Prevalence, Presentation and Outcomes of Silent Hypoxemia in COVID-19.

Dyspnea is reported in a minority of patients affected by coronavirus disease 2019 (COVID-19). Even patients with pneumonia can present hypoxemia without any respiratory distress, a phenomenon known as "silent" or "happy hypoxemia". During the current pandemic there were only a few studies conducted on this subject and these were quite heterogeneous. Therefore, the prevalence of "silent hypoxemia" varied substantially. While studies did not show a clear tendency of "silent hypoxemia" to poorer outcomes compared to hypoxemia presenting with dyspnea, several showed that patients with "silent hypoxemia" are not protected from poor outcomes either. There is a need for a uniform definition of "silent hypoxemia", in order to better guide clinicians and investigators. More studies are needed to shed light on the mechanisms of "silent hypoxemia", as well as its presentation and influence in the disease's progression and outcomes, so as to better assist physicians in the care of COVID-19 patients.

Understanding and Managing Severe Asthma in the Context of COVID-19.

Coronavirus disease 2019 (COVID-19) continues to spread across the world. Since the beginning of the pandemic, the question of whether asthma is a risk factor for getting the infection or for poor outcomes motivated a great debate. In the field of severe asthma and its treatment during COVID-19 pandemic, several issues are also pending. A literature review focused on the management of severe asthma patients in the context of COVID-19 is performed. The available evidence suggests that severe asthma patients do not have an increased risk of poor COVID-19 outcomes and that it is safe to treat asthmatic patients with inhaled corticosteroids (ICS) and biologics during the pandemic, even though some studies indicate that high doses of ICS may predispose to COVID-19. The chronic use of oral corticosteroid (OCS) might be associated with poor COVID-19 outcomes, although there is no complete agreement. There is very limited evidence concerning the use of triple therapy for asthma in the context of this pandemic. Ultimately, severe asthma patients should maintain their medication during the COVID-19 pandemic, including biologic agents. More studies are needed to address the role of asthma medications and asthma's different phenotypes on the incidence and course of COVID-19.

Biological therapies, asthma and coronavirus disease 2019.

PURPOSE OF REVIEW: As of June 2021, coronavirus disease 2019 (COVID-19) exceeded 180 million reported cases and was responsible for almost 4 million deaths globally. Asthma affects approximately 262 million people worldwide and is an important cause of morbidity and mortality. Presently, it appears asthma is neither associated with an increased risk of contracting COVID-19 nor with a risk of severe COVID-19 or COVID-19 related death. Regarding the severe asthma patients on biologics, questions remain. The purpose of this review is to discuss the evidence regarding the relationship between asthma, biologics and COVID-19. RECENT FINDINGS: The available evidence does not suggest that severe asthmatics on treatment with biologics have a higher risk of severe acute respiratory syndrome coronavirus 2 infection compared to the general population. It does not appear that they have a higher risk of severe disease or COVID-19 related death either. SUMMARY: This review suggests that treatment with biologics for severe asthma is safe and should be maintained during the COVID-19 pandemic. However, more studies are needed to address this question and the role of biological therapy on different asthma phenotypes.

COVID-19 therapy: What weapons do we bring into battle?

Urgent treatments, in any modality, to fight SARS-CoV-2 infections are desired by society in general, by health professionals, by Estate-leaders and, mainly, by the scientific community, because one thing is certain amidst the numerous uncertainties regarding COVID-19: knowledge is the means to discover or to produce an effective treatment against this global disease. Scientists from several areas in the world are still committed to this mission, as shown by the accelerated scientific production in the first half of 2020 with over 25,000 published articles related to the new coronavirus. Three great lines of publications related to COVID-19 were identified for building this article: The first refers to knowledge production concerning the virus and pathophysiology of COVID-19; the second regards efforts to produce vaccines against SARS-CoV-2 at a speed without precedent in the history of science; the third comprehends the attempts to find a marketed drug that can be used to treat COVID-19 by drug repurposing. In this review, the drugs that have been repurposed so far are grouped according to their chemical class. Their structures will be presented to provide better understanding of their structural similarities and possible correlations with mechanisms of actions. This can help identifying anti-SARS-CoV-2 promising therapeutic agents.

