Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 289
Filtrar
1.
J Sports Sci Med ; 23(2): 358-365, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38841631

RESUMO

Mixed-Team-Relay (MTR) triathlon is a novel Olympic discipline whose performance determinants and tactical behaviors have barely been studied. Additionally, a regulatory change has been made to the male and female relay order for the Paris 2024 Olympics. Therefore, this study aimed to determine the performance determinants and race dynamics as a function of competitive level on the new regulated MTR triathlon. Results from 129 national teams, (516 elite triathletes) across five MTR World Triathlon Series and two MTR European Championships in 2022 and 2023, were analyzed. Split times, average speeds, time behind the race leader (gap), partial and finishing positions, pack position as well as the rank positions of every segment, relay leg, and overall race were computed. Decision tree analyses were conducted as a predictive method for the overall results, and correspondence analyses were conducted to examine the relationship between the different relay legs and segments and the finishing positions. The performance of the fourth leg was the most relevant for overall result (30%), as well as the fourth running leg (16%) and the female legs performance (7%). Medallist relay teams were characterized by displaying a differential speed lower than 0.5 and 0.83 km/h, respectively, from the best-ranking athletes in the Legs 1 and 4. Furthermore, staying in the front pack after the second swimming leg showed a great relationship with achieving a medal position. New MTR triathlon rules shift race dynamics, emphasizing individual efforts in cycling and swimming, while maintaining the crucial importance of running.


Assuntos
Desempenho Atlético , Ciclismo , Comportamento Competitivo , Corrida , Natação , Humanos , Desempenho Atlético/fisiologia , Masculino , Ciclismo/fisiologia , Feminino , Corrida/fisiologia , Natação/fisiologia , Comportamento Competitivo/fisiologia , Esportes de Equipe
2.
Sci Rep ; 14(1): 10759, 2024 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730045

RESUMO

The evaluation of diagnostic systems is pivotal for ensuring the deployment of high-quality solutions, especially given the pronounced context-sensitivity of certain systems, particularly in fields such as biomedicine. Of notable importance are predictive models where the target variable can encompass multiple values (multiclass), especially when these classes exhibit substantial frequency disparities (imbalance). In this study, we introduce the Imbalanced Multiclass Classification Performance (IMCP) curve, specifically designed for multiclass datasets (unlike the ROC curve), and characterized by its resilience to class distribution variations (in contrast to accuracy or F ß -score). Moreover, the IMCP curve facilitates individual performance assessment for each class within the diagnostic system, shedding light on the confidence associated with each prediction-an aspect of particular significance in medical diagnosis. Empirical experiments conducted with real-world data in a multiclass context (involving 35 types of tumors) featuring a high level of imbalance demonstrate that both the IMCP curve and the area under the IMCP curve serve as excellent indicators of classification quality.


Assuntos
Neoplasias , Humanos , Neoplasias/classificação , Neoplasias/diagnóstico , Curva ROC , Algoritmos
3.
PLoS One ; 19(5): e0304154, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38776309

RESUMO

Membrane proteins are the main targets of therapeutic drugs and most of them are glycosylated. Glycans play pivotal roles in several biological processes, and glycosylation changes are a well-established hallmark of several types of cancer, including pancreatic cancer, that contribute to tumor growth. Mucin-4 (MUC-4) is a membrane glycoprotein which is associated with pancreatic cancer and metastasis, and it has been targeted as a promising vaccine candidate. In this study, Surface Plasmon Resonance Microscopy (SPRM) was implemented to study complex influences of the native N-glycan cellular environment on binding interactions to the MUC-4 receptor as this is currently the only commercially available label-free technique with high enough sensitivity and resolution to measure binding kinetics and heterogeneity on single cells. Such unique capability enables for a more accurate understanding of the "true" binding interactions on human cancer cells without disrupting the native environment of the target MUC-4 receptor. Removal of N-linked glycans in pancreatic cancer cells using PNGase F exposed heterogeneity in Concanavalin (Con A) binding by revealing three new binding populations with higher affinities than the glycosylated control cells. Anti-MUC-4 binding interactions of enzymatically N-linked deglycosylated pancreatic cancer cells produced a 25x faster association and 37x higher affinity relative to the glycosylated control cells. Lastly, four interaction modes were observed for Helix Pomatia Agglutinin (HPA) binding to the glycosylated control cells, but shifted and increased in activity upon removal of N-linked glycans. These results identified predominant interaction modes of glycan and MUC-4 in pancreatic cancer cells, the kinetics of their binding interactions were quantified, and the influence of N-linked glycans in MUC-4 binding interactions was revealed.


