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BACKGROUND: We evaluated co-administration of adjuvanted seasonal quadrivalent influenza vaccine (FLU-aQIV) and respiratory syncytial virus (RSV) prefusion F protein-based vaccine (RSVPreF3 OA) in ≥65-year-olds. METHODS: This phase 3, open-label trial randomized ≥65-year-olds to receive FLU-aQIV and RSVPreF3 OA concomitantly (Co-Ad) or sequentially, 1 month apart (Control). Primary objectives were to demonstrate the non-inferiority of FLU-aQIV and RSVPreF3 OA co-administration versus sequential administration in terms of hemagglutination inhibition (HI) titers for each FLU-aQIV strain and RSV-A and RSV-B neutralization titers, 1 month post-vaccination. Reactogenicity and safety were also assessed. RESULTS: Overall, 1045 participants were vaccinated (Co-Ad: 523; Control: 522). Non-inferiority of FLU-aQIV and RSVPreF3 OA co-administration versus sequential administration was demonstrated in terms of HI titers for the A/Victoria(H1N1), B/Victoria, and B/Yamagata influenza strains and RSV-A neutralization titers (upper limits [ULs] of 95% confidence intervals [CIs] for adjusted geometric mean titer [GMT] ratios [Control/Co-Ad] ≤1.50) but not for A/Darwin(H3N2) HI titers (95% CI UL = 1.53). The immune response to A/Darwin(H3N2) was further assessed post-hoc using a microneutralization assay; the post-vaccination adjusted GMT ratio (Control/Co-Ad) was 1.23 (95% CI: 1.06-1.42, ie, UL ≤1.50), suggesting an adequate immune response to A/Darwin(H3N2) following co-administration. RSV-B neutralization titers were comparable between groups (95% CI UL for adjusted GMT ratio ≤1.50). Solicited adverse events were mostly mild or moderate and transient; unsolicited and serious adverse event rates were balanced between groups. CONCLUSIONS: Adjuvanted FLU-aQIV and RSVPreF3 OA had acceptable reactogenicity/safety profiles when co-administered in ≥65-year-olds, without clinically relevant interference with the immune responses to either vaccine. CLINICAL TRIALS REGISTRATION: NCT05568797.
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AIM: We want to verify the correlation between the increasing use of novel nicotine-containing products (NNCPs) and non-nicotine delivery products (NNDPs) among young individuals and the escalating negative health consequences, necessitating their prohibition. METHODS: We performed a comprehensive analysis of the most relevant literature about the utilisation of NNCPs and NNDPs among young individuals and their health effects. RESULTS: Despite being initially seen as less harmful alternatives, for smokers aiming to quit, these products have become more popular due to misleading marketing claims. Teenagers using NNCPs and NNDPs, despite having no smoking history, are more likely to transition to tobacco smoking. Consistent use can lead to health issues like pulmonary damage, asthma, and cardiovascular and ocular problems. CONCLUSION: The EAP and the ECPCP endorse the WHO's appeal to outlaw these hazardous products. They urge European governments to forbid the sale of NNCPs and NNDPs to children and adolescents in order to safeguard their well-being. They also propose specific recommendations (box 4) to support this cause.
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When exploring the challenges of restoring degraded lakes, we often do not observe the expected results despite executing all planned activities. Our study elucidates the reasons that impede the recovery of submerged macrophytes despite ameliorated light conditions. When prolonged lake degradation occurs, subsequent efforts to increase light availability often prove insufficient, resulting in a persistent turbid water state. In this study, we attempted to determine the reasons for these failures through a germination test and propagule bank analysis conducted in bottom sediments from a severely degraded lake, which underwent restoration. Although the bottom sediments indicate relative potential in the number of oospores and seeds, their germination efficacy remained dismally low. Based on the germination test results and factors affecting the development of submerged macrophytes (physical and chemical parameters, lake morphology), we stated that improvement of light conditions in the lake could be insufficient to recover the vegetation, especially when the potential to renew diverse plant communities from sediments naturally is low. Our findings advocate for a paradigmatic shift in lake restoration strategies. A holistic approach that includes propagule bank assessments before embarking on restoration initiatives and enabling the identification of macrophyte resurgence potentials is recommended. We also advocate for a multifaceted restoration framework, emphasizing the indispensability of augmenting natural recovery mechanisms with targeted interventions. Consequently, in some cases, macrophyte reintroduction could be the only solution. By reintroducing autochthonic species to site-specific ecological dynamics, we anticipate an increased success rate in restituting submerged vegetation, thus catalyzing ecological regeneration within degraded lake ecosystems.