Novel 4-quinoline-thiosemicarbazone derivatives: Synthesis, antiproliferative activity, in vitro and in silico biomacromolecule interaction studies and topoisomerase inhibition.

Twelve 2-(quinolin-4-ylmethylene) hydrazinecarbothioamide derivatives were synthetized and their biological properties were investigated, among which, the ability to interact with DNA and BSA through UV-Vis absorption, fluorescence, Circular Dichroism, molecular docking and relative viscosity, antiproliferative activity against MCF-7 and T-47D mammary tumor cells and RAW-264.7 macrophages and inhibitory capacity of the enzyme topoisomerase IIα. In the binding study with DNA and BSA, all the compounds displayed affinity for interaction with both biomolecules, especially JF-92 (p-ethyl-substituted), with binding constant of 1.62 × 106 and 1.43 × 105, respectively, and DNA binding mode by intercalation. The IC50 values were obtained between 0.81 and 1.48 µM and topoisomerase inhibition results in 10 µM. Thus, we conclude that the reduction of the acridine to quinoline ring did not disrupt the antitumor action and that substitution patterns are important for biomolecule interaction affinity as they demonstrate the potential of these compounds for anticancer therapy.

Topoisomerase inhibition and albumin interaction studies of acridine-thiosemicarbazone derivatives.

In the present study, acridine-thiosemicarbazones (ATD) derivatives were tested for their interaction properties with BSA through UV-Vis absorption and fluorescence spectroscopic studies. Both hyperchromic and hypochromic effects, as well as red or blue shifts were demonstrated after the derivatives were added to the BSA. Values for the binding constant (Kb) ranged from 1.62 × 104 to 8.71 × 105 M-1 and quenching constant (KSV) from 3.46 × 102 to 7.83 × 103 M-1 indicating a good affinity to BSA protein. Complementary, two compounds were selected to assess their inhibition activity against topoisomerase IIα enzyme, of which derivative 3a presented the best result. Moreover, to evaluate protein-ligand interactions, as well as the antitopoisomerase potential of these compounds, tests of molecular modeling were performed between all compounds using the albumin and Topoisomerase IIα/DNA complex. Finally, in silico studies showed that all derivatives used in this research displayed good oral bioavailability potential.

Synthesis, DNA and protein interactions and human topoisomerase inhibition of novel Spiroacridine derivatives.

Nine new spiroacridine derivatives were synthetized by introducing cyano-N-acylhydrazone group between the acridine and phenyl-substituted rings followed by spontaneous cyclization. The new compounds were assayed for their DNA binding properties, human topoisomerase IIα inhibition and bovine serum albumin (BSA) interaction. Besides, docking analysis were performed in order to better understanding the biomolecule-compounds interactions. All compounds interacted with BSA which was demonstrated by the fluorescence suppression constant of 104 M-1. Compounds with chloro and NO2 substituents at that para-position on phenyl ring demonstrated the best results for BSA interaction. DNA binding constant determined by UV-vis data demonstrated high values for AMTAC-11 and AMTAC-14, 1.1 × 108 M-1 and 4.8 × 106 M-1, respectively, and all others presented constant values of 105 M-1. AMTAC-06 with chloro at para-position on phenyl ring presented a topoisomerase II inhibition of 84.34% in comparison to the positive controls used. Docking studies indicated that AMTAC-06 is able to intercalate the DNA base pairs at topoisomerase IIα active site, preventing DNA connection after break, in a process known as poisoning. Topoisomerase enzyme inhibition result was correlated to BSA interaction profile, since AMTAC-06 showed the best results in both analysis. The findings obtained here proved that methoxy or chloro substitution on phenyl ring at para-position is fundamental for in vitro activity of new spiroacridine derivatives, and indicates that AMTAC-06 is a promising entity and should serve as a lead compound in the development of new DNA and protein binders, as well as human topoisomerase II inhibitors.

