Reactivity of zinc fingers in oxidizing environments: insight from molecular models through activation strain analysis.

The reactivity of Zn2+ tetrahedral complexes with H2O2 was investigated in silico, as first step for the process of their disruption. The substrates were chosen to represent the cores of three different zinc finger protein motifs, i.e., a Zn2+ ion coordinated to four cysteines (CCCC), to three cysteines and one histidine (CCCH), and to two cysteines and two histidines (CCHH). The cysteine and histidine ligands were further simplified to methyl thiolate and imidazole, respectively. H2O2 was chosen as oxidizing agent because of its biological role as metabolic product and species involved in signaling processes. The mechanism of oxidation of a coordinated cysteinate to sulfenate-κS and the trends for the different substrates were rationalized through activation strain analysis and energy decomposition analysis in the framework of scalar relativistic DFT calculations at ZORA-M06/TZ2P ae // ZORA-BLYP-D3(BJ)/TZ2P. CCCC is oxidized most easily, an outcome explained considering both electrostatic and orbital interactions. The isomerization to sulfenate-κO was attempted to assess whether this step may affect the ligand dissociation; but it was found to introduce a kinetic barrier without improving the energetics of the dissociation. Lastly, ligand exchange with free thiolates and selenolates was investigated as trigger for ligand dissociation, possibly leading to metal ejection.

Inhibition of the morphological transition of Candida spp. by riparins I-IV.

Candida spp. is an opportunistic pathogen capable of causing superficial to invasive infections. Morphological transition is one of the main virulence factors of this genus and, therefore, is an important variable to be considered in pharmacological interventions. Riparins I, II, III, and IV are alkamide-type alkaloids extracted from the unripe fruit of Aniba riparia, whose remarkable pharmacological properties were previously demonstrated. This work aimed to evaluate in silico and in vitro the inhibitory effects of Riparins on the morphological transition of Candida albicans, Candida tropicalis, and Candida krusei. Molecular docking was applied to analyze the inhibitory effects of riparins against proteins such as N-acetylglucosamine, CYP-51, and protein kinase A (PKA) using the Ramachandran plot. The ligands were prepared by MarvinSketch and Spartan software version 14.0, and MolDock Score and Rerank Score were used to analyze the affinity of the compounds. In vitro analyses were performed by culturing the strains in humid chambers in the presence of riparins or fluconazole (FCZ). The morphology was observed through optical microscopy, and the size of the hyphae was determined using the ToupView software. In silico analysis demonstrated that all riparins are likely to interact with the molecular targets: GlcNAc (>50%), PKA (>60%), and CYP-51 (>70%). Accordingly, in vitro analysis showed that these compounds significantly inhibited the morphological transition of all Candida strains. In conclusion, this study demonstrated that riparins inhibit Candida morphological transition and, therefore, can be used to overcome the pathogenicity of this genus.

Unveiling the promising anticancer activity of palladium(II)-aryl complexes bearing diphosphine ligands: a structure-activity relationship analysis.

In continuation of our previous works on the cytotoxic properties of organopalladium compounds, in this contribution we describe the first systematic study of the anticancer activity of Pd(II)-aryl complexes. To this end, we have prepared and thoroughly characterized a wide range of palladium derivatives bearing different diphosphine, aryl and halide ligands, developing, when necessary, specific synthetic protocols. Most of the synthesized compounds showed remarkable cytotoxicity towards ovarian and breast cancer cell lines, with IC50 values often comparable to or lower than that of cisplatin. The most promising complexes ([PdI(Ph)(dppe)] and [PdI(p-CH3-Ph)(dppe)]), characterized by a diphosphine ligand with a low bite angle, exhibited, in addition to excellent cytotoxicity towards cancer cells, low activity on normal cells (MRC5 human lung fibroblasts). Specific immunofluorescence tests (cytochrome c and H2AX assays), performed to clarify the possible mechanism of action of this class of organopalladium derivatives, seemed to indicate DNA as the primary cellular target, whereas caspase 3/7 assays proved that the complex [PdI(Ph)(dppe)] was able to promote intrinsic apoptotic cell death. A detailed molecular docking analysis confirmed the importance of a diphosphine ligand with a reduced bite angle to ensure a strong DNA-complex interaction. Finally, one of the most promising complexes was tested towards patient-derived organoids, showing promising ex vivo cytotoxicity.

