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Since the COVID-19 pandemic emerged, vaccination has been the core strategy to mitigate the spread of SARS-CoV-2 in humans. This paper analyzes the impact of COVID-19 vaccination on hospitalizations and deaths in the state of Rio Grande do Norte, Brazil. We analyzed data from 23,516 hospitalized COVID-19 patients diagnosed between April 2020 and August 2021. We excluded the data from patients hospitalized through direct occupancy, unknown outcomes, and unconfirmed COVID-19 cases, resulting in data from 12,635 patients cross-referenced with the immunization status during hospitalization. Our results indicated that administering at least one dose of the immunizers was sufficient to significantly reduce the occurrence of moderate and severe COVID-19 cases among patients under 59 years. Considering the partially or fully immunized patients, the mean age is similar between the analyzed groups, despite the occurrence of comorbidities and higher than that observed among not immunized patients. Thus, immunized patients present lower Unified Score for Prioritization (USP) levels when diagnosed with COVID-19. Our data suggest that COVID-19 vaccination significantly reduced the hospitalization and death of elderly patients (60+ years) after administration of at least one dose. Comorbidities do not change the mean age of moderate/severe COVID-19 cases and the days required for the hospitalization of these patients.
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COVID-19 , Pandemias , Humanos , Idoso , Recém-Nascido , Pandemias/prevenção & controle , SARS-CoV-2 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/uso terapêutico , Brasil/epidemiologia , Hospitalização , VacinaçãoRESUMO
PURPOSE: This work investigated the endocytic pathways taken by poly(isobutylcyanoacrylate) (PIBCA) nanoparticles differing in their surface composition and architecture, assuming that this might determine their efficiency of intracellular drug delivery. METHODS: Nanoparticles (A0, A25, A100, R0, R25 ) were prepared by anionic or redox radical emulsion polymerization using mixtures of dextran and fucoidan (0, 25, 100 % in fucoidan). Cell uptake was evaluated by incubating J774A.1 macrophages with nanoparticles. Endocytic pathways were studied by incubating cells with endocytic pathway inhibitors (chlorpromazine, genistein, cytochalasin D, methyl-ß-cyclodextrin and nocodazole) and nanoparticle uptake was evaluated by flow cytometry and confocal microscopy. RESULTS: The fucoidan-coated PIBCA nanoparticles A25 were internalized 3-fold more efficiently than R25 due to the different architecture of the fucoidan chains presented on the surface. Different fucoidan density and architecture led to different internalization pathway preferred by the cells. Large A100 nanoparticles with surface was covered with fucoidan chains in a loop and train configuration were internalized the most efficiently, 47-fold compared with A0, and 3-fold compared with R0 and R25 through non-endocytic energy-independent pathways and reached the cell cytoplasm. CONCLUSION: Internalization pathways of PIBCA nanoparticles by J774A.1 macrophages could be determined by nanoparticle fucoidan surface composition and architecture. In turn, this influenced the extent of internalization and localization of accumulated nanoparticles within cells. The results are of interest for rationalizing the design of nanoparticles for potential cytoplamic drug delivery by controlling the nature of the nanoparticle surface.
