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1.
J Exp Clin Cancer Res ; 43(1): 264, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39304963

RESUMO

BACKGROUND: There has been a rise in endometrial cancer (EC) incidence leading to increased mortality. To counter this trend, improving the stratification of post-surgery recurrence risk and anticipating disease relapse and treatment resistance is essential. Liquid biopsy analyses offer a promising tool for these clinical challenges, though the best strategy for applying them in EC must be defined. This study was designed to determine the value of cfDNA/ctDNA monitoring in improving the clinical management of patients with localized and recurrent disease. METHODS: Plasma samples and uterine aspirates (UA) from 198 EC patients were collected at surgery and over time. The genetic landscape of UAs was characterized using targeted sequencing. Total cfDNA was analyzed for ctDNA presence based on the UA mutational profile. RESULTS: High cfDNA levels and detectable ctDNA at baseline correlated with poor prognosis for DFS (p-value < 0.0001; HR = 9.25) and DSS (p-value < 0.0001; HR = 11.20). This remained clinically significant when stratifying tumors by histopathological risk factors. Of note, cfDNA/ctDNA analyses discriminated patients with early post-surgery relapse and the ctDNA kinetics served to identify patients undergoing relapse before any clinical evidence emerged. CONCLUSIONS: This is the most comprehensive study on cfDNA/ctDNA characterization in EC, demonstrating its value in improving risk stratification and anticipating disease relapse in patients with localized disease. CtDNA kinetics assessment complements current strategies to monitor the disease evolution and the treatment response. Therefore, implementing cfDNA/ctDNA monitoring in clinical routines offers a unique opportunity to improve EC management. TRANSLATIONAL RELEVANCE: The study demonstrates that high levels of cfDNA and detectable ctDNA at baseline are strong indicators of poor prognosis. This enables more accurate risk stratification beyond traditional histopathological factors, allowing clinicians to identify high-risk patients who may benefit from more aggressive treatment and closer monitoring. Moreover, longitudinal analysis of cfDNA/ctDNA can detect disease recurrence months before clinical symptoms or imaging evidence appear. This early warning system offers a significant advantage in clinical practice, providing a window of opportunity for early intervention and potentially improving patient outcomes.


Assuntos
DNA Tumoral Circulante , Neoplasias do Endométrio , Humanos , Feminino , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/sangue , Neoplasias do Endométrio/patologia , DNA Tumoral Circulante/genética , DNA Tumoral Circulante/sangue , Pessoa de Meia-Idade , Idoso , Seguimentos , Prognóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/sangue , Medição de Risco/métodos , Ácidos Nucleicos Livres/genética , Ácidos Nucleicos Livres/sangue , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/patologia , Adulto , Idoso de 80 Anos ou mais
2.
Nat Nanotechnol ; 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39327513

RESUMO

Electrical current pulses can be used to manipulate magnetization efficiently via spin-orbit torques. Pulse durations as short as a few picoseconds have been used to switch the magnetization of ferromagnetic films, reaching the terahertz regime. However, little is known about the reversal mechanisms and energy requirements in the ultrafast switching regime. In this work we quantify the energy cost for magnetization reversal over seven orders of magnitude in pulse duration, in both ferromagnetic and ferrimagnetic samples, bridging quasi-static spintronics and femtomagnetism. To this end, we develop a method to stretch picosecond pulses generated by a photoconductive switch by an order of magnitude. Thereby we can create current pulses from picoseconds to durations approaching the pulse width available with commercial instruments. We show that the energy cost for spin-orbit torque switching decreases by more than an order of magnitude in all samples when the pulse duration enters the picosecond range. We project an energy cost of 9 fJ for a 100 × 100 nm2 ferrimagnetic device. Micromagnetic and macrospin simulations unveil a transition from a non-coherent to a coherent magnetization reversal with a strong modification of the magnetization dynamical trajectories as pulse duration is reduced. Our results show the potential for high-speed magnetic spin-orbit torque memories and highlight alternative magnetization reversal pathways at fast timescales.

