Добірка наукової літератури з теми "Approximately 379-approximately 440"

Using gigohm-seal recording, we studied ion channel expression in resting and activated T lymphocytes from mice. Both the number of channels per cell and the predominant type of K+ channel depend upon the state of activation of the cell. Unstimulated T cells express small numbers of K+ channels, typically a dozen per cell, and are heterogeneous, usually expressing either type n or type l K+ channels (see DeCoursey, T. E., K. G. Chandy, S. Gupta, and M. D. Cahalan. 1987. Journal of General Physiology. 89:379-404). 1 d after stimulation by the murine T cell mitogen concanavalin A, large numbers of type n K+ channels appear in enlarged, activated cells. Type n channels appear in activated cells with a time course consistent with that reported for mitogen-induced enhancement of protein synthesis. Voltage-gated tetrodotoxin-sensitive Na+ channels present in about one-third of unstimulated cells from the MRL-n strain are increased approximately 10-fold after activation.

Introduction: The exposure to ionizing radiation has increased significantly with the wide availability of computed tomography (CT) scans and portable imaging technology. We examine the pattern of use of inpatient diagnostic imaging and radiation exposure in the neuro-intensive care unit (Neuro ICU, N-ICU) patient population at a large academic medical center. Methods: We retrospectively evaluated all patients admitted to the Neuro ICU at our academic medical center from January 1 to December 31, 2013. The number and type of CT studies was collected, and the corresponding estimated radiation dose was calculated. We limited the evaluation to CT scans, which accounts for the majority of radiation exposure. Data were electronically collected and cross-referenced to the patients’ electronic medical records (EMR) and radiology records. Radiation dose estimates were calculated based on published reference values and conversion factors (CT head (2mSv)), CT angiography of the head and neck (7-10 mSv), Ct Chest /Abd/pelvis ( 10 mSv), CT cerebral perfusion analysis (3.3 mSv). Results: In the calendar year 2013, we had a total of 2353 admission encounters (F=1078). The mean age on admission was 56.55Y ± 16.7. The mean length of ICU stay was 6.3 days. Mechanical ventilation was initiated on 420 patients with a mean length on mechanical ventilation 5.09 days. 2028 CT scans were completed of which approximately 60% were head CT without contrast (n=1209). 379 patients had multiple CT studies. The mean number of studies was 3.8 ± 2. The number of patients with more thanthree3 studies during their ICU stay was 159. The maximum number of studies on a single patient was 21. Conclusion: Patients in the Neuro ICU are at a risk for significant exposure to ionizing radiation. Radiation exposure must be factored into the culture of quality and patient safety in the ICU.

In order to test the hypothesis that the trichothecene genotype composition of local populations of Fusarium graminearum is structured by specific habitats, a collection of 1,407 isolates was obtained from overwintered maize stubble, mature maize ears and wheat spikes, and the atmosphere 1.5 m aboveground during the flowering stage of these crops. These isolates were sampled at three diverse agricultural locations in New York State: namely, Aurora (sampled in 2012 and 2013) in central New York, Belmont (sampled in 2013) in southwestern New York, and Willsboro (sampled in 2013) in northeastern New York. Approximately 100 isolates of F. graminearum from each habitat were collected within a 10-mile2 area in each location. Polymerase chain reaction assays were used to identify three main B-trichothecene genotypes—3-acetyldeoxynivalenol (3-ADON), 15-ADON, or nivalenol (NIV)—based on amplification of portions of Tri3 and Tri12 genes. All but the NIV genotype were detected. The 15-ADON genotype predominated in most locations; frequencies were 92% (652/709) at Aurora, 78% (332/379) at Belmont, and 53% (167/319) at Willsboro. Frequencies of any genotype did not differ in general among the four habits in each location. An exception was in Aurora 2012, where only 5 in 24 3-ADON isolates were found in samplings from the air and grains of both crops. As viewed by the composition of trichothecene genotypes, local populations of F. graminearum appear not to be structured by these four habitats inclusive of pathogenic and saprophytic phases of the fungus life cycle. The similar frequency of 3-ADON and 15-ADON in eastern New York (Willsboro), which is less than 400 km away from the Aurora sampling location in the central area of the state, suggests that regional populations may be differentiated based on selection associated with climatic or landscape features not currently identified.

