What Ethanol metabolites as biological markers tell us about alcohol use

Alcohol and tobacco related disorders are the two leading and most expensive causes of illness in central Europe. In addition to self reports and questionnaires, biomarkers are of relevance in diagnosis and therapy of alcohol use disorders.Traditional biomarkers such as gamma glutamyl transpeptidase or mean corpuscualr volume are indirect biomarkers and are subject to influence of age, gender and non alcohol related diseases, among others.Direct ethanol metabolites such as ethyl glucuronide (EtG), ethyl sulphate (EtS) and phosphatidylethanol (PEth) are direct metabolites of ethanol, that are positive after intake of ethyl alcohol. They represent useful diagnostic tools for identifying alcohol use even more accurately than traditional biomarkers. Each of these drinking indicators remains positive in serum and urine for a characteristic time spectrum after the cessation of ethanol intake-EtG and EtS in urine up to 7 days, EtG in hair for months after ethanol has left the body. Applications include clinical routine use, emergency room settings, proof of abstinence in alcohol rehabilitation programs, driving under influence offenders, workplace testing, assessment of alcohol intake in the context of liver transplantation and fetal alcohol syndrome.

Comparing growth trajectories of risk behaviors from late adolescence through young adulthood: An accelerated design

Risk behaviors such as substance use or deviance are often limited to the early stages of the life course. Whereas the onset of risk behavior is well studied, less is currently known about the decline and timing of cessation of risk behaviors of different domains during young adulthood. Prevalence and longitudinal developmental patterning of alcohol use, drinking to the point of drunkenness, smoking, cannabis use, deviance, and HIV-related sexual risk behavior were compared in a Swiss community sample (N = 2,843). Using a longitudinal cohort-sequential approach to link multiple assessments with 3 waves of data for each individual, the studied period spanned the ages of 16 to 29 years. Although smoking had a higher prevalence, both smoking and drinking up to the point of drunkenness followed an inverted U-shaped curve. Alcohol consumption was also best described by a quadratic model, though largely stable at a high level through the late 20s. Sexual risk behavior increased slowly from age 16 to age 22 and then remained largely stable. In contrast, cannabis use and deviance linearly declined from age 16 to age 29. Young men were at higher risk for all behaviors than were young women, but apart from deviance, patterning over time was similar for both sexes. Results about the timing of increase and decline as well as differences between risk behaviors may inform tailored prevention programs during the transition from late adolescence to adulthood.

Smoking behaviour, former quit attempts and intention to quit in urban adolescents and young adults: A five-year longitudinal study

OBJECTIVES: To examine smoking behaviour, former quit attempts and intention to quit among Swiss adolescents and young adults over five year's time. STUDY DESIGN: five-year longitudinal study (2003, 2005 and 2008) based on a random urban community sample (N = 1345 complete cases). METHODS: Data were collected by computer-assisted telephone interviews with adolescents (16-17) and young adults (18-24). Main outcome measures included self-reported smoking behaviour, former quit attempts, smoking cessation methods and current intentions to quit smoking. RESULTS: Adolescents were more often non-smokers and less often daily smokers when compared to young adults at baseline (χ(2)(4) = 28.68, P < .001). Their smoking behaviour increased significantly from baseline to follow-up (T = 1445.50, r = .20, P < .001) in contrast to the stable smoking behaviour in young adults (χ(2)(2) = .12, n.s.). In longitudinal analyses young adults were also more stable in their smoking status at the later measurement points. In comparison adolescents changed their smoking status more often being non-smokers at baseline and smokers later on. Independently of the age group, the majority of smokers already had previously attempted to quit (65%) or intended to give up smoking at some point (72%). However only 17% were motivated to make the quit attempt within the next 6 months. Self-quitting was the preferred method, and 25% of the self-quitters had been successful. CONCLUSION: This study illustrates that different developments in smoking behaviour exist in adolescents and young adults. Our study reveals that a majority of smokers are willing to quit but often fail. Furthermore, the data indicates that for adolescents the focus should lie on primary prevention.

