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1.
PLoS One ; 19(7): e0298503, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38990849

RESUMO

Intolerance of Uncertainty (IU) is thought to lead to maladaptive behaviours and dysfunctional decision making, both in the clinical and healthy population. The seminal study reported by Luhmann and collaborators in 2011 showed that IU was negatively associated with choosing a delayed, but more certain and valuable, reward over choosing an immediate, but less certain and valuable, reward. These findings have been widely disseminated across the field of personality and individual differences because of their relevance to understand the role of IU in maladaptive behaviours in anxiety-related disorders. We conducted a study to replicate and extend Luhmann et al.'s results with a sample of 313 participants, which exceeded the size necessary (N = 266) to largely improve the statistical power of the original study by using the small telescopes approach. The results of our well powered study strongly suggest that the relationship between IU and the tendency to prefer an immediate, but less certain and less valuable reward is virtually negligible. Consequently, although this relationship cannot be definitely discarded, we conclude that it cannot be detected with Luhmann et al.'s (2011) decision-making task.


Assuntos
Tomada de Decisões , Recompensa , Humanos , Incerteza , Masculino , Feminino , Adulto , Adulto Jovem , Pessoa de Meia-Idade , Adolescente
2.
bioRxiv ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38979330

RESUMO

Variants in the poorly characterised oncoprotein, MORC2, a chromatin remodelling ATPase, lead to defects in epigenetic regulation and DNA damage response. The C-terminal domain (CTD) of MORC2, frequently phosphorylated in DNA damage, promotes cancer progression, but its role in chromatin remodelling remains unclear. Here, we report a molecular characterisation of full-length, phosphorylated MORC2, demonstrating its preference for binding open chromatin and functioning as a DNA sliding clamp. We identified a phosphate interacting motif within the CTD that dictates ATP hydrolysis rate and cooperative DNA binding. The DNA binding impacts several structural domains within the ATPase region. We provide the first visual proof that MORC2 induces chromatin remodelling through ATP hydrolysis-dependent DNA compaction, regulated by its phosphorylation state. These findings highlight phosphorylation of MORC2 CTD as a key modulator of chromatin remodelling, presenting it as a potential therapeutic target.

3.
Plant Cell ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38980154

RESUMO

Proteolysis, including post-translational proteolytic processing as well as protein degradation and amino acid recycling, is an essential component of the growth and development of living organisms. In this article, experts in plant proteolysis pose and discuss compelling open questions in their areas of research. Topics covered include the role of proteolysis in the cell cycle, DNA damage response, mitochondrial function, the generation of N-terminal signals (degrons) that mark many proteins for degradation (N-terminal acetylation, the Arg/N-degron pathway, and the chloroplast N-degron pathway), developmental and metabolic signaling (photomorphogenesis, abscisic acid and strigolactone signaling, sugar metabolism, and post-harvest regulation), plant responses to environmental signals (endoplasmic-reticulum associated degradation, chloroplast-associated degradation, drought tolerance, the growth-defense tradeoff)), and the functional diversification of peptidases. We hope these thought-provoking discussions help to stimulate further research.

4.
Sci Rep ; 14(1): 15550, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38969699

RESUMO

Acute myeloid leukaemia (AML) is a severe haematological neoplasm that originates from the transformation of haematopoietic stem cells (HSCs) into leukaemic stem cells (LSCs). The bone marrow (BM) microenvironment, particularly that of mesenchymal stromal cells (hMSCs), plays a crucial role in the maintenance of HSCs. In this context, we explored whether alterations in the secretome of hMSCs derived from AML patients (hMSC-AML) could impact HSC gene expression. Proteomic analysis revealed that the secretome of coculture assays with hMSC-AMLs and HSC from healthy donor is altered, with increased levels of secretory leukocyte protease inhibitor (SLPI), a protein associated with important processes for maintenance of the haematopoietic niche that has already been described to be altered in several tumours. Increased SLPI expression was also observed in the BM plasma of AML patients. Transcriptome analysis of HSCs cocultured with hMSC-AML in comparison with HSCs cocultured with hMSC-HD revealed altered expression of SLPI target genes associated with the cell cycle, proliferation, and apoptosis. Important changes were identified, such as increased expression levels of CCNA2, CCNE2, CCND2, CD133 and CDK1 and decreased levels of CDKN2A and IGFBP3, among others. Overall, these findings suggest that the altered secretome of coculture assays with hMSC-AMLs and HSC from healthy donor, particularly increased SLPI expression, can contribute to gene expression changes in HSCs, potentially influencing important molecular mechanisms related to AML development and progression.


