bluuebunny/crossref_metadata_2025 huggingface dataset:
OP94 Evidence for the Effectiveness Ofopiate Substitution Treatment in Relation to HIV Transmission in People who Inject Drugs: A Systematic Review and Meta-Analysis
Authors: MacArthur GJ , Minozzi S , Martin N , Vickerman P , Bruneau J , Davoli M , Hickman M
Published: September 2012

Background

Injecting drug use is a major risk factor for the acquisition and transmission of HIV among people who inject drugs (PWID), and between PWID and the wider community. Worldwide there are an estimated 15.9 million PWID of whom 3 million may be HIV-positive. Methadone and buprenorphine (opiate substitution treatments, OST) reduce heroin use, injecting risk behaviour, and drug related mortality and are included in the World Health Organization list of essential medicines. A small number of individual cohort studies and a Cochrane narrative systematic review suggest that OST may reduce HIV incidence, but no pooled quantitative synthesis has been carried out. We have undertaken a systematic review and meta-analysis of published and unpublished studies to quantify the effect of OST on HIV transmission.

Methods

Medline, EMBASE and PsychINFO were searched to October 2011 to identify studies that examined the effectiveness of OST in relation to HIV transmission. Authors of prospective studies that assessed HIV incidence in PWID were contacted to obtain unpublished data.

Results

Fifteen studies conducted in seven countries were relevant for inclusion. Data from ten of the studies were pooled, two of which were unpublished. Analysis included over 22,000 person-years of follow-up and 738 incident HIV infections. Preliminary random effects meta-analysis demonstrates that OST reduces risk of HIV transmission among PWID by 49% (RR 0.51, 95% CI 0.37–0.71; p<0.001) although there was significant heterogeneity between studies (I259.5%, χ222.2, p=0.008). Study-level covariates including publication year, gender, median age, and ethnicity of participants did not significantly influence the impact of OST in meta-regression analyses. However, sub-group analysis demonstrated that whilst continuous OST significantly reduced risk of HIV infection, the effectiveness of interrupted or detoxification treatment was less clear (RR 1.26, 95% CI 0.77–2.07; p=0.360).

Conclusion

These preliminary data provide further evidence that OST can reduce the risk of HIV infection among PWID and for the first time quantify the effect. Ensuring sufficient coverage of OST as part of a package of harm reduction interventions is critical to reduce the burden of HIV among PWID and to prevent onward transmission between PWID and to the wider community.
PS02 “We Can all just Get on a bus and Go”: Rethinking Independent Mobility in the Context of the Universal Provision of Free Bus Travel to Young Londoners
Authors: Goodman A , Jones A , Roberts H , Steinbach R , Green J
Published: September 2012

Background

Recent years have seen increasing attention to ‘independent mobility’ as a determinant of children’s physical health and psychosocial development. Previous research, however, largely frames independent mobility as a matter of having parental permission to travel without adults. It also predominantly focuses upon walking any cycling trips in the local area by young children. We therefore aimed to extend the independent mobility literature by examining mobility on public transport, mobility beyond the local area and mobility by adolescents. For this we use as a case study the recent provision of universal free bus travel to all young people in London, UK. We argue that idea of independent mobility can usefully be situated within the broader conception of opportunity and process freedoms which underpin Amartya Sen’s influential ‘capabilities approach’ to human development.

Methods

As part of theOn the busesstudy, 118 young Londoners (age 12–18, 65 females) took part in 43 in-depth interviews (group size 1–3, 61 individuals) and 10 focus groups (group size 4–8, 57 individuals). Interviews and focus groups elucidated tacit, or everyday, influences on and effects of young people’s transport mode choices. We analysed this data qualitatively, drawing on techniques from the constant comparative method, including initial micro-level open coding and an iterative approach to identifying and refining emerging conceptual categories.

Results

Free bus travel enhanced young Londoners’ capability to shape their daily mobility, both directly by increasing financial access and indirectly by facilitating the acquisition of the necessary skills, travelling companions and confidence. These capabilities in turn extended both opportunity freedoms (e.g. facilitating non-“necessary” recreational and social trips) and process freedoms (e.g. feeling more independent by decreasing reliance on parents). Moreover, the universal nature of the entitlement often seemed crucial as it meant that free bus travel was typically held by all of a peer group. This rendered buses a socially inclusive way for groups to travel and spend time together, thereby enhancing group-level capabilities.

Conclusion

We believe this attention to individual and group-level capabilities for self-determination provides the basis for a broader and more child-centered view of independent mobility than is typical in health research. The importance of the universal nature of the entitlement to free bus travel also provides an example of how policy interventions with universal coverage may have effects which are more than the ‘sum of the parts’ of alternative, targeted approaches.
PS05 Men With Prostate Cancer Make Positive Dietary Changes Following Treatment in a Randomised Trial: A Prospective Cohort Study
Authors: Avery KNL , Donovan JL , Gilbert R , Davis M , Emmett P , Down E , Oliver S , Neal DE , Hamdy FC , Lane JA
Published: September 2012

Background

Prostate cancer (PC) is the second most frequently diagnosed cancer of men worldwide. A healthy diet may improve clinical outcomes but there is currently no disease-specific dietary advice available to aid survivorship after a PC diagnosis. The effect of a PC diagnosis on men’s diet remains uncertain because, although cancer survivors report dietary changes, the direction and magnitude of changes are poorly understood. This study examined dietary changes in men before and after treatment for PC within the Prostate Testing for Cancer and Treatment (ProtecT) randomised trial.

