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To demonstrate the application of the proposed protocol, we have applied this approach to rare-variant datasets of schizophrenia. Compared with a method which only uses variant information, DECO is able to prioritize additional risk genes.

DECO can be used to analyze rare-variants and biological pathways or cell types for any disease. The package is available on Github https//github.com/hoangtn/DECO.

DECO can be used to analyze rare-variants and biological pathways or cell types for any disease. The package is available on Github https//github.com/hoangtn/DECO.A pentanucleotide TTTCA repeat insertion into a polymorphic TTTTA repeat element in SAMD12 causes benign adult familial myoclonic epilepsy. Although the precise determination of the entire SAMD12 repeat sequence is important for molecular diagnosis and research, obtaining this sequence remains challenging when using conventional genomic/genetic methods, and even short-read and long-read next-generation sequencing technologies have been insufficient. Incomplete information regarding expanded repeat sequences may hamper our understanding of the pathogenic roles played by varying numbers of repeat units, genotype-phenotype correlations, and mutational mechanisms. Here, we report a new approach for the precise determination of the entire expanded repeat sequence and present a workflow designed to improve the diagnostic rates in various repeat expansion diseases. We examined 34 clinically diagnosed benign adult familial myoclonic epilepsy patients, from 29 families using repeat-primed PCR, Southern blot, and long-ved SAMD12-negative cases were investigated using whole-genome long-read sequencing, and infrequent, disease-associated, repeat expansions were identified in two cases. The strategic workflow resolved two questionable SAMD12-positive cases and two previously SAMD12-negative cases, increasing the diagnostic yield from 69% (20/29 families) to 83% (24/29 families). This study indicates the significant utility of long-read sequencing technologies to explore the pathogenic contributions made by various repeat units in complex repeat expansions and to improve the overall diagnostic rate.Polyhistidine peptides (PHPs), sequences comprising only histidine residues (>His8), are effective cell-penetrating peptides for plant cells. Using PHP-fusion proteins, we aimed to deliver proteins into cultured plant cells from Nicotiana tabacum, Oryza sativa, and Cryptomeria japonica. Co-cultivation of cultured cells with fusion proteins combining maltose-binding protein (MBP), red fluorescent protein (RFP), and various PHPs (MBP-RFP-His8-His20) in one polypeptide showed the cellular uptake of fusion proteins in all plant cell lines. Maximum intracellular fluorescence was shown in MBP-RFP-His20. Further, adenylate cyclase (CyaA), a synthase of cyclic adenosine monophosphate (cAMP) activated by cytosolic calmodulin, was used as a reporter for protein delivery in living cells. Selleckchem Camostat A fusion protein combining MBP, RFP, CyaA, and His20 (MBP-RFP-CyaA-His20) was delivered into plant cells and increased intracellular fluorescence and cAMP production in all cell lines. The present study demonstrates that PHPs are effective carriers of proteins into the intracellular space of various cultured plant cells.The Deepwater Horizon oil spill response and clean-up (OSRC) involved over 9000 large and small vessels deployed in waters of the Gulf of Mexico across four states (Alabama, Florida, Louisiana, and Mississippi). For the GuLF STUDY, we developed exposure estimates of oil-related components for many work groups to capture a wide range of OSRC operations on these vessels, such as supporting the four rig vessels charged with stopping the spill at the wellhead; skimming oil; in situ burning of oil; absorbing and containing oil by boom; and environmental monitoring. Work groups were developed by (i) vessel activity; (ii) location (area of the Gulf or state); and (iii) time period. Using Bayesian methods, we computed exposure estimates for these groups for total hydrocarbons measured as total petroleum hydrocarbons (THC), benzene, toluene, ethylbenzene, xylene, and n-hexane (BTEX-H). Estimates of the arithmetic means for THC ranged from 0.10 ppm [95% credible interval (CI) 0.04, 0.38 ppm] in time periods 2 and 3 (16 July-30 September 2010) to 15.06 ppm (95% CI 10.74, 22.41 ppm) in time period 1a (22 April-15 May 2010). BTEX-H estimates were substantially lower (in the parts per billion range). Exposure levels generally fell over time and differed statistically by activity, location, and time for some groups. These exposure estimates have been used to develop job-exposure matrices for the GuLF STUDY.

In critically ill patients, maintaining appropriate serum potassium concentrations requires careful supplementation to correct hypokalemia but avoid hyperkalemia. At the study institution, an institution-based, nurse-driven standardized electrolyte replacement protocol is used in critically ill patients with a serum creatinine concentration of 2 mg/dL or less. If the serum creatinine concentration is greater than 2 mg/dL, electrolyte replacement requires a physician order.

To determine if standardized potassium supplementation is safe in critically ill patients with renal insufficiency not requiring renal replacement therapy.

This study was an institutional review board-approved, single-center, retrospective evaluation of critically ill patients receiving intravenous potassium replacement per protocol. Patients were grouped according to serum creatinine concentration (≤ 2 mg/dL or > 2 mg/dL) at the time of replacement. The primary outcome was the incidence of hyperkalemia (potassium concentration ≥ 5 mEq/L) following potassium replacement. Secondary outcomes were the incidence of hyperkalemia, change in serum potassium concentration, and need for hyperkalemia treatment. Outcomes were analyzed using χ2 and t tests.

Of 814 patients screened, 145 were included (99 with serum creatinine ≤ 2 mg/dL and 46 with serum creatinine > 2 mg/dL). The incidence of hyperkalemia was not different between groups (P = .57). Five patients experienced hyperkalemia; none received hyperkalemia treatment. Change in serum potassium was similar for patients in the 2 groups (P = .33).

A standardized, nurse-driven electrolyte replacement protocol can be used safely in critically ill patients with renal insufficiency not requiring renal replacement therapy.

A standardized, nurse-driven electrolyte replacement protocol can be used safely in critically ill patients with renal insufficiency not requiring renal replacement therapy.