3.
Mult Scler Relat Disord ; 91: 105861, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39265268

RESUMO

BACKGROUND: Patients with multiple sclerosis (MS) have to deal with a variable disease trajectory often associated with disability and productivity loss. OBJECTIVE: This study aimed to assess illness-related uncertainty and associated correlates in patients with relapsing-remitting multiple sclerosis (RRMS) beyond the near diagnosis phase. METHODS: We conducted a multicenter, non-interventional study including patients diagnosed with RRMS (2017 revised McDonald criteria) and a disease duration of 3 to 8 years. Perceived uncertainty was measured using the Mishel Uncertainty of Illness Scale (MUIS). Associations between the MUIS and different patient-based outcome measures were analyzed using Spearman's rank correlation. RESULTS: A total of 201 patients were studied (mean age (standard deviation): 38.7 (8.4) years, 71.4 % female). The median disease duration (interquartile range) was 6.0 (4.0-7.0) years and the median EDSS score was 1.0 (0.0-2.0). The mean MUIS score was 38.2 (10.8). Perceived uncertainty was positively correlated with fatigue (p < 0.001), symptom severity (p < 0.001), anxiety (p < 0.001), depressive symptoms (p < 0.001), and a threatening illness perception (p < 0.001), and negatively correlated with self-management (p < 0.001), self-efficacy (p < 0.001), processing speed (p < 0.001), knowledge of MS (p = 0.006), and quality of life (p < 0.001). CONCLUSION: Illness-related uncertainty was common in a population of mid-stage RRMS. Identifying uncertainty and its associated factors may be useful for implementing preventive strategies to help patients cope with the disease throughout life.

4.
Oncoimmunology ; 13(1): 2388304, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39135889

RESUMO

The Hodgkin and Reed - Sternberg (HRS) cells in classical Hodgkin Lymphoma (cHL) actively modify the immune tumor microenvironment (TME) attracting immunosuppressive cells and expressing inhibitory molecules. A high frequency of myeloid cells in the TME is correlated with an unfavorable prognosis, but more specific and rare cell populations lack precise markers. Myeloid-derived suppressor cells (MDSCs) have been identified in the peripheral blood of cHL patients, where they appear to be correlated with disease aggressiveness. TNFRSF9 (CD137) is a T cell co-stimulator expressed by monocytic and dendritic cells. Its expression has also been described in HRS cells, where it is thought to play a role in reducing antitumor responses. Here, we perform qualitative and quantitative analyses of lymphocytic and MDSC subtypes and determine the CD137 cell distribution in cHL primary tumors using multiplex immunofluorescence and automated multispectral imaging. The results were correlated with patients' clinical features. Cells were stained with specific panels of immune checkpoint markers (PD-1, PD-L1, CD137), tumor-infiltrating T lymphocytes (CD3, PD-1), and monocytic cells/MDSCs (CD68, CD14, CD33, Arg-1, CD11b). This approach allowed us to identify distinct phenotypes and to analyze spatial interactions between immune subpopulations and tumor cells. The results confirm CD137 expression by T, monocytic and HRS cells. In addition, the expression of CD137, T exhausted cells, and monocytic MDSCs (m-MDSCs) in the vicinity of malignant HRS cells were associated with a worse prognosis. Our findings reveal new elements of the TME that mediate immune escape, and confirm CD137 as a candidate target for immunotherapy in cHL.


CD137-expressing immune cells and HRS cells are more abundant and in closer proximity in refractory patients than in responders.Monocytic myeloid-derived suppressor cells (m-MDSCs) are associated with unfavorable outcomes and relapse in cHL, unlike granulocytic MDSCs (g-MDSCs), which are located far from HRS cells in non-responders.The cHL tumor microenvironment promotes immune escape in refractory patients by holistically driving polarization and/or recruitment of several cell types with increased expression of CD137 and PD-L1 checkpoints.