Assuntos
Mucina-4 , Neoplasias Pancreáticas , Polissacarídeos , Ligação Proteica , Ressonância de Plasmônio de Superfície , Humanos , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Ressonância de Plasmônio de Superfície/métodos , Polissacarídeos/metabolismo , Mucina-4/metabolismo , Linhagem Celular Tumoral , Glicosilação , Microscopia/métodos
4.
Artigo em Inglês | MEDLINE | ID: mdl-38775181

RESUMO

OBJECTIVE: Neurofilament heavy-chain gene (NEFH) variants are associated with multiple neurodegenerative diseases, however, their relationship with ALS has not been robustly explored. Still, NEFH is commonly included in genetic screening panels worldwide. We therefore aimed to determine if NEFH variants modify ALS risk. METHODS: Genetic data of 11,130 people with ALS and 7,416 controls from the literature and Project MinE were analysed. We performed meta-analyses of published case-control studies reporting NEFH variants, and variant analysis of NEFH in Project MinE whole-genome sequencing data. RESULTS: Fixed-effects meta-analysis found that rare (MAF <1%) missense variants in the tail domain of NEFH increase ALS risk (OR 4.55, 95% CI 2.13-9.71, p < 0.0001). In Project MinE, ultrarare NEFH variants increased ALS risk (OR 1.37 95% CI 1.14-1.63, p = 0.0007), with rod domain variants (mostly intronic) appearing to drive the association (OR 1.45 95% CI 1.18-1.77, pMadsen-Browning = 0.0007, pSKAT-O = 0.003). While in the tail domain, ultrarare (MAF <0.1%) pathogenic missense variants were also associated with higher risk of ALS (OR 1.94, 95% CI 0.86-4.37, pMadsen-Browning = 0.039), supporting the meta-analysis results. Finally, several tail in-frame deletions were also found to affect disease risk, however, both protective and pathogenic deletions were found in this domain, highlighting an intricated architecture that requires further investigation. INTERPRETATION: We showed that NEFH tail missense and in-frame deletion variants, and intronic rod variants are risk factors for ALS. However, they are not variants of large effect, and their functional impact needs to be clarified in further studies. Therefore, their inclusion in routine genetic screening panels should be reconsidered.

5.
Brain ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38743818

RESUMO

Despite advances in understanding the cellular and molecular processes underlying memory and cognition, and recent successful modulation of cognitive performance in brain disorders, the neurophysiological mechanisms remain underexplored. High frequency oscillations beyond the classic electroencephalogram spectrum have emerged as a potential neural correlate of fundamental cognitive processes. High frequency oscillations are detected in the human mesial temporal lobe and neocortical intracranial recordings spanning gamma/epsilon (60-150 Hz), ripple (80-250 Hz) and higher frequency ranges. Separate from other non-oscillatory activities, these brief electrophysiological oscillations of distinct duration, frequency and amplitude are thought to be generated by coordinated spiking of neuronal ensembles within volumes as small as a single cortical column. Although the exact origins, mechanisms, and physiological roles in health and disease remain elusive, they have been associated with human memory consolidation and cognitive processing. Recent studies suggest their involvement in encoding and recall of episodic memory with a possible role in the formation and reactivation of memory traces. High frequency oscillations are detected during encoding, throughout maintenance, and right before recall of remembered items, meeting a basic definition for an engram activity. The temporal coordination of high frequency oscillations reactivated across cortical and subcortical neural networks is ideally suited for integrating multimodal memory representations, which can be replayed and consolidated during states of wakefulness and sleep. High frequency oscillations have been shown to reflect coordinated bursts of neuronal assembly firing and offer a promising substrate for tracking and modulation of the hypothetical electrophysiological engram.

