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Tropical forests face increasing climate risk1,2, yet our ability to predict their response to climate change is limited by poor understanding of their resistance to water stress. Although xylem embolism resistance thresholds (for example, [Formula: see text]50) and hydraulic safety margins (for example, HSM50) are important predictors of drought-induced mortality risk3-5, little is known about how these vary across Earth's largest tropical forest. Here, we present a pan-Amazon, fully standardized hydraulic traits dataset and use it to assess regional variation in drought sensitivity and hydraulic trait ability to predict species distributions and long-term forest biomass accumulation. Parameters [Formula: see text]50 and HSM50 vary markedly across the Amazon and are related to average long-term rainfall characteristics. Both [Formula: see text]50 and HSM50 influence the biogeographical distribution of Amazon tree species. However, HSM50 was the only significant predictor of observed decadal-scale changes in forest biomass. Old-growth forests with wide HSM50 are gaining more biomass than are low HSM50 forests. We propose that this may be associated with a growth-mortality trade-off whereby trees in forests consisting of fast-growing species take greater hydraulic risks and face greater mortality risk. Moreover, in regions of more pronounced climatic change, we find evidence that forests are losing biomass, suggesting that species in these regions may be operating beyond their hydraulic limits. Continued climate change is likely to further reduce HSM50 in the Amazon6,7, with strong implications for the Amazon carbon sink.
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Carbono , Florestas , Árvores , Clima Tropical , Biomassa , Carbono/metabolismo , Secas , Árvores/crescimento & desenvolvimento , Árvores/metabolismo , Xilema/metabolismo , Chuva , Mudança Climática , Sequestro de Carbono , Estresse Fisiológico , DesidrataçãoRESUMO
T cell-focused cancer immunotherapy including checkpoint inhibitors and cell therapies has been rapidly evolving over the past decade. Nevertheless, there remains a major unmet medical need in oncology generally and immuno-oncology specifically. We have constructed an oncolytic adenovirus, Ad5/3-E2F-d24-aMUC1aCD3-IL-2 (TILT-322), which is armed with a human aMUC1aCD3 T cell engager and IL-2. TILT-322 treatment stimulated T cell cytotoxicity through the increased presence of granzyme B, perforin, and interferon-gamma. Additional immune profiling indicated TILT-322 increased gamma delta T cell activation and impacted other cell types such as natural killer cells and natural killer-like T cells that are traditionally involved in cancer immunotherapy. TILT-322 treatment also decreased the proportion of exhausted CD8+ T cells as demarked by immune checkpoint expression in ovarian ascites samples. Overall, our data showed that TILT-322 treatment led to an enhanced T cell activation and reversed T cell exhaustion translating into high antitumor efficacy when given locally or intravenously. The analysis of blood and tumors isolated from an in vivo patient-derived ovarian cancer xenograft model suggested TILT-322 mediated tumor control through improved T cell functions. Therefore, TILT-322 is a promising novel anti-tumor agent for clinical translation.
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Adenoviridae , Anticorpos Biespecíficos , Ascite , Interleucina-2 , Mucina-1 , Neoplasias Ovarianas , Ensaios Antitumorais Modelo de Xenoenxerto , Humanos , Neoplasias Ovarianas/terapia , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/genética , Feminino , Animais , Adenoviridae/genética , Camundongos , Linhagem Celular Tumoral , Ascite/terapia , Ascite/imunologia , Interleucina-2/metabolismo , Mucina-1/genética , Mucina-1/imunologia , Vetores Genéticos/genética , Vetores Genéticos/administração & dosagem , Terapia Viral Oncolítica/métodos , Vírus Oncolíticos/genética , Vírus Oncolíticos/imunologia , Ativação Linfocitária/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Modelos Animais de Doenças , Imunoterapia/métodos , Exaustão das Células TRESUMO
Human T-lymphotropic virus type 1 (HTLV-1) is classically associated with the HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), although the mechanisms of this neurological disorder remain unclear. In addition, some patients who develop "minor" neurological signs that do not meet diagnostic criteria for HAM/TSP are classified as asymptomatic carriers. This study aims to demonstrate the neurological symptoms of Brazilian patients living with HTLV-1 classified as not-HAM.TSP. This observational study evaluated patients treated in an HTLV reference center in Bahia, Brazil, between February 2022 and July 2023. The data were obtained through the analysis of medical records and neurological consultation. Those individuals classified as HAM/ TSP were excluded from this study. 74 patients were submitted to a careful neurological evaluation: 23 HAM/TSP, 22 were classified with intermediate syndrome (IS), and 29 were oligosymptomatic. Self-reported symptoms were significantly more common in the IS group, including urinary symptoms such as nocturia, urgency, incontinence, dysuria, weakness, paresthesia, lumbar pain, xerostomia, and xerophthalmia. Physical examination findings consistent with reduced vibratory and tactile sensitivity were more common in the IS group (p = 0.017 and p = 0.013). Alterations in the V and VIII cranial nerves were present in both groups. HTLV-1 can lead to the development of important neurological signs and symptoms in apparently asymptomatic individuals. This data highlights the need for more research into the neurological aspects of HTLV-1 infection and emphasizes the importance of early diagnosis, treatment, and support for individuals living with this virus.