Assuntos
Doença de Hodgkin , Células Supressoras Mieloides , Células de Reed-Sternberg , Microambiente Tumoral , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral , Humanos , Doença de Hodgkin/patologia , Doença de Hodgkin/imunologia , Doença de Hodgkin/metabolismo , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo , Microambiente Tumoral/imunologia , Células Supressoras Mieloides/metabolismo , Células Supressoras Mieloides/imunologia , Células Supressoras Mieloides/patologia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Células de Reed-Sternberg/patologia , Células de Reed-Sternberg/metabolismo , Idoso , Análise Espacial , Adulto Jovem , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Adolescente , Prognóstico , Biomarcadores Tumorais/metabolismo
5.
Clin Nucl Med ; 49(10): e513-e514, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39150354

RESUMO

ABSTRACT: A 58-year-old man with dysphagia and trismus symptoms presented a lobulated tumor in the right tonsil and ipsilateral laterocervical stony adenopathies in the physical examination. He had prostate carcinoma as clinical precedent. The tonsilar lesion showed focal FDG uptake (SUV max , 10.89) on PET/CT and increased glycemic metabolism in the left sacral wing (SUV max , 10.90) without clear morphological lesion in CT. There was also uptake of the tracer in sacrum in the bone scan. Metastatic involvement was suspected, requiring radioguided biopsy to determine the etiology. Due to radioguided biopsy, histological analysis of the metastasis was performed, with epidermoid carcinoma metastasis diagnosis.


Assuntos
Câmaras gama , Sacro , Humanos , Masculino , Pessoa de Meia-Idade , Biópsia Guiada por Imagem/instrumentação , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Sacro/diagnóstico por imagem , Sacro/patologia
6.
Pediatr Obes ; : e13162, 2024 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-39183454

RESUMO

INTRODUCTION: Clustering of cardiometabolic risk factors in childhood significantly increases the risk of atherosclerotic cardiovascular disease later in life. Identification of modifiable parental factors that contribute to offspring cardiometabolic health is critical for the prevention of disease. The objective was to identify factors associated with child cardiometabolic risk factors at age 5 years. METHODS: Triads from a longitudinal cohort were recalled at 5 years (n = 68). Dietary intake, anthropometrics, physical activity and serum-based risk factors were collected. Best subset selection, linear and logistic regressions were used to identify triad variables associated with increased risk of cardiometabolic risk factor clustering at age 5 years. RESULTS: In this cohort, best subset modelling revealed that increased paternal fat mass, serum low-density lipoproteins and triglycerides, maternal dietary added sugar and being female were associated with increased odds of offspring having two or more cardiometabolic risk factors at age 5 years. CONCLUSIONS: Dietary and exercise interventions prior to conception targeting paternal adiposity and dyslipidaemia as well as maternal dietary habits could decrease children's cardiometabolic risk in later life.

7.
Water Environ Res ; 96(8): e11086, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39082880

RESUMO

Conventional wastewater treatment plants (WWTPs) are not designed for the abatement of antibiotics, and their effluents are one of the main entry ways of these emerging contaminants to the aquatic environment, causing major concern due to their toxicity, persistence, and bioaccumulation. When wastewater containing antibiotics enters the bioreactor, they can impact microbial communities of the activated sludge, affecting biodegradation processes of organic matter and nutrients. There is scarce information about the effect of activated carbon on the activated sludge within the bioreactor in presence of antibiotics. In light of this, the effect of representative antibiotics, ciprofloxacin (CIP), nalidixic acid (NAL), and erythromycin (ERY), on the performance of a conventional activated sludge of a WWTP was analyzed by respirometry with and without activated carbon. NAL and ERY negatively affected the net heterotrophic biomass growth rate (r'x,H), with reduction percentages of 26%-90% and 31%-81%, respectively. The addition of activated carbon mitigated this effect, especially for ERY, with increments of even 8% in the r'x,H for the hybrid process when working with 5 ppm of ERY and 80 ppm of activated carbon compared with the value in the absence of antibiotic and activated carbon. This effect was attributed to the enhanced retention of ERY, in comparison to NAL, on the surface of the activated carbon, probably due to its higher molecular size and affinity towards the activated carbon (log Kow = 3.06). This effect was more marked at low sludge retention times (below 8 days). PRACTITIONER POINTS: Ciprofloxacin (CIP), nalidixic acid (NAL), and erythromycin (ERY) were studied. NAL and ERY exerted negative impact on heterotrophic growth rate. Effect of antibiotics on microorganisms in the presence of activated carbon was studied. Activated carbon was mainly relevant for ERY due to its adsorption retention. Enhancement by activated carbon was more significant at low sludge retention times.


