Social and epidemiological aspects of dengue were evaluated in an important metropolitan area in southern Brazil, from August 2012 to September 2014. Demographic, clinical, serological data were ...collected from patients with acute dengue symptoms treated at public health system units (HSUs). A systematic approach to analyze the spatial and temporal distribution of cases was developed, considering the temporal cross-correlation between dengue and weather, and the spatial correlation between dengue and income over the city’s census tracts. From the 878 patients with suggestive symptoms, 249 were diagnosed as positive dengue infection (28%). Considering the most statistically significant census tracts, a negative correlation was found between mean income and dengue (
r
= −0.65;
p
= 0.02; 95% CI: −0.03 to −0.91). The occurrence of dengue followed a seasonal distribution, and it was found to be three and four months delayed in relation to precipitation and temperature, respectively. Unexpectedly, the occurrence of symptomatic patients without dengue infection followed the same seasonal distribution, however its spatial distribution did not correlate with income. Through this methodology, we have found evidence that suggests a relation between dengue and poverty, which enriches the debate in the literature and sheds light on an extremely relevant socioeconomic and public health issue.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Mandatory vaccination for COVID-19 has been the object of heated debate in Brazil. This article discusses the legality and constitutionality of such a policy. First, it analyzes the laws, ...regulations, and Supreme Court decisions that provide for the possibility of mandatory COVID-19 vaccination. Subsequently, it analyzes the constitutionality of a mandatory vaccination policy through the proportionality method to address the conflict between, on one side, the right to individual autonomy, which includes the right to refuse a medical intervention, and, on the other, health policies that interfere with individual autonomy to protect the rights to life and health. The application of this method allows for the identification of key questions that need to be answered to determine the constitutionality of a mandatory vaccination program. These questions cannot be answered a priori and in the abstract because they depend on the concrete circumstances of the pandemic, on the characteristics of the vaccine(s) against COVID-19, and on how a mandatory vaccination policy might be designed and implemented by authorities.
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BFBNIB, INZLJ, NMLJ, NUK, PNG, PRFLJ, UL, UM, UPUK, ZRSKP
Volume measurements of maxillary sinus may be useful to identify diseases affecting paranasal sinuses. However, literature shows a lack of consensus in studies measuring the volume. This may be ...attributable to different computed tomography data acquisition techniques, segmentation methods, focuses of investigation, among other reasons. Furthermore, methods for volumetrically quantifying the maxillary sinus are commonly manual or semiautomated, which require substantial user expertise and are time-consuming. The purpose of the present study was to develop an automated tool for quantifying the total and air-free volume of the maxillary sinus based on computed tomography images. The quantification tool seeks to standardize maxillary sinus volume measurements, thus allowing better comparisons and determinations of factors that influence maxillary sinus size. The automated tool utilized image processing techniques (watershed, threshold, and morphological operators). The maxillary sinus volume was quantified in 30 patients. To evaluate the accuracy of the automated tool, the results were compared with manual segmentation that was performed by an experienced radiologist using a standard procedure. The mean percent differences between the automated and manual methods were 7.19% ± 5.83% and 6.93% ± 4.29% for total and air-free maxillary sinus volume, respectively. Linear regression and Bland-Altman statistics showed good agreement and low dispersion between both methods. The present automated tool for maxillary sinus volume assessment was rapid, reliable, robust, accurate, and reproducible and may be applied in clinical practice. The tool may be used to standardize measurements of maxillary volume. Such standardization is extremely important for allowing comparisons between studies, providing a better understanding of the role of the maxillary sinus, and determining the factors that influence maxillary sinus size under normal and pathological conditions.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Acquired deficiency of C1 inhibitor (AAE-C1-INH) is a very rare cause of recurrent angioedema, with few cases reported in the literature. We aimed to describe a series of patients with AAE-C1-INH who ...were diagnosed and received care at angioedema reference centers in Brazil, affiliated to the Brazilian Group of Studies on Hereditary Angioedema.
Fourteen patients from 8 Brazilian Angioedema Reference Centers, diagnosed with AAE-C1-INH, were included in this study. Clinical data collected included sex, date of birth, date of onset of symptoms, date of diagnosis, plasma levels of antigenic and/or functional C1-INH, levels of C4 and C1q, location and treatment of angioedema attacks, long-term prophylaxis, associated diseases, and definitive treatment.