Overview of dermatologic problems following liver transplantation

Liver transplantation recipients, like other solid organ transplantation recipients, have an increased risk of dermatologic problems due to their long-term immunosuppression and benefit from pre-and post-transplantation screenings, and management by a dermatologist and dermatologic care should be integrated into the comprehensive, multidisciplinary care of liver transplantation recipients [1,2]. Cutaneous findings include aesthetic alterations, infections, precancerous lesions, and malignancies. The severity of skin alterations ranges from benign, unpleasant changes to life-threatening conditions [3-5]. In addition to skin cancer diagnosis and management, visits with a dermatologist serve to educate and improve the patient's sun-protection behavior. Among all solid organ transplantations, liver transplantation requires the least amount of immunosuppression, sometimes even permitting its complete cessation [6]. As a result, patients who have undergone liver transplantation tend to have fewer dermatologic complications compared with other solid organ transplantation recipients [7]. However, due to the large volume of the liver, patients undergoing liver transplantation receive more donor lymphocytes than kidney, heart, or lung transplantation recipients. Because of the immunosuppression, the transplanted lymphocytes proliferate and rarely trigger graft-versus-host-disease [8,9]. This topic will provide an overview of dermatologic disorders that may be seen following liver transplantation. A detailed discussion of skin cancer following solid organ transplantation and the general management of patients following liver transplantation are discussed separately. (See "Development of malignancy following solid organ transplantation" and "Management of skin cancer in solid organ transplant recipients" and "Long-term management of adult liver transplant recipients".)

Hybridization and adaptive radiation

Whether interspecific hybridization is important as a mechanism that generates biological diversity is a matter of controversy. Whereas some authors focus on the potential of hybridization as a source of genetic variation, functional novelty and new species, others argue against any important role, because reduced fitness would typically render hybrids an evolutionary dead end. By drawing on recent developments in the genetics and ecology of hybridization and on principles of ecological speciation theory, I develop a concept that reconciles these views and adds a new twist to this debate. Because hybridization is common when populations invade new environments and potentially elevates rates of response to selection, it predisposes colonizing populations to rapid adaptive diversification under disruptive or divergent selection. I discuss predictions and suggest tests of this hybrid swarm theory of adaptive radiation and review published molecular phylogenies of adaptive radiations in light of the theory. Some of the confusion about the role of hybridization in evolutionary diversification stems from the contradiction between a perceived necessity for cessation of gene flow to enable adaptive population differentiation on the one hand [1], and the potential of hybridization for generating adaptive variation, functional novelty and new species 2, 3 and 4 on the other. Much progress in the genetics 5, 6, 7, 8 and 9 and ecology of hybridization 9, 10 and 11, and in our understanding of the role of ecology in speciation (see Glossary) 12, 13 and 14 make a re-evaluation timely. Whereas botanists traditionally stressed the diversity-generating potential of hybridization 2, 3 and 14, zoologists traditionally saw it as a process that limits diversification [1] and refer to it mainly in the contexts of hybrid zones (Box 1) and reinforcement of reproductive isolation [15]. Judging by the wide distribution of allopolyploidy among plants, many plant species might be of direct hybrid origin or descended from a hybrid species in the recent past [16]. The ability to reproduce asexually might explain why allopolyploid hybrid species are more common in plants than in animals. Allopolyploidy arises when meiotic mismatch of parental chromosomes or karyotypes causes hybrid sterility. Mitotic error, duplicating the karyotype, can restore an asexually maintained hybrid line to fertility. Although bisexual allopolyploid hybrid species are not uncommon in fish [17] and frogs [18], the difficulty with which allopolyploid animals reproduce, typically requiring gynogenesis[19], makes establishment and survival of allopolyploid animal species difficult.

The auxin influx carrier is essential for correct leaf positioning

Auxin is of vital importance in virtually every aspect of plant growth and development, yet, even after almost a century of intense study, major gaps in our knowledge of its synthesis, distribution, perception, and signal transduction remain. One unique property of auxin is its polar transport, which in many well-documented cases is a critical part of its mode of action. Auxin is actively transported through the action of both influx and efflux carriers. Inhibition of polar transport by the efflux inhibitor N-1-naphthylphthalamic acid (NPA) causes a complete cessation of leaf initiation, a defect that can be reversed by local application of the auxin, indole-3-acetic acid (IAA), to the responsive zone of the shoot apical meristem. In this study, we address the role of the auxin influx carrier in the positioning and outgrowth of leaf primordia at the shoot apical meristem of tomato. By using a combination of transport inhibitors and synthetic auxins, we demonstrate that interference with auxin influx has little effect on organ formation as such, but prevents proper localization of leaf primordia. These results suggest the existence of functional auxin concentration gradients in the shoot apical meristem that are actively set up and maintained by the action of efflux and influx carriers. We propose a model in which efflux carriers control auxin delivery to the shoot apical meristem, whereas influx and efflux carriers regulate auxin distribution within the meristem.

