Miracle-dz/UniFAR-FTUs huggingface dataset:
Inflammatory status in sepsis alters efficacy of interleukin-18 binding protein therapy*

ObjectiveSepsis remains a serious clinical problem, and multiple attempts at blocking inflammation have failed to decrease mortality rate. Interleukin-18 has been demonstrated to be an important component of the innate immune response to bacterial infections. DesignPrevious work demonstrated that elevated plasma concentrations of interleukin-6 obtained in the first 6 hrs of sepsis predict a worse outcome. Mice were subjected to cecal ligation and puncture and, on the basis of the plasma concentration of interleukin-6, were randomized to receive either interleukin-18 binding protein or vehicle approximately 8 hrs after the onset of sepsis. SettingUniversity research laboratory. SubjectsAdult, female BALB/c mice. InterventionsWe sought to determine the role of interleukin-18 in sepsis by blocking its biological activity with the interleukin-18 binding protein in the murine model of sepsis induced by cecal ligation and puncture. Measurements and Main ResultsIn this study, elevated plasma concentrations of interleukin-6 were associated with a worse outcome. Treatment with interleukin-18 binding protein decreased inflammation as determined by lower concentrations of plasma interleukin-6 obtained 48 hrs after the onset of sepsis. In mice with increased risk of dying, interleukin-18 binding protein slightly decreased mortality rate. However, in those mice with a predicted low mortality rate, interleukin-18 binding protein significantly increased mortality rate. ConclusionsIn this study, mice at low risk of death due to sepsis had decreased survival when treated with interleukin-18 binding protein. These results have potential implications for the use of interleukin-18 binding protein for treatment of chronic inflammatory conditions since it may place the host at increased risk of infectious complications.
The effects of organizational culture on turnover intention: The mediating role of job satisfaction, a case of Oromia Forest and Wild Life Enterprise

The purpose of this study was to identifying the effects of organizational culture on turnover intention with mediated role of satisfaction. Data were gathered by closed ended questionnaires distributed to five OFWELs in Oromia. The scales used were the organizational culture index, job satisfaction survey, and the turnover intention questionnaire. The collected data was statistically analyzed by SPSS 20 and AMOS 21. The data were collected using a questionnaire. Three hundred and fifteen (315) questionnaires were distributed and analyzed by using Structural Equation Model (SEM). To validate interdependence relationships between each variable, confirmatory factor analysis by using structural equation modeling (SEM) has been employed. Some of the results were as expected after theory examination, but others were surprisingly contradictive. Bureaucratic culture was significant with direct relationship with turnover intention. Based on the results, it is recommended that supportive culture could be practiced in OFWEs to gain satisfied and committed employees. Key words: Job satisfaction, organizational culture, turnover intention, Oromia Forest and Wild Life Enterprise.
Alteration in the Transcriptional Profile of Livers from Brain-dead Organ Donors

Background. There is evidence that brain death causes changes in peripheral organs. Marked inflammation is found in organs collected during experimental brain death and clinical studies indicate that, despite genetic mismatch, organs obtained from living donors show improved survival over those from brain-dead donors. The aim of the present clinical research was to explore changes in the transcriptional profile of livers from brain-dead organ donors. Methods. Using the cDNA macroarray technique, we compared gene expression in liver biopsies from 21 brain-dead organ donors and in normal liver tissue obtained during resection of benign focal lesions. Results. Analysis of gene expression showed significant differences in the mRNA levels of 117 genes. There was reduced expression of 93 genes whereas expression of 24 genes was enhanced. Downregulated pathways included transcripts related to morphogenesis, blood coagulation, complement cascade, amine metabolism, lipid metabolism, nucleic acid metabolism, biodegradation of xenobiotics, signal transduction, and transcription. Conversely, there was induction of genes related to acute phase response, damage-related response, electron transport, and energy metabolism. Conclusions. The present research demonstrates major changes in the transcriptional profile of livers from brain-dead organ donors. The presence of both down- and upregulated gene families suggests that the alteration in transcriptional profile is not a consequence of death-associated organ failure, but rather, an active change in regulatory mechanisms.
HMG-CoA reductase inhibitors activate the unfolded protein response and induce cytoprotective GRP 78 expression