Fourteen patients were identified with AAE-C1-INH. Most patients (10/14; 71.4%) were female. The median age at onset of symptoms was 56.5 years (range, 14-74 years; interquartile range IQR, 32-64 years), and median age at diagnosis was 58.0 years (range, 20-76 years; IQR, 38-65 years), with a median time until diagnosis of 2 years (range, 0-6 years; IQR, 1-3 years). The most common manifestations were cutaneous (face, eyelids, lips, trunk, hands, feet, and genitals). Most patient had low levels of C4 (13/14; 92.8%) and of antigenic C1-INH (8/14; 57.1%). Four had decreased functional activity of C1-INH (4/7; 57.1%) and C1q levels were low in 5 patients (5/12; 41.6%). Underlying diseases were identified in all 14 patients, with lymphoma of the splenic marginal zone and monoclonal gammopathy of undetermined significance being the most frequent. Nine patients (64.2%) needed long-term prophylactic treatment for recurrent angioedema and 5 patients (46.7%) required treatment for angioedema attacks. Most of them (12/14; 85.7%) had resolution of angioedema.
Therapy of AAE-C1-INH aims to control symptoms; however, diagnosis and treatment of the underlying disease, when present, should be an important target and may lead to the resolution of angioedema in patients with AAE-C1-INH.
O Torque Teno vírus (TTV) é um vírus pequeno, não envelopado, de genoma circular de DNA de fita simples e sentido negativo que está amplamente presente no viroma humano e, apesar de ser considerado ...não patogênico, causa uma viremia persistente e está distribuído mundialmente, sendo detectado em diversos fluidos corporais em até 90% dos indivíduos saudáveis. A eliminação deste vírus é majoritariamente realizada pelo sistema imunológico, refletindo na carga viral do indivíduo e, por conta disso, pacientes imunossuprimidos, como os pacientes submetidos à terapia renal substitutiva (TRS), tendem a apresentar uma carga viral maior que a dos indivíduos saudáveis. A saliva é considerado um método não invasivo e, por possuir uma maior taxa de detecção do DNA do TTV e maior carga viral em comparação a outros fluidos, como o plasma, pode ser eficaz como um biomarcador do sistema imunológico destes pacientes com imunossupressão.
O estudo apresentado pretende investigar a dinâmica de excreção do TTV em amostras de saliva de pacientes pediátricos com doença renal crônica (DRC) submetidos à TRS, a fim de estabelecer uma dinâmica de excreção viral e uma correlação entre a prevalência e carga viral com o impacto da terapia no sistema imunológico destes pacientes.
O estudo contou com um total de 86 indivíduos, separados em três grupos, sendo pacientes pediátricos, crianças (0-11 anos) e adolescentes (12-18 anos) e acompanhantes adultos (> 18 anos). Um total de 334 amostras de saliva foram coletadas da população de estudo no decorrer do tratamento, obtendo um máximo de 7 coletas e uma média de 4 coletas, sendo que a maioria dos indivíduos realizou 5 coletas. As amostras foram submetidas à extração de ácido nucleico total viral e detecção do TTV por PCR em tempo real quantitativo (qPCR).
O grupo de pacientes pediátricos crianças apresentou uma positividade média de 98,7% e uma carga viral média de 7,38 log cp/ml e o grupo de pacientes pediátricos adolescentes uma positividade média de 99% e uma carga viral média de 7,33 log cp/ml, enquanto o grupo dos acompanhantes apresentou uma positividade média de 95,6% e uma carga viral média de 5,73 log cp/ml.
Sendo assim, observou-se que os pacientes pediátricos obtiveram uma maior positividade e carga viral em comparação aos acompanhantes adultos e que o TTV apresentou uma alta taxa de detecção em saliva, podendo ser um marcador para a progressão da DRC e o andamento da TRS nestes pacientes.
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FIS, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The present study addresses the hypothesis that the activity of dipeptidyl peptidase IV (DPPIV), an enzyme that inactivates peptides that possess cardioprotective actions, correlates with adverse ...outcomes in heart failure (HF). The therapeutic potential of DPPIV inhibition in preventing cardiac dysfunction is also investigated.
