The emergency of SARS-CoV-2 in China started a novel challenge to the scientific community. As the virus turns pandemic, scientists try to map the cellular mechanisms and pathways of SARS-CoV-2 related to the pathogenesis of Coronavirus Disease 2019 (Covid-19). After transmembrane angiotensin-converting enzyme 2 (ACE2) has been found to be SARS-CoV-2 receptor, we hypothesized an immune-hematological mechanism for Covid-19 based on renin–angiotensin system (RAS) imbalance to explain clinical, laboratory and imaging findings on disease course. We believe that exaggerated activation of ACE/Angiotensin II (Ang II)/Angiotensin Type 1 (AT1) receptor RAS axis in line with reduction of ACE2/Angiotensin-(1-7)/Mas receptor may exert a pivotal role in the pathogenesis of Covid-19. In this perspective, we discuss potential mechanisms and evidence on this hypothesis.

The emergence of SARS-CoV-2/human/Wuhan/X1/2019, a virus belonging to the species Severe acute respiratory syndrome-related coronavirus, and the recognition of Coronavirus Disease 2019 (COVID-19) as a pandemic have highly increased the scientific research regarding the pathogenesis of COVID-19. The Renin Angiotensin System (RAS) seems to be involved in COVID-19 natural course, since studies suggest the membrane-bound Angiotensin-converting enzyme 2 (ACE2) works as SARS-CoV-2 cellular receptor. Besides the efforts of the scientific community to understand the virus' molecular interactions with human cells, few studies summarize what has been so far discovered about SARS-CoV-2 signaling mechanisms and its interactions with RAS molecules. This review aims to discuss possible SARS-CoV-2 intracellular signaling pathways, cell entry mechanism and the possible consequences of the interaction with RAS components, including Angiotensin II (Ang II), Angiotensin-(1-7) [Ang-(1-7)], Angiotensin-converting enzyme (ACE), ACE2, Angiotensin II receptor type-1 (AT1), and Mas Receptor. We also discuss ongoing clinical trials and treatment based on RAS cascade intervention. Data were obtained independently by the two authors who carried out a search in the PubMed, Embase, LILACS, Cochrane, Scopus, SciELO and the National Institute of Health databases using Medical Subject Heading terms as "SARS-CoV-2," "COVID-19," "Renin Angiotensin System," "ACE2," "Angiotensin II," "Angiotensin-(1-7)," and "AT1 receptor." Similarly to other members of Coronaviridae family, the molecular interactions between the pathogen and the membrane-bound ACE2 are based on the cleavage of the spike glycoprotein (S) in two subunits. Following the binding of the S1 receptor-binding domain (RBD) to ACE2, transmembrane protease/serine subfamily 2 (TMPRSS2) cleaves the S2 domain to facilitate membrane fusion. It is very likely that SARS-CoV-2 cell entry results in downregulation of membrane-bound ACE2, an enzyme that converts Ang II into Ang-(1-7). This mechanism can result in lung injury and vasoconstriction. In addition, Ang II activates pro-inflammatory cascades when binding to the AT1 Receptor. On the other

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Acute Kidney Injury (AKI) comprises a rapidly developed renal failure and is associated with high mortality rates. The Renin–Angiotensin System (RAS) plays a pivotal role in AKI, as the over-active RAS axis exerts major deleterious effects in disease progression. In this sense, the conversion of Angiotensin II (Ang II) into Angiotensin-(1-7) (Ang-(1-7)) by the Angiotensin-converting enzyme 2 (ACE2) is of utmost importance to prevent worse clinical outcomes. Previous studies reported the beneficial effects of oral diminazene aceturate (DIZE) administration, an ACE2 activator, in renal diseases models. In the present study, we aimed to evaluate the therapeutic effects of DIZE administration in experimental AKI induced by gentamicin (GM) in rats. Our findings showed that treatment with DIZE improved renal function and tissue damage by increasing Ang-(1-7) and ACE2 activity, and reducing TNF-α. These results corroborate with a raising potential of ACE2 activation as a strategy for treating AKI.