Diphenyl Diselenide Attenuates Mitochondrial Damage During Initial Hypoxia and Enhances Resistance to Recurrent Hypoxia.

Hypoxia plays a significant role in the development of various cerebral diseases, many of which are associated with the potential risk of recurrence due to mitochondrial damage. Conventional drug treatments are not always effective for hypoxia-related brain diseases, necessitating the exploration of alternative compounds. In this study, we investigated the potential of diphenyl diselenide [(PhSe)2] to ameliorate locomotor impairments and mitigate brain mitochondrial dysfunction in zebrafish subjected to hypoxia. Additionally, we explored whether these improvements could confer resistance to recurrent hypoxia. Through a screening process, an appropriate dose of (PhSe)2 was determined, and animals exposed to hypoxia received a single intraperitoneal injection of 100 mg/kg of the compound or vehicle. After 1 h from the injection, evaluations were conducted on locomotor deficits, (PhSe)2 content, mitochondrial electron transport system, and mitochondrial viability in the brain. The animals were subsequently exposed to recurrent hypoxia to assess the latency time to hypoxia symptoms. The findings revealed that (PhSe)2 effectively crossed the blood-brain barrier, attenuated locomotor deficits induced by hypoxia, and improved brain mitochondrial respiration by modulating complex III. Furthermore, it enhanced mitochondrial viability in the telencephalon, contributing to greater resistance to recurrent hypoxia. These results demonstrate the beneficial effects of (PhSe)2 on both hypoxia and recurrent hypoxia, with cerebral mitochondria being a critical target of its action. Considering the involvement of brain hypoxia in numerous pathologies, (PhSe)2 should be further tested to determine its effectiveness as a potential treatment for hypoxia-related brain diseases.

Investigation of the cytotoxicity, genotoxicity and antioxidant prospects of JM-20 on human blood cells: A multi-target compound with potential therapeutic applications.

JM-20 is a 1,5-benzodiazepine compound fused to a dihydropyridine fraction with different pharmacological properties. However, its potential toxic effects on blood cells have not yet been reported. Thus, the present study aimed to investigate, for the first time, the possible cytotoxicity of JM-20 through cell viability, cell cycle, morphology changes, reactive species (RS) to DCFH-DA, and lipid peroxidation in human leukocytes, its hemolytic effect on human erythrocytes, and its potential DNA genotoxicity using plasmid DNA in vitro. Furthermore, the compound's ability to reduce the DPPH radical was also measured. Human blood was obtained from healthy volunteers (30 ± 10 years old), and the leukocytes or erythrocytes were immediately isolated and treated with different concentrations of JM-20. A cytoprotective effect was exhibited by 10 µM JM-20 against 1 mM tert-butyl hydroperoxide (t-but-OOH) in the leukocytes. However, the highest tested concentrations of the compound (20 and 50 µM) changed the morphology and caused a significant decrease in the cell viability of leukocytes (p < 0.05, in comparison with Control). All tested concentrations of JM-20 also resulted in a significant increase in intracellular RS as measured by DCFH-DA in these cells (p < 0.05, in comparison with Control). On the other hand, the results point out a potent antioxidant effect of JM-20, which was similar to the classical antioxidant α-tocopherol. The IC50 value of JM-20 against the lipid peroxidation induced by (FeII) was 1.051 µM ± 0.21, while the IC50 value of α-tocopherol in this parameter was 1.065 µM ± 0.34. Additionally, 50 and 100 µM JM-20 reduced the DPPH radical in a statistically similar way to the 100 µM α-tocopherol (p < 0.05, in comparison with the control). No significant hemolysis in erythrocytes, no cell cycle changes in leukocytes, and no genotoxic effects in plasmid DNA were induced by JM-20 at any tested concentration. The in silico pharmacokinetic and toxicological properties of JM-20, derivatives, and nifedipine were also studied. Here, our findings demonstrate that JM-20 and its putative metabolites exhibit similar characteristics to nifedipine, and the in vitro and in silico data support the low toxicity of JM-20 to mammals.

