Isolation and Characterization of Protein Complexes of Overexpressed Human Serum Amyloid A from Cytokines-Induced Hepg2 Cells

Serum Amyloid A (SAA) is an apolipoprotein found in the serum of many vertebrate species and is associated with the acute-phase reaction in the body with expression levels reaching up to a 1000-fold increase. The loss of its alpha-helix conformation during its expression peak is directly linked to secondary amyloidosis. Recent studies have been suggested to play a role in cholesterol and HDL metabolism, retinol transport and tumor pathogenesis. Moreover, high SAA concentration in blood have been correlated with severe symptoms or death in patients with COVID-19. However, how this protein is involved in so many diseases is uncertain or not completely understood. Therefore, the purpose of this research is to determine which protein-protein interactions with SAA occur in human cells, and to predict its biochemical role based on new discovered complexes. Two major isoforms overexpressed during an acutephase reaction, human SAA1 and SAA2, are the focus of this study. Both are primarily produced in hepatocytes. HepG2 cells were cultured and induced with interleukin-1b, interleukin-6, LPS and retinol. Protein complexes associated with SAA will be isolated through a co-Immunoprecipitation technique, resolved by SDS-PAGE, and characterized by mass spectrometry. Our hypothesis focus on those protein complexes with SAA to explain how this protein lead other undiscovered metabolic pathways involved in both cellular and survival regulation. Special thanks to The Science and Technology Competency & Education Core (Stce) for Undergraduate and Graduate Junior Research Associates Working Program from the Puerto Rico IDeA Network Biomedical Research Excellence for funding part of this research.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

Academic Continuity Plan in Light of the COVID-19 Contingency: A comparative study between Mexico and Spain

Faced with the Covid-19 contingency, many public and private universities worldwide had to suspend all face-to-face activities and develop academic continuity plans with the objective of assuring the permanence of university formation. It is in this sense that this paper submits the results of a comparative study regarding the academic continuity plans developed by private institutions of higher learning originating from the Covid-19 pandemic. A qualitative design was used in a series of semi-structured online interviews of university professors from the University of Monterrey (Mexico) and the Francisco de Vitoria University (Spain). The analysis was carried out from a comparative point of view to determine convergences and divergences in four categories: access, availability, use and shaping of Information and Communication Technologies;academic activities;teaching-learning processes;face-to-face academic continuity. The results revealed that there are convergences in the four categories analyzed in both university contexts. It is evident that the academic continuity plans of the University of Monterrey and the Francisco de Vitoria universities share equivalent characteristics and strategies. Similarly, it is shown that both private universities developed actions within the administration departments in order to offer prompt and pertinent answers in coordination with other departments. Likewise, it became evident that both universities had continuous improvement projects prior to the contingency that allowed them an immediate response for the continuance of academic activities. Finally, this paper seeks to contribute to the literature on the effectiveness of private sector university academic continuity plans. © Univ Nacional de Educacion a Distancia (UNED). All Rights Reserved.

Ultra-hypofractionated whole breast radiotherapy as adyuvant treatment for early breast cancer

Radiotherapy is an essential treatment in the local control of breast cancer. Standard treatment is currently carried out in 15 daily sessions. At present, following the results of the phase III Fast-Foward trial and in view of the situation triggered by COVID-19, the number of sessions has been reduced to 5. We present the data of our series to evaluate the results of the extreme hypofractionation scheme as a radiotherapy treatment for breast cancer at the Multihospital Clinical Unit of Radiation Oncology of Aragón (UCMORA). Materials and Methods After implantation, 115 patients were treated with 3D conformal radiotherapy between April 2020 and May 2021 at UCMORA using the extreme hypofractionation scheme (26 Gy at 5.2 Gy per fraction in 5 fractions). Demographic, tumor, dosimetric and toxicity characteristics were analyzed. Results The mean age was 63.5 years. 53 patients were treated at the Lozano Blesa Clinical Universitary Hospital and 62 at the Miguel Servet Universitary Hospital, in total 59 right and 56 left breasts. The predominant histology was infiltrating ductal carcinoma (84.3%), followed by infiltrating lobular carcinoma (10.4%), ductal carcinoma in situ (4.3%) and mucinous (0.9%). 51.7% were luminal A, 39.1% luminal B, 1.8% Her2 positive and 7.8% triple negative. In relation to staging, we found 4pTis, 8pT1a, 45pT1b, 58pT1c, 2Nx, 8N0, 1Nmi and 13N1a. Only 45% had acute toxicity at one month after the end of treatment, predominantly G1 radiodermatitis (86.6%), followed by G2 (11.2%) and G3 (2.2%). When analyzing the dose-volume histograms, values were obtained for ipsilateral lung V8 between 1.32 and 21.2%, for the heart, in case of left breast a median for V1.5 of 8.2% and 1.05% for V7;in case of right breast the median Dmed for the heart was 0.5Gy (Figure Presented) Conclusion Ultra-hypofractionated whole breast radiotherapy as a radiation treatment for breast cancer is well tolerated, reduces costs and number of sessions, while increasing comfort for patients.