Disease progression and recurrence in women treated for vulvovaginal intraepithelial neoplasia

OBJECTIVE The malignant potential of intraepithelial neoplasia of the vulva and vagina after treatment is not well defined. Our objective was to examine risk factors for recurrence and invasive disease. METHODS Four hundred sixty-four women with biopsy proven high-grade intraepithelial neoplasia of the vulva and vagina were identified in the electronic databases of four colposcopy clinics. Inclusion criteria were a follow-up of more than one year, no history of invasive cancer and no invasive cancer within the first year after initial treatment. We investigated the potential factors associated with recurrence and progression using a logistic regression analysis to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS Of the 411 eligible patients, 123 patients (29.9%) recurred later than one year after initial treatment and 24 patients (5.8%) progressed to invasive disease. According to multivariate analyses, the risk factors associated with recurrence were multifocality (OR, 3.33; 95% CI, 2.02 to 5.51), immunosuppression (OR, 2.51; 95% CI, 1.09 to 5.81), excision as initial treatment (vs. laser evaporation; OR, 1.79; 95% CI, 1.11 to 2.91) and smoking (OR, 1.61; 95% CI, 1.02 to 2.55). Risk factors for progression to invasive disease were immunosuppression (OR, 4.00; 95% CI, 1.30 to 12.25), multifocality (OR, 3.05; 95% CI, 1.25 to 7.43) and smoking (OR, 2.97; 95% CI, 1.16 to 7.60), but not treatment modality. CONCLUSION Laser evaporation combined with extensive biopsy is at least as efficacious as initial treatment of intraepithelial neoplasia with excision. Smoking is a risk factor for both recurrence and progression to invasive disease. Hence, smoking cessation should be advised and maintaining a long follow-up period due to late relapses is necessary.

Venous thrombo-embolism as a complication of cross-sex hormone treatment of male-to-female transsexual subjects: a review

Administration of cross-sex hormones to male-to-female transsexual subjects, usually oestrogens + often anti-androgens, such as cyproterone acetate, carries a risk of venous thromboembolism (VTE). VTE usually occurs in the first year of oestrogen administration. Ethinyl oestradiol, due to its chemical structure, was in 2003 identified as a major factor in the occurrence of VTE. Most clinics do not prescribe ethinyl oestradiol any longer, but people who take hormones without medical supervision use often oral contraceptives containing ethinyl oestradiol, many times in overdose. Cessation of use of ethinyl oestradiol and peri-operative thrombosis prophylaxis for surgery have reduced prevalence rate of VTE. Other oral oestrogens should not be overdosed, and transdermal oestrogen is to be preferred. Thrombosis prophylaxis for surgery is mandatory. It seems advisable to stop hormone use at least 2 weeks before major surgery, to be resumed only after 3 weeks following full mobilisation.

Assessment of smoking behaviour in a dental setting: a 1-year follow-up study using self-reported questionnaire data and exhaled carbon monoxide levels.

OBJECTIVES This study analyses the changes in smoking habits over the course of 1 year in a group of patients referred to an oral medicine unit. MATERIALS AND METHODS Smoking history and behaviour were analysed at baseline and after 1 year based on a self-reported questionnaire and on exhaled carbon monoxide levels [in parts per million (ppm)]. During the initial examination, all smokers underwent tobacco use prevention and cessation counselling. RESULTS Of the initial group of 121 patients, 98 were examined at the follow-up visit. At the baseline examination, 33 patients (33.67 %) indicated that they were current smokers. One year later, 14 patients (42.24 % out of the 33 smokers of the initial examination) indicated that they had attempted to stop smoking at least once over the follow-up period and 15.15 % (5 patients) had quit smoking. The mean number of cigarettes smoked per day by current smokers decreased from 13.10 to 12.18 (p = 0.04). The exhaled CO level measurements showed very good correlation with a Spearman's coefficient 0.9880 for the initial visit, and 0.9909 for the follow-up examination. For current smokers, the consumption of one additional cigarette per day elevated the CO measurements by 0.77 ppm (p < 0.0001) at the baseline examination and by 0.84 ppm (p < 0.0001) at the 1-year follow-up. CONCLUSIONS In oral health care, where smoking cessation is an important aspect of the treatment strategy, the measurement of exhaled carbon monoxide shows a very good correlation with a self-reported smoking habit. CLINICAL RELEVANCE Measurement of exhaled carbon monoxide is a non-invasive, simple and objective measurement technique for documenting and monitoring smoking cessation and reduction.