JM-20 potently prevents the onset of caffeine-induced anxiogenic phenotypes in zebrafish (Danio rerio).

Anxiety is among the most prevalent mental disorders present in the general population. Benzodiazepines are the most commonly prescribed drugs for the treatment of anxiety. Using zebrafish as a model organism, we investigated the anxiolytic activity of JM-20, a novel hybrid molecule with a 1,5-benzodiazepine ring fused to a dihydropyridine moiety. Firstly, we carried out some assays to analyze the possible toxicity mediated by JM-20. For this, zebrafish were exposed to different JM-20 concentrations (0-5 µM) for 96 h. Then, using the novel tank test, we evaluated both locomotor and anxiety-like behavior of the animals. Furthermore, brain, liver and plasma were removed to assess toxicity parameters. JM-20 exposure did not cause changes on novel tank, and also did not alter brain viability, hepatic LDH and plasma ALT levels. Afterward, we investigated whether a pre-exposure to JM-20 would prevent the anxiogenic effect evoked by caffeine. In the novel tank test, caffeine significantly decreased the time spent at the top, as well as the number of transitions to the top area. Moreover, caffeine decreased both the total and average time spent in the lit area, as well as increased the number of risk episodes evaluated by the light-dark test. Whole-body cortisol levels were also increased by caffeine exposure. Interestingly, pre-treatment with JM-20 abolished all alterations induced by caffeine. The anxiolytic effect profile of JM-20 was similar to those found for diazepam (positive control). Our findings show, for the first time, the anxiolytic effect of JM-20 in zebrafish, and its relationship with cortisol regulation.

Screening for Differentially Expressed Memory Genes on a Diabetes Model Induced by High-Sugar Diet in Drosophila melanogaster: Potential Markers for Memory Deficits.

Type 2 diabetes mellitus (T2DM) has been shown to affect a series of cognitive processes including memory, increasing the risk for dementia, particularly Alzheimer's disease (AD). Although increasing evidence has supported that both diseases share common features, the pathophysiological mechanisms connecting these two disorders remain to be fully elucidated. Herein, we used Drosophila melanogaster fed on a high-sugar diet (HSD) to mimic T2DM, and investigate its effects on memory as well as identify potential molecular players associated with the memory deficits induced by HSD. Flies hatched from and reared on HSD for 7 days had a substantial decrease in short-term memory (STM). The screening for memory-related genes using transcriptome data revealed that HSD altered the expression of 33% of memory genes in relation to the control. Among the differentially expressed genes (DEGs) with a fold change (FC) higher than two, we found five genes, related to synapse and memory trace formation, that could be considered strong candidates to underlie the STM deficits in HSD flies: Abl tyrosine kinase (Abl), bruchpilot (Brp), minibrain (Mnb), shaker (Sh), and gilgamesh (Gish). We also analyzed genes from the dopamine system, one of the most relevant signaling pathways for olfactory memory. Interestingly, the flies fed on HSD presented a decreased expression of the Tyrosine hydroxylase (Ple) and Dopa decarboxylase (Ddc) genes, signals of a possible dopamine deficiency. In this work, we present promising biomarkers to investigate molecular networks shared between T2DM and AD.

Should ebselen be considered for the treatment of mercury intoxication? A minireview.

Mercury is a ubiquitous environmental contaminant and can be found in inorganic (Hg0, Hg+ and Hg2+) and organic forms (chiefly CH3Hg+ or MeHg+). The main route of human, mammals and bird exposure occurs via predatory fish ingestion. Occupational exposure to Hg0 (and Hg2+) can also occur; furthermore, in gold mining areas the exposure to inorganic Hg can also be high. The toxicity of electrophilic forms of Hg (E+Hg) is mediated by disruption of thiol (-SH)- or selenol (-SeH)-containing proteins. The therapeutic approaches to treat methylmercury (MeHg+), Hg0 and Hg2+ are limited. Here we discuss the potential use of ebselen as a potential therapeutic agent to lower the body burden of Hg in man. Ebselen is a safe drug for humans and has been tested in clinical trials (for instance, brain ischemia, noise-induce hearing loss, diabetes complications, bipolar disorders) at doses varying from 400 to 3600 mg per day. Two clinical trials with ebselen in moderate and severe COVID are also approved. Ebselen can be metabolized to an intermediate with -SeH (selenol) functional group, which has a greater affinity to electrophilic Hg (E+Hg) forms than the available thiol-containing therapeutic agents. Accordingly, as observed in vitro and rodent models in vivo, Ebselen exhibited protective effects against MeHg+, indicating its potential as a therapeutic agent to treat MeHg+ overexposure. The combined use of ebselen with thiol-containing molecules (e.g. N-acetylcysteine and enaramide)) is also commented, because they can have synergistic protective effects against MeHg+.