Aims Since apoptosis of macrophages induced by stress to the endoplasmic reticulum (ER) contributes to advanced atherosclerotic lesions, we sought to understand the effects of statins on the unfolded protein response (UPR). Methods and results We used pharmacological, biochemical, and siRNA (small interfering ribonucleic acid) approaches to determine the signalling cascades of statin-induced 78 kDa glucose-regulated protein (GRP78) gene transcription and its role in cytoprotection. Exposure of RAW264.7 macrophages to statins increased the expression of GRP78, activating transcription factor 6, X box protein-1, and phosphorylated eukaryotic translation initiation factor 2a, while it had no effect on CCAAT/enhancer binding protein-homologous protein. GRP78 induction was abolished by co-treatment with mevalonate and 1,2-bis(o-aminophenoxy)ethane-N, N, N0,N0-tetraacetic acid, indicating the involvement of both 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase-dependent and -independent mechanisms. Studies on promoter activity measurements indicated that phosphoinositide turnover, cellular homologue of v-src (c-Src), protein kinase C (PKC), extracellular signal-regulated kinase (ERK), and p38 are involved in upregulating GRP78 gene transcription. We also observed that elevation of intracellular Ca2þ and interruption of small G proteins are two bifurcated but cooperative signalling pathways for c-Src activation, leading to downstream activation of phospholipase C, PKC, ERK, and p38. Functionally we demonstrated that fluvastatin could protect macrophages from hypoxia-induced cell death through GRP78 induction. Conclusion We demonstrate a novel action of statins of inducing a cytoprotective UPR, providing new insights into the clinical potential of statins for ameliorating ER stress-related diseases.
Genetic variation in the mitochondrial cytochrome c oxidase subunit 1 within three species of Progamotaenia (Cestoda: Anoplocephalidae) from macropodid marsupials

Sequence variation within 3 morphologically defined species of the anoplocephalid cestode genus Progamotaenia (P. ewersi, P. macropodis and P. zschokkei) was investigated using the cytochrome c oxidase subunit 1 gene. The magnitude of genetic variation detected within each morphospecies suggests that, in each instance, several cryptic species are present. Within P. ewersi, 5 genetically distict groups of cestodes were detected, 1 shared by Macropus robustus and M. parryi in Queensland, 1 in M. agilis from Queensland, 1 in Petrogale assimilis from Queensland, 1 in Macropus fuliginosus from South Australia and 1 in Wallabia bicolor from Victoria. In P. macropodis, cestodes from M. robustus from Queensland, Western Australia and the Northern Territory, M. parryi from Queensland and M. eugenii from South Australia were genetically distinct from those in Wallabia bicolor from Queensland and Victoria and from M. fuliginosus from South Australia. P. zschokkei consisted of a number of genetically distinct groups of cestodes, 1 in Lagorchestes conspicillatus and L. hirsutus from Queensland and the Northern Territory respectively, 1 in Petrogale herberti, P. assimilis and M. dorsalis from Queensland, 1 in Onychogalea fraenata from Queensland, 1 in M. agilis from Queensland and 1 in Thylogale stigmatica and T. thetis from Queensland. In general, genetic groups within each morphospecies were host specific and occurred predominantly in a particular macropodid host clade. Comparison of genetic relationships of cestodes with the phylogeny of their hosts revealed examples of colonization (P. zschokkei in M. agilis) and of host switching (P. zschokkei in M. dorsalis).
Administration of the nitric oxide synthase inhibitor NG-methyl-l-arginine hydrochloride (546C88) by intravenous infusion for up to 72 hours can promote the resolution of shock in patients with severe sepsis: Results of a randomized, double-blind, placebo-controlled multicenter study (study no. 144-

