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1.
Artigo em Inglês | MEDLINE | ID: mdl-38500298

RESUMO

Standardised terminology in science is important for clarity of interpretation and communication. In invasion science - a dynamic and rapidly evolving discipline - the proliferation of technical terminology has lacked a standardised framework for its development. The result is a convoluted and inconsistent usage of terminology, with various discrepancies in descriptions of damage and interventions. A standardised framework is therefore needed for a clear, universally applicable, and consistent terminology to promote more effective communication across researchers, stakeholders, and policymakers. Inconsistencies in terminology stem from the exponential increase in scientific publications on the patterns and processes of biological invasions authored by experts from various disciplines and countries since the 1990s, as well as publications by legislators and policymakers focusing on practical applications, regulations, and management of resources. Aligning and standardising terminology across stakeholders remains a challenge in invasion science. Here, we review and evaluate the multiple terms used in invasion science (e.g. 'non-native', 'alien', 'invasive' or 'invader', 'exotic', 'non-indigenous', 'naturalised', 'pest') to propose a more simplified and standardised terminology. The streamlined framework we propose and translate into 28 other languages is based on the terms (i) 'non-native', denoting species transported beyond their natural biogeographic range, (ii) 'established non-native', i.e. those non-native species that have established self-sustaining populations in their new location(s) in the wild, and (iii) 'invasive non-native' - populations of established non-native species that have recently spread or are spreading rapidly in their invaded range actively or passively with or without human mediation. We also highlight the importance of conceptualising 'spread' for classifying invasiveness and 'impact' for management. Finally, we propose a protocol for classifying populations based on (i) dispersal mechanism, (ii) species origin, (iii) population status, and (iv) impact. Collectively and without introducing new terminology, the framework that we present aims to facilitate effective communication and collaboration in invasion science and management of non-native species.

2.
J Med Chem ; 67(7): 5603-5616, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38513080

RESUMO

Vaccines are one of the greatest achievements of modern medicine. Due to their safer profile, the latest investigations usually focus on subunit vaccines. However, the active component often needs to be coupled with an adjuvant to be effective and properly trigger an immune response. We are developing a new synthetic monosaccharide-based TLR4 agonist, such as glucosamine-derived compounds FP18 and FP20, as a potential vaccine adjuvant. In this study, we present a new FP20 derivative, FP20Hmp, with a hydroxylated ester linked to the glucosamine core. We show that the modification introduced improves the activity of the adjuvant and its solubility. This study presents the synthesis of FP20Hmp, its in vitro characterization, and in vivo activity while coupled with the ovalbumin antigen or in formulation with an enterococcal antigen. We show that FP20Hmp enables increased production of antigen-specific antibodies that bind to the whole bacterium.


Assuntos
Adjuvantes de Vacinas , Enterococcus faecium , Receptor 4 Toll-Like , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/química , Vacinas de Subunidades , Glucosamina
3.
Front Immunol ; 15: 1284056, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38440728

RESUMO

Bats are natural host reservoirs and have adapted a unique innate immune system that permits them to host many viruses without exhibiting symptoms. Notably, bat interferon stimulated genes (ISGs) have been shown to play antiviral roles. Interferon induced protein with tetratricopeptide repeats 5 (IFIT5) is a well-characterised ISG in humans with antiviral activities against negative-sense RNA viruses via inhibiting viral transcription. Here, we aim to investigate if Pteropus alecto (pa) IFIT5 (paIFIT5) possess the ability to inhibit negative-sense RNA viruses. Initially, gene syntenic and comparative structural analyses of multiple animals highlighted a high level of similarity between Pteropus alecto and human IFIT5 proteins. Our results showed that paIFIT5 was significantly inducible by viral and dsRNA stimulation. Transient overexpression of paIFIT5 inhibited the replication of vesicular stomatitis virus (VSV). Using minireplicon and transcription reporter assays, we demonstrated the ability of paIFIT5 specifically to inhibit H17N10 polymerase activity. Mechanistically, we noticed that the antiviral potential of paIFIT5 against negative sense RNA viruses was retributed to its interaction with 5'ppp containing RNA. Taken together, these findings highlight the genetic and functional conservation of IFIT5 among mammals.