Implementation of a Clinical Decision Support Tool for Improving Adherence to Lung Protective Ventilation Strategies

RATIONALE: Pre-pandemic, ARDS accounted for approximately 10% of all ICU admissions and 25% of ICU patients requiring mechanical ventilation (MV). Surges in severe Covid-19 cases have increased the number of ICU patients requiring MV for ARDS. It has been estimated that only 60% of ARDS cases are identified at any time during the clinical course, and only 34% of ARDS cases are identified when initial criteria are met. Additionally, it is estimated that only 60% of ARDS patients are managed with evidence based MV settings, including low tidal volume ventilation (LTV) of <6 cc/kg ideal body weight, plateau pressure <30 cm H2O, and low driving pressure <15 cm H2O. Adherence to lung protective ventilation strategies have been linked to decreased mortality in ARDS. We implemented a clinical decision support tool (CDST) to aid clinicians in the early recognition of ARDS and aid in implementation of lung protective ventilation strategies. METHODS: From March 2020 to March 2021 we used medical informatics (SickbayTM) to identify ICU patients requiring MV that met criteria for ARDS based on the Berlin Criteria. We monitored documentation of ARDS, MV tidal volume as cc/kg ideal body weight, plateau pressure, driving pressure, MV settings, arterial blood gas values (ABG), and PaO2 / FiO2. From March 2021 to October 2021, we implemented a CDST outlining above variables to aide ICU clinicians in 1) recognition of ARDS and 2) utilization of MV and ABG data to make evidence based MV changes. Lung protective strategies were automatically recorded every two hours via informatics software. The results were analyzed using a chi-squared test. RESULTS: There were 207 patients reviewed preimplementation of the CDST and 88 patients reviewed during implementation of the CDST. Implementation of the CDST resulted in improved detection and documentation of ARDS (63.8% vs 100%, p=.0001), improved adherence to LTV (53.9% vs 64.9%, p = .0005), and improved adherence to low plateau pressure (67.7% vs 71.8%, p=.20). There was a decrease in adherence to low driving pressure (36.6% vs 23.9%, p=.0003).CONCLUSIONS: Implementation of CDST is a low-cost, efficacious measure to aide clinicians in the detection and documentation of ARDS. Using CDST was associated with improved adherence to LTV and low plateau pressure MV strategies. We hypothesize that difficulty with adherence to low driving pressure is related to the respiratory mechanics of Covid-19 ARDS differing from other forms of ARDS. A validation cohort is needed to further support our findings.

COVID-19 and Sickle Cell Disease in the Province of Quebec: Morbidity and Mortality Rates Derived from the Provincial Registry