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Nanopartículas , Sistemas de Liberação de Medicamentos , Emulsões , PolissacarídeosRESUMO
INTRODUCTION: Validity and reproducibility of the clinician's eye (CE) to diagnose patella alta (PA) on a lateral knee radiography (radiograph) is unknown. METHODS: Cross-sectional study of 46 lateral knee x-rays. Three blind observers used CE, Insall-Salvati (IS), modified Insall-Salvati (mIS), and Caton-Deschamps (C-D) to determine patellar height. Sensitivity and specificity of each observer was compared with the musculoskeletal radiologist's C-D measurements. Intraobserver and interobserver agreement were assessed with intraclass correlation coefficient and Fleiss κ, respectively. Time needed to estimate patellar height for every method was recorded in seconds. Statistical differences between observers were calculated with a generalized estimating equation. Analysis of variance and post hoc Bonferroni test compared duration of each method (P < 0.05). Data were analyzed using Stata 15 (StataCorp). RESULTS: CE, IS, mIS, and C-D's sensitivity and specificity values are as follows: 77%, 92%; 94%, 52%; 67%, 58%; and 53%, 89%, respectively. Intraclass correlation coefficient and Fleiss κ of CE, IS, mIS, and C-D values are as follows: 0.66 and 0.43, 0.88 and 0.68, 0.54 and 0.09, and 0.68 and 0.59, respectively. CE was the second most sensitive and most specific method for diagnosis of PA, with moderate intraobserver and interobserver agreement. IS was the most sensitive method with good intraobserver and interobserver agreement. CE was significantly faster (P < 0.05) than all other conventional radiographic ratios. CONCLUSION: CE's sensitivity increases with observer's experience and is highly specific. If normal patellar height is diagnosed, no other ratios are necessary, even in the less experienced clinician. Intraobserver and interobserver reproducibilities were moderate and only inferior to the IS ratio. In case patellar height is uncertain with the CE, the IS ratio is the most sensitive and reproducible method to confirm the diagnosis of PA.
Assuntos
Patela , Estudos Transversais , Patela/diagnóstico por imagem , Radiografia , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Mass spectrometry imaging (MSI) of neurotransmitters has so far been mainly performed by matrix-assisted laser desorption/ionization (MALDI) where derivatization reagents, deuterated matrix and/or high resolution, or tandem MS have been applied to circumvent problems with interfering ion peaks from matrix and from isobaric species. We herein describe the application of desorption electrospray ionization mass spectrometry imaging (DESI)-MSI in rat brain coronal and sagittal slices for direct spatial monitoring of neurotransmitters and choline with no need of derivatization reagents and/or deuterated materials. The amino acids γ-aminobutyric (GABA), glutamate, aspartate, serine, as well as acetylcholine, dopamine, and choline were successfully imaged using a commercial DESI source coupled to a hybrid quadrupole-Orbitrap mass spectrometer. The spatial distribution of the analyzed compounds in different brain regions was determined. We conclude that the ambient matrix-free DESI-MSI is suitable for neurotransmitter imaging and could be applied in studies that involve evaluation of imbalances in neurotransmitters levels. Graphical Abstract á .
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Encéfalo/fisiologia , Neurotransmissores/análise , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Animais , Química Encefálica , Ratos , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
Recently, 3-nitrobenzonitrile (3-NBN) has been used to improve sensitivity of sonic-spray ionization mass spectrometry. Easy ambient sonic-spray ionization (EASI) is one of the simplest, gentlest and most used spray-based desorption/ionization ambient techniques, but limited sensitivity has been commonly taken as its major drawback. Herein we investigate the use of 3-NBN as a dopant in EASI-MS for improved sensitivity. Using a few typical EASI samples as test cases, the presence of 10 ppm (µg ml(-1) ) of 3-NBN in the spray solvent showed two to fourfold gains in EASI-MS sensitivity as measured both by total ion current and S/N ratios, accompanied with significant reductions in chemical noise. Sensitivity for DESI using 3-NBN as a dopant also improved and dopant DESI versus dopant EASI sensitivities were compared. The use of solvent dopants seems therefore to be a promising strategy to improve sensitivity for spray-based ambient MS techniques. Copyright © 2015 John Wiley & Sons, Ltd.
