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1.
Proc Natl Acad Sci U S A ; 121(25): e2400566121, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38870061

RESUMEN

Intrinsic and acquired resistance to mitogen-activated protein kinase inhibitors (MAPKi) in melanoma remains a major therapeutic challenge. Here, we show that the clinical development of resistance to MAPKi is associated with reduced tumor expression of the melanoma suppressor Autophagy and Beclin 1 Regulator 1 (AMBRA1) and that lower expression levels of AMBRA1 predict a poor response to MAPKi treatment. Functional analyses show that loss of AMBRA1 induces phenotype switching and orchestrates an extracellular signal-regulated kinase (ERK)-independent resistance mechanism by activating focal adhesion kinase 1 (FAK1). In both in vitro and in vivo settings, melanomas with low AMBRA1 expression exhibit intrinsic resistance to MAPKi therapy but higher sensitivity to FAK1 inhibition. Finally, we show that the rapid development of resistance in initially MAPKi-sensitive melanomas can be attributed to preexisting subclones characterized by low AMBRA1 expression and that cotreatment with MAPKi and FAK1 inhibitors (FAKi) effectively prevents the development of resistance in these tumors. In summary, our findings underscore the value of AMBRA1 expression for predicting melanoma response to MAPKi and supporting the therapeutic efficacy of FAKi to overcome MAPKi-induced resistance.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Resistencia a Antineoplásicos , Melanoma , Inhibidores de Proteínas Quinasas , Melanoma/tratamiento farmacológico , Melanoma/genética , Melanoma/metabolismo , Humanos , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Línea Celular Tumoral , Animales , Ratones , Quinasa 1 de Adhesión Focal/metabolismo , Quinasa 1 de Adhesión Focal/antagonistas & inhibidores , Ensayos Antitumor por Modelo de Xenoinjerto , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Femenino
2.
Brief Bioinform ; 25(3)2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38701414

RESUMEN

Gliomas are the most common type of malignant brain tumors, with glioblastoma multiforme (GBM) having a median survival of 15 months due to drug resistance and relapse. The treatment of gliomas relies on surgery, radiotherapy and chemotherapy. Only 12 anti-brain tumor chemotherapies (AntiBCs), mostly alkylating agents, have been approved so far. Glioma subtype-specific metabolic models were reconstructed to simulate metabolite exchanges, in silico knockouts and the prediction of drug and drug combinations for all three subtypes. The simulations were confronted with literature, high-throughput screenings (HTSs), xenograft and clinical trial data to validate the workflow and further prioritize the drug candidates. The three subtype models accurately displayed different degrees of dependencies toward glutamine and glutamate. Furthermore, 33 single drugs, mainly antimetabolites and TXNRD1-inhibitors, as well as 17 drug combinations were predicted as potential candidates for gliomas. Half of these drug candidates have been previously tested in HTSs. Half of the tested drug candidates reduce proliferation in cell lines and two-thirds in xenografts. Most combinations were predicted to be efficient for all three glioma types. However, eflornithine/rifamycin and cannabidiol/adapalene were predicted specifically for GBM and low-grade glioma, respectively. Most drug candidates had comparable efficiency in preclinical tests, cerebrospinal fluid bioavailability and mode-of-action to AntiBCs. However, fotemustine and valganciclovir alone and eflornithine and celecoxib in combination with AntiBCs improved the survival compared to AntiBCs in two-arms, phase I/II and higher glioma clinical trials. Our work highlights the potential of metabolic modeling in advancing glioma drug discovery, which accurately predicted metabolic vulnerabilities, repurposable drugs and combinations for the glioma subtypes.


Asunto(s)
Glioma , Humanos , Glioma/tratamiento farmacológico , Glioma/metabolismo , Glioma/patología , Cannabidiol/uso terapéutico , Cannabidiol/farmacología , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Animales , Modelos Biológicos , Línea Celular Tumoral , Compuestos Organofosforados/uso terapéutico , Compuestos Organofosforados/farmacología
3.
BMC Infect Dis ; 24(1): 99, 2024 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-38238680

