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INTRODUCTION: The Ad26.COV2·S (Janssen/Johnson & Johnson) COVID-19 vaccine, has been rarely associated with vaccine-induced immune thrombocytopenia and thrombosis (VITT). We investigated the prevalence of anti-PF4 antibody positivity, thrombocytopenia, D-dimer elevation, plasmatic thromboinflammatory markers, and platelet functional assays following Ad26.COV2·S vaccination in Rio de Janeiro, Brazil. METHODS: From July to September 2021, participants were assessed prior, 1, and 3 weeks post-vaccination. Platelet count and D-dimer were measured at each visit and anti-PF4 at week 3. A positive anti-PF4 prompted retrospective testing of the sample from week 0. Individuals with new thrombocytopenia or elevated D-dimer, positive anti-PF4, and 38 matched controls without laboratory abnormalities were evaluated for plasmatic p-selectin, tissue factor, and functional platelet activation assays. RESULTS: 630 individuals were included; 306 (48.57%) females, median age 28 years. Forty-two (6.67%) presented ≥1 laboratory abnormality in week 1 or 3. Five (0.79%) had thrombocytopenia, 31 (4.91%) elevated D-dimer, and 9 (1.57%) had positive anti-PF4 at week 3. Individuals with laboratory abnormalities and controls showed a slight increase in plasmatic p-selectin and tissue factor. Ten individuals with laboratory abnormalities yielded increased surface expression of p-selectin, and their ability to activate platelets in a FcγRIIa dependent manner was further evaluated. Two were partially inhibited by high concentrations of heparin and blockage of FcγRII with IV.3 antibody. Plasma obtained before vaccination produced similar results, suggesting a lack of association with vaccination. CONCLUSIONS: Vaccination with Ad26.COV2·S vaccine led to a very low frequency of low-titer positive anti-PF4 antibodies, elevation of D-dimer, and mild thrombocytopenia, with no associated clinically relevant increase in thromboinflammatory markers and platelet activation.
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COVID-19 , Produtos de Degradação da Fibrina e do Fibrinogênio , Ativação Plaquetária , Fator Plaquetário 4 , Humanos , Feminino , Masculino , Brasil/epidemiologia , Adulto , Fator Plaquetário 4/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Pessoa de Meia-Idade , Trombocitopenia/induzido quimicamente , SARS-CoV-2/imunologia , Adulto Jovem , Ad26COVS1 , Contagem de Plaquetas , Vacinação , Estudos Retrospectivos , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/efeitos adversos , Adolescente , Trombose/imunologia , Trombose/prevenção & controleRESUMO
The development of intelligent transportation systems (ITS), vehicular ad hoc networks (VANETs), and autonomous driving (AD) has progressed rapidly in recent years, driven by artificial intelligence (AI), the internet of things (IoT), and their integration with dedicated short-range communications (DSRC) systems and fifth-generation (5G) networks. This has led to improved mobility conditions in different road propagation environments: urban, suburban, rural, and highway. The use of these communication technologies has enabled drivers and pedestrians to be more aware of the need to improve their behavior and decision making in adverse traffic conditions by sharing information from cameras, radars, and sensors widely deployed in vehicles and road infrastructure. However, wireless data transmission in VANETs is affected by the specific conditions of the propagation environment, weather, terrain, traffic density, and frequency bands used. In this paper, we characterize the path loss based on the extensive measurement campaign carrier out in vehicular environments at 700 MHz and 5.9 GHz under realistic road traffic conditions. From a linear dual-slope path loss propagation model, the results of the path loss exponents and the standard deviations of the shadowing are reported. This study focused on three different environments, i.e., urban with high traffic density (U-HD), urban with moderate/low traffic density (U-LD), and suburban (SU). The results presented here can be easily incorporated into VANET simulators to develop, evaluate, and validate new protocols and system architecture configurations under more realistic propagation conditions.