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Portador Sadio , Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Paraparesia Espástica Tropical , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Vírus Linfotrópico T Tipo 1 Humano/patogenicidade , Paraparesia Espástica Tropical/virologia , Paraparesia Espástica Tropical/diagnóstico , Paraparesia Espástica Tropical/fisiopatologia , Portador Sadio/virologia , Infecções por HTLV-I/virologia , Infecções por HTLV-I/fisiopatologia , Infecções por HTLV-I/complicações , Infecções por HTLV-I/diagnóstico , Brasil/epidemiologia , IdosoRESUMO
Analyzing transcription data requires intensive statistical analysis to obtain useful biological information and knowledge. A significant portion of this data is affected by random noise or even noise intrinsic to the modeling of the experiment. Without robust treatment, the data might not be explored thoroughly, and incorrect conclusions could be drawn. Examining the correlation between gene expression profiles is one way bioinformaticians extract information from transcriptomic experiments. However, the correlation measurements traditionally used have worrisome shortcomings that need to be addressed. This paper compares five already published and experimented-with correlation measurements to the newly developed coincidence index, a similarity measurement that combines Jaccard and interiority indexes and generalizes them to be applied to vectors containing real values. We used microarray and RNA-Seq data from the archaeonHalobacterium salinarumand the bacteriumEscherichia coli, respectively, to evaluate the capacity of each correlation/similarity measurement. The utilized method explores the co-expressed metabolic pathways by measuring the correlations between the expression levels of enzymes that share metabolites, represented in the form of a weighted graph. It then searches for local maxima in this graph using a simulated annealing algorithm. We demonstrate that the coincidence index extracts larger, more comprehensive, and more statistically significant pathways for microarray experiments. In RNA-Seq experiments, the results are more limited, but the coincidence index managed the largest percentage of significant components in the graph.
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Escherichia coli , Halobacterium salinarum , Redes e Vias Metabólicas , Escherichia coli/genética , Escherichia coli/metabolismo , Halobacterium salinarum/metabolismo , Halobacterium salinarum/genética , Perfilação da Expressão Gênica/métodos , Biologia Computacional , Transcriptoma , Algoritmos , RNA-SeqRESUMO
The present study aimed to evaluate the anti-staphylococcal, antibiofilm, cytotoxicity and trypanocidal activity, mechanisms of parasite death and immunomodulatory effect of CrataBL encapsulated into liposomes (CrataBL-Lipo). CrataBL-Lipo were prepared by the freeze-thaw technique and characterized. Anti-staphylococcal and antibiofilm activities of CrataBL and CrataBL-Lipo were evaluated against standard and clinical strains of Staphylococcus aureus susceptible and resistant. Thus, broth microdilution method was performed to determine the Minimum Inhibitory Concentration (MIC). Antibiofilm activity at subinhibitory concentrations was evaluated using the crystal violet staining method. Cytotoxicity of CrataBL-Lipo was verified in L929 fibroblasts and J774A.1 macrophages by determining the inhibitory concentration necessary to kill 50 % of cells (IC50). Trypanocidal activities of CrataBL-Lipo was evaluated in Trypanosoma cruzi and the efficacy was expressed as the concentration necessary to kill 50 % of parasites (EC50). The mechanisms of parasite death and immunomodulatory effect of CrataBL-Lipo were evaluated using flow cytometry analysis. CrataBL-Lipo presented Ø of 101.9 ± 1.3 nm (PDI = 0.245), ζ of +33.8 ± 1.3 mV and %EE = 80 ± 0.84 %. CrataBL-Lipo presented anti-staphylococcal activity (MIC = 0.56 mg/mL to 0.72 mg/mL). CrataBL-Lipo inhibited 45.4 %-75.6 % of biofilm formation. No cytotoxicity of CrataBL-Lipo was found (IC50 > 100 mg/L). CrataBL-Lipo presented EC50 of 1.1 mg/L, presenting autophagy, apoptosis and necrosis as death profile. In addition, CrataBL-Lipo reduced the production of IL-10 and TNF-α levels, causing an immunomodulatory effect. CrataBL-Lipo has a therapeutic potential for the treatment of staphylococcal infections and Chagas disease exhibiting a high degree of selectivity for the microorganism, and immunomodulatory properties.