RESUMEN

BACKGROUND: Respiratory syncytial virus (RSV) is a highly infectious disease that poses a significant clinical and medical burden, as well as social disruption and economic costs, recognized by the World Health Organization as a public health issue. After several failed attempts to find preventive candidates (compounds, products, including vaccines), new alternatives might be available, one being nirsevimab, the first and only option approved for RSV prevention in neonates and infants during their first RSV season. The objective of this study was to develop a novel multi-criteria decision analysis (MCDA) framework for RSV antibody-based preventive alternatives and to use it to assess the value of nirsevimab vs. placebo as a systematic immunization approach to prevent RSV in neonates and infants during their first RSV season in Spain. METHODS: Based on a pre-established model called Vaccinex, an ad-hoc MCDA framework was created to reflect relevant attributes for the assessment of current and future antibody-based preventive measures for RSV. The estimated value of nirsevimab was obtained by means of an additive linear model combining weights and scores assigned by a multidisciplinary committee of 9 experts. A retest and three sensitivity analyses were conducted. RESULTS: Nirsevimab was evaluated through a novel framework with 26 criteria by the committee as a measure that adds value (positive final estimated value: 0.56 ± 0.11) to the current RSV scenario in Spain, by providing a high efficacy for prevention of neonates and infants. In addition, its implementation might generate cost savings in hospitalizations and to the healthcare system and increase the level of public health awareness among the general population, while reducing health inequities. CONCLUSIONS: Under a methodology with increasing use in the health field, nirsevimab has been evaluated as a measure which adds value for RSV prevention in neonates and infants during their first RSV season in Spain.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Recién Nacido , Lactante , Humanos , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Infecciones por Virus Sincitial Respiratorio/prevención & control , Antivirales , España , Técnicas de Apoyo para la Decisión
4.
Pediatr Dev Pathol ; 27(1): 96-101, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37903152

RESUMEN

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is an indolent non-Hodgkin lymphoma rarely seen in pediatric patients. MALT lymphoma most commonly involves the gastrointestinal tract or peri-orbital tissues, potentially as sequela of chronic antigenic stimulation or immune dysregulation. Rare cases of MALT lymphoma arising from the gynecologic tract have been reported in older adult patients. We present the unique case of a 16-year-old postpubescent female with MALT lymphoma localized to the gynecologic tract, who initially presented with abdominal fullness, abnormal uterine bleeding, and obstructive acute kidney injury secondary to urinary outflow obstruction. Intraoperatively, dense fibrosis of the uterus and left fallopian tube was noted which mimicked abdominal cocoon syndrome. She was treated with 6 cycles of bendamustine and rituximab with complete anatomic and metabolic remission. In this report we highlight a very unusual presentation of a rare malignancy in the pediatric population as well as unique treatment considerations given this patient's young age and tumor location.


Asunto(s)
Linfoma de Células B de la Zona Marginal , Linfoma no Hodgkin , Neoplasias Gástricas , Humanos , Femenino , Niño , Adolescente , Anciano , Linfoma de Células B de la Zona Marginal/diagnóstico , Linfoma de Células B de la Zona Marginal/complicaciones
5.
Artículo en Inglés | MEDLINE | ID: mdl-38733285

RESUMEN

BACKGROUND: Immunosuppressed (IS) patients, particularly solid organ transplant recipients and those on immunosuppressive therapy, face a higher incidence and recurrence of nonmelanoma skin cancers (NMSC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Mohs micrographic surgery (MMS) is the preferred treatment for high-risk NMSC due to its high cure rate and margin examination capabilities. However, IS patients may experience more complications, such as surgical site infections, and a greater risk of recurrence, making their outcomes a subject of interest. OBJECTIVES: This study aimed to compare IS and immunocompetent (IC) patients undergoing MMS for NMSC in terms of baseline characteristics, intra- and post-surgical complications, and postoperative recurrence rates. METHODS: The study utilized data from the REGESMOHS registry, a 7-year prospective cohort study in Spain. It included 5226 patients, categorizing them into IC (5069) and IS (157) groups. IS patients included solid organ transplant recipients, those on immunosuppressive treatments, individuals with haematological tumours and HIV-positive patients. Patient data, tumour characteristics, surgical details and outcomes were collected and analysed. RESULTS: IS patients demonstrated a higher proportion of SCC, multiple synchronous tumours and tumours invading deeper structures. Complex closures, unfinished MMS and more surgical sections were observed in the IS group. Although intra-operative morbidity was higher among IS patients, this difference became non-significant when adjusted for other variables such as year of surgery, antiplatelet/anticoagulant treatment or type of closure. Importantly, IS patients had a substantially higher recurrence rate (IRR 2.79) compared to IC patients. CONCLUSIONS: This study suggests that IS patients may be at a higher risk of development of AE such as bleeding or tumour necrosis and are at a higher risk of tumour recurrence. Close follow-up and consideration of the specific characteristics of NMSC in IS patients are crucial. Further research with extended follow-up is needed to better understand the long-term outcomes for this patient group.

