Time trends of chest pain symptoms and health related quality of life in coronary artery disease

BACKGROUND: There is at present a lack of knowledge of time trends in health related quality of life (HRQL) in common patients with coronary artery disease (CAD) treated in ordinary care. The objective of this study is to assess and compare time trends of health related quality of life (HRQL) and chest pain in patients with coronary artery disease. METHODS: 253 consecutive CAD patients in Stockholm County, Sweden – 197 males/56 females; 60 ± 8 years – were followed during two years. Perceived chest pain symptoms and three global assessments of HRQL were assessed at baseline, after one and after two years. EuroQol-5 dimension (EQ-5D) with a predefined focus on function and symptoms; the broader tapping global estimates of HRQL; EuroQol VAS (EQ-VAS) and Cardiac Health Profile (CHP) were used. Chest pain was ranked according to Canadian Cardiovascular Society (CCS). Change in HRQL was analysed by a repeated measurements ANOVA and chest pain symptoms were analysed by Friedman non-parametric ANOVA. RESULTS: Perceived chest pain decreased during the two years (p < 0.00022); CCS 0: 41–51%; CCS 1: 19–15%; CCS 2: 31–27%; CCS 3: 5–4% and CCS 4: 4–2%. By contrast, HRQL did not change: EQ-5D: 0.76 (CI 0.73–0.79) -0.78 (CI 0.75–0.81), EQ-VAS: 0.68 (CI 0.66–0.71)-0.68 (CI 0.65–0.71) and CHP: 0.66 (CI 0.64–0.69) -0.66 (CI 0.64–0.69). CONCLUSION: HRQL did not increase despite a reduction in the severity of chest pain during two years. This implies that the major part of HRQL in these consecutive ordinary patients with CAD is unresponsive to change in chest pain symptoms

Delineation of Subregions in the Early Postnatal Human Cerebellum for Design-Based Stereologic Studies

Recent design-based stereologic studies have shown that the early postnatal (<1 year of age) human cerebellum is characterized by very high plasticity and may thus be very sensitive to external and internal influences during the first year of life. A potential weakness of these studies is that they were not separately performed on functionally relevant subregions of the cerebellum, as was the case in a few design-based stereologic studies on the adult human cerebellum. The aim of the present study was to assess whether it is possible to identify unequivocally the primary, superior posterior, horizontal, ansoparamedian, and posterolateral fissures in the early postnatal human cerebellum, based on which functionally relevant subregions could be delineated. This was tested in 20 human post mortem cerebellar halves from subjects aged between 1 day and 11 months by means of a combined macroscopic and microscopic approach. We found that the superior posterior, horizontal, and posterolateral fissures can be reliably identified on all of the specimens. However, reliable and reproducible identification of the primary and ansoparamedian fissures was not possible. Accordingly, it appears feasible to perform subregion-specific investigations in the early postnatal human cerebellum when the identification of subregions is restricted to crus I (bordered by the superior posterior and horizontal fissures) and the flocculus (bordered by the posterolateral fissure). As such, it is recommended to define the entire cerebellar cortex as the region of interest in design-based stereologic studies on the early postnatal human cerebellum to guarantee reproducibility of results

Transformative Materials to Create 3D Functional Human Tissue Models In Vitro in a Reproducible Manner

Recreating human tissues and organs in the petri dish to establish models as tools in biomedical sciences has gained momentum. These models can provide insight into mechanisms of human physiology, disease onset, and progression, and improve drug target validation, as well as the development of new medical therapeutics. Transformative materials play an important role in this evolution, as they can be programmed to direct cell behavior and fate by controlling the activity of bioactive molecules and material properties. Using nature as an inspiration, scientists are creating materials that incorporate specific biological processes observed during human organogenesis and tissue regeneration. This article presents the reader with state-of-the-art developments in the field of in vitro tissue engineering and the challenges related to the design, production, and translation of these transformative materials. Advances regarding (stem) cell sources, expansion, and differentiation, and how novel responsive materials, automated and large-scale fabrication processes, culture conditions, in situ monitoring systems, and computer simulations are required to create functional human tissue models that are relevant and efficient for drug discovery, are described. This paper illustrates how these different technologies need to converge to generate in vitro life-like human tissue models that provide a platform to answer health-based scientific questions.</p

Dendritic glycopolymers based on dendritic polyamine scaffolds: view on their synthetic approaches, characteristics and potential for biomedical applications

