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1.
Cell ; 187(10): 2393-2410.e14, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38653235

RESUMO

SARS-CoV-2 and other sarbecoviruses continue to threaten humanity, highlighting the need to characterize common mechanisms of viral immune evasion for pandemic preparedness. Cytotoxic lymphocytes are vital for antiviral immunity and express NKG2D, an activating receptor conserved among mammals that recognizes infection-induced stress ligands (e.g., MIC-A/B). We found that SARS-CoV-2 evades NKG2D recognition by surface downregulation of MIC-A/B via shedding, observed in human lung tissue and COVID-19 patient serum. Systematic testing of SARS-CoV-2 proteins revealed that ORF6, an accessory protein uniquely conserved among sarbecoviruses, was responsible for MIC-A/B downregulation via shedding. Further investigation demonstrated that natural killer (NK) cells efficiently killed SARS-CoV-2-infected cells and limited viral spread. However, inhibition of MIC-A/B shedding with a monoclonal antibody, 7C6, further enhanced NK-cell activity toward SARS-CoV-2-infected cells. Our findings unveil a strategy employed by SARS-CoV-2 to evade cytotoxic immunity, identify the culprit immunevasin shared among sarbecoviruses, and suggest a potential novel antiviral immunotherapy.


Assuntos
COVID-19 , Evasão da Resposta Imune , Células Matadoras Naturais , Subfamília K de Receptores Semelhantes a Lectina de Células NK , SARS-CoV-2 , Humanos , SARS-CoV-2/imunologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , COVID-19/imunologia , COVID-19/virologia , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Animais , Citotoxicidade Imunológica , Regulação para Baixo , Pulmão/imunologia , Pulmão/virologia , Pulmão/patologia
2.
Cell ; 169(4): 766-766.e1, 2017 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-28475901

RESUMO

Macropinocytosis is the bulk ingestion of extracellular fluids via large endocytic vacuoles. This SnapShot provides an overview of physiological macropinocytosis in immune surveillance and its pathogenic contribution during infection and cancer proliferation.


Assuntos
Pinocitose , Animais , Endocitose , Humanos , Vigilância Imunológica , Infecções/imunologia , Vacúolos
3.
Blood ; 143(21): 2190-2200, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38306657

RESUMO

ABSTRACT: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, caused by somatic mutations in UBA1, is an autoinflammatory disorder with diverse systemic manifestations. Thrombosis is a prominent clinical feature of VEXAS syndrome. The risk factors and frequency of thrombosis in VEXAS syndrome are not well described, due to the disease's recent discovery and the paucity of large databases. We evaluated 119 patients with VEXAS syndrome for venous and arterial thrombosis and correlated their presence with clinical outcomes and survival. Thrombosis occurred in 49% of patients, mostly venous thromboembolism (VTE; 41%). Almost two-thirds of VTEs were unprovoked, 41% were recurrent, and 20% occurred despite anticoagulation. The cumulative incidence of VTE was 17% at 1 year from symptom onset and 40% by 5 years. Cardiac and pulmonary inflammatory manifestations were associated with time to VTE. M41L was positively associated specifically with pulmonary embolism by univariate (odds ratio [OR]: 4.58, confidence interval [CI] 1.28-16.21, P = .02) and multivariate (OR: 16.94, CI 1.99-144.3, P = .01) logistic regression. The cumulative incidence of arterial thrombosis was 6% at 1 year and 11% at 5 years. The overall survival of the entire patient cohort at median follow-up time of 4.8 years was 88%, and there was no difference in survival between patients with or without thrombosis (P = .8). Patients with VEXAS syndrome are at high risk of VTE; thromboprophylaxis should administered be in high-risk settings unless strongly contraindicated.


Assuntos
Trombose , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Trombose/etiologia , Trombose/genética , Trombose/epidemiologia , Adolescente , Enzimas Ativadoras de Ubiquitina/genética , Adulto Jovem , Fatores de Risco , Idoso , Criança , Trombose Venosa/etiologia , Trombose Venosa/epidemiologia , Trombose Venosa/genética , Incidência , Mutação , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/complicações , Pré-Escolar
4.
J Neurosci Res ; 102(4): e25336, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38656664