Assuntos
Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Células-Tronco Mesenquimais , Inibidor Secretado de Peptidases Leucocitárias , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Inibidor Secretado de Peptidases Leucocitárias/metabolismo , Inibidor Secretado de Peptidases Leucocitárias/genética , Técnicas de Cocultura , Transcriptoma , Feminino , Masculino , Perfilação da Expressão Gênica , Pessoa de Meia-Idade , Proteômica/métodos , Regulação Leucêmica da Expressão Gênica , Idoso , Adulto , Proliferação de Células/genética
5.
Chaos ; 34(6)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38885072

RESUMO

The equatorial region of the Earth's atmosphere serves as both a significant locus for phenomena, including the Madden-Julian Oscillation (MJO), and a source of formidable complexity. This complexity arises from the intricate interplay between nonlinearity and thermodynamic processes, particularly those involving moisture. In this study, we employ a normal mode decomposition of atmospheric reanalysis ERA-5 datasets to investigate the influence of nonlinearity and moisture on amplitude growth, propagation speed, and mode coupling associated with equatorially trapped waves. We focus our analysis on global-scale baroclinic Kelvin and Rossby waves, recognized as crucial components contributing to the variability of the MJO. We examine the dependence of wave amplitudes on the background moisture field in the equatorial region, as measured by total column water vapor. Our analysis demonstrates the crucial role of moisture in exciting these waves. We further investigate the dependence of the propagation speed of the waves on their amplitudes and the background moisture field. Our analysis reveals a robust correlation between the phase speed of the normal modes and their corresponding amplitude, whereas a weaker correlation is found between the eigenmodes' phase speed and the moisture field. Hence, our findings suggest that moisture plays a role in exciting the global-scale Rossby-Kelvin structure of the MJO. In this context, the propagation speed of the eigenmodes is mainly influenced by their amplitudes, underscoring the significant role of nonlinearity in wave propagation.

6.
Lancet Healthy Longev ; 5(7): e480-e492, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38945130

RESUMO

BACKGROUND: Together with environmental factors, intrinsic capacity (the composite of all the physical and mental capacities of an individual) has been proposed as a marker of healthy ageing. However, whether intrinsic capacity predicts major clinical outcomes is unclear. We aimed to explore the association of intrinsic capacity with functional decline and mortality in older adults. METHODS: In this systematic review and meta-analysis, we conducted a systematic search in MEDLINE (via PubMed), Scopus, and Web of Science from database inception to Feb 14, 2024, of observational longitudinal studies conducted in older adults (age ≥60 years) assessing the association of intrinsic capacity with impairment in basic activities of daily living (BADL) or instrumental activities of daily living (IADL) or risk of mortality. Estimates were extracted by two reviewers (JLS-S and W-HL) and were pooled using three-level meta-analytic models. The quality of each study was independently assessed by two authors (JLS-S and PLV) using the Newcastle-Ottawa Scale for longitudinal studies. Heterogeneity was evaluated using the I2 indicator at two levels: within-study (level 2) and between-study (level 3) variation. For associations between intrinsic capacity and IADL and BADL, we transformed data (standardised ß coefficients and odds ratios [ORs]) into Pearson product moment correlation coefficients (r) using Pearson and Digby formulas to allow comparability across studies. For associations between intrinsic capacity and risk of mortality, hazard ratios (HRs) with 95% CIs were extracted from survival analyses. This study is registered with PROSPERO, CRD42023460482. FINDINGS: We included 37 studies (206 693 participants; average age range 65·3-85·9 years) in the systematic review, of which 31 were included in the meta-analysis on the association between intrinsic capacity and outcomes; three studies (2935 participants) were included in the meta-analysis on the association between intrinsic capacity trajectories and longitudinal changes in BADL or IADL. Intrinsic capacity was inversely associated with longitudinal impairments in BADL (Pearson's r -0·12 [95% CI -0·19 to -0·04]) and IADL (-0·24 [-0·35 to -0·13]), as well as with mortality risk (hazard ratio 0·57 [95% CI 0·51 to 0·63]). An association was also found between intrinsic capacity trajectories and impairment in IADL (but not in BADL), with maintained or improved intrinsic capacity over time associated with a lower impairment in IADL (odds ratio 0·37 [95% CI 0·19 to 0·71]). There was no evidence of publication bias (Egger's test p>0·05) and there was low between-study heterogeneity (I2=18·4%), though within-study (I2=63·2%) heterogeneity was substantial. INTERPRETATION: Intrinsic capacity is inversely associated with functional decline and mortality risk in older adults. These findings could support the use of intrinsic capacity as a marker of healthy ageing, although further research is needed to refine the structure and operationalisation of this construct across settings and populations. FUNDING: None. TRANSLATIONS: For the Spanish and French translations of the abstract see Supplementary Materials section.


