COVID-19 cross-sectional study in Maricá, Brazil: The impact of vaccination coverage on viral incidence.

Population surveillance in COVID-19 Pandemic is crucial to follow up the pace of disease and its related immunological status. Here we present a cross-sectional study done in Maricá, a seaside town close to the city of Rio de Janeiro, Brazil. Three rounds of study sampling, enrolling a total of 1134 subjects, were performed during May to August 2021. Here we show that the number of individuals carrying detectable IgG antibodies and the neutralizing antibody (NAb) levels were greater in vaccinated groups compared to unvaccinated ones, highlighting the importance of vaccination to attain noticeable levels of populational immunity against SARS-CoV-2. Moreover, we found a decreased incidence of COVID-19 throughout the study, clearly correlated with the level of vaccinated individuals as well as the proportion of individuals with detectable levels of IgG anti-SARS-CoV-2 and NAb. The observed drop occurred even during the introduction of the Delta variant in Maricá, what suggests that the vaccination slowed down the widespread transmission of this variant. Overall, our data clearly support the use of vaccines to drop the incidence associated to SARS-CoV-2.

Doxycycline Decreases Atherosclerotic Lesions in the Aorta of ApoE-/- and Ovariectomized Mice with Correlation to Reduced MMP-2 Activity.

Atherogenic events promote changes in vessel walls, with alteration of the redox state, and increased activity of matrix metalloproteinases (MMPs). Thus, this study aims to evaluate aortic remodeling, MMP activity, and reactive oxygen species (ROS) levels after treatment with doxycycline in ApoE-/- and ovariectomized mice (OVX). Female ApoE-/--knockout mice (5 weeks) were submitted to ovariectomy surgery to induce experimental menopause. They then received chow enriched with 1% cholesterol to induce hypercholesterolemia. The animals were divided into two experimental groups: ApoE-/-/OVX vehicle and ApoE-/-/OVX doxycycline (30 mg/kg) administered by gavage once a day for 28 days (15th to the 18th week of life). Blood samples were collected to measure total cholesterol and fractions. The aorta was used for morphometry and to measure the activity and expression of MMP-2 and ROS levels. The ApoE-/-/OVX doxycycline group showed no change in total and fraction cholesterol levels. However, there was a reduction in ROS levels, MMP-2 expression, and activity that correlated with a decrease in atherosclerotic lesions relative to the ApoE-/-/OVX vehicle (p > 0.05). Therefore, we conclude that doxycycline in ApoE-/-/OVX animals promotes a reduction in atherosclerotic lesions by reducing ROS and MMP-2 activity and expression.

Current and future potential distributions of Helicoverpa punctigera (Lepidoptera: Noctuidae): is this the next FAW?

Helicoverpa punctigera (Wallengren), the native budworm, is an important highly polyphagous pest that has caused serious damage on a wide variety of crops in Australia. In Australia, its range overlaps that of its congener, Helicoverpa armigera (Hübner), a notorious invasive pest globally. We used CLIMEX, a bioclimatic niche modelling software package, to estimate the potential geographical distribution of H. punctigera under current and future climates (A1B scenario). Under both current and future climate conditions, the model indicates that H. punctigera could establish throughout the tropics and subtropics. Comparing the potential distributions under each climate scenario revealed that in the future its potential distribution is likely to shift poleward and into higher altitudes, into areas that are currently too cold as observed in the South of Brazil, Europe, North America, South East Asia, and South Pacific Islands including New Zealand. The projected potential distribution can inform pre- and post-border biosecurity strategies for the management of this pest in each country.

Dispersal of Trichogramma pretiosum Riley, 1879 (Hymenoptera: Trichogrammatidae) in cabbage, cucumber, and sweet corn.