Assuntos
Nitrilas/química , Nitrobenzenos/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Biocombustíveis/análise , Desenho de Equipamento , Glicerofosfolipídeos/análise , Indicadores e Reagentes/química , Azeite de Oliva/análise , Solventes/química , Solventes/classificação , Espectrometria de Massas por Ionização por Electrospray/instrumentaçãoRESUMO
Chemical cross-linking is an attractive low-resolution technique for structural studies of protein complexes. Distance constraints obtained from cross-linked peptides identified by mass spectrometry (MS) are used to construct and validate protein models. Amidinating cross-linkers such as diethyl suberthioimidate (DEST) have been used successfully in chemical cross-linking experiments. In this work, the application of a commercial diimidate cross-linking reagent, dimethyl suberimidate (DMS), was evaluated with model peptides and proteins. The peptides were designed with acetylated N-termini followed by random sequences containing two Lys residues separated by an Arg residue. After cross-linking reactions, intra- and intermolecular cross-linked species were submitted to CID and ECD dissociations to study their fragmentation features in the gas phase. Fragmentation of intramolecular peptides by collision induced dissociation (CID) demonstrates a unique two-step fragmentation pathway involving formation of a ketimine as intermediate. Electron capture and electron transfer dissociation (ECD and ETD) experiments demonstrated that the cyclic moiety is not dissociated. Intermolecular species demonstrated previously described fragmentation behavior in both CID and ECD experiments. The charge state distributions (CSD) obtained after reaction with DMS were compared with those obtained with disuccinimidyl suberate (DSS). CSDs for peptides and proteins were increased after their reaction with DMS, owing to the higher basicity of DMS modified species. These features were also observed in LC-MS experiments with bovine carbonic anhydrase II (BCA) after cross-linking with DMS and tryptic proteolysis. Cross-linked peptides derived from this protein were identified at high confidence and those species were in agreement with the crystal structure of BCA.
Assuntos
Reagentes de Ligações Cruzadas/química , Dimetil Suberimidato/química , Peptídeos/química , Proteínas/química , Proteômica/métodos , Animais , Anidrase Carbônica II/química , Bovinos , Modelos MolecularesRESUMO
Mass spectrometry (MS) is generally viewed as a highly complex and demanding technique, full of difficulties and apprehensions. Ease and simplicity have been infrequently used descriptors of MS but a series of revolutionary developments is turning a complex technique into a model of simplicity, making MS easier than ever. Focusing on spray-based ambient desorption/ionization techniques, we discuss how previously unthinkable goals for MS - (1) to bring it to a real world open atmosphere environment; (2) to perform fast, selective, and highly sensitive chemical and biochemical MS analysis with ease while (3) avoiding pre-separation and sample work-up for samples in their natural environment and therefore, at the end, (4) to make MS accessible in wherever MS is needed and by whoever needs it - have become feasible. Without compromising the unique combination of high speed, selectivity, sensitivity and separation competences, simplicity has become a new MS attribute - a fifth 'S' in the unique 5 S set of MS trademark features.
Assuntos
Espectrometria de Massas/economia , Espectrometria de Massas/métodos , Eletricidade , Desenho de Equipamento , Espectrometria de Massas/instrumentação , Miniaturização/instrumentação , Miniaturização/métodos , Preparações Farmacêuticas/análise , Espectrometria de Massas por Ionização por Electrospray/economia , Espectrometria de Massas por Ionização por Electrospray/instrumentação , Espectrometria de Massas por Ionização por Electrospray/métodos , VácuoRESUMO
An exceptionally easy to assemble source for ambient mass spectrometry is described. Based on Venturi easy ambient sonic-spray ionization (V-EASI), the source was further simplified by the use of a can of compressed air which simultaneously provides solution or solvent Venturi self-pumping and continuous, stable and abundant low-noise ion signal via voltage-free sonic-spraying. Further simplification was also attained by the use of inexpensive and readily commercially available parts: a surgical 2-way catheter, an aerosol can of compressed air, a 30 cm long fused-silica capillary and a hypodermic needle. This "Spartan" V-EASI source seems to offer one of the easiest and cheapest ways to make ions for ambient desorption/ionization mass spectrometry analysis of both liquid and solid samples.