Assuntos
Atividades Cotidianas , Mortalidade , Humanos , Idoso , Estudos Longitudinais , Atividades Cotidianas/psicologia , Mortalidade/tendências , Avaliação Geriátrica/métodos , Idoso de 80 Anos ou mais , Feminino , Masculino
7.
Clin Transl Sci ; 17(6): e13858, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38932491

RESUMO

Cognitive or motor impairment is common among individuals with neurofibromatosis type 1 (NF1), an autosomal dominant tumor-predisposition disorder. As many as 70% of children with NF1 report difficulties with spatial/working memory, attention, executive function, and fine motor movements. In contrast to the utilization of various Nf1 mouse models, here we employ an NF1+/ex42del miniswine model to evaluate the mechanisms and characteristics of these presentations, taking advantage of a large animal species more like human anatomy and physiology. The prefrontal lobe, anterior cingulate, and hippocampus from NF1+/ex42del and wild-type miniswine were examined longitudinally, revealing abnormalities in mature oligodendrocytes and astrocytes, and microglial activation over time. Imbalances in GABA: Glutamate ratios and GAD67 expression were observed in the hippocampus and motor cortex, supporting the role of disruption in inhibitory neurotransmission in NF1 cognitive impairment and motor dysfunction. Moreover, NF1+/ex42del miniswine demonstrated slower and shorter steps, indicative of a balance-preserving response commonly observed in NF1 patients, and progressive memory and learning impairments. Collectively, our findings affirm the effectiveness of NF1+/ex42del miniswine as a valuable resource for assessing cognitive and motor impairments associated with NF1, investigating the involvement of specific neural circuits and glia in these processes, and evaluating potential therapeutic interventions.


Assuntos
Modelos Animais de Doenças , Neurofibromatose 1 , Animais , Neurofibromatose 1/fisiopatologia , Neurofibromatose 1/complicações , Neurofibromatose 1/metabolismo , Camundongos , Neurofibromina 1/genética , Neurofibromina 1/metabolismo , Comportamento Animal , Masculino , Hipocampo/patologia , Hipocampo/metabolismo , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Oligodendroglia/metabolismo , Oligodendroglia/patologia , Humanos , Astrócitos/metabolismo , Astrócitos/patologia , Feminino
8.
Sci Rep ; 14(1): 13800, 2024 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877101

RESUMO

Adjuvants enhance, prolong, and modulate immune responses by vaccine antigens to maximize protective immunity and enable more effective immunization in the young and elderly. Most adjuvants are formulated with injectable vaccines. However, an intranasal route of vaccination may induce mucosal and systemic immune responses for enhancing protective immunity in individuals and be easier to administer compared to injectable vaccines. In this study, a next generation of broadly-reactive influenza hemagglutinin (HA) vaccines were developed using the Computationally Optimized Broadly Reactive Antigen (COBRA) methodology. These HA vaccines were formulated with Mastoparan 7 (M7-NH2) mast cell degranulating peptide adjuvant and administered intranasally to determine vaccine-induced seroconversion of antibodies against a panel of influenza viruses and protection following infection with H1N1 and H3N2 viruses in mice. Mice vaccinated intranasally with M7-NH2-adjuvanted COBRA HA vaccines had high HAIs against a panel of H1N1 and H3N2 influenza viruses and were protected against both morbidity and mortality, with reduced viral lung titers, following challenge with an H1N1 influenza virus. Additionally, M7-NH2 adjuvanted COBRA HA vaccines induced Th2 skewed immune responses with robust IgG and isotype antibodies in the serum and mucosal lung lavages. Overall, this intranasally delivered M7-NH2 -adjuvanted COBRA HA vaccine provides effective protection against drifted H1N1 and H3N2 viruses.


