Enhanced fatty acid oxidation through Metformin and Baicalin as therapy for COVID-19 and associated inflammatory states in lung and kidney

Progressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (COVID-19) pandemic. It is the final outcome of the acute respiratory distress syndrome (ARDS), characterized by an initial exacerbated inflammatory response and ultimate tissue scarring. Energy balance may be crucial for the recovery of clinical COVID-19. Hence, we asked if two key pathways involved in energy generation, AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling and fatty acid oxidation (FAO) could be beneficial. We tested the drugs Metformin (AMPk activator) and Baicalin (Cpt1A activator) in different experimental models mimicking COVID-19 associated inflammation in lung and kidney. We also studied two different cohorts of COVID19 patients that had been previously treated with Metformin. These drugs ameliorated lung damage in an ARDS animal model, while activation of AMPK/ACC signaling increased mitochondrial function and decreased TGF-beta-induced fibrosis, apoptosis and inflammation markers in lung epithelial cells. Similar results were observed with two new indole derivatives IND6 and IND8 with AMPK activating capacity. Consistently, a reduced stay in the intensive care unit was observed in COVID-19 patients previously exposed to Metformin. Baicalin also reduced kidney fibrosis in two animal models of kidney injury, another key target of COVID-19, while in vitro both drugs improved mitochondrial function and prevented TGF-beta-induced renal epithelial cell dedifferentiation. Our results support that strategies based on energy supply may prove useful in the prevention of COVID-19-induced lung and renal damage.Copyright © 2023

Meanings of social isolation for young Brazilians during the covid-19 pandemic

Introduction: The covid-19 pandemic has left a high number of infected and dead in the world, where several social measures have been imposed on the population, especially social isolation. Objective: Given this scenario, based on Vygotsky's socio-historical theory, this original article aimed to identify the meanings of social isolation in the covid-19 pandemic for Brazilian youth. Method: A survey was carried out, with the participation of 571 young Brazilians, women and men aged between 18 and 25, who answered a sociodemographic questionnaire and the Free Word Association Method (FWAM), analyzed with the help of IRaMuTeQ. Results: The results showed that virtualized socialization is insufficient for the social demand of young people, as evidenced by the most evoked words in category 1, "Homesickness” (χ² = 55,41);"Boredom” (χ² = 50,06);"Anxiety” (χ² = 42,67);"Loneliness” (χ² = 37,15);"Sadness” (χ² = 32,78). It was also identified that their routine was transformed with the insertion of obligations and leisure primarily in the home environment, demonstrated by the prevalence of words like "House” (χ² = 116,18);"Home Office” (χ² = 26,06);"Movie” (χ² = 26,06);"Mask” (χ² = 24,96);"Alcohol” (χ² = 21,67);"Lockdown” (χ² = 21,67), in category 2. Still, young people brought their resignifications in this period, in the face of collective responsibility, indicated by the choice of words in category 3, such as "Care” (χ² = 84,05);"Responsibility” (χ² = 59,21);"Respect” (χ² = 55,03);"Prevention” (χ² = 52,68);"Empathy” (χ² = 34,06);"Protection” (χ² = 21,99). Conclusions: It is concluded that isolation brought negative consequences on relationships and mental health of young people, but also a greater social awareness. © 2023, Universidad Simon Bolivar. All rights reserved.

Online Search Patterns about Vaccination: A National Study

Introduction: Google Trends is an online metadata platform that measures the relative search volume of every topic in online search engines. In medical settings, this behavior has been associated with active changes in people's perceptions and search for healthcare. This study aimed to evaluate the online search patterns of Portuguese extra-program and risk-based vaccination. Method(s): Analysis of the relative search volume was performed for extra-program and risk-based vaccines, in every Portuguese district between 2006 and 2021. Relative search volume was represented between 0 and 100 (highest interest in the query). Result(s): Rotavirus vaccine was consistently the most searched, followed by BCG and flu, the last of which, with abnormal peaks of search in November 2009 and October 2020. We registered a significant increase in the search for every vaccine in the last 5 years (p < 0.01). Particularly, during the COVID-19 pandemic, a more abrupt increase was registered for the flu vaccine, but most importantly for BCG (3,0[69,9] vs. 9,0[528,0]). Lisboa and Porto are the only Portuguese districts where percentual research is spread across all types of vaccines. On the other hand, in Portalegre, 84% of total searches correspond to BCG. Discussion and Conclusion(s): The recent increase in the interest in vaccination may translate into the investment of health professionals in primary prevention measures. However, the mediatic impact of pandemics is not neglectable. Health professionals must fight misinformation as it may have happened with the increasing interest in BCG, probably due to the protective association proposed with the infection by SARS-CoV-2.Copyright © 2022 The Author(s).