DNA binding and Topoisomerase inhibition: How can these mechanisms be explored to design more specific anticancer agents?

DNA is considered one of the most promising targets of molecules with anticancer activity potential. Its key role in various cell division mechanisms, which commands the intense multiplication of tumor cells, is considered in studies with compounds whose mechanisms of action suggest likeliness of interaction. In addition, inhibition of enzymes that actively participate in biological functions of cells such as Topoisomerase, is seen as a primary factor for conducting several events that result in cell death. Discovery of new anticancer chemotherapeutical capable of interacting with DNA and inhibiting Topoisomerase enzymes is highlighted in anticancer research. The present review aims at showing through distinct biological tests the performance of different candidates to anticancer drugs and their respective chemical modifications, which are crucial and/or determinant for DNA affinity and inhibition of important enzymes in cells' vital processe to either separately or synergistically optimize anticancer activity.

Synthesis of thiophene-thiosemicarbazone derivatives and evaluation of their in vitro and in vivo antitumor activities.

A series of thiophene-2-thiosemicarbazones derivatives (5-14) was synthesized, characterized and evaluated for their antitumor activity. They were tested in vitro against human tumor cell lines through the colorimetric method. The results revealed that compounds 7 and 9 were the most effective in inhibiting 50% of the cell growth after 48 h of treatment. As compound 7 showed a potent antiproliferative profile, it has been chosen for further studies in 786-0 cell line by flow cytometry. Treatments with compound 7 (50 µM) induced early phosphatidylserine exposure after 18 h of exposure and this process progressed phosphatidylserine exposure with loss of cell membrane integrity after 24 h of treatment, suggesting a time-dependent cell death process. Regarding the cell cycle profile, no changes were observed after treatment with compound 7 (25 µM), suggesting a mechanism of cell death independent on the cell cycle. The in vivo studies show that compound 7 possess low acute toxicity, being the doses of 30-300 mgKg(-1) chosen for studies in Ehrlich solid tumor model in mice. All doses were able to inhibit tumor development being the lowest one the most effective. Our findings highlight thiophene-2-thiosemicarbazones as a promising class of compounds for further studies concerning new anticancer therapies.

[Factors associated with mode of delivery in women with pre-eclampsia]. / Fatores associados à via de parto em mulheres com pré-eclâmpsia.

PURPOSE: To analyze the factors related to route of delivery in patients with pre-eclampsia. METHODS: A retrospective analytical study was conducted from January 2009 to January 2011, during which 250 medical records of patients diagnosed with pre-eclampsia who gave birth to live fetuses with a gestational age of 28 weeks or more were selected. The variables evaluated were: maternal age (19 years, 20-34 years and over 35 full years), gestational age at delivery (28-37 weeks and more than 37 weeks), parity (primiparous or multiparous), previous cesarean section, history of pre-eclampsia or chronic hypertension, current diagnosis of mild or severe pre-eclampsia, and birth weight of the newborn. The information was transcribed to a questionnaire based on the variables being investigated. The chi-square test was applied to identify the relationship between the variables, with the level of significance set at p<0.05, and the Odds Ratio (OR) was calculated only for the variables showing a statistically significant difference in order to determine the odds for the patient to be submitted to a cesarean section. RESULTS: In this study, we observed a 78.4% rate of cesarean delivery, with 54.1% of the patients submitted to the procedure having a gestational age of 28 to 37 weeks (OR=3.1; p<0.01). Patients with a history of pre-eclampsia were 2.5 times more likely to have cesarean delivery (OR=2.5; p<0.02). All patients who had had a previous cesarean were submitted to cesarean delivery in the current pregnancy (p<0.01). Pregnant women with severe pre-eclampsia were 3.3 times more likely to progress to cesarean delivery than those with mild pre-eclampsia (OR=3.3; p<0.01). CONCLUSION: After individual analysis, only gestational age and a diagnosis of severe pre-eclampsia showed significant differences, representing risk factors for this type of delivery.