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Antibacterianos , Biofilmes , Lipossomos , Testes de Sensibilidade Microbiana , Staphylococcus aureus , Tripanossomicidas , Trypanosoma cruzi , Biofilmes/efeitos dos fármacos , Trypanosoma cruzi/efeitos dos fármacos , Animais , Camundongos , Staphylococcus aureus/efeitos dos fármacos , Linhagem Celular , Antibacterianos/farmacologia , Tripanossomicidas/farmacologia , Macrófagos/efeitos dos fármacos , Lectinas/farmacologia , Fibroblastos/efeitos dos fármacos , Concentração Inibidora 50 , Sobrevivência Celular/efeitos dos fármacosRESUMO
AIMS: We developed three new analogs of the antimicrobial peptide (AMP) Citropin 1.1: DAN-1-13, AJP-1-1, and HHX-2-28, and tested their potential antimicrobial and antibiofilm activities against Staphylococcus aureus and S. pseudintermedius. Potential cytotoxic or hemolytic effects were determined using cultured human keratinocytes and erythrocytes to determine their safety. METHODS AND RESULTS: To assess the antimicrobial activity of each compound, minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) were determined against methicillin-resistant and methicillin-susceptible strains of S. aureus and S. pseudintermedius. Activity against newly formed and mature biofilms was determined in two clinical isolates using spectrophotometry and scanning electron microscopy (SEM). All three compounds exhibited antimicrobial and bactericidal activity against all studied S. aureus and S. pseudintermedius strains, with MICs ranging from 4-32 µg ml-1 and MBCs ranging from 8-128 µg ml-1. Subinhibitory concentrations of all compounds also showed ant-biofilm activity in the two tested isolates. All compounds exhibited limited cytotoxic and hemolytic activity. CONCLUSIONS: Novel analogs of Citropin 1.1 exhibit antimicrobial and bactericidal activities against S. aureus and S. pseudintermedius isolates and inhibit the biofilm formation of these bacteria.
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Antibacterianos , Biofilmes , Testes de Sensibilidade Microbiana , Staphylococcus aureus , Staphylococcus , Biofilmes/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Humanos , Antibacterianos/farmacologia , Staphylococcus/efeitos dos fármacos , Peptídeos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos/química , Eritrócitos/efeitos dos fármacos , Queratinócitos/efeitos dos fármacosRESUMO
BACKGROUND: Atrioventricular block (AVB) secondary to transient causes can recover with its correction. However, studies assessing predictors of recovery and long-term recurrence are lacking. METHODS: Patients with advanced or complete AVB who had a reversible cause admitted in a single expert center were retrospectively studied. Patients with AVB secondary to acute coronary syndromes were excluded from analysis. RESULTS: In a population of 162 patients, the main factors associated with recovery of rhythm without a permanent pacemaker (PPM) implantation were the presence of chronic kidney disease (CKD) on dialysis (OR 7.6; CI 95% 1.2-47.5 (p = .03)); greater serum potassium levels (OR 2.3; CI 95% 1.28-4.0 (p < .01)), higher dosage of bradycardic drugs (OR 2.2; CI 95% 1.13-4.4 (p = .02)), the association between different bradycardic drugs (OR 9.0; CI 95% 2.02-40.3 (p < .01)) and between drug therapy and hyperkaliemia (OR 5.2; CI 95% 1.8-15.1 (p < .01)). There was an overall high burden of conductions abnormalities which did not correlate with recovery of rhythm (OR 0.5; CI 95% 0.19-1.5 (p = .23)). In 29 patients (17.9%) there was a correction of the AVB. During a maximum follow-up of 130 months, 24 patients (82.8%) had a recurrence which warranted a PPM. In the overall cohort only five patients (3%) had sustained recovery of rhythm. CONCLUSIONS: Recovery of AVB was mainly observed with higher doses of drug therapy, higher serum potassium levels or a combination of factors and regardless of baseline conduction abnormalities. The high rate of recurrence during follow-up warrants a close follow-up or PPM implantation at index admission.
