Miracle-dz/UniFAR-FTUs huggingface dataset:
Serial measurements of the Nt-ProBNP during the dry state in patients with systolic heart failure are predictors of the long-term prognosis

Abstract Objective: To evaluate the long-term predictive value of serial Nt-ProBNP during dry-state in patients with systolic heart failure (SHF). Methods: Nt-ProBNP was measured quarterly during a 6-month dry-state period in 40 SHF outpatients. Events: all-cause mortality or hospitalization. Follow-up: 5 years. Results: The Nt-ProBNP >1000 pg/ml (baseline and 6 months) and the variation rate (VR) >30% were independently associated with the survival and composite endpoint curve. VR >30% added significant prognostic information to the single Nt-ProBNP 1000 pg/ml cut-off. Patients with at least one Nt-ProBNP determination >1000 pg/ml were at greater risk of death. Conclusion: Serial Nt-ProBNP measurements in patients with SHF during the dry-state are strong predictors of the long-term prognosis.
Decreased gene expression for telomeric-repeat binding factors and TIN2 in malignant hematopoietic cells.

BACKGROUND Details of mechanisms regulating telomere length are poorly understood in human hematopoietic cells. MATERIALS AND METHODS Gene expression for TRFs and TIN2 was studied in hematopoietic cell lines, blood or bone marrow cells from acute leukemia and in normal leukocyte fractions. RESULTS The telomeres were longest in normal leukocytes, shorter in patient samples and still shorter in malignant hematopoietic cell lines. TRF1 mRNA, TRF2 mRNA and TIN2 mRNA in three myeloblastic cell lines and six lymphoblastic cell lines were significantly less abundant than in the corresponding normal cell types. In patients with acute myeloid leukemia, expression of these gene was also less than in normal cells. In additional studies in culture, HL-60 cells with initially high telomerase activity and low expression of TRF mRNA and TIN2 mRNA differentiated into granulocytic and monocytic cells with low telomerase activity and high expression of these mRNAs. CONCLUSION In hematopoietic carcinogenesis, gene expression for suppressors of telomerase activity, such as TRF and TIN2, is decreased. These genes might hold promise for gene therapy against cancer.
Physiologically based pharmacokinetic model for chronic inhalation of 2-butoxyethanol.

2-Butoxyethanol (2BE) is used extensively in the production of cleaning agents and as a general solvent. It is primarily metabolized in the liver to 2-butoxyacetic acid (2BAA), which is excreted in urine. The objective of this study was to develop a physiologically based pharmacokinetic (PBPK) model describing the toxicokinetic behavior of 2BE and 2BAA in different species following repeated, long-term exposures. The PBPK model was first developed for short-term 2BE exposure to male rats. Allometric scaling was employed to estimate physiological and biochemical model parameters based on body weight. To accommodate differences in 2BE toxicokinetics in female rats, a higher Vmax for 2BE metabolism to 2BAA, higher plasma protein binding sites for 2BAA, and lower Vmax for 2BAA excretion through the kidney were incorporated into the model. For mice, a higher Vmax for 2BE metabolism to 2BAA for both sexes and higher plasma protein binding sites for 2BAA for female mice were also incorporated into the model. Subsequently, the model was expanded to simulate 2BE and 2BAA toxicokinetics for long-term, repeated exposures by incorporating time-dependent changes in model parameters. To reflect physiological/biochemical changes in animals during a chronic exposure, parameters for cardiac output, body composition, metabolic capacity, protein binding, or capacity of renal excretion were adjusted over time depending on species and sex. Sensitivity analysis was performed to better understand how sensitive model responses were to uncertainties in input parameters. The resulting PBPK model was used to simulate toxicokinetic data acquired during a 2-year inhalation toxicity and carcinogenicity study in male and female F344/N rats and B6C3F1 mice.
Circumplex Model of Affect: A Measure of Pleasure and Arousal During Virtual Reality Distraction Analgesia.

