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1.
Annu Rev Biochem ; 89: 159-187, 2020 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-32176523

RESUMO

This review focuses on imaging DNA and single RNA molecules in living cells to define eukaryotic functional organization and dynamic processes. The latest advances in technologies to visualize individual DNA loci and RNAs in real time are discussed. Single-molecule fluorescence microscopy provides the spatial and temporal resolution to reveal mechanisms regulating fundamental cell functions. Novel insights into the regulation of nuclear architecture, transcription, posttranscriptional RNA processing, and RNA localization provided by multicolor fluorescence microscopy are reviewed. A perspective on the future use of live imaging technologies and overcoming their current limitations is provided.


Assuntos
Núcleo Celular/ultraestrutura , Cromatina/ultraestrutura , DNA/ultraestrutura , Regulação da Expressão Gênica , RNA Mensageiro/ultraestrutura , Pequeno RNA não Traduzido/ultraestrutura , Animais , Núcleo Celular/genética , Núcleo Celular/metabolismo , Cromatina/metabolismo , DNA/genética , DNA/metabolismo , Replicação do DNA , Células Eucarióticas/metabolismo , Células Eucarióticas/ultraestrutura , Humanos , Microscopia de Fluorescência , Biossíntese de Proteínas , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Pequeno RNA não Traduzido/genética , Pequeno RNA não Traduzido/metabolismo , Imagem Individual de Molécula/instrumentação , Imagem Individual de Molécula/métodos , Coloração e Rotulagem/métodos , Telômero/metabolismo , Telômero/ultraestrutura , Transcrição Gênica
2.
Nat Rev Mol Cell Biol ; 22(7): 483-504, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33837370

RESUMO

Fine-tuning cellular physiology in response to intracellular and environmental cues requires precise temporal and spatial control of gene expression. High-resolution imaging technologies to detect mRNAs and their translation state have revealed that all living organisms localize mRNAs in subcellular compartments and create translation hotspots, enabling cells to tune gene expression locally. Therefore, mRNA localization is a conserved and integral part of gene expression regulation from prokaryotic to eukaryotic cells. In this Review, we discuss the mechanisms of mRNA transport and local mRNA translation across the kingdoms of life and at organellar, subcellular and multicellular resolution. We also discuss the properties of messenger ribonucleoprotein and higher order RNA granules and how they may influence mRNA transport and local protein synthesis. Finally, we summarize the technological developments that allow us to study mRNA localization and local translation through the simultaneous detection of mRNAs and proteins in single cells, mRNA and nascent protein single-molecule imaging, and bulk RNA and protein detection methods.


Assuntos
Biossíntese de Proteínas , Transporte de RNA , RNA Mensageiro/metabolismo , Animais , Grânulos Citoplasmáticos/metabolismo , Regulação da Expressão Gênica , Humanos , Ribonucleoproteínas/metabolismo
4.
Nucleic Acids Res ; 51(12): 6370-6388, 2023 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-37158240

RESUMO

Cells survive harsh environmental conditions by potently upregulating molecular chaperones such as heat shock proteins (HSPs), particularly the inducible members of the HSP70 family. The life cycle of HSP70 mRNA in the cytoplasm is unique-it is translated during stress when most cellular mRNA translation is repressed and rapidly degraded upon recovery. Contrary to its 5' untranslated region's role in maximizing translation, we discovered that the HSP70 coding sequence (CDS) suppresses its translation via the ribosome quality control (RQC) mechanism. The CDS of the most inducible Saccharomyces cerevisiae HSP70 gene, SSA4, is uniquely enriched with low-frequency codons that promote ribosome stalling during heat stress. Stalled ribosomes are recognized by the RQC components Asc1p and Hel2p and two novel RQC components, the ribosomal proteins Rps28Ap and Rps19Bp. Surprisingly, RQC does not signal SSA4 mRNA degradation via No-Go-Decay. Instead, Asc1p destabilizes SSA4 mRNA during recovery from heat stress by a mechanism independent of ribosome binding and SSA4 codon optimality. Therefore, Asc1p operates in two pathways that converge to regulate the SSA4 mRNA life cycle during stress and recovery. Our research identifies Asc1p as a critical regulator of the stress response and RQC as the mechanism tuning HSP70 synthesis.