RESUMO

Chronic neuroinflammation has been implicated in neurodegenerative disease pathogenesis. A key feature of neuroinflammation is neuronal loss and glial activation, including microglia and astrocytes. 4R-cembranoid (4R) is a natural compound that inhibits hippocampal pro-inflammatory cytokines and increases memory function in mice. We used the lipopolysaccharide (LPS) injection model to study the effect of 4R on neuronal density and microglia and astrocyte activation. C57BL/6J wild-type mice were injected with LPS (5 mg/kg) and 2 h later received either 4R (6 mg/kg) or vehicle. Mice were sacrificed after 72 h for analysis of brain pathology. Confocal images of brain sections immunostained for microglial, astrocyte, and neuronal markers were used to quantify cellular hippocampal phenotypes and neurons. Hippocampal lysates were used to measure the expression levels of neuronal nuclear protein (NeuN), inducible nitrous oxide synthase (iNOS), arginase-1, thrombospondin-1 (THBS1), glial cell-derived neurotrophic factor (GDNF), and orosomucoid-2 (ORM2) by western blot. iNOS and arginase-1 are widely used protein markers of pro- and anti-inflammatory microglia, respectively. GDNF promotes neuronal survival, and ORM2 and THBS1 are astrocytic proteins that regulate synaptic plasticity and inhibit microglial activation. 4R administration significantly reduced neuronal loss and the number of pro-inflammatory microglia 72 h after LPS injection. It also decreased the expression of the pro-inflammatory protein iNOS while increasing arginase-1 expression, supporting its anti-inflammatory role. The protein expression of THBS1, GDNF, and ORM2 was increased by 4R. Our data show that 4R preserves the integrity of hippocampal neurons against LPS-induced neuroinflammation in mice.


Assuntos
Hipocampo , Lipopolissacarídeos , Camundongos Endogâmicos C57BL , Neuroglia , Neurônios , Animais , Lipopolissacarídeos/toxicidade , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Camundongos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Neuroglia/efeitos dos fármacos , Neuroglia/metabolismo , Neuroglia/patologia , Masculino , Microglia/efeitos dos fármacos , Microglia/metabolismo , Microglia/patologia , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/patologia , Doenças Neuroinflamatórias/tratamento farmacológico , Fenótipo , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Astrócitos/patologia
5.
Plant Cell Environ ; 47(8): 2865-2878, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38616528

RESUMO

A trade-off between growth and defence against biotic stresses is common in plants. Fungal endophytes of the genus Epichloë may relieve this trade-off in their host grasses since they can simultaneously induce plant growth and produce antiherbivore alkaloids that circumvent the need for host defence. The Epichloë ability to decouple the growth-defence trade-off was evaluated by subjecting ryegrass with and without Epichloë endophytes to an exogenous treatment with gibberellin (GA) followed by a challenge with Rhopalosiphum padi aphids. In agreement with the endophyte-mediated trade-off decoupling hypothesis, the GA-derived promotion of plant growth increased the susceptibility to aphids in endophyte-free plants but did not affect the insect resistance in endophyte-symbiotic plants. In line with the unaltered insect resistance, the GA treatment did not reduce the concentration of Epichloë-derived alkaloids. The Epichloë mycelial biomass was transiently increased by the GA treatment but at the expense of hyphal integrity. The response of the phyllosphere bacterial microbiota to both GA treatment and Epichloë was also evaluated. Only Epichloë, and not the GA treatment, altered the composition of the phyllosphere microbiota and the abundance of certain bacterial taxa. Our findings clearly demonstrate that Epichloë does indeed relieve the plant growth-defence trade-off.


Assuntos
Endófitos , Epichloe , Giberelinas , Herbivoria , Lolium , Microbiota , Simbiose , Endófitos/fisiologia , Animais , Epichloe/fisiologia , Lolium/microbiologia , Lolium/crescimento & desenvolvimento , Lolium/fisiologia , Giberelinas/metabolismo , Afídeos/fisiologia , Bactérias , Alcaloides/metabolismo , Defesa das Plantas contra Herbivoria
6.
J Cardiovasc Electrophysiol ; 35(7): 1329-1339, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38664888

RESUMO

BACKGROUND: The efficacy and safety of adjunctive low-voltage area (LVA) ablation on outcomes of catheter ablation (CA) for atrial fibrillation (AF) remains uncertain. METHODS: PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) comparing CA with versus without LVA ablation for patients with AF. Risk ratios (RR) with 95% confidence intervals (CI) were pooled with a random-effects model. Our primary endpoint was recurrence of atrial tachyarrhythmia (ATA), including AF, atrial flutter, or atrial tachycardia. We used R version 4.3.1 for all statistical analyses. RESULTS: Our meta-analysis included 10 RCTs encompassing 1780 patients, of whom 890 (50%) were randomized to LVA ablation. Adjunctive LVA ablation significantly reduced recurrence of ATA (RR 0.76; 95% CI 0.67-0.88; p < .01) and reduced the number of redo ablation procedures (RR 0.54; 95% CI 0.35-0.85; p < .01), as compared with conventional ablation. Among 691 (43%) patients with documented LVAs on baseline substrate mapping, adjunctive LVA ablation substantially reduced ATA recurrences (RR 0.57; 95% CI 0.38-0.86; p < .01). There was no significant difference between groups in terms of periprocedural adverse events (RR 0.78; 95% CI 0.39-1.56; p = .49). CONCLUSIONS: Adjunctive LVA ablation is an effective and safe strategy for reducing recurrences of ATA among patients who undergo CA for AF.