Assuntos
Quirópteros , Vírus de RNA , Animais , Humanos , Interferons/genética , Quirópteros/genética , Repetições de Tetratricopeptídeos , Antivirais
4.
ACS Catal ; 14(5): 2883-2896, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38449532

RESUMO

The catalytic dehydrogenation of substituted alkenones on noble metal catalysts supported on carbon (Pt/C, Pd/C, Rh/C, and Ru/C) was investigated in an organic phase under inert conditions. The dehydrogenation and semihydrogenation of the enone starting materials resulted in aromatic compounds (primary products), saturated cyclic ketones (secondary products), and cyclic alcohols (minor products). Pd/C exhibits the highest catalytic activity, followed by Pt/C and Rh/C. Aromatic compounds remain the primary products, even in the presence of hydrogen donors. Joint experimental and theoretical analyses showed that the four catalytic materials stabilize a common dienol intermediate on the metal surfaces, formed by keto-enol tautomerization. This intermediate subsequently forms aromatic products upon dehydrogenation. The binding orientation of the enone reactants on the catalytic surface is strongly metal-dependent, as the M-O bond distance changes substantially according to the metal. The longer M-O bonds (Pt: 2.84 Å > Pd: 2.23 Å > Rh: 2.17 Å > Ru: 2.07 Å) correlate with faster reaction rates and more favorable keto-enol tautomerization, as shorter distances correspond to a more stabilized starting material. Tautomerization is shown to occur via a stepwise surface-assisted pathway. Overall, each of the studied metals exhibits a distinct balance of enthalpy and entropy of activation (ΔH°‡, ΔS°‡), offering unique possibilities in the realm of enone dehydrogenation reactions that can be achieved by suitable selection of catalytic materials.

5.
GE Port J Gastroenterol ; 31(1): 33-40, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38476306

RESUMO

Background: Endoscopic submucosal dissection (ESD) is a minimally invasive technique for en bloc resection of superficial neoplastic lesions, independent of their size. However, for giant gastrointestinal superficial neoplasia, the risk of invasive cancer is higher, and ESD is typically challenging. Despite the increasing literature on giant resections, data on their efficacy and safety are still lacking. Objective: The aim of this study was to describe ESD outcomes from a Portuguese center, compare them with other international studies, and analyze the possible risk factors influencing outcomes. Methods: We conducted a retrospective single-center review using a prospectively collected database, including patients with rectal ESD resections larger than 10 cm, between January 2016 and December 2021. Clinical, procedural, and pathological data were collected and analyzed. Revision of the literature for comparison with international results was done through PubMed. Data were analyzed and statistical analysis performed, using Microsoft Excel and SPSS, to identify significant risk factors. Results: The study included 15 rectal resections, with a mean diameter of 140.9 mm (range 105-270), corresponding to lesions of 125.9 mm (87-238). The overall en bloc resection rate was 100% (n = 15). According to ESGE criteria, procedure was considered curative in 53.3% (n = 8), non-curative with high risk in 13.3% (n = 2), and local-risk recurrence in 33.3% (n = 5). Adverse events occurred in 26.7% (n = 4): 1 minor perforation and 3 stenosis, most endoscopically managed. For non-curative resections with local-risk recurrence, surveillance without adjuvant therapy was performed in all cases. For high-risk non-curative resections, surgery was performed in 1 patient and adjuvant chemoradiation therapy in another. Follow-up (mean 16 months) demonstrated a recurrence rate of 0%. Statistical analysis revealed resection size ≥20 cm as a risk factor for perforation (p value 0.067), and involvement of ≥90% of the circumference and procedural time ≥4 h as risk factors for stenosis (p value 0.029 and 0.009, respectively). Conclusions: Although challenging, ESD for giant lesions seems effective and safe, with a still relevant rate of complications, which were mostly endoscopically treated. Rigorous characterization of lesions is crucial to predict and avoid complications or the need for therapy escalation.


