Differential time to positivity of blood cultures: a valid method for diagnosing catheter-related bloodstream infections in the intensive care unit

iii. Catheter-related bloodstream infection (CR-BSI) diagnosis usually involves catheter withdrawal. An alternative method for CR-BSI diagnosis is the differential time to positivity (DTP) between peripheral and catheter hub blood cultures. This study aims to validate the DTP method in short-term catheters. The results show a low prevalence of CR-BSI in the sample (8.4%). The DTP method is a valid alternative for CR-BSI diagnosis in those cases with monomicrobial cultures (80% sensitivity, 99% specificity, 92% positive predictive value, and 98% negative predictive value) and a cut-off point of 17.7 hours for positivity of hub blood culture may assess in CR-BSI diagnosis.

How market access shapes human capital investment in a peripheral country

Human capital endowment is one of the main factors influencing the level of development of a region. This paper analyses whether remoteness from economic activity has a negative effect on human capital accumulation and, consequently, on economic development. Making use of microdata this research proves that remoteness from economic activity has contributed to explain the divergences in the level of education observed across Spanish provinces over the last 50 years. The effect is significant even when controlling for the improvement of education supply. Nonetheless, the accessibility effect has been petering out since the 1960s due to the decreasing barriers to mobility.

HLA class II antigens (DR, DQ LOCI) and peripheral arthritis in ankylosing spondylitis.

Fifty one patients with ankylosing spondylitis (AS) were typed for HLA-A, B, C, DR, and DQ antigens. The antigen frequencies were compared with those of a normal population and with a B27 positive control group. All but one of the patients with AS were HLA-B27 positive. A positive linkage disequilibrium between Cw1, Cw2, DR1, and the B27 antigen was observed. Patients with AS showed a significant increase in DQw2 antigen compared with the B27 positive control group. No differences in antigenic frequencies were observed in patients having peripheral arthritis and patients with only axial involvement. Seven out of nine patients (78%) with an erosive peripheral arthritis were DR7 positive, suggesting that DR7 or genes closely linked could be related with a more aggressive peripheral joint involvement in patients with AS.

Combined intermittent hypoxia and surface muscle electrostimulation as a method to increase peripheral blood progenitor cell concentration.

Background: Our goal was to determine whether short-term intermittent hypoxia exposure, at a level well tolerated by healthy humans and previously shown by our group to increase EPO and erythropoiesis, could mobilizehematopoietic stem cells (HSC) and increase their presence in peripheral circulation. Methods: Four healthy male subjects were subjected to three different protocols: one with only a hypoxic stimulus (OH), another with a hypoxic stimulus plus muscle electrostimulation (HME) and the third with only muscle electrostimulation (OME). Intermittent hypobaric hypoxia exposureconsisted of only three sessions of three hours at barometric pressure 540 hPa (equivalent to an altitude of 5000 m) for three consecutive days, whereas muscular electrostimulation was performed in two separate periods of 25 min in each session. Blood samples were obtained from an antecubital vein on three consecutive days immediately before the experiment and 24 h, 48 h, 4 days and 7 days after the last day of hypoxic exposure. Results: There was a clear increase in the number of circulating CD34+ cells after combined hypobaric hypoxia and muscular electrostimulation. This response was not observed after the isolated application of the same stimuli. Conclusion: Our results open a new application field for hypobaric systems as a way to increase efficiency in peripheral HSC collection.

Combined intermittent hypoxia and surface muscle electrostimulation as a method to increase peripheral blood progenitor cell concentration.

Background: Our goal was to determine whether short-term intermittent hypoxia exposure, at a level well tolerated by healthy humans and previously shown by our group to increase EPO and erythropoiesis, could mobilizehematopoietic stem cells (HSC) and increase their presence in peripheral circulation. Methods: Four healthy male subjects were subjected to three different protocols: one with only a hypoxic stimulus (OH), another with a hypoxic stimulus plus muscle electrostimulation (HME) and the third with only muscle electrostimulation (OME). Intermittent hypobaric hypoxia exposureconsisted of only three sessions of three hours at barometric pressure 540 hPa (equivalent to an altitude of 5000 m) for three consecutive days, whereas muscular electrostimulation was performed in two separate periods of 25 min in each session. Blood samples were obtained from an antecubital vein on three consecutive days immediately before the experiment and 24 h, 48 h, 4 days and 7 days after the last day of hypoxic exposure. Results: There was a clear increase in the number of circulating CD34+ cells after combined hypobaric hypoxia and muscular electrostimulation. This response was not observed after the isolated application of the same stimuli. Conclusion: Our results open a new application field for hypobaric systems as a way to increase efficiency in peripheral HSC collection.