6.
Muscle Nerve ; 70(1): 36-41, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38712849

RESUMO

The amyotrophic lateral sclerosis (ALS) functional rating scale-revised (ALSFRS-R) has become the most widely utilized measure of disease severity in patients with ALS, with change in ALSFRS-R from baseline being a trusted primary outcome measure in ALS clinical trials. This is despite the scale having several established limitations, and although alternative scales have been proposed, it is unlikely that these will displace ALSFRS-R in the foreseeable future. Here, we discuss the merits of delta FS (ΔFS), the slope or rate of ALSFRS-R decline over time, as a relevant tool for innovative ALS study design, with an as yet untapped potential for optimization of drug effectiveness and patient management. In our view, categorization of the ALS population via the clinical determinant of post-onset ΔFS is an important study design consideration. It serves not only as a critical stratification factor and basis for patient enrichment but also as a tool to explore differences in treatment response across the overall population; thereby, facilitating identification of responder subgroups. Moreover, because post-onset ΔFS is derived from information routinely collected as part of standard patient care and monitoring, it provides a suitable patient selection tool for treating physicians. Overall, post-onset ΔFS is a very attractive enrichment tool that is, can and should be regularly incorporated into ALS trial design.


Assuntos
Esclerose Lateral Amiotrófica , Projetos de Pesquisa , Humanos , Esclerose Lateral Amiotrófica/diagnóstico , Ensaios Clínicos como Assunto/métodos , Progressão da Doença , Avaliação de Resultados em Cuidados de Saúde/normas , Índice de Gravidade de Doença
7.
Eur J Neurol ; 31(6): e16264, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38470068

RESUMO

BACKGROUND: This update of the guideline on the management of amyotrophic lateral sclerosis (ALS) was commissioned by the European Academy of Neurology (EAN) and prepared in collaboration with the European Reference Network for Neuromuscular Diseases (ERN EURO-NMD) and the support of the European Network for the Cure ALS (ENCALS) and the European Organization for Professionals and Patients with ALS (EUpALS). METHODS: Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess the effectiveness of interventions for ALS. Two systematic reviewers from Cochrane Response supported the guideline panel. The working group identified a total of 26 research questions, performed systematic reviews, assessed the quality of the available evidence, and made specific recommendations. Expert consensus statements were provided where insufficient evidence was available. RESULTS: A guideline mapping effort revealed only one other ALS guideline that used GRADE methodology (a National Institute for Health and Care Excellence [NICE] guideline). The available evidence was scarce for many research questions. Of the 26 research questions evaluated, the NICE recommendations could be adapted for 8 questions. Other recommendations required updates of existing systematic reviews or de novo reviews. Recommendations were made on currently available disease-modifying treatments, multidisciplinary care, nutritional and respiratory support, communication aids, psychological support, treatments for common ALS symptoms (e.g., muscle cramps, spasticity, pseudobulbar affect, thick mucus, sialorrhea, pain), and end-of-life management. CONCLUSIONS: This update of the guideline using GRADE methodology provides a framework for the management of ALS. The treatment landscape is changing rapidly, and further updates will be prepared when additional evidence becomes available.


Assuntos
Esclerose Lateral Amiotrófica , Esclerose Lateral Amiotrófica/terapia , Humanos , Europa (Continente) , Neurologia/normas , Neurologia/métodos , Doenças Neuromusculares/terapia
8.
Healthcare (Basel) ; 12(5)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38470628