Background: A dissecao endoscopica da submucosa (DES) e uma tecnica minimamente invasiva para ressecao em bloco de tumores superficiais, independentemente do seu tamanho. No entanto, nas neoplasias superficiais gastrointestinais gigantes, o risco de cancro invasivo esta aumentado e a DES e tipicamente desafiante. Apesar do incremento da literatura acerca de ressecoes gigantes, dados da sua eficacia e seguranca sao ainda escassos. Objetivo: Descricao de outcomes de DES de um centro portugues e comparacao com estudos internacionais. Analise de eventuais fatores de risco influenciando os outcomes. Métodos: Revisao retrospetiva de um centro, usando a sua base de dados prospectivamente colhida, incluindo pacientes com ressecoes rectais por DES maiores que 10 cm, entre janeiro 2016 e dezembro 2021. Dados clinicos, endoscopicos e patologicos foram colhidos e analisados. A literatura foi revista atraves do PubMed, para comparacao com resultados internacionais. A analise dos resultados e estatistica foi realizada, utilizando o Microsoft Excel e SPSS, para a identificacao de fatores de risco com impacto significativo nos outcomes. Resultados: O estudo incluiu um total de 15 ressecoes retais, com uma media de diametros de 140,9 mm (intervalo 105­270), correspondendo a lesoes 125,9 mm (intervalo 87­238). A taxa de ressecao em bloco foi de 100% (n = 15). Segundo os criterios da ESGE, o procedimento foi curativo em 53,3% (n = 8), nao curativo com alto risco em 13,3% (n = 2) e com risco de recorrencia local em 33,3% (n = 5). Eventos adversos ocorreram em 26,7% (n = 4): 1 microperfuracao e 3 estenoses, a maioria geridas endoscopicamente. Os 5 casos nao curativos com risco de recorrencia local ficaram apenas sob vigilancia. Nas resseccoes nao curativas de alto risco, um paciente foi submetido a cirurgia e outro a quimioradioterapia adjuvante. O follow-up (media de 16 meses) demonstrou uma taxa de recorrencia de 0%. A analise estatistica demonstrou o tamanho da resseccao ≥20 cm como fator de risco significativo para perfuracao (p value 0.067); e envolvimento de ≥ 90% da circunferencia do lumen e tempo de procedimento ≥4h como fatores de risco significativos para estenose (p value 0.029 e 0.009, respetivamente). Conclusão: Apesar de desafiante, a DES para lesoes gigantes parece eficaz e segura, com uma taxa de complicacoes importante, possiveis de tratamento endoscopico. A caracterizacao rigorosa destas lesoes e crucial para predizer e evitar complicacoes ou a necessidade de escalada terapeutica.

6.
Microb Cell Fact ; 23(1): 69, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38419048

RESUMO

We are interested in converting second generation feedstocks into styrene, a valuable chemical compound, using the solvent-tolerant Pseudomonas putida DOT-T1E as a chassis. Styrene biosynthesis takes place from L-phenylalanine in two steps: firstly, L-phenylalanine is converted into trans-cinnamic acid (tCA) by PAL enzymes and secondly, a decarboxylase yields styrene. This study focuses on designing and synthesizing a functional trans-cinnamic acid decarboxylase in Pseudomonas putida. To achieve this, we utilized the "wholesale" method, involving deriving two consensus sequences from multi-alignments of homologous yeast ferulate decarboxylase FDC1 sequences with > 60% and > 50% identity, respectively. These consensus sequences were used to design Pseudomonas codon-optimized genes named psc1 and psd1 and assays were conducted to test the activity in P. putida. Our results show that the PSC1 enzyme effectively decarboxylates tCA into styrene, whilst the PSD1 enzyme does not. The optimal conditions for the PSC1 enzyme, including pH and temperature were determined. The L-phenylalanine DOT-T1E derivative Pseudomonas putida CM12-5 that overproduces L-phenylalanine was used as the host for expression of pal/psc1 genes to efficiently convert L-phenylalanine into tCA, and the aromatic carboxylic acid into styrene. The highest styrene production was achieved when the pal and psc1 genes were co-expressed as an operon in P. putida CM12-5. This construction yielded styrene production exceeding 220 mg L-1. This study serves as a successful demonstration of our strategy to tailor functional enzymes for novel host organisms, thereby broadening their metabolic capabilities. This breakthrough opens the doors to the synthesis of aromatic hydrocarbons using Pseudomonas putida as a versatile biofactory.