ObjectiveTo assess the safety and efficacy of the nitric oxide synthase inhibitor 546C88 in patients with septic shock. The predefined primary efficacy objective was resolution of shock, defined as a mean arterial pressure ≥70 mm Hg in the absence of both conventional vasopressors and study drug, determined at the end of the 72-hr treatment period. DesignMulticentered, randomized, placebo-controlled, safety and efficacy study. SettingForty-eight intensive care units in Europe, North America, and Australia. PatientsA total of 312 patients with septic shock diagnosed within 24 hr before randomization. InterventionsPatients were randomly allocated to receive either 546C88 or placebo (5% dextrose) by intravenous infusion for up to 72 hrs. Conventional vasoactive therapy was restricted to norepinephrine, dopamine, and dobutamine. Study drug was initiated at 0.1 mL/kg/hr (5 mg/kg/hr 546C88) and titrated according to response up to a maximum rate of 0.4 mL/kg/hr with the objective to maintain mean arterial pressure at 70 mm Hg while attempting to withdraw any concurrent vasopressor(s). Measurements and Main ResultsRequirement for vasopressors, systemic hemodynamics, indices of organ function and safety (including survival up to day 28) were assessed. The median mean arterial pressure for both groups was maintained >70 mm Hg. Administration of 546C88 was associated with a decrease in cardiac index while stroke index was maintained. Resolution of shock at 72 hr was achieved by 40% and 24% of the patients in the 546C88 and placebo cohorts, respectively (p = .004). There was no evidence that treatment with 546C88 had any major adverse effect on pulmonary, hepatic, or renal function. Day 28 survival was similar for both groups. ConclusionsIn this study, treatment with the nitric oxide synthase inhibitor 546C88 promoted the resolution of shock in patients with severe sepsis. This was associated with an acceptable overall safety profile.
Anticipated Effort in Imagined Self-Rotation

Chronometric studies provide strong support that mental imagery recruits perceptual processes [Shepard and Cooper, 1982 Mental Images and Their Transformations (Cambridge, MA: MIT Press)]. Recent studies suggest that anticipated effort influences perception (Proffitt et al, 2003 Psychological Science 14 106–112). If anticipated effort influences perception and perception supports imagery, then anticipated effort may influence imagery. To examine the role of effort in mental imagery, participants in experiment 1 imagined self-rotation across two conditions of distance. Simulated rotation took 156 ms longer in larger settings, even though the amount of imagined angular rotation was the same in both settings. This finding suggests the start-to-goal arc is incorporated when imagining rotation through a given angle. Experiment 2 replicated the distance effect (232 ms) and added a variable for load. Simulated rotation took 167 ms longer with imaginary heavy loads. The results suggest that both spatial metrics and anticipated effort may play a role in the coding of mental imagery.
Lumbar Disc High‐intensity Zone: Correlation of Magnetic Resonance Imaging and Discography

Study Design. This study correlated a specific lumbar disc abnormality described as the high‐intensity zone observed on high‐field magnetic resonance imaging with discography. Objectives. To analyze the significance of high‐intensity zones in lumbar discs of symptomatic patients with low back/radicular pain. Summary of Background Data. Aprill and Bogduk described an 86% incidence of concordantly painful discography in lumbar discs exhibiting a posterior high‐intensity zone on T2‐weighted magnetic resonance imaging studies performed on back pain sufferers. They assert that the high‐intensity zone is a reliable marker of discogenic pain in symptomatic subjects. Methods. Consecutive cases of lumbar spine high‐field magnetic resonance imaging using T2‐weighted images on symptomatic patients followed by discography at all high‐intensity zone levels and at non‐high‐intensity zone control levels were reviewed until 100 high‐intensity zone discs in 63 patients were found. Seventeen lifelong asymptomatic (for low back/radicular pain) adults were also scanned as magnetic resonance imaging controls. All magnetic resonance scans and discograms were agreed on by at least two of the radiologist authors. Results. Eighty‐seven of 100 of the high‐intensity zone discs proved concordantly painful at discography. All 87 painful and concordant discs exhibited abnormal morphology with anular tears extending either well into or through the outer third of the anulus fibrosus. Sixtyfive of 67 non‐high‐intensity zone control discs were nonconcordant and of lower sensation intensity than the high‐intensity zone discs. Only one high‐intensity zone was found in the control subjects. Conclusions. In patients with symptomatic low back pain, the high‐intensity zone is a reliable marker of painful outer anular disruption.
Capacity, control, and content: the supply of think tank policy advice in India