The Determinants of Exit in Argentina: Core and Peripheral Regions

This paper analyses the regional determinants of exit in Argentina. We find evidence of a dynamic revolving door by which past entrants increase current exits, particularly in the peripheral regions. In the central regions, current and past incumbents cause an analogous displacement effect. Also, exit shows a U-shaped relationship with respect to the informal economy, although the positive effect is weaker in the central regions. These findings point to the existence of a core-periphery structure in the spatial distribution of exits. Key words: firm exit, count data models, Argentina JEL: R12; R30; C33

The effect of virtual reality on visual vertigo symptoms in patients with peripheral vestibular dysfunction: a pilot study.

Individuals with vestibular dysfunction may experience visual vertigo (VV), in which symptoms are provoked or exacerbated by excessive or disorientating visual stimuli (e.g. supermarkets). VV can significantly improve when customized vestibular rehabilitation exercises are combined with exposure to optokinetic stimuli. Virtual reality (VR), which immerses patients in realistic, visually challenging environments, has also been suggested as an adjunct to VR to improve VV symptoms. This pilot study compared the responses of sixteen patients with unilateral peripheral vestibular disorder randomly allocated to a VR regime incorporating exposure to a static (Group S) or dynamic (Group D) VR environment. Participants practiced vestibular exercises, twice weekly for four weeks, inside a static (Group S) or dynamic (Group D) virtual crowded square environment, presented in an immersive projection theatre (IPT), and received a vestibular exercise program to practice on days not attending clinic. A third Group D1 completed both the static and dynamic VR training. Treatment response was assessed with the Dynamic Gait Index and questionnaires concerning symptom triggers and psychological state. At final assessment, significant betweengroup differences were noted between Groups D (p = 0.001) and D1 (p = 0.03) compared to Group S for VV symptoms with the former two showing a significant 59.2% and 25.8% improvement respectively compared to 1.6% for the latter. Depression scores improved only for Group S (p = 0.01) while a trend towards significance was noted for Group D regarding anxiety scores (p = 0.07). Conclusion: Exposure to dynamic VR environments should be considered as a useful adjunct to vestibular rehabilitation programs for patients with peripheral vestibular disorders and VV symptoms.

The effect of virtual reality on visual vertigo symptoms in patients with peripheral vestibular dysfunction: a pilot study

Individuals with vestibular dysfunction may experience visual vertigo (VV), in which symptoms are provoked or exacerbated by excessive or disorientating visual stimuli (e.g. supermarkets). VV can significantly improve when customized vestibular rehabilitation exercises are combined with exposure to optokinetic stimuli. Virtual reality (VR), which immerses patients in realistic, visually challenging environments, has also been suggested as an adjunct to VR to improve VV symptoms. This pilot study compared the responses of sixteen patients with unilateral peripheral vestibular disorder randomly allocated to a VR regime incorporating exposure to a static (Group S) or dynamic (Group D) VR environment. Participants practiced vestibular exercises, twice weekly for four weeks, inside a static (Group S) or dynamic (Group D) virtual crowded square environment, presented in an immersive projection theatre (IPT), and received a vestibular exercise program to practice on days not attending clinic. A third Group D1 completed both the static and dynamic VR training. Treatment response was assessed with the Dynamic Gait Index and questionnaires concerning symptom triggers and psychological state. At final assessment, significant betweengroup differences were noted between Groups D (p = 0.001) and D1 (p = 0.03) compared to Group S for VV symptoms with the former two showing a significant 59.2% and 25.8% improvement respectively compared to 1.6% for the latter. Depression scores improved only for Group S (p = 0.01) while a trend towards significance was noted for Group D regarding anxiety scores (p = 0.07). Conclusion: Exposure to dynamic VR environments should be considered as a useful adjunct to vestibular rehabilitation programs for patients with peripheral vestibular disorders and VV symptoms.