Assuntos
Carboxiliases , Cinamatos , Pseudomonas putida , Estireno/metabolismo , Pseudomonas/genética , Pseudomonas/metabolismo , Carboxiliases/genética , Carboxiliases/metabolismo , Pseudomonas putida/metabolismo , Fenilalanina/metabolismo
7.
J Craniofac Surg ; 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363319

RESUMO

Blepharoplasty is a commonly performed cosmetic surgery worldwide to address the excess skin and fat on the upper eyelids. The purpose of this paper is to present a surgical variation on blepharoplasty, achieving more pleasant outcomes. This paper describes the cauterization + plication technique, which involves using a cauterizing tool to remove excess skin and fat from the upper eyelid before using sutures to create a crease. It provides valuable insights into the advantages and limitations of this technique, drawing on relevant literature and clinical experience. Muscle cauterization and plication technique is an upgrade from the traditional technique, producing more esthetically pleasing results. This study highlights the importance of understanding the different techniques available for blepharoplasty to achieve the best possible outcomes for patients.

8.
Environ Sci Pollut Res Int ; 31(2): 2129-2144, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38057673

RESUMO

Since starts the coronavirus disease 2019 (COVID-19) pandemic identified the presence of genomic fragments of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in various environmental matrices: domestic sewage, surface waters, and contaminated freshwater. Environmental monitoring of SARS-CoV-2 is a tool for evaluating trend curves over the months, compared to several clinical cases of the disease. The objective of this study was to monitor the SARS-CoV-2 in environmental samples collected in different sites in a metropolitan area of Porto Alegre, Southern Brazil. During 10 months from 2020 to 2021, 300 samples were collected weekly and biweekly from nine points located in 3 cities: one point from a wastewater treatment plant (WWTP) in São Leopoldo (fortnightly collection), two points in Dilúvio Stream in Porto Alegre (fortnightly collection), two points in Pampa and Luiz Rau Streams (weekly collection), and two points in public fountains (fortnightly collection) in Novo Hamburgo. After collection, samples were concentrated by ultracentrifugation, and viral nucleic acids were extracted using MagMax® Core Nucleic Acid Purifications kits and submitted to RT-qPCR, using E, N1, and N2 gene targets of SARS-CoV-2. Only 7% (3/41) samples from public fountains were positive, with a mean viral load (VL) of SARS-CoV-2 RNA of 5.02 × 101 gc/l (2.41~8.59 × 101 gc/l), while the streams had average VL of 7.43 × 105 gc/l (Pampa), 7.06 × 105 gc/l (Luiz Rau), 2.01 × 105 gc/l (Dilúvio), and 4.46 × 105 cg/l (WWTP). The results showed varying levels of viral presence in different sample types, with a demonstrated correlation between environmental viral load and clinical COVID-19 cases. These findings contribute to understanding virus persistence and transmission pathways in the environment. Continuous monitoring, especially in less developed regions, is crucial for early detection of vaccine resistance, new variants, and potential COVID-19 resurgence.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , RNA Viral , Brasil/epidemiologia , Monitoramento Ambiental
9.
Viruses ; 15(11)2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-38005815

RESUMO

In Brazil, the state of Tocantins, located in north-central Brazil, has experienced a significant number of cases of arboviral disease, particularly Dengue virus (DENV). This study aimed to deepen the knowledge on DENV circulation within that state by conducting full genome sequencing of viral genomes recovered from 61 patients between June 2021 and July 2022. There were a total of 8807 and 20,692 cases in 2021 and 2022, respectively, as reported by the state's Secretary of Health. Nucleotide sequencing confirmed the circulation of DENV serotype 1, genotype V and DENV serotype 2, genotype III in the State. Younger age groups (4 to 43 years old) were mostly affected; however, no significant differences were detected regarding the gender distribution of cases in humans. Phylogenetic analysis revealed that the circulating viruses belong to DENV-1 genotype V American and DENV-2 genotype III Southeast Asian/American. The Bayesian analysis of DENV-1 genotype V genomes sequenced here are closely related to genomes previously sequenced in the state of São Paulo. Regarding the DENV-2 genotype III genomes, these clustered in a distinct, well-supported subclade, along with previously reported isolates from the states of Goiás and São Paulo. The findings reported here suggest that multiple introductions of these genotypes occurred in the Tocantins state. This observation highlights the importance of major population centers in Brazil on virus dispersion, such as those observed in other Latin American and North American countries. In the SNP analysis, DENV-1 displayed 122 distinct missense mutations, while DENV-2 had 44, with significant mutations predominantly occurring in the envelope and NS5 proteins. The analyses performed here highlight the concomitant circulation of distinct DENV-1 and -2 genotypes in some Brazilian states, underscoring the dynamic evolution of DENV and the relevance of surveillance efforts in supporting public health policies.