Abstract: The dispersion capacity is fundamental to establish a biological control program with parasitoids. This information is used to determine the efficiency and the number of release points. Thus, the objective of this work was to determine the dispersion and to estimate the number of release points of Trichogramma pretiosum Riley, 1879 (Hymenoptera: Trichogrammatidae), in sweet corn, cucumber and cabbage in the Ceará State. The experiments were carried out in areas of maize with four leaf pairs (V4) and eight leaves pair (V8), stacked and cabbage. Unviable eggs of an alternative host were distributed in concentric circles of radius 2.5; 5.0; 9.0 and 12.0 m. Mean dispersal distance in the V4 stage maize was 4.7 m with a dispersion area of 48.6 m2, parasitism index of 18.4%, requiring 206 points/ha. In the V8 stage maize, the mean distance was 5.9 m, dispersion area of 60.3 m², mean parasitism index of 22.7% and 166 release points/ha. For the cucumber culture the mean distance was 6.0 m, dispersion area 62.2 m², mean parasitism index of 21.1% and 161 release points/ha. For cabbage the mean distance was 5.6 m, dispersion area of 56.8 m², mean parasitism index of 22.1% and 176 release points/ha.

Cell-type-specific dysregulation of RNA alternative splicing in short tandem repeat mouse knockin models of myotonic dystrophy.

Short tandem repeats (STRs) are prone to expansion mutations that cause multiple hereditary neurological and neuromuscular diseases. To study pathomechanisms using mouse models that recapitulate the tissue specificity and developmental timing of an STR expansion gene, we used rolling circle amplification and CRISPR/Cas9-mediated genome editing to generate Dmpk CTG expansion (CTGexp) knockin models of myotonic dystrophy type 1 (DM1). We demonstrate that skeletal muscle myoblasts and brain choroid plexus epithelial cells are particularly susceptible to Dmpk CTGexp mutations and RNA missplicing. Our results implicate dysregulation of muscle regeneration and cerebrospinal fluid homeostasis as early pathogenic events in DM1.

Intron retention induced by microsatellite expansions as a disease biomarker.

Expansions of simple sequence repeats, or microsatellites, have been linked to ∼30 neurological-neuromuscular diseases. While these expansions occur in coding and noncoding regions, microsatellite sequence and repeat length diversity is more prominent in introns with eight different trinucleotide to hexanucleotide repeats, causing hereditary diseases such as myotonic dystrophy type 2 (DM2), Fuchs endothelial corneal dystrophy (FECD), and C9orf72 amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). Here, we test the hypothesis that these GC-rich intronic microsatellite expansions selectively trigger host intron retention (IR). Using DM2, FECD, and C9-ALS/FTD as examples, we demonstrate that retention is readily detectable in affected tissues and peripheral blood lymphocytes and conclude that IR screening constitutes a rapid and inexpensive biomarker for intronic repeat expansion disease.

Myotonic Dystrophy and Developmental Regulation of RNA Processing.

Myotonic dystrophy (DM) is a multisystemic disorder caused by microsatellite expansion mutations in two unrelated genes leading to similar, yet distinct, diseases. DM disease presentation is highly variable and distinguished by differences in age-of-onset and symptom severity. In the most severe form, DM presents with congenital onset and profound developmental defects. At the molecular level, DM pathogenesis is characterized by a toxic RNA gain-of-function mechanism that involves the transcription of noncoding microsatellite expansions. These mutant RNAs disrupt key cellular pathways, including RNA processing, localization, and translation. In DM, these toxic RNA effects are predominantly mediated through the modulation of the muscleblind-like and CUGBP and ETR-3-like factor families of RNA binding proteins (RBPs). Dysfunction of these RBPs results in widespread RNA processing defects culminating in the expression of developmentally inappropriate protein isoforms in adult tissues. The tissue that is the focus of this review, skeletal muscle, is particularly sensitive to mutant RNA-responsive perturbations, as patients display a variety of developmental, structural, and functional defects in muscle. Here, we provide a comprehensive overview of DM1 and DM2 clinical presentation and pathology as well as the underlying cellular and molecular defects associated with DM disease onset and progression. Additionally, fundamental aspects of skeletal muscle development altered in DM are highlighted together with ongoing and potential therapeutic avenues to treat this muscular dystrophy. © 2018 American Physiological Society. Compr Physiol 8:509-553, 2018.

Impeding Transcription of Expanded Microsatellite Repeats by Deactivated Cas9.