Assuntos
Potenciais de Ação , Fibrilação Atrial , Ablação por Cateter , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Humanos , Fibrilação Atrial/cirurgia , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/diagnóstico , Ablação por Cateter/efeitos adversos , Resultado do Tratamento , Masculino , Fatores de Risco , Feminino , Pessoa de Meia-Idade , Frequência Cardíaca , Idoso , Fatores de Tempo
7.
Virol J ; 21(1): 1, 2024 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172919

RESUMO

BACKGROUND: The particle structure of Emiliania huxleyi virus (EhV), an algal infecting member of nucleocytoplasmic large DNA viruses (NCLDVs), contains an outer lipid membrane envelope similar to that found in animal viruses such as African swine fever virus (ASFV). Despite both being enveloped NCLDVs, EhV and ASFV are known for their stability outside their host environment. METHOD: Here we report for the first time, the application of a viability qPCR (V-qPCR) method to describe the unprecedented and similar virion thermal stability of both EhV and ASFV. This result contradicts the cell culture-based assay method that suggests that virus "infectivity" is lost in a matter of seconds (for EhV) and minutes (for ASFV) at temperature greater than 50 °C. Confocal microscopy and analytical flow cytometry methods was used to validate the V-qPCR data for EhV. RESULTS: We observed that both EhV and ASFV particles has unprecedented thermal tolerances. These two NCLDVs are exceptions to the rule that having an enveloped virion anatomy is a predicted weakness, as is often observed in enveloped RNA viruses (i.e., the viruses causing Porcine Reproductive and Respiratory Syndrome (PRRS), COVID-19, Ebola, or seasonal influenza). Using the V-qPCR method, we confirm that no PRRSV particles were detectable after 20 min of exposure to temperatures up to 100 °C. We also show that the EhV particles that remain after 50 °C 20 min exposure was in fact still infectious only after the three blind passages in bioassay experiments. CONCLUSIONS: This study raises the possibility that ASFV is not always eliminated or contained after applying time and temperature inactivation treatments in current decontamination or biosecurity protocols. This observation has practical implications for industries involved in animal health and food security. Finally, we propose that EhV could be used as a surrogate for ASFV under certain circumstances.


Assuntos
Vírus da Febre Suína Africana , Febre Suína Africana , Haptófitas , Suínos , Animais , Vírus da Febre Suína Africana/genética , Haptófitas/genética , Vírion , Reação em Cadeia da Polimerase
8.
Ann Bot ; 133(4): 509-520, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38320313

RESUMO

BACKGROUND AND AIMS: In the subfamily Poöideae (Poaceae), certain grass species possess anti-herbivore alkaloids synthesized by fungal endophytes that belong to the genus Epichloë (Clavicipitaceae). The protective role of these symbiotic endophytes can vary, depending on alkaloid concentrations within specific plant-endophyte associations and plant parts. METHODS: We conducted a literature review to identify articles containing alkaloid concentration data for various plant parts in six important pasture species, Lolium arundinaceum, Lolium perenne, Lolium pratense, Lolium multiflorum|Lolium rigidum and Festuca rubra, associated with their common endophytes. We considered the alkaloids lolines (1-aminopyrrolizidines), peramine (pyrrolopyrazines), ergovaline (ergot alkaloids) and lolitrem B (indole-diterpenes). While all these alkaloids have shown bioactivity against insect herbivores, ergovaline and lolitrem B are harmful for mammals. KEY RESULTS: Loline alkaloid levels were higher in the perennial grasses L. pratense and L. arundinaceum compared to the annual species L. multiflorum and L. rigidum, and higher in reproductive tissues than in vegetative structures. This is probably due to the greater biomass accumulation in perennial species that can result in higher endophyte mycelial biomass. Peramine concentrations were higher in L. perenne than in L. arundinaceum and not affected by plant part. This can be attributed to the high within-plant mobility of peramine. Ergovaline and lolitrem B, both hydrophobic compounds, were associated with plant parts where fungal mycelium is usually present, and their concentrations were higher in plant reproductive tissues. Only loline alkaloid data were sufficient for below-ground tissue analyses and concentrations were lower than in above-ground parts. CONCLUSIONS: Our study provides a comprehensive synthesis of fungal alkaloid variation across host grasses and plant parts, essential for understanding the endophyte-conferred defence extent. The patterns can be understood by considering endophyte growth within the plant and alkaloid mobility. Our study identifies research gaps, including the limited documentation of alkaloid presence in roots and the need to investigate the influence of different environmental conditions.