Assuntos
Vírus da Dengue , Dengue , Humanos , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Dengue/epidemiologia , Filogenia , Sorogrupo , Brasil/epidemiologia , Teorema de Bayes , Genótipo
11.
Saude e pesqui. (Impr.) ; 16(4): 11823, out./dez. 2023.
Artigo em Inglês, Português | LILACS-Express | LILACS | ID: biblio-1518423

RESUMO

Analisar a correlação entre estresse, ansiedade e depressão com a síndrome de Burnout em estudantes de graduação de uma universidade pública federal. Trata-se de um estudo exploratório-descritivo, com abordagem quantitativa, que utilizou um questionário on-line para coleta de dados, que ocorreu entre dezembro de 2021 e março de 2022, disponibilizado por e-mail. Participaram 169 discentes, e a correlação entre as variáveis sociodemográficas e as dimensões estresse, ansiedade e depressão evidenciou que os brasileiros, principalmente as mulheres e praticantes de alguma religião, mostraram escores mais elevados. Quanto à síndrome de Burnout, notaram-se valores altos para as dimensões exaustão emocional e eficácia profissional, mas escores baixos para a dimensão descrença. Ao verificar-se a correlação entre a escala de ansiedade, depressão e estresse e a síndrome de Burnout, percebeu-se uma relação negativa entre seus domínios e a eficácia estudantil. Revelou-se também uma correlação entre a depressão e a exaustão emocional.


To analyze the correlation between stress, anxiety, and depression with the Burnout syndrome in undergraduate students at a federal public university. This is an exploratory descriptive study, with a quantitative approach, which used an online questionnaire for data collection, which took place from December 2021 to March 2022, available by email. 169 students participated in the study, in which the correlation between sociodemographic variables and the dimensions stress, anxiety and depression showed that Brazilians, especially women and practitioners of some religion, showed higher scores. As for the Burnout syndrome, high values were observed for the emotional exhaustion and professional efficacy dimensions, but low scores for the disbelief dimension. When verifying the correlation between the anxiety, depression and stress scale and the Burnout syndrome, a negative relationship between its domains and student effectiveness was noticed. A correlation was also revealed between depression and emotional exhaustion.

12.
Aging Cell ; 22(12): e13983, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37858983

RESUMO

Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal genetic condition that arises from a single nucleotide alteration in the LMNA gene, leading to the production of a defective lamin A protein known as progerin. The accumulation of progerin accelerates the onset of a dramatic premature aging phenotype in children with HGPS, characterized by low body weight, lipodystrophy, metabolic dysfunction, skin, and musculoskeletal age-related dysfunctions. In most cases, these children die of age-related cardiovascular dysfunction by their early teenage years. The absence of effective treatments for HGPS underscores the critical need to explore novel safe therapeutic strategies. In this study, we show that treatment with the hormone ghrelin increases autophagy, decreases progerin levels, and alleviates other cellular hallmarks of premature aging in human HGPS fibroblasts. Additionally, using a HGPS mouse model (LmnaG609G/G609G mice), we demonstrate that ghrelin administration effectively rescues molecular and histopathological progeroid features, prevents progressive weight loss in later stages, reverses the lipodystrophic phenotype, and extends lifespan of these short-lived mice. Therefore, our findings uncover the potential of modulating ghrelin signaling offers new treatment targets and translational approaches that may improve outcomes and enhance the quality of life for patients with HGPS and other age-related pathologies.