Methods

This was a prospective cohort study embedded within the ProtecT randomised trial of treatments for PC. Participants were men aged 50–69 years tested for PC in primary care centres in nine areas of the UK. 3935 men completed a validated food frequency questionnaire before diagnosis and 678 with localised disease repeated the questionnaire one year later (response 82.7%). Pre-diagnosis dietary intakes of men with different diagnoses subsequently (negative diagnosis, at risk, localised PC, advanced PC) were compared using linear regression. Dietary changes after a diagnosis of localised PC were examined using non-parametric tests. Effects of cancer treatments (radical prostatectomy, conformal external beam radiotherapy or active monitoring) were examined using linear regression.

Results

Before diagnosis, all men consumed largely similar amounts of key nutrients and foods. The diagnosis of localised PC led to dietary changes in 29.2% of men. Changes observed were generally in a healthy direction, with 234 (34.7%) men eating more fresh tomatoes (p<0.0001) and 156 (23.5%) more tomato products (p=0.01). 271 (40.0%) men consumed more protein (p<0.0001) and 193 (28.6%) more fruit/vegetable juice (p<0.0001). Less macronutrients were obtained from dairy products (p<0.01). Men undergoing active monitoring (regular assessment of disease status) drank more fruit/vegetable juice than men who had received surgery (p=0.004).

Conclusion

Diagnosis of localised PC prompted around one third of men to adopt healthier diets and eat more ‘prostate-healthy’ foods. Dietary choices were influenced by treatment received, with more interest in dietary factors for survivorship in men undergoing active monitoring than those undergoing radical treatment. PC survivors are motivated to improve their diet and are able to access and act on healthy eating advice. Diagnosis of PC may serve as a “teachable moment”, thereby providing opportunities for clinicians to provide targeted advice that could be beneficial to general (and prostate-specific) health and to support survivorship.
PS06 Finding the Missing Units: Identifying Under-Reporting of Alcohol Consumption in England
Authors: Boniface S
Published: September 2012

Background

Alcohol sales coverage (reported consumption as a percentage of total sales) is typically 40–60%. This study explores how accidental under-estimation of alcohol in drinks poured at home might contribute to low sales coverage.

Methods

283 drinking adults (16+) completed a face-to-face survey comprising a questionnaire and pouring task on 12 occasions at six sites in and near London in summer 2011. Actual and perceived number of units poured in a ‘usual glass’ of wines and spirits is explored by demographic and social factors.

Results

There were 283 participants (54% women) who completed the questionnaire and pouring task. The 283 participants poured a total of 465 glasses of wine and spirits. 52% wine estimates and 42% spirit estimates were within 0.5 units of their actual value. More participants over-estimated the amount of alcohol they had poured than under-estimated. Multinomial logistic regression found significant risk factors for under-estimating wine were increasing volume of wine poured (RRR 1.02 95% CI 1.01–1.02, P<0.0001), belonging to a non-white ethnicity (RRR 3.88, 1.65–9.16, P=0.002), and being unemployed or retired (RRR 4.30, 1.08–17.07, P=0.038). Only the volume of spirits poured was a significant predictor of under-estimating spirits (RRR 1.04, 1.01–1.06, P=0.003). For both wines and spirits, not having a degree was significantly associated with an increased risk ofover-estimating the amount of alcohol poured.

Conclusion

As participants were more likely to over-estimate than under-estimate, this survey is not able to explain low sales coverage as a product of accidental under-estimation of the amount of alcohol poured drinks drunk at home. A future qualitative study will explore how recall accuracy may contribute to low sales coverage.
PS08 Is there a Protective Effect of High Mineral Content in Drinking Water on Coronary Heart Disease Mortality? A Cross-Sectional Ecological Study of a Large Population in Central England
Authors: Rudge GM , Mohammed MA
Published: September 2012

Background

It has been hypothesised that dissolved minerals in water, particularly calcium carbonate and magnesium carbonate, are protective against heart disease. Animal studies suggest biologically plausible mechanisms for this and statistically significant effects have been presented from several large ecological studies.

Setting

The West Midlands Government Office Region in central England, has a large and diverse population which has great variation in water hardness over a relatively small area. Our units of analysis were West Midlands neighbourhoods (lower level super output areas) falling in areas supplied by two water companies. We obtained exposure estimates from water industry measurements taken in 2007.

Methods

Using geographical information system software, digitised supply water supply maps were mapped to our neighbourhood geography. Having established the distribution of water hardness through neighbourhoods, we mapped tertiles of hardness and identified neighbourhoods inside them. To these we linked emergency myocardial infarction (MI) admissions for 45–74 year-old residents for a three year period, adjusting for the age distribution of the neighbourhoods, ethnic mix and socio-economic deprivation. We used a negative binomial model to determine the degree of association between water hardness and MI admission counts, adjusting for the other variables.

