Androgen Receptor Function Links Human Sexual Dimorphism to DNA Methylation

Sex differences are well known to be determinants of development, health and disease. Epigenetic mechanisms are also known to differ between men and women through X-inactivation in females. We hypothesized that epigenetic sex differences may also result from sex hormone functions, in particular from long-lasting androgen programming. We aimed at investigating whether inactivation of the androgen receptor, the key regulator of normal male sex development, is associated with differences of the patterns of DNA methylation marks in genital tissues. To this end, we performed large scale array-based analysis of gene methylation profiles on genomic DNA from labioscrotal skin fibroblasts of 8 males and 26 individuals with androgen insensitivity syndrome (AIS) due to inactivating androgen receptor gene mutations. By this approach we identified differential methylation of 167 CpG loci representing 162 unique human genes. These were significantly enriched for androgen target genes and low CpG content promoter genes. Additional 75 genes showed a significant increase of heterogeneity of methylation in AIS compared to a high homogeneity in normal male controls. Our data show that normal and aber

Qualitative analysis of round-table discussions on the business case and procurement challenges for hospital electronic prescribing systems

There is a pressing need to understand the challenges surrounding procurement of and business case development for hospital electronic prescribing systems, and to identify possible strategies to enhance the efficiency of these processes in order to assist strategic decision making.We organized eight multi-disciplinary round-table discussions in the United Kingdom. Participants included policy makers, representatives from hospitals, system developers, academics, and patients. Each discussion was digitally audio-recorded, transcribed verbatim and, together with accompanying field notes, analyzed thematically with NVivo9.We drew on data from 17 participants (approximately eight per roundtable), six hours of discussion, and 15 pages of field notes. Key challenges included silo planning with systems not being considered as part of an integrated organizational information technology strategy, lack of opportunity for interactions between customers and potential suppliers, lack of support for hospitals in choosing appropriate systems, difficulty of balancing structured planning with flexibility, and the on-going challenge of distinguishing “wants” and aspirations from organizational “needs”.Development of business cases for major investments in information technology does not take place in an organizational vacuum. Building on previously identified potentially transferable dimensions to the development and execution of business cases surrounding measurements of costs/benefits and risk management, we have identified additional components relevant to ePrescribing systems. These include: considerations surrounding strategic context, case for change and objectives, future service requirements and options appraisal, capital and revenue implications, timescale and deliverability, and risk analysis and management

Cyber Insurance

This volume covers a wide spectrum of issues relating to economic and political development enabled by information and communication technology (ICT)

The Daily Ardmoreite

Daily newspaper from Ardmore, Chickasaw Nation, Indian Territory. Coverage includes local, territorial, and United States national news along with advertising

Metabolic regulation of adipose tissue macrophage (ATM) function in obesity and diabetes

SIGNIFICANCE: Obesity and diabetes are associated with chronic activation of inflammatory pathways that are important mechanistic links between insulin resistance (IR), type 2 diabetes (T2D) and cardiovascular disease pathogenesis. The development of these metabolic diseases is associated with changes in the both the number and phenotype of adipose tissue macrophages. Emerging lines of evidence have shown that adipose tissue macrophages (ATM) release pro-inflammatory cytokines similar to classically-activated M1 macrophages, that directly contribute to IR or T2D. In contrast, adipose tissue from lean healthy individuals contains macrophages with a less inflammatory M2 phenotype. Recent Advances: Recent research has shown that macrophage phenotype is linked to profound changes in macrophage cellular metabolism. CRITICAL ISSUES: This review focuses on the role of macrophages in adipose tissue inflammation and obesity, and the metabolic changes in macrophage function that occur with activation that underpin their role in the pathogenesis of IR and T2D. We highlight current targets for altering macrophage metabolism from both within the field of metabolic disease and adipose tissue biology and more widely within inflammatory biology. FUTURE DIRECTIONS: As our knowledge of macrophage metabolic programming in adipose tissue builds, there will be increasing scope for targeting this aspect of macrophage biology as a therapeutic strategy in metabolic diseases

Metabolic regulation of adipose tissue macrophage (ATM) function in obesity and diabetes

SIGNIFICANCE: Obesity and diabetes are associated with chronic activation of inflammatory pathways that are important mechanistic links between insulin resistance (IR), type 2 diabetes (T2D) and cardiovascular disease pathogenesis. The development of these metabolic diseases is associated with changes in the both the number and phenotype of adipose tissue macrophages. Emerging lines of evidence have shown that adipose tissue macrophages (ATM) release pro-inflammatory cytokines similar to classically-activated M1 macrophages, that directly contribute to IR or T2D. In contrast, adipose tissue from lean healthy individuals contains macrophages with a less inflammatory M2 phenotype. Recent Advances: Recent research has shown that macrophage phenotype is linked to profound changes in macrophage cellular metabolism. CRITICAL ISSUES: This review focuses on the role of macrophages in adipose tissue inflammation and obesity, and the metabolic changes in macrophage function that occur with activation that underpin their role in the pathogenesis of IR and T2D. We highlight current targets for altering macrophage metabolism from both within the field of metabolic disease and adipose tissue biology and more widely within inflammatory biology. FUTURE DIRECTIONS: As our knowledge of macrophage metabolic programming in adipose tissue builds, there will be increasing scope for targeting this aspect of macrophage biology as a therapeutic strategy in metabolic diseases

HIPAA Compliance: An Institutional Theory Perspective

One would think that the enactment of the HIPAA and associated mandates on data security and privacy has brought a major shift in the information security management practices across the US healthcare sector. Unfortunately, recent industry reports indicate substantially low level of regulatory compliance, thus raising security concerns to US health IT infrastructure. This research develops a regulatory compliance model by drawing insights from institutional theory literature to identify the key drivers influencing compliance, both institutional and market forces - e.g. mix of state and federal privacy regulations, pressure from compliance leaders in the region, and the consumer demand for privacy among others. The primary contribution of this research lies in the novel application of institutional theory to explain the variability in regulatory compliance prevalent in the US healthcare sector