1,2,3,4-Tetrahydrobenzo[h][1,6]naphthyridines as a new family of potent peripheral-to-midgorge-site inhibitors of acetylcholinesterase: synthesis, pharmacological evaluation and mechanistic studies

A series of 1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridines differently substituted at positions 1, 5, and 9 have been designed from the pyrano[3,2-c]quinoline derivative 1, a weak inhibitor of acetylcholinesterase (AChE) with predicted ability to bind to the AChE peripheral anionic site (PAS), at the entrance of the catalytic gorge. Fourteen novel benzonaphthyridines have been synthesized through synthetic sequences involving as the key step a multicomponent Povarov reaction between an aldehyde, an aniline and an enamine or an enamide as the activated alkene. The novel compounds have been tested against Electrophorus electricus AChE (EeAChE), human recombinant AChE (hAChE), and human serum butyrylcholinesterase (hBChE), and their brain penetration has been assessed using the PAMPA-BBB assay. Also, the mechanism of AChE inhibition of the most potent compounds has been thoroughly studied by kinetic studies, a propidium displacement assay, and molecular modelling. We have found that a seemingly small structural change such as a double O → NH bioisosteric replacement from the hit 1 to 16a results in a dramatic increase of EeAChE and hAChE inhibitory activities (>217- and >154-fold, respectively), and in a notable increase in hBChE inhibitory activity (> 11-fold), as well. An optimized binding at the PAS besides additional interactions with AChE midgorge residues seem to account for the high hAChE inhibitory potency of 16a (IC50 = 65 nM), which emerges as an interesting anti-Alzheimer lead compound with potent dual AChE and BChE inhibitory activities.

1,2,3,4-Tetrahydrobenzo[h][1,6]naphthyridines as a new family of potent peripheral-to-midgorge-site inhibitors of acetylcholinesterase: synthesis, pharmacological evaluation and mechanistic studies

A series of 1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridines differently substituted at positions 1, 5, and 9 have been designed from the pyrano[3,2-c]quinoline derivative 1, a weak inhibitor of acetylcholinesterase (AChE) with predicted ability to bind to the AChE peripheral anionic site (PAS), at the entrance of the catalytic gorge. Fourteen novel benzonaphthyridines have been synthesized through synthetic sequences involving as the key step a multicomponent Povarov reaction between an aldehyde, an aniline and an enamine or an enamide as the activated alkene. The novel compounds have been tested against Electrophorus electricus AChE (EeAChE), human recombinant AChE (hAChE), and human serum butyrylcholinesterase (hBChE), and their brain penetration has been assessed using the PAMPA-BBB assay. Also, the mechanism of AChE inhibition of the most potent compounds has been thoroughly studied by kinetic studies, a propidium displacement assay, and molecular modelling. We have found that a seemingly small structural change such as a double O → NH bioisosteric replacement from the hit 1 to 16a results in a dramatic increase of EeAChE and hAChE inhibitory activities (>217- and >154-fold, respectively), and in a notable increase in hBChE inhibitory activity (> 11-fold), as well. An optimized binding at the PAS besides additional interactions with AChE midgorge residues seem to account for the high hAChE inhibitory potency of 16a (IC50 = 65 nM), which emerges as an interesting anti-Alzheimer lead compound with potent dual AChE and BChE inhibitory activities.

Catheterisation. Indwelling catheters in adults. Urethral and suprapubic. Evidence-based guidelines for best practice in urological health care

The EAUN Guidelines Working Group for indwelling catheters have prepared this guideline document to help nurses assess the evidence-based management of catheter care and to incorporate the guidelines’ recommendations into their clinical practice. These guidelines are not meant to be proscriptive, nor will adherence to these guidelines guarantee a successful outcome in all cases. Ultimately, decisions regarding care must be made on a case-by-case basis by healthcare professionals after consultation with their patients using their clinical judgement, knowledge and expertise.

