Minute Range Research Articles

Metabolically stable apelin analogs: development and functional role in water balance and cardiovascular function.

Apelin, a (neuro) vasoactive peptide, plays a prominent role in controlling water balance and cardiovascular functions. Apelin and its receptor co-localize with vasopressin in magnocellular vasopressinergic neurons. Apelin receptors (Apelin-Rs) are also expressed in the collecting ducts of the kidney, where vasopressin type 2 receptors are also present. Apelin and vasopressin interact at the brain and renal levels to maintain body fluid homeostasis by regulating diuresis in opposite directions. Apelin and angiotensin II have opposite effects on the regulation of blood pressure (BP). Angiotensin II, by binding to AT1 receptors present in VSMCs, induces intracellular calcium mobilization and vasoconstriction, while apelin, by binding to Apelin-R present on vascular endothelium, increases nitric oxide production and induces vasodilation. Apelin also plays a crucial role in the regulation of cardiac function. Apelin-deficient and Apelin-R-deficient mice develop progressive myocardial dysfunction with ageing and are susceptible to heart failure in response to pressure overload. Since the half-life of apelin is very short in vivo (in the minute range), several metabolically stable apelin analogs and non-peptidic Apelin-R agonists have been developed, with potential applications in diverse diseases. In this review, we highlight the interaction between apelin and vasopressin in the regulation of water balance and that between apelin and angiotensin II in the regulation of BP. Additionally, we underline the protective effects of apelin in cardiac function. Lastly, we discuss the beneficial effects of Apelin-R activation in different pathological states such as hyponatremia, hypertension, and heart failure.

QOL-12. ELECTRONIC ASSESSMENT OF QUALITY OF LIFE IN GLIOBLASTOMA PATIENTS USING THE EORTC-QLQ-C30/ EORTC-BN20 AND THE PROMIS SYSTEM IN CLINICAL PRACTICE

Abstract BACKGROUND Patient reported outcomes are essential to guide patient-care and to maintain quality of life. We aim to further assess feasibility of computer adaptations of the Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaire in the clinical setting and compare it with outcomes of the EORTC- QLQ-C30 and EORTC-BN20 questionnaires. METHODS Newly diagnosed patients with GBM were enrolled to assess feasibility. The PROMIS modules were selected to reflect the HRQoL domains assessed in the EORTC- QLQ-C30 and EORTC-BN20 questionnaires. PROMIS modules selected included anxiety, depression, fatigue, physical function, sleep disturbance, sleep-related impairment, social satisfaction role, applied cognitive ability and global health. EORTC instruments as well as PROMIS was answered to patients in the outpatient setting. Descriptive analysis was performed RESULTS 43 patients with 124 PROMIS/EORTC responses were included in this analysis. 31 patients completed the survey prior to or within 14 days of start of radiation, 12 patients completed a survey outside of the radiation window, and a total of 60 completed surveys were obtained between both patient groups. The median times to complete the EORTC-QLQ-C30 and the EORTC-BN20 surveys were 4.77 (range=2.05-18.6) and 2.63 (range=1.17- 24.83) minutes respectively. For the PROMIS instruments except global health, the median times to complete different modules ranged from 0.6- 1 minute (range= 0.15-7.77). For global health, the median time was 2.35 minutes (range= 1.02-21.12). Average time to complete all PROMIS questions was 8.65 minutes (range=3.32-66.01). CONCLUSIONS Real-time prospective assessment of the EORTC tools is similar to the PROMIS measures. While most response times were short, the ranges suggest that select patients might struggle. Patients were offered to participate online from home for convenience, but low computer literacy, limited internet access and burden of disease might limit participation.

Computational analysis of wind tower-equipped sunken greenhouse for optimum microclimate control in hot arid regions