Assuntos
Antibacterianos , Carvão Vegetal , Esgotos , Antibacterianos/farmacologia , Antibacterianos/química , Carvão Vegetal/química , Adsorção , Cinética , Poluentes Químicos da Água/química , Reatores Biológicos , Eliminação de Resíduos Líquidos/métodos , Processos Heterotróficos , Eritromicina/farmacologia
8.
J Environ Manage ; 365: 121643, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38968894

RESUMO

Phosphotungstic acid (HPW) and silicotungstic acid (HSiW) were tested as homogeneous and as heterogeneous catalysts (after immobilized on different supports as high surface area graphite -HSAG500-, montmorillonite -MMT- and alumina -Al2O3-) for the in situ transesterification of sewage sludge lipids. Both catalysts exhibited similar performance in homogeneous phase, with slightly higher biodiesel yield for HPW. When the different supports were tested with HPW, the maximum yield obtained follow the trend: MMT > HSAG500 > Al2O3, but a greater leaching of the heteropolyacid (HPA) was observed with MMT. Therefore, HSAG500 showed the best results with a good FAMEs profile. The percentage of active phase was optimized from 1 to 40%, reaching the optimum at 10%. A more heterogeneous surface is obtained with larger quantities, also favouring the HPA leaching. The reaction temperature and the use of sonication as pre-treatment were also optimized. The best results were obtained after sonication with HPW-HSAG500 (10%) as catalyst, catalyst/sludge ratio 1:2, MeOH/sludge ratio 33:1, 120 °C and 21 h of reaction time with a maximum biodiesel yield of 31.1 % (FAMEs/lipids). In view of the results obtained HPW supports on HSAG500 offers a novel alternative as heterogeneous acid catalyst for in situ transesterification using sewage sludge as raw material.


Assuntos
Biocombustíveis , Esgotos , Esgotos/química , Catálise , Esterificação , Ácido Fosfotúngstico/química , Óxido de Alumínio/química , Grafite/química
9.
Mod Pathol ; 37(9): 100551, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38936478

RESUMO

As around 25% to 30% of classical Hodgkin lymphoma (cHL) patients with advanced stages do not respond to standard therapies, the tumor microenvironment of cHL is one avenue that may be explored with the aim of improving risk stratification. CD4+ T cells are thought to be one of the main cell types in the tumor microenvironment. However, few immune signatures have been studied, and many of these lack related spatial data. Thus, our aim is to spatially resolve the CD4+ T cell subtypes that influence cHL outcome, depicting new immune signatures or transcriptional patterns that are in crosstalk with the tumor cells. This study was conducted using the NanoString GeoMx digital spatial profiling technology, based on the selection of distinct functional areas of patients' tissues followed by gene-expression profiling. The goals were to assess the differences in CD4+ T cell populations between tumor-rich and immune-predominant areas defined by different CD30 and PD-L1 expression levels and seek correlations with clinical metadata. Our results depict a complex map of CD4+ T cells with different functions and differentiation states that are enriched at distinct locations, the flux of cytokines and chemokines that could be related to these, and the specific relationships with the clinical outcome.


Assuntos
Linfócitos T CD4-Positivos , Doença de Hodgkin , Microambiente Tumoral , Humanos , Doença de Hodgkin/patologia , Doença de Hodgkin/imunologia , Linfócitos T CD4-Positivos/imunologia , Microambiente Tumoral/imunologia , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Perfilação da Expressão Gênica , Idoso , Adulto Jovem , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/patologia
10.
Pathobiology ; : 1-12, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38934185

