5,736 research outputs found
Life on a scale:Deep brain stimulation in anorexia nervosa
Anorexia nervosa (AN) is a severe psychiatric disorder marked by low body weight, body image abnormalities, and anxiety and shows elevated rates of morbidity, comorbidity and mortality. Given the limited availability of evidence-based treatments, there is an urgent need to investigate new therapeutic options that are informed by the disorder’s underlying neurobiological mechanisms. This thesis represents the first study in the Netherlands and one of a limited number globally to evaluate the efficacy, safety, and tolerability of deep brain stimulation (DBS) in the treatment of AN. DBS has the advantage of being both reversible and adjustable. Beyond assessing the primary impact of DBS on body weight, psychological parameters, and quality of life, this research is novel in its comprehensive approach. We integrated evaluations of efficacy with critical examinations of the functional impact of DBS in AN, including fMRI, electroencephalography EEG, as well as endocrinological and metabolic assessments. Furthermore, this work situates AN within a broader theoretical framework, specifically focusing on its manifestation as a form of self-destructive behavior. Finally, we reflect on the practical, ethical and philosophical aspects of conducting an experimental, invasive procedure in a vulnerable patient group. This thesis deepens our understanding of the neurobiological underpinnings of AN and paves the way for future research and potential clinical applications of DBS in the management of severe and enduring AN
The KINGS mouse as a model of beta cell endoplasmic reticulum (ER) stress and sex differences in diabetes.
Background: The KINGS mouse is a novel model of beta cell endoplasmic reticulum (ER) stress which shows stark sex differences in diabetes, with males developing overt and progressive hyperglycaemia whilst females are protected. Beta cell ER stress has been implicated in many types of diabetes and underpins numerous factors known to drive beta cell failure. Sex differences also exist in diabetes in humans with premenopausal women having a lower diabetes incidence compared to men. Further characterisation of the KINGS mice may provide valuable insight into these phenomena. Aims: The objectives of this thesis were to 1) further characterise beta cell ER stress and associated cellular response in the KINGS mice, 2) investigate the influence of sex hormones and beta cell ER stress manipulation on glycaemic control in the KINGS mice and 3) investigate whether diabetes development can be prevented in the male KINGS mice. Methods: Western blotting and immunofluorescent staining were used to investigate the expression of ER stress and unfolded protein response (UPR) markers in KINGS islets, as well as beta cell turnover and mass. To determine the influence of oestradiol on the KINGS phenotype, endogenous oestradiol was removed from female mice via ovariectomy, and exogenous oestradiol was delivered to male KINGS mice through implantation of oestradiol- containing capsules. A western diet was used to exacerbate beta cell ER stress in female KINGS mice, whilst liraglutide administration, TUDCA administration and removal of endogenous testosterone (via orchidectomy) was used in an attempt to reduce ER stress and prevent diabetes in the male KINGS mice. For all in vivo studies, glycaemic control was assessed through blood glucose concentration monitoring, glucose tolerance testing and insulin tolerance testing. Results: Male KINGS mice developed diabetes by 5-6 weeks of age whereas female KINGS mice were protected, in line with previous studies. Protein markers of ER stress and the UPR were observed in KINGS islets from 4 weeks of age and a sex difference was observed in expression profiles with males largely showing an increased expression of markers. Despite this, we did not observe a loss of beta cell mass in either male or female KINGS mice. However, subtle changes in beta cell proliferation and apoptosis in the male KINGS mice are suggestive of mild changes to beta cell turnover which may contribute to diabetes development. A western diet exacerbated beta cell ER stress in female KINGS mice, however this only led to a mild impairment in glycaemic control which was not as severe as that seen in male KINGS mice. This may suggest that even under conditions of further ER stress, female mice are still able to respond adaptively. Removal of endogenous oestradiol also exacerbated beta cell ER stress, however again this was only associated with a subtle impairment in glycaemic control. On the contrary, exogenous oestradiol delivery in the male KINGS mice prevented the development of overt diabetes. Treatment with liraglutide was used in an attempt to alleviate ER stress in the male KINGS mice. Although liraglutide prevented the development of diabetes and reduced blood glucose concentrations once diabetes was established, this protection only lasted during the treatment window and cessation of treatment was associated with increases in blood glucose concentrations. In addition, liraglutide had no effect on beta cell ER stress levels. Treatment with TUDCA, a chemical chaperone