RESUMO

The COVID-19 pandemic has had a profound impact on various aspects of our lives, affecting personal, occupational, economic, and social spheres. Much has been learned since the early 2020s, which will be very useful when the next pandemic emerges. In general, mobility and virus spread are strongly related. However, most studies analyze the impact of COVID-19 on mobility, but not much research has focused on analyzing the impact of mobility on virus transmission, especially from the point of view of monitoring virus incidence, which is extremely important for making sound decisions to control any epidemiological threat to public health. As a result of a thorough analysis of COVID-19 and mobility data, this work introduces a novel measure, the Infection Ratio (IR), which is not sensitive to underestimation of positive cases and is very effective in monitoring the pandemic's upward or downward evolution when it appears to be more stable, thus anticipating possible risk situations. For a bounded spatial context, we can infer that there is a significant threshold in the restriction of mobility that determines a change of trend in the number of infections that, if maintained for a minimum period, would notably increase the chances of keeping the spread of disease under control. Results show that IR is a reliable indicator of the intensity of infection, and an effective measure for early monitoring and decision making in smart cities.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38283061

RESUMO

Black gobies (Gobius niger) from the Finnish Archipelago, Baltic Sea, were screened for helminth infections in summer 2020. Helminths were identified morphologically and/or molecularly. Altogether 26 novel sequences were generated and analysed using maximum likelihood estimation. Morphological and phylogenetic analyses based on mitochondrial genes revealed the presence of 8 species belonging to the Digenea (Diplostomum mergi Lineage 3), Cestoda (Bothriocephalus scorpii), Nematoda (Contracaecum rudolphii A, Cucullanus sp. and Hysterothylacium aduncum), and Acanthocephala (a putative new species of Corynosoma, Corynosoma semerme and Neoechinorhynchus sp.). Phylogenetic and comparative sequence analyses revealed that the putative new acanthocephalan species is closely related to C. neostrumosum described from the Caspian seal, Pusa caspica, in the Caspian Sea. The black goby represents a new host record for four parasite species (Diplostomum mergi Lineage 3, Contracaecum rudolphii A, Corynosoma semerme and Corynosoma sp.). The Finnish Archipelago is a novel locality record for three species (Corynosoma sp., Diplostomum mergi Lineage 3 and Bothriocephalus scorpii).

10.
Parasitology ; 151(1): 24-44, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37953070

RESUMO

Hemiurid digeneans conspecific with Stomachicola muraenesocis Yamaguti, 1934 (the type species of the genus Stomachicola Yamaguti, 1934) were collected from the stomach of the daggertooth pike conger Muraenesox cinereus (Forsskål) off the Persian Gulf of Iran. This study aimed to provide a detailed characterization of Stom. muraenesocis, including measurements, illustrations and scanning electron microscopy (s.e.m.) representations. Comparisons with the original and previous descriptions revealed morphological and metrical variations in several features (i.e. body size and shape, arrangement of reproductive organs, soma to ecsoma length ratio, position of genital opening, number of vitelline tubules and extension of uterine coils) between Stom. muraenesocis from different hosts and localities. This study presents the first molecular sequence data associated with the small (18S) and large (28S) subunit nuclear ribosomal RNA genes (rDNA) for Stom. muraenesocis. Phylogenetic analyses of the 18S dataset placed Stom. muraenesocis as sister lineage to a clade formed of a group of species of Lecithaster Lühe, 1901 (Lecithasteridae Odhner, 1905). In contrast, phylogenetic analyses based on the 28S consistently recovered a sister relationship between Stom. muraenesocis and representatives of the Hemiuridae Looss, 1899. Further comprehensive phylogenetically based classification in light of morphology and taxonomic history of the Hemiuridae and Lecithasteridae is required to infer phylogenetic affinities and historical biogeography of Stomachicola. A comprehensive list of previously reported species of Stomachicola together with their associated hosts, localities and morphometric data is provided.