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Alzheimer's disease (AD) involves a neurodegenerative process that has not yet been prevented, reversed, or stopped. Continuing with the search for natural pharmacological treatments, flavonoids are a family of compounds with proven neuroprotective effects and multi-targeting behavior. The American genus Dalea L. (Fabaceae) is an important source of bioactive flavonoids. In this opportunity, we tested the neuroprotective potential of three prenylated flavanones isolated from Dalea species in a new in vitro pre-clinical AD model previously developed by us. Our approach consisted in exposing neural cells to conditioned media (3xTg-AD ACM) from neurotoxic astrocytes derived from hippocampi and cortices of old 3xTg-AD mice, mimicking a local neurodegenerative microenvironment. Flavanone 1 and 3 showed a neuroprotective effect against 3xTg-AD ACM, being 1 more active than 3. The structural requirements to afford neuroprotective activity in this model are a 5'-dimethylallyl and 4'-hydroxy at the B ring. In order to search the mechanistic performance of the most active flavanone, we focus on the flavonoid-mediated regulation of GSK-3ß-mediated tau phosphorylation previously reported. Flavanone 1 treatment decreased the rise of hyperphosphorylated tau protein neuronal levels induced after 3xTg-AD ACM exposure and inhibited the activity of GSK-3ß. Finally, direct exposure of these neurotoxic 3xTg-AD astrocytes to flavanone 1 resulted in toxicity to these cells and reduced the neurotoxicity of 3xTg-AD ACM as well. Our results allow us to present compound 1 as a natural prenylated flavanone that could be used as a precursor to development and design of future drug therapies for AD.
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Doença de Alzheimer , Flavanonas , Fármacos Neuroprotetores , Camundongos , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Camundongos Transgênicos , Proteínas tau/metabolismo , Flavanonas/farmacologia , Flavanonas/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Modelos Animais de Doenças , Fosforilação , Peptídeos beta-Amiloides/metabolismoRESUMO
Background: Atopic dermatitis (AD) is an inflammatory skin condition, often multifactorial in origin, and most commonly manifests during childhood. Although there remains a deficit in literature, current data suggest Honduras may have the highest prevalence and severity of AD among all Latin American countries. Objective: To assess the current prevalence of pediatric AD in Honduras and evaluate existing gaps in available literature to monitor disease burden. Methods: A comprehensive literature search was performed in March 2023. Articles were removed if they were published before 2007, were of the incorrect study design, or were focused on countries outside of Honduras. The articles were independently reviewed by 2 authors. Results: The initial literature search yielded 174 studies, of which 7 met inclusion criteria. AD prevalence rates in children in Honduras ranged from 0.7% to 40.0%. Limitations: Limitations include elements of study design, analytic methods, study populations, and limited articles. Conclusion: There appears to be a disproportionately higher prevalence and disease burden of pediatric AD in Honduras. Future research should acquire accurate data to further understand the prevalence, incidence, and severity of AD in Honduras.
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ABSTRACT The authors report full-field electroretinogram and optical coherence tomography findings of intravitreal melphalan retinal toxicity. An 18-month-old girl with unilateral group D retinoblastoma was evaluated with light-adapted 3 full-field electroretinogram protocol and optical coherence tomography (I-Stand optical coherence tomography, Optovue) after treatment with intravitreal melphalan for active vitreous seeds. After the third injection, the child developed retinal pigment epithelial changes near the injection site. The photopic response of the full-field electroretinogram standard flash cones showed a decrease in amplitude responses of waves a and b in the affected eye compared to the contralateral eye. Optical coherence tomography showed loss of photoreceptors and outer nuclear layers in the affected eye. Melphalan toxicity is dose-dependent, and despite its treatment benefits, it can affect vision. Our case shows an updated, in-depth retinal toxicity assessment of intravitreal melphalan in the human retina with optical coherence tomography and its correlation with electroretinogram changes.
