249 research outputs found

    Simplified Dosing of Gentamicin for Treatment of Sepsis in Bangladeshi Neonates

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    Extended-interval dosing of gentamicin has several advantages over conventional multiple-daily dosing for the treatment of sepsis. The study was conducted to evaluate the pharmacokinetics of gentamicin for the treatment of neonatal sepsis in predetermined doses at 24- or 48-hour intervals, according to weight category, and to develop a simplified protocol for use in peripheral healthcare settings in developing countries. This prospective observational study was conducted among 59 neonates admitted to the Special Care Nursery at Dhaka Shishu Hospital, Bangladesh, with suspected sepsis and treated with antibiotics, including gentamicin. Intravenous dosing of gentamicin according to weight category was: 10 mg every 48 hours if the infant weighed <2,000 g (n=23), 10 mg every 24 hours if the infant weighed 2,000–2,249 g (n=12), or 13.5 mg every 24 hours if the infant weighed 2,500–3,000 g (n=24). Peak and trough concentrations of gentamicin and the presence of signs of nephrotoxicity and ototoxicity were determined. The mean±standard deviation peak concentration of gentamicin was 12.3±3.7 µg/mL in infants weighing <2,000 g, 9.6±3.1 µg/mL in infants 2,000–2,249 g, and 10.0±3.4 µg/mL in infants 2,500–3,000 g. Initial peak concentration of gentamicin was >12 µg/mL in 28.8% and initial trough concentration was >2 µg/mL in 6.8% of the subjects. No signs of nephrotoxicity or ototoxicity were detected. Favourable pharmacokinetic parameters found with the simplified dosing regimen suggest that it is safe for the treatment of neonatal sepsis

    Quantum noise in current biased Josephson junction

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    Quantum fluctuations in a current biased Josephson junction, described in terms of the RCSJ-model, are considered. The fluctuations of the voltage and phase across the junction are assumed to be initiated by equilibrium current fluctuations in the shunting resistor. This corresponds to low enough temperatures, when fluctuations of the normal current in the junction itself can be neglected. We used the quantum Langevin equation in terms of random variables related to the limit cycle of the nonlinear Josephson oscillator. This allows to go beyond the perturbation theory and calculate the widths of the Josephson radiation lines

    Optimality of mutation and selection in germinal centers

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    The population dynamics theory of B cells in a typical germinal center could play an important role in revealing how affinity maturation is achieved. However, the existing models encountered some conflicts with experiments. To resolve these conflicts, we present a coarse-grained model to calculate the B cell population development in affinity maturation, which allows a comprehensive analysis of its parameter space to look for optimal values of mutation rate, selection strength, and initial antibody-antigen binding level that maximize the affinity improvement. With these optimized parameters, the model is compatible with the experimental observations such as the ~100-fold affinity improvements, the number of mutations, the hypermutation rate, and the "all or none" phenomenon. Moreover, we study the reasons behind the optimal parameters. The optimal mutation rate, in agreement with the hypermutation rate in vivo, results from a tradeoff between accumulating enough beneficial mutations and avoiding too many deleterious or lethal mutations. The optimal selection strength evolves as a balance between the need for affinity improvement and the requirement to pass the population bottleneck. These findings point to the conclusion that germinal centers have been optimized by evolution to generate strong affinity antibodies effectively and rapidly. In addition, we study the enhancement of affinity improvement due to B cell migration between germinal centers. These results could enhance our understandings to the functions of germinal centers.Comment: 5 figures in main text, and 4 figures in Supplementary Informatio

    Germinal center reutilization by newly activated B cells

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    Germinal centers (GCs) are specialized structures in which B lymphocytes undergo clonal expansion, class switch recombination, somatic hypermutation, and affinity maturation. Although these structures were previously thought to contain a limited number of isolated B cell clones, recent in vivo imaging studies revealed that they are in fact dynamic and appear to be open to their environment. We demonstrate that B cells can colonize heterologous GCs. Invasion of primary GCs after subsequent immunization is most efficient when T cell help is shared by the two immune responses; however, it also occurs when the immune responses are entirely unrelated. We conclude that GCs are dynamic anatomical structures that can be reutilized by newly activated B cells during immune responses