Transcription of expanded microsatellite repeats is associated with multiple human diseases, including myotonic dystrophy, Fuchs endothelial corneal dystrophy, and C9orf72-ALS/FTD. Reducing production of RNA and proteins arising from these expanded loci holds therapeutic benefit. Here, we tested the hypothesis that deactivated Cas9 enzyme impedes transcription across expanded microsatellites. We observed a repeat length-, PAM-, and strand-dependent reduction of repeat-containing RNAs upon targeting dCas9 directly to repeat sequences; targeting the non-template strand was more effective. Aberrant splicing patterns were rescued in DM1 cells, and production of RAN peptides characteristic of DM1, DM2, and C9orf72-ALS/FTD cells was drastically decreased. Systemic delivery of dCas9/gRNA by adeno-associated virus led to reductions in pathological RNA foci, rescue of chloride channel 1 protein expression, and decreased myotonia. These observations suggest that transcription of microsatellite repeat-containing RNAs is more sensitive to perturbation than transcription of other RNAs, indicating potentially viable strategies for therapeutic intervention.

Downregulation of the Glial GLT1 Glutamate Transporter and Purkinje Cell Dysfunction in a Mouse Model of Myotonic Dystrophy.

Brain function is compromised in myotonic dystrophy type 1 (DM1), but the underlying mechanisms are not fully understood. To gain insight into the cellular and molecular pathways primarily affected, we studied a mouse model of DM1 and brains of adult patients. We found pronounced RNA toxicity in the Bergmann glia of the cerebellum, in association with abnormal Purkinje cell firing and fine motor incoordination in DM1 mice. A global proteomics approach revealed downregulation of the GLT1 glutamate transporter in DM1 mice and human patients, which we found to be the result of MBNL1 inactivation. GLT1 downregulation in DM1 astrocytes increases glutamate neurotoxicity and is detrimental to neurons. Finally, we demonstrated that the upregulation of GLT1 corrected Purkinje cell firing and motor incoordination in DM1 mice. Our findings show that glial defects are critical in DM1 brain pathophysiology and open promising therapeutic perspectives through the modulation of glutamate levels.

Distal Alternative Last Exons Localize mRNAs to Neural Projections.

Spatial restriction of mRNA to distinct subcellular locations enables local regulation and synthesis of proteins. However, the organizing principles of mRNA localization remain poorly understood. Here we analyzed subcellular transcriptomes of neural projections and soma of primary mouse cortical neurons and two neuronal cell lines and found that alternative last exons (ALEs) often confer isoform-specific localization. Surprisingly, gene-distal ALE isoforms were four times more often localized to neurites than gene-proximal isoforms. Localized isoforms were induced during neuronal differentiation and enriched for motifs associated with muscleblind-like (Mbnl) family RNA-binding proteins. Depletion of Mbnl1 and/or Mbnl2 reduced localization of hundreds of transcripts, implicating Mbnls in localization of mRNAs to neurites. We provide evidence supporting a model in which the linkage between genomic position of ALEs and subcellular localization enables coordinated induction of localization-competent mRNA isoforms through a post-transcriptional regulatory program that is induced during differentiation and reversed in cellular reprogramming and cancer.

Biometric measurements involving the terminal portion of the thoracic duct on left cervical level IV: an anatomic study.

To determine the point of entrance of the thoracic duct in the venous system, as well as to evaluate some biometric measurements concerning its terminal portion, we conducted an anatomic study on 25 non-preserved cadavers. The termination of the thoracic duct occurred on the confluence between the left internal jugular vein and the left subclavian vein in 60 % of the individuals. The average results for the biometric measurements were: distance between the end of left internal jugular vein and omohyoid muscle 31.2 ± 2.7 mm; distance between the end of thoracic duct and the left internal jugular vein 0.0 ± 0.0 mm; distance between the end of thoracic duct and the left subclavian vein 3.6 ± 1.0 mm; distance between the end of thoracic duct and the left brachiocephalic vein 10.7 ± 3.1 mm. Moreover, it was identified that the left internal jugular vein length in level IV, measured between its entrance in the left subclavian vein and the omohyoid muscle, was able to predict the termination of the thoracic duct on the junction between the left internal jugular vein and the left subclavian vein (OR = 2.99) with high accuracy (79.3 %). In addition, the left internal jugular vein length at level IV was able to predict the localization of thoracic duct termination. Thus, this finding has practical value in minimizing the risk for a potential chyle leak during or after a left-sided neck dissection.