Results

We were able to accurately determine the mineral content of water supplied to 2,925 neighbourhoods with a total population of over 4.5 million. Contrary to other studies, we found just a small but non-significant negative correlation between hardness and MI admissions were seen in men, with an incidence rate ratio (IRR) of 0.97, per tertile, (0.92 – 1.03, p=0.37) and a small, non-significant positive one seen in women, IRR=1.02, (0.93 – 1.12, p=2).

Conclusion

We found no evidence of a protective effect of hard water against acute MI admission, contrary to other published studies. This may be because our methods allowed us to better account for possible confounding variables. We go on to hypothesise that as water supply networks developed historically, with soft water from upland areas being used supply the needs of rapidly industrialising areas and other areas left to use local groundwater, some interesting accidental correlations between neighbourhood socio-economic status and water hardness arose which may have confounded previous work. However, mass differential exposure to highly bio-available minerals, especially calcium and magnesium, does raise some interesting further questions about the relationship between water supply and population health, which our methods can be used to investigate further.
PS26 Prevalence and Associations of Limited Health Literacy in Chronic Kidney Disease: A Systematic Review
Authors: Fraser SDS , Roderick PJ , Casey M , Taal MW , Yuen HM , Nutbeam D
Published: September 2012

Background

Chronic kidney disease (CKD) is a prevalent and growing problem, strongly associated with obesity, diabetes, hypertension, and cardiovascular disease. Health inequalities are recognised throughout the CKD pathway, including prevalence of risk factors, prevalence of CKD, progression, and renal replacement therapy. There is evidence that an adequate level of health literacy (defined as ‘the cognitive and social skills which determine the motivation and ability of individuals to gain access to, understand, and use information in ways that promote and maintain good health’) contributes to improved disease management, and that inadequate health literacy is a potentially modifiable determinant of poor health outcomes and health inequalities in people with chronic disease. The aim of this review was to synthesise and critically appraise the literature evidence on the prevalence and associations of limited health literacy in CKD.

Methods

Seven databases were searched using terms for CKD and health literacy (HL). Cross sectional studies, and baseline data from cohort and randomised controlled trials were included where they assessed and presented the prevalence of limited HL using a validated tool in adults with CKD of any stage. The primary outcome was an objectively measured prevalence of limited HL in a population with CKD. The secondary outcome was associations of limited HL. Study quality was assessed by two reviewers using standardised criteria. Prevalence values were combined using a random effect model to give overall prevalence.

Results

82 studies were identified from searching, of which six met the inclusion criteria. The total number of people with CKD in all studies was 1,405. Five studies were in dialysis or transplant populations, and all were from the US. There was significant heterogeneity in the prevalence of limited HL (9% to 32% (median 25%, inter-quartile range 16%)). The pooled prevalence of limited HL in all studies was 22.7% (95% CI 20.6%, 24.8%). The review identified associations between limited HL and socioeconomic factors (lower education attainment, lower income), and certain process and outcome measures (lower likelihood of referral for transplant, higher mortality). Overall study quality was poor, with particular weaknesses of sampling and non-response.

Conclusion

Limited health literacy is common among people with CKD and independently associated with socioeconomic factors and health outcomes. It may represent an important determinant of inequality of outcomes in CKD. There is a need for further investigation of limited health literacy in people with pre-end stage CKD, and in UK CKD populations.
PS35 The Role of Time Preference in Smoking Cessation: A Longitudinal Analysis of Data from the Household Income and Labour Dynamics of Australia Survey, 2001-08
Authors: Adams J , Brown H
Published: September 2012

Background

‘Time preference’ is an economic concept that describes the trade-offs that individuals make between costs and benefits occurring at different points of time. Related psychological concepts include time perspective, impulsivity and delay of gratification. Present orientated people prefer immediate over future gains and place more value on these. Differences in how much value different individuals place on future outcomes are likely to play some role in present day behavioural decisions.

There is substantial cross-sectional evidence that smokers tend to have shorter term time preferences than non-smokers. However, few studies have explored the longitudinal relationship between time preference and smoking cessation.

We explored the relationship between time preference and smoking cessation in a general adult cohort using data from a large Australian longitudinal panel study: the Household Income and Labour Dynamics of Australia (HILDA) survey.

Methods

HILDA is a longitudinal, nationally representative, household survey which began in 2001. The focus of the survey is on economic and subjective well-being, and labour market and family dynamics. Data is collected by annual interview and self-complete questionnaire.

Members of the HILDA panel, aged 15–64, who responded to at least four waves of data collection between 2001 and 2008, and reported any level of tobacco consumption at any wave were included in the analyses.

Smoking cessation was measured using self-report questions. Time preference was measured using self-reported time period for financial planning. A range of sociodemographic (age, number of children, various markers of socio-economic position) and smoking-related (previous quit attempts, years smoked) co-variates were controlled for.

Results

1,817 individuals (representing 7,913 unique observations) were included in the analyses. In univariable analyses, both men and women who reported quitting smoking were more likely to have a longer term time preference in the data collection period immediately prior to quitting than those who did not quit (men: t(4,126)=4.59, p<0.001; women: t(3,783)=7.18, p<0.001). These relationships persisted after control for socio-demographic and smoking-related covariates (hazard ratio of quitting in those with longer vs shorter term time preference (95% confidence intervals) = 1.27 (1.03 – 1.57) in men; 1.31 (1.05 – 1.63) in women).