Assuntos
Alcaloides , Endófitos , Epichloe , Festuca , Lolium , Poliaminas , Alcaloides/metabolismo , Alcaloides/análise , Endófitos/química , Endófitos/fisiologia , Epichloe/química , Epichloe/fisiologia , Ergotaminas/metabolismo , Festuca/microbiologia , Festuca/fisiologia , Herbivoria , Compostos Heterocíclicos com 2 Anéis , Alcaloides Indólicos/metabolismo , Lolium/microbiologia , Lolium/fisiologia , Micotoxinas , Defesa das Plantas contra Herbivoria , Poaceae/microbiologia , Poaceae/metabolismo , Simbiose
9.
J Surg Res ; 295: 647-654, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38103322

RESUMO

INTRODUCTION: Nonoperative management (NOM) along with supportive care has been the adopted approach for traumatic rib fractures; however, surgical approaches have emerged recently to treat this common pathology. Despite this, there are no guidelines for surgical rib fixation in patients with traumatic rib fractures. METHODS: An institutional review board-approved retrospective cohort study was performed at the Puerto Rico Trauma Hospital aiming to compare the outcomes and complications between patients with traumatic rib fractures who undergo surgical fixation and their counterparts with NOM. The study period comprised from January 2016 through July 2020. Outcomes were evaluated with negative binomial and logistic regressions. RESULTS: Fifty patients were identified for the surgical rib fixation group, who were matched to 150 patients who received NOM. The majority of patients were male (91.5%), with a median (interquartile range) age of 53 (29) years. Concomitant chest injuries were significantly more prevalent in the operative group, such as flail segment (P < 0.001), number of fractures (P < 0.001), and displaced rib fractures (P < 0.001). Although hospital length of stay was 25% (95% confidence interval: 1.02-1.54) longer in the surgical group, this intervention was associated with an 85% (95% confidence interval: 0.03-0.70) lower mortality rate when compared to conservative management. CONCLUSIONS: Rib fixation may offer some benefits in selected patients with traumatic rib fractures, such as those with bilateral rib fractures, multiple displaced rib fractures, flail segment, and concomitant thoracic injuries. This study may serve as a guide for treatment strategy and patient selection regarding the surgical management of traumatic rib fractures.


Assuntos
Tórax Fundido , Fraturas das Costelas , Traumatismos Torácicos , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Fraturas das Costelas/complicações , Fraturas das Costelas/cirurgia , Estudos Retrospectivos , Tórax Fundido/etiologia , Traumatismos Torácicos/complicações , Tempo de Internação , Costelas , Fixação Interna de Fraturas/efeitos adversos
10.
Environ Res ; 246: 118119, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38191038

RESUMO

In this study, a precipitation-based synthesis method has been employed to prepare magnesium calcites with the general formula Ca1-xMgxCO3, with the objective of use them in the calcium looping (CaL) process for CO2 capture (CaL-CCS) and thermochemical energy storage (CaL-CSP). The structure and microstructure of the samples have been characterized. It has been found by X-ray diffraction that the samples with a Ca:Mg molar ratio of 0.5:0.5 and 0.55:0.45 are phase pure, while the samples with molar ratios of 0.7:0.3 and 0.8:0.2 are composed by two phases with different stoichiometry. In addition, the sample prepared with calcium alone shows the aragonite phase. The microstructure of the magnesium-containing samples is composed of nanocrystals, which are aggregated in spherical particles whereas the aragonite sample presents a typical rod-like morphology. The multicycle tests carried out under CaL-CCS conditions show that an increase on the MgO content in the calcined samples results in a reduced value of effective conversion when compared to aragonite. On the other hand, under CaL-CSP conditions, the samples with the higher MgO content exhibit nearly stable effective conversion values around 0.5 after 20 cycles, which improve the results obtained for aragonite and those reported for natural dolomite tested under the same conditions.


