Abdominal aortic calcification on a plain X-ray and the relation with significant coronary artery disease in asymptomatic chronic dialysis patients

BACKGROUND: Coronary artery disease (CAD) is common in asymptomatic chronic dialysis patients and plays an important role in their poor survival. Early identification of these high-risk patients could improve treatment and reduce mortality. Abdominal aortic calcification (AAC) has previously been associated with CAD in autopsy studies. Since the AAC can be quantified easily using a lateral lumbar X-ray we hypothesized that the extent of AAC as assessed on a lateral lumbar X-ray might be predictive of the presence of significant CAD in dialysis patients. METHODS: All patients currently enrolled in the ICD2 trial without a history of CABG or a PCI with stent implantation were included in this study. All patients underwent CT-angiography (CTA) and a lateral X-ray of the abdomen. AAC on X-ray was quantified using a previously validated scoring system whereupon the association between AAC and the presence of significant CAD was assessed. RESULTS: A total of 90 patients were included in this study (71% male, 67 ± 7 years old). Forty-six patients were found to have significant CAD. AAC-score was significantly higher in patients with CAD (10.1 ± 4.9 vs 6.3 ± 4.6 (p < 0.05). Multivariate regression analysis revealed that AAC score is an independent predictor for the presence of CAD with a 1,2 fold higher risk per point increase (p < 0.01). The AAC score has a sensitivity of 85% and a specificity of 57% for the presence of significant CAD. CONCLUSION: This study shows that abdominal aortic calcification as assessed on a lateral lumbar X-ray is predictive for the presence of significant coronary artery disease in asymptomatic dialysis patients. This simple, non-invasive and cheap screening method could contribute to early identification of patients eligible for further screening of CAD. TRIAL REGISTRATION: NTR948, registered 10-4-2007 ; ISRCTN20479861, registered 2-5-200

Implementing telehealth to support medical practice in rural/remote regions: what are the conditions for success?

BACKGROUND: Telehealth, as other information and communication technologies (ICTs) introduced to support the delivery of health care services, is considered as a means to answer many of the imperatives currently challenging health care systems. In Canada, many telehealth projects are taking place, mostly targeting rural, remote or isolated populations. So far, various telehealth applications have been implemented and have shown promising outcomes. However, telehealth utilisation remains limited in many settings, despite increased availability of technology and telecommunication infrastructure. METHODS: A qualitative field study was conducted in four remote regions of Quebec (Canada) to explore perceptions of physicians and managers regarding the impact of telehealth on clinical practice and the organisation of health care services, as well as the conditions for improving telehealth implementation. A total of 54 respondents were interviewed either individually or in small groups. Content analysis of interviews was performed and identified several effects of telehealth on remote medical practice as well as key conditions to ensure the success of telehealth implementation. RESULTS: According to physicians and managers, telehealth benefits include better access to specialised services in remote regions, improved continuity of care, and increased availability of information. Telehealth also improves physicians' practice by facilitating continuing medical education, contacts with peers, and access to a second opinion. At the hospital and health region levels, telehealth has the potential to support the development of regional reference centres, favour retention of local expertise, and save costs. Conditions for successful implementation of telehealth networks include the participation of clinicians in decision-making, the availability of dedicated human and material resources, and a planned diffusion strategy. Interviews with physicians and managers also highlighted the importance of considering telehealth within the broader organisation of health care services in remote and rural regions. CONCLUSION: This study identified core elements that should be considered when implementing telehealth applications with the purpose of supporting medical practice in rural and remote regions. Decision-makers need to be aware of the specific conditions that could influence telehealth integration into clinical practices and health care organisations. Thus, strategies addressing the identified conditions for telehealth success would facilitate the optimal implementation of this technology

DNA demethylation pathways: Additional players and regulators.

DNA demethylation can occur passively by "dilution" of methylation marks by DNA replication, or actively and independently of DNA replication. Direct conversion of 5-methylcytosine (5mC) to cytosine (C), as originally proposed, does not occur. Instead, active DNA methylation involves oxidation of the methylated base by ten-eleven translocations (TETs), or deamination of the methylated or a nearby base by activation induced deaminase (AID). The modified nucleotide, possibly together with surrounding nucleotides, is then replaced by the BER pathway. Recent data clarify the roles and the regulation of well-known enzymes in this process. They identify base excision repair (BER) glycosylases that may cooperate with or replace thymine DNA glycosylase (TDG) in the base excision step, and suggest possible involvement of DNA damage repair pathways other than BER in active DNA demethylation. Here, we review these new developments

The RNA-binding protein PTBP1 is necessary for B cell selection in germinal centers.

Antibody affinity maturation occurs in germinal centers (GCs), where B cells cycle between the light zone (LZ) and the dark zone. In the LZ, GC B cells bearing immunoglobulins with the highest affinity for antigen receive positive selection signals from helper T cells, which promotes their rapid proliferation. Here we found that the RNA-binding protein PTBP1 was needed for the progression of GC B cells through late S phase of the cell cycle and for affinity maturation. PTBP1 was required for proper expression of the c-MYC-dependent gene program induced in GC B cells receiving T cell help and directly regulated the alternative splicing and abundance of transcripts that are increased during positive selection to promote proliferation

Most gene fusions in cancer are stochastic events

Cancer-associated gene fusions resulting in chimeric proteins or aberrant expression of one or both partner genes are pathogenetically and clinically important in several hematologic malignancies and solid tumors. Since the advent of different types of massively parallel sequencing (MPS), the number of identified gene fusions has increased dramatically, prompting the question whether they all have a biologic impact. By ascertaining the chromosomal locations of 8934 genes involved in 10 861 gene fusions reported in the literature, we here show that there is a highly significant association between gene content of chromosomes and chromosome bands and number of genes involved in fusions. This strongly suggests that a clear majority of gene fusions detected by MPS are stochastic events associated with the number of genes available to participate in fusions and that most reported gene fusions are passengers without any pathogenetic importance

Genome organization and DNA accessibility control antigenic variation in trypanosomes.

Many evolutionarily distant pathogenic organisms have evolved similar survival strategies to evade the immune responses of their hosts. These include antigenic variation, through which an infecting organism prevents clearance by periodically altering the identity of proteins that are visible to the immune system of the host1. Antigenic variation requires large reservoirs of immunologically diverse antigen genes, which are often generated through homologous recombination, as well as mechanisms to ensure the expression of one or very few antigens at any given time. Both homologous recombination and gene expression are affected by three-dimensional genome architecture and local DNA accessibility2,3. Factors that link three-dimensional genome architecture, local chromatin conformation and antigenic variation have, to our knowledge, not yet been identified in any organism. One of the major obstacles to studying the role of genome architecture in antigenic variation has been the highly repetitive nature and heterozygosity of antigen-gene arrays, which has precluded complete genome assembly in many pathogens. Here we report the de novo haplotype-specific assembly and scaffolding of the long antigen-gene arrays of the model protozoan parasite Trypanosoma brucei, using long-read sequencing technology and conserved features of chromosome folding4. Genome-wide chromosome conformation capture (Hi-C) reveals a distinct partitioning of the genome, with antigen-encoding subtelomeric regions that are folded into distinct, highly compact compartments. In addition, we performed a range of analyses—Hi-C, fluorescence in situ hybridization, assays for transposase-accessible chromatin using sequencing and single-cell RNA sequencing—that showed that deletion of the histone variants H3.V and H4.V increases antigen-gene clustering, DNA accessibility across sites of antigen expression and switching of the expressed antigen isoform, via homologous recombination. Our analyses identify histone variants as a molecular link between global genome architecture, local chromatin conformation and antigenic variation