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1.
Plant Physiol Biochem ; 212: 108717, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38761542

RESUMO

Chloride (Cl-) is traditionally categorized as an antagonist of nitrate (NO3-) because Cl- hinders plant NO3- transport and accumulation. However, we have recently defined Cl- as a beneficial macronutrient for higher plants, due to specific functions that lead to more efficient use of water, nitrogen (N) and CO2 under optimal N and water supply. When accumulated in leaves at macronutrient levels, Cl- promotes growth through osmotic, physiological, metabolic, anatomical and cellular changes that improve plant performance under optimal NO3- nutrition. Nitrate over-fertilization in agriculture can adversely affect crop yield and nature, while its deficiency limits plant growth. To study the relationship between Cl- nutrition and NO3- availability, we have characterized different physiological responses such as growth and yield, N-use efficiency, water status, photosynthesis, leaf anatomy, pigments and antioxidants in tomato plants treated with or without 5 mM Cl- salts and increasing NO3- treatments (3-15 mM). First, we have demonstrated that 5 mM Cl- application can reduce the use of NO3- in the nutrient solution by up to half without detriment to plant growth and yield in tomato and other horticultural plants. Second, Cl- application reduced stress symptoms and improved plant growth under low-NO3- conditions. The Cl--dependent resistance to low-N stress resulted from: more efficient use of the available NO3-; improved plant osmotic and water status regulation; improved stomatal conductance and photosynthetic rate; and better antioxidant response. We proposed that beneficial Cl- levels increase the crop ability to grow better with lower NO3- requirements and withstand N deficiency, promoting a more sustainable and resilient agriculture.


Assuntos
Cloretos , Nitratos , Nitrogênio , Folhas de Planta , Solanum lycopersicum , Estresse Fisiológico , Nitratos/metabolismo , Nitratos/farmacologia , Cloretos/metabolismo , Nitrogênio/metabolismo , Solanum lycopersicum/metabolismo , Solanum lycopersicum/efeitos dos fármacos , Solanum lycopersicum/crescimento & desenvolvimento , Estresse Fisiológico/efeitos dos fármacos , Folhas de Planta/metabolismo , Folhas de Planta/efeitos dos fármacos , Fotossíntese/efeitos dos fármacos , Água/metabolismo , Antioxidantes/metabolismo
2.
Ocul Immunol Inflamm ; : 1-7, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691840

RESUMO

OBJECTIVE: To describe the efficacy and safety of adalimumab for the treatment of non-infectious uveitis (NIU) in four Uveitis Units from tertiary Spanish hospitals. METHODS: Multicenter and retrospective clinical cohort study including all patients with NIU treated with adalimumab from January 2012 to October 2022 in four uveitis units was performed. Efficacy was measured with the number of relapses, ocular inflammation and reduction in immunosuppression and corticosteroid dosage before and after adalimumab use. We collected data regarding adverse effects and examined the immunogenicity of adalimumab. RESULTS: One hundred and twenty-two patients (59% females), with a mean age of 48.6 years (SD = 14.8) accounting for 217 eyes were included. The majority (92.6%) were Caucasian. Uveitis analyzed were predominantly panuveitis (34.7%), bilateral (77.9%), acute (41.5%), and non-granulomatous (90%). Most of them were immune mediated (42.6%), and the main reason to initiate adalimumab was refractory disease (96.7%). The analysis was statistically significant due to the reduction in the number of immunosuppressive drugs as well as the dose of oral corticosteroids and the number of relapses during follow-up (p < 0.001). The decrease in ocular inflammation parameters and the improvement in visual acuity (p < 0.05) were also significant. There were no deaths due to the drug and only one reported case of serious infection. In total, 10.9% of 73 patients tested developed anti-adalimumab antibodies and 4.1% lupus-like. CONCLUSIONS: We consider adalimumab as a leading drug in the treatment of NIU with high safety and efficacy.