Measurements of DPPIV activity in blood samples obtained from 190 patients with HF and 42 controls demonstrated that patients with HF exhibited an increase of ≈130% in circulating DPPIV activity compared with healthy subjects. Furthermore, an inverse correlation was observed between serum DPPIV activity and left ventricular (LV) ejection fraction in patients with HF. Similarly, radiofrequency LV ablation-induced HF rats displayed higher DPPIV activity in the plasma (≈50%) and heart tissue (≈3.5-fold) compared with sham-operated rats. Moreover, positive correlations were observed between the plasma DPPIV activity and LV end-diastolic pressure and lung congestion. Two days after surgery, 1 group of LV ablation-induced HF rats was treated with the DPPIV inhibitor sitagliptin (40 mg/kg BID) for 6 weeks, whereas the remaining rats were administered water. Hemodynamic measurements demonstrated that radiofrequency LV-ablated rats treated with sitagliptin exhibited a significant attenuation of HF-related cardiac dysfunction, including LV end-diastolic pressure, systolic performance, and chamber stiffness. Sitagliptin treatment also attenuated cardiac remodeling and cardiomyocyte apoptosis and minimized pulmonary congestion.
Collectively, the results presented herein associate circulating DPPIV activity with poorer cardiovascular outcomes in human and experimental HF. Moreover, the results demonstrate that long-term DPPIV inhibition mitigates the development and progression of HF in rats.
Multiple molecular mechanisms are involved in the pathogenesis of type 2 diabetes (T2D), with potentially different effects across ancestries. Recent large-scale efforts by the Type 2 Diabetes Global ...Genomics Initiative (T2DGGI) have broadly described the genetic architecture of T2D, data that can be subsequently used to pinpoint causal molecular mechanisms leading to T2D in an ancestry-aware manner.
In this work, we sought to explore the causal effects of gene expression and proteins on T2D across ancestries by leveraging data from the latest T2DGGI multi-ancestry genome-wide association study (GWAS). We conducted two-sample Mendelian randomization (MR) using cis-expression and protein quantitative trait loci (eQTL/pQTL) data from various datasets of four different major ancestries. To corroborate our findings, we performed statistical colocalization using PWCoCo. We then performed meta-analyses across ancestries for molecular traits showing evidence of causality in at least one ancestry (5% FDR-adjusted MR p-value and PWCoCo posterior probability ≥ 0.5).
We found causal evidence for changes in the genetically regulated expression of 267 genes and 15 proteins with T2D risk in at least one ancestry. When meta-analyzing the results across ancestries, we found, for eQTLs, evidence of causality between 148 genes and T2D, including PABPC4, a high-confidence effector gene for T2D with evidence of ancestry-correlated heterogeneity (I2 = 85%). For pQTLs, NELL1, ANXA7, PCSK1, and CTRB2 were found to be causal to T2D risk in the cross-ancestry meta-analysis, with CTRB2 showing evidence of ancestral heterogeneity (I2 = 85%).
Our findings highlight the power of large-scale GWAS and multi-omics MR to identify causal pathways involved in T2D risk. Our results also show the existence of ancestry-correlated heterogeneity, which emphasizes the need for expanding investigations into non-European ancestry populations to better understand T2D etiology.
ABSTRACT Objective: ssess quantitatively and qualitatively tongue coating microbiota in ICU patients. Methods: Analytical observational study, convenience sample comprising 65 patients was included ...for medical report analysis and collection of general data, tongue coating assessment through visual inspection and microbiological sample collection for further laboratory analysis. The collection was performed by a single examiner using a sterile swab introduced and rubbing the posterior portion of the tongue close to the oropharynx. Results: Most patients (60%) belonged to the female sex, at mean age of 74.2 years. The main reasons for hospitalization were lung issues (26.2%) - prevailing associated comorbidities were diabetes (43.1%) and high blood pressure (66.2%). The mean length of stay in the ICU was one day. All patients presented tongue dorsum coating. There were Candida albicans (37%), Streptococcus parasanguinis (26.1%) and Streptococcus mitis (32.6%) in 1/3 of lingual extension. Streptococcus mitis (p=0,0265) was the most prevalent species. Conclusion: There was no significance between the amount of coating and number of observed species, although all assessed patients had presented coating. The most prevalent microorganisms were Candida albicans, Streptococcus parasanguinis and Streptococcus mitis.
