Varenicline decreases ethanol intake and increases dopamine release via neuronal nicotinic acetylcholine receptors in the nucleus accumbens

BACKGROUND AND PURPOSE Varenicline, a neuronal nicotinic acetylcholine receptor (nAChR) modulator, decreases ethanol consumption in rodents and humans. The proposed mechanism of action for varenicline to reduce ethanol consumption has been through modulation of dopamine (DA) release in the nucleus accumbens (NAc) via α4*-containing nAChRs in the ventral tegmental area (VTA). However, presynaptic nAChRs on dopaminergic terminals in the NAc have been shown to directly modulate dopaminergic signalling independently of neuronal activity from the VTA. In this study, we determined whether nAChRs in the NAc play a role in varenicline’s effects on ethanol consumption. EXPERIMENTAL APPROACH Rats were trained to consume ethanol using the intermittent-access two-bottle choice protocol for 10 weeks. Ethanol intake was measured after varenicline or vehicle was microinfused into the NAc (core, shell or core-shell border) or the VTA (anterior or posterior). The effect of varenicline treatment on DA release in the NAc was measured using both in vivo microdialysis and in vitro fast-scan cyclic voltammetry (FSCV). KEY RESULTS Microinfusion of varenicline into the NAc core and core-shell border, but not into the NAc shell or VTA, reduced ethanol intake following long-term ethanol consumption. During microdialysis, a significant enhancement in accumbal DA release occurred following systemic administration of varenicline and FSCV showed that varenicline also altered the evoked release of DA in the NAc. CONCLUSION AND IMPLICATIONS Following long-term ethanol consumption, varenicline in the NAc reduces ethanol intake, suggesting that presynaptic nAChRs in the NAc are important for mediating varenicline’s effects on ethanol consumption.

Rapid and highly efficient growth of graphene on copper by chemical vapor deposition of ethanol

The growth of graphene by chemical vapor deposition on metal foils is a promising technique to deliver large-area films with high electron mobility. Nowadays, the chemical vapor deposition of hydrocarbons on copper is the most investigated synthesis method, although many other carbon precursors and metal substrates are used too. Among these, ethanol is a safe and inexpensive precursor that seems to offer favorable synthesis kinetics. We explored the growth of graphene on copper from ethanol, focusing on processes of short duration (up to one min). We investigated the produced films by electron microscopy, Raman and X-ray photoemission spectroscopy. A graphene film with high crystalline quality was found to cover the entire copper catalyst substrate in just 20 s, making ethanol appear as a more efficient carbon feedstock than methane and other commonly used precursors.

A biomarker panel to discriminate between systemic inflammatory response syndrome and sepsis and sepsis severity

Introduction: In this study, we report on initial efforts to discover putative biomarkers for differential diagnosis of a systemic inflammatory response syndrome (SIRS) versus sepsis; and different stages of sepsis. In addition, we also investigated whether there are proteins that can discriminate between patients who survived sepsis from those who did not. Materials and Methods: Our study group consisted of 16 patients, of which 6 died and 10 survived. We daily measured 28 plasma proteins, for the whole stay of the patients in the ICU. Results: We observed that metalloproteinases and sE-selectin play a role in the distinction between SIRS and sepsis, and that IL-1, IP-10, sTNF-R2 and sFas appear to be indicative for the progression from sepsis to septic shock. A combined measurement of MMP-3, -10, IL-1, IP-10, sIL-2R, sFas, sTNF-R1, sRAGE, GM-CSF, IL-1 and Eotaxin allows for a good separation of patients that survived from those that died (mortality prediction with a sensitivity of 79% and specificity of 86%). Correlation analysis suggests a novel interaction between IL-1a and IP-10. Conclusion: The marker panel is ready to be verified in a validation study with or without therapeutic intervention.

Moderate physical activity level as a protective factor against metabolic syndrome in middle-aged and older women