Assuntos
Adjuvantes Imunológicos , Administração Intranasal , Anticorpos Antivirais , Glicoproteínas de Hemaglutininação de Vírus da Influenza , Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A Subtipo H3N2 , Vacinas contra Influenza , Infecções por Orthomyxoviridae , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/administração & dosagem , Animais , Camundongos , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Adjuvantes Imunológicos/administração & dosagem , Anticorpos Antivirais/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Infecções por Orthomyxoviridae/imunologia , Feminino , Camundongos Endogâmicos BALB C , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Adjuvantes de Vacinas/administração & dosagem
10.
Commun Biol ; 7(1): 687, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38839829

RESUMO

Understanding the factors influencing mosquitoes' fecundity and longevity is important for designing better and more sustainable vector control strategies, as these parameters can impact their vectorial capacity. Here, we address how mating affects midgut growth in Aedes aegypti, what role Juvenile Hormone (JH) plays in this process, and how it impacts the mosquito's immune response and microbiota. Our findings reveal that mating and JH induce midgut growth. Additionally, the establishment of a native bacterial population in the midgut due to JH-dependent suppression of the immune response has important reproductive outcomes. Specific downregulation of AMPs with an increase in bacteria abundance in the gut results in increased egg counts and longer lifespans. Overall, these findings provide evidence of a cross-talk between JH response, gut epithelial tissue, cell cycle regulation, and the mechanisms governing the trade-offs between nutrition, immunity, and reproduction at the cellular level in the mosquito gut.


Assuntos
Aedes , Fertilidade , Microbioma Gastrointestinal , Hormônios Juvenis , Animais , Aedes/microbiologia , Aedes/crescimento & desenvolvimento , Aedes/fisiologia , Hormônios Juvenis/metabolismo , Feminino , Aptidão Genética
11.
J Transl Med ; 22(1): 526, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38822352

RESUMO

BACKGROUND: Neutrophils are granulocytes with essential antimicrobial effector functions and short lifespans. During infection or sterile inflammation, emergency granulopoiesis leads to release of immature neutrophils from the bone marrow, serving to boost circulating neutrophil counts. Steady state and emergency granulopoiesis are incompletely understood, partly due to a lack of genetically amenable models of neutrophil development. METHODS: We optimised a method for ex vivo production of human neutrophils from CD34+ haematopoietic progenitors. Using flow cytometry, we phenotypically compared cultured neutrophils with native neutrophils from donors experiencing emergency granulopoiesis, and steady state neutrophils from non-challenged donors. We carry out functional and proteomic characterisation of cultured neutrophils and establish genome editing of progenitors. RESULTS: We obtain high yields of ex vivo cultured neutrophils, which phenotypically resemble immature neutrophils released into the circulation during emergency granulopoiesis. Cultured neutrophils have similar rates of ROS production and bacterial killing but altered degranulation, cytokine release and antifungal activity compared to mature neutrophils isolated from peripheral blood. These differences are likely due to incomplete synthesis of granule proteins, as demonstrated by proteomic analysis. CONCLUSION: Ex vivo cultured neutrophils are genetically tractable via genome editing of precursors and provide a powerful model system for investigating the properties and behaviour of immature neutrophils.