3.
Int J Mol Sci ; 25(5)2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38473705

RESUMO

Classic Hodgkin lymphoma (cHL) constitutes a B-cell neoplasm derived from germinal center lymphocytes. Despite high cure rates (80-90%) obtained with the current multiagent protocols, a significant proportion of cHL patients experience recurrences, characterized by a lower sensitivity to second-line treatments. The genomic background of chemorefractory cHL is still poorly understood, limiting personalized treatment strategies based on molecular features. In this study, using a targeted next-generation sequencing (NGS) panel specifically designed for cHL research, we compared chemosensitive and chemorefractory diagnostic tissue samples of cHL patients. Furthermore, we longitudinally examined paired diagnosis-relapsesamples of chemorefractory cHL in order to define patterns of dynamic evolution and clonal selection. Pathogenic variants in NOTCH1 and NOTCH2 genes frequently arise in cHL. Mutations in genes associated with epigenetic regulation (CREBBP and EP300) are particularly frequent in relapsed/refractory cHL. The appearance of novel clones characterized by mutations previously not identified at diagnosis is a common feature in cHL cases showing chemoresistance to frontline treatments. Our results expand current molecular and pathogenic knowledge of cHL and support the performance of molecular studies in cHL prior to the initiation of first-line therapies.


Assuntos
Doença de Hodgkin , Linfoma de Células B , Humanos , Doença de Hodgkin/patologia , Epigênese Genética , Linfoma de Células B/genética , Mutação , Centro Germinativo/metabolismo
4.
Laryngoscope Investig Otolaryngol ; 9(1): e1182, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38362196

RESUMO

Objective: To analyze the impact, performance, degree of specialization, and collaboration patterns of the worldwide scientific production on tissue engineering in otorhinolaryngology at the level of countries and institutions. Methods: Two different techniques were used, performance and science mapping analyses, using as samples all the available documents regarding tissue engineering focused on otorhinolaryngology applications. The dataset was retrieved from the Core Collection of the Web of Science database from 1900 to 2020. Social structure was analyzed using science mapping analysis with VOSviewer software. Results: The United States was the main producer, followed by Germany, and Japan. Malaysia and Germany had the highest Relative Specialization Index, indicating their greater relative interest in this area compared to other countries. The social structure analysis showed that the United States and Germany had significant co-authorship relationships with other countries. The University of California System, Kyoto University, and Harvard University were the leading institutions producing literature in this field. These latter two institutions showed the largest number of collaborations, although most of them were with institutions within their own country. There was a lack of connections between different communities of research. Conclusion: The United States is the main country driving progress in this research area, housing the most notable institutions. However, significant collaborations between these research centers are currently lacking. Encouraging greater cooperation among these institutions and their researchers would promote the exchange of knowledge, ultimately facilitating and accelerating advancements in this field.

5.
New Phytol ; 241(3): 984-999, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38098153

RESUMO

Plant hydraulics is crucial for assessing the plants' capacity to extract and transport water from the soil up to their aerial organs. Along with their capacity to exchange water between plant compartments and regulate evaporation, hydraulic properties determine plant water relations, water status and susceptibility to pathogen attacks. Consequently, any variation in the hydraulic characteristics of plants is likely to significantly impact various mechanisms and processes related to plant growth, survival and production, as well as the risk of biotic attacks and forest fire behaviour. However, the integration of hydraulic traits into disciplines such as plant pathology, entomology, fire ecology or agriculture can be significantly improved. This review examines how plant hydraulics can provide new insights into our understanding of these processes, including modelling processes of vegetation dynamics, illuminating numerous perspectives for assessing the consequences of climate change on forest and agronomic systems, and addressing unanswered questions across multiple areas of knowledge.