In this review we highlight the potential for biomedical applications of dendritic glycopolymers based on polyamine scaffolds. The complex interplay of the molecular characteristics of the dendritic architectures and their specific interactions with various (bio)molecules are elucidated with various examples. A special role of the individual sugar units attached to the dendritic scaffolds and their density is identified, which govern ionic and H-bond interactions, and biological targeting, but to a large extent are also responsible for the significantly reduced toxicity of the dendritic glycopolymers compared to their polyamine scaffolds. Thus, the application of dendritic glycopolymers in drug delivery systems for gene transfection but also as therapeutics in neurodegenerative diseases has great promisePublikacja w ramach programu Royal Society of Chemistry "Gold for Gold" 2014 finansowanego przez Uniwersytet Łódzk

Cardiac rehabilitation availability and delivery in Europe: How does it differ by region and compare with other high-income countries?: Endorsed by the European Association of Preventive Cardiology

Aims: The aims of this study were to establish cardiac rehabilitation availability and density, as well as the nature ofprogrammes, and to compare these by European region (geoscheme) and with other high-income countries.Methods: A survey was administered to cardiac rehabilitation programmes globally. Cardiac associations were engagedto facilitate programme identification. Density was computed using global burden of disease study ischaemic heartdisease incidence estimates. Four high-income countries were selected for comparison (N¼790 programmes) toEuropean data, and multilevel analyses were performed.Results: Cardiac rehabilitation was available in 40/44 (90.9%) European countries. Data were collected in 37 (94.8%country response rate). A total of 455/1538 (29.6% response rate) programme respondents initiated the survey.Programme volumes (median 300) were greatest in western European countries, but overall were higher than inother high-income countries (

Modeling the TNFα-Induced Apoptosis Pathway in Hepatocytes

The proinflammatory cytokine TNFα fails to provoke cell death in isolated hepatocytes but has been implicated in hepatocyte apoptosis during liver diseases associated with chronic inflammation. Recently, we showed that TNFα is able to sensitize primary murine hepatocytes cultured on collagen to Fas ligand-induced apoptosis and presented a mathematical model of the sensitizing effect. Here, we analyze how TNFα induces apoptosis in combination with the transcriptional inhibitor actinomycin D (ActD). Accumulation of reactive oxygen species (ROS) in response to TNFR activation turns out to be critical for sustained activation of JNK which then triggers mitochondrial pathway-dependent apoptosis. In addition, the amount of JNK is strongly upregulated in a ROS-dependent way. In contrast to TNFα plus cycloheximide no cFLIP degradation is observed suggesting a different apoptosis pathway in which the Itch-mediated cFLIP degradation and predominantly caspase-8 activation is not involved. Time-resolved data of the respective pro- and antiapoptotic factors are obtained and subjected to mathematical modeling. On the basis of these data we developed a mathematical model which reproduces the complex interplay regulating the phosphorylation status of JNK and generation of ROS. This model was fully integrated with our model of TNFα/Fas ligand sensitizing as well as with a published NF-κB-model. The resulting comprehensive model delivers insight in the dynamical interplay between the TNFα and FasL pathways, NF-κB and ROS and gives an example for successful model integration

Infection of Semen-Producing Organs by SIV during the Acute and Chronic Stages of the Disease

International audienceBACKGROUND: Although indirect evidence suggests the male genital tract as a possible source of persistent HIV shedding in semen during antiretroviral therapy, this phenomenon is poorly understood due to the difficulty of sampling semen-producing organs in HIV+ asymptomatic individuals. METHODOLOGY/PRINCIPAL FINDINGS: Using a range of molecular and cell biological techniques, this study investigates SIV infection within reproductive organs of macaques during the acute and chronic stages of the disease. We demonstrate for the first time the presence of SIV in the testes, epididymides, prostate and seminal vesicles as early as 14 days post-inoculation. This infection persists throughout the chronic stage and positively correlates with blood viremia. The prostate and seminal vesicles appear to be the most efficiently infected reproductive organs, followed by the epididymides and testes. Within the male genital tract, mostly T lymphocytes and a small number of germ cells harbour SIV antigens and RNA. In contrast to the other organs studied, the testis does not display an immune response to the infection. Testosteronemia is transiently increased during the early phase of the infection but spermatogenesis remains unaffected. CONCLUSIONS/SIGNIFICANCE: The present study reveals that SIV infection of the macaque male genital tract is an early event and that semen-producing organs display differential infection levels and immune responses. These results help elucidate the origin of HIV in semen and constitute an essential base to improving the design of antiretroviral therapies to eradicate virus from semen