RESUMO Os autores relatam os achados de eletrorretinograma de campo total e tomografia de coerência óptica (OCT) da toxicidade retiniana ao melfalan intravítreo. Menina de 18 meses com retinoblastoma foi avaliada com fases fotópicas do eletrorretinograma de campo total e tomografia de coerência óptica após o tratamento com melfalan intravítreo. Após a terceira injeção, a criança desenvolveu alterações do epitélio pigmentar da retina próximo ao local da injeção. A resposta fotópica do eletrorretinograma de campo total mostrou diminuição da amplitude das respostas das ondas a e b no olho afetado comparado com o olho sadio. A tomografia de coerência óptica mostrou alterações significativas nas camadas retinianas externas no olho comprometido. A toxicidade do melfalan é dose dependente e, apesar dos benefícios terapêuticos, podem causar alterações retinianas significativas. Este caso demonstra uma avaliação atual e aprofundada da toxicidade retiniana do melfalan intravítreo na retina humana através da tomografia de coerência óptica e sua correlação com as alterações no eletrorretinograma.
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ABSTRACT Purpose: To evaluate the quality of life and stress level related to visual function following pediatric cataract surgery in a Brazilian public hospital. Methods: This prospective study analyzed children aged 6-14 years old who underwent cataract surgery. The Childhood Stress Scale and Children's Visual Function Questionnaire (CVFQ) were used to assess stress levels and quality of life, respectively. Both instruments were applied by two psychologists before and after the surgery. Eye examination was performed by two ophthalmologists. Preoperative and postoperative data were compared. Results: In total, 23 children (32 eyes) were enrolled in the study, of which 9 had bilateral cataracts. The average age group at the time of surgery was 9.65 ± 2.26 (6-14) years old. One month after the surgery, the spherical equivalent was -0.90 ± 1.66D, and the corrected distance visual acuity was 0.13 ± 0.10 (0-0.3) LogMAR in bilateral cases and 0.50 ± 0.39 (0-1.3) LogMAR in unilateral cases (p<0.01). According to the Childhood Stress Scale, 77.7% of the bilateral cases and 57.1% of the unilateral cases had stable stress levels, and 34.7% of the children improved their stress level. The analysis of the CVFQ was based on scores for general health, general vision health, competence, personality, and treatment. After cataract surgery, 78.2% of the patients had improved or maintained CVFQ scores in the general health domain; 82.6%, general vision health; 95.6%, competence; 56.5%, personality; and 78.2%, treatment. Conclusion: Pediatric cataract surgery improves the visual function and the quality of life even in patients undergoing surgical procedures, without increasing the stress levels.
RESUMO Objetivo: Avaliar a qualidade de vida e o nível de estresse relacionada à função visual após a cirurgia de catarata pediátrica em um hospital público brasileiro. Métodos: Estudo prospectivo em crianças de seis a 14 anos submetidas à cirurgia de catarata. A Escala de Stresse Infantil e o Questionário de Função Visual em Crianças foram usados para avaliar o nível de estresse e a qualidade de vida, respectivamente. Ambos os instrumentos foram aplicados por duas psicólogas antes e após a cirurgia. O exame oftalmológico foi realizado por dois oftalmologistas. Os dados coletados no pré e pós-operatório foram comparados. Resultados: Vinte e três crianças (32 olhos) foram incluídas no estudo, nove delas apresentavam catarata bilateral. A média de idade na cirurgia foi de 9,65±2,26 (6 a 14) anos. Um mês após a cirurgia, o equivalente esférico foi de -0,90 ± 1,66D e a acuidade visual corrigida a distância foi de 0,13 ± 0,10 (0-0,3) LogMAR em casos bilaterais e 0,50 ± 0,39 (0-1,3) LogMAR em casos unilaterais (p<0.01). De acordo com a Escala de Stresse Infantil, 77,7% dos casos de catarata bilaterais, e 57,1% dos casos unilaterais mantiveram o nível de estresse e 34,7% das crianças melhoraram o nível de estresse. A análise do Questionário de Função Visual em Crianças foi baseada em pontuações para saúde geral, saúde geral da visão, competência, personalidade e tratamento. Após a cirurgia de catarata, 78,2% dos pacientes melhoraram ou mantiveram o escore do Questionário de Função Visual em Crianças na saúde geral, 82,6% na saúde geral da visão, 95,6% na competência, 56,5% na personalidade e 78,2% no tratamento. Conclusão: A cirurgia de catarata pediátrica melhora a função visual e a qualidade de vida em pacientes submetidos a procedimento cirúrgico, sem aumentar o nível de estresse.