OBJECTIVE Immersive virtual reality (VR) distraction provides clinically effective pain relief and increases subjective reports of "fun" in medical settings of procedural pain. The goal of this study was to better describe the variable of "fun" associated with VR distraction analgesia using the circumplex model (pleasure/arousal) of affect. MATERIALS AND METHODS Seventy-four healthy volunteers (mean age, 29 years; 37 females) received a standardized, 18-minute, multimodal pain sequence (alternating thermal heat and electrical stimulation to distal extremities) while receiving immersive, interactive VR distraction. Subjects rated both their subjective pain intensity and fun using 0-10 Graphic Rating Scales, as well as the pleasantness of their emotional valence and their state of arousal on 9-point scales. RESULTS Compared with pain stimulation in the control (baseline, no VR) condition, immersive VR distraction significantly reduced subjective pain intensity (P < 0.001). During VR distraction, compared with those reporting negative affect, subjects reporting positive affect did so more frequently (41 percent versus 9 percent), as well as reporting both greater pain reduction (22 percent versus 1 percent) and fun scores (7.0 ± 1.9 versus 2.4 ± 1.4). Several factors-lower anxiety, greater fun, greater presence in the VR environment, and positive emotional valence-were associated with subjective analgesia during VR distraction. CONCLUSIONS Immersive VR distraction reduces subjective pain intensity induced by multimodal experimental nociception. Subjects who report less anxiety, more fun, more VR presence, and more positive emotional valence during VR distraction are more likely to report subjective pain reduction. These findings indicate VR distraction analgesia may be mediated through anxiolytic, attentional, and/or affective mechanisms.
Involvement of brain‐derived neurotrophic factor in cannabinoid receptor‐dependent protection against excitotoxicity

Cannabinoid type 1 (CB1) receptors play a central role in the protection against excitotoxicity induced by treatment of mice with kainic acid (KA). As inactivation of CB1 receptor function in mice blocks KA‐induced increase of brain‐derived neurotrophic factor (BDNF) mRNA levels in hippocampus, the notion was put forward that BDNF might be a mediator, at least in part, of CB1 receptor‐dependent neuroprotection [Marsicano et al. (2003) Science, 302, 84–88]. To assess this signalling cascade in more detail, organotypic hippocampal slice cultures were used, as this in vitro system conserves morphological and functional properties of the hippocampus. Here, we show that both genetic ablation of CB1 receptors and pharmacological blockade with the specific CB1 receptor antagonist SR141716A increased the susceptibility of the in vitro cultures to KA‐induced excitotoxicity, leading to extensive neuronal death. Next, we found that the application of SR141716A to hippocampal cultures from wild‐type mice abolished the KA‐induced increase in BDNF protein levels. Therefore, we tried to rescue these organotypic cultures from neuronal death by exogenously applied BDNF. Indeed, BDNF was sufficient to prevent KA‐induced neuronal death after blockade of CB1 receptor signalling. In conclusion, our results strongly suggest that BDNF is a key mediator in CB1 receptor‐dependent protection against excitotoxicity, and further underline the physiological importance of the endogenous cannabinoid system in neuroprotection.
On the quantification of [18F]MPPF binding to 5-HT1A receptors in the human brain.

UNLABELLED Previous studies have shown that 4-(2'-methoxyphenyl)-1-[2'-(N-2"-pyridinyl)-p-[(18)F]fluorobenzamido]ethylpiperazine ([(18)F]MPPF) binds with high selectivity to serotonin (5-HT(1A)) receptors in man. However, in these studies, the calculation of the binding potential (BP, which equals receptor density divided by equilibrium dissociation constant) used a metabolite-corrected arterial input. The aim of this study was to determine whether metabolite correction and arterial sampling are essential for the assessment of BP. METHODS Five analytic methods using full datasets obtained from 6 healthy volunteers were compared. In addition, the clinical applicability of these methods was appraised. Three methods were based on Logan analysis of the dynamic PET data using metabolite-corrected and uncorrected arterial plasma input and cerebellar input. The other 2 methods consisted of a simplified reference tissue model and standard compartmental modeling. RESULTS A high correlation was found between BP calculated with Logan analysis using the metabolite-corrected plasma input (used as the reference method for this study) and Logan analysis using either the uncorrected arterial plasma input (r(2) = 0.95, slope = 0.85) or cerebellar input (r(2) = 0.98, slope = 0.91). A high correlation was also found between our reference method and the simplified reference tissue model (r(2) = 0.94, slope = 0.92). In contrast, a poor correlation was observed between our reference method and the standard compartmental model (r(2) = 0.45, slope = 1.59). CONCLUSION These results indicate that neither metabolite analysis nor arterial sampling is necessary for clinical evaluation of BP in the human brain with [(18)F]MPPF. Both the Logan analysis method with cerebellar input and the simplified reference tissue method can be applied clinically.
Beyond EU-US Trade Dynamics: TTIP Effects Related to Foreign Direct Investment and Innovation