6.
An Acad Bras Cienc ; 96(2): e20230043, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38808874

RESUMEN

Sesbania virgata (Cav.) Pers. seeds are protein sources with health and environmental benefits. In this research, proteins with lectin activity were identified in a protein fraction from S. virgata seeds (PFLA), as well its antioxidant and antimicrobial potentials, in addition to cytotoxic effects. To obtain PFLA, seed flour was homogenized in Glycine-NaOH (100 mM; pH 9.0; NaCl 150 mM) and precipitated in ammonium sulfate. PFLA concentrates bioactive lectins (32 HU/mL, 480 HU/gFa, 18.862 HU/mgP) and essential amino acids (13.36 g/100g protein). PFLA exerts antioxidant activity, acting as a promising metal chelating agent (~77% of activity). Analyzes of cell culture assay results suggest that antioxidant activity of PFLA may be associated with the recruitment of essential molecules to prevent the metabolic impairment of cells exposed to oxidative stress. PFLA (256 - 512 µg/mL) also exhibits antifungal activity, inhibiting the growth of Aspergillus flavus, Candida albicans, Candida tropicalis and Penicillium citrinum. Cytotoxic analysis indicates a tendency of low interference in the proliferation of 3T3 and HepG2 cells in the range of PFLA concentrations with biological activity. These findings support the notion that PFLA is a promising adjuvant to be applied in current policies on the management of metal ion chelation and fungal infections.


Asunto(s)
Antifúngicos , Antioxidantes , Semillas , Sesbania , Semillas/química , Antioxidantes/farmacología , Antifúngicos/farmacología , Antifúngicos/aislamiento & purificación , Antifúngicos/química , Sesbania/química , Humanos , Proteínas de Plantas/farmacología , Pruebas de Sensibilidad Microbiana , Animales , Ratones , Extractos Vegetales/farmacología , Extractos Vegetales/química , Células Hep G2
7.
Sensors (Basel) ; 24(2)2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38257623

RESUMEN

The accurate measurement of joint angles during patient rehabilitation is crucial for informed decision making by physiotherapists. Presently, visual inspection stands as one of the prevalent methods for angle assessment. Although it could appear the most straightforward way to assess the angles, it presents a problem related to the high susceptibility to error in the angle estimation. In light of this, this study investigates the possibility of using a new approach to angle calculation: a hybrid approach leveraging both a camera and LiDAR technology, merging image data with point cloud information. This method employs AI-driven techniques to identify the individual and their joints, utilizing the cloud-point data for angle computation. The tests, considering different exercises with different perspectives and distances, showed a slight improvement compared to using YOLO v7 for angle calculation. However, the improvement comes with higher system costs when compared with other image-based approaches due to the necessity of equipment such as LiDAR and a loss of fluidity during the exercise performance. Therefore, the cost-benefit of the proposed approach could be questionable. Nonetheless, the results hint at a promising field for further exploration and the potential viability of using the proposed methodology.


Asunto(s)
Terapia por Ejercicio , Fisioterapeutas , Humanos , Ejercicio Físico , Tecnología , Extremidad Superior
8.
Clin Immunol ; 256: 109806, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37827267

RESUMEN

The study of phenotypic and functional characteristics of immune cells involved in host response to SARS-CoV-2 is relevant for understanding COVID-19 pathogenesis and individual differences in disease progression. We have analyzed chemokine receptor expression in SARS-CoV-2-specific CD4+ T lymphocytes from vaccinated donors, and have found an increase of CCR9+ and CCR6+ cells. CCR9+ specific CD4+ cells are enriched in T regulatory (Treg) lymphocytes. These cells specifically show heterogeneous regulatory activity, associated with different profiles of CCR9/CCR6 expression, individual differences in IL-10 and IL-17 production, and variable FoxP3 and Notch4 expression. A higher heterogeneity in FoxP3 is selectively observed in convalescent individuals within vaccinated population. Accordingly, SARS-CoV-2-specific CD4+ lymphocytes from COVID-19 patients are also enriched in CCR9+ and CCR6+ cells. CCR6+ specific Treg lymphocytes are mainly increased in critically ill individuals, indicating a preferential role for these cells in lung injury pathogenesis. We provide experimental evidence for a SARS-CoV-2-specific Treg population with increased plasticity, which may contribute to the differential pathogenic response against SARS-CoV-2 among individuals, and underlie the development of autoimmune conditions following SARS-CoV-2 infection.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/metabolismo , Linfocitos T CD4-Positivos , Receptores de Quimiocina/metabolismo , Factores de Transcripción Forkhead/metabolismo , Linfocitos T Reguladores
9.
PLoS Comput Biol ; 18(1): e1009711, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-35085230

RESUMEN

Project-based learning (PBL) is a dynamic student-centred teaching method that encourages students to solve real-life problems while fostering engagement and critical thinking. Here, we report on a PBL course on metabolic network modelling that has been running for several years within the Master in Integrated Systems Biology (MISB) at the University of Luxembourg. This 2-week full-time block course comprises an introduction into the core concepts and methods of constraint-based modelling (CBM), applied to toy models and large-scale networks alongside the preparation of individual student projects in week 1 and, in week 2, the presentation and execution of these projects. We describe in detail the schedule and content of the course, exemplary student projects, and reflect on outcomes and lessons learned. PBL requires the full engagement of students and teachers and gives a rewarding teaching experience. The presented course can serve as a role model and inspiration for other similar courses.