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In the rapidly evolving urban advanced mobility (UAM) sphere, Vehicular Ad Hoc Networks (VANETs) are crucial for robust communication and operational efficiency in future urban environments. This paper quantifies VANETs to improve their reliability and availability, essential for integrating UAM into urban infrastructures. It proposes a novel Stochastic Petri Nets (SPN) method for evaluating VANET-based Vehicle Communication and Control (VCC) architectures, crucial given the dynamic demands of UAM. The SPN model, incorporating virtual machine (VM) migration and Edge Computing, addresses VANET integration challenges with Edge Computing. It uses stochastic elements to mirror VANET scenarios, enhancing network robustness and dependability, vital for the operational integrity of UAM. Case studies using this model offer insights into system availability and reliability, guiding VANET optimizations for UAM. The paper also applies a Design of Experiments (DoE) approach for a sensitivity analysis of SPN components, identifying key parameters affecting system availability. This is critical for refining the model for UAM efficiency. This research is significant for monitoring UAM systems in future cities, presenting a cost-effective framework over traditional methods and advancing VANET reliability and availability in urban mobility contexts.
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Molecules sourced from marine environments hold immense promise for the development of novel therapeutic drugs, owing to their distinctive chemical compositions and valuable medicinal attributes. Notably, Talarolide A and Talaropeptides A-D have gained recent attention as potential candidates for pharmaceutical applications. This study aims to explore the chemical reactivity of Talarolide A and Talaropeptides A-D through the application of molecular modeling and computational chemistry techniques, specifically employing Conceptual Density Functional Theory (CDFT). By investigating their chemical behaviors, the study seeks to contribute to the understanding of the potential pharmacological uses of these marine-derived compounds. The molecular geometry optimizations and frequency calculations were conducted using the Density Functional Tight Binding (DFTBA) method. This was followed by a subsequent round of geometry optimization, frequency analysis, and computation of electronic properties and chemical reactivity descriptors. We employed the MN12SX/Def2TZVP/H2O model chemistry, utilizing the Gaussian 16 program and the SMD solvation model. The analysis of the global reactivity descriptors arising from CDFT was achieved as well as the graphical comparison of the dual descriptor DD revealing the areas of the molecules with more propensity to suffer a nucleophilic or electrophilic attack. Additionally, Molinspiration and SwissTargetPrediction were considered for the calculation of molecular characteristics and predicted biological targets. These include enzymes, nuclear receptors, kinase inhibitors, GPCR ligands, and ion channel modulators. The graphical results show that Talarolide A and the Talaropeptides A-D are likely to behave as protease inhibitors.
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Receptores Acoplados a Proteínas G , Transdução de Sinais , Teoria da Densidade Funcional , Ligantes , Peptídeos/farmacologiaRESUMO
Significant advances in understanding the molecular complexity of the development and progression of pancreatic cancer have been made, but this disease is still considered one of the most lethal human cancers and needs new therapeutic options. In the present study, the antineoplastic effects of AD80, a multikinase inhibitor, were investigated in models of pancreatic cancer. AD80 reduced cell viability and clonogenicity and induced polyploidy in pancreatic cancer cells. At the molecular level, AD80 reduced RPS6 and histone H3 phosphorylation and induced γH2AX and PARP1 cleavage. Additionally, the drug markedly decreased AURKA phosphorylation and expression. In PANC-1 cells, AD80 strongly induced autophagic flux (consumption of LC3B and SQSTM1/p62). AD80 modulated 32 out of 84 autophagy-related genes and was associated with vacuole organization, macroautophagy, response to starvation, cellular response to nitrogen levels, and cellular response to extracellular stimulus. In 3D pancreatic cancer models, AD80 also effectively reduced growth independent of anchorage and cell viability. In summary, AD80 induces mitotic aberrations, DNA damage, autophagy, and apoptosis in pancreatic cancer cells. Our exploratory study establishes novel targets underlying the antineoplastic activity of the drug and provides insights into the development of therapeutic strategies for this disease.