RESUMO

INTRODUCTION: Lysyl oxidase-like 2 (LOXL2) expression and function is frequently altered in different cancers but scarcely explored in oral squamous cell carcinoma (OSCC). This prompted us to investigate the clinical relevance of LOXL2 expression pattern in OSCC and also a possible crosstalk with Hippo/YAP1 pathway signaling. METHODS: Immunohistochemical analysis of LOXL2 protein expression was performed in 158 OSCC patient samples, together with Yes-associated protein 1 (YAP1) activation status. Correlations with clinicopathological parameters and patient survival were assessed. RESULTS: Tumor cell-intrinsic LOXL2 expression showed two distinct expression patterns: diffuse cytoplasmic staining (64.6%) and heterogeneous perinuclear staining (35.4%). Remarkably, perinuclear LOXL2 staining was significantly associated with lymph node metastasis, advanced clinical stage and perineural invasion. Moreover, patients harboring tumors with perinuclear LOXL2 expression exhibited significantly poorer disease-specific survival (DSS) rates, and perinuclear LOXL2 positivity gradually increased in relation to YAP1 activation. Patients harboring tumors with concomitant perinuclear LOXL2 and fully active YAP1 exhibited the worst DSS. Multivariate Cox analysis further revealed combined perinuclear LOXL2 and fully active YAP1 as a significant independent predictor of poor DSS. CONCLUSION: Tumor-intrinsic perinuclear LOXL2 emerges as a clinically and biologically relevant feature associated with advanced disease, tumor aggressiveness, and poor prognosis in OSCC. Moreover, this study unprecedentedly uncovers a functional relationship between perinuclear LOXL2 and YAP1 activation with major prognostic implications. Notably, combined perinuclear LOXL2 and fully active YAP1 was revealed as independent predictor of poor prognosis. These findings encourage targeting oncogenic LOXL2 functions for personalized treatment regimens.

11.
Patient Prefer Adherence ; 18: 1163-1171, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38863945

RESUMO

Purpose: Shared decision-making is critical in multiple sclerosis (MS) due to the uncertainty of the disease trajectory over time and the large number of treatment options with differing efficacy, safety and administration characteristics. The aim of this study was to assess patients' decisional conflict regarding the choice of a disease-modifying therapy and its associated factors in patients with mid-stage relapsing-remitting multiple sclerosis (RRMS). Methods: A multicenter, non-interventional study was conducted. Adult patients with a diagnosis of RRMS (2017 revised McDonald criteria) and disease duration of 3 to 8 years were included. The level of uncertainty experienced by a patient when faced with making a treatment choice was assessed using the 4-item Decisional Conflict Scale. A battery of patient-reported and clinician-rated measures was administered to obtain information on symptom severity, illness perception, illness-related uncertainty, regret, MS knowledge, risk taking behavior, preferred role in the decision-making process, cognition, and self-management. Patients were recruited during routine follow-up visits and completed all questionnaires online using electronic tablets at the hospital. A multivariate logistic regression analysis was conducted. Results: A total of 201 patients were studied. Mean age (Standard deviation) was 38.7 (8.4) years and 74.1% were female. Median disease duration (Interquartile range) was 6.0 (4.0-7.0) years. Median EDSS score was 1.0 (0-2.0). Sixty-seven (33.3%) patients reported a decisional conflict. These patients had lower MS knowledge and more illness uncertainty, anxiety, depressive symptoms, fatigue, subjective symptom severity, a threatening illness perception, and poorer quality of life than their counterparts. Lack of decisional conflict was associated with MS knowledge (Odds ratio [OR]=1.195, 95% CI 1.045, 1.383, p=0.013), self-management (OR=1.049, 95% CI 1.013, 1.093, p=0.018), and regret after a healthcare decision (OR=0.860, 95% CI 0.756, 0.973, p=0.018) in the multivariate analysis. Conclusion: Decisional conflict regarding the selection of a disease-modifying therapy was a common phenomenon in patients with mid-stage RRMS. Identifying factors associated with decisional conflict may be useful to implement preventive strategies that help patients better understand their condition and strengthen their self-management resources.

13.
Mult Scler J Exp Transl Clin ; 10(2): 20552173241247680, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38638273

RESUMO

A multicenter study involving 204 adults with relapsing-remitting multiple sclerosis (RRMS) assessed the dimensionality and item characteristics of the Mishel-Uncertainty of Illness Scale (MUIS), a generic self-assessment tool. Mokken analysis identified two dimensions in the MUIS with an appropriate item and overall scale scalability after excluding nonclassifiable items. A refined 12-item MUIS, employing a grade response model, effectively discriminated uncertainty levels among RRMS patients (likelihood ratio test p-value = .03). These findings suggest the potential value of the 12-item MUIS as a reliable measure for assessing uncertainty associated with the course of illness in RRMS.

