Pharmacokinetics and antinociceptive effects of tramadol and its metabolite O-desmethyltramadol following intravenous administration in sheep

Although sheep are widely used as an experimental model for various surgical procedures there is a paucity of data on the pharmacokinetics and efficacy of analgesic drugs in this species. The aims of this study were to investigate the pharmacokinetics of intravenously (IV) administered tramadol and its active metabolite O-desmethyltramadol (M1) and to assess the mechanical antinociceptive effects in sheep. In a prospective, randomized, blinded study, six healthy adult sheep were given 4 and 6\u2009mg/kg tramadol and saline IV in a cross-over design with a 2-week wash-out period. At predetermined time points blood samples were collected and physiological parameters and mechanical nociceptive threshold (MNT) values were recorded. The analytical determination of tramadol and M1 was performed using high performance liquid chromatography. Pharmacokinetic parameters fitted a two- and a non-compartmental model for tramadol and M1, respectively. Normally distributed data were analysed by a repeated mixed linear model. Plasma concentration vs. time profiles of tramadol and M1 were similar after the two doses. Tramadol and M1 plasma levels decreased rapidly in the systemic circulation, with both undetectable after 6\u2009h following drug administration. Physiological parameters did not differ between groups; MNT values were not statistically significant between groups at any time point. It was concluded that although tramadol and M1 concentrations in plasma were above the human minimum analgesic concentration after both treatments, no mechanical antinociceptive effects of tramadol were reported. Further studies are warranted to assess the analgesic efficacy of tramadol in sheep

Neutron Star Radius-to-mass Ratio from Partial Accretion Disc Occultation as Measured through Fe Kα\alpha Line Profiles

We present a new method to measure the radius-to-mass ratio (R/M) of weakly magnetic, disc-accreting neutron stars by exploiting the occultation of parts of the inner disc by the star itself. This occultation imprints characteristic features on the X-ray line profile that are unique and are expected to be present in low mass X-ray binary systems seen under inclinations higher than ~65 degrees. We analyse a NuSTAR observation of a good candidate system, 4U 1636-53, and find that X-ray spectra from current instrumentation are unlikely to single out the occultation features owing to insufficient signal-to-noise. Based on an extensive set of simulations we show that large-area X-ray detectors of the future generation could measure R/M to ~2{\div}3% precision over a range of inclinations. Such is the precision in radius determination required to derive tight constraints on the equation of state of ultradense matter and it represents the goal that other methods too aim to achieve in the future.Comment: 17 pages, 8 figures; this is a pre-print edition of an article that has been accepted for publication in the Astrophysical Journa

A 3D Geological Model as a Base for the Development of a Conceptual Groundwater Scheme in the Area of the Colosseum (Rome, Italy)

Geological models are very useful tools for developing conceptual schemes owing to their capacity to optimize the management of stratigraphic information. This is particularly true in areas where archaeological heritage is exposed to hydrogeological hazards; 3D models can constitute the first step toward the construction of numerical models created to understand processes and plan mitigation actions to improve visitor safety and preserve archaeological heritage. This paper illustrates the results of a 3D hydrostratigraphic model of the site of the Colosseum in the Central Archaeological Area of Rome. In recent years, this area has experienced numerous floods caused by intense meteorological events. A new borehole survey provided the opportunity to update previous maps and cross sections and build a local scale 3D model. The resulting conceptual model was used to identify primary gaps in existing knowledge about the groundwater system and to optimize the planning of a piezometer monitoring network. Further studies can then focus on the development of groundwater numerical models to verify hypotheses regarding inflow-outflow dynamics and facilitate the optimization of water management

Feasibility and reference values of left atrial longitudinal strain imaging by two-dimensional speckle tracking

<p>Abstract</p> <p>Background</p> <p>The role of speckle tracking in the assessment of left atrial (LA) deformation dynamics is not established. We sought to determine the feasibility and reference ranges of LA longitudinal strain indices measured by speckle tracking in a population of normal subjects.</p> <p>Methods</p> <p>In 60 healthy individuals, peak atrial longitudinal strain (PALS) and time to peak longitudinal strain (TPLS) were measured using a 12-segment model for the left atrium. Values were obtained by averaging all segments (global PALS and TPLS) and by separately averaging segments measured in the two apical views (4- and 2-chamber average PALS and TPLS).</p> <p>Results</p> <p>Adequate tracking quality was achieved in 97% of segments analyzed. Inter and intra-observer variability coefficients of measurements ranged between 2.9% and 5.4%. Global PALS was 42.2 ± 6.1% (5–95° percentile range 32.2–53.2%), and global TPLS was 368 ± 30 ms (5–95° percentile range 323–430 ms). The 2-chamber average PALS was slightly higher than the 4-chamber average PALS (44.3 ± 6.0% vs 40.1 ± 7.9%, p < 0.0001), whereas no differences in TPLS were found (p = 0.93).</p> <p>Conclusion</p> <p>Speckle tracking is a feasible technique for the assessment of longitudinal myocardial LA deformation. Reference ranges of strain indices were reported.</p