Conclusion

Adult smokers with a longer term time preference are more likely to quit smoking. This does not exclude the possibility that quitting smoking simultaneously leads to development of longer term time preference. Interventions that encourage development of longer term time preference may enable smoking cessation.
PS40 Profiles of Polydrug Use at a Local and a National Level: Risk Factors and Associations with Mental Health and Functioning
Authors: Clark JL , Frissa S , Hatch S , Hotopf M
Published: September 2012

Background

Polydrug use is an understudied phenomenon with potential implications for individual functioning and health. Its frequency within the general public and its individual costs thus need to be documented. This study’s aims were to compare the types of polydrug users in the general public at a national and a local level, and to examine how risk factors and impairments differed between them.

Methods

Using comparable datasets from a local community in South East London during 2008–2010 (n=1,698) and from England in 2007 (n=7,403), latent class analysis was used to construct profiles of polydrug users. Eight binary indices reporting drug use in the last year for cannabis, amphetamine, cocaine, ecstasy, LSD, tranquilisers, crack, heroin, and two items for hazardous alcohol drinking and current cigarette smoking, were regressed on a latent variable of polydrug use with age and sex covariates. The latent class solution from each dataset was then used in a multinomial logistic regression comparing risk factors from socio-demographic, neighbourhood, social support, and mental health domains.

Results

Both datasets produced three class solutions with comparable proportions: in London, 61.6% were in the “Nondrug user” group, 30.5% in the “Moderate user group” (characterised by hazardous drinking, cigarettes and some cannabis use) and 7.9% in the “High Drug User” group (characterised by drug use across all substances); in the national dataset the proportions were 57.4%, 37.9 %, and 4.6% respectively. In a logistic regression comparing both polydrug user groups to the nonuser group, both samples reported higher odds for polydrug use and common mental disorder, suicidal ideation, and functional limitation; higher levels of education, stressful life events and a never-married status were also associated with polydrug use. Differences between the local and national samples for polydrug use were found on factors such as ethnicity, social support, and employment status. Further analysis revealed no difference between the “Moderate” and “High Drug” groups in the local sample for these risk factors and mental health indicators, whereas several dose-response relationships between these groups were found nationally.

Conclusion

Approximately a third of the general public both nationally and locally exhibit a pattern of moderate polydrug use associated with mental health and daily functioning impairments. Furthermore, local services and policy makers should note that higher education is a risk factor for polydrug use, and that factors related to employment and social support may be differentially linked to substance use depending on geographical residence.
Impact of operator and site experience on outcomes after angioplasty and stenting in the SAMMPRIS trial
Authors: Derdeyn Colin P , Fiorella David , Lynn Michael J , Barnwell Stanley L , Zaidat Osama O , Meyers Philip M , Gobin Y Pierre , Dion Jacques , Lane Bethany F , Turan Tanya N , Janis L Scott , Chimowitz Marc I ,   for the SAMMPRIS Trial Investigators
Published: September 2012

Background and purpose

To investigate the relationship between physician and site experience and the risk of 30 day hemorrhagic and ischemic strokes in the stenting arm of the Stenting and Aggressive Medical Management for the Prevention of Recurrent Ischemic Stroke (SAMMPRIS) trial.

Methods

Study records and an investigator survey were examined for physician and site related factors, including: number of Wingspan and aneurysm stents submitted for credentialing, number of study procedures performed in SAMMPRIS, years in practice after training, primary specialty, and site enrollment. Bivariate and multivariate analyses were performed to determine if these factors were associated with the 30 day rate of cerebrovascular events after angioplasty and stenting.

Results

213 patients underwent angioplasty alone (n=5) or angioplasty and stenting (n=208) with study devices by 63 interventionists at 48 sites. For credentialing, the median number of Wingspan and similar aneurysm stent cases submitted by study interventionists were 10 and 6, respectively. Interventionists with higher numbers (>10) of Wingspan cases submitted for credentialing tended to have higher rates of 30 day events (19.0% vs 9.9%) than those with <10 cases. High enrolling sites in the trial tended to have lower rates of hemorrhagic stroke (9.8% at sites enrolling <12 patients vs 2.7% at sites enrolling>12 patients).

Conclusions

Interventionists credentialed with less Wingspan experience were not responsible for the high rate of periprocedural stroke in SAMMPRIS. Hemorrhagic stroke may be related to low enrollment in the trial but not previous Wingspan experience.
PRIME NUMBERS, QUANTUM FIELD THEORY AND THE GOLDBACH CONJECTURE
Authors: SANCHIS-LOZANO MIGUEL-ANGEL , BARBERO G. J. FERNANDO , NAVARRO-SALAS JOSÉ
Published: September 2012