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Bloqueio Atrioventricular , Marca-Passo Artificial , Humanos , Estudos Retrospectivos , Fatores de Risco , Causalidade , Doença do Sistema de Condução Cardíaco/complicações , Potássio , Marca-Passo Artificial/efeitos adversosRESUMO
BACKGROUND: The European Union (EU) faces many health-related challenges. Burden of diseases information and the resulting trends over time are essential for health planning. This paper reports estimates of disease burden in the EU and individual 27 EU countries in 2019, and compares them with those in 2010. METHODS: We used the Global Burden of Disease 2019 study estimates and 95% uncertainty intervals for the whole EU and each country to evaluate age-standardised death, years of life lost (YLLs), years lived with disability (YLDs) and disability-adjusted life years (DALYs) rates for Level 2 causes, as well as life expectancy and healthy life expectancy (HALE). RESULTS: In 2019, the age-standardised death and DALY rates in the EU were 465.8 deaths and 20,251.0 DALYs per 100,000 inhabitants, respectively. Between 2010 and 2019, there were significant decreases in age-standardised death and YLL rates across EU countries. However, YLD rates remained mainly unchanged. The largest decreases in age-standardised DALY rates were observed for "HIV/AIDS and sexually transmitted diseases" and "transport injuries" (each -19%). "Diabetes and kidney diseases" showed a significant increase for age-standardised DALY rates across the EU (3.5%). In addition, "mental disorders" showed an increasing age-standardised YLL rate (14.5%). CONCLUSIONS: There was a clear trend towards improvement in the overall health status of the EU but with differences between countries. EU health policymakers need to address the burden of diseases, paying specific attention to causes such as mental disorders. There are many opportunities for mutual learning among otherwise similar countries with different patterns of disease.
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Anos de Vida Ajustados por Deficiência , União Europeia , Carga Global da Doença , Expectativa de Vida , Humanos , União Europeia/estatística & dados numéricos , Carga Global da Doença/tendências , Expectativa de Vida/tendências , Anos de Vida Ajustados por Deficiência/tendências , Masculino , Nível de Saúde , Feminino , Efeitos Psicossociais da DoençaRESUMO
OBJECTIVES: Sleep and internalizing problems escalate during adolescence and can negatively impact long-term health. However, the directionality of this risk-relationship remains poorly understood within a developmental context. The current study aimed to determine the directionality of this relationship in adolescents with no history of psychiatric disorder and whether sex at birth played a role in this relationship. METHODS: We used data from the Adolescent Brain Cognitive Development, an ongoing multisite longitudinal US study, that covered four waves (W1:9-11 years; W2:10-12 years; W3:11-13 years; W4:12-14 years). Analyses included 3,128 youth (50.99%girls) with no past or current psychiatric disorders at W1. The Sleep Disturbance Scale for Children and the Child Behavior Checklist were used to measure sleep and internalizing problems. Cross-lagged panel models were used to evaluate the cross-lagged relationships across waves. RESULTS: The sleep-internalizing cross-lagged relationship was unidirectional, with medium-large effect sizes: greater total sleep problems were associated with more severe internalizing problems at later waves (W2âW3, coefficient = 0.052, p = .021; W3âW4, coefficient = 0.091, p < .001), with problems in initiating and maintaining sleep predicting internalizing problems early on. Girls showed greater sleep-internalizing risk than boys. CONCLUSIONS: Sleep-internalizing relationships change across adolescence, becoming significant and more specific from early to mid-adolescence. Sleep interventions delivered in early adolescence, to girls in particular, may have a positive short and long-term impact on internalizing outcomes.