The international economic debate on the Transatlantic Trade and Investment Partnership (TTIP) has focused mainly on trade induced real income gains while the FDI related and innovation induced benefits have been largely neglected, although the EU and the US are leading FDI host countries and FDI source countries. Moreover, from a theoretical perspective a knowledge production function has to be considered in order to analyze FDI and innovation dynamics – and this can then be linked to output and economic growth, respectively. It is argued that such a Schumpeterian approach for an open economy is needed to understand deep integration dynamics while the standard CGE model used by Francois et al (2013) leads to an underestimation of deep integration projects such as TTIP. The panel data estimation of knowledge production functions for 20 EU countries between 2002-2012 shows clear empirical evidence that a rise of the number of researchers and of the FDI stock-GDP ratio (or related variables) will raise patent applications. Additionally, a higher per capita income – that could reflect trade related real income gains in the context of TTIP – also contributes to new knowledge and a fortiori to higher GDP. Time series data analysis for Germany indicates additionally that FDI induced higher innovation dynamics will raise output – combining trade benefits and FDI/innovation related real income gains plus transatlantic macroeconomic interdependency effects a real income gain of nearly 2% should be expected for Germany (and the EU): considerably higher than what the official TTIP report for the European Commission has suggested. The results also suggest positive employment effects.
Inactivation of NF-kappaB involved in osteoblast development through interleukin-6.

Osteoblasts undergo a process of proliferation and differentiation and are responsible for bone formation. In this study, we examined the relation between NF-kappaB, a key transcription factor in bone metabolism, and osteoblast maturation. NF-kappaB activity and expression of p50, a subunit of NF-kappaB, decreased during development of osteoblastic MC3T3-E1 cells. The secretion of IL-6 by osteoblast, which in combination with soluble IL-6 receptor induces conversion of fibroblasts to alkaline phosphatase-positive cells, also increased. p50 antisense oligonucleotide increased IL-6 mRNA expression. These results suggest that p50 regulates transcription of IL-6 and indirectly controls osteoblast maturation.
Recent changes in the management of blunt splenic injury: effect on splenic trauma patients and hospital implications.

INTRODUCTION Management of blunt splenic injury has been controversial with an increasing trend towards splenic conservation. A retrospective study was performed to identify the effect of this changed policy on splenic trauma patients and its implications. PATIENTS AND METHODS Data regarding patient demography, mode of splenic injury, CT grading, blood transfusion requirement, operative findings hospital stay and follow-up were collected. Statistical analysis of the data was performed using nonparametric Mann-Whitney tests RESULTS Over an 8-year period, only 21 patients were admitted with blunt splenic injury. Ten patients were managed operatively and 11 non-operatively. Non-operative management failed in one patient due to continued bleeding. Using Buntain's CT grading, the majority of grades I and II splenic injuries were managed non-operatively and grades III and IV were managed operatively ( P = 0.008). Blood transfusion requirement was significantly higher among the operative group (P = 0.004) but the non-operative group had a significantly longer hospital stay (P = 0.029). Among those managed non-operatively (median age, 24.5 years), a number of patients were followed up with CT scans with significant radiation exposure and unknown longterm consequences. CONCLUSIONS Non-operative management of blunt splenic trauma in adults can be performed with an acceptable outcome. Although CT is classed as the 'gold standard', initial imaging for detection and evaluation of blunt splenic injury, ultrasound can play a major role in follow-up imaging and potentially avoids major radiation exposure.
The P Domain of Norovirus Capsid Protein Forms Dimer and Binds to Histo-Blood Group Antigen Receptors