Assuntos
Senilidade Prematura , Progéria , Adolescente , Criança , Humanos , Camundongos , Animais , Progéria/tratamento farmacológico , Progéria/genética , Progéria/metabolismo , Senilidade Prematura/tratamento farmacológico , Senilidade Prematura/genética , Grelina/farmacologia , Qualidade de Vida , Pele/metabolismo , Lamina Tipo A/genética , Lamina Tipo A/metabolismo , Envelhecimento
13.
Gastrointest Endosc ; 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37879543

RESUMO

BACKGROUND AND AIMS: Circumferential endoscopic submucosal dissection (cESD) in the esophagus has been reported to be feasible in small Eastern case series. We assessed the outcomes of cESD in the treatment of early esophageal squamous cell carcinoma (ESCC) in Western countries. METHODS: We conducted an international study at 25 referral centers in Europe and Australia using prospective databases. We included all patients with ESCC treated with cESD before November 2022. Our main outcomes were curative resection according to European guidelines and adverse events. RESULTS: A total of 171 cESDs were performed on 165 patients. En bloc and R0 resections rates were 98.2% (95% confidence interval [CI], 95.0-99.4) and 69.6% (95% CI, 62.3-76.0), respectively. Curative resection was achieved in 49.1% (95% CI, 41.7-56.6) of the lesions. The most common reason for noncurative resection was deep submucosal invasion (21.6%). The risk of stricture requiring 6 or more dilations or additional techniques (incisional therapy/stent) was high (71%), despite the use of prophylactic measures in 93% of the procedures. The rates of intraprocedural perforation, delayed bleeding, and adverse cardiorespiratory events were 4.1%, 0.6%, and 4.7%, respectively. Two patients died (1.2%) of a cESD-related adverse event. Overall and disease-free survival rates at 2 years were 91% and 79%. CONCLUSIONS: In Western referral centers, cESD for ESCC is curative in approximately half of the lesions. It can be considered a feasible treatment in selected patients. Our results suggest the need to improve patient selection and to develop more effective therapies to prevent esophageal strictures.

14.
Nanoscale Horiz ; 8(12): 1700-1710, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-37819240

RESUMO

A selenium-containing metal-organic framework with remarkable antioxidant capacity and ROS-scavenging activity was constructed by a controlled de novo encapsulation approach of a glycoconjugate mimetic, specifically a sp2-iminoglycolipid bearing a selenoureido fragment (DSeU), within a zeolitic-imidazolate framework exoskeleton. Biocompatible and homogeneous nanosized particles of ∼70 nm (DSeU@ZIF8) were obtained, which could be efficiently internalized in cells, overcoming the poor solubility in biological media and limited bioavailability of glycolipids. The ZIF-particle served as nanocarrier for the intracellular delivery of the selenocompound to cells, promoted by the acidic pH inside endosomes/lysosomes. As demonstrated by in vitro studies, the designed DSeU@ZIF8 nanoparticles displayed a high antioxidant activity at low doses; lower intracellular ROS levels were observed upon the uptake of DSeU@ZIF8 by human endothelial cells. Even more interesting was the finding that these DSeU@ZIF8 particles were able to reverse to a certain level the oxidative stress induced in cells by pre-treatment with an oxidizing agent. This possibility of modulating the oxidative stress in living cells may have important implications in the treatment of diverse pathological complications that are generally accompanied with elevated ROS levels.


Assuntos
Antioxidantes , Nanopartículas , Humanos , Antioxidantes/uso terapêutico , Células Endoteliais , Espécies Reativas de Oxigênio , Estresse Oxidativo
15.
ACS Omega ; 8(39): 36412-36417, 2023 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-37810727

RESUMO

Lipopolysaccharide (LPS) mimicry leading to toll-like receptor 4 (TLR4) active compounds has been so far based mainly on reproducing the lipid A portion of LPS. Our work led to a series of structurally simplified synthetic TLR4 agonists in preclinical development as vaccine adjuvants called FPs. FPs bind MD2/TLR4 similarly to lipid A, inserting the lipid chains in the MD2 lipophilic cavity. A strategy to improve FPs' target affinity is introducing a monosaccharide unit in C6, mimicking the first sugar of the LPS core. We therefore designed a panel of FP derivatives bearing different monosaccharides in C6. We report here the synthesis and optimization of FPs' C6 glycosylation, which presented unique challenges and limitations. The biological activity of glycosylated FP compounds was preliminarily assessed in vitro in HEK-Blue cells. The new molecules showed a higher potency in stimulating TLR4 activation when compared to the parent molecule while maintaining TLR4 selectivity.