Assuntos
Proteínas de Saccharomyces cerevisiae , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ribossomos/genética , Ribossomos/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Códon/metabolismo , Biossíntese de Proteínas
5.
Annu Rev Genet ; 50: 267-291, 2016 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-27893965

RESUMO

Recent advancements in single-cell and single-molecule imaging technologies have resolved biological processes in time and space that are fundamental to understanding the regulation of gene expression. Observations of single-molecule events in their cellular context have revealed highly dynamic aspects of transcriptional and post-transcriptional control in eukaryotic cells. This approach can relate transcription with mRNA abundance and lifetimes. Another key aspect of single-cell analysis is the cell-to-cell variability among populations of cells. Definition of heterogeneity has revealed stochastic processes, determined characteristics of under-represented cell types or transitional states, and integrated cellular behaviors in the context of multicellular organisms. In this review, we discuss novel aspects of gene expression of eukaryotic cells and multicellular organisms revealed by the latest advances in single-cell and single-molecule imaging technology.


Assuntos
Regulação da Expressão Gênica , Análise de Célula Única/métodos , Animais , Cromatina/química , Cromatina/genética , Citoplasma/genética , Perfilação da Expressão Gênica/métodos , Humanos , Regiões Promotoras Genéticas , Biossíntese de Proteínas , RNA Mensageiro/análise , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Células-Tronco/fisiologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transcrição Gênica
6.
Dig Dis ; 42(3): 257-264, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38452742

RESUMO

INTRODUCTION: Risk factors for developing pancreatitis due to thiopurines in patients with inflammatory bowel disease (IBD) are not clearly identified. Our aim was to evaluate the predictive pharmacogenetic risk of pancreatitis in IBD patients treated with thiopurines. METHODS: We conducted an observational pharmacogenetic study of acute pancreatitis events in a cohort study of IBD patients treated with thiopurines from the prospectively maintained ENEIDA registry biobank of GETECCU. Samples were obtained and the CASR, CEL, CFTR, CDLN2, CTRC, SPINK1, CPA1, and PRSS1 genes, selected based on their known association with pancreatitis, were fully sequenced. RESULTS: Ninety-five cases and 105 controls were enrolled; a total of 57% were women. Median age at pancreatitis diagnosis was 39 years. We identified 81 benign variants (50 in cases and 67 in controls) and a total of 35 distinct rare pathogenic and unknown significance variants (10 in CEL, 21 in CFTR, 1 in CDLN2, and 3 in CPA1). None of the cases or controls carried pancreatitis-predisposing variants within the CASR, CPA1, PRSS1, and SPINK1 genes, nor a pathogenic CFTR mutation. Four different variants of unknown significance were detected in the CDLN and CPA1 genes; one of them was in the CDLN gene in a single patient with pancreatitis and 3 in the CPA1 gene in 5 controls. After the analysis of the variants detected, no significant differences were observed between cases and controls. CONCLUSION: In patients with IBD, genes known to cause pancreatitis seem not to be involved in thiopurine-related pancreatitis onset.


Assuntos
Doenças Inflamatórias Intestinais , Pancreatite , Sistema de Registros , Humanos , Feminino , Pancreatite/induzido quimicamente , Pancreatite/genética , Masculino , Adulto , Estudos de Casos e Controles , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/tratamento farmacológico , Pessoa de Meia-Idade , Predisposição Genética para Doença , Fatores de Risco , Variação Genética , Mercaptopurina/efeitos adversos , Mercaptopurina/uso terapêutico
7.
Am J Emerg Med ; 81: 92-98, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38713933

