Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic: Chilean Air Force Experience in the Air Transport of Critically Ill Patients-The First 100 Cases.

OBJECTIVE: Critical care air transport has played an important role during the coronavirus disease 2019 (COVID-19) pandemic. The goal of this article is to analyze results and lessons learned from the evacuation of the first 100 COVID-19 patients transported between medical facilities in Chile. METHODS: We reviewed prospective data of patients who were referred for air transport between March 27, 2020, and July 9, 2020. RESULTS: Of 115 referred patients, 100 were transported by air. All patients were intubated and mechanically ventilated. Hypertension, diabetes, and obesity were the most commonly observed comorbidities. Our service did not experience any major problems in patient care en route or among the crewmembers. We did not observe any severe acute respiratory syndrome coronavirus 2 infections among our flight team members during the study period. Twelve (12%) patients died at their destination intensive care unit, whereas the remaining 88 patients (88%) returned to their primary hospitals after recovery. CONCLUSIONS: Air transport of mechanically ventilated patients with COVID-19 infection has been shown to be a safe way of transport, with no in-flight deaths and an in-hospital mortality of 12%, which compares favorably with the in-hospital mortality of similar patients who did not undergo air transport.

Semi-annual oscillations in Saturn's low-latitude stratospheric temperatures.

Observations of oscillations of temperature and wind in planetary atmospheres provide a means of generalizing models for atmospheric dynamics in a diverse set of planets in the Solar System and elsewhere. An equatorial oscillation similar to one in the Earth's atmosphere has been discovered in Jupiter. Here we report the existence of similar oscillations in Saturn's atmosphere, from an analysis of over two decades of spatially resolved observations of its 7.8-microm methane and 12.2-microm ethane stratospheric emissions, where we compare zonal-mean stratospheric brightness temperatures at planetographic latitudes of 3.6 degrees and 15.5 degrees in both the northern and the southern hemispheres. These results support the interpretation of vertical and meridional variability of temperatures in Saturn's stratosphere as a manifestation of a wave phenomenon similar to that on the Earth and in Jupiter. The period of this oscillation is 14.8 +/- 1.2 terrestrial years, roughly half of Saturn's year, suggesting the influence of seasonal forcing, as is the case with the Earth's semi-annual oscillation.

In vitro comparison of two different mechanical circulatory support devices installed in series and in parallel.

This study investigates the novel approach of placing a ventricular assist pump in the descending aorta in series configuration with the heart and compares it with the two traditional approaches of left-ventricle-to-ascending-aorta (LV-AA) and left-ventricle-to-descending-aorta (LV-DA) placement in parallel with the heart. Experiments were conducted by using the in-house simulator of the cardiovascular blood-flow loop (SCVL). The results indicate that the use of the LV-AA in-parallel configuration leads to a significant improvement in the systemic and pulmonic flow as the level of continuous flow is increased; however, this approach is considered highly invasive. The use of the LV-DA in-parallel configuration leads to an improvement in the systemic and pulmonic flow at lower levels of continuous flow but at higher levels of pump support leads to retrograde flow. In both in-parallel configurations, increasing the level of pump continuous flow leads to a decrease in pulsatility to a certain extent. The results of placing the pump in the descending aorta in series configuration show that the pressure drop upstream of the pump facilitates cardiac output as a result of afterload reduction. In addition, the pressure rise downstream of the pump may assist with renal perfusion. However, at the same time, the pressure drop generated at the proximal part of the descending aorta induces a slight drop in carotid perfusion, which would be autoregulated by the brain in a native cardiovascular system. The pulse wave analysis shows that placing the pump in the descending aorta leads to improved pulsatility in comparison with the traditional in-parallel configurations.

Discovery of ITI-333, a Novel Orally Bioavailable Molecule Targeting Multiple Receptors for the Treatment of Pain and Other Disorders.

Development of more efficacious medications with improved safety profiles to manage and treat multiple forms of pain is a critical element of healthcare. To this end, we have designed and synthesized a novel class of tetracyclic pyridopyrroloquinoxalinone derivatives with analgesic properties. The receptor binding profiles and analgesic properties of these tetracyclic compounds were studied. Systematic optimizations of this novel scaffold culminated in the discovery of the clinical candidate, (6bR,10aS)-8-[3-(4-fluorophenoxy)propyl]-6b,7,8,9,10,10a-hexahydro-1H-pyrido[3',4':4,5]pyrrolo[1,2,3-de]quinoxalin-2(3H)-one (compound 5, ITI-333), which exhibited potent binding affinity to serotonin 5-HT2A (Ki = 8.3 nM) and µ-opioid receptors (MOR, Ki = 11 nM) and moderate affinity to adrenergic α1A (Ki = 28 nM) and dopamine D1 (Ki = 50 nM) receptors. ITI-333 acts as a 5-HT2A receptor antagonist, a MOR partial agonist, and an adrenergic α1A receptor antagonist. ITI-333 exhibited dose-dependent analgesic effects in rodent models of acute pain. Currently, this investigational new drug is in phase I clinical development.