Gamificação e crowdsourcing para melhoria do combate ao Aedes aegypti / Gamification and crowdsourcing for strengthening the combat against Aedes aegypti

OBJETIVOS: Criar um sistema baseado em conceitos de gamificação e crowdsourcing, para auxiliar no combate/prevenção ao Aedes aegypti. Com ênfase nos indicadores: número de notificações de focos do mosquito; tempo médio para gerar relatórios utilizados no planejamento e tempo médio entre a notificação e o recebimento da mesma pelo agente de campo. MÉTODOS: Trata-se de um estudo quantitativo-exploratório em parceria com as vigilâncias para a idealização, especificação, implementação e teste piloto do sistema proposto. RESULTADOS: Foi produzido um aplicativo móvel para a população realizar notificações que alimentam um sistema de informação na web, georreferenciado e usado pela VA/VE para apoio à gestão de seus serviços. No piloto foi verificado uma melhoria significativa nos indicadores considerados. CONCLUSÃO: O sistema poderá funcionar como um novo canal de denúncia, assim como auxiliar os processos e serviços da VA/VE para um combate mais eficiente e eficaz ao mosquito e às doenças por ele transmitidas.

OBJECTIVES: Develop and apply a gamified and crowdsourcing information system to speed up and improvedecision making by sanitary and health agencies ("VA/VE") as they attempt to prevent the spread of the zika, dengue, and chikungunya viruses transmitted by the Aedes aegypti mosquito. METHODS: Carry out a quantitative-exploratory study in partnership with VA/VE to specify, implement and (pilot) test the proposed system. RESULTS: The work produceda gamified, crowdsourced mobile app for the population to feed information on Aedes aegypti´s infestation into a georeferenced web information system. VA/VE use this web IS to manage their operations. The pilot test provided evidence that the partner VA/VE was able to make faster and better decisions. CONCLUSION: The proposed IS may serve as a newAedes aegypti infestation notification channel for the population and as a decision support system for VA/VE for more efficient and effective combat against the mosquito and related diseases.

Prognostic Value of TIMI Score versus GRACE Score in ST-segment Elevation Myocardial Infarction / Valor Prognóstico do Escore TIMI versus Escore GRACE no Infarto com Supradesnível do Segmento ST

Background: The TIMI Score for ST-segment elevation myocardial infarction (STEMI) was created and validated specifically for this clinical scenario, while the GRACE score is generic to any type of acute coronary syndrome. Objective: Between TIMI and GRACE scores, identify the one of better prognostic performance in patients with STEMI. Methods: We included 152 individuals consecutively admitted for STEMI. The TIMI and GRACE scores were tested for their discriminatory ability (C-statistics) and calibration (Hosmer-Lemeshow) in relation to hospital death. Results: The TIMI score showed equal distribution of patients in the ranges of low, intermediate and high risk (39 %, 27 % and 34 %, respectively), as opposed to the GRACE Score that showed predominant distribution at low risk (80 %, 13 % and 7%, respectively). Case-fatality was 11%. The C-statistics of the TIMI score was 0.87 (95%CI = 0.76 to 0.98), similar to GRACE (0.87, 95%CI = 0.75 to 0.99) - p = 0.71. The TIMI score showed satisfactory calibration represented by χ2 = 1.4 (p = 0.92), well above the calibration of the GRACE score, which showed χ2 = 14 (p = 0.08). This calibration is reflected in the expected incidence ranges for low, intermediate and high risk, according to the TIMI score (0 %, 4.9 % and 25 %, respectively), differently to GRACE (2.4%, 25% and 73%), which featured middle range incidence inappropriately. Conclusion: Although the scores show similar discriminatory capacity for hospital death, the TIMI score had better calibration than GRACE. These findings need to be validated populations of different risk profiles. .

