GLP-1 receptor stimulation of the lateral parabrachial nucleus reduces food intake: neuroanatomical, electrophysiological, and behavioral evidence.

The parabrachial nucleus (PBN) is a key nucleus for the regulation of feeding behavior. Inhibitory inputs from the hypothalamus to the PBN play a crucial role in the normal maintenance of feeding behavior, because their loss leads to starvation. Viscerosensory stimuli result in neuronal activation of the PBN. However, the origin and neurochemical identity of the excitatory neuronal input to the PBN remain largely unexplored. Here, we hypothesize that hindbrain glucagon-like peptide 1 (GLP-1) neurons provide excitatory inputs to the PBN, activation of which may lead to a reduction in feeding behavior. Our data, obtained from mice expressing the yellow fluorescent protein in GLP-1-producing neurons, revealed that hindbrain GLP-1-producing neurons project to the lateral PBN (lPBN). Stimulation of lPBN GLP-1 receptors (GLP-1Rs) reduced the intake of chow and palatable food and decreased body weight in rats. It also activated lPBN neurons, reflected by an increase in the number of c-Fos-positive cells in this region. Further support for an excitatory role of GLP-1 in the PBN is provided by electrophysiological studies showing a remarkable increase in firing of lPBN neurons after Exendin-4 application. We show that within the PBN, GLP-1R activation increased gene expression of 2 energy balance regulating peptides, calcitonin gene-related peptide (CGRP) and IL-6. Moreover, nearly 70% of the lPBN GLP-1 fibers innervated lPBN CGRP neurons. Direct intra-lPBN CGRP application resulted in anorexia. Collectively, our molecular, anatomical, electrophysiological, pharmacological, and behavioral data provide evidence for a functional role of the GLP-1R for feeding control in the PBN

Psychological Targets for Lung Cancer Screening Uptake: A Prospective Longitudinal Cohort Study

Introduction: Low uptake of low-dose computed tomography lung cancer screening by high-risk groups compromises its effectiveness and equity as a population-level early detection strategy. Numerous psychological factors are implicated qualitatively or retrospectively, but prospective data are needed to validate their associations with uptake behavior and specify psychological targets for intervention. / Methods: This is a prospective, longitudinal cohort study evaluating psychological correlates of lung cancer screening uptake. Ever-smokers (aged 55–77 y) were invited to a lung health check, at which low-dose computed tomography screening was offered through the SUMMIT Study—a multicenter screening implementation trial. One week after their screening invitation, 44,000 invitees were mailed the self-regulatory questionnaire for lung cancer screening. Regression analyses evaluated the constructs’ associations with uptake (telephoning for an appointment) and sociodemographic characteristics. / Results: Higher odds of uptake were associated with both positive and negative perceptions. Positive perceptions included lung cancer controllability, benefits of early diagnosis, improved survival when lung cancer is detected early, willingness to be treated, and believing smoking cessation is effective in reducing risk. Negative perceptions included a higher lung cancer risk perception, negative beliefs about the consequences of lung cancer, perceiving lung cancer as stigmatized, and a negative emotional response. Although current smokers held the highest risk perceptions, they also reported negative perceptions that could undermine how they behave in response to their risk. / Conclusions: Interventions to improve uptake should focus on changing perceptions that affect how an individual reacts when they believe their risk of lung cancer is high

Lung Screen Uptake Trial (LSUT): Randomized Controlled Clinical Trial Testing Targeted Invitation Materials