Assuntos
Antígenos CD34 , Neutrófilos , Humanos , Neutrófilos/metabolismo , Neutrófilos/citologia , Antígenos CD34/metabolismo , Células Cultivadas , Espécies Reativas de Oxigênio/metabolismo , Proteômica , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/citologia , Edição de Genes , Degranulação Celular , Células-Tronco/metabolismo , Células-Tronco/citologia , Citocinas/metabolismo , Fenótipo
12.
Eur J Heart Fail ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38837516

RESUMO

AIMS: Heart failure (HF) elicits a pro-inflammatory state, which is associated with impaired clinical outcomes, but no anti-inflammatory therapies have demonstrated a clinical benefit yet. Inflammatory pathways related with the interleukin-1 axis are overactivated during episodes of acute HF. Colchicine, an anti-inflammatory drug with proven benefits in acute pericarditis and ischaemic heart disease, may target this inflammatory response. This study aims to assess the efficacy of colchicine in acute HF patients. METHODS: COLICA is a multicentre, randomized, double-blind, placebo-controlled trial enrolling 278 patients across 12 sites. Patients presenting with acute HF, clinical evidence of congestion requiring ≥40 mg of intravenous furosemide and N-terminal pro-B-type natriuretic peptide (NT-proBNP) >900 pg/ml, are eligible for participation. Patients are enrolled irrespective of left ventricular ejection fraction, HF type (new-onset or not) and setting (hospital or outpatient clinic). Patients are randomized 1:1 within the first 24 h of presentation to either placebo or colchicine, with an initial loading dose of 2 mg followed by 0.5 mg every 12 h for 8 weeks (reduced dose if <70 kg, >75 years old, or glomerular filtration rate <50 ml/min/1.73 m2). The primary efficacy endpoint is the time-averaged proportional change in NT-proBNP concentrations from baseline to week 8. Key secondary and exploratory outcomes include symptoms, diuretic use, worsening HF episodes, related biomarkers of cardiac stress and inflammation, total and cardiovascular readmissions, mortality and safety events. CONCLUSION: COLICA will be the first randomized trial testing the efficacy and safety of colchicine for acute HF.

13.
J Sci Med Sport ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38839539

RESUMO

We quantified and compared the mechanical force demands relative to the maximum dynamic force (MDF) of 11 cyclists when pedaling at different intensities (ventilatory threshold, maximum lactate steady state, respiratory compensation point, and maximal aerobic power), cadences (free, 40, 60 and 80 rpm), and all-out resisted sprints. Relative force demands (expressed as %MDF) progressively increased with higher intensities (p < 0.001) and lower cadences (p < 0.001). Notwithstanding, relative force demands were low (<54 % MDF) for all conditions, even during the so-called 'torque training'. These results might be useful when programming on-bike resistance training to improve torque production capacity.

14.
Porto Biomed J ; 9(3): 255, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38911267
15.
Circulation ; 149(Suppl)May 16, 2024.
Artigo em Inglês | CONASS, Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1554725

RESUMO

INTRODUCTION: Coenzyme Q10 (CoQ10) has shown promising results as an adjuvant therapy to statins. However, the efficacy of this agent is still unclear. Hypothesis: The use of CoQ10 mitigates statin-related myopathic pain. METHODS: PubMed, Embase, and Cochrane databases were searched for randomized controlled trials (RCTs) comparing CoQ10 supplementation with placebo in patients taking statins. A random-effects model was employed to compute the mean difference (MD) with 95% confidence interval (CI). Statistical analysis was performed using R software 4.3.1. RESULTS: A total of 5 studies and 227 patients were included, of whom 48% were randomized to CoQ10 supplementation. Compared with placebo, CoQ10 had no effects on pain severity score (MD -0.94; 95% CI -3.80 to 1.91; p=0.5), and pain intensity score (MD -1.51; 95% CI -4.09 to 1.06; p = 0.2). Moreover, no association was found with low density lipoprotein cholesterol levels (MD -0.07; 95% CI -0.47 to 0.34; p = 0.7). CONCLUSIONS: In this meta-analysis of 5 RCTs, supplementation with CoQ10 did not yield statistically significant results. These findings suggest that CoQ10 has no impact on statin-related myopathic pain.