RESUMO

BACKGROUND: Digoxin poisonings are relatively common and potentially fatal, requiring immediate therapeutic intervention, with special attention to the patient's hemodynamic status and the presence of electrocardiographic and electrolytic disturbances. OBJECTIVE: To identify factors associated with seven-day and thirty-day mortality in digoxin poisoning. DESIGN, SETTINGS AND PARTICIPANTS: A retrospective, observational, multicenter study was conducted across 15 Hospital Emergency Departments (HED) in Spain. All patients over 18 years of age who presented to participating HEDs from 2015 to 2021 were included. The inclusion criteria encompassed individuals meeting the criteria for digoxin poisoning, whether acute or chronic. OUTCOMES MEASURE AND ANALYSIS: To identify independent factors associated with 7-day and 30-day mortality, a multivariate analysis was conducted. This analysis included variables of clinical significance, as well as those exhibiting a trend (p < 0.1) or significance in the bivariate analysis. MAIN FINDINGS: A total of 658 cases of digoxin poisoning were identified. Mortality rates were 4.5% (30 patients) at seven days and 11.1% (73 patients) at thirty days. Regarding 7-day mortality, the mean age of deceased patients was comparable to survivors (84.7 (8.9) vs 83.9 (7.9) years; p = ns). The multivariate analysis revealed that factors independently associated with 7-day mortality encompassed the extent of dependence assessed by the Barthel Index (BI 60-89 OR 0.28; 95% CI 0.10-0.77; p = 0.014 and BI>90 OR 0.22; 95% CI 0.08-0.63; p = 0.005), the identification of ventricular arrhythmias (OR 1.34; 95% CI 1.34-25.21; p = 0.019), and the presence of circulatory (OR 2.84; 95% CI 1.19-6.27; p = 0.019) and neurological manifestations (OR 2.67; 95% CI 1.13-6.27; p = 0.025). Factors independently associated with 30-day mortality encompassed extent of dependence (BI 60-89 OR 0.37; 95% CI 0.20-0.71; p = 0.003 and BI>90 OR 0.18; 95% CI 0.09-0.39; p < 0.001) and the identification of circulatory (OR 2.13; 95% CI 1.10-4.15; p = 0.025) and neurological manifestations (OR 2.39; 95% CI 1.25-3.89; p = 0.006). CONCLUSIONS: The study identifies the degree of dependency assessed by the Barthel Index and the presence of cardiovascular and neurological symptoms as independent predictors of both 7-day and 30-day mortality. Additionally, the detection of ventricular arrhythmia is also an independent factor for 7-day mortality.


Assuntos
Digoxina , Humanos , Feminino , Digoxina/intoxicação , Digoxina/sangue , Masculino , Estudos Retrospectivos , Idoso , Idoso de 80 Anos ou mais , Espanha/epidemiologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Fatores de Risco , Pessoa de Meia-Idade
8.
J Appl Toxicol ; 44(3): 445-454, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37828814

RESUMO

In a changing environmental scenario, acid rain can have a significant impact on aquatic ecosystems. Acidification is known to produce corrosion in metals, hence increasing their harmful effects on the environment, organisms and human health. The prevalent use of metallic nanoparticles (NPs) in everyday products raises concerns regarding exposure and nanotoxicity even in these acidified conditions. We thus report on the cytotoxic and genotoxic potential of nickel oxide (NiO-NP) and zinc oxide (ZnO-NP) NPs when suspended in aqueous media in light of pH variations (7.5 and 5). A modified microsuspension method of the Salmonella/microsome assay was adopted, and strains (TA97a, TA98, TA100, TA102) were exposed to NPs (10-1280 µg/plate) with and without a metabolization fraction. The acidic condition favored disaggregation and caused a decrease in NPs size. Mutagenicity was observed in all samples and different strains, with greater DNA base pair substitution damage (TA100 and TA102), but extrinsic conditions (pH) suggest different action mechanisms of NiO-NP and ZnO-NP on genetic content. Mutagenic activity was found to increase upon metabolic activation (TA98, TA100, and TA102) demonstrating the bioactivity of NiO-NP and ZnO-NP in relation to metabolites generated by the mammalian p450 system in vitro. Modifications in the Salmonella assay methodology increased cell exposure time. The observed responses recommend this modified assay as one of the methodologies of choice for nanoecotoxicological evaluation. These findings emphasize the significance of incorporating the environmental context when evaluating the toxicity of metal-based NPs.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Óxido de Zinco , Animais , Humanos , Ecossistema , Concentração de Íons de Hidrogênio , Mamíferos , Nanopartículas Metálicas/toxicidade , Mutagênicos , Nanopartículas/toxicidade , Óxido de Zinco/toxicidade
9.
J Biol Chem ; 298(5): 101796, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35248532