Online Search Patterns about Vaccination: A National Study

Introduction: Google Trends is an online metadata platform that measures the relative search volume of every topic in online search engines. In medical settings, this behavior has been associated with active changes in people's perceptions and search for healthcare. This study aimed to evaluate the online search patterns of Portuguese extra-program and risk-based vaccination. Method(s): Analysis of the relative search volume was performed for extra-program and risk-based vaccines, in every Portuguese district between 2006 and 2021. Relative search volume was represented between 0 and 100 (highest interest in the query). Result(s): Rotavirus vaccine was consistently the most searched, followed by BCG and flu, the last of which, with abnormal peaks of search in November 2009 and October 2020. We registered a significant increase in the search for every vaccine in the last 5 years (p < 0.01). Particularly, during the COVID-19 pandemic, a more abrupt increase was registered for the flu vaccine, but most importantly for BCG (3,0[69,9] vs. 9,0[528,0]). Lisboa and Porto are the only Portuguese districts where percentual research is spread across all types of vaccines. On the other hand, in Portalegre, 84% of total searches correspond to BCG. Discussion and Conclusion(s): The recent increase in the interest in vaccination may translate into the investment of health professionals in primary prevention measures. However, the mediatic impact of pandemics is not neglectable. Health professionals must fight misinformation as it may have happened with the increasing interest in BCG, probably due to the protective association proposed with the infection by SARS-CoV-2. Copyright © 2022 The Author(s). Published by S. Karger AG, Basel.

Assisting in the choice to fill a vacancy to compose the PROANTAR team: Applying VFT and the CRITIC-GRA-3N methodology

Antarctica is the southernmost continent of our planet, and it has been verified as the coldest region on earth. The Brazilian Antarctic Program (PROANTAR) has as its main objective the promotion of high-quality scientific research in the Antarctic region, seeking to understand the events that occur there. PROANTAR, coordinated by the Navy Commander, has some sectors that are based in Brazil and others that are located in the Antarctic continent. The military that volunteers to occupy any vacancy that is allocated to that continent needs, besides passing through several pre-established criteria, to pass the selection process. The purpose of this article is to help the Naval Administration in the selection of volunteer officers to occupy a vacancy in the Antarctic continent. To obtain the alternatives, the officers that best fit the established vacancy, and the criteria to be evaluated, Value-Focused Thinking (VFT) was applied. Next, with all the necessary data, the CRITIC-GRA-3N method was used as a Multicriteria Decision Support (MDS) technique, the CRITIC-GRA-3N method, the CRITIC Importance Through Intercriteria Correlation (CRITIC) method to obtain the criteria weights and the Grey Relational Analysis (GRA) method, with three normalizations, to order the alternatives. At the end of the application of the methods, the article can generate five ordinations of the volunteer officers to occupy the vacancy offered in PROANTAR. © 2022 The Authors. Published by Elsevier B.V.

Structuring and mathematical modeling for investment choice: a multi-method approach from Value-Focused Thinking and CRITIC-GRA-3N method

Investments should be decisions made by companies at a strategic level, aiming to maximize the return on invested capital. However, the evaluation required to obtain the best results demand, in addition to information about available assets, the ability of decision-makers to relate and weigh all the criteria that must be maximized or minimized to achieve the expected goal. This article plays an important role in supporting the decision making of a micro company, located in the state of Rio de Janeiro, which needs to invest the available amount in investment. In order to obtain the investment alternatives, as well as the evaluation criteria, the Value-Focused Thinking (VFT) was applied. After obtaining all necessary data, the CRITIC-GRA-3N method was used as a Multicriteria Decision Support technique, with the CRiteria Importance Through Intercriteria Correlation (CRITIC) method to generate the criteria weights and the Grey Relational Analysis (GRA) method, with three normalizations, to order the alternatives. With this, five ordinations were established, being the first three ordinations performed with the help of two normalizations and the last two ordinations being the arithmetic and geometric averages of the first three ordinations normalized with the third normalization. In the end it brought positive results to the microenterprise. © 2022 The Authors. Published by Elsevier B.V.

