Cardiac and metabolic effects of hypothermia and inhaled hydrogen sulfide in anesthetized and ventilated mice

Objective: To test the hypothesis whether inhaled hydrogen sulfide amplifies the effects of deliberate hypothermia during anesthesia and mechanical ventilation as hypothermia is used to provide organ protection after brain trauma or circulatory arrest. Awake mice inhaling hydrogen sulfide exhibit reduced energy expenditure, hypothermia, and bradycardia despite unchanged systolic heart function. In rodents, anesthesia alone causes decreased metabolic rate and thus hypothermia and bradycardia.Design: Prospective, controlled, randomized study. Setting: University animal research laboratory. Subjects: Male C57/B6 mice. Interventions: After surgical instrumentation (central venous, left ventricular pressure-conductance catheters, ultrasound flow probes on the portal vein and superior mesenteric artery), normo- or hypothermic animals (core temperature = 38°C and 27°C) received either 100 ppm hydrogen sulfide or vehicle over 5 hrs (3 hrs hydrogen sulfide during normothermia). Measurements and Main Results: During normothermia, hydrogen sulfide had no hemodynamic or metabolic effect. With or without hydrogen sulfide, hypothermia decreased blood pressure, heart rate, and cardiac output, whereas stroke volume, ejection fraction, and end-diastolic pressure remained unaffected. Myocardial and hepatic oxidative deoxyribonucleic acid damage (comet assay) and endogenous glucose production (rate of appearance of 1,2,3,4,5,6-13C6-glucose) were similar in all groups. Hypothermia comparably decreased CO2 production with or without inhaled hydrogen sulfide. During hypothermia, inhaled hydrogen sulfide increased the glucose oxidation rate (derived from the expiratory 13CO2/12CO2 ratio). This shift toward preferential carbohydrate utilization coincided with a significantly attenuated responsiveness of hepatic mitochondrial respiration to stimulation with exogenous cytochrome-c-oxidase (high-resolution respirometry). Conclusions: In anesthetized and mechanically ventilated mice, inhaled hydrogen sulfide did not amplify the systemic hemodynamic and cardiac effects of hypothermia alone. The increased aerobic glucose oxidation together with the reduced responsiveness of cellular respiration to exogenous cytochrome-c stimulation suggest that, during hypothermia, inhaled hydrogen sulfide improved the yield of mitochondrial respiration, possibly via the maintenance of mitochondrial integrity. Hence, inhaled hydrogen sulfide may offer metabolic benefit during therapeutic hypothermia

Riociguat treatment in patients with pulmonary arterial hypertension. Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension following Phase 3 randomized trials. The EXPosurE Registry RiociguaT in patients with pulmonary hypertension (EXPERT) study was designed to monitor the long-term safety of riociguat in clinical practice. Methods: EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study of patients treated with riociguat. Patients were followed for at least 1 year and up to 4 years from enrollment or until 30 days after stopping riociguat treatment. Primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs) coded using Medical Dictionary for Regulatory Activities preferred terms and System Organ Classes version 21.0, collected during routine clinic visits (usually every 3–6 months) and collated via case report forms. Results: In total, 326 patients with PAH were included in the analysis. The most common AEs in these patients were dizziness (11.7%), right ventricular (RV)/cardiac failure (10.7%), edema/peripheral edema (10.7%), diarrhea (8.6%), dyspnea (8.0%), and cough (7.7%). The most common SAEs were RV/cardiac failure (10.1%), pneumonia (6.1%), dyspnea (4.0%), and syncope (3.4%). The exposure-adjusted rate of hemoptysis/pulmonary hemorrhage was 2.5 events per 100 patient-years. Conclusion: Final data from EXPERT show that in patients with PAH, the safety of riociguat in clinical practice was consistent with clinical trials, with no new safety concerns identified and a lower exposure-adjusted rate of hemoptysis/pulmonary hemorrhage than in the long-term extension of the Phase 3 trial in PAH

Prevention and treatment of renal osteodystrophy in children on chronic renal failure: European guidelines

Childhood renal osteodystrophy (ROD) is the consequence of disturbances of the calcium-regulating hormones vitamin D and parathyroid hormone (PTH) as well as of the somatotroph hormone axis associated with local modulation of bone and growth cartilage function. The resulting growth retardation and the potentially rapid onset of ROD in children are different from ROD in adults. The biochemical changes of ROD as well as its prevention and treatment affect calcium and phosphorus homeostasis and are directly associated with the development of cardiovascular disease in pediatric renal patients. The aims of the clinical and biochemical surveillance of pediatric patients with CRF or on dialysis are prevention of hyperphosphatemia, avoidance of hypercalcemia and keeping the calcium phosphorus product below 5 mmol(2)/l(2). The PTH levels should be within the normal range in chronic renal failure (CRF) and up to 2–3 times the upper limit of normal levels in dialysed children. Prevention of ROD is expected to result in improved growth and less vascular calcification