Introduction Climate change is one of the 21st century’s biggest public health issues and health care contributes up to 10% of the emissions of greenhouse gases in developed countries. About 15 million laparoscopic procedures are performed annually worldwide and single-use medical equipment is increasingly used during these procedures. Little is known about costs and environmental footprint of this change in practice. Methods We employed Life Cycle Assessment method to evaluate and compare the environmental impacts of single-use, reusable, and mixed trocar systems used for laparoscopic cholecystectomies at three hospitals in southern Sweden. The environmental impacts were calculated using the IMPACT 2002+ method and a functional unit of 500 procedures. Monte Carlo simulations were used to estimate differences between trocar systems. Data are presented as medians and 2.5th to 97.5th percentiles. Financial costs were calculated using Life Cycle Costing. Results The single-use system had a 182% higher impact on resources than the reusable system [difference: 5160 MJ primary (4400–5770)]. The single-use system had a 379% higher impact on climate change than the reusable system [difference: 446 kg CO2eq (413–483)]. The single-use system had an 83% higher impact than the reusable system on ecosystem quality [difference: 79 PDF*m2*yr (24–112)] and a 240% higher impact on human health [difference: 2.4x10-4 DALY/person/yr (2.2x10-4-2.6x10-4)]. The mixed and single-use systems had a similar environmental impact. Differences between single-use and reusable trocars with regard to resource use and ecosystem quality were found to be sensitive to lower filling of machines in the sterilization process. For ecosystem quality the difference between the two were further sensitive to a 50% decrease in number of reuses, and to using a fossil fuel intensive electricity mix. Differences regarding effects on climate change and human health were robust in the sensitivity analyses. The reusable and mixed trocar systems were approximately half as expensive as the single-use systems (17360 € and 18560 € versus 37600 €, respectively). Conclusion In the Swedish healthcare system the reusable trocar system offers a robust opportunity to reduce both the environmental impact and financial costs for laparoscopic surgery.

We examined the time course of changes in osmotic water permeability (Pf, micron/s), lumen-to-bath 22Na+ flux (Jl----b, pmol.min-1.mm-1), and transepithelial voltage (VT, mV) in response to arginine vasopressin (AVP) in isolated perfused rat and rabbit cortical collecting ducts (CCD). CCDs were isolated from “normal” (untreated) animals and animals 4-14 days after an intramuscular depot injection of deoxycorticosterone pivalate (DOC; 35 mg/rabbit, 5 mg/rat). In the normal rat CCD, 220 pM AVP added to the bathing solution increased Pf from approximately 0 to 981 +/- 120, Jl----b from 24 +/- 5 to 62 +/- 9, and VT from -0.7 +/- 0.6 to -4.0 +/- 0.6 (mean +/- SE; P less than 0.05). The effect of AVP on Pf in DOC-treated rats was not significantly different, but the effects on Jl----b and VT were greater. Jl----b rose from a control value of 78 +/- 16 to 192 +/- 14 with AVP, and VT hyperpolarized from -4.2 +/- 1.6 to -12.2 +/- 0.4. All of these effects of AVP in the normal and DOC-treated rat CCD persisted for greater than or equal to 90-150 min. In DOC-treated rabbit tubules, AVP caused a stable increase in Pf from 9 +/- 6 to 800 +/- 199, which was significantly greater than in normal tubules (379 +/- 32). In the normal rabbit CCD we confirmed previous observations that AVP produces only a transient increase in Na+ absorption and VT; Jl----b increased from 76 +/- 4 to 96 +/- 7 during the period 15-25 min after AVP addition but subsequently fell to 80 +/- 6; VT transiently hyperpolarized from -55 +/- 7 to -64 +/- 8 at 3-8 min after AVP and then fell to -54 +/- 9. In DOC-treated rabbit CCDs, AVP produced no change whatsoever in Jl----b, which was not significantly different from the control value of 99 +/- 7, nor in VT, which was -68 +/- 8 mV. These results indicate fundamental differences in the response of the rat and rabbit CCD to AVP and the presence or absence of synergistic interactions with mineralocorticoids, which may relate to their differing response to other autacoids.