Assuntos
Esocidae , Trematódeos , Animais , Esocidae/genética , Filogenia , Peixes , Dados de Sequência Molecular , DNA Ribossômico/genética , RNA Ribossômico 28S/genética
11.
Chempluschem ; 89(5): e202300579, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38116999

RESUMO

The H2O@HKUST-1 and DMF@HKUST-1 systems were experimental and computationally assessed, employing XRD/TGA/FT-IR/DFT-calculations, evidencing that H2O or DMF coordinated to Cu, modulating HKUST-1 photocatalytic properties. DMF@HKUST-1 has narrower bandgap promoting higher-crystallinity and light-harvesting. H2O@HKUST-1 showed smaller particle sizing and sharp morphology. Theoretical models, (H2O)1@HKUST-1 and (DMF)1@HKUST-1, containing one coordinated molecule, elucidated bandgap modulation associated with infiltration. H2O@HKUST-1/DMF@HKUST-1 presented bandgaps [eV] of 3.6/3.4, by Tauc plots, and 3.55/3.26, by theoretical calculations, narrowing bandgap, compared with non-solvated HKUST-1(HKUST-1NS). Both composites raised the valence band (VB) and lowered the conduction band (CB), but DMF@HKUST-1 most raised VB. Topological analysis revealed that guests i) with higher electronic density, raised VB, and ii) induced π-backbonding, lowering CB. DMF@HKUST-1 presented a higher photocatalytic hydrogen evolution (µmol), 26.45, in the first 30 min of the reaction, nevertheless, H2O@HKUST-1 presented a competitive activity, of 17.32. In large periods, H2O@HKUST-1/DMF@HKUST-1 showed practically the same hydrogen evolution, 45.50/49.03.

12.
J Pediatr Hematol Oncol ; 46(2): e131-e136, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38132672

RESUMO

Mexican and Hispanic children in Mexico and the United States, respectively, have the highest incidence and worst outcomes of pre-B acute lymphoblastic leukemia (ALL) compared with other racial/ethnic groups. Terminal deoxynucleotidyl transferase (TdT) is an intranuclear DNA polymerase normally present on immature lymphocytes (TdT-positive) and distinguishes ALL from mature lymphoid malignancies. We performed a multisite retrospective study to determine the incidence of TdT-negative precursor B-cell acute lymphoblastic leukemia (pre-B ALL) among Mexican, Caucasian, and US-born Hispanic children to correlate TdT expression with patient characteristics and known prognostic factors. Fisher exact test was performed for categorical variables and the Wilcoxon rank-sum test was used for continuous variables. TdT-negative pre-B ALL was most frequently identified in patients with National Cancer Institute high-risk disease ( P =0.014). TdT-negative expression was also most frequently associated with hypodiploid pre-B ALL ( P =0.001) and KMT2A gene rearrangement ( P =0.0012). Mexican children had the highest incidence of TdT-negative ALL compared with Caucasians and US Hispanics ( P <0.001), with an increased incidence of poor prognostic features as well. This study demonstrates significant differences in TdT-negative expression, genomic alterations, and leukemic ploidy based on race and ethnicity.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Prognóstico , Estudos Retrospectivos , México/epidemiologia , Incidência , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , DNA Nucleotidilexotransferase/metabolismo , Doença Aguda
13.
J Hum Kinet ; 89: 269-278, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38053956

RESUMO

This study aimed to determine the importance of the different relay legs and sport disciplines in the overall result of the triathlon Mixed Team Relay (MTR) events. The study analysed the results of 80 Mixed Team Relay triathlon teams (n = 320 professional triathletes) corresponding to the top ten finishers at the World Championships in Hamburg from 2013 to 2020. Split times, average speeds, time behind the race leader (gap), partial and finishing positions, as well as the rank positions of every segment, relay leg, and overall race were computed. Decision tree analyses were conducted as a predictive method for the overall results, and correspondence analyses were conducted to examine the relationship between the different relay legs and segments and the finishing positions. Running was the variable with the greatest importance (32%) in the overall result, followed by female team members (17%) and the third relay leg (17%). The swimming segments (1%) and the fourth relay leg (1%) had the lowest relevance. Medallist relay teams were characterised by cycling and running faster than 10.99 m/s and 5.59 m/s, respectively, with time gaps of less than 43 seconds by the end of the third relay leg. A reliable and accurate prediction model for the medallists' and finalists' team positions in the Mixed Team Relay triathlon was obtained. The running disciplines and performance of female team members, especially in the third leg, were ascertained to be the most significant determinants for the overall Mixed Team Relay result.

