Perspectives on Video Games as Art

In their article Perspectives on Video Games as Art Jeroen Bourgonjon, Geert Vndermeer­sche, Kris Rutten and Niels Quinten engage in discussing whether or not video games can be considered a form of art. Although this question has already been discussed elaborately, the debate is guided by many differ­ent and often conflicting positions. The aim of this article is to revisit this debate by mapping out a range of perspectives on video games as art. The authors explore the relation between games and differ­ent definitions and functions of art, different motives of artists, and the potential impact of the arts. The authors postulate that the discussion about the art status of video games is neither singular nor straightforward, and that the artistic possibilities of video games should instead be assessed by confronting a number of interrelated perspectives

Tissue Engineering of Human Heart Valve Leaflets: A Novel Bioreactor for a Strain-Based Conditioning Approach

Current mechanical conditioning approaches for heart valve tissue engineering concentrate on mimicking the opening and closing behavior of the leaflets, either or not in combination with tissue straining. This study describes a novel approach by mimicking only the diastolic phase of the cardiac cycle, resulting in tissue straining. A novel, yet simplified, bioreactor system was developed for this purpose by applying a dynamic pressure difference over a closed tissue engineered valve, thereby inducing dynamic strains within the leaflets. Besides the use of dynamic strains, the developing leaflet tissues were exposed to prestrain induced by the use of a stented geometry. To demonstrate the feasibility of this strain-based conditioning approach, human heart valve leaflets were engineered and their mechanial behavior evaluated. The actual dynamic strain magnitude in the leaflets over time was estimated using numerical analyses. Preliminary results showed superior tissue formation and non-linear tissue-like mechanical properties in the strained valves when compared to non-loaded tissue strips. In conclusion, the strain-based conditioning approach, using both prestrain and dynamic strains, offers new possibilities for bioreactor design and optimization of tissue properties towards a tissue-engineered aortic human heart valve replacemen

Clinical and economic impact of non-adherence in COPD:A systematic review

BACKGROUND: Medication for Chronic Obstructive Pulmonary Disease (COPD) has shown to substantially reduce symptoms and slow progression of disease. However, non-adherence to medication is common and associated with worsened clinical and economic outcomes. OBJECTIVE: The objective of this study was to perform a systematic review of published literature to assess the impact of non-adherence to COPD medication on clinical and economic outcomes. METHODS: A search in PubMed and Web of Science databases was conducted of original studies published from database inception to 2012. Studies must report on the association between adherence to COPD medication and outcomes, published in English in peer-reviewed journals and full texts needed to be available. RESULTS: Twelve full articles were included in the review. Most studies were retrospective database studies. Seven studies reported on the association between adherence and clinical outcomes, two on mortality, three on costs, four on quality of life and one on work productivity. Results indicated a clear association between adherence and both clinical and economic outcomes. Evidence from studies revealed increased hospitalizations, mortality, quality of life and loss of productivity among non-adherent patients. CONCLUSION: This review revealed a clear association between non-adherence to COPD medication and worsened clinical and economic outcomes making non-adherent patients a priority for cost-effective interventions.</p

Cochrane corner: Is integrated disease management for patients with COPD effective?

Patients with COPD experience respiratory symptoms, impairments of daily living and recurrent exacerbations. The aim of integrated disease management (IDM) is to establish a programme of different components of care (ie, self-management, exercise, nutrition) in which several healthcare providers (ie, nurses, general practitioners, physiotherapists, pulmonologists) collaborate to provide efficient and good quality of care. The aim of this Cochrane systematic review was to evaluate the effectiveness of IDM on quality of life, exercise tolerance and exacerbation related outcomes. Searches for all available evidence were carried out in various databases. Included randomised controlled trials (RCTs) consisted of interventions with multidisciplinary (≥2 healthcare providers) and multitreatment (≥2 components) IDM interventions with duration of at least 3 months. Two reviewers independently searched, assessed and extracted data of all RCTs. A total of 26 RCTs were included, involving 2997 patients from 11 different countries with a followup varying from 3 to 24 months. In all 68% of the patients were men, with a mean age of 68 years and a mean forced expiratory volume in 1 s (FEV1) predicted value of 44.3%. Patients treated with an IDM programme improved significantly on quality of life scores and reported a clinically relevant improvement of 44 m on 6 min walking distance, compared to controls. Furthermore, the number of patients with ≥1 respiratory related hospital admission reduced from 27 to 20 per 100 patients. Duration of hospitalisation decreased significantly by nearly 4 days

Traditional Cardiovascular Risk Factors Are Stronger Related to Carotid Intima-Media Thickness Than to Presence of Carotid Plaques in People Living With HIV

BACKGROUND: Cardiovascular disease is a major cause of morbidity and mortality in people living with HIV, who are at higher risk than the general population. We assessed, in a large cohort of people living with HIV, which cardiovascular, HIV-specific, and lipoproteomic markers were associated with carotid intima-media thickness (cIMT) and carotid plaque presence. We also studied guideline adherence on lipid-lowering medication in individuals with high and very high risk for cardiovascular disease. METHODS AND RESULTS: In 1814 individuals with a median (interquartile range) age of 53 (44–60) years, we found a carotid plaque in 909 (50.1%) and a median (interquartile range) intima-media thickness of 0.66 (0.57–0.76) mm. Ultrasonography was used for the assessment of cIMT and plaque presence. Univariable and multivariable regression models were used for associations with cIMT and presence of plaques. Age, Black race, body mass index, type 2 diabetes, and smoking (pack years) were all positively associated with higher cIMT. Levels of high-density lipoprotein cholesterol, specifically medium and large high-density lipoprotein subclasses, were negatively associated with higher cIMT. Only age and prior myocardial infarction were positively related to the presence of a carotid plaque. Lipid-lowering treatment was prescribed in one-third of people living with HIV, who are at high and very high risk for cardiovascular disease. CONCLUSIONS: Traditional cardiovascular risk factors were significantly associated with higher cIMT but not with carotid plaques, except for age. HIV-specific factors were not associated with both ultrasound measurements. Future studies are needed to elucidate which factors contribute to plaque formation. Improvement of guideline adherence on prescription of lipid-lowering treatment in high-and very high-risk patients for cardiovascular disease is recommended.</p