Assuntos
Cálcio , Magnésio , Cálcio/química , Magnésio/química , Dióxido de Carbono/química , Óxido de Magnésio , Carbonato de Cálcio/química
11.
Cell Mol Life Sci ; 80(2): 55, 2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36729338

RESUMO

Chemokine ligands and receptors regulate the directional migration of leukocytes. Post-translational modifications of chemokine receptors including O-glycosylation and tyrosine sulfation have been reported to regulate ligand binding and resulting signaling. Through in silico analyses, we determined potential conserved O-glycosylation and sulfation sites on human and murine CC chemokine receptors. Glyco-engineered CHO cell lines were used to measure the impact of O-glycosylation on CC chemokine receptor CCR5, while mutation of tyrosine residues and treatment with sodium chlorate were performed to determine the effect of tyrosine sulfation. Changing the glycosylation or tyrosine sulfation on CCR5 reduced the receptor signaling by the more positively charged CCL5 and CCL8 more profoundly compared to the less charged CCL3. The loss of negatively charged sialic acids resulted only in a minor effect on CCL3-induced signal transduction. The enzymes GalNAc-T1 and GalNAc-T11 were shown to be involved in the process of chemokine receptor O-glycosylation. These results indicate that O-glycosylation and tyrosine sulfation are involved in the fine-tuning and recognition of chemokine interactions with CCR5 and the resulting signaling.


Assuntos
Quimiocinas , Transdução de Sinais , Cricetinae , Animais , Humanos , Camundongos , Quimiocinas/metabolismo , Processamento de Proteína Pós-Traducional , Receptores CCR5/genética , Células CHO , Tirosina/metabolismo , Ligação Proteica
12.
AIDS Res Ther ; 21(1): 17, 2024 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-38515183

RESUMO

BACKGROUND: As the population of people with HIV ages, concerns over managing age-related comorbidities, polypharmacy, immune recovery, and drug-drug interactions while maintaining viral suppression have arisen. We present pooled TANGO and SALSA efficacy and safety results dichotomized by age (< 50 and ≥ 50 years). METHODS: Week 48 data from the open-label phase 3 TANGO and SALSA trials evaluating switch to once-daily dolutegravir/lamivudine (DTG/3TC) fixed-dose combination vs continuing current antiretroviral regimen (CAR) were pooled. Proportions of participants with HIV-1 RNA ≥ 50 and < 50 copies/mL (Snapshot, intention-to-treat exposed) and safety were analyzed by age category. Adjusted mean change from baseline in CD4 + cell count was assessed using mixed-models repeated-measures analysis. RESULTS: Of 1234 participants, 80% of whom were male, 29% were aged ≥ 50 years. Among those aged ≥ 50 years, 1/177 (< 1%) DTG/3TC participant and 3/187 (2%) CAR participants had HIV-1 RNA ≥ 50 copies/mL at 48 weeks; proportions with HIV-1 RNA < 50 copies/mL were high in both treatment groups (≥ 92%), consistent with overall efficacy and similar to observations in participants aged < 50 years (≥ 93%). Regardless of age category, CD4 + cell count increased or was maintained from baseline with DTG/3TC. Change from baseline in CD4 + /CD8 + ratio was similar across age groups and between treatment groups. One CAR participant aged < 50 years had confirmed virologic withdrawal, but no resistance was detected. In the DTG/3TC group, incidence of adverse events (AEs) was similar across age groups. Proportions of AEs leading to withdrawal were low and comparable between age groups. Although drug-related AEs were generally low, across age groups, drug-related AEs were more frequent in participants who switched to DTG/3TC compared with those who continued CAR. While few serious AEs were observed in both treatment groups, more were reported in participants aged ≥ 50 years vs < 50 years. CONCLUSIONS: Among individuals with HIV-1, switching to DTG/3TC maintained high rates of virologic suppression and demonstrated a favorable safety profile, including in those aged ≥ 50 years despite higher prevalence of concomitant medication use and comorbidities. TRIAL REGISTRATION NUMBER: TANGO, NCT03446573 (February 27, 2018); SALSA, NCT04021290 (July 16, 2019).