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Chemokines guide immune cells during their response against pathogens and tumors. Various techniques exist to determine chemokine production, but none to identify cells that directly sense chemokines in vivo. We have generated CCL3-EASER (ErAse, SEnd, Receive) mice that simultaneously report for Ccl3 transcription and translation, allow identifying Ccl3-sensing cells, and permit inducible deletion of Ccl3-producing cells. We infected these mice with murine cytomegalovirus (mCMV), where Ccl3 and NK cells are critical defense mediators. We found that NK cells transcribed Ccl3 already in homeostasis, but Ccl3 translation required type I interferon signaling in infected organs during early infection. NK cells were both the principal Ccl3 producers and sensors of Ccl3, indicating auto/paracrine communication that amplified NK cell response, and this was essential for the early defense against mCMV. CCL3-EASER mice represent the prototype of a new class of dual fluorescence reporter mice for analyzing cellular communication via chemokines, which may be applied also to other chemokines and disease models.
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Comunicação Celular , Quimiocina CCL3 , Modelos Animais , Biossíntese de Proteínas , Transcrição Gênica , Animais , Camundongos , Comunicação Celular/imunologia , Quimiocina CCL3/genética , Quimiocina CCL3/imunologia , Técnicas de Introdução de Genes , Camundongos Transgênicos , Muromegalovirus , Biossíntese de Proteínas/efeitos dos fármacos , Biossíntese de Proteínas/imunologia , Transcrição Gênica/imunologia , Células Matadoras Naturais/imunologia , Interferon beta/farmacologia , Infecções por Herpesviridae/imunologiaRESUMO
Introduction: The health crisis of the last 3 years has revealed the weaknesses of the child and family support system based on the professional use of digital resources in social agencies. This study addresses three aims: to examine the level of professional digital competence; to analyze the user profiles in a variety of digital resources; and to test the impact of level of competences and user profiles on four aspects: professional practice, family satisfaction with the services, child and family wellbeing, and family autonomy in the exercise of the parenting role. Methods: Participants were 148 practitioners from social agencies who voluntarily responded to an online survey with 47 questions. Results and discussion: Results showed that professionals perceive themselves as more competent in areas of information / data management and communication / collaboration than in the creation of digital content, security measures, and technical problem solving. Websites, email, and instant messaging were the sources more frequently used and with higher satisfaction, than structured programs, social networks and multimedia content. Variability in the user profiles showed three clusters: Cluster 1 Social network user (n = 13), Cluster 2 Diversified user (n = 75) and Cluster 3 Communicative instant user (n = 60). Participants in Cluster 2 compared to those in the other clusters were the most proficient on their digital competences and acknowledge the positive impact of digital resources on their professional practice and the psychological and social wellbeing of families. This study points the need for improvement in professionals' digital competences in some of the measured areas and the user profile of digital resources since both provide benefits on professional practice and family autonomy and wellbeing.
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[This corrects the article DOI: 10.1016/j.mtbio.2023.100935.].