This research focuses on designing, computationally modeling, and assessing a novel sunken greenhouse equipped with wind towers to create an optimum microclimate capable of enhancing crop productivity and quality while minimizing energy consumption in hot arid climates that present challenges like extreme ambient temperatures and intense solar irradiation. Three innovative, energy-efficient, and cost-effective techniques were integrated into the proposed greenhouse design: (1) Wind tower-driven natural ventilation, (2) fully sunken greenhouse structure, and (3) direct evaporative cooling. The airflow dynamics, solar heat transfer, and the interaction of moist air within the greenhouse environment were investigated to analyze the system’s performance and optimize its design. The results showed efficient ventilation rates and great improvement in the greenhouse’s internal microclimate in terms of temperature and relative humidity. The average airflow velocity inside the greenhouse, measured at 1 m height, ranged from 0.11 to 0.69 m/s for nominal wind speeds of 1–6 m/s, while air changes per minute range is 0.28–1.7. Even under extreme ambient conditions (30–45 °C, 15–50 % humidity), the proposed greenhouse mostly maintained temperatures below 35 °C, reducing interior air temperatures by up to 11.7 °C from the ambient and increasing humidity by up to 57.1 %. The economic feasibility comparison of the proposed greenhouse to a conventional active-cooled greenhouse showed a remarkable 74.5 % reduction in the life cycle cost of the microclimate control technique.

Temporoorbital pulse rate can be obtained in ball pythons (Python regius) of any size and age and agrees with heart rate.

Currently, a standardised technique to obtain pulse rate in reptiles is lacking. We evaluated the feasibility of obtaining a temporoorbital pulse rate in ball pythons of various ages and sizes and whether it agreed with the heart rate. Heart rate and pulse rate were recorded in 40 ball pythons (Python regius) weighing between 0.05 and 2.2 kg using a standard veterinary ultrasonic Doppler flow detector. The temporoorbital pulse rate was obtained on the dorsal aspect of the head at the level of the temporoorbital artery. Each measurement was performed in a randomised fashion by two operators, who were blinded to each other's results. Pulse rate and heart rate were successfully obtained for all snakes. The median heart rate was 60beats per minute (bpm)(range 48‒88 bpm), and the median pulse rate was 60bpm (range 48‒88 bpm). The mean difference between the pulse rate and heart rate was 1.2 beats (95% limits of agreement: ‒10.6 to 13.0). When pulse rate and heart rate were measured at the same time, they were synchronous. Only healthy snakes were included. Temporoorbital pulse rates can be easily obtained in ball pythons of any size. This novel method to assess peripheral pulse allows for a more complete cardiovascular evaluation in this species.

Real-world experience with the new pulsed solid-state Thulium: YAG laser (Thulio) for endoscopic enucleation of the prostate

PurposeThe solid-state Thulium laser (Tm: YAG) is a novel alternative to the widely used Holmium laser for endoscopic enucleation of the prostate (EEP) due to its relatively high peak power. The aim of this study was to examine the efficacy and safety of a new pulsed Tm: YAG laser in its first application in humans.MethodsData were retrospectively collected for the first 103 patients who underwent EEP with a new pulsed solid-state Tm: YAG laser (Thulio®, Dornier MedTech Systems GmbH, Weßling, Germany). Peri- and postoperative data were assessed. Procedure-specific complications were graded using Clavien-Dindo Classifications (CDC). Patients were interviewed 15 months after the surgery to evaluate functional and long-term outcomes. Statistical analysis was performed with Statistical Package for the Social Sciences (SPSS®).ResultsThe mean preoperative prostate volume was 105.6 ± 55.0 ml. Median enucleation speed was 4.1 g per minute (range 1.1–9.7). Short-term postoperative complications occurred in 21 patients (20.4%), but no high-grade complications (CDC ≥ IV) were observed. Five patients suffered gross haematuria and required reintervention (CDC IIIb; 4.9%). After 15 months, 76 patients (73.8%) participated in the follow-up interview, where seven patients (9.2%) reported complications, including two reinterventions for urethral strictures (CDC IIIb; 2.6%). Most patients reported an improvement in continence (54.0%) and urine stream (93.4%), but no difference in erectile function (81.6%). No persistent dysuria was reported. Patient satisfaction with the surgery results was very high (96.1%).ConclusionEndoscopic enucleation of the prostate with the new pulsed solid-state Tm: YAG laser is a safe and effective option for surgical BPH treatment.Trial registrationGerman Clinical Trials Register number: DRKS00031676. Registration date: 10 May 2023, retrospectively registered.