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The narrow genetics of most crops is a fundamental vulnerability to food security. This makes wild crop relatives a strategic resource of genetic diversity that can be used for crop improvement and adaptation to new agricultural challenges. Here, we uncover the contribution of one wild species accession, Arachis cardenasii GKP 10017, to the peanut crop (Arachis hypogaea) that was initiated by complex hybridizations in the 1960s and propagated by international seed exchange. However, until this study, the global scale of the dispersal of genetic contributions from this wild accession had been obscured by the multiple germplasm transfers, breeding cycles, and unrecorded genetic mixing between lineages that had occurred over the years. By genetic analysis and pedigree research, we identified A. cardenasii-enhanced, disease-resistant cultivars in Africa, Asia, Oceania, and the Americas. These cultivars provide widespread improved food security and environmental and economic benefits. This study emphasizes the importance of wild species and collaborative networks of international expertise for crop improvement. However, it also highlights the consequences of the implementation of a patchwork of restrictive national laws and sea changes in attitudes regarding germplasm that followed in the wake of the Convention on Biological Diversity. Today, the botanical collections and multiple seed exchanges which enable benefits such as those revealed by this study are drastically reduced. The research reported here underscores the vital importance of ready access to germplasm in ensuring long-term world food security.
Assuntos
Arachis/genética , Produtos Agrícolas/genética , Sementes/genética , África , Ásia , Mapeamento Cromossômico/métodos , DNA de Plantas/genética , Marcadores Genéticos/genética , Variação Genética/genética , Genoma de Planta/genética , Hibridização Genética/genética , Oceania , Melhoramento Vegetal/métodos , Especificidade da EspécieRESUMO
BACKGROUND: The Golden Syrian hamster (Mesocricetus auratus), Ferrets (Mustela putorius furo), and macaques have been described as useful laboratory animals naturally susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. OBJECTIVES: To study the mechanism of lung injury, we describe the histopathological features of SARS-CoV-2 infection in Golden Syrian hamsters inoculated intranasally with the A.2 Brazilian strain. METHODS: Hamsters were intranasally inoculated with the A.2 variant and euthanised at 3-, 5-, 10- and 15-days post-inoculation. The physical examination and body weight were recorded daily. Neutralising antibodies and viral RNA load of the respiratory tract were assessed during necropsies. FINDINGS: The coronavirus disease 2019 (COVID-19) model presented body weight loss, high levels of respiratory viral RNA load, severe segmentary pneumonitis, and bronchial fistula besides lymphatic trapping and infiltration, like the human SARS-COV-2 pathogenesis. The presence of subepithelial lymphoeosinophilic infiltrate was highlighted in our results; it contributed to the detachment of SARS-CoV-2 nucleocapsid-positive epithelial cells resulting in the infectious cell plugs. MAIN CONCLUSIONS: The SARS-CoV-2 caused segmentary pneumonia and vascular damage. In our comprehension, the infectious cell plugs, as being aspirated from the upper respiratory tract into the terminal bronchial lumen, work as a "Trojan horse", thus contributing to the dissemination of the SARS-CoV-2 infection into specific regions of the deep lung parenchyma.
Assuntos
COVID-19 , Modelos Animais de Doenças , Células Epiteliais , Mesocricetus , SARS-CoV-2 , Animais , COVID-19/patologia , Células Epiteliais/virologia , Lesão Pulmonar/virologia , Lesão Pulmonar/patologia , Carga Viral , Cricetinae , RNA Viral/análise , Pulmão/patologia , Pulmão/virologia , Masculino , BrasilRESUMO
PURPOSE: There are no clinical treatments to prevent/revert age-related alterations associated with oocyte competence decline in the context of advanced maternal age. Those alterations have been attributed to oxidative stress and mitochondrial dysfunction. Our study aimed to test the hypothesis that in vitro maturation (IVM) medium supplementation with antioxidants (resveratrol or phloretin) may revert age-related oocyte competence decline. METHODS: Bovine immature oocytes were matured in vitro for 23 h (young) and 30 h (aged). Postovulatory aged oocytes (control group) and embryos obtained after fertilization were examined and compared with oocytes supplemented with either 2 µM of resveratrol or 6 µM phloretin (treatment groups) during IVM. RESULTS: Aged oocytes had a significantly lower mitochondrial mass and proportion of mitochondrial clustered pattern, lower ooplasmic volume, higher ROS, lower sirtuin-1 protein level, and a lower blastocyst rate in comparison to young oocytes, indicating that postovulatory oocytes have a lower quality and developmental competence, thus validating our experimental model. Supplementation of IVM medium with antioxidants prevented the generation of ROS and restored the active mitochondrial mass and pattern characteristic of younger oocytes. Moreover, sirtuin-1 protein levels were also restored but only following incubation with resveratrol. Despite these findings, the blastocyst rate of treatment groups was not significantly different from the control group, indicating that resveratrol and phloretin could not restore the oocyte competence of postovulatory aged oocytes. CONCLUSION: Resveratrol and phloretin can both revert the age-related oxidative stress and mitochondrial dysfunction during postovulatory aging but were insufficient to enhance embryo developmental rates under our experimental conditions.