RESUMO

All cells possess an internal stress response to cope with environmental and pathophysiological challenges. Upon stress, cells reprogram their molecular functions to activate a survival mechanism known as the heat shock response, which mediates the rapid induction of molecular chaperones such as the heat shock proteins (HSPs). This potent production overcomes the general suppression of gene expression and results in high levels of HSPs to subsequently refold or degrade misfolded proteins. Once the damage or stress is repaired or removed, cells terminate the production of HSPs and resume regular functions. Thus, fulfillment of the stress response requires swift and robust coordination between stress response activation and completion that is determined by the status of the cell. In recent years, single-cell fluorescence microscopy techniques have begun to be used in unravelling HSP-gene expression pathways, from DNA transcription to mRNA degradation. In this review, we will address the molecular mechanisms in different organisms and cell types that coordinate the expression of HSPs with signaling networks that act to reprogram gene transcription, mRNA translation, and decay and ensure protein quality control.


Assuntos
Proteínas de Choque Térmico , Proteostase , Proteínas de Choque Térmico/metabolismo , Resposta ao Choque Térmico/fisiologia , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Transdução de Sinais
10.
Clin Gastroenterol Hepatol ; 21(2): 406-414.e7, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35124272

RESUMO

BACKGROUND & AIMS: There is conflicting evidence regarding the prevalence of and risk factors for metabolic-associated fatty liver disease (MAFLD) in patients with inflammatory bowel disease (IBD). We aimed to determine MAFLD prevalence and risk factors in IBD patients. METHODS: Cross-sectional, case-control study included all consecutive IBD patients treated at 2 different university hospitals. Controls were subjects randomly selected from the general population and matched by age, sex, type 2 diabetes status, and body mass index in a 1:2 ratio. MAFLD was confirmed by controlled attenuation parameter. Liver biopsies were collected when MAFLD with significant liver fibrosis was suspected. In addition, age- and fibrosis stage-paired non-IBD patients with biopsy-proven MAFLD served as a secondary control group. RESULTS: Eight hundred thirty-one IBD patients and 1718 controls were included. The prevalence of MAFLD and advanced liver fibrosis (transient elastography ≥9.7 kPa) was 42.00% and 9.50%, respectively, in IBD patients and 32.77% and 2.31%, respectively, in the general population (P < .001). A diagnosis of IBD was an independent predictor of MAFLD (adjusted odds ratio, 1.99; P < .001) and an independent risk factor for advanced liver fibrosis (adjusted odds ratio, 5.55; P < .001). Liver biopsies were obtained from 40 IBD patients; MAFLD was confirmed in all cases, and fibrosis of any degree was confirmed in 25 of 40 cases (62.5%). Body mass index and type 2 diabetes prevalence were significantly lower in IBD-MAFLD patients than in severity-paired patients with biopsy-proven MAFLD. CONCLUSIONS: MAFLD and liver fibrosis are particularly prevalent in IBD patients, regardless of the influence of classic metabolic risk factors.


