Interaction of GC376, a SARS-COV-2 MPRO inhibitor, with model lipid membranes

Partitioning and effect of antiviral GC376, a potential SARS-CoV-2 inhibitor, on model lipid membranes was studied using dynamic light scattering (DLS), UV–VIS spectrometry, Excimer fluorescence, Differential scanning calorimetry (DSC) and Small- and Wide-angle X-ray scattering (SAXS/WAXS). Partition coefficient of GC376 between lipid and water phase was found to be low, reaching KP = 46.8 ± 18.2. Results suggest that GC376 partitions into lipid bilayers at the level of lipid head-groups, close to the polar/hydrophobic interface. Changes in structural and thermodynamic properties strongly depend on the GC376/lipid mole ratio. Already at lowest mole ratios GC376 induces increase of lateral pressures, mainly in the interfacial region of the bilayer. Hereby, the pre- and main-transition temperature of the lipid system increases, what is attributed to tighter packing of acyl chains induced by GC376. At GC376/DPPC ≥ 0.03 mol/mol we detected formation of domains with different GC376 content resulting in the lateral phase separation and changes in both, main transition temperature and enthalpy. The observed changes are attributed to the response of the system on the increased lateral stresses induced by partitioning of GC376. Obtained results are discussed in context of liposome-based drug delivery systems for GC376 and in context of indirect mechanism of virus replication inhibition.

Patients' referral through a Minor Ailment Service in community pharmacy

Introduction: Consultation of minor ailments and direct product request are frequent in community pharmacy in Spain, although every pharmacy offers the service following their own criteria. Standard Operational Procedures (SOP) and referral criteria agreed between community pharmacists (CPs) and general practitioners (GPs) are needed to deliver a safer service. Referral criteria set the limits of action for each healthcare professional (CPs and GPs) when managing patients. Following the positive findings of an impact study, a roll out was required to translate the evidence-based approach into usual practice. Objective(s): The aim was to characterise the referrals between CPs and GPs through a Minor Ailment Service (MAS, service offered in community pharmacy following the SOP). Method(s): A 12-month pragmatic study with hybrid effectiveness-implementation design was planned from October 2020 in Spain. The co-designed MAS service had several components: agreed SOP with GP scientific organisations, protocols for ailments divided into five groups (dermatological, digestive, related to pain, upper respiratory tract related and others) including referral criteria, information technology (IT) based consultation protocol and training before and during the study. Patients were followed up by pharmacists after ten days of the service. All data were collected through an IT system (SEFAC eXPERT) as a by-product of service delivery and implementation. Outcomes for the first fifteen months (up to December 2021) are shown. Result(s): 1246 pharmacists from 24 provinces in Spain were trained having a reach of 14083 consultations. 1858 (13.2%) patients were referred to the GP. 2193 referral criteria were detected, most patients referred had one single referral criteria (n = 965, 80.8%). Referral criteria detected were red flags such as temperature over 38degreeC, dyspnoea, etc. (n = 846, 39.5%);patients' age (n = 398, 18.6%), symptom duration (n = 361, 16.9%);patients' treatments for other health problems different than the minor ailment consulted (n = 263, 12.3%);other patients' health problems (n = 186, 8.7%) and others (n = 85, 4.0%). Minor ailments more frequently referred were joint pain (n = 190, 10.2%), cough (n = 106, 5.7%), dermatitis (n = 104, 5.6%) and heartburn (n = 63, 3.4%). Conclusion(s): High-risk patients (patients with symptoms/condition that do not appear to be minor ailments) can be assessed by CPs and referred to be evaluated and diagnosed by GPs. The use of co-designed management protocols strengthened the identification of red flags in patients suffering minor ailments to be referred when necessary. Joint pain and cough were two of the minor ailments more frequently referred, which could be a result of the study being undertaken during COVID19 pandemic. CPs can perform clinically, referring patients and acting as a triage point through MAS to increase patients' safety.

Academic stress and emotional exhaustion in university students in the context of virtual education

One of the main repercussions of the COVID-19 pandemic in the educational field was the migration from face-to-face to virtual modality, which forced students to adapt to this new scenario. Currently, universities are beginning to gradually return to face-to-face or blended education, however, many of them still continue to provide the educational service virtually, which has favorable aspects, as well as some limitations. In this sense, the present investigation aimed to determine the relationship between academic stress and emotional exhaustion in students of the branch of a Peruvian private university in the context of virtual education. The approach was quantitative, the design was non-experimental and the type was descriptive-correlational with a transectional cut. The sample consisted of 273 students to whom the SISCO Inventory of Academic Stress and the Emotional Tiredness Scale were applied, instruments with adequate psychometric properties (validity based on content and reliability). The results indicate that 31.1% of the students had moderate levels of academic stress, 34.4% had moderate levels of emotional exhaustion and it was determined that Spearman's rho correlation coefficient between both variables was 0.731 with a p-value lower than the level of significance (p<0.01). It was concluded that there is a direct and significant relationship between academic stress and emotional exhaustion, which is why it is necessary for the university institution to design and execute preventive and corrective programs that allow students to reduce the prevalence of the problems addressed and improve their levels of psychological well-being, as well as their quality of life. Copyright © 2022, Venezuelan Society of Pharmacology and Clinical and Therapeutic Pharmacology. All rights reserved.