The microbiome of the Maculinea-Myrmica host-parasite interaction

Maculinea (=Phengaris) are endangered butterflies that are characterized by a very complex biological cycle. Maculinea larvae behave as obligate parasites whose survival is strictly dependent on both particular food plants and species-specific Myrmica ants. In this interaction, Maculinea caterpillars induce Myrmica workers to retrieve and rear them in the nest by chemical and acoustic deception. Social insect symbiotic microorganisms play a key role in intraspecific and interspecific communication; therefore, it is possible that the Maculinea caterpillar microbiome might be involved in the chemical cross-talk by producing deceptive semiochemicals for host ants. To address this point, the microbiota of Maculinea alcon at different larval stages (phytophagous early larvae, intermediate larvae, carnivorous late larvae) was analyzed by using 16S rRNA-guided metabarcoding approach and compared to that of the host ant Myrmica scabrinodis. Structural and deduced functional profiles of the microbial communities were recorded, which were used to identify specific groups of microorganisms that may be involved in the chemical cross-talk. One of the most notable features was the presence in all larval stages and in the ants of two bacteria, Serratia marcescens and S. entomophila, which are involved in the chemical cross-talk between the microbes and their hosts

FITFES: A Wearable Myoelectrically Controlled Functional Electrical Stimulator Designed Using a User-Centered Approach

Myoelectrically Controlled Functional Electrical Stimulation (MeCFES) has proven to be a useful tool in the rehabilitation of the hemiplegic arm. This paper reports the steps involved in the development of a wearable MeCFES device (FITFES) through a user-centered design. We defined the minimal viable features and functionalities requirements for the device design from a questionnaire-based survey among physiotherapists with experience in functional electrical stimulation. The result was a necklace layout that poses minimal hindrance to task-oriented movement therapy, the context in which it is aimed to be used. FITFES is battery-powered and embeds a standard low power Bluetooth module, enabling wireless control by using PC/Mobile devices vendor specific built-in libraries. It is designed to deliver a biphasic, charge-balanced stimulation current pulses of up to 113 mA with a maximum differential voltage of 300 V. The power consumption for typical clinical usage is 320 mW at 20mA stimulation current and of less than $10~\mu \text{W}$ in sleep mode, thus ensuring an estimated full day of FITFES therapy on a battery charge. We conclude that a multidisciplinary user-centered approach can be successfully applied to the design of a clinically and ergonomically viable prototype of a wearable myoelectrically controlled functional electrical stimulator to be used in rehabilitation

Stress echo 2020: the international stress echo study in ischemic and non-ischemic heart disease

BACKGROUND: Stress echocardiography (SE) has an established role in evidence-based guidelines, but recently its breadth and variety of applications have extended well beyond coronary artery disease (CAD). We lack a prospective research study of SE applications, in and beyond CAD, also considering a variety of signs in addition to regional wall motion abnormalities. METHODS: In a prospective, multicenter, international, observational study design, > 100 certified high-volume SE labs (initially from Italy, Brazil, Hungary, and Serbia) will be networked with an organized system of clinical, laboratory and imaging data collection at the time of physical or pharmacological SE, with structured follow-up information. The study is endorsed by the Italian Society of Cardiovascular Echography and organized in 10 subprojects focusing on: contractile reserve for prediction of cardiac resynchronization or medical therapy response; stress B-lines in heart failure; hypertrophic cardiomyopathy; heart failure with preserved ejection fraction; mitral regurgitation after either transcatheter or surgical aortic valve replacement; outdoor SE in extreme physiology; right ventricular contractile reserve in repaired Tetralogy of Fallot; suspected or initial pulmonary arterial hypertension; coronary flow velocity, left ventricular elastance reserve and B-lines in known or suspected CAD; identification of subclinical familial disease in genotype-positive, phenotype- negative healthy relatives of inherited disease (such as hypertrophic cardiomyopathy). RESULTS: We expect to recruit about 10,000 patients over a 5-year period (2016-2020), with sample sizes ranging from 5,000 for coronary flow velocity/ left ventricular elastance/ B-lines in CAD to around 250 for hypertrophic cardiomyopathy or repaired Tetralogy of Fallot. This data-base will allow to investigate technical questions such as feasibility and reproducibility of various SE parameters and to assess their prognostic value in different clinical scenarios. CONCLUSIONS: The study will create the cultural, informatic and scientific infrastructure connecting high-volume, accredited SE labs, sharing common criteria of indication, execution, reporting and image storage of SE to obtain original safety, feasibility, and outcome data in evidence-poor diagnostic fields, also outside the established core application of SE in CAD based on regional wall motion abnormalities. The study will standardize procedures, validate emerging signs, and integrate the new information with established knowledge, helping to build a next-generation SE lab without inner walls