Genotoxicity and cytotoxicity potential of organoselenium compounds in human leukocytes in vitro.

In the current work, cytotoxicity and genotoxicity of different organoselenium compounds were examined using Trypan blue exclusion and alkaline comet assays with silver staining respectively. Leukocytes were subjected to a 3-hour incubation with organoselenium compounds at concentrations of 1, 5, 10, 25, 50, and 75 µM, or with the control vehicle (DMSO), at a temperature of 37 °C. The viability of the cells was evaluated using the Trypan blue exclusion method, while DNA damage was analyzed through the alkaline comet assay with silver staining. The exposure of leukocytes to different organoselenium compounds including i.e. (Z)-N-(pyridin-2-ylmethylene)-1-(2-((2-(1-((E)-pyridin-2-ylmethyleneamino)ethyl)phenyl)diselanyl)phenyl)ethanamine (C1), 2,2'(1Z,1'E)-(1,1'-(2,2'-diselanediylbis(2,1-phenylene))bis(ethane-1,1-diyl)) bis(azan-1-yl-1-ylidene)bis -methan-1-yl-1-ylidene)diphenol (C2), and dinaphthyl diselenide (NapSe)2, At concentrations ranging from 1 to 5 µM, no significant DNA damage was observed, as indicated by the absence of a noteworthy increase in the Damage Index (DI). Our results suggest that the organoselenium selenium compounds tested were not genotoxic and cytotoxic to human leukocytes in vitro at lower concentration. This study offers further insights into the genotoxicity profile of these organochalcogens in human leukocytes. Their genotoxicity and cytotoxicity effects at higher concentration are probably mediated through reactive oxygen species generation and their ability to catalyze thiol oxidation.

In silico evidences of Mpro inhibition by a series of organochalcogen-AZT derivatives and their safety in Caenorhabditis elegans.

BACKGROUND: The new coronavirus (SARS-CoV-2) pandemic emerged in 2019 causing millions of deaths. Vaccines were quickly developed and made available in 2021. Despite the availability of vaccines, some subjects refuse to take the immunizing or present comorbities, therefore developing serious cases of COVID-19, which makes necessary the development of antiviral drugs. Previous studies have demonstrated that ebselen, a selenium-containing molecule, can inhibit SARS-CoV-2 Mpro. In addition, selenium is a trace element that has antiviral and anti-inflammatory properties. Zidovudine (AZT) has been widely used against HIV infections and its action against SARS-CoV-2 may be altered by the structural modification with organochalcogen moieties, but this hypothesis still needs to be tested. METHODS: In the present work we evaluated the Mpro inhibition capacity (in silico), the safety and antioxidant effect of six organochalcogen AZT-derivatives using the free-living nematode Caenorhabditis elegans, through acute (30 min) and chronic (48) exposure protocols. RESULTS: We observed that the molecules were safe at a concentration range of 1-500 µM and did not alter any toxicological endpoint evaluated. Furthermore, the molecules are capable to decrease the ROS formation stimulated by hydrogen peroxide, to modulate the expression of important antioxidant enzymes such superoxide-dismutase-3 and glutathione S-transferese-4 and to stimulate the translocation of the DAF-16 to the cell nucleus. In addition, the molecules did not deplete thiol groups, which reinforces their safety and contribution to oxidative stress resistance. CONCLUSIONS: We have found that compounds S116l (a Tellurium AZT-derivative) and S116h (a Selenium-AZT derivative) presented more promising effects both in silico and in vivo, being strong candidates for further in vivo studies.