16.
Lancet ; maio.2024.
Artigo em Inglês | CONASS, Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1555077

RESUMO

BACKGROUND Transcatheter aortic valve implantation is an established, guideline-endorsed treatment for severe aortic stenosis. Precise sizing of the balloon-expandable Myval transcatheter heart valve (THV) series with the aortic annulus is facilitated by increasing its diameter in 1•5 mm increments, compared with the usual 3 mm increments in valve size. The LANDMARK trial aimed to show non-inferiority of the Myval THV series compared with the contemporary THVs Sapien Series (Edwards Lifesciences, Irvine, CA, USA) or Evolut Series (Medtronic, Minneapolis, MN, USA). METHODS In this prospective, multinational, randomised, open-label, non-inferiority trial across 31 hospitals in 16 countries (Germany, France, Sweden, the Netherlands, Italy, Spain, New Zealand, Portugal, Greece, Hungary, Poland, Slovakia, Slovenia, Croatia, Estonia, and Brazil), 768 participants with severe symptomatic native aortic stenosis were randomly assigned (1:1) to the Myval THV or a contemporary THV. Eligibility was primarily decided by the heart team in accordance with 2021 European Society of Cardiology guidelines. As per the criteria of the third Valve Academic Research Consortium, the primary endpoint at 30 days was a composite of all-cause mortality, all stroke, bleeding (types 3 and 4), acute kidney injury (stages 2­4), major vascular complications, moderate or severe prosthetic valve regurgitation, and conduction system disturbances resulting in a permanent pacemaker implantation. Non-inferiority of the study device was tested in the intention-to-treat population using a non-inferiority margin of 10•44% and assuming an event rate of 26•10%. This trial is registered with ClinicalTrials.gov, NCT04275726, and EudraCT, 2020-000137-40, and is closed to new participants. FINDINGS Between Jan 6, 2021, and Dec 5, 2023, 768 participants with severe symptomatic native aortic stenosis were randomly assigned, 384 to the Myval THV and 384 to a contemporary THV. 369 (48%) participants had their sex recorded as female, and 399 (52%) as male. The mean age of participants was 80•0 years (SD 5•7) for those treated with the Myval THV and 80•4 years (5•4) for those treated with a contemporary THV. Median Society of Thoracic Surgeons scores were the same in both groups (Myval 2•6% [IQR 1•7­4•0] vs contemporary 2•6% [1•7­4•0]). The primary endpoint showed non-inferiority of the Myval (25%) compared with contemporary THV (27%), with a risk difference of ­2•3% (one-sided upper 95% CI 3•8, pnon-inferiority<0•0001). No significant difference was seen in individual components of the primary composite endpoint. INTERPRETATION In individuals with severe symptomatic native aortic stenosis, the Myval THV met its primary endpoint at 30 days.

17.
Crit Care ; 28(1): 165, 2024 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750543

RESUMO

BACKGROUND: Mechanical ventilation, a lifesaving intervention in critical care, can lead to damage in the extracellular matrix (ECM), triggering inflammation and ventilator-induced lung injury (VILI), particularly in conditions such as acute respiratory distress syndrome (ARDS). This review discusses the detailed structure of the ECM in healthy and ARDS-affected lungs under mechanical ventilation, aiming to bridge the gap between experimental insights and clinical practice by offering a thorough understanding of lung ECM organization and the dynamics of its alteration during mechanical ventilation. MAIN TEXT: Focusing on the clinical implications, we explore the potential of precise interventions targeting the ECM and cellular signaling pathways to mitigate lung damage, reduce inflammation, and ultimately improve outcomes for critically ill patients. By analyzing a range of experimental studies and clinical papers, particular attention is paid to the roles of matrix metalloproteinases (MMPs), integrins, and other molecules in ECM damage and VILI. This synthesis not only sheds light on the structural changes induced by mechanical stress but also underscores the importance of cellular responses such as inflammation, fibrosis, and excessive activation of MMPs. CONCLUSIONS: This review emphasizes the significance of mechanical cues transduced by integrins and their impact on cellular behavior during ventilation, offering insights into the complex interactions between mechanical ventilation, ECM damage, and cellular signaling. By understanding these mechanisms, healthcare professionals in critical care can anticipate the consequences of mechanical ventilation and use targeted strategies to prevent or minimize ECM damage, ultimately leading to better patient management and outcomes in critical care settings.