Rationale: Low uptake of low-dose computed tomography (LDCT) lung cancer screening, particularly by current smokers of a low socioeconomic position, compromises effectiveness and equity. Objectives: To compare the effect of a targeted, low-burden, and stepped invitation strategy versus control on uptake of hospital-based Lung Health Check appointments offering LDCT screening. Methods: In a two-arm, blinded, between-subjects, randomized controlled trial, 2,012 participants were selected from 16 primary care practices using these criteria: 1) aged 60 to 75 years, 2) recorded as a current smoker within the last 7 years, and 3) no prespecified exclusion criteria contraindicating LDCT screening. Both groups received a stepped sequence of preinvitation, invitation, and reminder letters from their primary care practitioner offering prescheduled appointments. The key manipulation was the accompanying leaflet. The intervention group’s leaflet targeted psychological barriers and provided low-burden information, mimicking the concept of the U.K. Ministry of Transport’s annual vehicle test (“M.O.T. For Your Lungs”). Measurements and Main Results: Uptake was 52.6%, with no difference between intervention (52.3%) and control (52.9%) groups in unadjusted (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.82–1.16) or adjusted (OR, 0.98; 95% CI, 0.82–1.17) analyses. Current smokers were less likely to attend (adjusted OR, 0.70; 95% CI, 0.56–0.86) than former smokers. Socioeconomic deprivation was significantly associated with lower uptake for the control group only (P < 0.01). Conclusions: The intervention did not improve uptake. Regardless of trial arm, uptake was considerably higher than previous clinical and real-world studies, particularly given that the samples were predominantly lower socioeconomic position smokers. Strategies common to both groups, including a Lung Health Check approach, could represent a minimum standard. Clinical trial registered with www.clinicaltrials.gov (NCT02558101) and registered prospectively with the International Standard Registered Clinical/Social Study (N21774741)

Access to housing subsidies, housing status, drug use and HIV risk among low-income U.S. urban residents

<p>Abstract</p> <p>Background</p> <p>Much research has shown an association between homelessness and unstable housing and HIV risk but most has relied on relatively narrow definitions of housing status that preclude a deeper understanding of this relationship. Fewer studies have examined access to housing subsidies and supportive housing programs among low-income populations with different personal characteristics. This paper explores personal characteristics associated with access to housing subsidies and supportive housing, the relationship between personal characteristics and housing status, and the relationship between housing status and sexual risk behaviors among low-income urban residents.</p> <p>Methods</p> <p>Surveys were conducted with 392 low-income residents from Hartford and East Harford, Connecticut through a targeted sampling plan. We measured personal characteristics (income, education, use of crack, heroin, or cocaine in the last 6 months, receipt of welfare benefits, mental illness diagnosis, arrest, criminal conviction, longest prison term served, and self-reported HIV diagnosis); access to housing subsidies or supportive housing programs; current housing status; and sexual risk behaviors. To answer the aims above, we performed univariate analyses using Chi-square or 2-sided ANOVA's. Those with significance levels above (0.10) were included in multivariate analyses. We performed 2 separate multiple regressions to determine the effects of personal characteristics on access to housing subsidies and access to supportive housing respectively. We used multinomial main effects logistic regression to determine the effects of housing status on sexual risk behavior.</p> <p>Results</p> <p>Being HIV positive or having a mental illness predicted access to housing subsidies and supportive housing, while having a criminal conviction was not related to access to either housing subsidies or supportive housing. Drug use was associated with poorer housing statuses such as living on the street or in a shelter, or temporarily doubling up with friends, acquaintances or sex partners. Living with friends, acquaintances or sex partners was associated with greater sexual risk than those living on the street or in other stable housing situations.</p> <p>Conclusions</p> <p>Results suggest that providing low-income and supportive housing may be an effective structural HIV prevention intervention, but that the availability and accessibility of these programs must be increased.</p

Social acceptability of treatments for adolescent idiopathic scoliosis: a cross-sectional study

BACKGROUND: There are no data on social acceptability of scoliosis. Aim. To elicit evidence-based opinions on therapeutic strategies for adolescent idiopathic scoliosis in a sample of families with not affected children, so to understand the social perception of this issue. METHODS: Design. Cross-sectional study. Setting. Secondary schools in 4 northern Italian regions. Participants. Parents of children in the age group at risk of and not affected by scoliosis (Pre-test group = 100, Study group = 3,162). Interventions. Questionnaire: five specific and evidence-based questions regarding scoliosis treatment options and a socio-demographic section. Methodology. "Role-playing" in which it was required to normal people to answer what they would have chosen if they had been in the situation proposed. Main outcome measures. Perception of acceptability of treatments for adolescent idiopathic scoliosis in the general population (social acceptability) RESULTS: The families support the use of screening (94.8%) at school, immediate bracing (76.4%) for scoliosis with a 60% risk of progression, but also therapeutic exercises (86.9%) in cases with a 25% risk of progression. CONCLUSION: There is a growing tendency to consider not only the efficacy, effectiveness and efficiency of treatments, but also their acceptability. This patient-centred aspect is especially more important in areas (like adolescent idiopathic scoliosis) in which there is some evidence on the efficacy of treatments, but not strong and definitive (RCTs). Adolescent idiopathic scoliosis treatments should thus be carefully considered also in the light of their social acceptability