14.
EJHaem ; 5(1): 70-75, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38406538

RESUMO

The value of circulating tumor DNA (ctDNA) as a biomarker of disease activity in classic Hodgkin lymphoma (cHL) patients has not yet been well established. By profiling primary tumors and ctDNA, we identified common variants between primary tumors and longitudinal plasma samples in most of the cases, confirming high spatial and temporal heterogeneity. Although ctDNA analyses mirrored HRS cell genetics overall, the prevalence of variants shows that none of them can be used as a single biomarker. Conversely, the estimation of hGE/mL, based on measures of total ctDNA, reflects disease activity and is almost perfectly correlated with standard parameters such as PET/CT that are associated with refractoriness.

15.
Sci Rep ; 14(1): 710, 2024 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-38184757

RESUMO

Classic Hodgkin lymphoma (cHL) is characterized by a rich immune microenvironment as the main tumor component. It involves a broad range of cell populations, which are largely unexplored, even though they are known to be essential for growth and survival of Hodgkin and Reed-Sternberg cells. We profiled the gene expression of 25 FFPE cHL samples using NanoString technology and resolved their microenvironment compositions using cell-deconvolution tools, thereby generating patient-specific signatures. The results confirm individual immune fingerprints and recognize multiple clusters enriched in refractory patients, highlighting the relevance of: (1) the composition of immune cells and their functional status, including myeloid cell populations (M1-like, M2-like, plasmacytoid dendritic cells, myeloid-derived suppressor cells, etc.), CD4-positive T cells (exhausted, regulatory, Th17, etc.), cytotoxic CD8 T and natural killer cells; (2) the balance between inflammatory signatures (such as IL6, TNF, IFN-γ/TGF-ß) and MHC-I/MHC-II molecules; and (3) several cells, pathways and genes related to the stroma and extracellular matrix remodeling. A validation model combining relevant immune and stromal signatures identifies patients with unfavorable outcomes, producing the same results in an independent cHL series. Our results reveal the heterogeneity of immune responses among patients, confirm previous findings, and identify new functional phenotypes of prognostic and predictive utility.


Assuntos
Doença de Hodgkin , Humanos , Doença de Hodgkin/genética , Matriz Extracelular , Células Mieloides , Células de Reed-Sternberg , Linfócitos T CD4-Positivos , Antígenos de Histocompatibilidade Classe II , Microambiente Tumoral/genética
16.
Int J Obes (Lond) ; 48(4): 542-549, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38245658

RESUMO

BACKGROUND: Rodent models suggest that in utero exposure to under and overnutrition programs offspring physical activity (PA) behaviors. Such nexus has not been established in humans. This study evaluated the association of early pregnancy maternal adiposity with offspring PA at age 2 years (2-yo-PA) taking into consideration prenatal and postnatal factors. METHODS: Women (n = 153) were enrolled early in pregnancy (<10 weeks). At enrollment, maternal adiposity [air displacement plethysmography, fat mass index (FMI, kg/m2)] and PA (accelerometers, activity counts) were measured, and age, race, and education self-reported. Gestational weight gain was measured at the research facility. Offspring birthweight and sex were self-reported. At age 2 years, parental feeding practices (child feeding questionnaire) were assessed, whereas anthropometrics (length and weight) and physical activity (accelerometers) were objectively measured. Offspring body mass index z-scores were calculated. Generalized linear regression analysis modeled the association of maternal FMI and 2-yo-PA [average activity counts (AC)4/day]. RESULTS: In bivariate associations, 2-yo-PA did not associate with maternal FMI (ß = -0.22, CI = -0.73 to 0.29, p = 0.398). However, maternal FMI interacted with offspring sex in association with 2-yo-PA. Specifically, 2-yo-PA was lower in girls (ß = -1.14, CI = -2.1 to -0.18, p = 0.02) compared to boys when maternal FMI was ≥7 kg/m2. When stratified by sex, 2-yo-PA of girls negatively associated with maternal FMI (ß = -0.82, CI = -1.43 to 0.29, p = 0.009) while no association was found between maternal FMI and boy's PA (ß = 0.32, CI = -0.38 to 1.01, p = 0.376). CONCLUSIONS: The association of 2-yo-PA and early pregnancy maternal adiposity was modified by offspring sex. Offspring's physical activity decreased with increasing early pregnancy adiposity maternal in girls but not boys in second parity dyads.