Increased atherosclerosis in a mouse model of glycogen storage disease type 1a

Glycogen storage disease type 1a (GSD Ia) is an inborn error of carbohydrate metabolism. Despite severe hyperlipidemia, GSD Ia patients show limited atherogenesis compared to age-and-gender matched controls. Employing a GSD Ia mouse model that resembles the severe hyperlipidemia in patients, we here found increased atherogenesis in GSD Ia. These data provide a rationale for investigating atherogenesis in GSD Ia in a larger patient cohort.</p

Systematic analysis of relationships between plasma branched-chain amino acid concentrations and cardiometabolic parameters:an association and Mendelian randomization study

Abstract Background Branched-chain amino acids (BCAAs; valine, leucine, and isoleucine) are essential amino acids that are associated with an increased risk of cardiometabolic diseases (CMD). However, there are still only limited insights into potential direct associations between BCAAs and a wide range of CMD parameters, especially those remaining after correcting for covariates and underlying causal relationships. Methods To shed light on these relationships, we systematically characterized the associations between plasma BCAA concentrations and a large panel of 537 CMD parameters (including atherosclerosis-related parameters, fat distribution, plasma cytokine concentrations and cell counts, circulating concentrations of cardiovascular-related proteins and plasma metabolites) in 1400 individuals from the Dutch population cohort LifeLines DEEP and 294 overweight individuals from the 300OB cohort. After correcting for age, sex, and BMI, we assessed associations between individual BCAAs and CMD parameters. We further assessed the underlying causality using Mendelian randomization. Results A total of 838 significant associations were detected for 409 CMD parameters. BCAAs showed both common and specific associations, with the most specific associations being detected for isoleucine. Further, we found that obesity status substantially affected the strength and direction of associations for valine, which cannot be corrected for using BMI as a covariate. Subsequent univariable Mendelian randomization (UVMR), after removing BMI-associated SNPs, identified seven significant causal relationships from four CMD traits to BCAA levels, mostly for diabetes-related parameters. However, no causal effects of BCAAs on CMD parameters were supported. Conclusions Our cross-sectional association study reports a large number of associations between BCAAs and CMD parameters. Our results highlight some specific associations for isoleucine, as well as obesity-specific effects for valine. MR-based causality analysis suggests that altered BCAA levels can be a consequence of diabetes and alteration in lipid metabolism. We found no MR evidence to support a causal role for BCAAs in CMD. These findings provide evidence to (re)evaluate the clinical importance of individual BCAAs in CMD diagnosis, prevention, and treatment

Modeling Phenotypic Heterogeneity of Glycogen Storage Disease Type 1a Liver Disease in Mice by Somatic CRISPR/CRISPR-associated protein 9-Mediated Gene Editing

BACKGROUND AND AIMS: Patients with glycogen storage disease type 1a (GSD‐1a) primarily present with life‐threatening hypoglycemia and display severe liver disease characterized by hepatomegaly. Despite strict dietary management, long‐term complications still occur, such as liver tumor development. Variations in residual glucose‐6‐phosphatase (G6PC1) activity likely contribute to phenotypic heterogeneity in biochemical symptoms and complications between patients. However, lack of insight into the relationship between G6PC1 activity and symptoms/complications and poor understanding of the underlying disease mechanisms pose major challenges to provide optimal health care and quality of life for GSD‐1a patients. Currently available GSD‐1a animal models are not suitable to systematically investigate the relationship between hepatic G6PC activity and phenotypic heterogeneity or the contribution of gene‐gene interactions (GGIs) in the liver. APPROACH AND RESULTS: To meet these needs, we generated and characterized a hepatocyte‐specific GSD‐1a mouse model using somatic CRISPR/CRISPR‐associated protein 9 (Cas9)–mediated gene editing. Hepatic G6pc editing reduced hepatic G6PC activity up to 98% and resulted in failure to thrive, fasting hypoglycemia, hypertriglyceridemia, hepatomegaly, hepatic steatosis (HS), and increased liver tumor incidence. This approach was furthermore successful in simultaneously modulating hepatic G6PC and carbohydrate response element‐binding protein, a transcription factor that is activated in GSD‐1a and protects against HS under these conditions. Importantly, it also allowed for the modeling of a spectrum of GSD‐1a phenotypes in terms of hepatic G6PC activity, fasting hypoglycemia, hypertriglyceridemia, hepatomegaly and HS. CONCLUSIONS: In conclusion, we show that somatic CRISPR/Cas9‐mediated gene editing allows for the modeling of a spectrum of hepatocyte‐borne GSD‐1a disease symptoms in mice and to efficiently study GGIs in the liver. This approach opens perspectives for translational research and will likely contribute to personalized treatments for GSD‐1a and other genetic liver diseases