“Jo wunderbar so im apriu kann man nicht mehr erwarten, capisci?” Multilingualism in a German language class for retired Italian migrants in Berne

Our proposal presents some aspects and results of a project of the University of Bern dealing with the consequences of retirement on multilingual competences. Referring to De Bot (2007), who defined "language related major life events" as moments in life relevant for changes in multilingual competences, we assume that retirement can be a turning point in a language biography. Firstly, there are phenomena, such as the cessation of the use of a foreign language, which was formerly related to work. Secondly, retirement might elicit the improvement of foreign language skills as a way to spend excess time after retirement or as a “cognitive exercise”. Many language schools have identified the people of advanced age as a group of major interest and increasingly offer so-called 50+ (fifty plus) courses in their curriculum. Furthermore, the concept of lifelong learning is increasingly gaining importance, as the reference by the European commission (LLP) indicates. However, most of the programs are intended for educated middle-class people and there are considerably fewer offers for people who are less familiar with learning environments in general. The present paper aims at investigating the multilingual setting of an offer of the second kind: a German language course designed for retired, established Italian workforce migrants living in the city of Berne, Switzerland. The multilingual setting is given by the facts that migrants living in Berne are confronted with diglossia (Standard German and Swissgerman dialects), that the Canton of Berne is bilingual (German and French) and that the migrants' mother tongue, Italian, is one of the Swiss national languages. As previous studies have shown, most of the Italian migrants have difficulties with the acquisition of Standard German due to the diglossic situation (Werlen, 2007) or never even learnt any of the German varieties. Another outcome of the linguistic situation the migrants are confronted with in Berne, is the usage of a continuum of varieties between Swissgerman dialect and Standard German (Zanovello-Müller, 1998). Therefore, in the classroom we find several varieties of German, as well as the Italian language and its varieties. In the present paper we will investigate the use of multilingual competences within the classroom and the dynamics of second language acquisition in a setting of older adults (>60 years old), learning their host country’s language after 40 years or more of living in it. The methods applied are an ethnographic observation of the language class, combined with qualitative interviews to gain in-depth information of the subjects’ life stories and language biographies.

Volitional processes and daily smoking: Examining inter- and intraindividual associations around a quit attempt

The Health Action Process Approach (HAPA) assumes that volitional processes are important for effective behavioral change. However, intraindividual associations have not yet been tested in the context of smoking cessation. This study examined the inter- and intraindividual associations between volitional HAPA variables and daily smoking before and after a quit attempt. Overall, 100 smokers completed daily surveys on mobile phones from 10 days before until 21 days after a self-set quit date, including self-efficacy, action planning, action control, and numbers of cigarettes smoked. Negative associations between volitional variables and daily numbers of cigarettes smoked emerged at the inter- and intraindividual level. Except for interindividual action planning, associations were stronger after the quit date than before the quit date. Self-efficacy, planning and action control were identified as critical inter- and intraindividual processes in smoking cessation, particularly after a self-set quit attempt when actual behavior change is performed.

The impact of smoking on HPV infection and the development of anogenital warts

PURPOSE: The worldwide prevalence of human papillomavirus (HPV) infection is estimated at 9-13 %. Persistent infection can lead to the development of malignant and nonmalignant diseases. Low-risk HPV types are mostly associated with benign lesions such as anogenital warts. In the present systematic review, we examined the impact of smoking on HPV infection and the development of anogenital warts, respectively. METHODS: A systematic literature search was performed using MEDLINE database for peer-reviewed articles published from January 01, 1985 to November 30, 2013. Pooled rates of HPV prevalence were compared using the χ (2) test. RESULTS: In both genders, smoking is associated with higher incidence and prevalence rates for HPV infection, whereas the latter responds to a dose-effect relationship. The overall HPV prevalence for smoking patients was 48.2 versus 37. 5 % for nonsmoking patients (p < 0.001) (odds ratio (OR) = 1.5, 95 % confidence interval (CI) 1.4-1.7). Smoking does also increase persistence rates for high-risk HPV infection, while this correlation is debatable for low-risk HPV. The incidence and recurrence rates of anogenital warts are significantly increased in smokers. CONCLUSIONS: Most current data demonstrate an association between smoking, increased anogenital HPV infection, and development of anogenital warts. These data add to the long list of reasons for making smoking cessation a keystone of patient health.