Seismotectonic Movements in the Minute Range of Periods Before the Catastrophic Earthquake in Japan March 11, 2011

The vertical movements measured by a broadband seismic stations located around Tohoku earthquake 11.03. 2011 with magnitude 9 are calculated. It is shown that during the 15 years before the earthquake the closest to epicenter MAJO station located 386 km from the epicenter the quiet daily variations was demonstrated. Seismic pulses with the durations of a few minutes and amplitudes bigger 10% of the diurnal variations of tidal velocities were revealed in 2009 year. They appeared under quiet meteorological and geomagnetic conditions. These pulses are not found on the records of the stations remoted more 700 km from epicenter. It is hypothesized that sharp changes in the low frequency seismic noise reflect the tectonic deformations in the lithosphere of Japan and adjoin part of Pacific Ocean.

Respiratory rate monitoring in ICU patients and healthy volunteers using electrical impedance tomography: a validation study

Objective. The respiratory rate (RR) is considered one of the most informative vital signals. A well-validated standard for RR measurement in mechanically ventilated patient is capnography; a noninvasive technique for expiratory CO2 measurements. Reliable RR measurements in spontaneously breathing patients remains a challenge as continuous mainstream capnography measurements are not available. This study aimed to assess the accuracy of RR measurement using electrical impedance tomography (EIT) in healthy volunteers and intensive care unit (ICU) patients on mechanical ventilation and spontaneously breathing post-extubation. Comparator methods included RR derived from both capnography and bioimpedance electrocardiogram (ECG) measurements. Approach. Twenty healthy volunteers wore an EIT belt and ECG electrodes while breathing through a capnometer within a 10–40 breaths per minute (BPM) range. Nineteen ICU patients underwent similar measurements during pressure support ventilation and spontaneously breathing after extubation from mechanical ventilation. Stable periods with regular breathing and no artefacts were selected, and agreement between measurement methods was assessed using Bland–Altman analysis for repeated measurements. Main result. Bland–Altman analysis revealed a bias less than 0.2 BPM, with tight limits of agreement (LOA) ±1.5 BPM in healthy volunteers and ventilated ICU patients when comparing EIT to capnography. Spontaneously breathing ICU patients had wider LOA (±2.5 BPM) when comparing EIT to ECG bioimpedance, but gold standard comparison was unavailable. RR measurements were stable for 91% of the time for capnography, 68% for EIT, and 64% of the ECG bioimpedance signals. After extubation, the percentage of stable periods decreased to 48% for EIT signals and to 55% for ECG bioimpedance. Significance. In periods of stable breathing, EIT demonstrated excellent RR measurement accuracy in healthy volunteers and ICU patients. However, stability of both EIT and ECG bioimpedance RR measurements declined in spontaneously breathing patients to approximately 50% of the time.

Relationship between transient ischemic dilatation and changes in heart rate during gated SPECT acquisition in a low-risk population without perfusion defects.

Transient ischemic dilatation (TID) in myocardial perfusion single photon emission computed tomography (SPECT) is considered a marker of poor prognosis. However, it has been suggested that some cases are due to apparent volumetric changes secondary to differences in heart rate (HR) at the time of acquisition. We assessed the correlation between transient dilatation and HR in low risk patients with no perfusion defects. We retrospectively analyzed patients sent for 99mTc-MIBI SPECT using a 2-day protocol. We recorded the median HR during acquisition and the HR difference (HRD) between the rest and post-stress. We obtained the medium ventricular volume, end-diastolic volume (EDV), and end-systolic volume (ESV). We included patients in which TID using medium ventricular volume (TIDMV) was ≥1.2. TID was also calculated for the EDV and ESV (TIDEDV, TIDESV). We excluded patients with known coronary artery disease, perfusion defects, various ECG disorders, positive stress test, or ESV < 10 ml. From a total of 2006 patients, 63 (50 exercise, 13 dipyridamole) met the criteria for analysis (age 63.8 ± 9.7, 44 men). TIDMV was 1.29 ± 0.09 and HRD 9.8 beats per minute (BPM) (range -10 to 41). There was positive correlation between HRD and TIDMV ( r = 0.51, P < 0.001) and TIDEDV ( r = 0.5, P < 0.001), but not TIDESV ( r = 0.23, P = 0.07). Correlation was stronger when HRD was ≥10 BPM ( r = 0.67, P < 0.001). TID without perfusion defects should be interpreted with caution in the presence of HRD ≥ 10 BPM during post-stress acquisition.