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Soropositividade para HIV , HIV-1 , Oxazinas , Piperazinas , Piridonas , Humanos , Masculino , Feminino , Lamivudina/efeitos adversos , Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Antirretrovirais/uso terapêutico , Soropositividade para HIV/tratamento farmacológico , RNA
13.
J Cardiothorac Vasc Anesth ; 38(3): 649-659, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38228424

RESUMO

OBJECTIVE: To verify the impact of preoperative levosimendan on patients with severe left ventricular dysfunction (ejection fraction <35%) undergoing isolated coronary artery bypass grafting. DESIGN: A meta-analysis. SETTING: Hospitals. PARTICIPANTS: The authors included 1,225 patients from 6 randomized controlled trials. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The authors performed a meta-analysis of trials that compared preoperative levosimendan with placebo or no therapy, reporting efficacy and safety endpoints. Statistical analyses used mean differences and risk ratios (RR), with a random effects model. Six studies were included, comprising 1,225 patients, of whom 615 (50.2%) received preoperative levosimendan, and 610 (49.8%) received placebo/no therapy. Preoperative levosimendan showed a lower risk of all-cause mortality (RR 0.31; 95% CI 0.16-0.60; p < 0.01; I2 = 0%), postoperative acute kidney injury (RR 0.44; 95% CI 0.25-0.77; p < 0.01; I2 = 0%), low-cardiac-output syndrome (RR 0.45; 95% CI 0.30-0.66; p < 0.001; I2 = 0%), and postoperative atrial fibrillation (RR 0.49; 95% CI 0.25-0.98; p = 0.04; I2 = 85%) compared to control. Moreover, levosimendan significantly reduced the need for postoperative inotropes and increased the cardiac index at 24 hours postoperatively. There were no differences between groups for perioperative myocardial infarction, hypotension, or any adverse events. CONCLUSION: Preoperative levosimendan in patients with severe left ventricular dysfunction undergoing isolated coronary artery bypass grafting was associated with reduced all-cause mortality, low-cardiac-output syndrome, acute kidney injury, postoperative atrial fibrillation, and the need for circulatory support without compromising safety.


Assuntos
Injúria Renal Aguda , Fibrilação Atrial , Simendana , Disfunção Ventricular Esquerda , Humanos , Injúria Renal Aguda/etiologia , Fibrilação Atrial/etiologia , Baixo Débito Cardíaco/tratamento farmacológico , Baixo Débito Cardíaco/etiologia , Cardiotônicos/uso terapêutico , Ponte de Artéria Coronária/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Simendana/uso terapêutico
14.
Artigo em Inglês | MEDLINE | ID: mdl-38591168

RESUMO

Summary: Background. The clinical and pathophysiological heterogeneity of atopic dermatitis (AD) endophenotypes is associated with wide diversity in response to therapy. The aim of this study was to evaluate the response to dupilumab in a group of AD patients and identify clinical/immunological features associated with different patterns of response. Methods. A retrospective observational study was performed, including 30 adults with AD who completed 12 months treatment with dupilumab, in a Portuguese Immunoallergology Department. Demographic, clinical, and immunological data were analyzed, including total serum IgE, sensitization to aeroallergens, peripheral eosinophilia and inflammatory biomarkers (sedimentation rate, C-reactive protein and lactate dehydrogenase-LDH). Patients who achieved EASI-75/EASI ≤ 7, SCORAD-75/SCORAD ≤ 24, NRS-pruritus ≤ 4 or DLQI≤5 at 6 months of treatment were considered responders and those that achieved all these goals at 16 weeks were considered super-responders. Results. Clinical evaluation revealed a significant reduction in median SCORAD, EASI, DLQI, NRS-pruritus and NRS-sleep over 12 months on dupilumab (p less than 0.01), in parallel with decrease in serum Th2 pathway biomarkers and LDH. All patients responded to dupilumab, and 26.7% were super-responders, supporting that dupilumab is highly effective in moderate to severe Th2-high AD. Conclusions. In this cohort, none of the evaluated biomarkers at baseline were associated with a better/earlier clinical response to dupilumab. Dupilumab treatment for 52 weeks resulted in a significant and sustained reduction in blood levels of total IgE and allergen-specific IgE to aeroallergens. The potential long-term clinical benefit of these effects, even after discontinuing dupilumab therapy in patients with AD, should be explored to a greater extent.