Assuntos
Mudança Climática , Ecossistema , Água/fisiologia , Solo , Produtos Agrícolas , Secas
6.
Rev. esp. patol ; 56(4): 233-242, Oct-Dic, 2023. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-226956

RESUMO

Introducción: El cáncer de pulmón es la principal causa de muerte por cáncer en nuestro país. El cáncer de pulmón de células no pequeñas (CPCNP) representa el paradigma de la medicina personalizada. El objetivo principal de este trabajo es estudiar la frecuencia en nuestro medio de las variantes clínicamente significativas más frecuentemente descritas en CPCNP. Material y métodos: Se estudia la expresión inmunohistoquímica de TTF1, p40 y PD-L1 y la frecuencia de variantes genéticas mediante secuenciación masiva (NGS) con un panel de 52 genes, en 174 muestras incluidas en parafina de CPNCP en 169 pacientes (111 hombres y 52 mujeres) de la provincia de Cádiz. Resultados: La expresión inmunohistoquímica de TTF1, p40 y PD-L1 fue positiva en el 87%, el 0% y el 46% de los adenocarcinomas y en el 0%, el 100% y el 41% de los carcinomas escamosos. En NGS, las variantes de un solo nucleótido (SNV) más frecuentes fueron KRAS (36%), EGFR (14%), BRAF (10%), PIK3CA (8%) y MET (3%). Las variantes en el número de copias (CNV) más frecuentes fueron las amplificaciones en NF1 (30%), EGFR (18%), CCND1 (9%), MYC (9%) y KRAS (7%). En mujeres, las SNV en EGFR fueron más frecuentes que en hombres (p<0,0001). El adenocarcinoma es el tipo histológico más frecuente con SNV en KRAS (p=0,007361) o en EGFR (p<0,0001). En 16 pacientes (9,47%) se detectaron fusiones génicas, 9 casos en el gen MET. Conclusiones: Detectamos nuevas asociaciones entre expresión inmunohistoquímica y algunas variantes génicas, que podrían tener impacto en el tratamiento de pacientes de CPNCP.(AU)


Introduction: Lung cancer is the leading cause of cancer death in our country. Non-small cell lung cancer (NSCLC) represents the paradigm of personalized medicine. The main objective of this study is analysing the distribution of the most frequently described clinically significant variants in NSCLC, in our environment. Material and methods: We studied the immunohistochemical expression of TTF1, p40 and PD-L1 and the genetic variants frequency using Next-Generation Sequencing (NGS) with a panel of 52 genes, in 174 NSCLC paraffin-embedded samples in 169 patients (111 men and 52 women) from the province of Cádiz. Results: The immunohistochemical expression of TTF1, p40 and PD-L1 was positive in 87%, 0% and 46% in adenocarcinoma, and 0%, 100% and 41% in squamous cell carcinoma. In NGS, the most common single nucleotide variants (SNVs) were KRAS (36%), EGFR (14%), BRAF (10%), PIK3CA (8%), and MET (3%). The most frequent copy number variants (CNVs) were amplifications in NF1 (30%), EGFR (18%), CCND1 (9%), MYC (9%) and KRAS (7%). In women, SNV in EGFR are more frequent than in men (P<.0001). Adenocarcinoma is the most frequent histological type with SNV in KRAS (P=.007361) or in EGFR (P<.0001). Gene fusions were detected in 16 patients (9.47%), in 9 cases in the MET gene. Conclusions: We detected associations, not described so far, between immunohistochemical expression and specific gene variants, which could have an impact on the treatment of NSCLC patients.(AU)


Assuntos
Humanos , Masculino , Feminino , Imuno-Histoquímica , Carcinoma Pulmonar de Células não Pequenas/genética , Genes erbB-1 , Sequenciamento de Nucleotídeos em Larga Escala , Espanha , Neoplasias Pulmonares/genética , Biologia Celular
7.
Rev Clin Esp ; 223(5): 262-269, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37929276