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BACKGROUND: The effects of adverse life events on physical and psychological health, with DNA methylation (DNAm) as a critical underlying mechanism, have been extensively studied. However, the epigenetic resemblance between mother and child in the context of neglectful caregiving, and whether it may be shaped by the emotional impact of maternal stressful events and the duration of co-residence (indexed by child age), remains unknown. The present study examined mother-child similarity in methylation profiles, considering the potential effect of mother adversity, mother empathy, neglect-control group, child age (an index of years of mother-child co-residence), and mother age. Using Illumina Epic arrays, we quantified DNAm in 115 mother-child saliva samples. We obtained a methylation similarity index by computing correlation coefficients between methylation profiles within dyads, for the entire epigenome, and five specific genes related to stress and empathy: NR3C1, FKPB5, OXTR, SCL6A4, and BDNF. RESULTS: The methylation profiles of the mother-child familial pairs significantly correlated as compared to mother-child random pairs for the entire epigenome and NR3C1, FKBP5, OXTR and BDNF genes. Next, multiple linear regression models observed associations of mother adversity, child age, and neglect-control group on mother-child methylation similarity, only significant in mother-child familial pairs, after correcting for multiple comparisons. Higher mother adversity was associated with lower mother-child methylation similarity for the epigenome-wide analysis, for the BDNF gene, and in the neglect-control group for the OXTR gene. In turn, being an older child (longer co-residence) was associated with higher mother-child methylation similarity. CONCLUSIONS: Mother adversity and co-residence time are modulating factors in the intergenerational methylation process that offer a window into development-dependent adaptations that can be affected by both hereditary and environmental factors, significantly observed only in biological dyads. A twofold implication for child well-being emerges, one is positive in that children of mothers exposed to life adversity or neglect did not necessarily inherit their methylation patterns. The other is concerning due to the influence of time spent living together, which affects similarity with the mother and potentially increases the risk of inheriting an epigenetic profile associated with future dysfunctional parenting patterns. This underscores the importance of the 'the earlier, the better' recommendation by the Child Protection System, which is not always followed.
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Metilação de DNA , Mães , Feminino , Humanos , Criança , Adolescente , Mães/psicologia , Fator Neurotrófico Derivado do Encéfalo/genética , Epigenoma , Relações Mãe-Filho , Epigênese GenéticaAssuntos
Transplante de Coração , Doadores de Tecidos , Fístula Vascular , Humanos , Fístula Vascular/diagnóstico por imagem , Fístula Vascular/etiologia , Resultado do Tratamento , Masculino , Lesões do Sistema Vascular/diagnóstico por imagem , Lesões do Sistema Vascular/etiologia , Lesões do Sistema Vascular/cirurgia , Lesões do Sistema Vascular/terapia , Angiografia Coronária , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/lesões , Pessoa de Meia-Idade , Traumatismos Cardíacos/etiologia , Traumatismos Cardíacos/diagnóstico por imagem , Traumatismos Cardíacos/terapiaRESUMO
Glaucoma is a multifactorial pathology involving the immune system. The subclinical immune response plays a homeostatic role in healthy situations, but in pathological situations, it produces imbalances. Optical coherence tomography detects immune cells in the vitreous as hyperreflective opacities and these are subsequently characterised by computational analysis. This study monitors the changes in immunity in the vitreous in two steroid-induced glaucoma (SIG) animal models created with drug delivery systems (microspheres loaded with dexamethasone and dexamethasone/fibronectin), comparing both sexes and healthy controls over six months. SIG eyes tended to present greater intensity and a higher number of vitreous opacities (p < 0.05), with dynamic fluctuations in the percentage of isolated cells (10 µm2), non-activated cells (10-50 µm2), activated cells (50-250 µm2) and cell complexes (>250 µm2). Both SIG models presented an anti-inflammatory profile, with non-activated cells being the largest population in this study. However, smaller opacities (isolated cells) seemed to be the first responder to noxa since they were the most rounded (recruitment), coinciding with peak intraocular pressure increase, and showed the highest mean Intensity (intracellular machinery), even in the contralateral eye, and a major change in orientation (motility). Studying the features of hyperreflective opacities in the vitreous using OCT could be a useful biomarker of glaucoma.
