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OBJECTIVES/SPECIFIC AIMS: The food reward circuitry regulates hedonic eating especially in relation to palatable hypercaloric foods, which can lead to chronic overeating and consequent overweight and obesity. Evidence supports that there is considerable overlap within the brain reward circuitry between palatable hypercaloric food intake and substance addiction. The goal of this study was to identify associations between addiction-related genes and body mass index. We hypothesized that addiction-related genes potentially participate in the food reward circuitry if they are associated with obesity traits. METHODS/STUDY POPULATION: A secondary analysis was conducted with 1093 African American adolescents and young adults from the New Mother’s Study. Anthropometric, genetic, demographic and lifestyle measurements were available at the 18-year follow-up assessments. A total of 1350 single nucleotide polymorphisms mapped to 127 addiction-related genes were assessed. A total of 186 ancestry informative markers were used to adjust for population stratification. Generalized estimating equation models were used to identify genetic associations, including additive, dominant, and recessive models, and control for correlations within families. RESULTS/ANTICIPATED RESULTS: The participants ranged from 15 to 23 years of age. Of them, 42.7% were overweight or obese. Significant associations with body mass index were identified for 13 single nucleotide polymorphisms mapped to 11 addiction-related genes, including LEP (p 0.027–<0.001). Most of these genes are involved in dopaminergic, opioidergic, serotonergic pathways, and stress. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results support the role of dopaminergic and opioidergic pathways in the food reward circuitry, and suggest a potential involvement of serotonergic pathways and genes related to stress in the food reward circuitry. Further investigation of the identified genes will facilitate delineation and understanding of the brain food reward system and its relationship with obesity.
One of the most consistent findings in social epidemiology is an inverse relationship between indicators of SES and most types of illness. However, a growing body of research on HIV in sub-Saharan Africa suggests an intriguing reversal of this pattern, particularly with respect to HIV among women. In Cameroon, specifically, high-SES women have higher rates of HIV infection compared with low-SES women. Using data from the 2004 Cameroon DHS, this study explored the relationships between SES and HIV and tested a multivariate model designed to highlight the distinctive factors associated with increased risk of HIV among women in different SES classes. The results revealed that high-SES women who reported engaging in riskier sexual behaviour had the highest levels of HIV infection. Surprisingly, among this group increased knowledge of HIV, more domestic decision-making authority and access to health care did not reduce vulnerability. Meanwhile, among low-SES women relative gender inequality was significantly related to HIV risk. Specifically, among this group of women, having a partner with higher education was strongly associated with greater HIV risk. The results suggest that different approaches targeting each sub-group are needed to effectively combat the disease.
Numerous studies have shown that there are acute cognitive side-effects of chemotherapy for breast cancer. Presumably, patients are more concerned about chronic treatment effects. This report from a prospective longitudinal study compares cognitive functioning in 56 breast cancer patients 1 year after chemotherapy to that of 56 healthy individuals. Neuropsychological test scores were combined into verbal memory, visual memory, working memory, and processing speed scores, as well as an overall summary score, and analyzed using multi-level growth modeling. Frequency of cognitive decline was assessed using regression-based change scores. There was significant rebound in the overall summary score from end of treatment to 1-year follow-up as well as a substantial reduction in the frequency of cognitive decline. However, more than one-third of the breast cancer patients who showed cognitive decline immediately following completion of chemotherapy showed persistent cognitive decline 1 year later. Furthermore, recovery was not seen in all cognitive domains. In fact, the rebound was significant only for working memory. Longer multi-site studies are recommended to explore the risk factors for and the permanence of these longer-term cognitive effects. (JINS, 2013, 20, 1–10)
Polymeric materials are widely used in power generation and energy storage applications. Deoxyribonucleic acid (DNA) biopolymer-based hybrids have been found to display interesting electrical characteristics, such as a relatively high dielectric constant, good resistivity and dielectric breakdown behavior, and are promising as insulating dielectrics for capacitor applications. This research describes the processing, test structure design, and electrical characterization of DNA-sol-gel hybrids for energy storage applications.
The potential of bio-dielectrics for thin film transistor applications was explored via the incorporation of titanium dioxide (TiO2) nanoparticles, rutile form, a high dielectric constant (ε) ceramic, in the deoxyribonucleic acid (DNA) bio-polymer. The DNA-ceramic hybrid films were fabricated from stable suspensions of the TiO2 nanoparticles in viscous, aqueous DNA solutions. Dielectric characterization revealed that the incorporation of TiO2 in DNA resulted in enhanced dielectric constant (14.3 at 1 kHz for 40 wt % TiO2) relative to that of DNA in the entire frequency range of 1 kHz-1 MHz. Variable temperature dielectric measurements, in the 20-80°C range, of the DNA-TiO2 films revealed that the ceramic additive stabilizes DNA against large temperature dependent variations in both ε and the dielectric loss factor tan δ. The bulk resistivity of the DNA-TiO2 hybrid films was measured to be two to three orders of magnitude higher than that of the control DNA films, indicating their potential for utilization as insulating dielectrics in transistor and capacitor applications.