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Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder without a cure, despite the enormous number of investigations and therapeutic approaches. AD is a consequence of microglial responses to "damage signals", such as aggregated tau oligomers, which trigger a neuro-inflammatory reaction, promoting the misfolding of cytoskeleton structure. Since AD is the most prevalent cause of dementia in the elderly (>60 years old), new treatments are essential to improve the well-being of affected subjects. The pharmaceutical industry has not developed new drugs with efficacy for controlling AD. In this context, major attention has been given to nutraceuticals and novel bioactive compounds, such as molecules from the Andean Shilajit (AnSh), obtained from the Andes of Chile. Primary cultures of rat hippocampal neurons and mouse neuroblastoma cells were evaluated to examine the functional and neuroprotective role of different AnSh fractions. Our findings show that AnSh fractions increase the number and length of neuronal processes at a differential dose. All fractions were viable in neurons. The AnSh fractions inhibit tau self-aggregation after 10 days of treatment. Finally, we identified two candidate molecules in M3 fractions assayed by UPLC/MS. Our research points to a novel AnSh-derived fraction that is helpful in AD. Intensive work toward elucidation of the molecular mechanisms is being carried out. AnSh is an alternative for AD treatment or as a coadjuvant for an effective treatment.
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Since glucose reuptake by neurons is mostly independent of insulin, it has been an intriguing question whether insulin has or not any roles in the brain. Consequently, the identification of insulin receptors in the central nervous system has fueled investigations of insulin functions in the brain. It is also already known that insulin can influence glucose reuptake by neurons, mostly during activities that have the highest energy demand. The identification of high density of insulin receptors in the hippocampus also suggests that insulin may present important roles related to memory. In this context, studies have reported worse performance in cognitive tests among diabetic patients. In addition, alterations in the regulation of central insulin pathways have been observed in the brains of Alzheimer's disease (AD) patients. In fact, some authors have proposed AD as a third type of diabetes and recently, our group proposed insulin resistance as a common link between different AD hypotheses. Therefore, in the present narrative review, we intend to revise and gather the evidence of disturbed insulin signaling in experimental animal models of AD.
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Doença de Alzheimer , Resistência à Insulina , Animais , Insulina/metabolismo , Receptor de Insulina/metabolismo , Modelos Animais , Encéfalo , Glucose/metabolismo , Modelos Animais de DoençasRESUMO
Cryptococcus neoformans and C. gattii species complexes (phylum: Basidiomycota) are environmental yeasts and are the main cause of human cryptococcosis worldwide. The most recent molecular typing studies in Latin America have focused on the intertropical region. Thus, this study aimed to update the knowledge of human cryptococcosis in the South American temperate region. We obtained and analyzed 116 C. neoformans/C. gattii species complexes isolates from the Public Health Surveillance Laboratory between 2008-2013 and 2017-2021 (C. gattii species complex = 1 and C. neoformans species complex = 115). The average patient age was 45 years, with an overall male:female ratio of 3.1:1. The proportion of HIV-negative patients was significantly higher in the second study period. Restriction fragment length polymorphism typing of URA5 gene revealed that the C. neoformans species complex comprised 75.7% VNI, 2.6% VNII, 0.9% VNIII, 1.7% VNIV, 17.4% VNII/VNIV hybrids, and one C. neoformans isolate (0.9%) misidentified as VGI; the C. gattii species complex isolates comprised one VGII. The overall case fatality rate was 49.5%, with no differences in lethality between VNI and hybrid isolates. Of the four isolates responsible for episodes of reoccurrence, only one had a genotype different from the first episode. Antifungal susceptibility testing revealed that most isolates fell below the local epidemiological cut-off value. This study provides additional information for the analysis of C. neoformans/C. gattii species complexes dynamics in the South American temperate region.
