ZNF804a Regulates Expression of the Schizophrenia-Associated Genes PRSS16, COMT, PDE4B, and DRD2

ZNF804a was identified by a genome-wide association study (GWAS) in which a single nucleotide polymorphism (SNP rs1344706) in ZNF804a reached genome-wide statistical significance for association with a combined diagnosis of schizophrenia (SZ) and bipolar disorder. Although the molecular function of ZNF804a is unknown, the amino acid sequence is predicted to contain a C2H2-type zinc-finger domain and suggests ZNF804a plays a role in DNA binding and transcription. Here, we confirm that ZNF804a directly contributes to transcriptional control by regulating the expression of several SZ associated genes and directly interacts with chromatin proximal to the promoter regions of PRSS16 and COMT, the two genes we find upregulated by ZNF804a. Using immunochemistry we establish that ZNF804a is localized to the nucleus of rat neural progenitor cells in culture and in vivo. We demonstrate that expression of ZNF804a results in a significant increase in transcript levels of PRSS16 and COMT, relative to GFP transfected controls, and a statistically significant decrease in transcript levels of PDE4B and DRD2. Furthermore, we show using chromatin immunoprecipitation assays (ChIP) that both epitope-tagged and endogenous ZNF804a directly interacts with the promoter regions of PRSS16 and COMT, suggesting a direct upregulation of transcription by ZNF804a on the expression of these genes. These results are the first to confirm that ZNF804a regulates transcription levels of four SZ associated genes, and binds to chromatin proximal to promoters of two SZ genes. These results suggest a model where ZNF804a may modulate a transcriptional network of SZ associated genes

Identification of Novel Genetic Loci Associated with Thyroid Peroxidase Antibodies and Clinical Thyroid Disease

Peer reviewe

Urgent-start peritoneal dialysis: is it ready for prime time?

Purpose of reviewThis review aims to provide an up-to-date summary of the definition, current practice and evidence regarding the role of urgent-start peritoneal dialysis (USPD) in patients with end-stage kidney disease who present with unplanned dialysis requirement without functional access.Recent findingsUSPD can be broadly defined as peritoneal dialysis initiation within the first 2 weeks after catheter insertion. Published practice patterns, in terms of catheter insertion approach, peritoneal dialysis initiation time or initial fill volume, are highly variable. Most evidence comes from small, retrospective, single-center observational studies and only one randomized controlled trial. Compared with conventional-start peritoneal dialysis, USPD appears to moderately increase the risk of mechanical complications, such as dialysate leak (relative risk 3.21, 95% confidence interval 1.73-5.95), but does not appear to adversely affect technique or patient survival. USPD may also reduce the risk of bacteremia compared with urgent-start hemodialysis delivered by central venous catheter (CVC).SummaryUSPD represents an important opportunity to establish patients with urgent, unplanned dialysis requirements on a cost-effective, home-based dialysis modality with lower serious infection risks than the alternative option of hemodialysis via CVC. Robust, well executed trials are required to better inform optimal practice and safeguard patient-centered and patient-reported outcomes

Buffalo Sacrifice and Megalithic Cults in the Shamanism of Orissa tribes. A Central-Asiatic Model.

All articles are free to read 3 months after the publication date. \ud \ud ABSTRACT\ud \ud \ud BACKGROUND AND OBJECTIVES: Ultrasound is a common and necessary part of acute care medicine, but may present an infection risk to patients secondary to transfer of infectious agents between patients. Our primary objective was to detect blood contamination on ultrasound equipment in emergency departments (EDs) and intensive care units. Secondary objectives included detection of microbial contamination and determination of factors associated with contamination.\ud \ud DESIGN AND SETTING: We tested ultrasound equipment used in five EDs and five ICUs for blood and microbial contamination, and collated and analysed contamination data using tables and multiple logistic regression.\ud \ud MAIN OUTCOME MEASURES AND RESULTS: We performed 109 tests for blood and 131 tests for microbial contamination, with 61% of samples testing positive for blood contamination (95% CI, 52%–71%) and 48% testing positive for microbiological contamination (95% CI, 40%–57%). Transducer leads and transducers had high blood contamination (88% and 57%, respectively) and microbiological contamination (62% and 46%, respectively). Equipment from ICUs was less likely to test positive (odds ratio, 0.55; 95% CI, 0.37–0.79). Only 51% of blood-contaminated samples were visibly stained, and visible staining was not associated with microbiological contamination (57%; P =1).\ud \ud CONCLUSION: Our results show significant contamination of ultrasound equipment, and that visual inspection of equipment is neither sufficient nor reliable in excluding contamination. Ultrasound equipment is a possible factor in the transmission of infectious diseases in EDs and ICUs. Guidelines must be formulated, disseminated and rapidly adopted to ensure the safety of the most acutely ill patients exposed to ultrasound procedures in acute care settings