Inter-geosphere interaction in the infrasonic range

On the basis of experimental data from laser strainmeters, a laser nanobarograph, and a laser meter of hydrosphere pressure variations, we studied inter-geosphere interaction in microseismic range (2–20 s) and in minute range (4–17 min). We established general patterns of transformation of the Earth’s crust upper layer oscillations into atmospheric oscillations, and atmospheric oscillations—into oscillations of the Earth’s crust upper layer in the specified ranges. Besides, we show that transformation coefficient has seasonal dependence, associated with different elastic characteristics of the Earth’s crust upper layer in winter and summer due to negative winter temperatures and high positive summer temperatures, and also different moisture saturation of the soils.

Methylthiosulfonate-Based Cysteine Modifiers as Alternative Inhibitors of Mercurial-Sensitive Aquaporins.

(1) Background: Several members of the ubiquitous aquaporin family, AQP, of water and neutral solute channels carry a cysteine residue in the selectivity filter region. Traditionally, toxic mercury-containing compounds are used to bind to the cysteine as covalent AQP inhibitors for physiological studies or analysis of structure-function relationships. (2) Methods: We tested thiol-reactive methylthiosulfonate reagents, MTS, as alternative Cys modifiers for AQP inhibition. Three MTS reagents transferring S-alkyl moieties of increasing size, i.e., S-methyl, S-n-propyl, and S-benzyl, were used with yeast-expressed water-selective AQP1 and the aquaglyceroporin AQP9. Respective Cys-to-Ala variants and mouse erythrocytes that naturally express AQP1 and AQP9 served as controls. (3) Results: Both wildtype AQP isoforms were inhibited by the Cys modifiers in a size-dependent manner, whereas the Cys-to-Ala-variants exhibited resistance. Sub-millimolar concentrations and incubation times in the minute range were sufficient. The modifications were reversible by treatment with the thiol reagents acetylcysteine, ACC, and dithiothreitol, DTT. (4) Conclusions: MTS reagents represent a valid alternative of low toxicity for the inhibition of mercurial-sensitive AQPs.

Insect biomass density: measurement of seasonal and daily variations using an entomological optical sensor

Insects are major actors in Earth’s ecosystems and their recent decline in abundance and diversity is alarming. The monitoring of insects is paramount to understand the cause of this decline and guide conservation policies. In this contribution, an infrared laser-based system is used to remotely monitor the biomass density of flying insects in the wild. By measuring the optical extinction caused by insects crossing the 36-m long laser beam, the Entomological Bistatic Optical Sensor System used in this study can evaluate the mass of each specimen. At the field location, between July and December 2021, the instrument made a total of 262,870 observations of insects for which the average dry mass was 17.1 mg and the median 3.4 mg. The daily average mass of flying insects per meter cube of air at the field location has been retrieved throughout the season and ranged between near 0 to 1.2 mg/m3. Thanks to its temporal resolution in the minute range, daily variations of biomass density have been observed as well. These measurements show daily activity patterns changing with the season, as large increases in biomass density were evident around sunset and sunrise during Summer but not during Fall.

Catheter ablation of atrial arrhythmias by using a multipolar grid-patterned high density mapping catheter in patients with congenital heart disease: a single-center experience