Motivated by the Goldbach conjecture in number theory and the Abelian bosonization mechanism on a cylindrical two-dimensional space–time, we study the reconstruction of a real scalar field as a product of two real fermion (so-called prime) fields whose Fourier expansion exclusively contains prime modes. We undertake the canonical quantization of such prime fields and construct the corresponding Fock space by introducing creation operators [Formula: see text] — labeled by prime numbers p — acting on the vacuum. The analysis of our model, based on the standard rules of quantum field theory and the assumption of the Riemann hypothesis, allows us to prove that the theory is not renormalizable. We also comment on the potential consequences of this result concerning the validity or breakdown of the Goldbach conjecture for large integer numbers.
UNDERSTANDING LORENTZ VIOLATION WITH RASHBA INTERACTION
Authors: AJAIB MUHAMMAD ADEEL
Published: September 2012

Rashba spin–orbit interaction is a well-studied effect in condensed matter physics and has important applications in spintronics. The standard model extension (SME) includes a CPT-even term with the coefficient Hμν, which leads to the Rashba interaction term. From the limit available on the coefficient Hμν in the SME we derive a limit on the Rashba coupling constant for Lorentz violation. In condensed matter physics the Rashba term is understood as resulting from an asymmetry in the confining potential at the interface of two different types of semiconductors. Based on this interpretation we suggest that a possible way of inducing the Hμν term in the SME is with an asymmetry in the potential that confines us to three spatial dimensions.
LINEAR-TIME 3-APPROXIMATION ALGORITHM FOR THE r-STAR COVERING PROBLEM
Authors: LINGAS ANDRZEJ , WASYLEWICZ AGNIESZKA , ŻYLIŃSKI PAWEŁ
Published: September 2012

The complexity status of the minimum r-star cover problem for orthogonal polygons had been open for many years, until 2004 when Ch. Worman and J. M. Keil proved it to be polynomially tractable (Polygon decomposition and the orthogonal art gallery problem, IJCGA 17(2) (2007), 105-138). However, since their algorithm has Õ(n17)-time complexity, where Õ(·) hides a polylogarithmic factor, and thus it is not practical, in this paper we present a linear-time 3-approximation algorithm. Our approach is based upon the novel partition of an orthogonal polygon into so-called o-star-shaped orthogonal polygons.
Alterations in sleep architecture in response to experimental sleep curtailment are associated with signs of positive energy balance
Authors: Shechter Ari , O'Keeffe Majella , Roberts Amy L. , Zammit Gary K. , RoyChoudhury Arindam , St-Onge Marie-Pierre
Published: September 2012

Sleep reduction is associated with increased energy intake and weight gain, though few studies have explored the relationship between sleep architecture and energy balance measures in the context of experimental sleep restriction. Fourteen males and 13 females (body mass index: 22–26 kg/m2) participated in a crossover sleep curtailment study. Participants were studied under two sleep conditions: short (4 h/night; 0100–0500 h) and habitual (9 h/night; 2200–0700 h), for 5 nights each. Sleep was polysomnographically recorded nightly. Outcome measures included resting metabolic rate (RMR), feelings of appetite-satiety, and ad libitum food intake. Short sleep resulted in reductions in stage 2 sleep and rapid eye movement (REM) sleep duration ( P < 0.001), as well as decreased percentage of stage 2 sleep and REM sleep and increased slow wave sleep (SWS) percentage ( P < 0.05). Linear mixed model analysis demonstrated a positive association between stage 2 sleep duration and RMR ( P = 0.051). Inverse associations were observed between REM sleep duration and hunger ( P = 0.031) and between stage 2 sleep duration and appetite for sweet ( P = 0.015) and salty ( P = 0.046) foods. Stage 2 sleep percentage was inversely related to energy consumed ( P = 0.024). Stage 2 sleep ( P = 0.005), SWS ( P = 0.008), and REM sleep ( P = 0.048) percentages were inversely related to fat intake, and SWS ( P = 0.040) and REM sleep ( P = 0.050) were inversely related to carbohydrate intake. This study demonstrates that changes in sleep architecture are associated with markers of positive energy balance and indicate a means by which exposure to short sleep duration and/or an altered sleep architecture profile may lead to excess weight gain over time.
Isolated duodenal exclusion increases energy expenditure and improves glucose homeostasis in diet-induced obese rats
Authors: Muñoz Rodrigo , Carmody Jill S. , Stylopoulos Nicholas , Davis Philip , Kaplan Lee M.
Published: September 2012

Roux-en-Y gastric bypass (RYGB) in rodent models reduces food intake (FI), increases resting energy expenditure (EE), and improves glycemic control. We have shown that mimicking the duodenal component of RYGB by implantation of a 10-cm endoluminal sleeve device (ELS-10) induces weight loss and improves glycemic control in diet-induced obese (DIO) rats. We sought to determine the mechanisms and structural requirements of these effects. We examined the effects of ELS-10 devices implanted in male DIO rats on body weight, food intake (FI), meal patterns, total and resting EE, and multiple parameters of glucose homeostasis, comparing them with sham-operated (SO) rats and with SO rats weight matched to the ELS-10-treated group. To determine the extent of duodenal exclusion required to influence metabolic outcomes, we compared the effects of implanting 10-, 4-, or 1-cm ELS devices. ELS-10 rats exhibited 13% higher total and 9% higher resting EE than SO controls. ELS-10 rats also exhibited enhanced postprandial GLP-1 secretion and improved glucose tolerance and insulin sensitivity out of proportion to the effects of weight loss alone. Implantation of 4- or 1-cm ELS devices had no effect on EE and limited effects on glucose homeostasis. Complete duodenal exclusion with ELS-10 induces weight loss by decreasing FI and increasing EE and improves glycemic control through weight loss-independent mechanisms. Thus signals originating in the proximal small intestine appear to exert a direct influence on the physiological regulation of EE and glucose homeostasis. Their selective manipulation could provide effective new therapies for obesity and diabetes that mimic the benefits of RYGB.
Modulation of vH+-ATPase is part of the functional adaptation of sheep rumen epithelium to high-energy diet
Authors: Kuzinski Judith , Zitnan Rudolf , Albrecht Elke , Viergutz Torsten , Schweigel-Röntgen Monika
Published: September 2012