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BACKGROUND: Severe primary graft dysfunction (PGD) is a major cause of early mortality after heart transplant, but the impact of donor organ preservation conditions on severity of PGD and survival has not been well characterized. METHODS: Data from US adult heart-transplant recipients in the Global Utilization and Registry Database for Improved Heart Preservation-Heart Registry (NCT04141605) were analyzed to quantify PGD severity, mortality, and associated risk factors. The independent contributions of organ preservation method (traditional ice storage vs controlled hypothermic preservation) and ischemic time were analyzed using propensity matching and logistic regression. RESULTS: Among 1,061 US adult heart transplants performed between October 2015 and December 2022, controlled hypothermic preservation was associated with a significant reduction in the incidence of severe PGD compared to ice (6.6% [37/559] vs 10.4% [47/452], p = 0.039). Following propensity matching, severe PGD was reduced by 50% (6.0% [17/281] vs 12.1% [34/281], respectively; p = 0.018). The Kaplan-Meier terminal probability of 1-year mortality was 4.2% for recipients without PGD, 7.2% for mild or moderate PGD, and 32.1%, for severe PGD (p < 0.001). The probability of severe PGD increased for both cohorts with longer ischemic time, but donor hearts stored on ice were more likely to develop severe PGD at all ischemic times compared to controlled hypothermic preservation. CONCLUSIONS: Severe PGD is the deadliest complication of heart transplantation and is associated with a 7.8-fold increase in probability of 1-year mortality. Controlled hypothermic preservation significantly attenuates the risk of severe PGD and is a simple yet highly effective tool for mitigating post-transplant morbidity.
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Transplante de Coração , Preservação de Órgãos , Humanos , Preservação de Órgãos/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Disfunção Primária do Enxerto/prevenção & controle , Disfunção Primária do Enxerto/epidemiologia , Disfunção Primária do Enxerto/etiologia , Sistema de Registros , Adulto , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologia , Taxa de Sobrevida/tendências , Doadores de Tecidos , Sobrevivência de Enxerto , IdosoRESUMO
Pyriproxyfen is an insecticide currently employed in numerous countries for the management of agricultural and indoor pests. Several studies indicate that this insecticide has been detected in multiple rivers, with concentrations reaching as high as 99.59 ng/L in the Júcar River in Spain. Therefore, the determination of some biochemical and genetic effects of this insecticide on aquatic organisms could serve as an early warning mechanism to identify potential disruptions in various biomarkers. Based on this, Daphnia magna organisms were exposed to pyriproxyfen sublethal concentrations for 21 days. Some biochemical parameters, including cholesterol, triglycerides, glucose, lactate, and LDH activity, were determined. Additionally, some genetic biomarkers associated with oxidative stress, heat shock proteins, lipid metabolism, hemoglobin, metallothioneins, and vitellogenin synthesis were evaluated in daphnids exposed to the insecticide for 21 days. LDH activity increased significantly in those daphnids exposed to the highest insecticide concentration (14.02 µg/L), while cholesterol levels decreased significantly. In contrast, glucose, total proteins, and triglycerides remained unaffected in D. magna exposed to pyriproxyfen. On the other hand, exposure to the insecticide led to notable alterations in gene expression among individuals. Specifically, genes associated with lipid metabolism and reproduction exhibited a significant reduction in gene expression. Fabd expression was decreased by approximately 20% in exposed daphnids, while vtg expression was suppressed as much as 80% when compared to control values. Furthermore, it was observed that the hgb1 and hgb2 genes, associated with hemoglobin synthesis, exhibited significant overexpression. Notably, the dysfunction observed in both hemoglobin genes was linked to an increase in pigmentation in Daphnia magna during the course of the experiment. These alterations in gene expression could serve as effective indicators of early contamination even at low pesticide concentrations.
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In recent years, there has been a notable surge in investments directed towards developing new railway lines and revitalising existing ones, reflecting a global commitment to enhance transportation infrastructure [...].