Assuntos
Diabetes Mellitus Tipo 2 , Doenças Inflamatórias Intestinais , Hepatopatia Gordurosa não Alcoólica , Humanos , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Doenças Inflamatórias Intestinais/complicações , Cirrose Hepática/complicações , Cirrose Hepática/epidemiologia , Fatores de Risco , Masculino , Feminino
11.
J Toxicol Environ Health B Crit Rev ; 26(3): 172-199, 2023 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-36775848

RESUMO

This review examined the mutagenicity and genotoxicity associated with exposure to outdoor air pollutants in Brazil. A search was performed on the Web of Science database using a combination of keywords that resulted in 134 articles. After applying exclusion criteria, a total of 75 articles were obtained. The articles were classified into three categories: (1) studies with plants and animals, (2) in vitro studies, and (3) human biomonitoring. The investigations were conducted in 11 of 27 Brazilian states with the highest prevalence in the southeast and south regions. Only 5 investigations focused on the effects of burning biomass on the quality of outdoor air. Plants, especially Tradescantia pallida, were the main air pollution biomonitoring tool. When available, a significant association between levels of air pollutants and genetic damage was described. Among the in vitro studies, Salmonella/microsome is the most used test to evaluate mutagenesis of outdoor air in Brazil (n = 26). Human biomonitoring studies were the least frequent category (n = 18). Most of the investigations utilized micronucleus bioassay, in oral mucosa cells (n = 15) and lymphocytes (n = 5), and the comet assay (n = 6). The analysis in this study points to the existence of gaps in genotoxicity studies and our findings indicate that future studies need to address the variety of potential sources of pollution existing in Brazil. In addition to extent of the impacts, consideration should be given to the enormous Brazilian biodiversity, as well as the determination of the role of socioeconomic inequality of the population in the observed outcomes.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Animais , Humanos , Brasil , Mutagênicos/toxicidade , Monitoramento Ambiental/métodos , Poluentes Atmosféricos/toxicidade , Mutagênese , Plantas , Material Particulado/toxicidade , Testes de Mutagenicidade
12.
Gen Comp Endocrinol ; 330: 114143, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36244430

RESUMO

The vitellogenin is composed by polypeptides that are precursors of egg yolk proteins that provides embryo and larvae nutrition. The mRNA encoding for vitellogenin Ab (Vtg-Ab; 4,536 bp long and 1,512 amino acids) were obtained by RNA-Seq library sequencing of pirarucu gonads. The Vtg-Ab sequences had high homology with Vtgs of other three teleosts species of the order Osteoglossiformes. The transcript of ovarian Vtg was identified based on structural criteria, and so we classify the Vtg of pirarucu as Vtg-Ab due to the truncated or shortened phosvitin (N-terminal end) and phosvitinless domain (C-terminal end). The Vtg-Ab of pirarucu present two major deletions with 133 amino acids in the Lipovitellin I domain and 89 amino acids in the truncated or shortened Phosvitin domain, both located in the N-terminal end region. The three-dimensional (3-D) structure Vtg-Ab protein shows the presence of a typical 4α-helices bundle protein that runs in anti-parallel. In general, the characterization of Vtg-Ab may be the useful elucidation of the hormonal regulation of vitellogenesis and improve the production of pirarucu for broodstock management in aquaculture and preparation of Vtg antibody production (species-specific) for sex identification.


Assuntos
Fosvitina , Vitelogeninas , Animais , Vitelogeninas/metabolismo , Fosvitina/genética , Sequência de Aminoácidos , Peixes/genética , Aminoácidos
13.
J Nerv Ment Dis ; 211(2): 141-149, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36095251

RESUMO

ABSTRACT: People exposed to potentially traumatic events (PTEs) may develop distinct symptom patterns, which may require different therapeutic approaches. We aimed to identify classes of people exposed to PTEs based on the presence of posttraumatic stress disorder (PTSD) clusters, anxiety, and depression and to explore which cognitive factors (rumination, worry, and negative cognitions) are associated with class membership. Latent class analyses were conducted to identify subgroups of 258 PTE-exposed Spanish adults. A three-class solution emerged: a resilient class with low odds of all symptoms ( n = 188); a partial PTSD class, characterized by partial PTSD clusters, moderate anxiety, and low depression ( n = 36); and a high symptom class, characterized by high PTSD, moderate anxiety, and low depression ( n = 34). These classes related meaningfully to rumination, worry, and negative cognitions. Distinct symptom patterns of PTSD clusters, anxiety, and depression can be distinguished in people exposed to PTEs and relate to cognitive risk factors of psychopathology.