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The production of counterfeited drugs is a criminal problem that carries serious risks to public health in the worldwide. In Brazil, Viagra and Cialis are the most counterfeit medicines, being used to inhibit the phosphodiesterase type 5 (PDE-5), treating thus, problems related to erectile dysfunction. X-ray fluorescence (XRF) is a suitable technique to control the quality of new pharmaceutical formulations and distinguish between authentic and counterfeit tablets. XRF has advantageous features like multielemental capability, good detectivity, high precision, short analysis times, and is nondestructive, which makes it suitable to be extended to a great variety of samples. In this work, the inorganic fingerprinting chemical of forty-one commercial samples (Viagra, Cialis, Lazar, Libiden, Maxfil, Plenovit, Potent 75, Rigix, V-50, Vimax and Pramil) and fifty-six counterfeit samples (Viagra and Cialis) were obtained from XRF data. XRF presented an excellent analytical methodology for semi-quantitative determination of active ingredient (in case of sildenafil citrate that presents S in its structure) and excipients such as calcium phosphate, titanium oxide and iron oxide (P, Ca, Ti and Fe). The matrix data were allied to chemometric methods (Principal Component Analysis and Hierarchical Cluster Analysis) to classify the tablets investigated between authentic and counterfeit, grouping the samples into of seven groups: A, B, C, D and E (counterfeit group) and F and G (authentic group).
Assuntos
Carbolinas/análise , Medicamentos Falsificados/análise , Inibidores da Fosfodiesterase 5/análise , Piperazinas/análise , Sulfonas/análise , Brasil , Carbolinas/química , Química Farmacêutica/métodos , Medicamentos Falsificados/química , Análise Multivariada , Inibidores da Fosfodiesterase 5/química , Piperazinas/química , Análise de Componente Principal , Saúde Pública , Purinas/análise , Purinas/química , Citrato de Sildenafila , Espectrometria por Raios X/métodos , Sulfonas/química , Comprimidos/química , TadalafilaRESUMO
Meta-chlorophenylpiperazine (m-CPP) is a new illicit drug that has been sold as ecstasy tablets. Easy ambient sonic-spray ionization mass spectrometry (EASI-MS) and X-ray fluorescence spectrometry (XRF) are shown to provide relatively simple and selective screening tools to distinguish m-CPP tablets from tablets containing amphetamines (mainly 3,4-methylenedioxymethamphetamine (MDMA)). EASI-MS detects the active ingredients in their protonated forms: [m-CPP + H](+) of m/z 197, [MDMA + H](+) of m/z 194, and [2MDMA + HCl + H](+) of m/z 423 and other ions from excipients directly on the tablet surface, providing distinct chemical fingerprints. XRF identifies Cl, K, Ca, Fe, and Cu as inorganic ingredients present in the m-CPP tablets. In contrast, higher Cl concentrations and a more diverse set of elements (P, Cl, Ca, Fe, Cu, Zn, Pt, V, Hf, Ti, Pt, and Zr) were found in MDMA tablets. Principal component analysis applied to XRF data arranged samples in three groups: m-CPP tablets (four samples), MDMA tablets (twenty three samples), and tablets with no active ingredients (three samples). The EASI-MS and XRF techniques were also evaluated to quantify m-CPP in ecstasy tablets, with concentrations ranging from 4 to 40 mg of m-CPP per tablets. The m-CPP could only be differentiated from its isomers (o-CPP and for the three isomers p-CPP) by traveling wave ion mobility mass spectrometry and NMR measurements.