RAZÕES HEMATOLÓGICAS NA COVID-19: DIFERENÇAS ENTRE PACIENTES COM E SEM NECESSIDADE DE VENTILAÇÃO MECÂNICA INVASIVA

Objetivos Investigar as diferenças na Razão Neutrófilo-Linfócito (NLR), Razão Neutrófilo-Linfócito derivada (d-NLR), Razão Linfócito-Monócito (LMR), Razão Plaquetas-Linfócitos (PLR), Razão Neutrófilos-Plaquetas (NPR) e Índice de Inflamação Sistêmica (SII) entre pacientes COVID-19 com e sem necessidade de ventilação mecânica invasiva e um grupo controle saudável. Material e Métodos Foram incluídos pacientes com diagnóstico de COVID-19 admitidos no Hospital Universitário de Santa Maria (HUSM) no período de 1°de março de 2020 a 31 de março de 2021. Foram excluídos pacientes com falta de informações nos prontuários, com câncer, internados por acidentes graves, com lúpus, apendicite, transferidos para outros hospitais, gestantes e menores de 18 anos, resultando em 212 pacientes. Foi incluído um grupo controle com 198 indivíduos saudáveis. Os dados do primeiro hemograma após internação foram obtidos do prontuário eletrônico do hospital. A partir desses dados, calculou-se: Razão Neutrófilo-Linfócito (NLR), razão neutrófilo-linfócito derivada (d-NLR, divisão do total de neutrófilos por leucócitos menos neutrófilos totais), Razão Linfócito-Monócito (LMR), Razão Plaquetas-Linfócitos (PLR), razão neutrófilos-plaquetas (NPR) e índice de inflamação sistêmica (SII, multiplicação de plaquetas por neutrófilos totais seguida de divisão por linfócitos totais). Os pacientes foram estratificados em com necessidade de Ventilação Mecânica Invasiva (VMI) (n=129) e sem Necessidade de Ventilação Mecânica Invasiva (NVMI) (n=83). O estudo foi aprovado pelo Comitê de Ética em Pesquisa da UFSM (CAAE 30917320.5.0000.5346). Resultados As razões calculadas apresentaram as seguintes medianas e intervalos interquartis para grupo controle, NIMV e IMV respectivamente: NLR 1,75 (1,42‒2,24), 6,58 (3,29‒12,7), 14,5 (8,10‒23,2);d-NLR 1,28 (1,07‒1,64), 4,00 (2,23‒7,33), 8,09 (4,81‒12,89);LMR 3,89 (3,22‒5,02), 2,00 (1,25‒3,07), 1,53 (1,00‒2,73);PLR 101 (84‒119), 227 (159‒400), 310 (207‒441);NPR 0,02 (0,01‒0,02), 0,02 (0,02‒0,04), 0,04 (0,03‒0,06);SII 387 (302‒522), 1748 (739,6‒2705), 3115 (1429‒5769). Todas as razões calculadas apresentaram resultados significativamente diferentes (p<0,001) entre o grupo controle e o grupo de pacientes com COVID-19. NLR, d-NLR, NPR e SII apresentaram diferença significativa entre grupo controle, VMI e NVMI. Discussão O hemograma é um exame realizado rotineiramente na maioria dos laboratórios, portanto as razões hematológicas representam parâmetros alternativos que não agregam custo e não requerem análises adicionais. Estas razões já demonstraram diferença em pacientes com outras doenças e no caso da COVID-19 para outros parâmetros, como mortalidade, por exemplo. Nosso trabalho demonstrou que existe diferença significativa entre pacientes com e sem necessidade de intubação, o que ainda não havia sido descrito anteriormente. Conclusão Embora mais estudos sejam necessários, os índices hematológicos abordados neste trabalho são potenciais auxiliares na tomada de decisão clínica quanto à necessidade de ventilação mecânica invasiva.

