosome 9p21.3 is a candidate to influence extreme longevity owing to its association with age-related diseases, notably coronary artery...     

Cervical intraepithelial neoplasia grade 2 or worse in Galicia,Spain: HPV 16 prevalence and vaccination impact

Introduction

The etiology of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) can influence the efficacy of Public Health preventive strategies. This study aimed to determine the high-risk papillomavirus (HR-HPV) prevalence in CIN2+ cases in unvaccinated women in Galicia (Spain), the expected impact of bivalent vaccination, and the distribution of HPV 16 in squamous lesions.

Material and methods

Ninety-four histologically confirmed cases of CIN2+ (2009–2010) were retrospectively studied: 23 CIN2, 58 CIN3− squamous carcinoma in situ (CIN3-CIS), 5 adenocarcinoma in situ (AIS), and 8 invasive squamous cervical cancer (SCC). Linear Array HPV Genotyping Test (Roche Diagnostics, Mannheim, Germany) was performed on the cervical specimens. Bivalent vaccination impact was calculated, based on regional vaccination coverage data, local HR-HPV prevalence, and reported efficacy (direct and cross-protection) of the vaccine.

Results

HR-HPV prevalence was 96.8%. The most frequent genotypes were HPV 16 (48.8–58.2%) and HPV 31 (9.3%–12.1%), considering single infections or single-multiple infections, respectively (hierarchical attribution). In squamous lesions, HPV 16 prevalence in women younger than 45 years of age increased in severe lesions (CIN3-CIS/SCC, OR 4.2), and was higher than in older women (OR 5.5). The vaccine could reduce the cumulative incidence of CIN2+ by 50.6% (direct protection), or by 62.7% (direct and cross-protection).

Conclusion

HPV vaccination could have a great impact in women younger than 45 years of age due to the high prevalence of HPV 16 in their lesions.