Patterns, predictors, variations, and temporal trends in emergency medical service hospital prenotification for acute ischemic stroke.

BACKGROUND#ENTITYSTARTX02014;: Emergency medical services (EMS) hospital prenotification of an incoming stroke patient is guideline recommended as a means of increasing the timeliness with which stroke patients are evaluated and treated. Still, data are limited with regard to national use of, variations in, and temporal trends in EMS prenotification and associated predictors of its use. METHODS AND RESULTS#ENTITYSTARTX02014;: We examined 371 988 patients with acute ischemic stroke who were transported by EMS and enrolled in 1585 hospitals participating in Get With The Guidelines-Stroke from April 1, 2003, through March 31, 2011. Prenotification occurred in 249 197 EMS-transported patients (67.0%) and varied widely by hospital (range, 0% to 100%). Substantial variations by geographic regions and by state, ranging from 19.7% in Washington, DC, to 93.4% in Montana, also were noted. Patient factors associated with lower use of prenotification included older age, diabetes mellitus, and peripheral vascular disease. Prenotification was less likely for black patients than for white patients (adjusted odds ratio 0.94, 95% confidence interval 0.92-0.97, P<0.0001). Hospital factors associated with greater EMS prenotification use were absence of academic affiliation, higher annual volume of tissue plasminogen activator administration, and geographic location outside the Northeast. Temporal improvements in prenotification rates showed a modest general increase, from 58.0% in 2003 to 67.3% in 2011 (P temporal trend <0.0001). CONCLUSIONS#ENTITYSTARTX02014;: EMS hospital prenotification is guideline recommended, yet among patients transported to Get With The Guidelines-Stroke hospitals it is not provided for 1 in 3 EMS-arriving patients with acute ischemic stroke and varies substantially by hospital, state, and region. These results support the need for enhanced implementation of stroke systems of care. (J Am Heart Assoc. 2012;1:e002345 doi: 10.1161/JAHA.112.002345.)

Alssat Development Status and Its Applications in Trade Studies

The development of the Advanced Life Support (ALS) Sizing Analysis Tool (ALSSAT) using Microsoft Excel was initiated by the Crew and Thermal Systems Division (CTSD) of Johnson Space Center (JSC) in 1997 to support the ALS and Exploration Offices in Environmental Control and Life Support System (ECLSS) design and studies. It aids the user in performing detailed sizing of the ECLSS based on suggested default values or user inputs for different combinations of the ALS regenerative system technologies (Ref. 1, 2). This analysis tool will assist the user in performing ECLSS preliminary design and trade studies as well as system optimization efficiently and economically. Since ALSSAT's latest publication in ICES 2001 (Ref. 1) describing the development of ALSSAT with its Air Revitalization Subsystem (ARS), Water Management Subsystem (WMS), and Biomass Subsystem (Biomass) mass balance sheets, ALSSAT has been expanded to include mass balance and sizing models for the remaining three ALS subsystems, namely, the Solid Waste Management Subsystem (SWMS), the Food Management Subsystem (FMS), and the Thermal Control Subsystem (TCS). The external interfaces, including the Extravehicular Activities (EVA) and Human Accommodations (HA), were implemented into ALSSAT in 2002. The overall mass balance sheet, which integrates the six ALS subsystems and the external interfaces applicable to the ECLSS, was also developed. In 2003, ALSSAT was upgraded to include the consideration of redundancy and contingency options in the ECLSS, as well as more ALS regenerative technology selections. ALSSAT has been used for the Metric Calculation for FY02 and FY03 (Ref. 3). Several trade studies were conducted in 2003. The analytical results will be presented in this paper

On-Call Duty Effects on Sleep-State Physiological Stability in Male Medical Interns

Background: On-call duty among medical interns is characterized by sleep deprivation and stressful working conditions, both of which alter cardiac autonomic modulation. We hypothesized that sleep stability decreased in medical interns during on-call duty. We used cardiopulmonary-coupling (CPC) analysis to test our hypothesis. Methods: We used electrocardiogram (ECG)-based CPC analysis to quantify physiological parameters of sleep stability in 13 medical interns during on-call and on-call duty-free periods. There were ten 33.5-h on-call duty shifts per month for interns, each followed by 2 on-call duty-free days, over 3 months. Measurements during sleep were collected before, during, and after an on-call shift. Measurements were repeated 3 months later during an on-call duty-free period. Results: The medical interns had significantly reduced stable sleep, and displayed increased latency to the first epoch of stable sleep during the on-call night shift, compared to the pre-call and on-call duty-free nights. Interns also had significantly increased rapid-eye-movement (REM) sleep during the on-call night shift, compared to the pre-call and on-call duty-free nights. Conclusion: Medical interns suffer disrupted sleep stability and continuity during on-call night shifts. The ECG-based CPC analysis provides a straightforward means to quantify sleep quality and stability in medical staff performing shift work under stressful conditions

Methadone-Mediated Autonomic Functioning of Male Patients with Heroin Dependence: The Influence of Borderline Personality Pattern