ABSTRACT Despite growing research on policy advice, little is known about how and why the nature of policy advice varies. We hypothesize that examining policy capacity and control within the policy advisory system (PAS) is useful in this regard. We examine how government capacity, think tank capacity, and think tank autonomy influence the content of policy advice in India. We code policy advice based on content analysis of 60 knowledge products from think tanks in India and estimate policy capacity of government departments and think tanks based on their respective staff strengths and budgets. We find that the nature of policy advice, specifically whether it is long-term or short-term, varies based on think tank capacity as well as government capacity; high capacity think tanks tend to provide more long-term advice to high capacity governments. As the PAS within developing countries have less capacity to generate strategic policy advice, variations can be expected in the kinds of policy advice supplied by the PAS in developing countries vis-à-vis OECD countries. Thus, the PAS literature can be extended to developing countries by studying the dynamics between the content of advice, capacity, and control.
An automated approach for the diagnosis of multiple faults in FPGA interconnects

This paper presents a new fine-grain diagnostics technique that is able to locate multiple interconnect faults of an FPGA. The proposed methodology uses the concept of remove, reroute and replace technique to automatically diagnose the precise location of the faulty interconnect resources and to self-repair them. In this technique, the net under test (NUT) is removed completely and rerouted using the unused fault-free net, and then the original NUT is replaced segment by segment for testing. The fault models we use are stuck at open, stuck at close and resistive open. The proposed methodology was implemented and tested on the Spartan series FPGAs via an automated approach utilizing parallel port communication. The automation program has been written in PERL and C languages. The experiment results show that approximately 34 faulty resources could be tested per second. Moreover this method uses minimal input output blocks. This proposed technique provides high degree of resolution in exactly locating the multiple interconnect faults and thus provides 100% fault coverage.
Translocation Products in Acute Myeloid Leukemia Activate the Wnt Signaling Pathway in Hematopoietic Cells

ABSTRACT The acute myeloid leukemia (AML)-associated translocation products AML1-ETO, PML-retinoic acid receptor alpha (RARα), and PLZF-RARα encode aberrant transcription factors. Several lines of evidence suggest similar pathogenetic mechanisms for these fusion proteins. We used high-density oligonucleotide arrays to identify shared target genes in inducibly transfected U937 cells expressing AML1-ETO, PML-RARα, or PLZF-RARα. All three fusion proteins significantly repressed the expression of 38 genes and induced the expression of 14 genes. Several of the regulated genes were associated with Wnt signaling. One of these, plakoglobin (γ-catenin), was induced on the mRNA and protein level by all three fusion proteins. In addition, primary AML blasts carrying one of the fusion proteins significantly overexpressed plakoglobin. The plakoglobin promoter was cloned and shown to be induced by AML1-ETO, with promoter activation depending on the corepressor and histone deacetylase binding domains. The induction of plakoglobin by AML fusion proteins led to downstream signaling and transactivation of TCF- and LEF-dependent promoters, including the c-myc promoter, which was found to be bound by plakoglobin in vivo after AML1-ETO expression. β-Catenin protein levels and TCF and LEF target genes such as c-myc and cyclin D1 were found to be induced by the fusion proteins. On the functional level, a dominant negative TCF inhibited colony growth of AML1-ETO-positive Kasumi cells, whereas plakoglobin transfection into myeloid 32D cells enhanced proliferation and clonal growth. Injection of plakoglobin-expressing 32D cells into syngeneic mice accelerated the development of leukemia. Transduction of plakoglobin into primitive murine hematopoietic progenitor cells preserved the immature phenotype during colony growth, suggesting enhanced self-renewal. These data provide evidence that activation of Wnt signaling is a common feature of several balanced translocations in AML.
Reverse Genetics of Escherichia coliGlycerol Kinase Allosteric Regulation and Glucose Control of Glycerol Utilization In Vivo