This study describes the epidemiological and molecular trends of human cryptococcosis according to the public health Uruguayan surveillance network. The findings provide additional information for analyzing the Cryptococcusneoformans/C. gattii species complexes in the South American temperate region.
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Criptococose , Cryptococcus gattii , Cryptococcus neoformans , Humanos , Masculino , Feminino , Animais , Antifúngicos/farmacologia , Uruguai/epidemiologia , Criptococose/epidemiologia , Criptococose/microbiologia , Criptococose/veterinária , Tipagem Molecular/veterinária , Genótipo , Técnicas de Tipagem Micológica/veterináriaRESUMO
Neurodegenerative diseases such as Alzheimer's disease have been classically studied from a purely neuronocentric point of view. More recent evidences support the notion that other cell populations are involved in disease progression. In this sense, the possible pathogenic role of glial cells like astrocytes is increasingly being recognized. Once faced with tissue damage signals and other stimuli present in disease environments, astrocytes suffer many morphological and functional changes, a process referred as reactive astrogliosis. Studies from murine models and humans suggest that these complex and heterogeneous responses could manifest as disease-specific astrocyte phenotypes. Clear understanding of disease-associated astrocytes is a necessary step to fully disclose neurodegenerative processes, aiding in the design of new therapeutic and diagnostic strategies. In this work, we present the transcriptomics characterization of neurotoxic astrocytic cultures isolated from adult symptomatic animals of the triple transgenic mouse model of Alzheimer's disease (3xTg-AD). According to the observed profile, 3xTg-AD neurotoxic astrocytes show various reactivity features including alteration of the extracellular matrix and release of pro-inflammatory and proliferative factors that could result in harmful effects to neurons. Moreover, these alterations could be a consequence of stress responses at the endoplasmic reticulum and mitochondria as well as of concomitant metabolic adaptations. Present results support the hypothesis that adaptive changes of astrocytic function induced by a stressed microenvironment could later promote harmful astrocyte phenotypes and further accelerate or induce neurodegenerative processes.
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Doença de Alzheimer , Humanos , Camundongos , Animais , Doença de Alzheimer/metabolismo , Camundongos Transgênicos , Astrócitos/metabolismo , Transcriptoma , Modelos Animais de DoençasRESUMO
Epidemiological studies show that having a history of cancer protects from the development of Alzheimer's Disease (AD), and vice versa, AD protects from cancer. The mechanism of this mutual protection is unknown. We have reported that the peripheral blood mononuclear cells (PBMC) of amnestic cognitive impairment (aMCI) and Alzheimer's Disease (AD) patients have increased susceptibility to oxidative cell death compared to control subjects, and from the opposite standpoint a cancer history is associated with increased resistance to oxidative stress cell death in PBMCs, even in those subjects who have cancer history and aMCI (Ca + aMCI). Cellular senescence is a regulator of susceptibility to cell death and has been related to the pathophysiology of AD and cancer. Recently, we showed that cellular senescence markers can be tracked in PBMCs of aMCI patients, so we here investigated whether these senescence markers are dependent on having a history of cancer. Senescence-associated ßeta-galactosidase (SA-ß-Gal) activity, G0-G1 phase cell-cycle arrest, p16 and p53 were analyzed by flow cytometry; phosphorylated H2A histone family member X (γH2AX) by immunofluorescence; IL-6 and IL-8 mRNA by qPCR; and plasmatic levels by ELISA. Senescence markers that were elevated in PBMCs of aMCI patients, such as SA-ß-Gal, Go-G1 arrested cells, IL-6 and IL-8 mRNA expression, and IL-8 plasmatic levels, were decreased in PBMCs of Ca + aMCI patients to levels similar to those of controls or of cancer survivors without cognitive impairment, suggesting that cancer in the past leaves a fingerprint that can be peripherally traceable in PBMC samples. These results support the hypothesis that the senescence process might be involved in the inverse association between cancer and AD.