14.
Glycobiology ; 33(12): 1182-1192, 2023 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-37792857

RESUMO

Factors regulating macrophage effector function represent potential targets to optimize the efficacy of antibody-mediated therapies. Macrophages are myeloid cells capable of engulfing and destroying diseased or damaged target cells. Antibodies binding to the target cell surface can engage macrophage Fc gamma receptors (FcγRs) to elicit antibody-dependent cellular phagocytosis (ADCP), a process that contributes to treatments mediated by anti-tumor antibodies. Conversely, macrophage ADCP of apoptotic T cells is also linked to tolerance in the tumor environment. Here we evaluated the role of asparagine(N)-linked glycans in the function of macrophages derived from primary human monocytes. Macrophages treated with kifunensine, an inhibitor of N-glycan processing, exhibited greater target binding and ADCP of antibody-coated target cells. Kifunensine treatment increased ADCP of both rituximab-coated Raji B cells and trastuzumab-coated SKBR3 cells. ADCP required FcγRs; inhibiting CD64 / FcγRI led to the greatest reduction, followed by CD32 / FcγRII and then CD16 / FcγRIII in most donors. Kifunensine treatment also increased the antibody-binding affinity of CD16. Differences in the abundance of phosphorylated immune receptors, including Siglec-9, CD32a, and LAIR-1 correlated with the increased ADCP. These results demonstrate that N-glycan processing regulates macrophage effector function.


Assuntos
Macrófagos , Neoplasias , Humanos , Macrófagos/metabolismo , Fagocitose , Monócitos/metabolismo , Polissacarídeos/metabolismo , Citotoxicidade Celular Dependente de Anticorpos
15.
Rev. esp. patol. torac ; 35(3): 202-210, oct. 2023. ilus, tab, graf
Artigo em Espanhol | IBECS | ID: ibc-227389

RESUMO

Introducción y objetivos: La valoración del efecto de la rehabilitación respiratoria domiciliaria (PRRD) en bronquiectasias no fibrosis quística (BQ no FQ) es un campo poco explorado hasta la fecha. El objetivo fue evaluar cómo influye un PRRD piloto en la disnea, la calidad de vida y en los trastornos del estado de ánimo así como su relación con la gravedad de la enfermedad. Material y métodos: Ensayo clínico no farmacológico en pacientes con BQ no FQ del Hospital Universitario Virgen Macarena. Se aleatorizó en: 1) grupo estudio (GE): programa de entrenamiento (resistencia y fuerza) en domicilio durante 8 semanas, 2) grupo control (GC): medidas educacionales por escrito. Se evaluó la gravedad de la enfermedad con el E-FACED, síntomas (cuestionario de Leicester (LCQ) y disnea (escala mMRC)), la calidad de vida (cuestionario de enfermedades respiratorias de Saint George (SGRQ)) y ansiedad y depresión (cuestionario hospitalario de ansiedad y depresión (HADS). Resultados: Después de 8 semanas en el GE existió mejoría en disnea de 0,46 ± 0,80, p = 0,010 y en la esfera física del LCQ de -0,68 ± 1,2, p = 0,043. Se produjo una mejoría en SGRQ actividad (-9 puntos, p = 0,025) y en el SGRQ total un cambio clínicamente relevante (-7 puntos, p = 0,063). La escala de depresión descendió 2,3 ± 4,2 puntos, p = 0,044. La gravedad no se relacionó con ninguna variable. Conclusiones: El PRRD mostró un claro beneficio en calidad de vida, síntomas y depresión de nuestros pacientes con BQ no FQ. (AU)