Rural sanitation: scenarios and public policies for the Brazilian semi-arid region

Brazil's primary sanitation sector has been neglected, especially concerning rural sanitation. Population dispersion and the difficulty of access in many rural communities bring more significant challenges to the universalization of the service and, consequently, vulnerabilities for the population. The present work builds a theoretical framework about the context of rural sanitation in Brazil, with history, weaknesses in the sector, the impact of COVID-19 and new technologies, and central public policies in the State of Pernambuco. It is known that COVID-19 has caused considerable challenges that, added to the obstacles to national sanitation, result in greater vulnerability to the population, especially for indigenous peoples, quilombolas, and diffuse rural communities. In the State of Pernambuco, certain policies, such as the One Million Rural Cisterns Program (P1MC), One Land and Two Waters Program (P1 + 2), Agua Doce Program and Operacao Pipa Program, significantly improved the quality of life of the rural population. However, these measures are not enough to remedy the sector's shortcomings. Although alternative sanitation technologies bring hope to the sector, there is a long way to go towards the universalization of sanitation.

Impact of COVID-19 pandemic on breast cancer neoadjuvant therapy: a retrospective institutional analysis

Background: COVID-19 pandemic motivated a reorganization of healthcare institutions, which may have led to a negative impact on cancer patients' treatment. This study compared the pathological response (PR) rate to neoadjuvant chemotherapy (NACT) in breast cancer (BC) patients who underwent treatment before (BCv) and during (DCv) the COVID-19 pandemic at our institution.

Information System Security Risk Priority Number: A New Method for Evaluating and Prioritization Security Risk in Information System Applying FMEA

The emergence of the COVID-19 pandemic led several organizations around the world and in the most varied areas of activity, to move from the intention to implement a digital transformation in the medium/long-term, to an instant obligation to apply the digital transformation. The organizations’ ability to adapt immediately meant their survival and even in some cases a positive evolution of their business. The digital transformation applied in an abrupt way has uncovered some critical factors for its success. One of the most relevant factors will be information security. Many of the digital systems put into operation more intensively during the pandemic, have shown to be highly fragile on issues related to information security. One relevant problem of the organizations is the low effectiveness and efficiency of financial, human, and material resources, allocated to the reduction or mitigation of the risks identified in their information systems. This study aims to offer a new method for prioritizing security risks. The new proposed method directs the organizations resources to more effectively and efficiently actions to reduce or mitigate the identified vulnerabilities of the information system. © 2022, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

Investments in times of pandemics: An approach by the SAPEVO-M-NC method

The consequences of the pandemic caused by the new coronavirus in the most diverse sectors of the Brazilian economy, are overwhelming, and its effects are still difficult to measure completely. There are several possible scenarios being considered, such as prolonged depression, 'U' or 'V' recovery. Due to such volatility, risks and uncertainties, the investor, before investing, must carefully analyze the alternatives available in the market. Given the above, this article aims to propose different ways of distributing a financial portfolio, considering five investment funds, which were evaluated in the light of five criteria, by two investors who work in the financial market. Therefore, the SAPEVO-M-NC multicriteria decision aid method was used to evaluate the alternatives, as well as their composition in the investment portfolios. The adoption of the methodology made it possible to carry out the distribution of the portfolio in a clear and consistent way, showing itself as an efficient practical tool for the proposed approach. © 2021 The authors and IOS Press.

Strategic analysis for the installation of field hospitals for COVID-19 control: An approach based on P-median model

Concerning the expansion of the coronavirus in the world, the search for the development of solutions related to the control and mitigation of the pandemic situation became constant. The paper addresses an analysis of localities for the installation of field hospitals, highly requested as a point of treatment for COVID-19. In this scenario, a framework based on the P-median approach and mathematical programming is proposed, enabling an optimization model as an analysis format for the problematic situation. To support the implementation of the model, a computational tool for data processing was developed, integrating an optimization model to the geographical evaluation, exploring in the analysis numerical and graphical resources. As a validation of the study, a case study in the city of Rio de Janeiro - Brazil is presented, analyzing 162 neighborhoods and determining seven favorable localities for the installation of field hospitals. © 2021 The authors and IOS Press.

Sars-cov-2 infects and replicates in cells of the human pancreas

Introduction: Viral infections may trigger diabetes. Clinical data suggest infection with the pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), may impact glucose homeostasis in patients. Notably, cases of new-onset diabetes upon SARS-CoV-2 infection have been reported. However, experimental evidence of pancreatic infection is still controversial. Aims & Methods: Here, we employ cadaveric human pancreatic islets, as well as pancreatic tissue from deceased COVID-19 patients to investigate the impact of SARS-CoV-2 on the pancreas. Results: We show that human β-cells express viral entry proteins ACE2 and TMPRSS2, making them susceptible to SARS-CoV-2 infection and replication. Our data further demonstrates that SARS-CoV-2 infects and replicates in ex vivo cultured human islets and infection. This infection is associated with morphological, transcriptional and functional changes, such as reduction of insulin-secretory granules in β-cells and impaired glucose-stimulated insulin secretion. In COVID-19 post-mortem examinations, we detected SARS-CoV-2 nucleocapsid protein in pancreatic exocrine cells, and in cells that stain positive for the β-cell marker NKX6.1 in all patients investigated. Conclusion: Taken together, our data define the human pancreas as a target of SARS-CoV-2 infection and suggest that β-cell infection might contribute to the metabolic dysregulation observed in patients with COVID- 19.