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The aim was to synthesize and characterize fucoidan-coated poly(isobutylcyanoacrylate) nanoparticles. The nanoparticles were prepared by anionic emulsion polymerization (AEP) and by redox radical emulsion polymerization (RREP) of isobutylcyanoacrylate using fucoidan as a new coating material. The nanoparticles were characterized, and their cytotoxicity was evaluated in vitro on J774 macrophage and NIH-3T3 fibroblast cell lines. Cellular uptake of labeled nanoparticles was investigated by confocal fluorescence microscopy. Results showed that both methods were suitable to prepare stable formulations of fucoidan-coated PIBCA nanoparticles. Stable dispersions of nanoparticles were obtained by AEP with up to 100% fucoidan as coating material. By the RREP method, stable suspensions of nanoparticles were obtained with only up to 25% fucoidan in a blend of polysaccharide composed of dextran and fucoidan. The zeta potential of fucoidan-coated nanoparticles was decreased depending on the percentage of fucoidan. It reached the value of -44 mV for nanoparticles prepared by AEP with 100% of fucoidan. Nanoparticles made by AEP appeared more than four times more cytotoxic (IC(50) below 2 µg/mL) on macrophages J774 than nanoparticles made by RREP (IC(50) above 9 µg/mL). In contrast, no significant difference in cytotoxicity was highlighted by incubation of the nanoparticles with a fibroblast cell line. On fibroblasts, both types of nanoparticles showed similar cytotoxicity. Confocal fluorescence microscopy observations revealed that all types of nanoparticles were taken up by both cell lines. The distribution of the fluorescence in the cells varied greatly with the type of nanoparticles.
Assuntos
Antineoplásicos/toxicidade , Sistemas de Liberação de Medicamentos , Nanopartículas/toxicidade , Polissacarídeos/toxicidade , Adsorção , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Linhagem Celular , Cianoacrilatos/química , Cianoacrilatos/toxicidade , Composição de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Emulsões , Embucrilato , Excipientes/química , Fibroblastos/efeitos dos fármacos , Fibroblastos/fisiologia , Fluorescência , Formazans/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/fisiologia , Camundongos , Microscopia Confocal , Nanopartículas/química , Tamanho da Partícula , Phaeophyceae , Fitoterapia , Extratos Vegetais , Polimerização , Polissacarídeos/química , Polissacarídeos/metabolismo , Sais de Tetrazólio/metabolismoRESUMO
O granuloma periférico de células gigantes (GPCG) é definido como uma enfermidade benigna, de etiopatogênese incerta, proliferativa e reacional do tecido conjuntivo fibroso ou do periósteo, que se caracteriza histologicamente pela presença de células gigantes multinucleadas. O objetivo deste artigo é relatar um caso de GPCG em mulher branca, de 56 anos, apresentando nódulo sangrante ao toque, coloração vermelha com pequenas áreas esbranquiçadas e áreas ulceradas, limites definidos, consistência resiliente, base pediculada, com 2,0 cm diâmetro, assintomática, circundando o dente 38, que se apresentava com mobilidade. Radiograficamente observou-se perda óssea significativa em região do dente 38, cujo diagnóstico inicial foi de granuloma piogênico. O diagnóstico definitivo foi obtido após biópsia excisional em cuja análise microscópica se identificou presença de células gigantes multinucleadas. O acompanhamento clínico pós-operatório evidenciou favorável reparação cicatricial da área operada, sem recidiva após 2 anos de acompanhamento.
The peripheral giant cell granuloma (GPCG) is defined as a benign disorder of uncertain etiopathogenesis, and proliferative reaction of the fibrous connective tissue or the periosteum, which is characterized histologically by the presence of multinucleated giant cells. The purpose of this study is report a case of GPCG in a white women, with 56 years old, presenting nodule bleeding to the touch, red and white with small ulcerated areas, defined limits, resilient consistency, pedicled base with 2.0 cm diameter, asymptomatic, involving the permanent lower left third molar, that it was presented with mobility. Radiographically there was significant bone loss in this tooth region, whose initial diagnosis was pyogenic granuloma. The definitive diagnosis was obtained after excisional biopsy in which microscopic examination it was identified e presence of multinucleated giant cells. The clinical postoperative presented favorable cicatricial repairing of the operated area without recurrence after two years of monitoring.