The screens culture: impact on ADHD

Children’s use of electronic media, including Internet and video gaming, has increased dramatically to an average in the general population of roughly 3 h per day. Some children cannot control their Internet use leading to increasing research on “internet addiction.” The objective of this article is to review the research on ADHD as a risk factor for Internet addiction and gaming, its complications, and what research and methodological questions remain to be addressed. The literature search was done in PubMed and Psychinfo, as well as by hand. Previous research has demonstrated rates of Internet addiction as high as 25% in the population and that it is addiction more than time of use that is best correlated with psychopathology. Various studies confirm that psychiatric disorders, and ADHD in particular, are associated with overuse, with severity of ADHD specifically correlated with the amount of use. ADHD children may be vulnerable since these games operate in brief segments that are not attention demanding. In addition, they offer immediate rewards with a strong incentive to increase the reward by trying the next level. The time spent on these games may also exacerbate ADHD symptoms, if not directly then through the loss of time spent on more developmentally challenging tasks. While this is a major issue for many parents, there is no empirical research on effective treatment. Internet and off-line gaming overuse and addiction are serious concerns for ADHD youth. Research is limited by the lack of measures for youth or parents, studies of children at risk, and studies of impact and treatment

Scaler Rates from the Pierre Auger Observatory: A New Proxy of Solar Activity

The modulation of low-energy galactic cosmic rays reflects interplanetary magnetic field variations and can provide useful information on solar activity. An array of ground-surface detectors can reveal the secondary particles, which originate from the interaction of cosmic rays with the atmosphere. In this work, we present an investigation of the low-threshold rate (scaler) time series recorded in 16 yr of operation by the Pierre Auger Observatory surface detectors in Malargüe, Argentina. Through an advanced spectral analysis, we detected highly statistically significant variations in the time series with periods ranging from the decadal to the daily scale. We investigate their origin, revealing a direct connection with solar variability. Thanks to their intrinsic very low noise level, the Auger scalers allow a thorough and detailed investigation of the galactic cosmic-ray flux variations in the heliosphere at different timescales and can, therefore, be considered a new proxy of solar variability

Improving the photon sensitivity of the Pierre Auger Observatory with the AugerPrime Radio Detector

The AugerPrime upgrade represents a significant enhancement in the capability of the Pierre Auger Observatory to detect air showers. Central to this advancement is the installation of a radio antenna atop each existing Surface Detector station, constituting the Radio Detector (RD). The RD enhances the sensitivity of the Surface Detector to the electromagnetic component of air showers. Hence, the new detector presents an opportunity for the discovery of rare particles such as ultra-high-energy photons. This contribution shows the development efforts towards an RD trigger with focus on the detection of rare particles. The radio trigger designed for the detection of photon-induced events will be outlined, and the challenge of a radio background consisting of human-made noise is discussed. The trigger efficiency and reconstruction accuracy are studied with simulations. The presentation will conclude by summarizing the effectiveness of the new detector component

Towards a Cosmic-Ray Energy Scale with the Auger Engineering Radio Array

Radio detection of cosmic-ray (CR) induced extensive air showers with digital antenna arrays is a matured technique by now. At the Pierre Auger Observatory, the Auger Engineering Radio Array (AERA) has been measuring air-shower signals in conjunction with the particle detectors of the surface detector (SD) for over ten years. For an absolute determination of the CR energy with the Auger baseline detectors, the shower size estimator from the SD is calibrated with the energy scale of the fluorescence detector (FD). However, AERA has an independent access to the energy scale through the reconstructed radio signals. The hybrid detectors at the Pierre Auger Observatory offer the unique opportunity to compare the two independent energy scales. In this contribution, we present our envisaged methodology for cross-checking the agreement between the energy scales of the FD and AERA using hybrid SD-AERA shower data and simulations. We show individual steps of our radio signal reconstruction and highlight the key ingredients for calibrated energy measurements

Drone-based calibration of AugerPrime radio antennas at the Pierre Auger Observatory

Radio emissions of extensive air showers can be observed at the Pierre Auger Observatory with the AugerPrime Radio Detector (RD). As part of the AugerPrime upgrade, RD is being installed on 1660 water-Cherenkov detectors on an area of about 3000 km2 and consists of dual-polarized Short Aperiodic Loaded Loop Antennas (SALLA). To achieve high measurement precision, RD needs to be well-calibrated, which requires the antenna response pattern to be well-known. We introduce a method to measure the directional response of the SALLA using a well-defined biconical antenna mounted to a drone. The drone-based setup possesses active stabilization and precise pointing with the use of a gimbal. Additionally, the drone’s position is tracked using differential GPS with O(cm) precision. This setup allows us to precisely extract the antenna response pattern from any direction in the frequency range of 30 − 80 MHz. In a recent in-situ campaign, calibration measurements of the AugerPrime radio detector have been performed. First results of these measurements are presented and compared to simulations

Ground observations of a space laser for the assessment of its in-orbit performance

The wind mission Aeolus of the European Space Agency was a groundbreaking achievement for Earth observation. Between 2018 and 2023, the space-borne lidar instrument ALADIN onboard the Aeolus satellite measured atmospheric wind profiles with global coverage which contributed to improving the accuracy of numerical weather prediction. The precision of the wind observations, however, declined over the course of the mission due to a progressive loss of the atmospheric backscatter signal. The analysis of the root cause was supported by the Pierre Auger Observatory in Argentina whose fluorescence detector registered the ultraviolet laser pulses emitted from the instrument in space, thereby offering an estimation of the laser energy at the exit of the instrument for several days in 2019, 2020 and 2021. The reconstruction of the laser beam not only allowed for an independent assessment of the Aeolus performance, but also helped to improve the accuracy in the determination of the laser beam's ground track on single pulse level. The results presented in this paper set a precedent for the monitoring of space lasers by ground-based telescopes and open new possibilities for the calibration of cosmic-ray observatories.Comment: 10 pages, 10 figure