15.
Artigo em Inglês | MEDLINE | ID: mdl-38913398

RESUMO

Summary: Background. Grass and olive pollens have overlapping pollination periods and are common allergens in the Iberian Peninsula. The objective is to determine the sensitization pattern to major Phleum pratense and Olea europaea pollens in the Portuguese population with pollen allergic rhinitis (AR) using molecular allergen diagnosis (MAD). Methods. Seasonal AR patients (≥ 12 years), with positive skin prick tests (SPT) to Phleum and Olea were recruited from 16 centers. Using ALEX2, specific IgE to Phl p1, Phl p2, Phl p5, Phl p6, Phl p7, Phl p 12, Ole e1, Ole e7 and Ole e9 were determined. Immunoblotting of Olea allergic patients was performed. Results. Included 175 patients (55.4% female; mean age 31.6 ± 13.3 years; 85.7% adults; 40% asthmatic, Coast 28%/Inland 72% and North 29.1%/Centre 20.6%/South 50.3%). Considering Phleum MAD, 85.7% were sensitized to Phl p1, 45.7% to Phl p2, 50.3% to Phl p5, 45.7%, to Phl p6, 10.9% to Phl p7 and 22.9% to Phl p12. Sensitization to Ole e1 was found in 56.6%, to Ole e7 in 1.7% and Ole e9 in 3.4% patients. Sensitization to Phl p7 was more frequent in asthmatics (17.4% vs 6.6%; p = 0.044). Sensitization to Phl p5, Phl p6, Phl p12 and Ole e1 was more frequent in inland. Regarding sensitization patterns: 53.1% patients were sensitized to both species genuine´ sIgE, 38.3% to Phleum and 3.4% only to Olea species' sIgE. Immunoblotting of Olea allergic patients showed a high intensity band that may correspond to Ole e12. Conclusions. MAD showed "genuine" Grass and Olea sensitization in approximately 50% of our patients.

16.
Artigo em Inglês | MEDLINE | ID: mdl-38919151

RESUMO

Summary: Background. Vespula spp. and Polistes spp. are relevant species in South Europe, with Vespa velutina nigrithorax (VVN) being considered a public health problem. We aimed to characterize a cohort of Portuguese patients referred for large local reaction (LLR) and/or systemic reaction (SR) to vespids. In patients treated with venom immunotherapy (VIT), induction protocol and frequency of adverse reactions were evaluated. Methods. Retrospective study including patients with LLR and SR to vespids referred to our Immunoallergology Department (2008-2022). Results. A total of 129 patients were evaluated, the majority were male adults (n = 77, 59.7%), from rural areas. From these, 51 patients had SR (Mueller classification: 7.8% grade I, 19.6% grade II, 37.3% grade III, 35.3% grade IV). We found no differences regarding the levels of total serum IgE, basal serum tryptase value, sIgE levels to the eliciting venom or their molecular components, regarding the severity of the SR that motivated the referral to our clinic. In the SR group, previous LLR Hymenoptera sting were reported in 15.7%. Thirty-eight patients (74.5%) initiated VIT: 22 with wasp venom, 14 with paper wasp venom and 2 with Vespa velutina venom. There was one mild systemic reaction, not requiring adrenaline and 4 LLR. Re-stings after VIT occurred in 16 patients, without any systemic or local reactions. Currently, eleven patients remain under VIT. Conclusions. Most vespid-venom allergic patients are male adults from rural areas. Sensitization to wasp venom was present in 52.9%, paper wasp in 33.3% and Vespa velutina in 13.7%. The frequency of adverse reactions during both induction and maintenance phases appears to be low. Despite a reduced sample size, our experience with VVN VIT, suggests its safety.

17.
Sensors (Basel) ; 24(8)2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38676194

RESUMO

Sprinting is a decisive action in soccer that is considerably taxing from a neuromuscular and energetic perspective. This study compared different calculation methods for the metabolic power (MP) and energy cost (EC) of sprinting using global positioning system (GPS) metrics and electromyography (EMG), with the aim of identifying potential differences in performance markers. Sixteen elite U17 male soccer players (age: 16.4 ± 0.5 years; body mass: 64.6 ± 4.4 kg; and height: 177.4 ± 4.3 cm) participated in the study and completed four different submaximal constant running efforts followed by sprinting actions while using portable GPS-IMU units and surface EMG. GPS-derived MP was determined based on GPS velocity, and the EMG-MP and EC were calculated based on individual profiles plotting the MP of the GPS and all EMG signals acquired. The goodness of fit of the linear regressions was assessed by the coefficient of determination (R2), and a repeated measures ANOVA was used to detect changes. A linear trend was found in EMG activity during submaximal speed runs (R2 = 1), but when the sprint effort was considered, the trend became exponential (R2 = 0.89). The EMG/force ratio displayed two different trends: linear up to a 30 m sprint (R2 = 0.99) and polynomial up to a 50 m sprint (R2 = 0.96). Statistically significant differences between the GPS and EMG were observed for MP splits at 0-5 m, 5-10 m, 25-30 m, 30-35 m, and 35-40 m and for EC splits at 5-10 m, 25-30 m, 30-35 m, and 35-40 m (p ≤ 0.05). Therefore, the determination of the MP and EC based on GPS technology underestimated the neuromuscular and metabolic engagement during the sprinting efforts. Thus, the EMG-derived method seems to be more accurate for calculating the MP and EC in this type of action.