Efforts to Attenuate the Spread of Infection (EASI): a prospective, observational multicentre survey of ultrasound equipment in Australian emergency departments and intensive care units

All articles are free to read 3 months after the publication date. ABSTRACT BACKGROUND AND OBJECTIVES: Ultrasound is a common and necessary part of acute care medicine, but may present an infection risk to patients secondary to transfer of infectious agents between patients. Our primary objective was to detect blood contamination on ultrasound equipment in emergency departments (EDs) and intensive care units. Secondary objectives included detection of microbial contamination and determination of factors associated with contamination. DESIGN AND SETTING: We tested ultrasound equipment used in five EDs and five ICUs for blood and microbial contamination, and collated and analysed contamination data using tables and multiple logistic regression. MAIN OUTCOME MEASURES AND RESULTS: We performed 109 tests for blood and 131 tests for microbial contamination, with 61% of samples testing positive for blood contamination (95% CI, 52%–71%) and 48% testing positive for microbiological contamination (95% CI, 40%–57%). Transducer leads and transducers had high blood contamination (88% and 57%, respectively) and microbiological contamination (62% and 46%, respectively). Equipment from ICUs was less likely to test positive (odds ratio, 0.55; 95% CI, 0.37–0.79). Only 51% of blood-contaminated samples were visibly stained, and visible staining was not associated with microbiological contamination (57%; P =1). CONCLUSION: Our results show significant contamination of ultrasound equipment, and that visual inspection of equipment is neither sufficient nor reliable in excluding contamination. Ultrasound equipment is a possible factor in the transmission of infectious diseases in EDs and ICUs. Guidelines must be formulated, disseminated and rapidly adopted to ensure the safety of the most acutely ill patients exposed to ultrasound procedures in acute care settings

Dysbindin Modulates Prefrontal Cortical Glutamatergic Circuits and Working Memory Function in Mice

Behavioral genetic studies of humans have associated variation in the DTNBP1 gene with schizophrenia and its cognitive deficit phenotypes. The protein coded for by DTNBP1, dysbindin, is expressed within forebrain glutamatergic neurons, where it interacts with proteins involved in vesicular trafficking and exocytosis. In order to further delineate the cellular, physiological and behavioral phenotypes associated with reduced dysbindin expression, we conducted studies in mice carrying a null mutation within the dtnbp1 gene. Dysbindin mutants exhibited impairments of spatial working memory as compared with wild-type controls; heterozygous mice exhibited intermediate levels of cognitive dysfunction. Deep layer pyramidal neurons recorded in the prefrontal cortex of mutant mice exhibited reductions in paired-pulse facilitation, and evoked and miniature excitatory post-synaptic currents, indicating a difference in the function of pre-synaptic glutamatergic terminals, as well as elevated spike thresholds. Taken together, these data indicate that dysbindin potently regulates excitatory transmission in prefrontal cortex, potentially through a pre-synaptic mechanism, and consequently modulates cognitive functions depending upon this brain region, providing new insights into the molecular mechanisms underlying cortical dysfunction in schizophrenia

GWAS in autoimmune thyroid disease: redefining our understanding of pathogenesis

The ability of the immune system to protect the body from attack by foreign antigens is essential for human survival. The immune system can, however, start to attack the body's own organs. An autoimmune response against components of the thyroid gland affects 2-5 of the general population. Considerable familial clustering is also observed in autoimmune thyroid disease (AITD). Teasing out the genetic contribution to AITD over the past 40 years has helped unravel how immune disruption leads to disease onset. Breakthroughs in genome-wide association studies (GWAS) in the past decade have facilitated screening of a greater proportion of the genome, leading to the identification of a before unimaginable number of AITD susceptibility loci. This Review will focus on the new susceptibility loci identified by GWAS, what insights these loci provide about the pathogenesis of AITD and how genetic susceptibility loci shared between different autoimmune diseases could help explain disease co-clustering within individuals and families. This Review also discusses where future efforts should be focused to translate this step forward in our understanding of the genetic contribution to AITD into a better understanding of disease presentation and progression, and improved therapeutic options.© 2013 Macmillan Publishers Limited. All rights reserved