Employability initiatives are becoming increasingly popular in government discourse as a means of tackling worklessness. Here we discuss the findings of a small-scale, qualitative study which mapped the impacts of a multi-intervention programme on participants’ health, wellbeing and employability. Each of the 13 interventions was independently appraised through focus groups or semi-structured interviews. Thematic analyses revealed that participants from all interventions reported increased self-confidence, with several individuals suggesting that project involvement had facilitated their movement into the labour market. While the findings illustrate some positive outcomes, we argue that government policy needs to consider more carefully strategies that also address the demand side of the labour market.
The inflammatory response is a central component of sepsis as it drives the physiological alterations that are recognized as systemic inflammatory response syndrome (SIRS). In contrast to the hypothesis of exuberant inflammatory response in sepsis is the finding that septic patients may have a relative anti-inflammatory environment. Cellular death may be a key factor in sepsis and its related mortality. Cells that are destined to die can do so by two mechanisms: apoptosis and necrosis. In sepsis, cytokine-induced coagulopathy triggers increased activity of tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) and decreased levels of the natural anticoagulant protein C on mononuclear and endothelial cells. Critical illness related corticosteroid insufficiency (CIRCI) occurs as a result of either a decrease in adrenal steroid production. In patients with severe sepsis, a strategy of glycaemic control using intravenous insulin should include a nutritional protocol with preferential use of the enteral route.
This chapter discusses the cell-based model of coagulation, regulation of coagulation, and bleeding disorders. The disorders include congenital disorders and acquired disorders such as thrombocytopenia, disseminated intravascular coagulation (DIC) and microangiopathic haemolytic anaemia. Thrombocytopenia may occur because of impaired production, sequestration, increased consumption, and enhanced degradation. Activated protein C has been shown to reduce mortality in sepsis especially in patients with DIC and multi-organ failure. During the resuscitation of patients who have suffered a major haemorrhage, factors that can contribute to associated coagulopathy are: hypothermia, metabolic acidosis, and consumption of clotting products. Heparin-induced thrombocytopenia (HIT) usually occurs 5-10 days following exposure to heparin. It is a pro-thrombotic disorder and can lead to significant venous and arterial thrombosis. HIT usually resolves following the discontinuation of heparin over a few days. Management includes the prompt removal of all heparin containing medication and the substitution of a direct thrombin inhibitor to control clotting.
The initial assessment of the critically ill patient should begin with a brief, targeted history and an appraisal of the patient's vital signs to identify life threatening abnormalities that merit immediate attention. The goals of resuscitation are usually achieved by the use of supplemental oxygen, fluid or red blood cell transfusion, inotropic support or antibiotics as needed. Physiological Scoring Systems (PSS) developed from the recognition that critically ill patients, and in particular patients who suffered cardiac arrests, often had long periods of deterioration before the crisis or medical emergency occurred. Medical emergency teams (METs) and critical care outreach (CCO) teams aim to provide critical care skills rapidly to critically ill patients. Referrals to the critical care services may happen from any level, but the final decision to admit a patient to a critical care bed should be made by an experienced critical care physician.
The critical care unit manages patients with a vast range of disease and injuries affecting every organ system. The unit can initially be a daunting environment, with complex monitoring equipment producing large volumes of clinical data. Core Topics in Critical Care Medicine is a practical, comprehensive, introductory-level text for any clinician in their first few months in the critical care unit. It guides clinicians in both the initial assessment and the clinical management of all CCU patients, demystifying the critical care unit and providing key knowledge in a concise and accessible manner. The full spectrum of disorders likely to be encountered in critical care are discussed, with additional chapters on transfer and admission, imaging in the CCU, structure and organisation of the unit, and ethical and legal issues. Written by Critical Care experts, Core Topics in Critical Care Medicine provides comprehensive, concise and easily accessible information for all trainees.
The passing of a postgraduate examination in intensive care medicine (ICM) identifies the successful individual to all as someone who has been trained to a high standard in ICM. The knowledge required to thrive in clinical practice as well as examinations in ICM is broad based involving most hospital speciality areas. This chapter focuses on two examinations, namely, the Intercollegiate Diploma in Intensive Care Medicine (DICM), and European Diploma in Intensive Care Medicine (EDIC). Success in professional examinations requires a substantial investment of time. Candidates preparing for examinations must avail themselves of all the educational opportunities at local, regional and national levels in ICM. In the UK, there are many specialist society ICM meetings such as the Intensive Care Society. The internet offers a wealth of useful websites relating to ICM and all can be used to prepare for diploma examinations. Preparation for diploma examinations extends ICM knowledge.