Ruminal vacuolar H+-ATPase (vH+-ATPase) activity is regulated by metabolic signals. Thus, we tested whether its localization, expression, and activity were changed by different feeding. Young male sheep ( n = 12) were either fed hay ad libitum (h) or hay ad libitum plus additional concentrate (h/c) for 2 wk. The vH+-ATPase B subunit signal was predominantly found in the cell membrane and cytosol of rumen epithelial cells (REC) with basal/parabasal phenotype. The elevated number (threefold) of these cells in rumen mucosa of h/c-fed sheep reflects a high proliferative capacity and, explains the 2.3-fold increase of the total number of vH+-ATPase-expressing REC. However, in accordance with a 58% reduction of the vH+-ATPase B subunit mRNA expression in h/c-fed sheep, its protein amount per single REC was decreased. Using the fluorescent probe BCECF and selective inhibitors (foliomycin, amiloride), the contribution of vH+-ATPase and Na+/H+exchanger to intracellular pH (pHi) regulation was investigated. REC isolated from h/c-fed sheep keep their pHiat a significantly higher level (6.91 ± 0.03 vs. 6.74 ± 0.05 in h-fed sheep). Foliomycin or amiloride decreased pHiby 0.16 ± 0.02 and 0.57 ± 0.04 pH units when applied to REC from h-fed sheep, but the effects were markedly reduced (−88 and −33%) after concentrate feeding. Nevertheless, we found that REC proliferation rate and [cAMP]iwere reduced after foliomycin-induced vH+-ATPase inhibition. Our results provide the first evidence for a role of vH+-ATPase in regulation of REC proliferation, most probably by linking metabolically induced pHichanges to signaling pathways regulating this process.
Intrinsic proinflammatory signaling in podocytes contributes to podocyte damage and prolonged proteinuria
Authors: Brähler Sebastian , Ising Christina , Hagmann Henning , Rasmus Melanie , Hoehne Martin , Kurschat Christine , Kisner Tuelay , Goebel Heike , Shankland Stuart , Addicks Klaus , Thaiss Friedrich , Schermer Bernhard , Pasparakis Manolis , Benzing Thomas , Brinkkoetter Paul Thomas
Published: September 2012

Inflammation conveys the development of glomerular injury and is a major cause of progressive kidney disease. NF-κB signaling is among the most important regulators of proinflammatory signaling. Its role in podocytes, the epithelial cells at the kidney filtration barrier, is poorly understood. Here, we inhibited NF-κB signaling in podocytes by specific ablation of the NF-κB essential modulator (NEMO, IKKγ). Podocyte-specific NEMO-deficient mice (NEMOpko) were viable and did not show proteinuria or overt changes in kidney morphology. After induction of glomerulonephritis, both NEMOpkoand control mice developed significant proteinuria. However, NEMOpkomice recovered much faster, showing rapid remission of proteinuria and restoration of podocyte morphology. Interestingly, quantification of infiltrating macrophages, T-lymphocytes, and granulocytes at day 7 revealed no significant difference between wild-type and NEMOpko. To further investigate the underlying mechanisms, we created a stable NEMO knockdown mouse podocyte cell line. Again, no overt changes in morphology were observed. Translocation of NF-κB to the nucleus after stimulation with TNFα or IL-1 was sufficiently inhibited. Moreover, secretion of proinflammatory chemokines from podocytes after stimulation with TNFα or IL-1 was significantly reduced in NEMO-deficient podocytes and in glomerular samples obtained at day 7 after induction of nephrotoxic nephritis. Collectively, these results show that proinflammatory activity of NF-κB in podocytes aggravates proteinuria in experimental glomerulonephritis in mice. Based on these data, it may be speculated that immunosuppressive drugs may not only target professional immune cells but also podocytes directly to convey their beneficial effects in various types of glomerulonephritis.
Effects of ankle extensor muscle afferent inputs on hip abductor and adductor activity in the decerebrate walking cat
Authors: Bolton D. A. E. , Misiaszek J. E.
Published: September 2012