RESUMO

Antecedentes: El síndrome de Wiskott-Aldrich (SWA) es un raro trastorno ligado al cromosoma X que se considera que afecta predominantemente a varones. Objetivo: El objetivo de este estudio consistía en investigar la incidencia y la mortalidad intrahospitalaria del SWA en España, así como el sesgo de género. Métodos: Se llevó a cabo un estudio epidemiológico retrospectivo poblacional en 97 pacientes con SWA diagnosticados en hospitales españoles entre 1997 y 2017, utilizando para ello datos del Sistema Nacional de Vigilancia de Datos Hospitalarios. Resultados: Nuestros resultados revelaron que la incidencia anual media del SAW en España fue de 1,1 caso por cada 10 millones de habitantes (IC del 95 %, 0,45-2,33). El riesgo relativo fue mayor en los varones que en las mujeres (2,42). El diagnóstico de SWA se establece a una edad más avanzada en las mujeres (mediana de 47 años) que en los varones (mediana de 5,5 años). Únicamente los varones ingresaron en el hospital en al menos 10 ocasiones diferentes y todas las muertes se detectaron en varones. La tasa de mortalidad intrahospitalaria fue del 9,28 % en el SAW y la mayoría de las muertes se asociaron a hemorragia cerebral o infección. Conclusiones: El SWA, una enfermedad rara, se diagnostica a una edad más avanzada en las mujeres y la mortalidad se observó exclusivamente en varones, asociada en la mayoría de los casos a hemorragia cerebral e infección.

8.
J Clin Pathol ; 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37977655

RESUMO

AIMS: The prognostic impact of programmed death-ligand 1 (PD-L1) cells in classic Hodgkin lymphoma (cHL) tumour microenvironment remains undefined. METHODS: Model development via Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis guidelines were followed. PD-L1+ and CD30+ tumoral Reed-Sternberg cells were quantified through whole slide imaging and digital image analysis in 155 digital histopathological slides of cHL. Univariate and multivariate survival analyses were performed. The analyses were reproduced for patients with advanced stages (IIB, III and IV) using the Advanced-stage cHL International Prognostic Index. RESULTS: The PD-L1/CD30 ratio was statistically significantly associated with survival outcomes. Patients with a PD-L1/CD30 ratio above 47.1 presented a shorter overall survival (mean OS: 53.7 months; 95% CI: 28.7 to 78.7) in comparison with patients below this threshold (mean OS: 105.4 months; 95% CI: 89.6 to 121.3) (p=0.04). When adjusted for covariates, the PD-L1/CD30 ratio retained prognostic impact, both for the OS (HR: 1.005; 95% CI: 1.002 to 1.008; p=0.000) and the progression-free survival (HR: 3.442; 95% CI: 1.045 to 11.340; p=0.04) in a clinical and histopathological multivariate model including the male sex (HR: 3.551; 95% CI: 0.986 to 12.786; p=0.05), a percentage of tumoral cells ≥10.1% (HR: 1.044; 95% CI: 1.003 to 1.087; p=0.03) and high risk International Prognostic Score (≥3 points) (HR: 6.453; 95% CI: 1.970 to 21.134; p=0.002). CONCLUSIONS: The PD-L1/CD30 ratio identifies a group of cHL patients with an increased risk of treatment failure. Its clinical application can be performed as it constitutes an easy to implement pathological information in the diagnostic work-up of patients with cHL.

9.
Rev Esp Patol ; 56(4): 233-242, 2023.
Artigo em Espanhol | MEDLINE | ID: mdl-37879820

RESUMO

INTRODUCTION: Lung cancer is the leading cause of cancer death in our country. Non-small cell lung cancer (NSCLC) represents the paradigm of personalized medicine. The main objective of this study is analysing the distribution of the most frequently described clinically significant variants in NSCLC, in our environment. MATERIAL AND METHODS: We studied the immunohistochemical expression of TTF1, p40 and PD-L1 and the genetic variants frequency using Next-Generation Sequencing (NGS) with a panel of 52 genes, in 174 NSCLC paraffin-embedded samples in 169 patients (111 men and 52 women) from the province of Cádiz. RESULTS: The immunohistochemical expression of TTF1, p40 and PD-L1 was positive in 87%, 0% and 46% in adenocarcinoma, and 0%, 100% and 41% in squamous cell carcinoma. In NGS, the most common single nucleotide variants (SNVs) were KRAS (36%), EGFR (14%), BRAF (10%), PIK3CA (8%), and MET (3%). The most frequent copy number variants (CNVs) were amplifications in NF1 (30%), EGFR (18%), CCND1 (9%), MYC (9%) and KRAS (7%). In women, SNV in EGFR are more frequent than in men (P<.0001). Adenocarcinoma is the most frequent histological type with SNV in KRAS (P=.007361) or in EGFR (P<.0001). Gene fusions were detected in 16 patients (9.47%), in 9 cases in the MET gene. CONCLUSIONS: We detected associations, not described so far, between immunohistochemical expression and specific gene variants, which could have an impact on the treatment of NSCLC patients.