ABSTRACT Noroviruses (NVs) are the most important pathogen of epidemic nonbacterial gastroenteritis. The recent finding that NVs recognize human histo-blood group antigens (HBGAs) as receptors provided a new approach to study the pathogenesis of NVs. Using computational and site-directed mutagenesis approaches, our investigators previously identified a plausible binding pocket in the P domain of the NV capsids. In this study, we further characterize the role of the P domain in the interaction with human HBGA receptors using three NV strains representing three binding patterns. Our results show that the isolated P domain, although it did not form virus-like particles (VLPs), formed dimers, and the dimers bound HBGAs with the same patterns as those of the intact viral capsids. In contrast, the S domain, which formed small, thin-layer VLPs, did not bind A, B, or H HBGAs. A chimera containing the S domain of VA387 and the P domain of MOH revealed a binding pattern of the P donor strain (MOH). Deletion experiments revealed that an intact P domain is necessary for receptor binding. The P domain dimers are stable over a broad range of pH (2 to 11) or under strong denaturing conditions. Taken together, our results suggest that the P domain of NV contains essential elements for strain-specific binding to receptors. Further study of the P domain will provide useful information about the virus-receptor interaction. The high yield and easy production of the recombinant P protein in the Escherichia coli expression system will provide a simple approach to this goal.
Transcription Analysis of Two Disparate rRNA Operons in the Halophilic Archaeon Haloarcula marismortui

ABSTRACT The genome of the halophilic archaeon Haloarcula marismortui contains two rRNA operons designated rrnAand rrnB. Genomic clones of the two operons and their flanking regions have been sequenced, and primary transcripts and processing intermediates derived from each operon have been characterized. The 16S, 23S, and 5S genes from the two operons were found to differ at 74 of 1,472 positions, 39 of 2,922 positions, and 2 of 122 positions, respectively. This degree of sequence divergence for multicopy (paralogous) rRNA genes was 10- to 50-fold or more higher than anticipated. The two operons exhibit other profound differences that include (i) the presence in rrnA and the absence inrrnB of tRNAAla and tRNACys genes in the intergenic and distal regions, respectively, (ii) divergent 5′ flanking sequences, and (iii) distinct pathways for processing and maturation of 16S rRNA. Processing and maturation of 16S and 23S rRNA from rrnA operon transcripts and of 23S rRNA fromrrnB operon transcripts follow the canonical halophilic pathway, whereas maturation of 16S rRNA from rrnB operon transcripts follows an unusual and different pathway that is apparently devoid of any 5′ processing intermediate.
Should all dysfunctional high-voltage leads be extracted? Results of a single-centre long-term registry.

AIMS A considerable number of lead defects occurs during long-term cardioverter defibrillator therapy. Evidence-based strategies for the handling of chronically implanted, non-functional high-voltage (HV) leads are mandatory. METHODS AND RESULTS Patient outcome after abandonment of HV leads was retrospectively compared with patient outcome following other lead revision strategies and following primary implantation. A total of 903 consecutive patients undergoing 997 implantable cardioverter defibrillator (ICD) implantations or lead revisions were followed for a mean period of 48.8 ± 37.8 months. One or more additional HV leads were placed in 60 patients. An additional pace/sense lead was implanted in 13 patients. Extraction and replacement of a dysfunctional HV lead was performed in 21 patients. The overall rate of complications including artefact sensing, ineffective defibrillation, symptomatic subclavian vein thrombosis, and other lead defects did not differ between patients with and without an additional HV lead (10.0 vs. 8.9%, P = 0.32). Survival without lead associated complications did not differ between groups. Results remained unchanged after correction for covariates. CONCLUSIONS Abandoned HV leads did not increase the risk of ICD system-related complications in the majority of patients. Thus, a general lead extraction policy of dysfunctional HV leads cannot be advised in an average ICD population. Recommendations may not apply for young and physically active patients, in whom HV lead extraction must be considered.
"Delivering" on the MDGs?: equity and maternal health in Ghana, Ethiopia and Kenya.