Assuntos
Antioxidantes , Desenvolvimento Embrionário , Fertilização in vitro , Técnicas de Maturação in Vitro de Oócitos , Oócitos , Estresse Oxidativo , Animais , Oócitos/efeitos dos fármacos , Oócitos/crescimento & desenvolvimento , Bovinos , Feminino , Desenvolvimento Embrionário/efeitos dos fármacos , Técnicas de Maturação in Vitro de Oócitos/métodos , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/farmacologia , Fertilização in vitro/métodos , Ovulação/efeitos dos fármacos , Blastocisto/efeitos dos fármacos , Blastocisto/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Envelhecimento/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Resveratrol/farmacologiaRESUMO
All patient refined-diagnosis related groups (APR-DRGs) includes severity of illness (SOI) and risk of mortality (ROM) subclasses. For predictions, both subscales are used together or interchangeably. We aimed to compare SOI and ROM by evaluating the reliability and agreement between both. We performed a retrospective observational study using mainland Portuguese public hospitalisations of adult patients from 2011 to 2016. Reliability (quadratic weighted kappa) and agreement (proportion of agreement) between SOI and ROM were analysed overall and by APR-DRG. While overall reliability and agreement between SOI and ROM were high (weighted kappa: 0.717, 95% CI 0.717-0.718; proportion of agreement: 69.0%, 95% CI 69.0-69.0) there was high heterogeneity across APR-DRGs, ranging from 0.016 to 0.846 on reliability and from 23.1% to 94.8% on agreement. Most of APR-DRGs (263 out of 284) showed a higher proportion of episodes with ROM level above the SOI level than the opposite. In conclusion, SOI and Risk of Mortality measures must be clearly distinguished and are 'two scales of different concepts' rather than 'two sides of the same coin'. However, this is more evident for some APR-DRGs than for others.
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OBJECTIVE: This review aims to assess structural, chemical, and mechanical properties of coronal dentin after endodontic irrigation. MATERIALS AND METHODS: Reporting followed the PRISMA extension for scoping reviews. An electronic search was carried out in PubMed, Embase, and Cochrane Library. Records filtered by language and published up to November 4, 2022 were independently screened by two researchers. Studies evaluating structural, chemical, or mechanical properties of human permanent coronal dentin after irrigation within the scope of nonsurgical root canal treatment were included. Data were extracted regarding study type, sample description and size, experimental groups, outcome, evaluation method, and main findings. RESULTS: From the initial 1916 studies, and by adding 2 cross-references, 11 in vitro studies were included. Seven studies provide ultrastructural and/or chemical characterization, and six assessed microhardness and/or flexural strength. One percent to 8% sodium hypochlorite (NaOCl) and 1%-17% ethylenediaminetetraacetic acid (EDTA) were the most commonly tested solutions, with contact times of 2-240 min (NaOCl) and 1-1440 min (EDTA) being evaluated. CONCLUSIONS: Overall, the literature is consensual regarding the inevitable impact of NaOCl and chelating agents on coronal dentin, with both deproteinizing and decalcifying effects being concentration- and time-dependent. The alteration of mechanical parameters further confirmed the surface and subsurface ultrastructural and chemical changes. CLINICAL SIGNIFICANCE: Endodontic treatment success highly depends on restorative sealing. Understanding the result of exposing coronal dentin, the main substrate for bonding, to irrigants' action is crucial. The deproteinizing and decalcifying effects of NaOCl and chelating agents are both concentration- and time-dependent, causing surface and subsurface ultrastructural, chemical, and mechanical alterations.