Abstract Objective Catheter ablation of arrhythmias in patients with congenital heart disease (CHD) remains challenging and time-consuming. A novel diagnostic catheter with a multipolar grid-patterned electrode configuration for high density mapping may reduce mapping time and enhance ablation success. Here we describe our experience of catheter ablation by using a multipolar grid-patterned mapping catheter in patients with CHD suffered from atrial tachycardia. Methods All patients with CHD underwent catheter ablation for atrial tachycardia by using multipolar grid-patterned high density mapping catheter between 04/2018 and 12/2021 were enrolled. Primary success was defined as non-inducibility of atrial tachycardia. Only the first catheter ablation was included in the study. Results A total of 37 consecutive patients (median age 34.2±33.0 years (range 7–65), female n=20) underwent 37 ablation procedures with initial high density mapping. The underlying heart defects were s/p ASD-closure (n=2), ASD-closure and corrected partial anomalous pulmonary venous return (n=2), corrected unroofed coronary sinus (n=1), pulmonary valve commissurotomy (n=2), repaired Tetralogy of Fallot (n=2), tricuspid and pulmonary valve replacement in PA/IVS (n=1), mitral valve replacement (n=1), Hypoplastic right heart syndrome (n=1), atrial switch procedure for dTGA (n=7), TA with Glenn shunt (n=1), Ross operation (n=1), Fontan palliation (tricuspid atresia n=6, DILV n=5, HLHS n=1, DORV n=1, dTGA n=1, criss-cross heart n=1, single ventricle n=1). A history of previous ablation was positive in 8 patients. During mapping of the cardiac chambers, the mean value of total collected points and used points were 32657.8±46171 and 3851.6±3295.5 respectively. Mean mapping and fluoroscopy time were 62.1±40.7 minute (range 3–178) and 11.4±8.5 minutes (range 0–32.2), respectively. There were 69 atrial tachycardia substrates in the 37 patients (median 2, range 1–4 per patient). All tachycardia substrates were completely ablated in 33/37 (89.2%) patients and partially in 4/37 (11.8%) patients. Acute success was achieved with successful ablation of 65 of 69 (94.2%) atrial substrates. During a median follow-up time of 20 months (range 5–49), recurrence rate was 5/65 (7.7%) atrial substrates in 5/37 (13.5%) patients. Comparison of 16 patients with Fontan palliation to the 23 patients without Fontan operation showed higher partially success rate in the patients with Fontan palliation (4/16 vs. 0/21, p=0.028). Conclusion In this series, high density mapping allowed elucidation of the tachycardia mechanism in all patients with a high primary ablation success, a limited radiation exposure and a low rate of arrhythmia recurrence. Funding Acknowledgement Type of funding sources: None.

Validation and calibration of models to estimate photosynthetically active radiation considering different time scales and sky conditions

Photosynthetically Active Radiation (PAR) is a fundamental parameter for developing plant productivity models. Nevertheless, instrumentation for measuring PAR and to record it is scarce at conventional meteorological stations. Several procedures have therefore been proposed for PAR estimation. In this work, 21 previously published analytical models that correlate PAR with easily available meteorological parameters are collected. Although longer time scales were considered in the original publications, a minute range was applied in this work to calibrate the PAR models. In total, more than 10 million input records were gathered from the SURFRAD station network from a 10-year long time series with data frequencies recorded every 1 min. The models were calibrated both globally, using data from all stations and locally, with data from each station. After calibration, the models were validated for minute, hourly and daily data, obtaining low fitting errors at the different stations in all cases, both when using the globally calibrated models and with the models calibrated for each location. Although the PAR results in general improved for locally calibrated models, the use of local models is not justified, since the global models presented offered very satisfactory PAR results for the different climatic conditions where the meteorological stations are located. Thus, PAR estimation model should then be selected, solely considering the meteorological variables available at the specific location. When applying the globally calibrated models to input data classified according to sky conditions (from clear to overcast), the PAR models continued to perform satisfactorily, although the error statistics of some models for overcast skies worsened.

Long-Duration Sound-Induced Facilitation Changes Population Activity in the Inferior Colliculus.

The inferior colliculus (IC) is at the midpoint of the auditory system and integrates virtually all information ascending from the auditory brainstem, organizes it, and transmits the results to the auditory forebrain. Its abundant, excitatory local connections are crucial for this task. This study describes a long duration sound (LDS)-induced potentiation in the IC that changes both subsequent tone-evoked responses and spontaneous activity. Afterdischarges, changes of spontaneous spiking following an LDS, were seen previously in single neurons. Here, we used multi-channel probes to record activity before and after a single, tetanic sound and describe the changes in a population of IC neurons. Following a 60 s narrowband-noise stimulation, a subset of recording channels (∼16%) showed afterdischarges. A facilitated response spike rate to tone pips following an LDS was also observed in ∼16% of channels. Both channels with an afterdischarge and channels with facilitated tone responses had higher firing rates in response to LDS, and the magnitude of the afterdischarges increased with increased responses to the LDS. This is the first study examining the effect of LDS stimulation on tone-evoked responses. This observed facilitation in vivo has similarities to post-tetanic potentiation in vitro as both manner of induction (strong stimulation for several seconds) as well as time-course of the facilitation (second to minute range) are comparable. Channels with and without facilitation appear to be intermixed and distributed widely in the central nucleus of IC, and this suggests a heretofore unknown property of some IC neurons or their circuits. Consequently, this sound-evoked facilitation may enhance the sound-evoked output of these neurons, while, simultaneously, most other IC neurons have reduced or unchanged output in response to the same stimulus.

CT coronary angiogram in children with Kawasaki patients: experience in 52 patients.