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Doença de Alzheimer , Disfunção Cognitiva , Neoplasias , Humanos , Leucócitos Mononucleares , Doença de Alzheimer/genética , Interleucina-6 , Interleucina-8 , Testes Neuropsicológicos , Disfunção Cognitiva/genética , Cognição , RNA MensageiroRESUMO
OBJECTIVE: The objective of the present study was to provide statewide estimates of real-world effectiveness in reducing the odds of one primary (symptomatic COVID-19 infection) and two secondary outcomes (hospitalization and severe COVID-19 infection) by four vaccines BNT162b2 (Pfizer-BioNTech), ChAdOx1 (AstraZeneca), Ad5-nCoV (CanSinoBIO), and CoronaVac (Sinovac Life Sciences), used in Northeast Mexico. DESIGN: We conducted a test-negative case-control study and analyzed statewide surveillance data from December 2020 to August 2021. SITE: Primary attention and hospitalization. PARTICIPANTS: Two inclusion criteria were applied, age≥18 years and having a real-time reverse-transcriptase-polymerase-chain-reaction assay or a rapid test for antigen detection in postnasal samples (N=164,052). The vaccination was considered complete if at least 14 days had passed since the application of the single or second dose and the beginning of symptomatology. INTERVENTIONS: Does not apply. MAIN MEASUREMENTS: Point and 95% confidence intervals (CI) of vaccine effectiveness were calculated per type of vaccine using the formula 1 - odds ratio, adjusted by sex and age. RESULTS: Complete vaccination offered from none (CoronaVac - Sinovac) to 75% (95%CI 71, 77) (BNT162b2 - Pfizer) effectiveness in reducing symptomatic COVID-19 infection, regardless of sex and age. The fully ChAdOx1 (AstraZeneca) scheme reached the maximum effectiveness in hospitalization (80%, 95%CI 69, 87) and the fully BNT162b2 (Pfizer) scheme the maximum effectiveness in severity (81%, 95%CI 64, 90). CONCLUSIONS: More studies are needed to compare benefits of different vaccines and guide policy makers select the best option for their population.
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COVID-19 , SARS-CoV-2 , Humanos , Adolescente , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacina BNT162 , Estudos de Casos e Controles , México/epidemiologiaRESUMO
With the increasing prevalence of Alzheimer's disease (AD) and difficulties in finding effective treatments, it is essential to discover alternative therapies through new approaches. In this regard, non-pharmacological therapies, such as physical exercise, have been proposed and explored for the treatment of AD. Recent studies have suggested that resistance exercise (RE) is an effective strategy for promoting benefits in memory and cognitive function, producing neuroprotective and anti-inflammatory effects, and reducing amyloid load and plaques, thereby reducing the risk, and alleviating the neurodegeneration process of AD and other types of dementia in the elderly. In addition, RE is the exercise recommended by the World Health Organization for the elderly due to its benefits in improving muscle strength and balance, and increasing autonomy and functional capacity, favoring improvements in the quality of life of the elderly population, who is more likely to develop AD and other types of dementia. In this mini-review, we discuss the impact of RE on humans affected by MCI and AD, and animal models of AD, and summarize the main findings regarding the effects of RE program on memory and cognitive functions, neurotrophic factors, Aß deposition and plaque formation, as well as on neuroinflammation. Overall, the present review provides clinical and preclinical evidence that RE plays a role in alleviating AD symptoms and may help to understand the therapeutic potential of RE, thereby continuing the advances in AD therapies.