Assuntos
Transtornos de Estresse Pós-Traumáticos , Adulto , Humanos , Transtornos de Estresse Pós-Traumáticos/psicologia , Depressão/etiologia , Depressão/psicologia , Transtornos de Ansiedade/complicações , Ansiedade/etiologia , Cognição
14.
Sleep Breath ; 27(3): 1135-1142, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-35904665

RESUMO

OBJECTIVE: To investigate the association between multimorbidity and sleep medication use in women. METHODS: A population-based cross-sectional study was conducted on women (20-69 years) in Southern Brazil. Sleep medications were identified using the Therapeutic and Chemical Anatomical Classification. Multimorbidity was operationalized according to two cutoff points: diagnosis of either two or more or three or more chronic conditions and presence or absence of obesity. Explanatory variables included sociodemographic, behavioral, and health factors including obesity and common mental disorders (CMD) (assessed using the Self-Reporting Questionnaire 20 for CMD). Crude and adjusted prevalence ratios (PR) and 95% confidence intervals (95%CIs) were estimated with Poisson regression with robust variance using various adjustment models. RESULTS: In a sample of 1128 women, the prevalence of sleep medications was 14.3% (95%CI 12.2-16.3). After adjustments, the association between multimorbidity and sleep medication use yielded the following PR: multimorbidity ≥ 2:1.78 (95%CI, 1.23-2.56) and multimorbidity ≥ 3:1.90 (95%CI, 1.36-2.68). When obesity was included in the model, the effect was in the same direction but smaller, indicating that the presence of multimorbidity had an independent effect on the use of sleep medications, even after adjusting for CMD. CONCLUSION: The presence of multimorbidity increased the probability of using sleep medications by approximately 80%, regardless of the observed cutoff point, inclusion of obesity in multimorbidity, and adjustment for CMD. Specific aspects of some chronic conditions may interfere with sleep quality, predisposing women to begin use of these medications at early ages and, consequently, to continue their use throughout later life.


Assuntos
Multimorbidade , Obesidade , Humanos , Feminino , Brasil/epidemiologia , Estudos Transversais , Doença Crônica , Obesidade/epidemiologia , Sono
15.
Parasitol Res ; 122(1): 77-84, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36282319

RESUMO

Toxoplasma gondii is an obligate intracellular parasite that causes toxoplasmosis, and its congenital transmission is of paramount concern. During embryonic development, infection with the parasite causes irreversible damage to the still-forming fetus's central nervous system (CNS). In the pathogenesis of neurotoxoplasmosis, purinergic receptors prejudice neuroprotection, neuroinflammation, and activation of microbicide mechanisms against the parasitic vacuole. This study used curcumin as a treatment for neural precursor cells (NPCs) infected with T. gondii. The congenital toxoplasmosis induction consisted of maternal infection with the VEG strain, and NPCs were obtained from the telencephalon of mouse embryos. Curcumin at increasing concentrations was administered in vitro to analyze NPC metabolic activity, cell number, and size, as well as neurogliogenesis, proving to be effective in recovering the size of infected NPCs. Curcumin partially re-established impaired neurogenesis. Purinergic A1, A2A, and P2X7 receptors may be related to neuroprotection, neuroinflammatory control, and activation of mechanisms for inducing the parasite's death. ERK 1/2 was highly expressed in infected cells, while its expression rates decreased after the addition of the treatment, highlighting the possible anti-inflammatory action of curcumin. These findings suggest that curcumin treats neurological perturbations induced by toxoplasmosis.