CT is an accepted non-invasive imaging tool to assess the coronary arteries in adults; however, its utilisation in children is limited by high heart rate and lack of standardised protocol. We sought to assess diagnostic quality and factors that affect image quality of CT in assessing coronary artery lesions in Kawasaki patients less than 18 years of age. CT coronary angiography was performed on patients with Kawasaki disease diagnosed with coronary aneurysm or suspected to have coronary stenosis. Studies were performed using electrocardiogram-gated protocols. General anaesthesia was used in patients who were not cooperative for breathing control. Heart rate, image quality, and effective radiation dose were documented. Fifty-two Kawasaki patients underwent CT coronary angiography to assess coronary artery lesions. Median heart rate was 88 beats per minute (range 50-165 beats/minute). Image quality was graded as excellent in 34 (65%) patients, good in 17 (32%), satisfactory in 1, and poor in 1 patient. Coronary artery aneurysm was found in 25 (bilateral = 6, unilateral = 19, multiple = 11). Thrombus was found in 11 patients resulting in partial and total occlusion in 8 and 3 patients, respectively. Coronary stenosis was noted in 2 patients. The effective radiation dose was 1.296 millisievert (median 0.81 millisievert). Better diagnostic imaging quality was significantly related to lower heart rate (p = 0.007). Electrocardiogram-triggered CT coronary angiography provides a good diagnostic assessment of coronary artery lesions in children with Kawasaki disease.

Machine learning predicts blood lactate levels in children after cardiac surgery in paediatric ICU.

Although serum lactate levels are widely accepted markers of haemodynamic instability, an alternative method to evaluate haemodynamic stability/instability continuously and non-invasively may assist in improving the standard of patient care. We hypothesise that blood lactate in paediatric ICU patients can be predicted using machine learning applied to arterial waveforms and perioperative characteristics. Forty-eight post-operative children, median age 4 months (2.9-11.8 interquartile range), mean baseline heart rate of 131 beats per minute (range 33-197), mean lactate level at admission of 22.3 mg/dL (range 6.3-71.1), were included. Morphological arterial waveform characteristics were acquired and analysed. Predicting lactate levels was accomplished using regression-based supervised learning algorithms, evaluated with hold-out cross-validation, including, basing prediction on the currently acquired physiological measurements along with those acquired at admission, as well as adding the most recent lactate measurement and the time since that measurement as prediction parameters. Algorithms were assessed with mean absolute error, the average of the absolute differences between actual and predicted lactate concentrations. Low values represent superior model performance. The best performing algorithm was the tuned random forest, which yielded a mean absolute error of 3.38 mg/dL when predicting blood lactate with updated ground truth from the most recent blood draw. The random forest is capable of predicting serum lactate levels by analysing perioperative variables, including the arterial pressure waveform. Thus, machine learning can predict patient blood lactate levels, a proxy for haemodynamic instability, non-invasively, continuously and with accuracy that may demonstrate clinical utility.

Apelin and Vasopressin: The Yin and Yang of Water Balance.

Apelin, a (neuro)vasoactive peptide, plays a prominent role in controlling body fluid homeostasis and cardiovascular functions. Experimental data performed in rodents have shown that apelin has an aquaretic effect via its central and renal actions. In the brain, apelin inhibits the phasic electrical activity of vasopressinergic neurons and the release of vasopressin from the posterior pituitary into the bloodstream and in the kidney, apelin regulates renal microcirculation and counteracts in the collecting duct, the antidiuretic effect of vasopressin occurring via the vasopressin receptor type 2. In humans and rodents, if plasma osmolality is increased by hypertonic saline infusion/water deprivation or decreased by water loading, plasma vasopressin and apelin are conversely regulated to maintain body fluid homeostasis. In patients with the syndrome of inappropriate antidiuresis, in which vasopressin hypersecretion leads to hyponatremia, the balance between apelin and vasopressin is significantly altered. In order to re-establish the correct balance, a metabolically stable apelin-17 analog, LIT01-196, was developed, to overcome the problem of the very short half-life (in the minute range) of apelin in vivo. In a rat experimental model of vasopressin-induced hyponatremia, subcutaneously (s.c.) administered LIT01-196 blocks the antidiuretic effect of vasopressin and the vasopressin-induced increase in urinary osmolality, and induces a progressive improvement in hyponatremia, suggesting that apelin receptor activation constitutes an original approach for hyponatremia treatment.