Strategic Study for Managing the Portfolio of IT Courses Offered by a Corporate Training Company: An Approach in the Light of the ELECTRE-MOr Multicriteria Hybrid Method

The globalization of business and the consequent exposure to global competition, besides the economic and social changes caused by the COVID-19 pandemic made the Training & Development (TD) sector increasingly important for professionals in the corporate environment. In this sense, managing stakeholders and a portfolio of clients, as well as analyzing the relationship between customer and service, are necessary and strategic for the success of professional training organizations. This paper aims to support the strategic process of portfolio formation of TD courses offered by a company in the Information Technology (IT) training sector in Brazil, through the application of the ELECTRE-MOr multicriteria sorting method. We have obtained a categorization of several courses, aiming to define which ones should be prioritized, maintained, or discarded by the company's management. The results showed that, among the analyzed courses, only 17% should be prioritized, 61% maintained, and 22% discarded by the company. © 2021 World Scientific Publishing Company.

Inpatient psychiatry care during coronavirus 2019 pandemic lockdown: Results from a department of psychiatry in northern Portugal

IntroductionCOVID-19 pandemic and the consequent containment measures have a negative impact on mental health. Simultaneously, the fear of infection can discourage patients from seeking necessary care.ObjectivesWe aim to compare sociodemographic and clinical characteristics of inpatients admitted during the COVID-19 confinement period in Portugal vs. inpatients admitted in the same period the previous year.MethodsRetrospective observational study of inpatients admitted between March 19th 2020 and May 1st 2020 and the analog period of 2019 in a psychiatry inpatient unit of a tertiary hospital. Descriptive analysis of the results was performed using the SPSS software, version 26.0.ResultsDuring the lockdown period, there were 30 admissions to the psychiatry inpatient unit, 55.2% less than the same period last year (n=67). The proportion of compulsory admissions and the average length of stay did not differ between the two periods. Regarding sociodemographic characteristics, in the confinement period inpatients were similar to the ones in the same period of 2019. In both periods, the majority of patients had previous psychiatric history (lockdown vs. same period last year: 95.5% and 90.0%) and a similar proportion of readmissions rate (previous year) was similar in the two groups (49.9% vs 47.6%). At discharge, the most frequent diagnostic groups were mood disorders (33.3% (n=10) and 34.3% (n=23)) and schizophrenia, schizotypal and delusional disorders (26,7% (n=8) and 31.3% (n=21)).ConclusionsAlthough there was an expressive reduction of admissions to the psychiatry inpatient unit during lockdown, the clinical characteristics of these patients were analogous to the same period in the previous year.

Choosing flying hospitals in the fight against the COVID-19 pandemic: structuring and modeling a complex problem using the VFT and ELECTRE-MOr methods

The increase in the number of cases of the new coronavirus has threatened the capacity of health systems worldwide, with several states declaring the collapse of the hospital system. In order to find a way to support Brazil in the fight against the pandemic, this article used the Value-Focused Thinking (VFT) and ELECTRE-MOr methods to select the most suitable hospital aircraft to be acquired by the Brazilian government. The airplanes would be used in aeromedical evacuations, supporting the fight against the pandemic, especially in regions where there are no more ICU beds available, transporting patients to other locations with greater structure, technological and technical experience. To this end, six models manufactured by Embraer, employed in aeromedical evacuations, were evaluated in the light of operational, technical and commercial criteria. This paper aims to solve a problem of extreme relevance to academia and society, as it proposes the application of a new Multi-Criteria Decision Support (MCDS) method to contribute to the solution of a problem that affects millions of people in Brazil and worldwide. After the application of the methods, Legacy 450 and Praetor 500 aircrafts were chosen as the most indicated to be acquired by the Government and used as hospital aircrafts in the fight against the pandemic.