Pharmacologic profile of ITI-333: a novel molecule for treatment of substance use disorders.

RATIONALE: Medications are urgently needed to treat symptoms of drug withdrawal and mitigate dysphoria and psychiatric comorbidities that drive opioid abuse and relapse. ITI-333 is a novel molecule in development for treatment of substance use disorders, psychiatric comorbidities, and pain. OBJECTIVE: Characterize the preclinical profile of ITI-333 using pharmacological, behavioral, and physiological assays. METHODS: Cell-based assays were used to measure receptor binding and intrinsic efficacy of ITI-333; animal models were employed to assess effects on opioid reinstatement, precipitated oxycodone withdrawal, and drug abuse liability. RESULTS: In vitro, ITI-333 is a potent 5-HT2A receptor antagonist (Ki = 8 nM) and a biased, partial agonist at µ-opioid (MOP) receptors (Ki = 11 nM; lacking ß-arrestin agonism) with lesser antagonist activity at adrenergic α1A (Ki = 28 nM) and dopamine D1 (Ki = 50 nM) receptors. In vivo, ITI-333 blocks 5-HT2A receptor-mediated head twitch and MOP receptor-mediated effects on motor hyperactivity in mice. ITI-333 alone is a naloxone-sensitive analgesic (mice) which suppresses somatic signs of naloxone-precipitated oxycodone withdrawal (mice) and heroin cue-induced reinstatement responding without apparent tolerance or physical dependence after chronic dosing (rats). ITI-333 did not acutely impair gastrointestinal or pulmonary function (rats) and was not intravenously self-administered by heroin-maintained rats or rhesus monkeys. CONCLUSIONS: ITI-333 acts as a potent 5-HT2A receptor antagonist, as well a biased MOP receptor partial agonist with low intrinsic efficacy. ITI-333 mitigates opioid withdrawal/reinstatement, supporting its potential utility as a treatment for OUD.

In-vitro investigation of cerebral-perfusion effects of a rotary blood pump installed in the descending aorta.

This study describes use of a cardiovascular simulator to replicate the hemodynamic responses of the cerebrovascular system with a mechanical circulatory support device operating in the descending aorta. To do so, a cerebral autoregulation unit was developed which replicates the dilation and constriction of the native cerebrovascular resistance system and thereby regulates the cerebral flow rate within defined limits. The efficacy of the replicated autoregulation mechanism was investigated by introducing a number of step alterations in mean aortic pressure and monitoring the cerebral flow. The steady responses of the cerebral flow to changes in mean aortic pressure were in good agreement with clinical data. Next, a rotary pump, modeling a mechanical circulatory support device, was installed in the descending aorta and the hemodynamic responses of the cerebral system were investigated over a wide range of pump operating conditions. Insertion of a mechanical circulatory support device in the descending aorta presented an improved cardiac output as a result of afterload reduction. It was observed that the primary drop in cerebral flow, caused by the pump in the descending aorta, was compensated over the course of five seconds due to a gradual decrease in cerebrovascular resistance. The experimental results suggest that the implantation of a mechanical circulatory support device in the descending aorta, a less invasive procedure than typical mechanical circulatory support implantation, will not have an adverse effect on the cognitive function, provided that the cerebral autoregulation is largely unimpaired.

Heritable, de novo resistance to leaf rust and other novel traits in selfed descendants of wheat responding to inoculation with wheat streak mosaic virus.