LIT01-196, a Metabolically Stable Apelin-17 Analog, Normalizes Blood Pressure in Hypertensive DOCA-Salt Rats via a NO Synthase-dependent Mechanism.

Apelin is a neuro-vasoactive peptide that plays a major role in the control of cardiovascular functions and water balance, but has an in-vivo half-life in the minute range, limiting its therapeutic use. We previously developed LIT01-196, a systemically active metabolically stable apelin-17 analog, produced by chemical addition of a fluorocarbon chain to the N-terminal part of apelin-17. LIT01-196 behaves as a potent full agonist for the apelin receptor and has an in vivo half-life in the bloodstream of 28 min after intravenous (i.v.) and 156 min after subcutaneous (s.c.) administrations in conscious normotensive rats. We aimed to investigate the effects of LIT01-196 following systemic administrations on arterial blood pressure, heart rate, fluid balance and electrolytes in conscious normotensive and hypertensive deoxycorticosterone acetate (DOCA)-salt rats. Acute i.v. LIT01-196 administration, in increasing doses, dose-dependently decreases arterial blood pressure with ED50 values of 9.8 and 3.1 nmol/kg in normotensive and hypertensive rats, respectively. This effect occurs for both via a nitric oxide-dependent mechanism. Moreover, acute s.c. LIT01-196 administration (90 nmol/kg) normalizes arterial blood pressure in conscious hypertensive DOCA-salt rats for more than 7 h. The LIT01-196-induced blood pressure decrease remains unchanged after 4 consecutive daily s.c. administrations of 90 nmol/kg, and does not induce any alteration of plasma sodium and potassium levels and kidney function as shown by the lack of change in plasma creatinine and urea nitrogen levels. Activating the apelin receptor with LIT01-196 may constitute a novel approach for the treatment of hypertension.

UNSUPERVISED DISAGGREGATION OF WATER HEATER LOAD FROM SMART METER DATA PROCESSING

In the residential sector, electric water heaters are appliances with a relatively high power consumption and a significant thermal inertia, which is particularly suitable for Demand Response schemes. The success of efficient DR schemes via the control of water heaters presupposes an accurate estimate of their power demand at each instant. Although the load of water heaters is rarely directly measured, a large penetration of Smart Meters (SMs) in distribution grids enables to indirectly infer this information on a large scale via load disaggregation. For that purpose, a considerable number of Non-Intrusive Load Monitoring (NILM) approaches are suggested in the literature. However, they require data streams at a time resolution in the range of one second or higher, which is not realistic for standard SMs. Hence, this paper proposes an unsupervised approach to detect and disaggregate the load profile of water heaters from standard SM data with a time resolution in the minute range. Evaluated on multiple real loads with sub-metering, the proposed approach achieves a Normalized Mean Absolute Error (NMAE) lower than 2% and a precision generally higher than 92% with time resolutions between 5 and 15 minutes.

Intraoperative angiography during coronary artery bypass grafting.

The aim of this study was to evaluate the incidence rate of technical failure of graft patency while performing intra-operative angiography after coronary artery bypass grafting. This prospective pilot study included 50 patients with multi-vessel coronary artery disease who underwent coronary artery bypass grafting, in addition to intra-operative angiographic graft assessments, on open-chest. Overall, 144 grafts and 160 distal anastomoses were assessed in a hybrid operating room. Intra-operative angiography allowed the identification of 23 angiographic defects (15.9% of all grafts) in 22 patients (44%): three graft defects (2% of all grafts), 17 anastomotic defects (10.6% of all distal anastomoses), and three target artery errors (1.8% of all grafted arteries). Ten re-interventions (43.4%) were performed based on the angiographic defects detected. During the follow-up period, computed tomography angiography of the attached grafts at a mean of 224 days (range, 80-318 days) showed that all repaired grafts were patent. During surgery, the total mean dose of radiation was 1.848 ± 0.54 mSv (range, 0.78-3.4 mSv) per patient and investigation time was 19.4 ± 4.94 minute (range, 9-31 minute). Intra-operative angiography is a powerful tool allowing the identification of graft defects, anastomotic defects and target vessel errors. Assuming relatively low level of exposure to radiation and short investigation time, intra-operative angiography could be included in routine practice as safe procedure improving surgery quality.