Aims and objectives To investigate whether physical activity is a protective factor against metabolic syndrome in middle-aged and older women. Background Socio-demographic and lifestyle behaviour factors contribute to metabolic syndrome. To minimise the risk of metabolic syndrome, several global guidelines recommend increasing physical activity level. However, only limited research has investigated the relationship between physical activity levels and metabolic syndrome in middle-aged and older women after adjusting for socio-demographic and lifestyle behaviour factors. Design Cross-sectional design. Methods A convenience sample of 326 middle-aged and older women was recruited. Metabolic syndrome was confirmed according to the National Cholesterol Education Program, Adult Treatment Panel III guidelines, and physical activity levels were measured by the International Physical Activity Questionnaire. Results The sample had a mean age of 60•9 years, and the prevalence of metabolic syndrome was 43•3%. Postmenopausal women and women with low socioeconomic status (low-education background, without personal income and currently unemployed) had a significantly higher risk of developing metabolic syndrome. After adjusting for significant socio-demographic and lifestyle behaviour factors, the women with moderate or high physical activity levels had a significantly lower (OR = 0•10; OR = 0•11, p < 0•001) risk of metabolic syndrome and a lower risk for each specific component of metabolic syndrome, including elevated fasting plasma glucose (OR = 0•29; OR = 0•26, p = 0•009), elevated blood pressure (OR = 0•18; OR = 0•32, p = 0•029), elevated triglycerides (OR = 0•41; OR = 0•15, p = 0•001), reduced high-density lipoprotein (OR = 0•28; OR = 0•27, p = 0•004) and central obesity (OR = 0•31; OR = 0•22, p = 0•027). Conclusions After adjusting for socio-demographic and lifestyle behaviour factors, physical activity level was a significant protective factor against metabolic syndrome in middle-aged and older women. Higher physical activity levels (moderate or high physical activity level) reduced the risk of metabolic syndrome in middle-aged and older women. Relevance to clinical practice Appropriate strategies should be developed to encourage middle-aged and older women across different socio-demographic backgrounds to engage in moderate or high levels of physical activity to reduce the risk of metabolic syndrome.

The effect of the ecstasy 'come-down' on the diagnosis of ecstasy dependence

Background: The existence of an ecstasy dependence syndrome is controversial. We examined whether the acute after-effects of ecstasy use (i.e., the “come-down”) falsely lead to the identification of ecstasy withdrawal and the subsequent diagnosis of ecstasy dependence. Methods: The Structured Clinical Interview for DSM-IV-TR Disorders: Research Version (SCID-RV) was administered to 214 Australian ecstasy users. Ecstasy withdrawal was operationalized in three contrasting ways: (i) as per DSM-IV criteria; (ii) as the expected after effects of ecstasy (a regular come-down); or (iii) as a substantially greater or longer come-down than on first use (intense come-down). These definitions were validated against frequency of ecstasy use, readiness to change and ability to resist the urge to use ecstasy. Confirmatory factor analyses were used to see how they aligned with the overall dependence syndrome. Results: Come-down symptoms increased the prevalence of withdrawal from 1% (DSM-IV criterion) to 11% (intense come-downs) and 75% (regular come-downs). Past year ecstasy dependence remained at 31% when including the DSM-IV withdrawal criteria and was 32% with intense come-downs, but increased to 45% with regular come-downs. Intense come-downs were associated with lower ability to resist ecstasy use and loaded positively on the dependence syndrome. Regular come-downs did not load positively on the ecstasy dependence syndrome and were not related to other indices of dependence. Conclusion: The acute after-effects of ecstasy should be excluded when assessing ecstasy withdrawal as they can lead to a false diagnosis of ecstasy dependence. Worsening of the ecstasy come-down may be a marker for dependence.

Patient perspectives of using a web based intervention program for patients with type 2 diabetes and acute coronary syndrome

Introduction Research highlights patients with dual diagnoses of type 2 diabetes and acute coronary syndrome (ACS) have higher readmission rates and poorer health outcomes than patients with singular chronic conditions. Despite this, there is a lack of education programs targeted for this dual diagnosis population to improve self-management and decrease negative health outcomes. There is evidence to suggest that internet based interventions may improve health outcomes for patients with singular chronic conditions, however there is a need to develop an evidence base for ACS patients with comorbid diabetes. There is a growing awareness of the importance of a participatory model in developing effective online interventions. That is, internet interventions are more effective if end users’ perceptions of the intervention are incorporated in their final development prior to testing in large scale trials. Objectives This study investigated patients’ perspectives of the web-based intervention designed to promote self-management of the dual conditions in order to refine the intervention prior to clinical trial evaluation. Methods An interpretive approach with thematic analysis was used to obtain deeper understanding regarding participants’ experience when using web-application interventions for patients with ACS and type 2 diabetes. Semi-structured interviews were undertaken on a purposive sample of 30 patients meeting strict inclusion and exclusion criteria to obtain their perspectives on the program. Results Preliminary results indicate patients with dual diagnoses express more complex needs than those with a singular condition. Participants express a positive experience with the proposed internet intervention and emerging themes include that the web page is seen as easy to use and comforting as a support, in that patients know they are not alone. Further results will be reported as they become available. Conclusion The results indicate potential for patient acceptability of the newly developed internet intervention for patients with ACS and comorbid diabetes. Incorporation of patient perspectives into the final development of the intervention is likely to maximise successful outcomes of any future trials that utilise this intervention. Future quantitative evaluation of the effectiveness of the intervention is being planned.