Assuntos
Cavidade Pulpar , Dentina , Humanos , Ácido Edético/análise , Ácido Edético/farmacologia , Dentina/química , Irrigantes do Canal Radicular/análise , Irrigantes do Canal Radicular/farmacologia , Quelantes/análise , Quelantes/farmacologiaRESUMO
Autism Spectrum Disorder (ASD) is an early onset neurodevelopmental disorder characterized by impaired social interaction and communication, and repetitive patterns of behavior. Family studies show that ASD is highly heritable, and hundreds of genes have previously been implicated in the disorder; however, the etiology is still not fully clear. Brain imaging and electroencephalography (EEG) are key techniques that study alterations in brain structure and function. Combined with genetic analysis, these techniques have the potential to help in the clarification of the neurobiological mechanisms contributing to ASD and help in defining novel therapeutic targets. To further understand what is known today regarding the impact of genetic variants in the brain alterations observed in individuals with ASD, a systematic review was carried out using Pubmed and EBSCO databases and following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This review shows that specific genetic variants and altered patterns of gene expression in individuals with ASD may have an effect on brain circuits associated with face processing and social cognition, and contribute to excitation-inhibition imbalances and to anomalies in brain volumes.
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Transtorno do Espectro Autista , Encéfalo , Neuroimagem , Humanos , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/diagnóstico por imagem , Neuroimagem/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/metabolismo , Eletroencefalografia , Predisposição Genética para DoençaRESUMO
Dupuytren's disease (DD) is a prevalent fibroproliferative disorder of the hand, shaped by genetic, epigenetic, and environmental influences. The extracellular matrix (ECM) is a complex assembly of diverse macromolecules. Alterations in the ECM's content, structure and organization can impact both normal physiological functions and pathological conditions. This study explored the content and organization of glycosaminoglycans, proteoglycans, and collagen in the ECM of patients at various stages of DD, assessing their potential as prognostic indicators. This research reveals, for the first time, relevant changes in the complexity of chondroitin/dermatan sulfate structures, specifically an increase of disaccharides containing iduronic acid residues covalently linked to either N-acetylgalactosamine 6-O-sulfated or N-acetylgalactosamine 4-O-sulfated, correlating with the disease's severity. Additionally, we noted an increase in versican expression, a high molecular weight proteoglycan, across stages I to IV, while decorin, a small leucine-rich proteoglycan, significantly diminishes as DD progresses, both confirmed by mRNA analysis and protein detection via confocal microscopy. Coherent anti-Stokes Raman scattering (CARS) microscopy further demonstrated that collagen fibril architecture in DD varies importantly with disease stages. Moreover, the urinary excretion of both hyaluronic and sulfated glycosaminoglycans markedly decreased among DD patients.Our findings indicate that specific proteoglycans with galactosaminoglycan chains and collagen arrangements could serve as biomarkers for DD progression. The reduction in glycosaminoglycan excretion suggests a systemic manifestation of the disease.
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Colágeno , Decorina , Contratura de Dupuytren , Proteoglicanas , Humanos , Contratura de Dupuytren/metabolismo , Contratura de Dupuytren/patologia , Colágeno/metabolismo , Proteoglicanas/metabolismo , Decorina/metabolismo , Matriz Extracelular/metabolismo , Masculino , Progressão da Doença , Feminino , Dermatan Sulfato/metabolismo , Pessoa de Meia-Idade , Idoso , Versicanas/metabolismo , Versicanas/genética , Glicosaminoglicanos/metabolismo , Sulfatos de Condroitina/metabolismo , PolissacarídeosRESUMO
Woody invasive alien species can have profound impacts on ecosystem processes and functions, including fire regulation, which can significantly affect landscape resilience. Acacia dealbata, a widespread invasive alien plant in the Iberian Peninsula, holds well-known fire-adaptation traits (e.g., massive soil seed banks and heat-stimulated seed germination). In this study, we assess to what extent fire suppression and land-use strategies could affect the potential distribution of A. dealbata in a fire-prone transboundary protected mountain area of Portugal and Spain, using Habitat Suitability Models. Specifically, we predicted changes in habitat suitability for A. dealbata between years 2010 and 2050. We explored the potential impacts of two land-use strategies ('Business-as-usual' or 'High Nature Value farmlands') combined with three levels of fire suppression effectiveness using the biomod2 package in R. We also considered the potential effects of two climate change