Introduction and objectives: the assessment of the effect of home-based pulmonary rehabilitation programmes (HPRP) in noncystic fibrosis bronchiectasis (non-CF BQ) is a field that has been little explored to date. Our objective was to evaluate how a pilot HPRP influences dyspnoea, quality of life and mood disorders and their relationship the severity of the disease. Material and methods: we present non-pharmacological clinical trial in patients with non-CF BQ at the Virgen Macarena University Hospital. It was randomized into1) study group (SG): received training program (resistance and strength) at home for 8 weeks and 2) control group (CG): received written educational measures. We assessed the impact of the program on disease severity (E-FACED), symptoms (Leicester Questionnaire (LCQ) and dyspnea (mMRC scale)), and quality of life (Saint George RespiratoryQuestionnaire) and anxiety and depression (Anxiety and Depression Hospital (HAD)). Results: after 8 weeks there was an improvement in dyspnoea of 0.46 ± 0,80, p = 0.010 and in the physical sphere of the LCQ of -0.68 ± 1.2, p = 0.043.There was an improvement in SGRQ activity (-9 points, p = 0.025) and in the total SGRQ a clinically relevant change (-7 points, p = 0.063).The depression scale decreased 2.3 ± 4.2 points, p = 0.044. There was no relationship between severity and any of the variables studied. Conclusions: the PRRD showed a clear benefit in quality of life, symptoms and depression of our patients with non-CF BQ. KeywordsMesH: Non-cystic fibrosis bronchiectasis, homebased respiratory rehabilitation, impact quality of life. (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Bronquiectasia/reabilitação , Dispneia/reabilitação , Qualidade de Vida , Emoções , Espanha , Grupos Controle , Inquéritos e Questionários
16.
Anal Biochem ; 680: 115317, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37699507

RESUMO

Glycan node analysis (GNA) is a molecularly bottom-up glycomics technique based on the relative quantification of glycan linkage-specific monosaccharide units ("glycan nodes"). It was originally applied to blood plasma/serum, where it detected and predicted progression, reoccurrence, and survival in different types of cancer. Here, we have adapted this technology to previously inaccessible membrane glycoproteins from cultured cells. The approach is facilitated by methanol/chloroform precipitation of cell lysates and a "liquid phase permethylation" (LPP) procedure. LPP gave better signal-to-noise, yield and precision for most of the glycan nodes from membrane glycoproteins/glycolipids than the conventional solid phase permethylation approach. This GNA approach in cell lysates revealed that specific glycan features such as antennary fucosylation, N-glycan branching, and α2,6-sialylation were elevated in hepatocellular carcinoma (HepG2) cells relative to leukemia cells (THP-1 and K562) and normal donor PBMCs. Additional nodes commonly associated with glycolipids were elevated in the leukemia cells relative to HepG2 cells and PBMCs. Exposure of HepG2 cells to a fucosyltransferase inhibitor resulted in a significant reduction in the relative abundance of 3,4-substituted GlcNAc, which represents antennary fucosylation-providing further proof-of-concept that downregulation of glycosyltransferase activity is detected by shifts in glycan node expression-now detectable in membrane glycoproteins.


Assuntos
Clorofórmio , Leucemia , Humanos , Regulação para Baixo , Glicolipídeos , Glicoproteínas de Membrana
19.
Animals (Basel) ; 13(15)2023 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-37570315

RESUMO

Canine mammary carcinomas (CMC) are associated with major aggressive clinical behavior and high mortality. The current standard of care is based on surgical resection, without an established effective treatment scheme, highlighting the urgent need to develop novel effective therapies. Vascular endothelial growth factor (VEGF) is a key regulator of tumor angiogenesis and progression in the majority of solid cancers, including human and canine mammary carcinomas. The first therapy developed to target VEGF was bevacizumab, a recombinant humanized monoclonal antibody, which has already been approved as an anticancer agent in several human cancers. The goal of this work was to establish the therapeutic value of MB02 bevacizumab biosimilar in CMC. First, through different in silico approaches using the MUSCLE multiple-sequence alignment tool and the FoldX protein design algorithm, we were able to predict that canine VEGF is recognized by bevacizumab, after showing an extremely high sequence similarity between canine and human VEGF. Further, by using an ELISA-based in vitro binding assay, we confirmed that MB02 biosimilar was able to recognize canine VEGF. Additionally, canine VEGF-induced microvascular endothelial cell proliferation was inhibited in a concentration-dependent manner by MB02 biosimilar. These encouraging results show a high potential for MB02 as a promising therapeutic agent for the management of CMC.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...