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BACKGROUND: Black heart transplant patients are at higher risk of acute rejection (AR) and death than White patients. We hypothesized that this risk may be associated with higher levels of donor-derived cell-free DNA (dd-cfDNA) and cell-free mitochondrial DNA. METHODS: The Genomic Research Alliance for Transplantation is a multicenter, prospective, longitudinal cohort study. Sequencing was used to quantitate dd-cfDNA and polymerase chain reaction to quantitate cell-free mitochondrial DNA in plasma. AR was defined as ≥2R cellular rejection or ≥1 antibody-mediated rejection. The primary composite outcome was AR, graft dysfunction (left ventricular ejection fraction <50% and decrease by ≥10%), or death. RESULTS: We included 148 patients (65 Black patients and 83 White patients), median age was 56 years and 30% female sex. The incidence of AR was higher in Black patients compared with White patients (43% versus 19%; P=0.002). Antibody-mediated rejection occurred predominantly in Black patients with a prevalence of 20% versus 2% (P<0.001). After transplant, Black patients had higher levels of dd-cfDNA, 0.09% (interquartile range, 0.001-0.30) compared with White patients, 0.05% (interquartile range, 0.001-0.23; P=0.003). Beyond 6 months, Black patients showed a persistent rise in dd-cfDNA with higher levels compared with White patients. Cell-free mitochondrial DNA was higher in Black patients (185â 788 copies/mL; interquartile range, 101 252-422 133) compared with White patients (133 841 copies/mL; interquartile range, 75â 346-337â 990; P<0.001). The primary composite outcome occurred in 43% and 55% of Black patients at 1 and 2 years, compared with 23% and 27% in White patients, P<0.001. In a multivariable model, Black patient race (hazard ratio, 2.61 [95% CI, 1.35-5.04]; P=0.004) and %dd-cfDNA (hazard ratio, 1.15 [95% CI, 1.03-1.28]; P=0.010) were associated with the primary composite outcome. CONCLUSIONS: Elevated dd-cfDNA and cell-free mitochondrial DNA after heart transplant may mechanistically be implicated in the higher incidence of AR and worse clinical outcomes in Black transplant recipients. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02423070.
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Ácidos Nucleicos Livres , Insuficiência Cardíaca , Transplante de Coração , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , DNA Mitocondrial/genética , Ácidos Nucleicos Livres/genética , Estudos Longitudinais , Estudos Prospectivos , Fatores Raciais , Volume Sistólico , Biomarcadores , Rejeição de Enxerto/genética , Função Ventricular Esquerda , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/cirurgia , Transplante de Coração/efeitos adversos , Doadores de TecidosRESUMO
RATIONALE: In-stent reocclusion after endovascular therapy has a negative impact on outcomes in acute ischemic stroke (AIS) due to tandem lesions (TL). Optimal antiplatelet therapy approach in these patients to avoid in-stent reocclusion is yet to be elucidated. AIMS: To assess efficacy and safety of intravenous tirofiban versus intravenous aspirin in patients undergoing MT plus carotid stenting in the setting of AIS due to TL. SAMPLE SIZE ESTIMATES: Two hundred forty patients will be enrolled, 120 in every treatment arm. METHODS AND DESIGN: A multicenter, prospective, randomized, controlled (aspirin group), assessor-blinded clinical trial will be conducted. Patients fulfilling the inclusion criteria will be randomized at MT onset to the experimental or control group (1:1). Intravenous aspirin will be administered at a 500-mg single dose and tirofiban at a 500-mcg bolus followed by a 200-mcg/h infusion during the first 24 h. All patients will be followed for up to 3 months. STUDY OUTCOMES: Primary efficacy outcome will be the proportion of patients with carotid in-stent thrombosis within the first 24 h after MT. Primary safety outcome will be the rate of symptomatic intracranial hemorrhage. DISCUSSION: This will be the first clinical trial to assess the best antiplatelet therapy to avoid in-stent thrombosis after MT in patients with TL. TRIAL REGISTRATION: The trial is registered as NCT05225961. February, 7th, 2022.