Assuntos
Adenocarcinoma , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Masculino , Humanos , Feminino , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Antígeno B7-H1 , Proteínas Proto-Oncogênicas p21(ras) , Adenocarcinoma/genética , Receptores ErbB/genética
10.
Sci Rep ; 13(1): 13492, 2023 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-37596295

RESUMO

Tissue engineering is a relatively recent research area aimed at developing artificial tissues that can restore, maintain, or even improve the anatomical and/or functional integrity of injured tissues. Otolaryngology, as a leading surgical specialty in head and neck surgery, is a candidate for the use of these advanced therapies and medicinal products developed. Nevertheless, a knowledge-based analysis of both areas together is still needed. The dataset was retrieved from the Web of Science database from 1900 to 2020. SciMAT software was used to perform the science mapping analysis and the data for the biomedical translation identification was obtained from the iCite platform. Regarding the analysis of the cognitive structure, we find consolidated research lines, such as the generation of cartilage for use as a graft in reconstructive surgery, reconstruction of microtia, or the closure of perforations of the tympanic membrane. This last research area occupies the most relevant clinical translation with the rest of the areas presenting a lower translational level. In conclusion, Tissue engineering is still in an early translational stage in otolaryngology, otology being the field where most advances have been achieved. Therefore, although otolaryngologists should play an active role in translational research in tissue engineering, greater multidisciplinary efforts are required to promote and encourage the translation of potential clinical applications of tissue engineering for routine clinical use.


Assuntos
Microtia Congênita , Otolaringologia , Humanos , Engenharia Tecidual , Ciência Translacional Biomédica , Cognição
11.
J Exp Bot ; 74(15): 4597-4612, 2023 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-37115664

RESUMO

The differential stomatal regulation of transpiration among plant species in response to water deficit is not fully understood, although several hydraulic traits have been reported to influence it. This knowledge gap is partly due to a lack of direct and concomitant experimental data on transpiration, stomatal conductance, and hydraulic traits. We measured sap flux density (Js), stomatal conductance (gs), and different hydraulic traits in five crop species. Our aim was to contribute to establishing the causal relationship between water consumption and its regulation using a hydraulic trait-based approach. The results showed that the species-specific regulation of Js by gs was overall coordinated with the functional hydraulic traits analysed. Particularly relevant was the negative and significant relationship found between the Huber value (Hv) and its functional analogue ratio between maximum Js and gs (Jsmax/gsmax) which can be understood as a compensation to maintain the hydraulic supply to the leaves. The Hv was also significantly related to the slope of the relationship between gs and Js response to vapour pressure deficit and explained most of its variability, adding up to evidence recognizing Hv as a major trait in plant water relations. Thus, a hydraulic basis for regulation of tree water use should be considered.


Assuntos
Transpiração Vegetal , Árvores , Árvores/fisiologia , Pressão de Vapor , Transpiração Vegetal/fisiologia , Folhas de Planta/fisiologia , Água , Produtos Agrícolas , Estômatos de Plantas/fisiologia
14.
Reumatol. clín. (Barc.) ; 19(1): 45-48, Ene. 2023. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-214164

RESUMO

Antecedentes y objetivo: La tuberculosis osteoarticular representa el 2-5% de las presentaciones de la tuberculosis. El objetivo fue calcular la incidencia y describir las características epidemiológicas de los pacientes con tuberculosis osteoarticular que recibieron atención hospitalaria en España entre 1997-2018. Método: Se realizó un estudio retrospectivo de los pacientes atendidos con tuberculosis osteoarticular en los hospitales españoles entre los años 1997 y 2018, a través del Conjunto Mínimo Básico de Datos al alta hospitalaria, usando los códigos del CIE-9-MC y CIE-10. Resultados principales: Se detectaron 5710 pacientes con tuberculosis osteoarticular durante los 22 años. La incidencia anual media del periodo se situó en 6 casos por millón de habitantes (IC95% 5,58-6,30). Existió una diferencia significativa entre la incidencia media anual por millón de habitantes del primer periodo (1997-2007) de 6,95 y la del segundo (2008-2018) de 5,35 (p<0,001). Conclusión: La incidencia de la tuberculosis osteoarticular en España es baja, se ha reducido a lo largo de 22 años y predomina en hombres.(AU)