Fundamento: O Escore TIMI para infarto com supradesnível do segmento ST (IAMcSST) foi criado e validado especificamente para este cenário clínico, enquanto o Escore GRACE é genérico para qualquer tipo de síndrome coronariana aguda. Objetivo: Identificar qual dos escores, TIMI ou GRACE, apresenta melhor desempenho prognóstico em pacientes com IAMcSST. Métodos: Foram incluídos 152 indivíduos consecutivamente internados por IAMcSST. Os escores TIMI e GRACE foram testados quanto a sua capacidade discriminatória (estatística-C) e calibração (teste Hosmer-Lemeshow), em relação ao desfecho óbito hospitalar. Resultados: O Escore TIMI apresentou distribuição equitativa de pacientes nas faixas de baixo, intermediário e alto risco (39%, 27% e 34%, respectivamente), diferente do Escore GRACE que apresentou distribuição predominante em baixo risco (80%, 13% e 7%, respectivamente). A letalidade da amostra foi de 11%. A estatística-C do Escore TIMI foi de 0,87 (95% IC = 0,76 - 0,98), semelhante ao GRACE (0,87; 95% IC = 0,75-0,99) - p = 0,71. O Escore TIMI apresentou calibração satisfatória, representada por χ2 de 1,4 (p = 0,92), nitidamente superior à calibração do Escore GRACE, que apresentou χ2 de 14 (p = 0,08). Esta calibração se reflete em incidências esperadas para as faixas de baixo, intermediário e alto risco de acordo com o Escore TIMI (0%, 4,9% e 25%, respectivamente), diferente do GRACE (2,4%, 25% e 73%) que caracterizou inadequadamente a faixa intermediária. Conclusão: Os escores TIMI e GRACE apresentam semelhante capacidade discriminatória em relação a óbito hospitalar, porém o Escore TIMI possui calibração superior ao GRACE. Para populações de risco diferente da nossa amostra, esta conclusão ...

Prognostic value of TIMI score versus GRACE score in ST-segment elevation myocardial infarction.

BACKGROUND: The TIMI Score for ST-segment elevation myocardial infarction (STEMI) was created and validated specifically for this clinical scenario, while the GRACE score is generic to any type of acute coronary syndrome. OBJECTIVE: Between TIMI and GRACE scores, identify the one of better prognostic performance in patients with STEMI. METHODS: We included 152 individuals consecutively admitted for STEMI. The TIMI and GRACE scores were tested for their discriminatory ability (C-statistics) and calibration (Hosmer-Lemeshow) in relation to hospital death. RESULTS: The TIMI score showed equal distribution of patients in the ranges of low, intermediate and high risk (39 %, 27 % and 34 %, respectively), as opposed to the GRACE Score that showed predominant distribution at low risk (80 %, 13 % and 7%, respectively). Case-fatality was 11%. The C-statistics of the TIMI score was 0.87 (95%CI = 0.76 to 0.98), similar to GRACE (0.87, 95%CI = 0.75 to 0.99) - p = 0.71. The TIMI score showed satisfactory calibration represented by χ2 = 1.4 (p = 0.92), well above the calibration of the GRACE score, which showed χ2 = 14 (p = 0.08). This calibration is reflected in the expected incidence ranges for low, intermediate and high risk, according to the TIMI score (0 %, 4.9 % and 25 %, respectively), differently to GRACE (2.4%, 25% and 73%), which featured middle range incidence inappropriately. CONCLUSION: Although the scores show similar discriminatory capacity for hospital death, the TIMI score had better calibration than GRACE. These findings need to be validated populations of different risk profiles.

Proteína C-Reativa Incrementa o Valor Prognóstico do Escore GRACE em Síndromes Coronarianas Agudas? / Does C-reactive Protein Add Prognostic Value to GRACE Score in Acute Coronary Syndromes?