Assuntos
Adiposidade , Obesidade Materna , Masculino , Criança , Gravidez , Humanos , Feminino , Pré-Escolar , Obesidade , Índice de Massa Corporal , Exercício Físico , Antropometria
17.
Trials ; 25(1): 35, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38195586

RESUMO

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.


Assuntos
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 Assunto
18.
Energy Fuels ; 37(19): 14836-14844, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37817863

RESUMO

MOFs are potential adsorbents for methane separation from nitrogen, including recovery in diluted streams. However, water and carbon dioxide can seriously affect the adsorption performance. Three commercial MOFs, basolite C300, F300, and A100, were studied under similar conditions to fugitive methane streams, such as water (75 and 100% relative humidity) and carbon dioxide (0.33%) presence in a fixed bed. The presence of available open metal sites of copper (Cu2+) and aluminum (Al3+) in the case of basolite C300 and A100, respectively, constitutes a clear drawback under humid conditions, since water adsorbs on them, leading to significant methane capacity losses. Surprisingly, basolite F300 is the most resistant material due to its amorphous structure, which hinders water access. The combination of carbon dioxide and water creates a synergy that seriously affects basolite A100, closely related to its breathing effect, but does not constitute an important issue for basolite C300 and F300.

19.
AJNR Am J Neuroradiol ; 44(11): 1275-1281, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37827717

RESUMO

BACKGROUND AND PURPOSE: Several nonrandomized studies have demonstrated the effectiveness of balloon guide catheters in treating patients with anterior circulation large-vessel occlusion. However, their impact on the elderly populations has been underreported. We aimed to analyze the effect of balloon guide catheters in a cohort of elderly patients (80 years of age or older) with anterior circulation large-vessel occlusion. MATERIALS AND METHODS: Consecutive patients from June 2019 to June 2022 were collected from the ROSSETTI Registry. Demographic and clinical data, angiographic endovascular technique, and clinical outcome were compared between balloon guide catheter and non-balloon guide catheter groups. We studied the association between balloon guide catheters and the rate of complete recanalization after a single first-pass effect modified TICI 2c-3, as well as their association with functional independence at 3 months. RESULTS: A total of 808 patients were included during this period, 465 (57.5%) of whom were treated with balloon guide catheters. Patients treated with balloon guide catheters were older, had more neurologic severity at admission and lower baseline ASPECTS, and were less likely to receive IV fibrinolytics. No differences were observed in terms of the modified first-pass effect between groups (45.8 versus 39.9%, P = .096). In the multivariable regression analysis, balloon guide catheter use was not independently associated with a modified first-pass effect or the final modified TICI 2c-3, or with functional independence at 3 months. CONCLUSIONS: In our study, balloon guide catheter use during endovascular treatment of anterior circulation large-vessel occlusion in elderly patients did not predict the first-pass effect, near-complete final recanalization, or functional independence at 3 months. Further studies, including randomized clinical trials, are needed to confirm these results.


Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Humanos , Catéteres , Sistema de Registros , Estudos Retrospectivos , Stents , Trombectomia/métodos , Resultado do Tratamento , Idoso de 80 Anos ou mais
20.
Sci Adv ; 9(36): eadh5562, 2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37672590

RESUMO

Electrically controllable nonvolatile magnetic memories show great potential for the replacement of conventional semiconductor-based memory technologies. Here, we experimentally demonstrate ultrafast spin-orbit torque (SOT)-induced coherent magnetization switching dynamics in a ferromagnet. We use an ultrafast photoconducting switch and a coplanar strip line to generate and guide a ~9-picosecond electrical pulse into a heavy metal/ferromagnet multilayer to induce ultrafast SOT. We then use magneto-optical probing to investigate the magnetization dynamics with sub-picosecond resolution. Ultrafast heating by the approximately 9 picosecond current pulse induces a thermal anisotropy torque which, in combination with the damping-like torque, coherently rotates the magnetization to obtain zero-crossing of magnetization in ~70 picoseconds. A macro-magnetic simulation coupled with an ultrafast heating model agrees well with the experiment and suggests coherent magnetization switching without any incubation delay on an unprecedented time scale. Our work proposes a unique magnetization switching mechanism toward markedly increasing the writing speed of SOT magnetic random-access memory devices.

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