Electrical stimulation of the lateral gastrocnemius-soleus (LGS) nerve at group I afferent strength leads to adaptations in the amplitude and timing of extensor muscle activity during walking in the decerebrate cat. Such afferent feedback in the stance leg might result from a delay in stance onset of the opposite leg. Concomitant adaptations in hip abductor and adductor activity would then be expected to maintain lateral stability and balance until the opposite leg is able to support the body. As many hip abductors and adductors are also hip extensors, we hypothesized that stimulation of the LGS nerve at group I afferent strength would produce increased activation and prolonged burst duration in hip abductor and adductor muscles in the premammillary decerebrate walking cat. LGS nerve stimulation during the extensor phase of the locomotor cycle consistently increased burst amplitude of the gluteus medius and adductor femoris muscles, but not pectineus or gracilis. In addition, LGS stimulation prolonged the burst duration of both gluteus medius and adductor femoris. Unexpectedly, long-duration LGS stimulus trains resulted in two distinct outcomes on the hip abductor and adductor bursting pattern: 1) a change of burst duration and timing similar to medial gastrocnemius; or 2) to continue rhythmically bursting uninterrupted. These results indicate that activation of muscle afferents from ankle extensors contributes to the regulation of activity of some hip abductor and adductor muscles, but not all. These results have implications for understanding the neural control of stability during locomotion, as well as the organization of spinal locomotor networks.
Can proprioceptive training improve motor learning?
Authors: Wong Jeremy D. , Kistemaker Dinant A. , Chin Alvin , Gribble Paul L.
Published: September 2012

Recent work has investigated the link between motor learning and sensory function in arm movement control. A number of findings are consistent with the idea that motor learning is associated with systematic changes to proprioception (Haith A, Jackson C, Mial R, Vijayakumar S. Adv Neural Inf Process Syst 21: 593–600, 2008; Ostry DJ, Darainy M, Mattar AA, Wong J, Gribble PL. J Neurosci 30: 5384–5393, 2010; Vahdat S, Darainy M, Milner TE, Ostry DJ. J Neurosci 31: 16907–16915, 2011). Here, we tested whether motor learning could be improved by providing subjects with proprioceptive training on a desired hand trajectory. Subjects were instructed to reproduce both the time-varying position and velocity of novel, complex hand trajectories. Subjects underwent 3 days of training with 90 movement trials per day. Active movement trials were interleaved with demonstration trials. For control subjects, these interleaved demonstration trials consisted of visual demonstration alone. A second group of subjects received visual and proprioceptive demonstration simultaneously; this group was presented with the same visual stimulus, but, in addition, their limb was moved through the target trajectory by a robot using servo control. Subjects who experienced the additional proprioceptive demonstration of the desired trajectory showed greater improvements during training movements than control subjects who only received visual information. This benefit of adding proprioceptive training was seen in both movement speed and position error. Interestingly, additional control subjects who received proprioceptive guidance while actively moving their arm during demonstration trials did not show the same improvement in positional accuracy. These findings support the idea that the addition of proprioceptive training can augment motor learning, and that this benefit is greatest when the subject passively experiences the goal movement.
Optical illusion alters M1 excitability after mirror therapy: a TMS study
Authors: Läppchen C. H. , Ringer T. , Blessin J. , Seidel G. , Grieshammer S. , Lange R. , Hamzei F.
Published: September 2012

The contralesional primary motor cortex (M1) has been suggested to be involved in the motor recovery after mirror therapy, but whether the ipsilesional M1 is influenced by the contralesional M1 via transcallosal interhemispheric inhibition (IHI) is still unclear. The present study investigated the change of IHI as well as the intracortical inhibition and intracortical facilitation of both M1 induced by training in a mirror with the use of transcranial magnetic stimulation (TMS). In this 2 × 2 factorial design (time × group), healthy subjects exercised standardized motor skills with their right hand on four consecutive days. Either a mirror (mirror group) or a board (control group) was positioned between their hands. Before and after training TMS was applied along with training tests of both hands. Tests were the same motor skills exercised daily by both groups. Tests of the untrained left hand improved significantly more in the mirror group than in the control group after training ( P = 0.02) and showed a close correlation with an increase of intracortical inhibition of M1left. IHI did not show any difference between investigation time points and groups. The present study confirms the previous suggestion of the involvement of the “contralesional” left-side (ipsilateral to the hand behind the mirror) M1 after mirror therapy, which is not mediated by IHI. Even with the same motor skill training (both groups performed same motor skills) but with different visual information, different networks are involved in training-induced plasticity.
An evaluation of in vivo voltage-sensitive dyes: pharmacological side effects and signal-to-noise ratios after effective removal of brain-pulsation artifacts
Authors: Grandy T. H. , Greenfield S. A. , Devonshire I. M.
Published: September 2012