Assuntos
Curcumina , Células-Tronco Neurais , Toxoplasma , Toxoplasmose Cerebral , Toxoplasmose Congênita , Feminino , Gravidez , Animais , Camundongos , Toxoplasma/fisiologia , Curcumina/farmacologia , Toxoplasmose Congênita/parasitologia
16.
Am J Drug Alcohol Abuse ; 49(6): 705-722, 2023 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-38011685

RESUMO

Background: Previous studies have reviewed the evidence on the increase in alcohol consumption after a terrorist attack. However, an increase does not necessarily imply the presence of an alcohol use disorder.Objectives: To conduct a systematic and meta-analytic review of the literature on the prevalence of increased alcohol consumption and alcohol use disorders in adult exposed to terrorism.Methods: A search of PsycINFO, MEDLINE and PTSDpubs identified 29 studies published up to March 2023 in which 38 adult samples totaling 282,753 persons exposed to terrorism were assessed. Using inverse variance heterogeneity models, pooled prevalence rates of increased alcohol use and alcohol use disorders were calculated.Results: 6% (95% CI [2.9, 9.5]) of the adults exposed to a terrorist attack increased their alcohol consumption. The prevalence of increased alcohol use varied depending on the degree of exposure (p = .006, R2 = .18) and the procedure for measuring increases (p = .043, R2 = .37). The prevalence of alcohol use disorders in adults exposed to a terrorist attack was 5.5% (95% CI [3.7, 7.5]), a rate that was not higher than that obtained in the general population and varied depending on the type of alcohol disorder (p = .015, R2 = .30).Conclusions: A relevant number of adults exposed to terrorist attacks will subsequently increase their alcohol consumption, but this increase is not associated with an increase in the prevalence of alcohol use disorders. Effects of terrorism on people's health are potentially widespread, but concerns of excessive alcohol use after terrorist attacks may be unwarranted.


Assuntos
Alcoolismo , Transtornos de Estresse Pós-Traumáticos , Terrorismo , Adulto , Humanos , Consumo de Bebidas Alcoólicas/epidemiologia , Prevalência , Transtornos de Estresse Pós-Traumáticos/epidemiologia
17.
Drug Chem Toxicol ; 46(1): 155-165, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34930069

RESUMO

Curcumin is an active polyphenol substance found in the highest concentrations in the roots of Curcuma longa. Its health benefits have led to recent increases in the consumption of curcumin. It has anti-inflammatory and antioxidant activities and is a potent neuroprotective against diseases of the brain. Nevertheless, its low bioavailability and its relative difficulty crossing the blood-brain barrier limit curcumin's use for these purposes. Curcumin-loaded nanoparticles may be an effective treatment for several diseases although there is a paucity of studies reporting its safety in the central nervous system (CNS). Therefore, this study aimed to identify non-neurotoxic concentrations of free curcumin and two nanoformulations of curcumin. Cell lines BV-2 and SH-SY5Y, both originating from the CNS, were evaluated after 24, 48, and 72 h of treatment with free curcumin and nanocapsules We measured viability, proliferation, and dsDNA levels. We measured levels of reactive oxygen species and nitric oxide as proxies for oxidative stress in culture supernatants. We found that free curcumin was toxic at 10 and 20 µM, principally at 72 h. Nanoformulations were more neurotoxic than the free form. Safe concentrations of free curcumin are between 1-5 µM, and these concentrations were lower for nanoformulations. We determined the ideal concentrations of free curcumin and nanocapsules serving as a basis for studies of injuries that affect the CNS.