Daily negative affect and smoking after a self-set quit attempt: The role of dyadic invisible social support in a daily diary study

Objectives Social support receipt from one's partner is assumed to be beneficial for successful smoking cessation. However, support receipt can have costs. Recent research suggests that the most effective support is unnoticed by the receiver (i.e., invisible). Therefore, this study examined the association between everyday levels of dyadic invisible emotional and instrumental support, daily negative affect, and daily smoking after a self-set quit attempt in smoker–non-smoker couples. Methods Overall, 100 smokers (72.0% men, mean age M = 40.48, SD = 9.82) and their non-smoking partners completed electronic diaries from a self-set quit date on for 22 consecutive days, reporting daily invisible emotional and instrumental social support, daily negative affect, and daily smoking. Results Same-day multilevel analyses showed that at the between-person level, higher individual mean levels of invisible emotional and instrumental support were associated with less daily negative affect. In contrast to our assumption, more receipt of invisible emotional and instrumental support was related to more daily cigarettes smoked. Conclusions The findings are in line with previous results, indicating invisible support to have beneficial relations with affect. However, results emphasize the need for further prospective daily diary approaches for understanding the dynamics of invisible support on smoking cessation.

Clinical importance of risk variants in the dihydropyrimidine dehydrogenase gene for the prediction of early-onset fluoropyrimidine toxicity.

We investigated the clinical relevance of dihydropyrimidine dehydrogenase gene (DPYD) variants to predict severe early-onset fluoropyrimidine (FP) toxicity, in particular of a recently discovered haplotype hapB3 and a linked deep intronic splice site mutation c.1129-5923C>G. Selected regions of DPYD were sequenced in prospectively collected germline DNA of 500 patients receiving FP-based chemotherapy. Associations of DPYD variants and haplotypes with hematologic, gastrointestinal, infectious, and dermatologic toxicity in therapy cycles 1-2 and resulting FP-dose interventions (dose reduction, therapy delay or cessation) were analyzed accounting for clinical and demographic covariates. Fifteen additional cases with toxicity-related therapy delay or cessation were retrospectively examined for risk variants. The association of c.1129-5923C>G/hapB3 (4.6% carrier frequency) with severe toxicity was replicated in an independent prospective cohort. Overall, c.1129-5923G/hapB3 carriers showed a relative risk of 3.74 (RR, 95% CI = 2.30-6.09, p = 2 × 10(-5)) for severe toxicity (grades 3-5). Of 31 risk variant carriers (c.1129-5923C>G/hapB3, c.1679T>G, c.1905+1G>A or c.2846A>T), 11 (all with c.1129-5923C>G/hapB3) experienced severe toxicity (15% of 72 cases, RR = 2.73, 95% CI = 1.61-4.63, p = 5 × 10(-6)), and 16 carriers (55%) required FP-dose interventions. Seven of the 15 (47%) retrospective cases carried a risk variant. The c.1129-5923C>G/hapB3 variant is a major contributor to severe early-onset FP toxicity in Caucasian patients. This variant may substantially improve the identification of patients at risk of FP toxicity compared to established DPYD risk variants (c.1905+1G>A, c.1679T>G and c.2846A>T). Pre-therapeutic DPYD testing may prevent 20-30% of life-threatening or lethal episodes of FP toxicity in Caucasian patients.

Management of patients during hunger strike and refeeding phase

OBJECTIVE Hunger strikers resuming nutritional intake may develop a life-threatening refeeding syndrome (RFS). Consequently, hunger strikers represent a core challenge for the medical staff. The objective of the study was to test the effectiveness and safety of evidence-based recommendations for prevention and management of RFS during the refeeding phase. METHODS This was a retrospective, observational data analysis of 37 consecutive, unselected cases of prisoners on a hunger strike during a 5-y period. The sample consisted of 37 cases representing 33 individual patients. RESULTS In seven cases (18.9%), the hunger strike was continued during the hospital stay, in 16 episodes (43.2%) cessation of the hunger strike occurred immediately after admission to the security ward, and in 14 episodes (37.9%) during hospital stay. In the refeed cases (n = 30), nutritional replenishment occurred orally, and in 25 (83.3%) micronutrients substitutions were made based on the recommendations. The gradual refeeding with fluid restriction occurred over 10 d. Uncomplicated dyselectrolytemia was documented in 12 cases (40%) within the refeeding phase. One case (3.3%) presented bilateral ankle edemas as a clinical manifestation of moderate RFS. Intensive medical treatment was not necessary and none of the patients died. Seven episodes of continued hunger strike were observed during the entire hospital stay without medical complications. CONCLUSIONS Our data suggested that seriousness and rate of medical complications during the refeeding phase can be kept at a minimum in a hunger strike population. This study supported use of recommendations to optimize risk management and to improve treatment quality and patient safety in this vulnerable population.