OBJECTIVES The Millennium Development Goals (MIDGs) have put maternal health in the mainstream, but there is a need to go beyond the MDGs to address equity within countries. We argue that MDG focus on maternal health is necessary but not sufficient. This paper uses Demographic and Health Survey (DHS) data from Kenya, Ethiopia and Ghana to examine a set of maternal health indicators stratified along five different dimensions. The study highlights the interactive and multiple forms of disadvantage and demonstrates that equity monitoring for the MDGs is possible, even given current data limitations. METHODS We analyse DHS data from Ghana, Kenya and Ethiopia on four indicators: skilled birth attendant, contraceptive prevalence rate, AIDS knowledge and access to a health facility. We define six social strata along five different dimensions: poverty status, education, region, ethnicity and the more traditional wealth quintile. Data are stratified singly (e.g. by region) and then stratified simultaneously (e.g. by region and by education) in order to examine the compounded effect of dual forms of vulnerability. RESULTS Almost all disparities were found to be significant, although the stratifier with the strongest effect on health outcomes varied by indicator and by country. In some cases, urban-dwelling is a more significant advantage than wealth and in others, educational status trumps poverty status. The nuances of this analysis are important for policymaking processes aimed at reaching the MDGs and incorporating maternal health in national development plans. CONCLUSIONS The article highlights the following key points about inequities and maternal health: 1) measuring and monitoring inequity in access to maternal health is possible even in low resource settings-using current data 2) statistically significant health gaps exist not just between rich and poor, but across other population groups as well, and multiple forms of disadvantage confer greater risk and 3) policies must be aligned with reducing health gaps in access to key maternal health services.
Front and backstage in the workplace

Purpose The ability of employees to handle work-related demands, structure their own work and manage workflow is highly important in today’s complex organisations. This paper aims to explore the impact of the office environment on employees’ ability to control interaction, structure their own work processes and handle work-related demands. The focus is on the influence of the physical premises, especially on how work within private, privileged and public work zones may affect perceptions of, and possibilities to control, customer interactions and other work-related demands. Design/methodology/approach The paper is based on a qualitative case study of a Norwegian finance corporation. The core method was semi-structured interviews, carried out with 29 employees and managers. The triangulated research design included observations, field notes, user logs and document analyses. Findings The findings indicate that, in a customer-centred work process, separate zones for customer-related work and for internal work provide employees with increased scope to handle work demands and perceive control in their work. Zoning helped structure the workflow and provided employees with new resources in customer interaction and other work tasks. Originality/value Broadening the focus on environmental control and work-related demands from individual coping to social interaction may provide more insight into factors influencing work processes and employee well-being in emerging workplace concepts.
A unique isolated dwarf spheroidal galaxy atD = 1.9 Mpc

We present a photometric and spectroscopic study of the unique isolated nearby dwarf spheroidal (dSph) galaxy KKR 25. The galaxy was resolved into stars with Hubble Space Telescope/Wide Field Planetary Camera 2 including old red giant branch and red clump. We have constructed a model of the resolved stellar populations and measured the star formation rate and metallicity as a function of time. The main star formation activity period occurred about 12.6–13.7 Gyr ago. These stars are mostly metal poor, with a mean metallicity [Fe/H] ∼ −1 to −1.6 dex. About 60 per cent of the total stellar mass was formed during this event. There are indications of intermediate-age star formation in KKR 25 between 1 and 4 Gyr with no significant signs of metal enrichment for these stars. Long-slit spectroscopy was carried out using the Russian 6-m telescope of the integrated starlight and bright individual objects in the galaxy. We have discovered a planetary nebula (PN) in KKR 25. This is the first known PN in a dSph galaxy outside the Local Group. We have measured its oxygen abundance 12 + log (O/H) = 7.60 ± 0.07 dex and a radial velocity V_h = −79 km s^(−1). We have analysed the stellar density distribution in the galaxy body. The galaxy has an exponential surface brightness profile with a central light depression. We discuss the evolutionary status of KKR 25, which belongs to a rare class of very isolated dwarf galaxies with spheroidal morphology.