Name-calling by a child diagnosed with asperger’s syndrome

Rendle-Short, Wilkinson, and Danby show how social interaction is directly relevant to maintaining friendships, mental health and well-being, and supportive peer relations. Using conversation analysis, the chapter focuses on conversational participants’ pursuit of affiliation and intimacy from a language as action perspective. It focuses on the use of derogatory naming practices by a 10-year-old girl diagnosed with Asperger’s Syndrome. The analysis shows how derogatory address terms, part of a wider pattern of behaviour evident in this child’s interaction, result in behaviour that might be thought of as impolite or lacking in restraint. It also illustrates how a single case study can draw attention to the context-specific nature of interaction when working with children with Asperger’s Syndrome. The chapter contributes to our understanding of the difficulty in pinpointing, with precision and with clear evidence, what counts as a ‘social interaction difficulty’ due to the context specific nature of interaction.

Inter-cycle variability of ignition delay in an ethanol fumigated common rail diesel engine

An experimental study has been performed to investigate the ignition delay of a modern heavy-duty common-rail diesel engine run with fumigated ethanol substitutions up to 40% on an energy basis. The ignition delay was determined through the use of statistical modelling in a Bayesian framework this framework allows for the accurate determination of the start of combustion from single consecutive cycles and does not require any differentiation of the in-cylinder pressure signal. At full load the ignition delay has been shown to decrease with increasing ethanol substitutions and evidence of combustion with high ethanol substitutions prior to diesel injection have also been shown experimentally and by modelling. Whereas, at half load increasing ethanol substitutions have increased the ignition delay. A threshold absolute air to fuel ratio (mole basis) of above ~110 for consistent operation has been determined from the inter-cycle variability of the ignition delay, a result that agrees well with previous research of other in-cylinder parameters and further highlights the correlation between the air to fuel ratio and inter-cycle variability. Numerical modelling to investigate the sensitivity of ethanol combustion has also been performed. It has been shown that ethanol combustion is sensitive to the initial air temperature around the feasible operating conditions of the engine. Moreover, a negative temperature coefficient region of approximately 900{1050 K (the approximate temperature at fuel injection) has been shown with for n-heptane and n-heptane/ethanol blends in the numerical modelling. A consequence of this is that the dominate effect influencing the ignition delay under increasing ethanol substitutions may rather be from an increase in chemical reactions and not from in-cylinder temperature. Further investigation revealed that the chemical reactions at low ethanol substitutions are different compared to the high (> 20%) ethanol substitutions.

Néstor-Guillermo Progeria Syndrome: a biochemical insight into Barrier-to-Autointegration Factor 1, alanine 12 threonine mutation

Background Premature aging syndromes recapitulate many aspects of natural aging and provide an insight into this phenomenon at a molecular and cellular level. The progeria syndromes appear to cause rapid aging through disruption of normal nuclear structure. Recently, a coding mutation (c.34G > A [p.A12T]) in the Barrier to Autointegration Factor 1 (BANF1) gene was identified as the genetic basis of Néstor-Guillermo Progeria syndrome (NGPS). This mutation was described to cause instability in the BANF1 protein, causing a disruption of the nuclear envelope structure. Results Here we demonstrate that the BANF1 A12T protein is indeed correctly folded, stable and that the observed phenotype, is likely due to the disruption of the DNA binding surface of the A12T mutant. We demonstrate, using biochemical assays, that the BANF1 A12T protein is impaired in its ability to bind DNA while its interaction with nuclear envelope proteins is unperturbed. Consistent with this, we demonstrate that ectopic expression of the mutant protein induces the NGPS cellular phenotype, while the protein localizes normally to the nuclear envelope. Conclusions Our study clarifies the role of the A12T mutation in NGPS patients, which will be of importance for understanding the development of the disease.

Using culture to manage the transition into university: Conceptualising the dynamics of withdrawal and engagement

This conceptual paper explored the purposes of using culture in the process of coping with stress by looking how first year undergraduate students used cultural elements and activities to aid their transition into university. Results supported two key conceptualisations of the use of culture. Firstly, results indicated that students used culture either for withdrawal purposes, i.e., for escaping from the stressful situation, or for engagement purposes, i.e., for actively engaging with the stressful situation. Secondly, the results suggested three different forms of using culture to engage with stressful situations: mood management, learning, and personal interaction. While the results of the study resonate with the distinction between avoidance versus approach-oriented coping strategies that are widely explored in the stress and coping literature, they also suggest that the relationship between withdrawal and engagement might be dynamic with those two strategies serving distinct purposes in the process of coping with stress. The paper thus suggests that there is a need to develop process-oriented models of coping that would allow identifying patterns in the way people fluctuate between withdrawal and engagement that support and facilitate their personal growth and development.