A Novel Survival Analysis-Based Approach for Predicting Behavioral Probability of Default

Obtaining an accurate model for predicting the probability of default is a critical requirement for financial institutions. Nowadays, COVID19 has produced high economic instability bringing borrowers’ delinquencies as well as moratorium regulations. During the KYC process for applicants, it is essential to estimate the probability of default for avoiding write-offs. However, there are several borrowers who, due to the pandemic, could have lost their jobs or decreased their income, producing several borrowers’ delinquencies, even write-offs by frequent delinquencies. Consequently, having a behavioral model for estimating the probability of default during the loan lifetime is vital for financial institutions. Hence, in this paper, we propose the first survival analysis-based approach for predicting the behavioral probability of default. We collected two real financial databases from different countries with different borrowers’ characteristics. From our experimental results, we can conclude that Logistic Hazard provides better results than Deep Hit for predicting the behavioral probability of default. Based on our experimentation and the risk analysis experts, Deep Hit provides inconsistent results for forecasts greater than six months while considering the financial changes due to the COVID19. Otherwise, Logistic Hazard is more accurate in forecasting the behavioral probability of default for a year, and it shows results more appropriate to risk analysis experts. © 2022, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Clinical Attributes and Risk Factors for In- Hospital Mortality among Covid-19 Patients in a Community Hospital Setting: A Propensity Matched Analysis

Background. New York City emerged as the Epicenter for Covid-19 due to novel Coronavirus SARS-CoV-2 soon after it was declared a Global Pandemic in early 2020 by the WHO. Covid-19 presents with a wide spectrum of illness from asymptomatic to severe respiratory failure, shock, multiorgan failure and death. Although the overall fatality rate is low, there is significant mortality among hospitalized patients. There is limited information exploring the impact of Covid-19 in community hospital settings in ethnically diverse populations. We aimed to identify risk factors for Covid-19 mortality in our institution. Methods. We conducted a retrospective cohort study of hospitalized in our institution for Covid 19 from March 1st to June 21st 2020. It comprised of 425 discharged patients and 245 expired patients. Information was extracted from our EMR which included demographics, presenting symptoms, and laboratory data. We propensity matched 245 expired patients with a concurrent cohort of discharged patients. Statistically significant covariates were applied in matching, which included age, gender, race, body mass index (BMI), diabetes mellitus, and hypertension. The admission clinical attributes and laboratory parameters and outcomes were analyzed. Results. The mean age of the matched cohort was 66.9 years. Expired patients had a higher incidence of dyspnea (P < 0.001) and headache (0.031). In addition, expired patients had elevated CRP- hs (mg/dl) ≥ 123 (< .0001), SGOT or AST (IU/L) ≥ 54 (p < 0.001), SGPT or ALT (IU/L) ≥ 41 (p < 0.001), and creatinine (mg/dl) ≥ 1.135 (0.001), lower WBC counts (k/ul) ≥ 8.42 (0.009). Furthermore, on multivariate logistic regression, dyspnea (OR = 2.56, P < 0.001), creatinine ≥ 1.135 (OR = 1.79, P = 0.007), LDH(U/L) > 465 (OR = 2.18, P = 0.001), systolic blood pressure < 90 mm Hg (OR = 4.28, p = .02), respiratory rate > 24 (OR = 2.88, p = .001), absolute lymphocyte percent (≤ 12%) (OR = 1.68, p = .001) and procalcitonin (ng/ml) ≥ 0.305 (OR = 1.71, P = .027) predicted in- hospital mortality in all matched patients. Conclusion. Our case series provides admission clinical characteristics and laboratory parameters that predict in- hospital mortality in propensity Covid 19 matched patients with a large Hispanic population. These risk factors will require further validation.

The impact of coronavirus on our mental health

The Coronavirus represents the greatest threat to physical health in modern times. Simultaneously, fear of the unknown and the fear of the very real repercussions of the virus is threatening to impact the mental health of many around the world. To provide insights on the impact of Coronavirus on our mental health, we are constantly monitoring millions of conversations on Twitter each day, and analysing this enormous amount of data by means of psychological models trained with artificial intelligence techniques and deep neural networks. © 2020 Sociedad Espanola para el Procesamiento del Lenguaje Natural. All rights reserved.