Fatores associados à via de parto em mulheres com pré-eclâmpsia / Factors associated with mode of delivery in women with pre-eclampsia

OBJETIVO: Analisar os fatores relacionados à via de parto em pacientes com pré-eclâmpsia. MÉTODOS: Estudo do tipo analítico e retrospectivo, realizado no período entre janeiro de 2009 e janeiro de 2011, no qual foram selecionados 250 prontuários de pacientes com diagnóstico de pré-eclampsia e que deram à luz a conceptos vivos, com idade gestacional igual ou superior a 28 semanas. As variáveis avaliadas foram: idade materna (até 19 anos, de 20 a 34 anos e acima de 35 anos completos), idade gestacional no momento do parto (28−37 semanas e acima de 37 semanas), paridade (primípara ou multípara), antecedente de cesárea, antecedente de pré-eclâmpsia ou hipertensão arterial crônica, diagnóstico atual de pré-eclâmpsia leve ou grave e peso do recém-nascido. As informações foram transcritas para um questionário elaborado e baseado nas variáveis a serem investigadas. Foi realizado o teste do χ2 para identificar relação entre as variáveis. As variáveis que tiveram p<0,05 apresentaram diferença estatística. Só para essas variáveis foi calculada a Odds Ratio (OR), mostrando a razão de chances de ter parto cesáreo. RESULTADOS: No estudo realizado, observou-se que 78,4% dos partos foram cesáreas. Das cesáreas realizadas, 54,1% foram de pacientes com 28 a 37 semanas de idade gestacional (OR=3,1; p<0,01). Pacientes com antecedentes de pré-eclâmpsia tiveram mais chance de ter parto cesáreo (OR=2,5; p<0,02). Todas as pacientes com cesárea anterior evoluíram para parto cesáreo na gestação atual (p<0,01). As gestantes com pré-eclâmpsia grave tiveram 3,3 vezes mais chance de evoluir para parto cesáreo do que as com pré-eclâmpsia leve (OR=3,3; p<0,01). CONCLUSÃO: ...

PURPOSE: To analyze the factors related to route of delivery in patients with pre-eclampsia. METHODS: A retrospective analytical study was conducted from January 2009 to January 2011, during which 250 medical records of patients diagnosed with pre-eclampsia who gave birth to live fetuses with a gestational age of 28 weeks or more were selected. The variables evaluated were: maternal age (19 years, 20−34 years and over 35 full years), gestational age at delivery (28−37 weeks and more than 37 weeks), parity (primiparous or multiparous), previous cesarean section, history of pre-eclampsia or chronic hypertension, current diagnosis of mild or severe pre-eclampsia, and birth weight of the newborn. The information was transcribed to a questionnaire based on the variables being investigated. The chi-square test was applied to identify the relationship between the variables, with the level of significance set at p<0.05, and the Odds Ratio (OR) was calculated only for the variables showing a statistically significant difference in order to determine the odds for the patient to be submitted to a cesarean section. RESULTS: In this study, we observed a 78.4% rate of cesarean delivery, with 54.1% of the patients submitted to the procedure having a gestational age of 28 to 37 weeks (OR=3.1; p<0.01). Patients with a history of pre-eclampsia were 2.5 times more likely to have cesarean delivery (OR=2.5; p<0.02). All patients who had had a previous cesarean were submitted to cesarean delivery in the current pregnancy (p<0.01). Pregnant women with severe pre-eclampsia were 3.3 times more likely to progress to cesarean delivery than those with mild pre-eclampsia (OR=3.3; p<0.01). CONCLUSION: After individual analysis, only gestational age and a diagnosis of severe pre-eclampsia showed significant differences, representing risk factors for this type of delivery. .