16.
Sci Total Environ ; 904: 166774, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37660804

RESUMO

The increasing use of plastics and the growing concern about their impact on the environment and living beings makes it necessary to study how microplastics (MP) affect aquaculture systems. In order to gain an in-depth understanding of these systems, this study covers the water intake, the purification treatment at the inlet, the water in the culture tanks, as well as the feed used in the feeding and the organism itself. For this purpose, five samples were taken, both in the water line, feed and sea bass during the weeks of the experiment. It is shown that the available purification systems reduce the amount of MP entering from the receiving environment. However, new MP are observed in the sea bass tank, which may be due mainly to those added through the feed and found in the feed, as well as in the piping and other materials used in current aquaculture systems (PTFE, PA, among others). If focusing on the feed that can reach the consumer, in the case of this study, carried out with sea bass, some types of MP (PE, PTFE, PS and PA) were found in 4 head samples and 4 skin/muscle samples. Although inlet water purification systems manage to reduce a high percentage of MPs in the system, it is observed that there are other access routes that should be considered and reduced in aquaculture facilities to prevent them from reaching the human consumer.


Assuntos
Bass , Poluentes Químicos da Água , Animais , Humanos , Microplásticos , Plásticos , Bass/fisiologia , Aquicultura , Água , Politetrafluoretileno
17.
Med. segur. trab ; 69(270): 28-39, 14 sept. 2023. tab
Artigo em Espanhol | IBECS | ID: ibc-225333

RESUMO

Objetivo: Estimar el grado de alfabetización para la salud (AS) de las técnicas en cuidados auxiliares de enfermería (TCAE) y del personal no sanitario perteneciente a la plantilla laboral de 4 hospitales españoles.Método: Estudio descriptivo-correlacional, siendo la población diana las TCAE a quienes se preguntó, mediante formulario online HLS-EU-Q16 (Health Literacy Survey - European Union), con escala Likert de 4 valores (de 1 muy fácil a 4 muy difícil). Resultados: Respondieron 477 profesionales. Los resultados para la AS global fueron: media 1,95 ± 0,03 y mediana 1,94. El nivel de alfabetización en salud (NAS) demostró AS suficiente en 293 (61,43%) individuos. La mediana sobre la AS de los 3 componentes del cuestionario fue: cuidado sanitario = 2, prevención de enfermedades = 2 y promo-ción de la salud = 1,75. El ítem sobre sobre la manera de abordar problemas de salud mental es el que presentó mayor dificultad con media de 2,45 ± 0,04 y mediana igual a 2. No hubo diferencias significativas entre TCAE y el personal no sanitario.Conclusiones: El grado de AS de las TCAE resultó ser bueno, tanto a nivel global como en las dimensiones de aten-ción y cuidado sanitario, prevención de enfermedades y promoción de la salud. Asimismo, el nivel de alfabetización en salud que se obtuvo resultó ser suficiente en la mayoría de ellas. No se encontró diferencias con el personal no sanitario perteneciente a la plantilla laboral de 4 hospitales estudiados (AU)


Objetive: To estimate the degree of health literacy (HL) of nursing auxiliary care technicians (NACT) and non-health personnel belonging to the workforce of 4 Spanish hospitals.Method: A descriptive-correlational research, with NACT as target population. They were asked, using the online form HLS-EU-Q16 (Health Literacy Survey - European Union), with a Likert scale of 4 values (from 1 very easy to 4 very difficult).Results: 477 professionals answered the form. The results for global SA were: mean 1.95 ± 0.03 and median 1.94. The health literacy level (HLL) demonstrated sufficient HL in 293 (61.43%) individuals. The median on the HL for the 3 components of the questionnaire was: health care = 2, disease prevention = 2 and health promotion = 1.75. The item about how to deal with mental health problems showed the greatest difficulty with a mean of 2.45 ± 0.04 and a median equal to 2. There were no significant differences between NACT and non-health personnel. Conclusions: The HL grade of the NACTs turned out to be good, both globally and in the dimensions of attention and health care, disease prevention and health promotion. Likewise, the level of health literacy obtained turned out to be enough in most of them. No differences were found with the non-health personnel belonging to the workforce of the 4 hospitals researched (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Recursos Humanos em Hospital , Pessoal Técnico de Saúde , Assistentes de Enfermagem , Letramento em Saúde , Inquéritos e Questionários , Estudos Transversais , Espanha
18.
Cancers (Basel) ; 15(16)2023 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-37627177