scenarios (RCP4.5 and RCP8.5). Our modeling approach demonstrated a strong capacity to predict habitat suitability using either climate or land-cover information alone (AUC climate = 0.947; AUC LC = 0.957). According to climate-based models, A. dealbata thrives under conditions characterized by higher precipitation seasonality, higher precipitation in the warmest month, and higher minimum temperature in the coldest month. Regarding land cover, A. dealbata thrives mainly in landscapes dominated by urban areas and evergreen forest plantations. Our models forecasted that habitat suitability by 2050 could either increase or decrease depending on the specific combinations of fire suppression, land-use, and climate scenarios. Thus, a combination of business-as-usual and fire-exclusion strategies would enhance habitat suitability for the species. Conversely, management promoting High Nature Value farmlands would decrease the available suitable habitat, particularly under low fire suppression efforts. These findings suggest that promoting sustainable farming activities could impede the spread of A. dealbata by reducing habitat availability, while strategies aiming at fire-exclusion could facilitate its expansion, likely by enabling establishment and large seed production. This study highlights the complex interplay between fire-prone invasive species, fire and land-use strategies, and climate change; and thus the need to consider the interactions between land-use and fire management to promote invasive species control and landscape resilience.
Assuntos
Mudança Climática , Ecossistema , Incêndios , Espécies Introduzidas , Espanha , Conservação dos Recursos Naturais , PortugalRESUMO
ABSTRACT: Ribeiro, N, Martinho, DV, Pereira, JR, Rebelo, A, Monasterio, X, Gonzalo-Skok, O, Valente-dos-Santos, J, and Tavares, F. Injury risk in elite young male soccer players: a review on the impact of growth, maturation, and workload. J Strength Cond Res XX(X): 000-000, 2024-The long-term development of young male soccer players involves a prolonged period of significant adjustments, highlighting the importance of studying the complex interaction between dynamic variables, including workload, and inherent elements like growth and maturity. This analysis examines the intricate connections involving the development, maturity, workload, and susceptibility to injuries among adolescent male soccer players. Significantly, these connections become prominent at the peak height velocity (PHV) period, a crucial moment in maturation. Growth rates vary among individuals, and higher rates have been associated with an increased risk of injury in young soccer players, particularly during periods of rapid growth. Identifying possible risk factors and understanding the complex connections between them is crucial to developing specific methods for reducing the risk of injury. Sharing this valuable information with essential stakeholders is crucial for guaranteeing young athletes' comprehensive growth and maturation process. Furthermore, this review emphasizes the immediate need for long-term studies and thorough injury analyses to comprehend better the dynamic interactions that influence injury patterns in young male soccer players. This review will allow practitioners to better understand the main modifiable and nonmodifiable risk factors for injury and provide essential information focusing on practical strategies, facilitating more informed decision making by all stakeholders. The review aims to clarify these complexities and offer crucial insights that can assist in designing and implementing efficient strategies to reduce the risk of injury, specifically for the challenges faced during PHV and within the broader framework of long-term athletic development in young soccer.
RESUMO
Thermostability is an important and desired feature of therapeutic proteins and is critical for the success or failure of protein drugs development. It can be increased by PEGylation-binding of poly(ethylene glycol) moieties-or glycosylation-post-translational modification to add glycans. Here, the thermostability and thermodynamic parameters of native, PEGylated, and glycosylated versions of the antileukemic enzyme crisantaspase were investigated. First-order kinetics was found to describe the irreversible deactivation process. Activation energy of the enzyme-catalyzed reaction (E*) was estimated for native, PEGylated, and glycosylated enzyme (10.2, 14.8, and 18.8 kJ mol-1 respectively). Half-life decreased progressively with increasing temperature, and longer half-life was observed for PEG-crisantaspase (87.74 min) at 50 °C compared to the native form (9.79 min). The activation energy of denaturation of PEG-crisantaspase (307.1 kJ mol-1) was higher than for crisantaspase (218.1 kJ mol-1) and Glyco-crisantaspase (120.0 kJ mol-1), which means that more energy is required to overcome the energy barrier of the unfolding process. According to our results, PEG-crisantaspase is more thermostable than its native form, while Glyco-crisantaspase is more thermosensitive.