ABSTRACT Reverse genetics is used to evaluate the roles in vivo of allosteric regulation of Escherichia coli glycerol kinase by the glucose-specific phosphocarrier of the phosphoenolpyruvate:glycose phosphotransferase system, IIAGlc (formerly known as IIIglc), and by fructose 1,6-bisphosphate. Roles have been postulated for these allosteric effectors in glucose control of both glycerol utilization and expression of the glpK gene. Genetics methods based on homologous recombination are used to place glpKalleles with known specific mutations into the chromosomal context of the glpK gene in three different genetic backgrounds. The alleles encode glycerol kinases with normal catalytic properties and specific alterations of allosteric regulatory properties, as determined by in vitro characterization of the purified enzymes. TheE. coli strains with these alleles display the glycerol kinase regulatory phenotypes that are expected on the basis of the in vitro characterizations. Strains with different glpRalleles are used to assess the relationships between allosteric regulation of glycerol kinase and specific repression in glucose control of the expression of the glpK gene. Results of these studies show that glucose control of glycerol utilization and glycerol kinase expression is not affected by the loss of IIAGlc inhibition of glycerol kinase. In contrast, fructose 1,6-bisphosphate inhibition of glycerol kinase is the dominant allosteric control mechanism, and glucose is unable to control glycerol utilization in its absence. Specific repression is not required for glucose control of glycerol utilization, and the relative roles of various mechanisms for glucose control (catabolite repression, specific repression, and inducer exclusion) are different for glycerol utilization than for lactose utilization.
Impact of pharmacist involvement in the transitional care of high-risk patients through medication reconciliation, medication education, and postdischarge call-backs (IPITCH Study).

BACKGROUND Previous data suggest that direct pharmacist interaction with patients through medication reconciliation, discharge counseling, and postdischarge phone calls decreases the number of adverse drug events (ADEs) and plays an overall positive role in transitional care. Previous studies have evaluated pharmacist involvement in improving transitional care, but these studies did not include multiple postdischarge follow-up phone calls. OBJECTIVES The objectives of this study were to assess the impact of pharmacist involvement in transitions of care as measured by decreased medication errors (MEs) and ADEs, patients' knowledge related to communication about their medications as measured by improvement in the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) scores, and 30-day all-cause inpatient readmissions and emergency department (ED) visits. METHODS This was a prospective, randomized, single-period longitudinal study that occurred from November 2012 through June 2013 at an urban, tertiary, academic medical center. Patients admitted to 2 designated internal medicine units on high-risk medications or with greater than 3 prescription medications upon discharge were included for randomization. The control group received the usual hospital standard of care. The study group received face-to-face medication reconciliation, a patient-specific pharmaceutical care plan, discharge counseling, and postdischarge phone calls on days 3, 14, and 30 to provide education and assess study endpoints. RESULTS A total of 278 patients were included in the final analysis, with 141 in the control group and 137 in the study group. Fifty-five patients (39%) in the control arm experienced an inpatient readmission or ED visit within 30-days postdischarge compared to 34 patients (24.8%) in the study arm (P = 0.01). Eighteen patients (12.8%) in the control group experienced an ADEs or MEs compared to 11 patients (8%) in the study group (P > 0.05). The HCAHPS scores during the study period showed a 9% improvement for the assessed questionnaire domain (P > 0.05). CONCLUSIONS This study demonstrated that pharmacist involvement in hospital discharge transitions of care had a positive impact on decreasing composite inpatient readmissions and ED visits. Statistically significant difference in medication-related events and HCAHPS scores were not observed. Patients with moderately complex medication regimens benefited from a continuity of care involving a pharmacy team during transitions in care.
Regulation of Vascular Smooth Muscle Contraction: Changes in Experimental Hypertension

Recent evidence bearing on the following control points for vascular smooth muscle contraction is reviewed: contractile protein, energy metabolism, excitation-contraction coupling, excitation. A study of the vascular smooth muscle of the femoral artery from rats with DCA hypertension demonstrated that it differs from similar muscle from control animals in that it has an increased tendency to develop spontaneous rhythmicity; it responds to lower concentrations of epinephrine, KCl, and CaCl2; and the maximum tension it is able to develop is less. It cannot be determined whether these changes are the cause or the result of the hypertension.