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

Atherosclerotic vascular disease associated with chronic kidney disease

Cardiovascular risk increases as glomerular filtration rate (GFR) declines in progressive renal disease and is maximal in patients with end-stage renal disease requiring maintenance dialysis. Atherosclerotic vascular disease, for which hyperlipidemia is the main risk factor and lipid-lowering therapy is the key intervention, is common. However, the pattern of dyslipidemia changes with low GFR and the association with vascular events becomes less clear. While the pathophysiology and management of patients with early chronic kidney disease (CKD) is similar to the general population, advanced and end-stage CKD is characterized by a disproportionate increase in fatal events, ineffectiveness of statin therapy, and greatly increased risk associated with coronary interventions. The most effective strategies to reduce atherosclerotic cardiovascular disease in CKD are to slow the decline in renal function or to restore renal function by transplantation

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

Effects of transfusing older red blood cells and platelets on obstetric patient outcomes: A retrospective cohort study

Objective: To investigate associations between transfusion of blood products close to the end of shelf-life and clinical outcomes in obstetric inpatients. Methods: Mortality and morbidity were compared in patients transfused exclusively with red blood cells (RBC) stored for less than 21 days (fresh) versus RBC stored for 35 days or longer (old), and platelets (PLT) stored for 3 days or fewer (fresh) versus 4 days or longer (old) in Queensland, Australia from 2007 to 2013. Multivariable models were used to examine associations between these groups of blood products and clinical end points. Results: There were 3371 patients who received RBC and 280 patients who received PLT of the eligible storage durations. Patients transfused with old RBC received fewer transfusions (2.7 ± 1.8 vs. 2.3 ± 1.0 units; P < 0.001). However, a higher rate of single-unit transfusions was also seen in those patients who exclusively received old RBC (252 [9.3%] vs. 92 [13.7%]; P = 0.003). Comparison of fresh vs. old blood products revealed no differences in the quantities of transfused RBC (9.5 ± 5.9 vs. 9.1 ± 5.2 units; P = 0.680) or PLT (1.5 ± 0.8 vs. 1.4 ± 1.1 units; P = 0.301) as well as the length of hospital stay for RBC (3 [2–5] vs. 3 [2–5] days; P = 0.124) or PLT (5 [4–8] vs. 6 [4–9] days; P = 0.120). Conclusion: Transfusing exclusively older RBC or PLT was not associated with increased morbidity or mortality.</p

Regression mapping of association between the human leukocyte antigen region and Graves' disease

The human leukocyte antigen class II genes DRB1, DQB1, and DQA1 are associated with Graves disease (GD), but, because of strong linkage disequilibrium within this region, the primary etiological variant(s) remains unknown. In the present study, 871 patients with GD and 621 control subjects were genotyped at the DRB1, DQB1, and DQA1 loci. All three loci were associated with GD (P = 1.45 x 10-12, P = 3.20 x 10-5, and P = 9.26 x 10-12, respectively). Stepwise logistic-regression analysis showed that the association could be explained by either DRB1 or DQA1 but not by DQB1. To extend previous results, the amino acid sequence of the exon 2-encoded peptide-binding domain of DRB1 was predicted for each subject, and, by use of logistic regression, each position was analyzed for association with GD. Of 102 amino acids, 70 were uninformative; of the remaining 32 amino acids, 13 were associated with GD (P values ranged from 2.20x10-4 to 1.2x10-12). The strongest association was at position B74. This analysis is consistent with the possibility that position B74 of exon 2 of the DRB1 molecule may have a specific and central role in autoantigen presentation by DRB1 to T lymphocytes. However, we cannot yet exclude a primary role for DQA1 or for other polymorphisms that affect DRB1 function or expression