Introduction Approximately 1500 people live with sickle cell disease (SCD) in the province of Quebec, Canada. Public health has recognized these patients as immunocompromised. SCD patients may be at higher risk of developing severe COVID-19 infection due to their underlying pro-inflammatory and thrombogenic state, splenic dysfunction and secondary organopathies. Descriptions about disease severity and mortality rates in SCD vary widely. From the SECURE-SCD registry, Mucalo et al. recently reported a 0.3% and 4.7% mortality rate in children and adults, respectively. In the French registry, Arlet and colleagues reported a 2.4% death rate among those hospitalized with COVID-19 and SCD, not different from the general population. As a result, the COVID-19 morbidity and mortality rates among the SCD population remain uncertain. Objectives The primary objectives of our study are to describe the epidemiology, baseline characteristics and clinical outcomes of SCD patients with COVID-19 infection in the province of Quebec. In addition, we aim to identify risk factors for hospitalization and severe forms of COVID-19. Methods We built a web-based SCD-COVID-19 registry regrouping 7 adult and 4 paediatric tertiary care hospitals in the province of Quebec in June 2020. All SCD patients with a confirmed SARS-CoV-2 infection by PCR test were included in the study. We compared the prevalence of infection and hospitalization rates of SCD patients to the general population of Quebec using the epidemiological data from the INSPQ (National Institute of Public Health of Quebec) public database. We retrospectively analyzed data included between March 11, 2020 to March 1, 2021. Relative risk was calculated using bilateral association measures (exact fisher, mid-p or chi-squared tests, as appropriate) to compare the incidence of infection and hospitalization of SCD patients to the population of Quebec and to assess risk factors of hospitalization among SCD patients. Results During the first 12 months of the pandemic, 74 patients were included in the registry. The male to female ratio was 1:1.12. Median age was 23 years, ranging from 8 months to 68 years old. SS-Sbeta 0 genotypes were present in 51% of cases, while 49% were SC or Sbeta +. The majority of patients were on disease modifying therapy: 54% were on hydroxyurea and 17.5% on exchange transfusion therapy. The incidence of reported COVID-19 infection was significantly higher in SCD patients compared to the general population (4.9% vs. 3.5% p=0,002) (Table 1). Even more strikingly, SCD had rate of hospitalization 10-times greater than the general population (33.8 vs 3.2%, p<0,001). Nevertheless, the risk of admission to the intensive care unit was similar between SCD patients and the general population (24.0% vs. 24.1%, p=0.99). No death was recorded amongst SCD patients with COVID-19 compared to a death rate in the general population in Quebec of less than 70 years old of 48-78 for 100 000 infections (male-female). A history of acute chest syndrome (ACS) in the last year (OR 2.6 [1.5-4.6], p=0.04) and arterial hypertension (OR 3.3 [2.3-4.8], p=0.01) were associated with a higher risk of hospitalization (Table 2). On the other hand, there was no statistically significant association with age, sex, genotype, ABO blood group, baseline SCD therapy, or other comorbidities (chronic renal disease, obesity, pulmonary hypertension, chronic lung disease and previous admission to ICU) in our cohort. Conclusions Similar to other reports, we found that SCD patients were at much greater risk of hospitalization compared to the general population. We however found no increased risk of mortality or disease complication. This contrasts with results from other registries. A history of ACS and hypertension were associated with a higher risk of hospitalization. Whether social determinants of health could explain some of the outcome variability between different countries merit further investigation. Furthermore, we believe that registries are critical to monitor the impact of preventive measures. As vacci ation is ongoing, it will be important to consider its impact on hospitalization and death rate among SCD population. Recruitment to the registry is ongoing and updated data will be presented at the meeting. [Formula presented] Disclosures: Soulieres: BMS: Membership on an entity's Board of Directors or advisory committees;Novartis: Research Funding. Forté: Novartis: Honoraria;Canadian Hematology Society: Research Funding;Pfizer: Research Funding.

Inter-rater agreement of the modified motor United Parkinson's Disease Rating Scale (mUPDRS-III) for tele-health evaluation in Mexican Parkinson's disease (PD) patients during the COVID19 era

Objective: To evaluate the inter-rater reliability of the mUPDRS-III in Mexican PD patients evaluated during the COVID19 pandemic through telemedicine. Background: A modified version of the MDS-UPDRS part III for virtual administration has been previously validated, and has been proposed as a useful alternative to face-to-face follow-up of patients with PD. Limitations of it's use include the lack of evaluation of rigidity and postural impairment and technological barriers such as low-speed connection and poor access to webyielding devices in remote areas (e.g. rural Mexico). Design/Methods: 46 PD patients (mean age 65.34 ± 11.87 years, 58.7% male) were evaluated through web-based consultation (Cisco Webex). A brief follow-up questionnaire of symptoms, medications and current status was performed. Motor evaluation with the mUPDRS-III scale was applied independently by three movement disorders specialists. Agreement and reliability were evaluated using inter-rater correlation coefficient (ICC) and Kendall's concordance coefficient accordingly. Results: Total mUPDRS-III score (ICC 0.96, 95%CI 0.94-0.97;Kendall's W 0.038, p<0.005) and four motor domain sub-scores-Language and Facial Expression (ICC 0.85, 95%CI 0.76-0.91;Kendall's W 0.18, p<0.005), Bradykinesia (ICC 0.93, 95%CI 0.88-0.96;Kendall's W 0.25, p 0.005), Tremor (ICC 0.86, 95%CI 0.78-0.92;Kendall's W 0.233, p<0.005), Gait and Posture (ICC 0.97, 95%CI 0.95-0.98;Kendall's W 0.018, p 0.434)-showed good to excellent agreement but slight to poor concordance. Conclusions: We observed good agreement for motor domain sub-scores, as well as for the total scale score. This might confirm that the mUPDRS-III, albeit its intrinsic limitations, is a reproducible tool for the clinical follow-up of patients when face-to-face visits are not available. Nonetheless, the concordance values were poor which could be attributed to differences in rater perception of individual items due to technological barriers and to the sample's homogeneity. Further analysis and test-retest might be useful to elucidate this phenomenon.