Background and objective: Osteoarticular tuberculosis represents 2-5% of the manifestations of tuberculosis. The objective was to calculate the incidence and describe the epidemiological characteristics of patients with osteoarticular tuberculosis who received hospital care in Spain between 1997-2018. Methods: A retrospective study was conducted of patients treated with osteoarticular tuberculosis in Spanish hospitals between 1997 and 2018, using the data from the Minimum Basic Data Set at hospital discharge, using the ICD-9-CM and ICD-10 codes. Results: 5710 patients with osteoarticular tuberculosis were detected over the 22 years in Spain. The mean annual incidence for the period was 6 cases per million inhabitants (95% CI 5.58-6.30). There was a significant difference between the mean annual incidence per million inhabitants of the first period (1997-2007) of 6.95 and that of the second (2008-2018) of 5.35 (p <.001). Conclusions: The incidence of osteoarticular tuberculosis in Spain is low, has reduced over 22 years and predominates in men.(AU)


Assuntos
Humanos , Masculino , Feminino , Tuberculose Osteoarticular/epidemiologia , Incidência , Tuberculose , Espanha , Estudos Retrospectivos
15.
Anat Sci Educ ; 16(1): 171-182, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35068075

RESUMO

Students' metacognitive skills and perceptions are considered important variables for high-quality learning. In this study, students' perceptions were used to identify histological threshold concepts (integrative, irreversible, transformative, and troublesome) in three health sciences curricula. A specific questionnaire was developed and validated to characterize students' perceptions of histological threshold concepts. A sample of 410 undergraduate students enrolled in the dentistry, medicine, and pharmacy degree programs participated in the study. Concepts assessed in the study were clustered to ten categories (factors) by exploratory and confirmatory factor analysis. Concepts linked to tissue organization and tissue functional states received the highest scores from students in all degree programs, suggesting that the process of learning histology requires the integration of both static concepts related to the constituent elements of tissues and dynamic concepts such as stem cells as a tissue renewal substrate, or the euplasic, proplasic and retroplasic states of tissues. The complexity of integrating static and dynamic concepts may pose a challenging barrier to the comprehension of histology. In addition, several differences were detected among the students in different degree programs. Dentistry students more often perceived morphostructural concepts as threshold concepts, whereas medical students highlighted concepts related to two-dimensional microscopic identification. Lastly, pharmacy students identified concepts related to tissue general activity as critical for the comprehension and learning of histology. The identification of threshold concepts through students' perceptions is potentially useful to improve the teaching and learning process in health sciences curricula.


Assuntos
Anatomia , Estudantes de Medicina , Humanos , Anatomia/educação , Currículo , Aprendizagem , Estudantes de Medicina/psicologia , Percepção
16.
Front Oncol ; 12: 1000762, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338756