Assuntos
Matriz Extracelular , Pulmão , Respiração Artificial , Síndrome do Desconforto Respiratório , Humanos , Matriz Extracelular/metabolismo , Síndrome do Desconforto Respiratório/terapia , Síndrome do Desconforto Respiratório/fisiopatologia , Respiração Artificial/efeitos adversos , Respiração Artificial/métodos , Pulmão/fisiopatologia , Pulmão/metabolismo , Lesão Pulmonar Induzida por Ventilação Mecânica/fisiopatologia , Lesão Pulmonar Induzida por Ventilação Mecânica/prevenção & controle , Metaloproteinases da Matriz/metabolismo , Animais
19.
Sports Med ; 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38709451

RESUMO

BACKGROUND: Preterm birth and low birthweight (LBW) might be associated with reduced physical fitness, although evidence remains inconclusive. OBJECTIVE: To examine the influence of preterm birth and LBW on physical fitness, as well as to assess whether variables such as gestational age, birthweight, or age at assessment moderate these effects. METHODS: PubMed, Scopus, and PsycINFO were systematically searched from inception to 7 December 2023 for case-control and cohort studies analyzing the association between preterm birth or LBW (or gestational age or birthweight as continuous variables) with at least one physical fitness-related outcome (i.e., cardiorespiratory fitness (CRF), muscle strength, flexibility, speed, agility). Random-effects meta-analysis and meta-regression models were used to estimate the pooled effect size, as well as to examine potential associations between the magnitude of the effect and gestational age, birthweight, or age at assessment. RESULTS: Fifty-two studies (n = 920,603 participants, average age ranging from 4.7 to 34.4 years) were included. Preterm birth was associated with reduced CRF (standardized mean difference (SMD) = -0.38, 95% confidence interval (CI) = -0.51 to -0.25) and muscle strength (SMD = -0.44, 95% CI = -0.79 to -0.08). LBW was associated with reduced CRF (SMD = -0.40, 95% CI = -0.64 to -0.17), muscle strength (SMD = -0.18, 95% CI = -0.24 to -0.13), flexibility (SMD = -0.11, 95% CI = -0.22 to -0.01), and agility (SMD = -0.99, 95% CI = -1.91 to -0.07). Meta-regression analyses showed that a lower gestational age or birthweight were associated with larger reductions in physical fitness, whereas no consistent association was found for the age at assessment. CONCLUSION: Both preterm birth and LBW seem associated with reduced physical fitness regardless of age, with larger reductions overall observed in individuals with lower gestational age or birthweight. These findings might support the implementation of preventive strategies (e.g., fitness monitoring and physical exercise interventions) in these populations through the life course. PROSPERO registration: CRD42021231845.

20.
J Econ Entomol ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38717590

RESUMO

The current study evaluated the potential enhancement of lauric acid (LA) in black soldier fly, Hermetia illucens, (L.) (Diptera: Stratiomyidae) larvae (BSFL), a source of this short-chain fatty acid which has antimicrobial and immunostimulatory properties. Replicate groups of BSFL were reared on either the coconut or Gainesville diet for 7 days. After the rearing period, BSFL were harvested, purged, dried, and subjected to proximate, fatty acid and amino acid compositions, and pepsin digestibility analyses. Results demonstrate changes in proximate composition. BSFL reared on the coconut had significantly (P = 0.002) higher lipid content (47.3% vs. 25.2%) on a dry-matter basis. The LA concentration in BSFL produced on the coconut was 31% greater than those reared on Gainesville, resulting in almost 150% more LA. Furthermore, BSFL-fed coconut had reduced crude protein (29.7% of dry weight) and ash (3.7% of dry weight) relative to those fed Gainesville (43.4% and 7.5% for crude protein and ash, respectively) but higher pepsin digestibility (91.0% vs. 87.0%). The relative amounts of various amino acids in the 2 BSFL meals did not differ extensively, with statistically lower concentrations of only phenylalanine and tryptophan and higher concentrations of alanine, arginine, isoleucine, leucine, and serine in BSFL reared on coconut. Results demonstrate that the nutritional composition of BSFL can be manipulated, and an enhancement of LA concentrations of 150% was achieved with coconut, which has value for BSFL as a feed for various livestock, including aquaculture. Lower protein content is a tradeoff in terms of BSFL value as a feed additive.

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