BACKGROUND: We hypothesize that the population with borderline personality shows different autonomic response to methadone compared to individuals with other personalities. This study applies heart rate variability (HRV) measurements and the Tridimensional Personality Questionnaire (TPQ) to examine this hypothesis. METHODOLOGY/PRINCIPAL FINDINGS: Forty-four male patients with heroin dependence were recruited from a methadone maintenance treatment program. Eight personality patterns were classified according to the TPQ norm used in Taiwan. The borderline pattern (BP, composed of high novelty seeking, high harm avoidance and low reward dependence) and the other personality patterns (OP) were separated into two groups. We compared the HRV profiles between the BP and OP groups. Correlation and regression analysis were performed to clarify relationship between HRV differences and the borderline index (BI, a new concept defined by us, which is calculated as novelty seeking + harm avoidance - reward dependence). The HRV targets investigated included low frequency (LF) power, high frequency (HF) power, total power (TP), normalized LF (LF%), and LF/HF. No baseline HRV parameters showed any inter-group difference. The BP group had a significantly lower ΔHF and a higher ΔLF/HF than the OP group. The personality dimension, reward dependence, showed a negative correlation with ΔLF/HF and ΔLF%. BI was negatively correlated with ΔHF and positively correlated with ΔLF/HF and ΔLF%. CONCLUSIONS/SIGNIFICANCE: Borderline personality individuals show increased sympathetic activity and decreased parasympathetic activity compared to other personalities after taking methadone. The results support the hypothesis that there is an interaction between borderline personality and autonomic modulation

3′-End Sequencing for Expression Quantification (3SEQ) from Archival Tumor Samples

Gene expression microarrays are the most widely used technique for genome-wide expression profiling. However, microarrays do not perform well on formalin fixed paraffin embedded tissue (FFPET). Consequently, microarrays cannot be effectively utilized to perform gene expression profiling on the vast majority of archival tumor samples. To address this limitation of gene expression microarrays, we designed a novel procedure (3′-end sequencing for expression quantification (3SEQ)) for gene expression profiling from FFPET using next-generation sequencing. We performed gene expression profiling by 3SEQ and microarray on both frozen tissue and FFPET from two soft tissue tumors (desmoid type fibromatosis (DTF) and solitary fibrous tumor (SFT)) (total n = 23 samples, which were each profiled by at least one of the four platform-tissue preparation combinations). Analysis of 3SEQ data revealed many genes differentially expressed between the tumor types (FDR<0.01) on both the frozen tissue (∼9.6K genes) and FFPET (∼8.1K genes). Analysis of microarray data from frozen tissue revealed fewer differentially expressed genes (∼4.64K), and analysis of microarray data on FFPET revealed very few (69) differentially expressed genes. Functional gene set analysis of 3SEQ data from both frozen tissue and FFPET identified biological pathways known to be important in DTF and SFT pathogenesis and suggested several additional candidate oncogenic pathways in these tumors. These findings demonstrate that 3SEQ is an effective technique for gene expression profiling from archival tumor samples and may facilitate significant advances in translational cancer research

The role of taxonomic expertise in interpretation of metabarcoding studies

Abstract The performance of DNA metabarcoding approaches for characterizing biodiversity can be influenced by multiple factors. Here, we used morphological assessment of taxa in zooplankton samples to develop a large barcode database and to assess the congruence of taxonomic identification with metabarcoding under different conditions. We analysed taxonomic assignment of metabarcoded samples using two genetic markers (COI, 18S V1–2), two types of clustering into molecular operational taxonomic units (OTUs, ZOTUs), and three methods for taxonomic assignment (RDP Classifier, BLASTn to GenBank, BLASTn to a local barcode database). The local database includes 1042 COI and 1108 18S (SSU) barcode sequences, and we added new high-quality sequences to GenBank for both markers, including 109 contributions at the species level. The number of phyla detected and the number of taxa identified to phylum varied between a genetic marker and among the three methods used for taxonomic assignments. Blasting the metabarcodes to the local database generated multiple unique contributions to identify OTUs and ZOTUs. We argue that a multi-marker approach combined with taxonomic expertise to develop a curated, vouchered, local barcode database increases taxon detection with metabarcoding, and its potential as a tool for zooplankton biodiversity surveys

Development and Initial Testing of the Stroke Rapid-Treatment Readiness Tool

ABSTRACTNo instruments are currently available to help health systems identify target areas for reducing door-to-needle times for the administration of intravenous tissue plasminogen activator to eligible patients with ischemic stroke. A 67-item Likert-scale survey was administered by telephone to stroke personnel at 252 U.S. hospitals participating in the “Get With The Guidelines-Stroke” quality improvement program. Factor analysis was used to refine the instrument to a four-factor 29-item instrument that can be used by hospitals to assess their readiness to administer intravenous tissue plasminogen activator within 60 minutes of patient hospital arrival

