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Although systematic colorectal cancer screening is efficacious, many programmes suffer from low uptake. Few behavioural or attitudinal factors have been identified as being associated with participation in colorectal cancer screening. We explored knowledge, beliefs about cancer, subjective health literacy, emotional attitudes to screening, and social influences among individuals invited to a population-based screening programme. Regression modelling of a cross-sectional survey of 2299 individuals (users and non-users) of a population-based Faecal Immunochemical Test (FIT) screening programme in Dublin was conducted. Questions were derived from previous theoretically-informed qualitative work and assessed using previously used and validated measures. The primary outcome variable was uptake status (User/Participation or Non-User/Non-participation); multivariable logistic regression was used to estimate the odds ratios (OR) for screening participation. Stronger fatalistic beliefs independently predicted lower uptake (OR = 0.94; 95% CI 0.90-0.98; P = 0.003). Those aged less then 65 who disagreed that "cancer can often be cured" also had lower uptake (OR = 0.43; 95% CI 0.22-0.82 P = 0.017). Agreement that the test was disgusting and tempting fate predicted lower uptake (OR = 0.16 95% CI 0.10-0.27 p less then 0.001), while the influence of a partner on decision to be screened was associated with higher uptake (OR = 1.32; 95% CI 1.15-1.50 P less then 0.001). Negative cancer-related and screening-related beliefs and emotions are associated with non-participation in FIT (-based screening). Research is warranted to explore if these negative beliefs and emotions are modifiable and, if so, whether this would improve screening uptake. The association between the influence of a partner and screening participation present a challenge around improving uptake among those not in co-habiting relationships.Since GLUT3 is vital for fueling neurotransmission, we examined in-vivo the adult phenotype carrying the conditional homozygous glut3 gene mutation (KO) in glutamate-excitatory neurons. These KO mice demonstrated sex-specific differences in brain and body weights (p = 0.0001 and p = 0.01 each) with reduced GLUT3 protein in cerebral cortices and brain stem (p = 0.005). In patch clamp studies the glut3 KO mice displayed a shorter latency to and enhanced paroxysmal activity (p = 0.01 and p = 0.015 each) in pyramidal neurons upon application of a GABAA antagonist, supporting hyperexcitability. Further, associated changes in neurobehavior consisted of reduced latency to fall in the rotorod motor test related to incoordination, increased distance traveled in total and periphery versus center in open field testing suggesting hyperactivity with anxiety (p = 0.0013 in male, p = 0.045 in female), reduced time freezing reminiscent of disrupted contextual fear conditioning (p = 0.0033), decreased time in target quadrant seen with spatial cognitive memory water maze testing (p = 0.034), and enhanced sociability particularly for novelty reflecting a lack of inhibition/impulsivity (p = 0.038). Some of these features were equally pronounced in males and females (cognitive) while others were seen in females (anxiety and impulsivity). We conclude that GLUT3 in adult glutamate-excitatory neurons is essential for maintaining neurotransmitory equipoise regulating excitation with maintenance of motor coordination and activity, cognition, spatial memory and normal fear for both contextual events and novelty with tempered sociability. While sex-specificity was forthcoming for some of these behaviors, our findings collectively suggest that loss-of-function glut3 gene mutations or polymorphisms may underlie an endophenotype of attention deficit-hyperactivity disorder.Addiction is a chronic brain disease that has dramatic health and socioeconomic consequences worldwide. Multiple approaches have been used for decades to clarify the neurobiological basis of this disease and to identify novel potential treatments. This review summarizes the main brain networks involved in the vulnerability to addiction and specific innovative technological approaches to investigate these neural circuits. First, the evolution of the definition of addiction across the Diagnostic and Statistical Manual of Mental Disorders (DSM) is revised. We next discuss several innovative experimental techniques that, combined with behavioral approaches, have allowed recent critical advances in understanding the neural circuits involved in addiction, including DREADDs, calcium imaging, and electrophysiology. All these techniques have been used to investigate specific neural circuits involved in vulnerability to addiction and have been extremely useful to clarify the neurobiological basis of each specific component of the addictive process. These novel tools targeting specific brain regions are of great interest to further understand the different aspects of this complex disease. This article is part of the special issue on 'Vulnerabilities to Substance Abuse.'.Multivariate Curve Resolution (MCR) was used to determine the phase purity of pharmaceutical co-crystals from mid infrared spectra. An in-silico coformer screening was used to choose one of ten potential coformers. This analysis used quantum chemistry simulation to predict which coformers are thermodynamically inclined to form cocrystals with the model drug, hydrochlorothiazide. The coformer chosen was nicotinamide. check details An experimental solvent screening by ultrasound assisted slurry co-crystallization was performed to evaluate the capacity of the method to determine phase purity. Afterwards, slurry and slow evaporation co-crystallizations were performed at 10, 25, and 40 °C using 7 solvent systems, and two levels of agitation for the evaporation co-crystallization (on and off). Mid infrared spectroscopy (MIRS) analysis of the products of these co-crystallizations was used to develop an MCR model to determine co-crystal phase purity. The MCR results were compared with a reference co-crystal. Experimental design (DoE) was used to investigate the effect of solvents, temperature, and agitation on the purity of co-crystals produced by slurry and evaporation co-crystallization. DoE revealed that evaporation co-crystallization with agitating at 65 rpm formed co-crystals with greater phase purity. The optimal temperature varied with the solvent used.
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