Computational analysis of the interactions between Ebselen and derivatives with the active site of the main protease from SARS-CoV-2.

The main protease (Mpro) of the novel coronavirus SARS-CoV-2 is a key target for developing antiviral drugs. Ebselen (EbSe) is a selenium-containing compound that has been shown to inhibit Mpro in vitro by forming a covalent bond with the cysteine (Cys) residue in the active site of the enzyme. However, EbSe can also bind to other proteins, like albumin, and low molecular weight compounds that have free thiol groups, such as Cys and glutathione (GSH), which may affect its availability and activity. In this study, we analyzed the Mpro interaction with EbSe, its analogues, and its metabolites with Cys, GSH, and albumin by molecular docking. We also simulated the electronic structure of the generated molecules by density functional theory (DFT) and explored the stability of EbSe and one of its best derivatives, EbSe-2,5-MeClPh, in the catalytic pocket of Mpro through covalent docking and molecular dynamics. Our results show that EbSe and its analogues bound to GSH/albumin have larger distance between the selenium atom of the ligands and the sulfur atom of Cys145 of Mpro than the other compounds. This suggests that EbSe and its GSH/albumin-analogues may have less affinity for the active site of Mpro. EbSe-2,5-MeClPh was found one of the best molecules, and in molecular dynamics simulations, it showed to undergo more conformational changes in the active site of Mpro, in relation to EbSe, which remained stable in the catalytic pocket. Moreover, this study also reveals that all compounds have the potential to interact closely with the active site of Mpro, providing us with a concept of which derivatives may be promising for in vitro analysis in the future. We propose that these compounds are potential covalent inhibitors of Mpro and that organoselenium compounds are molecules that should be studied for their antiviral properties.

Ebselen and Diphenyl Diselenide Inhibit SARS-CoV-2 Replication at Non-Toxic Concentrations to Human Cell Lines.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was the causative agent of the COVID-19 pandemic, a global public health problem. Despite the numerous studies for drug repurposing, there are only two FDA-approved antiviral agents (Remdesivir and Nirmatrelvir) for non-hospitalized patients with mild-to-moderate COVID-19 symptoms. Consequently, it is pivotal to search for new molecules with anti-SARS-CoV-2 activity and to study their effects in the human immune system. Ebselen (Eb) is an organoselenium compound that is safe for humans and has antioxidant, anti-inflammatory, and antimicrobial properties. Diphenyl diselenide ((PhSe)2) shares several pharmacological properties with Eb and is of low toxicity to mammals. Herein, we investigated Eb and (PhSe)2 anti-SARS-CoV-2 activity in a human pneumocytes cell model (Calu-3) and analyzed their toxic effects on human peripheral blood mononuclear cells (PBMCs). Both compounds significantly inhibited the SARS-CoV-2 replication in Calu-3 cells. The EC50 values for Eb and (PhSe)2 after 24 h post-infection (hpi) were 3.8 µM and 3.9 µM, respectively, and after 48 hpi were 2.6 µM and 3.4 µM. These concentrations are safe for non-infected cells, since the CC50 values found for Eb and (PhSe)2 on Calu-3 were greater than 200 µM. Importantly, the concentration rates tested on viral replication were not toxic to human PBMCs. Therefore, our findings reinforce the efficacy of Eb and demonstrate (PhSe)2 as a new candidate to be tested in future trials against SARS-CoV-2 infection/inflammation conditions.

Night fasting as an alternative to improve nutritional support and glycaemic control in hospitalised patients with exclusive enteral nutrition.