Abstract We demonstrated that G-CSF signaling in lineage-negative marrow myeloid progenitors induces C-terminal SHP2 tyrosine phosphorylation more potently than does M-CSF signaling and that SHP2 knockdown in marrow or in the 32Dcl3 cell line reduces Cebpa gene transcription and impairs granulopoiesis.1,2 We also found that Runx1 directly activates Cebpa transcription via promoter elements and via a +37 kb enhancer and that Runx1 gene deletion reduces Cebpa mRNA and impairs granulopoiesis.3 Runx1 is phosphorylated by Src kinase on five tyrosines and dephosphorylated by SHP2, and RUNX1(5F) enhances megakaryopoiesis and rescues CD8 T cell development, whereas RUNX1(5D) is ineffective.4 Mutation to F prevents while change to D or E mimics phosphorylation. These findings suggested that in myeloid cells there exists a G-CSF to SHP2 to RUNX1 to Cebpa activation pathway directing granulopoiesis. We compared wild-type (WT) murine RUNX1b and a series of variants, Y260/375/378/379/386F (5F), Y260F (1F), Y375/378/379/386F (4F), 5D, 1D, and 4D for activation in 293T cells of a reporter with four RUNX1-binding sites linked to the TK promoter and the luciferase cDNA. Expression was compared by Western blotting. WT stimulated the reporter 5-fold on average, relative to empty CMV vector, 5D activated the reporter 15-fold, while 5F was nearly inactive. 4F was also nearly inactive, while 4D had WT activity, as did the 1F and 1D variants. Both 4F and 5F were expressed at or above WT levels; interestingly, 5D, but not 4D or 1D, was expressed at much higher levels than the other variants. A similar pattern was obtained with the MCSFR-Luc reporter. To further query the activity of the four C-terminal tyrosines, we evaluated the activity of Y375/378F (2F*), Y379/386F (2F), 2E, Y375F, Y378F, Y379F, and Y386F. The single residue mutations retained WT activity, whereas both the 2F* and 2F variants demonstrated significant reduction despite expression at or above WT levels. The 2E variant expressed at levels below WT but had increased activity. We then transfected the RUNX1 reporter with activated Src, Runx1, or both – in several experiments Src stimulated the reporter approximately 3-fold, on average, RUNX1 4-fold, and the combination 35-fold. In the same experiments, Src + 5F led to only 6.6-fold activation, and synergy was also lost if the reporter lacked the RUNX1-binding sites. These findings, together with the observation that SHP2 directly activates Src family kinases downstream of G-CSF receptor signaling,5 raises the possibility that in myeloid cells there actually is a G-CSF to SHP2 to Src to Runx1 to Cebpa activation pathway. Consistent with this idea, we find that the 5D variant has reduced interaction with co-expressed HDAC3 relative to WT, as assessed by co-IP, whereas the 5F variant has increased interaction. We previously found that RUNX1-ER stimulates endogenous Cebpa transcription when activated in 32Dcl3 cells. As the ER segment has trans-activating activity, to evaluate RUNX1 variants we utilizing the zinc-inducible MT promoter. Preliminary analysis indicates that both WT RUNX1b and its 5D variant can induce C/EBPa protein and RNA in this context. We previously found that exogenous RUNX1-ER can rescue granulopoiesis when transduced into marrow from Runx1(flox/flox);Mx1-Cre mice subjected 4 weeks earlier to pIpC injections. We now have constructed MIGC retroviral vectors expressing RUNX1, 5F, or 5D and GFP-Cre. These, or the empty MIG or MIGC vectors, were packaged and transduced into marrow isolated from RUNX1(flox/flox) mice. Three days later, lineage-depleted, GFP+ cells were cultured in methylcellulose with IL-3, IL-6, and SCF. Compared with MIG, MIGC reduced the percent CFU-G amongst CFU-G+CFU-M, from 55+/-1% to 10+/-2%; WT RUNX1 or 5D partially rescued granulopoiesis, to 31+/- 8% or 23+/-9% respectively, whereas 5F transduction led to only 4+/-1% CFU-G. In summary, in 293T cells and potentially in myeloid cells Src kinase activates Runx1 and this may favor granulopoiesis. 1. Jack et al. Blood 114:2172, 2009. 2. Zhang and Friedman. Blood 118:2266, 2011. 3. Guo et al. Blood 119:4408, 2012. 4. Huang et al. Genes Dev. 26:1587, 2012. 5. Futami et al. Blood 118:1077, 2011. Disclosures: Cantor: AMGEN: Membership on an entity’s Board of Directors or advisory committees.