RESUMO

Classic Hodgkin lymphoma (cHL) constitutes the most frequent lymphoma in young adults. Its histopathology is unique as a scattered tumor population, termed Hodgkin Reed-Sternberg (HRS) cells is diluted in a prominent tumor microenvironment (TME) composed of T lymphocytes, B lymphocytes, macrophages, neutrophils, eosinophils and histiocytes. Traditionally, the identification of prognostic biomarkers in the cHL TME has required visual inspection and manual counting by pathologists. The advent of whole-slide imaging (WSI) and digital image analysis methods could significantly contribute to improve this essential objective in cHL research, as a 10-20% of patients are still refractory or relapsed after conventional chemotherapy. In this work, we have digitized a total of 255 diagnostic cHL slides and quantified the proportion of HRS cells (CD30), B cells (CD20) and T cells (CD3) by digital image analysis. Data obtained where then correlated with the overall survival (OS) and progression free survival (PFS) of cHL patients. Quantification of HRS cells, B cells and T cells reflects the biological heterogeneity of the different cHL histological subtypes analyzed. A percentage of 2.00% of HRS cells statistically significantly discriminated between patients achieving a complete metabolic response (CMR) and refractory or relapsed (R/R) patients both for the OS (P=0.001) and PFS (P=0.005). Furthermore, patients with a percentage of T cells below the 26.70% in the TME showed a statistically significantly shorter OS (P=0.019) and PFS (P=0.041) in comparison with patients above this threshold. A subgroup of patients with a low content of T cells and high content of HRS cells exhibited a special aggressive clinical course. Currently, there is the need to implement quantitative and easy scalable methods to enhance clinical translation, as the cHL TME plays a central role in the clinical course of the disease. The results of this study could contribute to the identification of prognostic biomarkers specifically looking at the cHL TME and their inclusion in future clinical trials.

17.
Mol Omics ; 18(10): 1015-1028, 2022 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-36382626

RESUMO

Digital pathology and genomics are increasingly used to improve our understanding of lymphoid neoplasms. Algorithms for quantifying cell populations in the lymph node and genetics can be integrated to identify new biomarkers with prognostic impact in classic Hodgkin lymphoma (cHL). In 16 cHL patients, we have performed whole slide imaging (WSI) analysis and quantification of CD30+, CD20+, CD3+ and MUM1+ cells in whole tissue slides, and Next Generation Sequencing (NGS) in formalin fixed paraffin-embedded (FFPE) tissue, using a widely used NSG panel (Oncomine® Focus Assay) to define genetic variants underlying tumor development. The different cell populations could be successfully identified in scanned slides of cHL, supporting the inclusion of WSI in the histopathological evaluation of cHL as an adequate method for the quantification of different cell populations. We also performed genetic profiling in FFPE samples of cHL leading to the identification of copy number variations in the Neurofibromin 1 gene (17q11.2) and the Androgen Receptor gene (Xq12) accompanied by chromosomal gains and losses in CDK4, KRAS and FGFR2 genes. Progression-free survival (PFS) was statistically significantly higher in cHL patients with amplification in the NF1 gene combined with CD3+ cells above 28.6% (p = 0.006) and MUM1+ cells above 21.8% (p < 0.001). Moreover, patients with MUM1+ cells above 21.8% showed a statistically significantly higher PFS when combined with amplification of the AR gene (p < 0.001) and wild-type KRAS (p < 0.001). The integration of WSI analysis and DNA sequencing could be useful to improve our understanding of the biology of cHL and define risk subgroups.


Assuntos
Doença de Hodgkin , Humanos , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/genética , Doença de Hodgkin/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Variações do Número de Cópias de DNA , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/genética
18.
Artigo em Inglês | MEDLINE | ID: mdl-36078219

RESUMO

(1) Background: Fear of falling has become a significant health problem in older adults and is already considered as important as falling because of its long-term detrimental effects on older adults' physical and psychosocial functioning. The aim of this study was to analyze the associations between both upper and lower limb strength, gait parameters and cognitive impairment with fear of falling in older adults. (2) Methods: A cross-sectional study involving 115 older-adult participants was used to assess the impact of both upper (Handgrip dynamometer, TKK 5401 Grip-D, Takey, Tokyo, Japan) and lower limb strength (Chair stand test), gait parameters (OptoGait-System Bolzano, Bolzano, Italy) and cognitive impairment (COWAT word association test) with fear of falling in older adults (Falls Efficacy Scale-International FES-I). (3) Results: Multivariate linear regression analysis showed several independent associations with the fear of falling. A higher time to perform the Chair Stand test was associated with higher scores in FES-I (R2 = 0.231), while a lower score in both Semantic Fluency (S COWA) and Phonologic Fluency (P COWA) was associated with a decreased score in FES-I (R2 = 0.052 and 0.035). (4) Conclusions: Both higher step and stride length (OptoGait), lower body strength (Chair test) and both poorer semantic (S COWA) and phonologic (P COWA) fluency were all associated with fear of falling.