BACKGROUND: Enteral nutrition (EN) assists in the nutritional status of hospitalised patients unable to feed orally. The aim of this study was to determine which method-continuous EN or discontinuous EN, a diet in which the infusion is discontinued for 4h during the night,-is more effective in meeting nutrient recommendations and improving glycaemic control and biochemical parameters related to protein anabolism. METHODS: Patients were divided into two groups: discontinuous (EN administered in mL/h, 18h/day, 4-h night fasting) and continuous (EN administered in mL/h, 22h/day). All patients with EN receive the diet over a 22-h daily period, in which the diet is suspended for two hours/day for daily hospital routines such as bathing, and physiotherapy, and followed for seven days. Evaluated data: prescribed and administered volume, calories, protein, and fibre; capillary blood glucose; erythrogram; serum albumin. RESULTS: 52 patients were followed-up, with 23 (44.2%) in the discontinuous group and 29 (55.8%) in the continuous group. Compared with the continuous group, the discontinuous group received volumes closer to those prescribed, equal or higher calories, and more protein. The capillary glucose values were within the reference range in the discontinuous group, while the continuous group presented elevated values. Both groups presented hypoalbuminaemia, haemoglobin, and haematocrit below the reference values; however, in the discontinuous group, the serum albumin values improved during hospitalisation relative to the continuous. CONCLUSIONS: The method involving discontinuation of EN for 4h was more effective in meeting nutrient recommendations compared with the continuous method. Additionally, in the discontinuous group, we observed a better control of glycaemia when compared to that of the continuous group.

Acid sphingomyelinase (ASM) and COVID-19: A review of the potential use of ASM inhibitors against SARS-CoV-2.

In the last 2 years, different pharmacological agents have been indicated as potential inhibitors of SARS-CoV-2 in vitro. Specifically, drugs termed as functional inhibitors of acid sphingomyelinase (FIASMAs) have proved to inhibit the SARS-CoV-2 replication using different types of cells. Those therapeutic agents share several chemical structure characteristics and some well-known representatives are fluoxetine, escitalopram, fluvoxamine, and others. Most of the FIASMAs are primarily used as effective therapeutic agents to treat different pathologies, therefore, they are natural drug candidates for repositioning strategy. In this review, we summarize the two main proposed mechanisms mediating acid sphingomyelinase (ASM) inhibition and how they can explain the inhibition of SARS-CoV-2 replication by FIASMAs. The first mechanism implies a disruption in the lysosomal pH fall as the endosome-lysosome moves toward the interior of the cell. In fact, changes in cholesterol levels in endosome-lysosome membranes, which are associated with ASM inhibition is thought to be mediated by lysosomal proton pump (ATP-ase) inactivation. The second mechanism involves the formation of an extracellular ceramide-rich domain, which is blocked by FIASMAs. The ceramide-rich domains are believed to facilitate the SARS-CoV-2 entrance into the host cells.

Diphenyl Diselenide and SARS-CoV-2: in silico Exploration of the Mechanisms of Inhibition of Main Protease (Mpro) and Papain-like Protease (PLpro).

The SARS-CoV-2 pandemic has prompted global efforts to develop therapeutics. The main protease of SARS-CoV-2 (Mpro) and the papain-like protease (PLpro) are essential for viral replication and are key targets for therapeutic development. In this work, we investigate the mechanisms of SARS-CoV-2 inhibition by diphenyl diselenide (PhSe)2 which is an archetypal model of diselenides and a renowned potential therapeutic agent. The in vitro inhibitory concentration of (PhSe)2 against SARS-CoV-2 in Vero E6 cells falls in the low micromolar range. Molecular dynamics (MD) simulations and density functional theory (DFT) calculations [level of theory: SMD-B3LYP-D3(BJ)/6-311G(d,p), cc-pVTZ] are used to inspect non-covalent inhibition modes of both proteases via π-stacking and the mechanism of covalent (PhSe)2 + Mpro product formation involving the catalytic residue C145, respectively. The in vitro CC50 (24.61 µM) and EC50 (2.39 µM) data indicate that (PhSe)2 is a good inhibitor of the SARS-CoV-2 virus replication in a cell culture model. The in silico findings indicate potential mechanisms of proteases' inhibition by (PhSe)2; in particular, the results of the covalent inhibition here discussed for Mpro, whose thermodynamics is approximatively isoergonic, prompt further investigation in the design of antiviral organodiselenides.

Profile of Maternal Mortality of COVID-19 in Ceará, in the Period of 2020.

