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.

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.

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.

High proportion of cactus species threatened with extinction.

A high proportion of plant species is predicted to be threatened with extinction in the near future. However, the threat status of only a small number has been evaluated compared with key animal groups, rendering the magnitude and nature of the risks plants face unclear. Here we report the results of a global species assessment for the largest plant taxon evaluated to date under the International Union for Conservation of Nature (IUCN) Red List Categories and Criteria, the iconic Cactaceae (cacti).

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.

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.

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.

New mescaline concentrations from 14 taxa/cultivars of Echinopsis spp. (Cactaceae) ("San Pedro") and their relevance to shamanic practice.

Aim Of The Study: The aim of the present study is to determine in a procedurally uniform manner the mescaline concentrations in stem tissue of 14 taxa/cultivars of the subgenus Trichocereus of the genus Echinopsis (Cactaceae) and to evaluate the relationship (if any) between mescaline concentration and actual shamanic use of these plants.

Materials And Methods: Columnar cacti of the genus Echinopsis, some of which are used for diagnostic and therapeutic purposes by South American shamans in traditional medicine, were selected for analysis because they were vegetative clones of plants of documented geographic origin and/or because they were known to be used by practitioners of shamanism. Mescaline content of the cortical stem chlorenchyma of each cactus was determined by Soxhlet extraction with methanol, followed by acid-base extraction with water and dichloromethane, and high-pressure liquid chromatography (HPLC).

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.

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.

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.