Assuntos
Disfunção Cognitiva , Medo , Idoso , Disfunção Cognitiva/epidemiologia , Estudos Transversais , Medo/psicologia , Força da Mão , Humanos , Força Muscular , Desempenho Físico Funcional
19.
Artigo em Inglês | MEDLINE | ID: mdl-36078324

RESUMO

BACKGROUND: The purpose of the present study was to compare the influence of an acute bout of high-intensity functional training (HIFT) with an acute bout of moderate-intensity continuous training (MICT) on measures of cognitive function. METHODS: Sixty-nine young adults (Mean ± SD: age = 21.01 ± 2.79 yrs; body mass = 69.65 ± 6.62 kg; height = 1.74 ± 0.05 m; Body Mass Index = 22.8 ± 1.41) gave informed consent and were randomly divided into three groups. The HIFT group, with 27 participants, performed a high-intensity (>85% Max. HR) circuit of functional exercises for 30 min. The MICT group, with 28 participants, performed moderate-intensity (70-80% Max. HR) continuous training on a cyclo-ergometer. The control group did not perform any activity. The Stroop Test, Word Recall and N-Back Test were completed to assess during the familiarization period, immediately before and immediately after the training's bouts. RESULTS: The repeated measures ANOVA did not show significant mean differences for any group. However, the T-Test for the paired samples demonstrated very significant differences in the Stroop Test, in terms of fastest response time (FRT; mean difference (MD) = -1.14, p < 0.01, d = 0.9), mean response time (MRT; MD = -2.16, p < 0.01, d = 0.66) and the number of correct answers (NCA; MD = 1.08, p < 0.05, d = 0.5) in the HIFT group and in the MICT group (FRT; MD = -1.79, p < 0.01, d = 0.9), (MRT; MD = -3.07, p < 0.01, d = 0.9) (NCA; MD = 1.54, p < 0.05, d = 0.5). CONCLUSIONS: There were no differences in the control group. HIFT and MICT may elicit specific influences on cognitive function, mainly in executive function and selective attention.


Assuntos
Treinamento Intervalado de Alta Intensidade , Adolescente , Adulto , Índice de Massa Corporal , Cognição , Terapia por Exercício , Humanos , Adulto Jovem
20.
Plant Cell Environ ; 45(8): 2366-2380, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35538021

RESUMO

The relative contribution of carbon sources generated from leaves and fruits photosynthesis for triacylglycerol biosynthesis in the olive mesocarp and their interaction with water stress was investigated. With this aim, altered carbon source treatments were combined with different irrigation conditions. A higher decrease in mesocarp oil content was observed in fruits under girdled and defoliated shoot treatment compared to darkened fruit conditions, indicating that both leaf and fruit photosynthesis participate in carbon supply for oil biosynthesis being leaves the main source. The carbon supply and water status affected oil synthesis in the mesocarp, regulating the expression of DGAT and PDAT genes and implicating DGAT1-1, DGAT2, PDAT1-1, and PDAT1-2 as the principal genes responsible for triacylglycerol biosynthesis. A major role was indicated for DGAT2 and PDAT1-2 in well-watered conditions. Moreover, polyunsaturated fatty acid content together with FAD2-1, FAD2-2 and FAD7-1 expression levels were augmented in response to modified carbon supply in the olive mesocarp. Furthermore, water stress caused an increase in DGAT1-1, DGAT1-2, PDAT1-1, and FAD2-5 gene transcript levels. Overall, these data indicate that oil content and fatty acid composition in olive fruit mesocarp are regulated by carbon supply and water status, affecting the transcription of key genes in both metabolic pathways.


Assuntos
Olea , Carbono/metabolismo , Desidratação/metabolismo , Ácidos Graxos/metabolismo , Frutas/genética , Frutas/metabolismo , Olea/genética , Olea/metabolismo , Triglicerídeos/metabolismo
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