Background: Alzheimer’s disease (AD) is the most prevalent neurological disorder worldwide, affecting approximately 24 million individuals. Despite more than a century of research on AD, its pathophysiology is still not fully understood. Objective: Recently, genetic studies of AD have focused on analyzing the general expression profile by employing high-throughput genomic techniques such as microarrays. Current research has leveraged bioinformatics advancements in genetic science to build upon previous efforts. Methods: Data from the GSE118553 dataset used in this investigation, and the analyses carried out using programs such as Limma and BioBase. Differentially expressed genes (DEGs) and differentially expressed microRNAs (DEmiRs) associated with AD identified in the studied areas of the brain. Target genes of the DEmiRs identified using the MultiMiR package. Gene ontology (GO) completed using the Enrichr website, and the protein-protein interaction (PPI) network for these genes drawn using STRING and Cytoscape software. Results: The findings introduced DEGs including CTNNB1, PAK2, MAP2K1, PNPLA6, IGF1R, FOXL2, DKK3, LAMA4, PABPN1, and GDPD5, and DEmiRs linked to AD (miR-106A, miR-1826, miR-1253, miR-10B, miR-18B, miR-101-2, miR-761, miR-199A1, miR-379 and miR-668), (miR-720, miR-218-2, miR-25, miR-602, miR-1226, miR-548K, miR-H1, miR-410, miR-548F2, miR-181A2), (miR-1470, miR-651, miR-544, miR-1826, miR-195, miR-610, miR-599, miR-323, miR-587 and miR-340), and (miR-1282, miR-1914, miR-642, miR-1323, miR-373, miR-323, miR-1322, miR-612, miR-606 and miR-758) in cerebellum, frontal cortex, temporal cortex, and entorhinal cortex, respectively. Conclusions: The majority of the genes and miRNAs identified by our findings may be employed as biomarkers for prediction, diagnosis, or therapy response monitoring.

Background: Patients receiving maintenance hemodialysis have multiple comorbidities and are at high risk of presenting to the hospital. However, the incidence and cost of acute health care utilization in the in-center hemodialysis population and how this compares with other populations is poorly understood. Objective: To determine the rate, pattern, and cost of emergency department visits and hospitalizations in patients receiving in-center hemodialysis compared with a matched general population. Design: Population-based matched cohort study. Setting: We used linked administrative health care databases from Ontario, Canada. Patients: We included 25 379 patients (incident and prevalent) receiving in-center hemodialysis between January 1, 2010, and December 31, 2018. Patients were matched on birth date (±2 years), sex, and cohort entry date using a 1:4 ratio to 101 516 individuals from the general population. Measurements: Our primary outcomes were emergency department visits (allowing for multiple visits per individual) and hospital admissions from the emergency department. We also assessed all-cause hospitalizations, all-cause readmissions within 30 days of discharge from the original hospitalization, length of stay for hospital admissions (including multiple visits per individual), and the financial cost of these admissions. Methods: We presented the rate, percentage, median (25th, 75th percentiles), and incidence rate per 1000 person-years for emergency department visits and hospitalizations. Individual-level health care costs for emergency department visits and all-cause hospitalization were estimated using resource intensity weights multiplied by the cost per weighted case. Results: Patients receiving in-center hemodialysis had substantially more comorbidities (eg, diabetes) than the matched general population. Eighty percent (n = 20 309) of patients receiving in-center hemodialysis had at least 1 emergency department visit compared with 56% (n = 56 452) of individuals in the matched general population, over a median follow-up of 1.8 years (25th, 75th percentiles: 0.7, 3.6) and 5.2 (2.5, 8.4) years, respectively. The incidence rate of emergency department visits, allowing for multiple visits per individual, was 2274 per 1000 person-years (95% confidence interval [CI]: 2263, 2286) for patients receiving in-center hemodialysis, which was almost 5 times as high as the matched general population (471 per 1000 person-years; 95% CI: 469, 473). The rate of hospital admissions from the emergency department and the rate of all-cause hospital admissions in the in-center hemodialysis population was more than 7 times as high as the matched general population (hospital admissions from the emergency department: 786 vs 101 per 1000 person-years; all-cause hospital admissions: 1056 vs 139 per 1000 person-years). The median number of all-cause hospitalization days per patient year was 4.0 (0, 16.5) in the in-center hemodialysis population compared with 0 (0, 0.5) in the matched general population. The cost per patient-year for emergency department visits in the in-center hemodialysis population was approximately 5.5 times as high as the matched general population while the cost of hospitalizations in the in-center hemodialysis population was approximately 11 times as high as the matched general population (emergency department visits: CAN$ 1153 vs CAN$ 209; hospitalizations: CAN$ 21 151 vs CAN$ 1873 [all costs in 2023 CAN$]). Limitations: External generalizability and we could not determine whether emergency department visits and hospitalizations were preventable. Conclusions: Patients receiving in-center hemodialysis have high acute health care utilization. These results improve our understanding of the burden of disease and the associated costs in the in-center hemodialysis population, highlight the need to improve acute outcomes, and can aid health care capacity planning. Additional research is needed to address the risk of hospitalization after controlling for patient comorbidities. Trial registration: This is not applicable as this is a population-based matched cohort study and not a clinical trial.