Assuntos
Curcumina , Nanocápsulas , Neuroblastoma , Humanos , Curcumina/farmacologia , Nanocápsulas/toxicidade , Linhagem Celular , Estresse Oxidativo
18.
J Digit Imaging ; 36(5): 2259-2277, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37468696

RESUMO

Peri-implantitis can cause marginal bone remodeling around implants. The aim is to develop an automatic image processing approach based on two artificial intelligence (AI) techniques in intraoral (periapical and bitewing) radiographs to assist dentists in determining bone loss. The first is a deep learning (DL) object-detector (YOLOv3) to roughly identify (no exact localization is required) two objects: prosthesis (crown) and implant (screw). The second is an image understanding-based (IU) process to fine-tune lines on screw edges and to identify significant points (intensity bone changes, intersections between screw and crown). Distances between these points are used to compute bone loss. A total of 2920 radiographs were used for training (50%) and testing (50%) the DL process. The mAP@0.5 metric is used for performance evaluation of DL considering periapical/bitewing and screws/crowns in upper and lower jaws, with scores ranging from 0.537 to 0.898 (sufficient because DL only needs an approximation). The IU performance is assessed with 50% of the testing radiographs through the t test statistical method, obtaining p values of 0.0106 (line fitting) and 0.0213 (significant point detection). The IU performance is satisfactory, as these values are in accordance with the statistical average/standard deviation in pixels for line fitting (2.75/1.01) and for significant point detection (2.63/1.28) according to the expert criteria of dentists, who establish the ground-truth lines and significant points. In conclusion, AI methods have good prospects for automatic bone loss detection in intraoral radiographs to assist dental specialists in diagnosing peri-implantitis.


Assuntos
Perda do Osso Alveolar , Peri-Implantite , Dente , Humanos , Inteligência Artificial , Próteses e Implantes
19.
Issues Ment Health Nurs ; 44(9): 844-853, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37643368

RESUMO

The health crisis caused by the COVID-19 pandemic has negatively influenced the work of health staff, especially nurses. Stressors that affect nurses have been intensified and new stressors have also emerged, threatening their well-being and job performance. The main objective of this study is to analyze the role of nurses´ personal resources in the relationship between job stressors and job performance during the COVID-19. Sample is composed of 438 nurses from 39 Spanish cities. This is a cross-sectional study. The results confirm the full mediation of resilience in the relationship between stressors and job performance, and the moderation of self-efficacy in the relationship between resilience and job performance, and in the full mediation. This study highlight the role played by self-efficacy as the main personal resource in buffering the effect of stressors on nurses´ performance. Resilience only becomes crucial in individuals with low levels of self-efficacy beliefs. Managers of health institutions and hospitals are invited to invest resources in strengthening the personal resources of health staff, especially self-efficacy beliefs, and resilience to ensure that their performance remains adequate.


Assuntos
Esgotamento Profissional , COVID-19 , Enfermeiras e Enfermeiros , Humanos , Estudos Transversais , Pandemias , Inquéritos e Questionários , Adaptação Psicológica , Satisfação no Emprego
20.
Environ Monit Assess ; 195(6): 648, 2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37160623

RESUMO

Freshwater blue spaces (FBS), such as ponds, are key elements of the urban landscape and are under strong anthropogenic pressure. Land-use types and diversity may exert a negative or positive impact on FBS' water quality depending on their nature and arrangement. The information available in this respect is remarkably scarcer for water bodies in the Global South than for the north. Thus, we aim to identify and quantify the land-use types in a 500-m buffer zone of urban ponds in the Pampean region (Argentina) to assess their impact on water quality. We based our study on 15 FBS located in neighborhoods of Buenos Aires province during cold and warm seasons. We analyzed physical, chemical, and biological variables, and estimated water conditions by means of water quality indexes (WQIs) and quality guidelines. We quantified the dominant land-use type and the diversity of uses in the ponds' buffer zones, and evaluated their relationships with WQIs. Our results showed that WQIs were negatively related to a high proportion of residential areas in the adjacent zone, while positively to recreational ones. The diversity of land uses did not influence the water quality. We propose a new WQIpond with fewer key response variables, and as sensitive as the currently used WQIobjetive. We conclude that water quality from urban ponds in the Pampean region can be affected by dominant land-use type in the adjacent area but also the quality of their water supply sources (superficial and/or underground), clandestine wastewater discharges, and non-point pollution.


Assuntos
Monitoramento Ambiental , Qualidade da Água , Argentina , Cidades , Água Doce
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