RESUMO Objetivo: Avaliar quantitativa e qualitativamente a microbiota da saburra lingual em pacientes internados em UTI. Métodos: Estudo observacional analítico, amostra de conveniência composta por 65 pacientes para análise de laudo médico e coleta de dados gerais, avaliação da saburra lingual por inspeção visual e coleta de amostra microbiológica para posterior análise laboratorial. A coleta foi realizada por um único examinador por meio de swab estéril introduzida e fricção na porção posterior de língua próxima à orofaringe. Resultados: A maioria dos pacientes (60%) pertencia ao sexo feminino, com média de idade de 74,2 anos. Os principais motivos de internação foram problemas pulmonares (26,2%) - as comorbidades associadas predominantes foram diabetes (43,1%) e hipertensão arterial (66,2%). O tempo de internação médio na UTI foi de um dia. Todos os pacientes apresentavam saburra do dorso da língua. Havia Candida albicans (37%), Streptococcus parasanguinis (26,1%) e Streptococcus mitis (32,6%) em 1/3 da extensão lingual. Streptococcus mitis (p=0,0265) foi a espécie mais prevalente. Conclusões: Não houve significância entre a quantidade de recobrimento e o número de espécies observadas, embora todos os pacientes avaliados tenham apresentado recobrimento. Os microrganismos mais prevalentes foram Candida albicans, Streptococcus parasanguinis e Streptococcus mitis.
The objective of this study was to develop and validate a computational tool to assist radiological decisions on necrotizing enterocolitis.
Patients that exhibited clinical signs and radiographic ...evidence of Bell's stage 2 or higher were included in the study, resulting in 64 exams. The tool was used to classify localized bowel wall thickening and intestinal pneumatosis using full-width at half-maximum measurements and texture analyses based on wavelet energy decomposition. Radiological findings of suspicious bowel wall thickening and intestinal pneumatosis loops were confirmed by both patient surgery and histopathological analysis. Two experienced radiologists selected an involved bowel and a normal bowel in the same radiography. The full-width at half-maximum and wavelet-based texture feature were then calculated and compared using the Mann–Whitney U test. Specificity, sensibility, positive and negative predictive values were calculated.
The full-width at half-maximum results were significantly different between normal and distended loops (median of 10.30 and 15.13, respectively). Horizontal, vertical, and diagonal wavelet energy measurements were evaluated at eight levels of decomposition. Levels 7 and 8 in the horizontal direction presented significant differences. For level 7, median was 0.034 and 0.088 for normal and intestinal pneumatosis groups, respectively, and for level 8 median was 0.19 and 0.34, respectively.
The developed tool could detect differences in radiographic findings of bowel wall thickening and IP that are difficult to diagnose, demonstrating the its potential in clinical routine. The tool that was developed in the present study may help physicians to investigate suspicious bowel loops, thereby considerably improving diagnosis and clinical decisions.
O objetivo deste estudo foi desenvolver e validar uma ferramenta computacional para auxiliar as decisões radiológicas na enterocolite necrotizante.
Pacientes que exibiam sinais clínicos e evidências radiográficas do estágio 2 ou superior de Bell foram incluídos no estudo, que resultou em 64 exames. A ferramenta foi usada para classificar o aumento localizado da espessura da parede intestinal e a pneumatose intestinal com medidas de largura total a meia altura e análises de textura baseadas na decomposição da energia wavelet. Os achados radiológicos de aumento suspeito da espessura da parede intestinal e das alças na pneumatose intestinal foram confirmados pela cirurgia e análise histopatológica do paciente. Dois radiologistas experientes selecionaram um intestino afetado e um intestino normal na mesma radiografia. A largura total a meia altura e a característica da textura baseada em wavelet foram então calculadas e comparadas com o uso do teste U de Mann-Whitney. Foram calculados a especificidade, sensibilidade, valores preditivos positivos e negativos.
Os resultados da largura total a meia altura foram significativamente diferentes entre a alça normal e a distendida (mediana de 10,30 e 15,13, respectivamente). Medidas de energia wavelet horizontal, vertical e diagonal foram avaliadas em oito níveis de decomposição. Os níveis 7 e 8 na direção horizontal apresentaram diferenças significativas. Para o nível 7, as medianas foram 0,034 e 0,088 para os grupos normal e com pneumatose intestinal, respectivamente, e para o nível 8, as medianas foram 0,19 e 0,34, respectivamente.
A ferramenta desenvolvida pode detectar diferenças nos achados radiográficos do aumento da espessura da parede intestinal e PI de difícil diagnóstico, demonstra seu potencial na rotina clínica. A ferramenta desenvolvida no presente estudo pode ajudar os médicos a investigar alças intestinais suspeitas e melhorar consideravelmente o diagnóstico e as decisões clínicas.
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FIS, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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