Fast Blue and Diamidino Yellow as retrograde tracers in peripheral nerves: efficacy of combined nerve injection and capsule application to transected nerves in the adult rat

Capsule application of Diamidino Yellow (DY) to the cut end of the sciatic nerve immediately followed by capsule application of Fast Blue (FB) resulted in approximate to 95% double-labelled dorsal root ganglion neurones (DRGn) and motoneurones (Mn). Nerve injection of DY followed either immediately or 2 months later by capsule application of FB resulted in approximate to 90% double-labelled DRGn and Mn, indicating that DY and FB label similar populations of DRGn and Mn, and that insignificant DY fading occurred during this period. Inversing the order of application, however, i.e. nerve injection of FB followed immediately by capsule application of DY, resulted in double labelling in only approximate to 10% of the DRGn and Mn. These percentages increased to 70% of the DRGn and 60% of the Mn when the FB injection was followed 1 or 2 months after by the DY application, indicating that DY uptake is blocked by recent administration of FB. The results indicate that DY and FB might be useful for sequential labelling before and after nerve injury as a tool to investigate the accuracy of sensory and motor regeneration.

Estimations of topographically correct regeneration to nerve branches and skin after peripheral nerve injury and repair.

Peripheral nerve injury is typically associated with long-term disturbances in sensory localization, despite nerve repair and regeneration. Here, we investigate the extent of correct reinnervation by back-labeling neuronal soma with fluorescent tracers applied in the target area before and after sciatic nerve injury and repair in the rat. The subpopulations of sensory or motor neurons that had regenerated their axons to either the tibial branch or the skin of the third hindlimb digit were calculated from the number of cell bodies labeled by the first and/or second tracer. Compared to the normal control side, 81% of the sensory and 66% of the motor tibial nerve cells regenerated their axons back to this nerve, while 22% of the afferent cells from the third digit reinnervated this digit. Corresponding percentages based on quantification of the surviving population on the experimental side showed 91%, 87%, and 56%, respectively. The results show that nerve injury followed by nerve repair by epineurial suture results in a high but variable amount of topographically correct regeneration, and that proportionally more neurons regenerate into the correct proximal nerve branch than into the correct innervation territory in the skin

Causality and contagion in peripheral EMU public debt markets: a dynamic approach

Our research aims to analyze the causal relationships in the behavior of public debt issued by peripheral member countries of the European Economic and Monetary Union -EMU-, with special emphasis on the recent episodes of crisis triggered in the eurozone sovereign debt markets since 2009. With this goal in mind, we make use of a database of daily frequency of yields on 10-year government bonds issued by five EMU countries -Greece, Ireland, Italy, Portugal and Spain-, covering the entire history of the EMU from its inception on 1 January 1999 until 31 December 2010. In the first step, we explore the pair-wise causal relationship between yields, both for the whole sample and for changing subsamples of the data, in order to capture the possible time-varying causal relationship. This approach allows us to detect episodes of contagion between yields on bonds issued by different countries. In the second step, we study the determinants of these contagion episodes, analyzing the role played by different factors, paying special attention to instruments that capture the total national debt -domestic and foreign- in each country.

Macroautophagic process was differentially modulated by long-term moderate exercise in rat brain and peripheral tissues

The autophagic process is a lysosomal degradation pathway, which is activated during stress conditions, such as starvation or exercise. Regular exercise has beneficial effects on human health, including neuroprotection. However, the cellular mechanisms underlying these effects are incompletely understood. Endurance and a single bout of exercise induce autophagy not only in brain but also in peripheral tissues. However, little is known whether autophagy could be modulated in brain and peripheral tissues by long-term moderate exercise. Here, we examined the effects on macroautophagy process of long-term moderate treadmill training (36 weeks) in adult rats both in brain (hippocampus and cerebral cortex) and peripheral tissues (skeletal muscle, liver and heart). We assessed mTOR activation and the autophagic proteins Beclin 1, p62, LC3B (LC3B-II/LC3B-I ratio) and the lysosomal protein LAMP1, as well as the ubiquitinated proteins. Our results showed in the cortex of exercised rats an inactivation of mTOR, greater autophagy flux (increased LC3-II/LC3-I ratio and reduced p62) besides increased LAMP1. Related with these effects a reduction in the ubiquitinated proteins was observed. No significant changes in the autophagic pathway were found either in hippocampus or in skeletal and cardiac muscle by exercise. Only in the liver of exercised rats mTOR phosphorylation and p62 levels increased, which could be related with beneficial metabolic effects in this organ induced by exercise. Thus, our findings suggest that long-term moderate exercise induces autophagy specifically in the cortex