Nongenomic mechanisms of physiological estrogen-mediated dopamine efflux

<p>Abstract</p> <p>Background</p> <p>Neurological diseases and neuropsychiatric disorders that vary depending on female life stages suggest that sex hormones may influence the function of neurotransmitter regulatory machinery such as the dopamine transporter (DAT).</p> <p>Results</p> <p>In this study we tested the rapid nongenomic effects of several physiological estrogens [estradiol (E₂), estrone (E₁), and estriol (E₃)] on dopamine efflux via the DAT in a non-transfected, NGF-differentiated, rat pheochromocytoma (PC12) cell model that expresses membrane estrogen receptors (ERs) α, β, and GPR30. We examined kinase, ionic, and physical interaction mechanisms involved in estrogenic regulation of the DAT function. E₂-mediated dopamine efflux is DAT-specific and not dependent on extracellular Ca²⁺-mediated exocytotic release from vesicular monoamine transporter vesicles (VMATs). Using kinase inhibitors we also showed that E₂-mediated dopamine efflux is dependent on protein kinase C and MEK activation, but not on PI3K or protein kinase A. In plasma membrane there are ligand-independent associations of ERα and ERβ (but not GPR30) with DAT. Conditions which cause efflux (a 9 min 10^-9M E₂treatment) cause trafficking of ERα (stimulatory) to the plasma membrane and trafficking of ERβ (inhibitory) away from the plasma membrane. In contrast, E₁and E₃can inhibit efflux with a nonmonotonic dose pattern, and cause DAT to leave the plasma membrane.</p> <p>Conclusion</p> <p>Such mechanisms explain how gender biases in some DAT-dependent diseases can occur.</p

The novel curcumin analog FLLL32 decreases STAT3 DNA binding activity and expression, and induces apoptosis in osteosarcoma cell lines

<p>Abstract</p> <p>Background</p> <p>Curcumin is a naturally occurring phenolic compound shown to have a wide variety of antitumor activities; however, it does not attain sufficient blood levels to do so when ingested. Using structure-based design, a novel compound, FLLL32, was generated from curcumin. FLLL32 possesses superior biochemical properties and more specifically targets STAT3, a transcription factor important in tumor cell survival, proliferation, metastasis, and chemotherapy resistance. In our previous work, we found that several canine and human osteosarcoma (OSA) cell lines, but not normal osteoblasts, exhibit constitutive phosphorylation of STAT3. Compared to curcumin, we hypothesized that FLLL32 would be more efficient at inhibiting STAT3 function in OSA cells and that this would result in enhanced downregulation of STAT3 transcriptional targets and subsequent death of OSA cells.</p> <p>Methods</p> <p>Human and canine OSA cells were treated with vehicle, curcumin, or FLLL32 and the effects on proliferation (CyQUANT^®), apoptosis (SensoLyte^®Homogeneous AMC Caspase- 3/7 Assay kit, western blotting), STAT3 DNA binding (EMSA), and vascular endothelial growth factor (VEGF), survivin, and matrix metalloproteinase-2 (MMP2) expression (RT-PCR, western blotting) were measured. STAT3 expression was measured by RT-PCR, qRT- PCR, and western blotting.</p> <p>Results</p> <p>Our data showed that FLLL32 decreased STAT3 DNA binding by EMSA. FLLL32 promoted loss of cell proliferation at lower concentrations than curcumin leading to caspase-3- dependent apoptosis, as evidenced by PARP cleavage and increased caspase 3/7 activity; this could be inhibited by treatment with the pan-caspase inhibitor Z-VAD-FMK. Treatment of OSA cells with FLLL32 decreased expression of survivin, VEGF, and MMP2 at both mRNA and protein levels with concurrent decreases in phosphorylated and total STAT3; this loss of total STAT3 occurred, in part, via the ubiquitin-proteasome pathway.</p> <p>Conclusions</p> <p>These data demonstrate that the novel curcumin analog FLLL32 has biologic activity against OSA cell lines through inhibition of STAT3 function and expression. Future work with FLLL32 will define the therapeutic potential of this compound <it>in vivo</it>.</p

Impact of Obesity on Pediatric Acute Recurrent and Chronic Pancreatitis

OBJECTIVE: The aim of this study was to assess the impact of obesity on pediatric acute recurrent pancreatitis or chronic pancreatitis (CP). METHODS: We determined body mass index (BMI) status at enrollment in INSPPIRE (INternational Study group of Pediatric Pancreatitis: In search for a cuRE) cohort using CDC criteria for pediatric-specific BMI percentiles. We used the Cochran-Armitage test to assess trends and the Jonckheere-Terpstra test to determine associations. RESULTS: Of 446 subjects (acute recurrent pancreatitis, n = 241; CP, n = 205), 22 were underweight, 258 normal weight, 75 overweight, and 91 were obese. The BMI groups were similar in sex, race, and age at presentation. Hypertriglyceridemia was more common in overweight or obese. Obese children were less likely to have CP and more likely to have acute inflammation on imaging. Compared with children with normal weight, obese or overweight children were older at first acute pancreatitis episode and diagnosed with CP at an older age. Obese or overweight children were less likely to undergo medical or endoscopic treatment, develop exocrine pancreatic insufficiency, and require total pancreatectomy with islet autotransplantation. Diabetes was similar among all groups. CONCLUSIONS: Obesity or overweight seems to delay the initial acute pancreatitis episode and diagnosis of CP compared with normal weight or underweight. The impact of obesity on pediatric CP progression and severity deserves further study