Ocular refractive and biometric characteristics in patients with tilted disc syndrome

BACKGROUND Tilted disc syndrome (TDS) is associated with characteristic ocular findings. The purpose of this study was to evaluate the ocular, refractive, and biometric characteristics in patients with TDS. METHODS This case-control study included 41 eyes of 25 patients who had established TDS and 40 eyes of 20 healthy control subjects. All participants underwent a complete ocular examination, including refraction and analysis using Fourier transformation, slit lamp biomicroscopy, pachymetry, keratometry, and ocular biometry. Corneal topography examinations were performed in the syndrome group only. RESULTS There were no significant differences in spherical equivalent (P = 0.13) and total astigmatism (P = 0.37) between groups. However, mean best spectacle-corrected visual acuity (Log Mar) was significantly worse in TDS patients (P = 0.003). The lenticular astigmatism was greater in the syndrome group, whereas the corneal component was greater in controls (P = 0.059 and P = 0.028, respectively). The measured biometric features were the same in both groups, except for the lens thickness and lens-axial length factor, which were greater in the TDS group (P = 0.007 and P = 0.055, respectively). CONCLUSIONS Clinically significant lenticular astigmatism, more oblique corneal astigmatism, and thicker lenses were characteristic findings in patients with TDS.

Ocular refractive and biometric characteristics in patients with tilted disc syndrome

Purpose: To evaluate the ocular refractive and biometric characteristics in patients with tilted disc syndrome (TDS). Methods: This case-control study comprised 41 eyes of 25 patients with established TDS and forty eyes of 20 age- and sex-matched healthy control subjects. All had a complete ocular examination including refraction and analysis using Fourier transformation, slit lamp biomicroscopy, pachymetry keratometry, and ocular biometry. Corneal topography examinations were performed in the syndrome group only. Results: There were no significant differences in spherical equivalent (p = 0.334) and total astigmatism (p= 0.246) between groups. However, mean best spectacular corrected visual acuity was significantly worse in TDS patients (P < 0.001). The lenticular astigmatism was significantly greater in the syndrome group, while the corneal component was greater in the controls (p = 0.004 and p = 0.002, respectively). The measured biometric features were the same in both groups, except for the lens thickness, relative lens position, and lens-axial length factor which were greater in the TDS group (p = 0.002, p = 0.015, and p = 0.025, respectively). Conclusions: Clinically significant lenticular astigmatism, more oblique corneal astigmatism, and thicker lens were characteristic findings in patients with TDS.

Anodized nanoporous WO3 Schottky contact structure for hydrogen and ethanol sensing

This paper reports the development of nanoporous tungsten trioxide (WO3) Schottky diode-based gas sensors. Nanoporous WO3 films were prepared by anodic oxidation of tungsten foil in ethylene glycol mixed with ammonium fluoride and a small amount of water. Anodization resulted in highly ordered WO3 films with a large surface-to-volume ratio. Utilizing these nanoporous structures, Schottky diode-based gas sensors were developed by depositing a platinum (Pt) catalytic contact and tested towards hydrogen gas and ethanol vapour. Analysis of the current–voltage characteristics and dynamic responses of the sensors indicated that these devices exhibited a larger voltage shift in the presence of hydrogen gas compared to ethanol vapour at an optimum operating temperature of 200 °C. The gas sensing mechanism was discussed, associating the response to the intercalating H+ species that are generated as a result of hydrogen and ethanol molecule breakdowns onto the Pt/WO3 contact and their spill over into nanoporous WO3.

Superior perilimbal epitheliopathy in recurrent corneal erosion syndrome

Purpose To highlight the finding of occult areas of poor epithelial adhesion in the superior perilimbal cornea in a minority of patients with recalcitrant recurrent corneal erosion syndrome presenting with corneal erosion elsewhere on the corneal surface. Patient population 31 eyes of 31 consecutive patients with corneal erosion undergoing mechanical debridement of the epithelium prior to diamond burr keratectomy for recurrent corneal erosion. Methods Determine the location and incidence of poor epithelial adhesion distant from the initial erosion by use of mechanical debridement with a dry microsponge. Results During debridement, 8 of 31 eyes (25.8%) displayed a large arcuate area of occult dysfunction of adhesion in the superior perilimbal area. None of these patients showed recurrence over a mean of 18 month after diamond burr keratectomy (95% confidence interval 0-36.9%). Conclusion Mechanical debridement with a microsponge identified a significant minority of patients with poor adhesion in the superior perilimbal cornea away from the area of obvious erosion and increased the target area for diamond burr keratectomy. This two pronged approach allowed successful management of this group.