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Aspirina , AVC Isquêmico , Trombose , Tirofibana , Humanos , Aspirina/efeitos adversos , Aspirina/uso terapêutico , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Estudos Prospectivos , Tirofibana/efeitos adversos , Tirofibana/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
Implementing parenting programs in real-world community settings is fundamental to making effective programs widely available and consequently improving the lives of children and their families. Despite the literature acknowledging that the high-quality implementation of parenting programs is particularly challenging in real-world community settings, little is known about how the programs are implemented in these settings. This scoping review followed the methodological framework described by the Joanna Briggs Institute to map evidence on how evidence-based parenting programs have been implemented under real-world conditions. A systematic search of 12 scientific databases, gray literature, and the reference lists of the included studies identified 1918 records, of which 145 were included in the review. Fifty-three parenting programs were identified in studies documenting implementation in real-world community settings worldwide. Most studies included families in psychosocial risk engaged with family-support agencies. The qualitative synthesis identified several implementation outcomes, adaptations, barriers, and facilitators. Most studies reported a maximum of two implementation outcomes, mainly fidelity and acceptability. Providers frequently made adaptations, mainly to bring down barriers and to tailor the program to improve its fit. Findings highlight the need for a more detailed description of the implementation of programs, with greater consistency in terminology, operationalization, and measurement of implementation outcomes across studies. This will promote a more transparent, consistent, and accurate evaluation and reporting of implementation and increase the public health impact of parenting programs. Future studies should also assess the impact of adaptations and the cost-effectiveness and sustainability of programs in real-world community settings.
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Poder Familiar , Criança , Humanos , Poder Familiar/psicologiaRESUMO
Cardiac allograft vasculopathy (CAV) is a significant determinant of long-term survival in heart transplant recipients. Standard CAV screening typically utilizes invasive coronary angiography (ICA). Quantitative flow ratio (QFR) is a computational method for functional testing of coronary stenosis, and may add diagnostic value to ICA in assessing CAV. Consecutive subjects who received heart transplantation and underwent two separate routine coronary angiograms between January 2013 and April 2016 were enrolled. Coronary angiograms and IVUS were performed per local protocol at 1, 2, 3 and 5 years post-transplant. QFR was calculated offline. CAV was assessed semi-quantitively based on coronary angiogram results. Twenty-two patients were enrolled. Mean time from transplant to first included ICA was 2.1 years. QFR in at least 1 coronary vessel was interpretable in 19/22 (86%) of initial ICA (QFR1). QFR1 correlated well with the CAV score derived from the second ICA (CAV2) with a clustering of CAV at lower QFR values. In a receiver-operating characteristic (ROC) analysis, an optimal QFR threshold of 0.88 yielded 0.94 sensitivity and 0.67 specificity (AUC of 0.79) for at least non-obstructive subsequent CAV. Initial angiographically and intravascular ultrasound derived CAV severity poorly predicted subsequent CAV severity. QFR derived from invasive coronary angiography predicts subsequent development of CAV more accurately than angiography and intravascular ultrasound. This novel method of coronary flow assessment in recipients of heart transplantation may be useful to diagnose and predict subsequent CAV development.
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Doença da Artéria Coronariana , Transplante de Coração , Humanos , Angiografia Coronária/métodos , Valor Preditivo dos Testes , Transplante de Coração/efeitos adversos , Coração , Aloenxertos/irrigação sanguínea , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/terapiaRESUMO
Cardiovascular diseases (CVD) continue to be the main cause of death in our country. Adequate control of lipid metabolism disorders is a key challenge in cardiovascular prevention that is far from being achieved in real clinical practice. There is a great heterogeneity in the reports of lipid metabolism from Spanish clinical laboratories, which may contribute to its poor control. For this reason, a working group of the main scientific societies involved in the care of patients at vascular risk, has prepared this document with a consensus proposal on the determination of the basic lipid profile in cardiovascular prevention, recommendations for its realization and unification of criteria to incorporate the lipid control goals appropriate to the vascular risk of the patients in the laboratory reports.