The aim of this paper is to describe the profile of maternal mortality of COVID-19 in the state of Ceará, Brazil, in the period 2020. Ecological, exploratory, cross-sectional study, with secondary data from the Influenza Epidemiological Surveillance Information System, were made available by the Obstetric Observatory Brazilian COVID-19. A total of 485 pregnant and postpartum women were included, and the analysis considered the notifications from the year 2020. The variables of interest and the outcome (death/cure by COVID-19) were analyzed in a descriptive way. Most pregnant and postpartum women were between 20 and 35 years old, brown/white skin color and residing in an urban area. The proportion of deaths was 5.8% in the year 2020. In that period, the rates of hospitalization in the ward increased by 95.5%, 12.6% of hospitalization in the Unit of Intensive Care (ICU), and 7.2% needed invasive ventilatory support. Maternal mortality from COVID-19 suggests an emergency in terms of the development of health actions and policies due to the aggravation and risks due to this disease.

COVID-19 in Rio de Janeiro, Brazil: a perspective on epidemiological events / COVID-19 no Rio de Janeiro, Brasil: uma perspectiva sobre eventos epidemiológicos

Introduction: the progression of SARS-CoV-2 highlighted the Americas region for the number of COVID-19 cases and deaths. In Brazil, the Southeast region was one of the most affected, especially the state of Rio de Janeiro, due to its cosmopolitan characteristics.Objective: to analyze temporal variations in the incidence, mortality and lethality of COVID-19 in the state of Rio de Janeiro from January 2020 to December 2022.Methods: ecological time-series study with publicly available data on COVID-19 cases and deaths. Crude incidence, mortality, and fatality rates, and estimates of percent daily change (DPC) were analyzed using Prais-Winsten linear regression. With calculation of crude rates were performed using Microsoft Excel 2019, and DPC estimates were performed using STATA MP 17.0 software.Results: 2.5 million cases and 76 thousand COVID-19 deaths were confirmed in the state of Rio de Janeiro from 2020 to 2022, with lethality declining from 4.89% to 0.60%. The highest lethality occurred in May 2020 (11.59%), October 2021 (9.13%) and March 2022 (6.78%), showing a stationary trend. In 2020, incidence and mortality rates peaked in December (797.76 per 100,000 inhabitants) and May (43.96 per 100,000 inhabitants), respectively, followed by subsequent declines. Incidence trend was increasing in 2020 and stationary in 2022, while mortality decreased in 2021 and 2022 after stability in 2020.Conclusion: The incidence of COVID-19 peaked in 2020 and subsequently declined, suggesting partial transmission control. Mortality stabilized after 2020, indicating evolution in health care. Lethality showed a stationary trend, indicating an improvement in hospital capacity. The divergent behavior of the epidemiological indicators reflected the complex dynamics of the pandemic in the analyzed state. There were 790 thousand deaths from COVID-19 in the State of Rio de Janeiro in the period from 2020 to 2022.

Introdução: a progressão do SARS-CoV-2 destacou a região das Américas pelo número de casos e óbitos de COVID-19. No Brasil, a região Sudeste foi uma das mais afetadas, em especial o estado do Rio de Janeiro, devido suas características cosmopolitas.Objetivo: analisar as variações temporais da incidência, mortalidade e letalidade da COVID-19 no estado do Rio de Janeiro no período de janeiro de 2020 a dezembro de 2022.Método: estudo ecológico de séries temporais com dados de acesso público de casos e óbitos de COVID-19. Analisou-se as taxas brutas de incidência, mortalidade e letalidade, e estimativas das taxas de variação percentual diária (DPC) utilizando a regressão linear de Prais-Winsten. Para o cálculo das taxas brutas usou-se o aplicativo Microsoft Excel 2019, e na estimativa da DPC o software STATA MP 17.0.Resultados: foram confirmados 2,5 milhões de casos e 76 mil óbitos por COVID-19 no estado do Rio de Janeiro, no período de 2020 a 2022, com letalidade declinando de 4,89% para 0,60%. A maior letalidade ocorreu em maio de 2020 (11,59%), outubro de 2021 (9,13%) e março de 2022 (6,78%), com tendência estacionária no período. Em 2020, as taxas de incidência e mortalidade, atingiu pico em dezembro (797,76/100 mil hab.), com posterior declínio e em maio (43,96/100 mil hab.), também com posterior queda, respectivamente. A tendência de incidência foi crescente em 2020 e estacionária em 2022, a mortalidade decresceu em 2021 e 2022, após estabilidade em 2020.Conclusão: a incidência de COVID-19 atingiu pico em 2020 e decresceu posteriormente, sugerindo controle parcial da transmissão. A mortalidade se estabilizou após 2020, indicando evolução da assistência à saúde. A letalidade apresentou tendência estacionária no período, sinalizando melhoria da capacidade hospitalar. O comportamento divergente dos indicadores epidemiológicos refletiu a complexa dinâmica da pandemia no estado do Rio de Janeiro. Houve 790 mil óbitos por COVID-19 no Estado do Rio de Janeiro no período de 2020 a 2022.