In the current study, we investigated pharmacological side effects and signal-to-noise ratios (SNRs) of two commonly used voltage-sensitive dyes (VSDs): the blue dye RH-1691 (1 mg/ml) and the red dye di-4-ANEPPS (0.1 mg/ml), applied in vivo to the rat barrel cortex. Blue dyes are often favored over red dyes in in vivo studies due to their apparent superior SNR, partly because their fluorescence spectrum is farther away from the hemoglobin absorption spectrum, making them less prone to heartbeat-associated brain-pulsation artifacts (BPA). We implemented a previously reported template-based BPA removal algorithm and evaluated its applicability to di-4-ANEPPS before comparing characteristics of the two dyes. Somatosensory-evoked potentials (SEPs) were also recorded. Whereas SEPs recorded before and after application of di-4-ANEPPS failed to exhibit demonstrable differences, RH-1691 caused a significant and prolonged increase in SEP amplitude for several hours. In contrast, neither dye influenced the spontaneous cortical activity as assessed by the spectral content of the EEG. Both dyes turned out to be strikingly similar with respect to changes in fractional fluorescence as a function of SEP response amplitude, as well as regarding shot noise characteristics after removal of the BPA. Thus there is strong evidence that the increased SNR for RH-1691 is a consequence of an artificially increased signal. When applying an appropriate BPA removal algorithm, di-4-ANEPPS has proven to be suitable for single-trial in vivo VSD imaging (VSDI) and produces no detectable neurophysiological changes in the system under investigation. Taken together, our data argue for a careful re-evaluation of pharmacological side effects of RH-1691 and support the applicability of di-4-ANEPPS for stable single-trial in vivo VSDI recordings.
NMDA induces persistent inward and outward currents that cause rhythmic bursting in adult rodent motoneurons
Authors: Manuel Marin , Li Yaqing , ElBasiouny Sherif M. , Murray Katie , Griener Anna , Heckman C. J. , Bennett David J.
Published: September 2012

N-methyl-d-aspartate (NMDA) receptors are of critical importance for locomotion in the developing neonatal spinal cord in rats and mice. However, due to profound changes in the expression of NMDA receptors in development between the neonatal stages and adulthood, it is unclear whether NMDA receptors are still an important component of locomotion in the adult rodent spinal cord. To shed light on this issue, we have taken advantage of recently developed preparations allowing the intracellular recording of adult motoneurons that control the tail in the sacrocaudal spinal cord of adult mice and rats. We show that in the adult sacrocaudal spinal cord, NMDA induces rhythmic activity recorded on the ventral roots, often coordinated from left to right, as in swimming motions with the tail (fictive locomotion). The adult motoneurons themselves are intrinsically sensitive to NMDA application. That is, when motoneurons are synaptically isolated with TTX, NMDA still causes spontaneous bursts of rhythmic activity, depending on the membrane potential. We show that these bursts in motoneurons depend on an NMDA-mediated persistent inward current and are terminated by the progressive activation of a persistent outward current. These results indicate that motoneurons, along with the central pattern generator, can actively participate in the production of swimminglike locomotor activity in adult rodents.
The temporal characteristics of Ca2+ entry through L-type and T-type Ca2+ channels shape exocytosis efficiency in chick auditory hair cells during development
Authors: Levic Snezana , Dulon Didier
Published: September 2012

During development, synaptic exocytosis by cochlear hair cells is first initiated by patterned spontaneous Ca2+ spikes and, at the onset of hearing, by sound-driven graded depolarizing potentials. The molecular reorganization occurring in the hair cell synaptic machinery during this developmental transition still remains elusive. We characterized the changes in biophysical properties of voltage-gated Ca2+ currents and exocytosis in developing auditory hair cells of a precocial animal, the domestic chick. We found that immature chick hair cells (embryonic days 10–12) use two types of Ca2+ currents to control exocytosis: low-voltage-activating, rapidly inactivating (mibefradil sensitive) T-type Ca2+ currents and high-voltage-activating, noninactivating (nifedipine sensitive) L-type currents. Exocytosis evoked by T-type Ca2+ current displayed a fast release component (RRP) but lacked the slow sustained release component (SRP), suggesting an inefficient recruitment of distant synaptic vesicles by this transient Ca2+ current. With maturation, the participation of L-type Ca2+ currents to exocytosis largely increased, inducing a highly Ca2+ efficient recruitment of an RRP and an SRP component. Notably, L-type-driven exocytosis in immature hair cells displayed higher Ca2+ efficiency when triggered by prerecorded native action potentials than by voltage steps, whereas similar efficiency for both protocols was found in mature hair cells. This difference likely reflects a tighter coupling between release sites and Ca2+ channels in mature hair cells. Overall, our results suggest that the temporal characteristics of Ca2+ entry through T-type and L-type Ca2+ channels greatly influence synaptic release by hair cells during cochlear development.
Brain surface temperature under a craniotomy
Authors: Kalmbach Abigail S. , Waters Jack
Published: September 2012

Many neuroscientists access surface brain structures via a small cranial window, opened in the bone above the brain region of interest. Unfortunately this methodology has the potential to perturb the structure and function of the underlying brain tissue. One potential perturbation is heat loss from the brain surface, which may result in local dysregulation of brain temperature. Here, we demonstrate that heat loss is a significant problem in a cranial window preparation in common use for electrical recording and imaging studies in mice. In the absence of corrective measures, the exposed surface of the neocortex was at ∼28°C, ∼10°C below core body temperature, and a standing temperature gradient existed, with tissue below the core temperature even several millimeters into the brain. Cooling affected cellular and network function in neocortex and resulted principally from increased heat loss due to convection and radiation through the skull and cranial window. We demonstrate that constant perfusion of solution, warmed to 37°C, over the brain surface readily corrects the brain temperature, resulting in a stable temperature of 36–38°C at all depths. Our results indicate that temperature dysregulation may be common in cranial window preparations that are in widespread use in neuroscience, underlining the need to take measures to maintain the brain temperature in many physiology experiments.