previously found to reduce beta cell ER stress, had no impact on blood glucose concentrations in the KINGS mice. However, removal of endogenous testosterone through orchidectomy prevented the development of overt diabetes. Conclusion: In this study we have confirmed that the KINGS mutation drives beta cell ER stress and that sex differences exist in beta cell response to this. Interestingly, an adaptive response to beta cell ER stress was still maintained in female KINGS mice when ER stress was exacerbated through a western diet. We also found that whilst oestradiol likely contributes in-part to sex differences in diabetes, it cannot be the sole mediator and other factors must be involved. Indeed, we found that endogenous testosterone removal prevented the development of diabetes in male mice. Liraglutide treatment also prevented diabetes development in male mice, however this was likely to be mediated through mechanisms unrelated to beta cell ER stress. Further study is required to investigate how testosterone removal and liraglutide protect male mice.</div
Functional Nanomaterials and Polymer Nanocomposites: Current Uses and Potential Applications
This book covers a broad range of subjects, from smart nanoparticles and polymer nanocomposite synthesis and the study of their fundamental properties to the fabrication and characterization of devices and emerging technologies with smart nanoparticles and polymer integration
LIPIcs, Volume 251, ITCS 2023, Complete Volume
LIPIcs, Volume 251, ITCS 2023, Complete Volum
Effects of municipal smoke-free ordinances on secondhand smoke exposure in the Republic of Korea
ObjectiveTo reduce premature deaths due to secondhand smoke (SHS) exposure among non-smokers, the Republic of Korea (ROK) adopted changes to the National Health Promotion Act, which allowed local governments to enact municipal ordinances to strengthen their authority to designate smoke-free areas and levy penalty fines. In this study, we examined national trends in SHS exposure after the introduction of these municipal ordinances at the city level in 2010.MethodsWe used interrupted time series analysis to assess whether the trends of SHS exposure in the workplace and at home, and the primary cigarette smoking rate changed following the policy adjustment in the national legislation in ROK. Population-standardized data for selected variables were retrieved from a nationally representative survey dataset and used to study the policy action’s effectiveness.ResultsFollowing the change in the legislation, SHS exposure in the workplace reversed course from an increasing (18% per year) trend prior to the introduction of these smoke-free ordinances to a decreasing (−10% per year) trend after adoption and enforcement of these laws (β2 = 0.18, p-value = 0.07; β3 = −0.10, p-value = 0.02). SHS exposure at home (β2 = 0.10, p-value = 0.09; β3 = −0.03, p-value = 0.14) and the primary cigarette smoking rate (β2 = 0.03, p-value = 0.10; β3 = 0.008, p-value = 0.15) showed no significant changes in the sampled period. Although analyses stratified by sex showed that the allowance of municipal ordinances resulted in reduced SHS exposure in the workplace for both males and females, they did not affect the primary cigarette smoking rate as much, especially among females.ConclusionStrengthening the role of local governments by giving them the authority to enact and enforce penalties on SHS exposure violation helped ROK to reduce SHS exposure in the workplace. However, smoking behaviors and related activities seemed to shift to less restrictive areas such as on the streets and in apartment hallways, negating some of the effects due to these ordinances. Future studies should investigate how smoke-free policies beyond public places can further reduce the SHS exposure in ROK
Towards a General Complex Systems Model of Economic Sanctions with Some Results Outlining Consequences of Sanctions on the Russian Economy and the World
The main purpose of this paper is to present a complex nonlinear modelling approach to analyzing mixed capitalist economic systems. An application of a more elaborate version of this model is to explore the consequences of sanctions on the Russian economy and evaluate the model’s predictive successes or failures. Furthermore, the formal expanded nonlinear model presented in the appendix may be seen as an initial step to put the analysis of economic sanctions within a formal complex socio-economic systems framework. The results obtained from this structural complex multisectoral model so far seem fairly accurate in terms of agreement with measured values of observable economic variables. The political consequences are uncertain and are to be explored separately in a companion paper and ultimately in a book length treatment.
Methodologically, the paper also presents the case for using Social Accounting Matrix (SAM)-based models for understanding problems of analyzing sanctions in an economywide context. Linear as well as Nonlinear models are presented in the appendix. The nonlinear modelling approach might prove to be especially relevant for studying the properties of multiple equilibria and complex dynamics
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