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Melatonin is a hormone secreted by the pineal gland, it can be associated with circadian rhythms, aging and neuroprotection. Melatonin levels are decreased in sporadic Alzheimer's disease (sAD) patients, which suggests a relationship between the melatonergic system and sAD. Melatonin may reduce inflammation, oxidative stress, TAU protein hyperphosphorylation, and the formation of ß-amyloid (Aß) aggregates. Therefore, the objective of this work was to investigate the impact of treatment with 10 mg/kg of melatonin (i.p) in the animal model of sAD induced by the intracerebroventricular (ICV) infusion of 3 mg/kg of streptozotocin (STZ). ICV-STZ causes changes in the brain of rats similar to those found in patients with sAD. These changes include; progressive memory decline, the formation of neurofibrillary tangles, senile plaques, disturbances in glucose metabolism, insulin resistance and even reactive astrogliosis characterized by the upregulation of glucose levels and glial fibrillary acidic protein (GFAP). The results show that ICV-STZ caused short-term spatial memory impairment in rats after 30 days of STZ infusion without locomotor impairment which was evaluated on day 27 post-injury. Furthermore, we observed that a prolonged 30-day treatment with melatonin can improve the cognitive impairment of animals in the Y-maze test, but not in the object location test. Finally, we demonstrated that animals receiving ICV-STZ have high levels of Aß and GFAP in the hippocampus and that treatment with melatonin reduces Aß levels but does not reduce GFAP levels, concluding that melatonin may be useful to control the progression of amyloid pathology in the brain.
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Background: Major atopic diseases such as atopic dermatitis (AD), allergic rhinitis (AR), and asthma share the same atopic background, but they often show differences in their epidemiological behavior. Objective: We aimed to report the profile of these atopic diseases in a large Mexican population, including their age-related incidences, male:female (M:F) ratios, recent time trends, and association with altitude. Methods: Registries from the largest, nationwide health institution in Mexico (more than 34 million insured subjects), were reviewed. New cases of AD, AR, and asthma diagnosed each year by family physicians from 2007 to 2019 were adjusted by the corresponding insured population to estimate incidence rates. Results: Incidences of the 3 atopic diseases were highest in the 0-4 years age-group and progressively decreased thereafter until adolescence. Asthma and AR, but not AD, were more frequent in males during childhood (M:F ratios of 1.5, 1.3, and 0.95, respectively), but predominated in females during adulthood (M:F ratios of 0.52, 0.68, and 0.73, respectively). Time trends showed an initial increasing trend of annual incidences, with a peak around 2009-2011, and a downward trend afterward. This decreasing trend was seen in all age-groups and was more evident for AD (â¼50% drop) and asthma (â¼40% drop) than for AR (â¼20% drop). Geographical distribution suggested that incidences of asthma and AR, but not of AD, had an inverse association with altitude. Conclusion: Annual incidences of the 3 major atopic diseases have declined in recent years in almost all age groups, and their epidemiological profile during the life span showed contrasting differences according to age, sex, and ecological association with altitude, mainly regarding AD.
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Alzheimer's dementia (AD) is a neurodegenerative disorder that causes memory loss and dementia in older adults. Intracellular accumulation of Aß causes an imbalance in the oxidative status and cognitive dysfunctions. Besides oxidative stress and loss of memory, Alzheimer's patients show dysfunction of the circadian rhythms. The objective of this work was to evaluate the consequences of an intracerebroventricular injection of Aß (1-42) on temporal patterns of cognitive performance, as well as on lipid peroxidation, protein oxidation and total antioxidant capacity levels, in the rat temporal cortex. Holtzman male rats from control and Aß-injected groups were used in this study. We found that MDA, protein carbonyls and total antioxidant capacity levels displayed day-night oscillations in the rat temporal cortex and spatial memory performance also varied rhythmically. An intracerebroventricular injection of Aß (1-42) modified temporal patterns of cognitive performance as well as daily profiles of parameters of oxidative stress. Thus, elevated levels of Aß aggregates induces alterations in daily rhythmicity of parameters of oxidative stress and, consequently, would affect cellular clock activity, affecting the spatial memory performance in the AD.