Fundamento: O valor prognóstico incremental da dosagem plasmática de Proteína C-reativa (PCR) em relação ao Escore GRACE não está estabelecido em pacientes com síndromes coronarianas agudas sem supradesnivelamento do segmento ST (SCA). Objetivo: Testar a hipótese de que a medida de PCR na admissão incrementa o valor prognóstico do escore GRACE em pacientes com SCA. Métodos: Foram estudados 290 indivíduos, internados consecutivamente por SCA, os quais tiveram material plasmático colhido na admissão para dosagem de PCR por método de alta sensibilidade (nefelometria). Desfechos cardiovasculares durante hospitalização foram definidos pela combinação de óbito, infarto não fatal ou angina refratária não fatal. Resultados: A incidência de eventos cardiovasculares durante hospitalização foi 15% (18 óbitos, 11 infartos, 13 anginas), tendo a PCR apresentado estatística-C de 0,60 (95% IC = 0,51 - 0,70; p = 0,034) na predição desses desfechos. Após ajuste para o Escore GRACE, PCR elevada (definida pelo melhor ponto de corte) apresentou tendência a associação com eventos hospitalares (OR = 1,89; 95% IC = 0,92 - 3,88; p = 0,08). No entanto, a adição da variável PCR elevada no modelo GRACE não promoveu incremento significativo na estatística-C, a qual variou de 0,705 para 0,718 (p = 0,46). Da mesma forma, não houve reclassificação de risco significativa com a adição da PCR no modelo preditor (reclassificação líquida = 5,7%; p = 0,15). Conclusão Embora PCR possua associação com desfechos hospitalares, esse marcador inflamatório não incrementa o valor prognóstico do Escore GRACE. .

Background: The incremental prognostic value of plasma levels of C-reactive protein (CRP) in relation to GRACE score has not been established in patients with acute coronary syndrome (ACS) with non-ST segment elevation. Objective: To test the hypothesis that CRP measurements at admission increases the prognostic value of GRACE score in patients with ACS. Methods: A total of 290 subjects, consecutively admitted for ACS, with plasma material obtained upon admission CRP measurement using a high-sensitivity method (nephelometry) were studied. Cardiovascular outcomes during hospitalization were defined by the combination of death, nonfatal myocardial infarction or nonfatal refractory angina. Results: The incidence of cardiovascular events during hospitalization was 15% (18 deaths, 11 myocardial infarctions, 13 angina episodes) with CRP showing C-statistics of 0.60 (95% CI = 0.51-0.70, p = 0.034) in predicting these outcomes. After adjustment for the GRACE score, elevated CRP (defined as the best cutoff point) tended to be associated with hospital events (OR = 1.89, 95% CI = 0.92 to 3.88, p = 0.08). However, the addition of the variable elevated CRP in the GRACE model did not result in significant increase in C-statistics, which ranged from 0.705 to 0.718 (p = 0.46). Similarly, there was no significant reclassification of risk with the addition of CRP in the predictor model (net reclassification = 5.7 %, p = 0.15). Conclusion: Although CRP is associated with hospital outcomes, this inflammatory marker does not increase the prognostic value of the GRACE score. .

Does C-reactive protein add prognostic value to GRACE score in acute coronary syndromes?

BACKGROUND: The incremental prognostic value of plasma levels of C-reactive protein (CRP) in relation to GRACE score has not been established in patients with acute coronary syndrome (ACS) with non-ST segment elevation. OBJECTIVE: To test the hypothesis that CRP measurements at admission increases the prognostic value of GRACE score in patients with ACS. METHODS: A total of 290 subjects, consecutively admitted for ACS, with plasma material obtained upon admission CRP measurement using a high-sensitivity method (nephelometry) were studied. Cardiovascular outcomes during hospitalization were defined by the combination of death, nonfatal myocardial infarction or nonfatal refractory angina. RESULTS: The incidence of cardiovascular events during hospitalization was 15% (18 deaths, 11 myocardial infarctions, 13 angina episodes) with CRP showing C-statistics of 0.60 (95% CI = 0.51-0.70, p = 0.034) in predicting these outcomes. After adjustment for the GRACE score, elevated CRP (defined as the best cutoff point) tended to be associated with hospital events (OR = 1.89, 95% CI = 0.92 to 3.88, p = 0.08). However, the addition of the variable elevated CRP in the GRACE model did not result in significant increase in C-statistics, which ranged from 0.705 to 0.718 (p = 0.46). Similarly, there was no significant reclassification of risk with the addition of CRP in the predictor model (net reclassification = 5.7 %, p = 0.15). CONCLUSION: Although CRP is associated with hospital outcomes, this inflammatory marker does not increase the prognostic value of the GRACE score.