Prevalência de colonização por Streptococcus agalactiae em gestantes atendidas em maternidade do Ceará, no Brasil, correlacionando com os resultados perinatais / Prevalence of the colonization by Streptococcus agalactiae in pregnant women from a maternity in Ceará, Brazil, correlating with perinatal outcomes

OBJETIVO: Analisar a prevalência de Streptococcus agalactiae, um estreptococo do Grupo B, em gestantes e seus possíveis fatores de risco, bem como o impacto perinatal e a suscetibilidade antimicrobiana das colonizadas. MÉTODOS: Foram avaliadas 213 gestantes a partir de 20 semanas de gestação, independente dos fatores de risco, atendidas em um hospital-escola terciário da zona Norte do Estado de Ceará, no Brasil. O cálculo do tamanho amostral ocorreu por conveniência. Foi utilizada técnica do swab estéril único para coleta de secreção das regiões vaginal e perianal. As amostras recém-obtidas eram armazenadas em meio de transporte Stuart e, no laboratório, inoculadas em meio seletivo Todd-Hewitt adicionado de gentamicina (8 ug/mL) e ácido nalidíxico (15 ug/mL), com posterior subcultivo em placas em ágar-sangue. Nos materiais eram realizados teste de Gram, catalase com peróxido de oxigênio e CAMP (Christie, Atkins, Munch-Petersen), sendo confirmados sorologicamente com Streptococcal Grouping Kit, Oxoid®. As positivas foram submetidas a testes de suscetibilidade antimicrobiana. Foram também avaliadas variáveis socioeconômicas, reprodutivas, clínico-obstétricas e neonatais. Os dados foram analisados utilizando o programa Epi-Info 6.04. RESULTADOS: A prevalência de colonização encontrada foi de 9,8 por cento pelo teste de CAMP, embora apenas 4,2 por cento pelo sorológico. O único fator de proteção observado foi cor da pele branca (p=0,01, 0.45>OR>0.94, IC95 por cento). Não foi observada diferença de prevalência do estreptococo do Grupo B com outras variáveis reprodutivas ou obstétricas. Ocorreu infecção em apenas um dos recém-nascidos de mães colonizadas, entretanto revelou-se infecção por Pseudomonas spp. Foi encontrada resistência para ampicilina (4/9) e cefalotina (4/9), penicilina (4/9 casos), eritromicina (3/9), clindamicina (7/9) e cloranfenicol (1/9). CONCLUSÕES: A taxa de infecção foi inferior à encontrada em outros estudos, embora também notou-se grande taxa de resistência aos antibióticos mais utilizados no tratamento. São necessários novos estudos no Brasil, com grupos geograficamente semelhantes, para a validação desses resultados.

PURPOSE: To assess the prevalence of Streptococcus agalactiae, a Group B streptococcus, in pregnant women, and their possible risk factors, as well as the impact of perinatal colonization and antimicrobial susceptibility. METHODS: We evaluated 213 pregnant women from 20 weeks of gestation, regardless of risk factors, attending a tertiary teaching hospital. The technique used was a single sterile swab to collect secretions from the vaginal and perianal regions. The newly obtained samples were stored in Stuart transport medium and taken to the laboratory, where they were inoculated in Todd-Hewitt selective medium supplemented with Gentamicin (8 ug/mL) and nalidixic acid (15 ug/mL), with subsequent cultivation on blood agar plates. The materials were tested with Gram, catalase with hydrogen peroxide and CAMP (Christie, Atkins, Munch-Petersen), and results were serologically confirmed with the Streptococcal Grouping Kit, Oxoid®. The positive samples were tested for antimicrobial susceptibility. We also assessed socioeconomic, reproductive, clinical, and obstetric variables, and newborn care. Statistical analysis was performed with Epi-Info 6.04. RESULTS: The prevalence of colonization obtained by field tests was 9.8 percent by CAMP test, but only 4.2 percent by serology. The only protective factor was white skin color (p=0.01, 0.45>OR>0.94, 95 percentCI). There was no difference in prevalence of Group B streptococcus regarding other reproductive and obstetric variables. Infection occurred in only one of the newborns from colonized mothers; although it was revealed infection with Pseudomonas spp. High resistance to ampicillin (4/9), cephalothin (4/9), penicillin (4/9), erythromycin (3/9), clindamycin (7/9), and cloramphenicol (1/9) was detected. CONCLUSIONS: The infection rate was lower than that found in other studies, although a high rate of resistance to antibiotics commonly used for treatment was detected. Since there are no studies on the prevalence of Group B streptococcus in Ceará, we cannot perform a comparative analysis of the population, and further studies are needed with geographically similar groups to validate these results.