Stable resistance to infection with Wheat streak mosaic virus (WSMV) can be evolved de novo in selfing bread wheat lines subjected to cycles of WSMV inoculation and selection of best-performing plants or tillers. To learn whether this phenomenon might be applied to evolve resistance de novo to pathogens unrelated to WSMV, we examined the responses to leaf rust of succeeding generations of the rust- and WSMV-susceptible cultivar 'Lakin' following WSMV inoculation and derived rust-resistant sublines. After three cycles of the iterative protocol five plants, in contrast to all others, expressed resistance to leaf and stripe rust. A subset of descendant sublines of one of these, 'R1', heritably and uniformly expressed the new trait of resistance to leaf rust. Such sublines, into which no genes from a known source of resistance had been introgressed, conferred resistance to progeny of crosses with susceptible parents. The F1 populations produced from crosses between, respectively, susceptible and resistant 'Lakin' sublines 4-3-3 and 4-12-3 were not all uniform in their response to seedling inoculation with race TDBG. In seedling tests against TDBG and MKPS races the F2s from F1 populations that were uniformly resistant had 3∶1 ratios of resistant to susceptible individuals but the F2s from susceptible F1 progenitors were uniformly susceptible. True-breeding lines derived from resistant individuals in F2 populations were resistant to natural stripe and leaf rust inoculum in the field, while the 'Lakin' progenitor was susceptible. The next generation of six of the 'Lakin'-derived lines exhibited moderate to strong de novo resistance to stem rust races TPMK, QFCS and RKQQ in seedling tests while the 'Lakin' progenitor was susceptible. These apparently epigenetic effects in response to virus infection may help researchers fashion a new tool that expands the range of genetic resources already available in adapted germplasm.

The organization of thanatology.

This article explores, using Wilensky's Model of Professionalization, the emergence of professional organizations within the thanatology. The authors review the history of four organizations--The Foundation of Thanatology, Ars Moriendi, The Forum for Death Education and Counseling (now the Association for Death Education and Counseling: A Thanatology Organization [ADEC]), and The International Work Group on Death, Dying, and Bereavement (IWG). The authors speculate on some of the reasons that the first two failed while IWG and ADEC remain viable-while noting challenges that these remaining thanatological organizations will experience as they seek to continue to stay relevant.

Lysostaphin-coated mesh prevents staphylococcal infection and significantly improves survival in a contaminated surgical field.

Mesh and wound infections during hernia repair are predominantly caused by Staphylococcus aureus. Human acellular dermis (HAD) is known to lose its integrity in the face of large bacterial loads. The goal of this study was to determine if lysostaphin (LS), a naturally occurring anti-Staphylococcal protein, can protect HAD mesh from S. aureus infection. HAD samples, 3 cm × 3 cm, were implanted in the onlay fashion on the anterior abdominal wall of rats (n = 75). Subjects were grouped based on presence of antimicrobial bound to HAD (none or LS) and presence of S. aureus inoculum (sterile, 106, 108 CFU). At 60 days, meshes were explanted, and bacterial growth, histology, and mesh tensile strength were examined. None of the controls receiving bacterial inoculation without LS survived to 60 days. All LS-HAD sterile and LS-106 animals survived to explantation. The LS-HAD 108 group had a mortality rate of 50 per cent. All surviving LS-treated animals (n = 25) had negative wound and mesh cultures. Blinded gross and histologic evaluation and measured tensile strengths between all LS groups were comparable. Animals implanted with LS-HAD had a dramatically improved rate of survival. All animals surviving to 60 days had completely cleared S. aureus from their wounds with maintenance of mesh integrity and tensile strength. These findings strongly suggest the clinical use of LS-treated mesh in contaminated fields may translate into a more durable hernia repair.

A fuzzy model of glucose regulation.

We present a detailed glucose regulation model using fuzzy inference system (FIS) descriptions of hormonal control action and the familiar Michaelis-Menten (M-M) kinetic description for glucose transport. The fuzzy M-M model is compared and contrasted with a well-known comprehensive glucose model. The two models give similar results for glucose response, endogenous glucose production, and total uptake. The fuzzy M-M model features a renal subsystem that provides 25% of the endogenous glucose production. The work demonstrates the successful application of fuzzy logic and fuzzy inference to biological modelling. The flexibility of fuzzy inference, a linguistic description technique, permits conceptually simple statements about nonlinear processes.

Swallowed ocular prostheses: report of three cases in children with retinoblastoma.

PURPOSE: To report 3 instances of 2 children who swallowed their ocular prostheses. METHODS: A 30-month-old boy whose eye had been enucleated for retinoblastoma swallowed his ocular prosthesis on 2 different occasions, and a 32-month-old boy whose eye had also been enucleated for retinoblastoma swallowed his ocular prosthesis once. RESULTS: In the second child, an abdominal radiograph was obtained, but the swallowed prosthesis was not apparent, and radiographic imaging of the recovered prosthesis failed to demonstrate an identifiable object. In each case, the prosthesis was recovered in the child's stool without incident several weeks later. Neither child had physical complications as a result of the swallowing events. CONCLUSIONS: We report 3 instances in which a child fitted for an ocular prosthesis after enucleation swallowed his prosthesis and had no untoward effects. The failure of imaging to detect the prostheses in the second child is attributed to the radiolucent nature of materials used in the manufacture of the prosthesis. Each of the children was having life stresses in addition to his medical treatment that may have accounted for his behavior.