    Simplified Dosing of Gentamicin for Treatment of Sepsis in Bangladeshi Neonates

    Get PDF
    Extended-interval dosing of gentamicin has several advantages over conventional multiple-daily dosing for the treatment of sepsis. The study was conducted to evaluate the pharmacokinetics of gentamicin for the treatment of neonatal sepsis in predetermined doses at 24- or 48-hour intervals, according to weight category, and to develop a simplified protocol for use in peripheral healthcare settings in developing countries. This prospective observational study was conducted among 59 neonates admitted to the Special Care Nursery at Dhaka Shishu Hospital, Bangladesh, with suspected sepsis and treated with antibiotics, including gentamicin. Intravenous dosing of gentamicin according to weight category was: 10 mg every 48 hours if the infant weighed &lt;2,000 g (n=23), 10 mg every 24 hours if the infant weighed 2,000-2,249 g (n=12), or 13.5 mg every 24 hours if the infant weighed 2,500-3,000 g (n=24). Peak and trough concentrations of gentamicin and the presence of signs of nephrotoxicity and ototoxicity were determined. The mean\ub1standard deviation peak concentration of gentamicin was 12.3\ub13.7 \u3bcg/mL in infants weighing &lt;2,000 g, 9.6\ub13.1 \u3bcg/mL in infants 2,000-2,249 g, and 10.0\ub13.4 \u3bcg/mL in infants 2,500-3,000 g. Initial peak concentration of gentamicin was &gt;12 \u3bcg/mL in 28.8% and initial trough concentration was &gt;2 \u3bcg/mL in 6.8% of the subjects. No signs of nephrotoxicity or ototoxicity were detected. Favourable pharmacokinetic parameters found with the simplified dosing regimen suggest that it is safe for the treatment of neonatal sepsis

    Magnetic resonance imaging after most common form of concussion

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    <p>Abstract</p> <p>Background</p> <p>Until now there is a lack of carefully controlled studies with conventional MR imaging performed exclusively in concussion with short lasting loss of consciousness (LOC).</p> <p>Methods</p> <p>A MR investigation was performed within 24 hours and after 3 months in 20 patients who had suffered a concussion with a verified loss of consciousness of maximally 5 minutes. As a control group, 20 age- and gender matched patients with minor orthopaedic injuries had a MR investigation using the same protocol.</p> <p>Results</p> <p>In a concussion population with an average LOC duration of 1. 4 minutes no case with unequivocal intracranial traumatic pathology was detected.</p> <p>Conclusion</p> <p>An ordinary concussion with short lasting LOC does not or only seldom result in a degree of diffuse axonal injury (DAI) that is visualized by conventional MR with field strength of 1.0 Tesla (T). Analysis of earlier MR studies in concussion using field strength of 1.5 T as well as of studies with diffusion tensor MR imaging (MR DTI) reveal methodological shortcomings, in particular use of inadequate control groups. There is, therefore, a need for carefully controlled studies using MR of higher field strength and/or studies with MR DTI exclusively in common concussion with LOC of maximally 5 minutes.</p

    The Relationship between Emotional Intelligence and Cool and Hot Cognitive Processes: A Systematic Review

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    Although emotion and cognition were considered to be separate aspects of the psyche in the past, researchers today have demonstrated the existence of an interplay between the two processes. Emotional intelligence (EI), or the ability to perceive, use, understand, and regulate emotions, is a relatively young concept that attempts to connect both emotion and cognition. While EI has been demonstrated to be positively related to well-being, mental and physical health, and non-aggressive behaviors, little is known about its underlying cognitive processes. The aim of the present study was to systematically review available evidence about the relationship between EI and cognitive processes as measured through “cool” (i.e., not emotionally laden) and “hot” (i.e., emotionally laden) laboratory tasks. We searched Scopus and Medline to find relevant articles in Spanish and English, and divided the studies following two variables: cognitive processes (hot vs. cool) and EI instruments used (performance-based ability test, self-report ability test, and self-report mixed test). We identified 26 eligible studies. The results provide a fair amount of evidence that performance-based ability EI (but not self-report EI tests) is positively related with efficiency in hot cognitive tasks. EI, however, does not appear to be related with cool cognitive tasks: neither through self-reporting nor through performance-based ability instruments. These findings suggest that performance-based ability EI could improve individuals’ emotional information processing abilities.This research was financed by the Spanish Ministry of Economy (PSI2012-37490) and the Innovation and Development Agency of Andalusia,Spain(SEJ-07325)

    Space- and time-resolved investigation on diffusion kinetics of human skin following macromolecule delivery by microneedle arrays

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    Microscale medical devices are being developed for targeted skin delivery of vaccines and the extraction of biomarkers, with the potential to revolutionise healthcare in both developing and developed countries. The effective clinical development of these devices is dependent on understanding the macro-molecular diffusion properties of skin. We hypothesised that diffusion varied according to specific skin layers. Using three different molecular weights of rhodamine dextran (RD) (MW of 70, 500 and 2000 kDa) relevant to the vaccine and therapeutic scales, we deposited molecules to a range of depths (0–300 µm) in ex vivo human skin using the Nanopatch device. We observed significant dissipation of RD as diffusion with 70 and 500 kDa within the 30 min timeframe, which varied with MW and skin layer. Using multiphoton microscopy, image analysis and a Fick’s law analysis with 2D cartesian and axisymmetric cylindrical coordinates, we reported experimental trends of epidermal and dermal diffusivity values ranging from 1–8 µm2 s-1 to 1–20 µm2 s-1 respectively, with a significant decrease in the dermal-epidermal junction of 0.7–3 µm2 s-1. In breaching the stratum corneum (SC) and dermal-epidermal junction barriers, we have demonstrated practical application, delivery and targeting of macromolecules to both epidermal and dermal antigen presenting cells, providing a sound knowledge base for future development of skin-targeting clinical technologies in humans
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