Development of an in vitro periodontal biofilm model for assessing antimicrobial and host modulatory effects of bioactive molecules

Background: Inflammation within the oral cavity occurs due to dysregulation between microbial biofilms and the host response. Understanding how different oral hygiene products influence inflammatory properties is important for the development of new products. Therefore, creation of a robust host-pathogen biofilm platform capable of evaluating novel oral healthcare compounds is an attractive option. We therefore devised a multi-species biofilm co-culture model to evaluate the naturally derived polyphenol resveratrol (RSV) and gold standard chlorhexidine (CHX) with respect to anti-biofilm and anti-inflammatory properties.&lt;p&gt;&lt;/p&gt; Methods: An in vitro multi-species biofilm containing &lt;i&gt;S. mitis, F. nucleatum, P. Gingivalis&lt;/i&gt; and &lt;i&gt;A. Actinomycetemcomitans&lt;/i&gt; was created to represent a disease-associated biofilm and the oral epithelial cell in OKF6-TERT2. Cytotoxicity studies were performed using RSV and CHX. Multi-species biofilms were either treated with either molecule, or alternatively epithelial cells were treated with these prior to biofilm co-culture. Biofilm composition was evaluated and inflammatory responses quantified at a transcriptional and protein level.&lt;p&gt;&lt;/p&gt; Results: CHX was toxic to epithelial cells and multi-species biofilms at concentrations ranging from 0.01-0.2%. RSV did not effect multi-species biofilm composition, but was toxic to epithelial cells at concentrations greater than 0.01%. In co-culture, CHX-treated biofilms resulted in down regulation of the inflammatory chemokine IL-8 at both mRNA and protein level. RSV-treated epithelial cells in co-culture were down-regulated in the release of IL-8 protein, but not mRNA.&lt;p&gt;&lt;/p&gt; Conclusions: CHX possesses potent bactericidal properties, which may impact downstream inflammatory mediators. RSV does not appear to have bactericidal properties against multi-species biofilms, however it did appear to supress epithelial cells from releasing inflammatory mediators. This study demonstrates the potential to understand the mechanisms by which different oral hygiene products may influence gingival inflammation, thereby validating the use of a biofilm co-culture model.&lt;p&gt;&lt;/p&gt

Alcohol consumption and lifetime change in cognitive ability:a gene × environment interaction study

Studies of the effect of alcohol consumption on cognitive ability are often confounded. One approach to avoid confounding is the Mendelian randomization design. Here, we used such a design to test the hypothesis that a genetic score for alcohol processing capacity moderates the association between alcohol consumption and lifetime change in cognitive ability. Members of the Lothian Birth Cohort 1936 completed the same test of intelligence at age 11 and 70 years. They were assessed for recent alcohol consumption in later life and genotyped for a set of four single-nucleotide polymorphisms in three alcohol dehydrogenase genes. These variants were unrelated to late-life cognition or to socioeconomic status. We found a significant gene × alcohol consumption interaction on lifetime cognitive change (p = 0.007). Individuals with higher genetic ability to process alcohol showed relative improvements in cognitive ability with more consumption, whereas those with low processing capacity showed a negative relationship between cognitive change and alcohol consumption with more consumption. The effect of alcohol consumption on cognitive change may thus depend on genetic differences in the ability to metabolize alcohol

Lung Screen Uptake Trial: results from a single lung cancer screening round

The Lung Screen Uptake Trial tested a novel invitation strategy to improve uptake and reduce socioeconomic and smoking-related inequalities in lung cancer screening (LCS) participation. It provides one of the first UK-based 'real-world' LCS cohorts. Of 2012 invited, 1058 (52.6%) attended a 'lung health check'. 768/996 (77.1%) in the present analysis underwent a low-dose CT scan. 92 (11.9%) and 33 (4.3%) participants had indeterminate pulmonary nodules requiring 3-month and 12-month surveillance, respectively; 36 lung cancers (4.7%) were diagnosed (median follow-up: 1044 days). 72.2% of lung cancers were stage I/II and 79.4% of non-small cell lung cancer had curative-intent treatment