Prevalence of diabetic foot and its risk factors in the state of espirito santo, brazil

Introdução: O Pé Diabético (PD) é a principal causa de amputações não traumáticas nos países ocidentais, causando morte ou incapacidade física e mental, má qualidade de vida e alto custo para a sociedade. Objetivo: Analisar a prevalência de DF e fatores de risco relacionados na população diabética residente no Estado do Espírito Santo, Brasil. Métodos: Estudo transversal, descritivo, com delineamento de série temporal, utilizando dados secundários de morbidade de indivíduos com DF residentes no Estado do Espírito Santo, cadastrados e acompanhados pelo Sistema de Cadastro e Acompanhamento de Hipertensos e Diabéticos. Resultados: Dos 64.196 diabéticos, 3,9% tinham DM tipo 1, 10,9% DM tipo 2 e 85,2% eram hipertensos. A prevalência de DF foi de 2,9% no DM tipo 1, 3,3% no DM tipo 2 e 4,5% no DM com hipertensão. Maiores taxas de DF foram observadas no sexo masculino, com idade acima de 60 anos no DM tipo 1 e tipo 2, e até 19 anos no DM com hipertensão, tabagismo, sedentarismo, Infarto Agudo do Miocárdio (IAM), AVC e Doença Renal Crônica (DRC) ). Nos indivíduos com excesso de peso, a prevalência de DF foi maior apenas no DM tipo 1. Houve associação significativa em todas as variáveis exceto sobrepeso em ambos os tipos de DM, sedentarismo e acidente vascular cerebral no DM tipo 1. Conclusão: Os achados mostraram importantes prevalências de DF, com maior concentração em homens com mais de 60 anos, sobre tabagismo, sedentarismo, IAM, AVC e DRC, com associação estatística significativa nas variáveis analisadas, com exceção do excesso de peso em ambos os tipos de DM, como bem como sedentarismo e acidente vascular cerebral no DM tipo 1.

Introduction: Diabetic Foot (DF) is the leading cause of non-traumatic amputations in Western countries, causing death or physical and mental disability, poor quality of life and high cost to society. Objetive: To analyze the prevalence of DF and related risk factors in the diabetic population residing in Espírito Santo State, Brazil. Methods: Cross-sectional, descriptive study with time series design, using secondary data on morbidity of individuals with DF living in the State of Espírito Santo, registered and followed by the Hypertensive and Diabetic Registration and Monitoring System. Results: From 64,196 diabetic patients, 3.9% had Type 1 DM, 10.9% Type 2 DM and 85.2% had hypertension. The prevalence of DF was 2.9% in type 1 DM, 3.3% in type 2 DM and 4.5% in DM with hypertension. Higher rates of DF were observed in males, aged over 60 years in type 1 and type 2 DM, and up to 19 years in DM with hypertension, smoking, sedentary lifestyle, Acute Myocardial Infarction (AMI), stroke and Cronic Kidney disease (CKD). In overweight individuals, the prevalence of DF was higher only in type 1 DM. There was a significant association in all variables except overweight in both types of DM, sedentary lifestyle and stroke in type 1 DM. Conclusion: Findings showed important prevalence of DF, with higher concentration in men older than 60 years, on smoking, sedentary lifestyle, AMI, stroke and CKD, with significant statistical association in the analized variables, except for overweight in both types of DM, as well as sedentary lifestyle and stroke in type 1 DM.