[Prevalence of the colonization by Streptococcus agalactiae in pregnant women from a maternity in Ceará, Brazil, correlating with perinatal outcomes]. / Prevalência de colonização por Streptococcus agalactiae em gestantes atendidas em maternidade do Ceará, no Brasil, correlacionando com os resultados perinatais.

PURPOSE: To assess the prevalence of Streptococcus agalactiae, a Group B streptococcus, in pregnant women, and their possible risk factors, as well as the impact of perinatal colonization and antimicrobial susceptibility. METHODS: We evaluated 213 pregnant women from 20 weeks of gestation, regardless of risk factors, attending a tertiary teaching hospital. The technique used was a single sterile swab to collect secretions from the vaginal and perianal regions. The newly obtained samples were stored in Stuart transport medium and taken to the laboratory, where they were inoculated in Todd-Hewitt selective medium supplemented with Gentamicin (8 ug/mL) and nalidixic acid (15 ug/mL), with subsequent cultivation on blood agar plates. The materials were tested with Gram, catalase with hydrogen peroxide and CAMP (Christie, Atkins, Munch-Petersen), and results were serologically confirmed with the Streptococcal Grouping Kit, Oxoid®. The positive samples were tested for antimicrobial susceptibility. We also assessed socioeconomic, reproductive, clinical, and obstetric variables, and newborn care. Statistical analysis was performed with Epi-Info 6.04. RESULTS: The prevalence of colonization obtained by field tests was 9.8% by CAMP test, but only 4.2% by serology. The only protective factor was white skin color (p=0.01, 0.45>OR>0.94, 95%CI). There was no difference in prevalence of Group B streptococcus regarding other reproductive and obstetric variables. Infection occurred in only one of the newborns from colonized mothers; although it was revealed infection with Pseudomonas spp. High resistance to ampicillin (4/9), cephalothin (4/9), penicillin (4/9), erythromycin (3/9), clindamycin (7/9), and cloramphenicol (1/9) was detected. CONCLUSIONS: The infection rate was lower than that found in other studies, although a high rate of resistance to antibiotics commonly used for treatment was detected. Since there are no studies on the prevalence of Group B streptococcus in Ceará, we cannot perform a comparative analysis of the population, and further studies are needed with geographically similar groups to validate these results.

Pesquisa de anticorpos para o virus da AIDS em parturientes com vida sexual promíscua na área de Belém: estudo piloto / Research of antibodies for AIDS's viruses in parturient with promiscuos sexual life in the area of Belém

Estudaram-se 63 parturientes (entre 800 selecionadas) com história de vida sexual promíscua, quanto a presença de anticorpos para o vírus da AIDS. Utilizando-se método imunoenzimático competitivo ("Wellcozyme ant-HTL III")näo se detectaram amostras de soro positivo no grupo sob estudo. Soros do cordäo umbilical dos recém-natos, embora sistematicamente colhidos, näo foram testados face a total negatividade observada nos espécimes maternos