Stoichiometry deviation in amorphous zirconium dioxide

Amorphous zirconia (a-ZrO₂) has been simulated using a synergistic combination of state-of-the-art methods: employing reverse Monte-Carlo, molecular dynamics and density functional theory together. This combination has enabled the complex chemistry of the amorphous system to be efficiently investigated. Notably, the a-ZrO₂ system was observed to accommodate excess oxygen readily – through the formation of neutral peroxide (O₂²⁻) defects – a result that has implications not only in the a-ZrO₂ system, but also in other systems employing network formers, intermediates and modifiers. The structure of the a-ZrO₂ system was also determined to have edge-sharing characteristics similar to structures reported in the amorphous TeO₂ system and other chalcogenide-containing glasses.

The accommodation mechanism for excess oxygen in amorphous ZrO₂ is identified using state-of-the-art methods: employing reverse Monte-Carlo, molecular dynamics and density functional theory together. Excess oxygen is predicted to enter amorphous ZrO₂ exothermically from O₂.     

Variability of the Middle Meningeal Artery Subject to the Shape of Skull

Objectives Endovascular embolization of the middle meningeal artery (MMA) is currently considered one of the basic methods to treat acute bleeding and a posttraumatic aneurysm. The present research correlates the morphological characteristics of the MMA with individual skull shape. Design A prospective cohort study. Setting Hospital of University of Jordan (Amman, Jordan) from 2012 to 2013. Participants A total of 50 patients without known vascular pathology in the carotid system underwent routine magnetic resonance angiography examination of the head and neck. Main Outcome Measures The length and outer diameter of extracranial, intraosseous, and intracranial segments of the MMA were measured in patients with dolichocephalic, mesocephalic, and brachycephalic types of skulls. Results The brachycephalic patients have the most inauspicious anatomical precondition for endovascular intervention of the MMA due to the narrowest lumen of the vessel, high probability of a tortuous extracranial part, and pronounced inflexion at the transmission of the intraosseous segment to the intracranial one. Conclusions The morphological characteristics of the MMA have a close correlation with individual skull shape.     

Attitudes Toward Health-Seeking Behaviors of College Students in Ukraine

This study elicited multiple perspectives on attitudes towards help-seeking behaviors associated with mental health problems of college students in Ukraine. It employed a sequential mixed method design. First, focus groups were conducted with students and psychologists. These data were analyzed and used to develop a survey. The survey was subsequently administered to psychiatrists, the primary providers of services to people with psychiatric problems in Ukraine. Findings from the focus groups revealed four help-seeking behaviors: 1) friends and partners, (2) alcohol use, (3) family support, and (4) conventional and alternative mental health services. Students and psychiatrists differed in their beliefs about help-seeking behaviors. Although psychiatrists believed students sought help from mental health and/or addictions professionals, students reported using self-medication and social network support. Implications include a troubling gap in perceptions between the students impacted and the professional communities that should be serving them.     

Effect of Aprotinin and Avifavir® Combination Therapy for Moderate COVID-19 Patients

COVID-19 is a contagious multisystem inflammatory disease caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We studied the efficacy of Aprotinin (nonspecific serine proteases inhibitor) in combination with Avifavir^® or Hydroxychloroquine (HCQ) drugs, which are recommended by the Russian Ministry of Health for the treatment therapy of moderate COVID-19 patients. This prospective single-center study included participants with moderate COVID-19-related pneumonia, laboratory-confirmed SARS-CoV-2, and admitted to the hospitals. Patients received combinations of intravenous (IV) Aprotinin (1,000,000 KIU daily, 3 days) and HCQ (cohort 1), inhalation (inh) treatment with Aprotinin (625 KIU four times per day, 5 days) and HCQ (cohort 2) or IV Aprotinin (1,000,000 KIU daily for 5 days) and Avifavir (cohort 3). In cohorts 1–3, the combination therapy showed 100% efficacy in preventing the transfer of patients (n = 30) to the intensive care unit (ICU). The effect of the combination therapy in cohort 3 was the most prominent, and the median time to SARS-CoV-2 elimination was 3.5 days (IQR 3.0–4.0), normalization of the CRP concentration was 3.5 days (IQR 3–5), of the D-dimer concentration was 5 days (IQR 4 to 5); body temperature was 1 day (IQR 1–3), improvement in clinical status or discharge from the hospital was 5 days (IQR 5–5), and improvement in lung lesions of patients on 14 day was 100%.     

In vivo metabolism of the new synthetic cannabinoid APINAC in rats by GC–MS and LC–QTOF-MS

The recent appearance of APINAC (AKB-57, ACBL(N)-018, adamantan-1-yl 1-pentyl-1H-indazole-3-carboxylate) in the market of the so-called novel psychoactive substances resulted in the need of defining its characteristics and searching its metabolites for subsequent detection in biological samples. The structure of the APINAC molecule has great similarity to the molecules of other synthetic cannabinoids. Here we report on the in vivo metabolism of APINAC using rats as an experimental model. Rat urine samples were analyzed by using gas chromatography–mass spectrometry and liquid chromatography–high resolution mass spectrometry. Data were acquired via time-of-flight mass scan, followed by Auto MS and triggered product ion scans. The predominant metabolic pathway for APINAC was ester hydrolysis yielding a wide variety of N-pentylindazole-3-carboxylic acid metabolites and 1-adamantanol metabolites. Ten metabolites for APINAC were identified, with the majority generated by hydroxylation, carbonylation, and carboxylation with or without glucuronidation. Therefore, in vivo metabolic profiles in rats were generated for APINAC. N-Pentylindazole-3-carboxylic acid, hydroxylated N-pentylindazole-3-carboxylic acid, and 1-adamantanol are likely the best targets to incorporate into analytical screening methods for drugs analysis. The presented mass spectra and retention time data may be useful for detection of these compounds in human urine.     

Water balance and pharmacokinetics of ketamine during anesthesia in roentgen-endovascular procedures in children

Forty-seven children, aged 2 to 12, with different pathologies, who underwent the abdominal aortography with the bolus introduction of 60% verografin, i.e. a radiopaque contrast agent (RCA), 2-3 ml/kg for 2-3 sec. The osmolar index of blood went up sharply, diuresis increased 7-fold and the aldosterone content topped 2-fold the original level. Simultaneously, the plasma concentration of ketamine was reducing by 2 times faster than in children who were not administered RCA. An additional introduction of an anesthetic made on minute 3 after RCA injection was suggested to modify the anesthesia management scheme.     

Efficient optimization strategy for marginal hits active against abl tyrosine kinases

Primary high-throughput screening of commercially available small molecules collections often results in hit compounds with unfavorable ADME/Tox properties and low IP potential. These issues are addressed empirically at follow-up lead development and optimization stages. In this work, we describe a rational approach to the optimization of hit compounds discovered during screening of a kinase focused library against abl tyrosine kinase. The optimization strategy involved application of modern chemoinformatics techniques, such as automatic bioisosteric transformation of the initial hits, efficient solution-phase combinatorial synthesis, and advanced methods of knowledge-based libraries design.