INFORMATIVE CONTACT, THE OTHER SIDE OF THE PANDEMIC

Along with the current pandemic, there may be an increase in unreasonable behaviors, such as panic purchases or non-compliance with prevention measures. These behaviors are assimilated to contagion from the fake news. To analyze how information is transmitted and how it can lead to the appearance of less than optimal actions, different mechanisms in the behavioral sciences were discussed to improve the follow-up of the recommendations. It concludes with recommendations to improve the application of public policies and practices in the population during crises like the current one.

Restarting care-related activities in the context of COVID-19: Prioritization, protocols, and procedures. experience of a gastroenterology outpatient unit in Bogotá, Colombia

The Colombian Government ordered a mandatory nationwide quarantine in March 2020 due to the spread of the SARS-CoV-2 virus. Since then, outpatient endoscopy units were closed and only urgent procedures were performed in the hospital setting, resulting in a repression of sensitive, priority and elective outpatient endoscopic procedures. The rate of spread of the virus was contained and it did not progress exponentially as in other countries;in the meantime, gastroenterology services were provided in the form of teleconsultation. The mitigation measures and the containment of the virus allowed the Mayor’s Office of Bogotá and the National Government to issue notices with recommendations for the provision of some regulated outpatient services in May 2020, thus creating a window of opportunity to care for patients with sensitive diseases. Under this legal and epidemiological framework, the provision of digestive endoscopy services was restarted at EMDIAGNOSTICA S.A.S. This study presents the strategies for scheduling and performing endoscopic procedures in an outpatient gastroenterology unit during COVID-19 pandemia in Colombia and describes a system for prioritizing procedures according to medical criteria, ranging from care by teleconsultation and/ or an application of a telephone survey and the use of a medically necessary, time-sensitive (MENTS) scale adapted for digestive endoscopy. It also describes changes in infrastructure, methodology implemented for protection of human talent and patients, and post procedure follow-up for feedback, safety and satisfaction degree evaluation in care. © 2020 Asociación Colombiana de Gastroenterología.

Colombian consensus for the prevention, diagnosis and treatment of thrombotic conditions in adults with COVID-19: applying GRADE Evidence to Decision (EtD) Frameworks

Introduction: recent studies have reported the occurrence of thrombotic phenomena or coagulopathy in patients with COVID-19. There are divergent positions regarding the prevention, diagnosis, and treatment of these phenomena, and current clinical practice is based solely on deductions by extension from retrospective studies, case series, observational studies, and international guidelines developed prior to the pandemic. Objective: to generate a group of recommendations on the prevention, diagnosis and management of thrombotic complications associated with COVID-19. Methods: a rapid guidance was carried out applying the GRADE Evidence to Decision (EtD) frameworks and an iterative participation system, with statistical and qualitative analysis. Results: 31 clinical recommendations were generated focused on: a) Coagulation tests in symptomatic adults with suspected infection or confirmed SARS CoV-2 infection;b) Thromboprophylaxis in adults diagnosed with COVID-19 (Risk scales, thromboprophylaxis for outpatient, in-hospital management, and duration of thromboprophylaxis after discharge from hospitalization), c) Diagnosis and treatment of thrombotic complications, and d) Management of people with previous indication of anticoagulant agents. Conclusions: recommendations of this consensus guide clinical decision-making regarding the prevention, diagnosis, and treatment of thrombotic phenomena in patients with COVID-19, and represent an agreement that will help decrease the dispersion in clinical practices according to the challenge imposed by the pandemic.