The last decade was crucial for our understanding of the renin-angiotensin-aldosterone system (RAAS) as a two-axis, counterregulatory system, divided into the classical axis, formed by angiotensin-converting enzyme (ACE), angiotensin II (Ang II), and the angiotensin type 1 receptor (AT1R), and the alternative axis comprising angiotensin-converting enzyme 2 (ACE2), angiotensin-(1-7) (Ang-(1-7)), and the Mas receptor. Breakthrough discoveries also took place, with other RAAS endopeptides being described, including alamandine and angiotensin A. In this review, we characterize the two RAAS axes and the role of their components in pediatric kidney diseases, including childhood hypertension (HTN), pediatric glomerular diseases, congenital abnormalities of the kidney and urinary tract (CAKUT), and chronic kidney disease (CKD). We also present recent findings on potential interactions between the novel coronavirus, SARS-CoV-2, and components of the RAAS, as well as potential implications of coronavirus disease 2019 (COVID-19) for pediatric kidney diseases.

Background: The survival of premature newborns increased in the last decades due to advances in neonatal care. The physiology of this group is still under investigation, once the incomplete organogenesis entails functional particularities that are not yet clarified by current clinical knowledge. The immature kidneys are especially susceptible to acute injury with potential long-term impacts. Current diagnostic parameters of acute kidney injury are limited among the preterm population. The commonly used serum creatinine protein constitutes a poor biomarker to predict early lesions as it is susceptible to several factors, including muscle mass and gestational age. Objective: The present review explores the evidence on nephrogenesis, renal function, and acute kidney injury in neonatology, as well as studies on renal function biomarkers and their potential application for diagnosis, follow-up, and prognosis in preterm newborns. Results: Premature newborns reach full-term gestational age with reduced number and quality of nephrons. Consequently, the glomerular filtration rate and tubular function become impaired and are proportional to the gestational age. Despite having a high incidence among the pediatric population, acute kidney injury is still underdiagnosed and poorly managed due to the absence of proper, sensible, and non-invasive biomarkers. Although cystatin C, NGAL, and KIM-1, are promising urinary markers, current literature remains inconsistent. Conclusion: Further research is needed to properly identify and standardize sensible and specific urinary biomarkers to better assess kidney function in preterm newborns.

Introdução: O câncer de mama é o tipo de neoplasia com maior incidência e mortalidade na população feminina no mundo. Observa-se aumento da incidência do câncer de mama e redução da mortalidade associados à detecção precoce. Objetivo: Analisar indicadores de rastreamento de câncer de mama a partir dos registros de mamografias realizadas em mulheres brasileiras, no período de junho de 2009 a julho de 2015. Método: Estudo transversal, utilizando dados secundários do Sistema de Informação do Controle do Câncer de Mama (Sismama), referentes aos registros dos exames de mamografia realizados pelo Sistema Único de Saúde (SUS) na população feminina entre junho de 2009 e julho de 2015. Foram calculadas as proporções de cada variável para compor os indicadores selecionados por ano. Resultados: Foram analisados 14.926.700 registros de mamografias, sendo 96,8% de rastreamento (MMGr) e 3,2% diagnósticas (MMGd). Pouco mais da metade das MMGr (52,5%) foram realizadas na faixa etária de 50 a 69 anos, seguida pela faixa etária de 40 a 49 anos (35,9%). Observou-se uma tendência de aumento na proporção de MMGr na faixa preconizada (50-69 anos) no período estudado, além de maior proporção de entrega do resultado do exame inferior a 30 dias (tanto para MMGd como MMGr), com diferenças entre as Regiões. Conclusão: O cumprimento das medidas propostas pelo Ministério da Saúde para diagnóstico precoce do câncer de mama não ocorre de maneira uniforme no território nacional. Emerge a necessidade de desenvolver estratégias em saúde que contemplem as inequidades existentes entre as Regiões do país.

The world is looking forward to a prompt response by the scientifi c community in order to overcome the fi rst pandemic of the 21 st century. This study aimed to provide an overview of scientifi c output on COVID-19 during its fi rst year. We assembled information regarding 60,830 articles related to COVID-19 indexed in the WoS database from January 24 to December 13, 2020. Only 4 countries accounted for about 60% of the articles (USA, China, Italy, and England) and 12 countries accounted for about 95% of the world scientifi c output on COVID-19 (USA,