RESUMO

Testicular cancer is common in young men, and early detection and multimodality treatment can lead to successful outcomes. This study aims to identify sociodemographic and risk factors associated with higher testicular cancer mortality and poorer survival rates, while examining the impact of diagnostic and treatment procedures on reducing mortality. The retrospective ecological study analyzed mortality data from testicular cancer in Brazil from 2001 to 2020. Sociodemographic variables such as marital status, age, birth period, year of death (cohort), race, and geographic region were assessed. Risk factors included cryptorchidism and pesticide exposure. Data were subjected to statistical analysis, which revealed an increasing trend in mortality after 2011 among persons born after 1976 in the 15-40 age group. Individuals in the South Region, whites, and singles had higher age-standardized mortality rates (ASMRs), while singles had lower survival rates. The Northeast region had a higher survival rate. Fungicides and insecticides increase ASMR in Brazil. Herbicides increase ASMR in the Northeast and Midwest regions and insecticides increase ASMR in the Northeast, Southeast, and Midwest regions. High rates of implementation of diagnostic procedures in the Midwest were not sufficient to reduce ASMR. No treatment procedure was associated with mortality at the national or regional level.

19.
Virol J ; 20(1): 181, 2023 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-37587490

RESUMO

BACKGROUND: Influenza A virus (IAV) is endemic in pigs globally and co-circulation of genetically and antigenically diverse virus lineages of subtypes H1N1, H1N2 and H3N2 is a challenge for the development of effective vaccines. Virosomes are virus-like particles that mimic virus infection and have proven to be a successful vaccine platform against several animal and human viruses. METHODS: This study evaluated the immunogenicity of a virosome-based influenza vaccine containing the surface glycoproteins of H1N1 pandemic, H1N2 and H3N2 in pigs. RESULTS: A robust humoral and cellular immune response was induced against the three IAV subtypes in pigs after two vaccine doses. The influenza virosome vaccine elicited hemagglutinin-specific antibodies and virus-neutralizing activity. Furthermore, it induced a significant maturation of macrophages, and proliferation of B lymphocytes, effector and central memory CD4+ and CD8+ T cells, and CD8+ T lymphocytes producing interferon-γ. Also, the vaccine demonstrated potential to confer long-lasting immunity until the market age of pigs and proved to be safe and non-cytotoxic to pigs. CONCLUSIONS: This virosome platform allows flexibility to adjust the vaccine content to reflect the diversity of circulating IAVs in swine in Brazil. The vaccination of pigs may reduce the impact of the disease on swine production and the risk of swine-to-human transmission.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A , Vacinas contra Influenza , Influenza Humana , Humanos , Animais , Suínos , Vacinas Combinadas , Imunidade Humoral , Linfócitos T CD8-Positivos , Vírus da Influenza A Subtipo H3N2 , Virossomos
20.
Methods Mol Biol ; 2700: 57-74, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37603174

RESUMO

Fluorescent chemical probes are used nowadays as a chemical resource to study the physiology and pharmacology of several important endogenous receptors. Different fluorescent groups have been coupled with known ligands of these receptors, allowing the visualization of their localization and trafficking. One of the most important molecular players of innate immunity and inflammation are the Toll-Like Receptors (TLRs). These Pattern-Recognition Receptors (PRR) have as natural ligands microbial-derived pathogen-associated molecular patterns (PAMPs) and also endogenous molecules called danger-associated molecular patterns (DAMPs). These ligands activate TLRs to start a response that will determine the host's protection and overall cell survival but can also lead to chronic inflammation and autoimmune syndromes. TLRs action is tightly related to their subcellular localization and trafficking. Understanding this trafficking phenomenon can enlighten critical molecular pathways that might allow to decipher the causes of different diseases. In this chapter, the study of function, localization and trafficking of TLRs through the use of chemical probes will be discussed. Furthermore, an example protocol of the use of fluorescent chemical probes to study TLR4 trafficking using high-content analysis will be described.


Assuntos
Corantes Fluorescentes , Receptores Toll-Like , Humanos , Ligantes , Alarminas , Inflamação , Moléculas com Motivos Associados a Patógenos
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