Assuntos
Eletromiografia , Metabolismo Energético , Sistemas de Informação Geográfica , Corrida , Futebol , Humanos , Futebol/fisiologia , Corrida/fisiologia , Masculino , Eletromiografia/métodos , Adolescente , Metabolismo Energético/fisiologia , Atletas , Desempenho Atlético/fisiologia
18.
J Strength Cond Res ; 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39016269

RESUMO

ABSTRACT: Zabaloy, S, Freitas, TT, Alcaraz, PE, Gálvez-González, J, Pereira, LA, Comyns, T, Loturco, I, and Healy, R. Relative acceleration and maximum velocity in rugby players according to age category and playing position. J Strength Cond Res XX(X): 000-000, 2024-This study aimed to: (a) assess the intrasession reliability of the acceleration time constant (i.e., τ) and τ-derived measures; (b) analyze the influence of τ and maximum velocity (Vmax) on 40-m sprint performance and to compare various sprint-related outcomes among rugby players from different playing positions and age categories; and (c) explore the associations between τ and several sprint performance metrics. A total of 300 male rugby players volunteered to participate in this study and were divided into age categories (i.e., under-14 [U14]: n = 91, age: 12.6 ± 0.5 years; under-16 [U16]: n = 85, age: 14.8 ± 0.5 years; under-18 [U18]: n = 75, age: 16.6 ± 0.5 years; and Seniors: n = 49, age: 24.2 ± 4.1 years). The results demonstrated good to excellent reliability for all measured parameters (intraclass correlation coefficient >0.75 and coefficient of variation <9.0%). Younger players (i.e., U14 and U16) displayed lower τ values (effect size: moderate to large; p < 0.02) compared with their older peers (i.e., U18 and Seniors), regardless of their playing position. Moreover, τ was associated with sprint performance metrics at varying levels of correlations (Rho: small to almost perfect; p < 0.001). In conclusion, younger players exhibited lower τ values than their older counterparts, irrespective of their playing positions. The model employed in this study demonstrated its accuracy in assessing several key sprint performance metrics, offering insights that can enhance sprint training programs for rugby players, which can be based on the associations observed among these different variables.

19.
Nurs Inq ; : e12635, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38558441

RESUMO

Our goal was to explore self-care practices among men who have sex with men in the context of Mpox in Brazil. This study used qualitative research methods, including interviews and thematic analysis, to collect and analyze data from male participants across the Brazilian territory. The narratives unveil men's perspectives on self-care, risk reduction, and health beliefs during the Mpox pandemic. Our findings highlight a multifaceted approach to self-care among men, encompassing hygiene, physical contact management, mask usage, skin lesion vigilance, and adherence to official guidelines. Men's attitudes toward sexual behaviors emphasize the importance of reducing sexual partners, practicing safe sex, and combating misinformation through accurate information dissemination. The development of these behaviors and self-care practices can be facilitated by nurses guided by Dorothea Orem's Self-Care Theory, supported by patient-centered care, with strategies to address and confront the stigma associated with the disease and provide emotional support. Thus, the study underscores the pivotal role of self-care in mitigating infection risks, especially in the context of emerging infectious diseases. It acknowledges the impact of socio-cultural factors and healthcare policies on men's preventive measures. However, it also recognizes limitations, such as potential bias due to stigma concerns and a nonrepresentative sample. Ultimately, the research advocates for tailored education, promotion of gender equity, and healthcare empowerment to effectively manage health risks in such contexts.

20.
J Environ Sci (China) ; 140: 230-241, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38331503

RESUMO

Cigarette butts (CBs) are one of the most common types of litter in the world. Due to the toxic substances they contain, the waste generated poses a harmful risk to the environment, and therefore there is an urgent need for alternative solutions to landfill storage. Thus, this work presents a possible revalorization of this waste material, which implies interesting environmental benefits. CBs were used as sacrificial templates for the preparation of CaO-based materials by impregnation with calcium and magnesium nitrates followed by flaming combustion. These materials presented enhanced porosity for their use in the Calcium Looping process applied either to thermochemical energy storage or CO2 capture applications. The influence of the concentration of Ca and Mg in the impregnating solutions on the multicycle reactivity of the samples was studied. An improved multicycle performance was obtained in terms of conversion for both applications.


Assuntos
Dióxido de Carbono , Produtos do Tabaco , Dióxido de Carbono/química , Cálcio , Resíduos , Fenômenos Físicos
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