ABSTRACT
Despite positive trends, life expectancy in Serbia is well below the average for the WHO European Region.The probability of dying from one of the main noncommunicable diseases (NCDs) between the ages of30 and 69 years is 20%. This has significant socioeconomic consequences for the development of thecountry and calls for an immediate strengthening of the health system to respond to the growing burdenof NCDs. Despite significant progress and political commitment in Serbia, the outcomes of NCDs couldstill be improved. This report reviews the challenges and opportunities facing the health system in Serbiain scaling up core services for the prevention, early diagnosis and management of NCDs. The report alsoprovides examples of good practice in care. Policy recommendations are made for further action, based onthe assessment.
Subject(s)
Chronic Disease , Noncommunicable Diseases , Cardiovascular Diseases , Delivery of Health Care , Universal Health Insurance , Primary Health Care , SerbiaABSTRACT
Functional genomic elements are marked by characteristic DNA and histone modification signatures. How combinatorial chromatin modification states are recognized by epigenetic reader proteins and how this is linked to their biological function is largely unknown. Here we provide a detailed molecular analysis of chromatin recognition by the lysine demethylase KDM2A. Using biochemical approaches we identify a nucleosome interaction module within KDM2A consisting of a CXXC type zinc finger, a PHD domain and a newly identified Heterochromatin Protein 1 (HP1) interaction motif that mediates direct binding between KDM2A and HP1. This nucleosome interaction module enables KDM2A to decode nucleosomal H3K9me3 modification in addition to CpG methylation signals. The multivalent engagement with DNA and HP1 results in a nucleosome binding circuit in which KDM2A can be recruited to H3K9me3-modified chromatin through HP1, and HP1 can be recruited to unmodified chromatin by KDM2A. A KDM2A mutant deficient in HP1-binding is inactive in an in vivo overexpression assay in zebrafish embryos demonstrating that the HP1 interaction is essential for KDM2A function. Our results reveal a complex regulation of chromatin binding for both KDM2A and HP1 that is modulated by DNA- and H3K9-methylation, and suggest a direct role for KDM2A in chromatin silencing.
Subject(s)
Chromosomal Proteins, Non-Histone/chemistry , Chromosomal Proteins, Non-Histone/metabolism , F-Box Proteins/chemistry , F-Box Proteins/metabolism , Jumonji Domain-Containing Histone Demethylases/chemistry , Jumonji Domain-Containing Histone Demethylases/metabolism , Animals , Animals, Genetically Modified , Cell Line , Chromobox Protein Homolog 5 , Chromosomal Proteins, Non-Histone/genetics , CpG Islands , Cricetinae , DNA Methylation , F-Box Proteins/genetics , HEK293 Cells , HeLa Cells , Histones/metabolism , Humans , Jumonji Domain-Containing Histone Demethylases/genetics , Models, Genetic , Mutation , Neoplasms/genetics , Neoplasms/metabolism , Nucleosomes/genetics , Nucleosomes/metabolism , Protein Interaction Domains and Motifs , Recombinant Fusion Proteins/chemistry , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Two-Hybrid System Techniques , Zebrafish , Zinc FingersABSTRACT
This publication summarizes the findings of a series of technical reports by many experts involved in assessing the effectiveness of pharmaceutical policy on generic essential medicines markets in the context of the Hungarian health system. Within the framework of certain agreements, WHO provided technical advice in collaboration with local experts and with involvement from international consultants. The primary objective of this report is to provide an overview of the development of incentives to use generics in the Hungarian health system up to the end of 2011, focusing in particular on the reference pricing system and assessing what impact these incentives have had in recent years.
Subject(s)
Drugs, Generic , Health Policy , Healthcare Financing , Health Care Sector , Commerce , HungaryABSTRACT
This report reviews health system challenges and opportunities in Hungary to scale up core services for the prevention, early diagnosis and management of diabetes. Diabetes is used in the report as a lens to assess the effectiveness of the health system in addressing the noncommunicable disease (NCD) burden. Although NCD mortality in general has been decreasing over the past 20 years, the prevalence of diabetes remains high and is growing. The report found good progress implementing innovative intersectorial nutrition policies including the Public Health Product Tax. At the same time, core individual services such as early detection and proactive management of diabetes and its complications require further efforts. The main barrier to better diabetes and NCD control in Hungary was found to be the lack of citizen empowerment; the population generally has a low level of health literacy and lacks the knowledge and skills to manage their own health. Other problems identified include a mismatch between the incentive system and the requirements for effective diabetes management, with current measures focusing on processes rather than outcomes. These challenges need to be addressed within a context of a shortage of human resources and a lack of standardized training in diabetes adapted to different cadres of health personnel. The report ends with six strategic recommendations to address these challenges.