Asunto(s)
Redes y Vías Metabólicas , Aprendizaje Basado en Problemas , Biología de Sistemas/educación , Humanos , Estudiantes , Pensamiento
10.
Pediatr Dev Pathol ; 26(4): 352-361, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37082924

RESUMEN

BACKGROUND: Focal nodular hyperplasia (FNH) is a benign liver lesion classically presenting in young females. In children, FNH is rare and its detailed clinicopathologic characteristics remain largely unknown. Furthermore, there are no studies comparing pediatric FNH features to those presenting in adults. METHODS: In this study, we analyzed a total of 47 FNH cases in pediatric patients (age range: 23 days to 18 years) from 3 centers and compared them to a cohort of 31 FNH cases in adult patients (age range: 20-64 years). RESULTS: Of the pediatric cases, 13 cases (28%) had a history of a prior malignancy of which 4 were treated with chemoradiation and stem cell transplantation (SCT), 5 with chemoradiation alone and 3 with chemotherapy and SCT. In the pediatric cases 41 (87%) had a central scar and 46 (98%) had fibrous septa. Both pediatric and adult FNH were more common in female patients. Cases in pediatric patients were also significantly associated with larger size (P = .047), absence of dystrophic vessels (P = .001), absence of sinusoidal dilatation (P = .029), pseudoacini formation (P = .013), and steatosis (P = .029). CONCLUSION: In our experience although most cases of pediatric FNH show the classic histologic features seen in adults, some significant differences exist, and awareness of these findings could aid in the evaluation of these rare cases.


Asunto(s)
Hiperplasia Nodular Focal , Neoplasias Hepáticas , Neoplasias , Adulto , Niño , Femenino , Humanos , Persona de Mediana Edad , Adulto Joven , Quimioradioterapia , Hiperplasia Nodular Focal/diagnóstico , Hiperplasia Nodular Focal/terapia , Hiperplasia Nodular Focal/complicaciones , Hígado/patología , Neoplasias Hepáticas/patología , Neoplasias/patología , Estudios Retrospectivos , Recién Nacido , Lactante , Preescolar , Adolescente , Masculino
11.
Artículo en Inglés | MEDLINE | ID: mdl-36950898

RESUMEN

INTRODUCTION: There is still a need to develop a simple algorithm to identify patients likely to need complex Mohs micrographic surgery (MMS) and optimize MMS schedule. The main objectives of this study are to identify factors associated with a complex MMS and develop a predictor model of the number of stages needed in surgery and the need for a complex closure. MATERIALS AND METHODS: A nationwide prospective cohort study (REGESMOHS, the Spanish Mohs surgery registry) was conducted including all patients with a histological diagnosis of basal cell carcinoma (BCC). Factors related to three or more stages and a complex closure (that needing a flap and/or a graft) were explored and predictive models were constructed and validated to construct the REGESMOSH scale. RESULTS: A total of 5226 patients that underwent MMS were included in the REGESMOHS registry, with 4402 (84%) having a histological diagnosis of BCC. A total of 3689 (88.9%) surgeries only needed one or two stages and 460 (11.1%) required three or more stages. A model to predict the need for three or more stages included tumour dimension, immunosuppression, recurrence, location in risk areas, histological aggressiveness and previous surgery. Regarding the closure type, 1616 (38.8%) surgeries were closed using a non-complex closure technique and 2552 (61.2%) needed a complex closure. A model to predict the need for a complex closure included histological aggressiveness, evolution time, patient age, maximum tumour dimension and location. CONCLUSION: We present a model to predict MMS needing ≥3 stages and a complex closure based on epidemiological and clinical data validated in a large population (with real practice variability) including different centres that could be easily implemented in clinical practice. This model could be used to optimize surgery schedule and properly inform patients about the surgery duration.

12.
Mikrochim Acta ; 190(3): 97, 2023 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-36806984

RESUMEN

A fast and efficient method was developed for obtaining europium(III)-doped surface-modified carbon dots with a hydrophobic coating. This surface functionalization improved the dispersibility of the nanoparticles in non-polar media, as well as modified the accessibility of water molecules to the europium ions. These two features allowed studying the application of doped carbon dots as moisture nanochemosensor, demonstrating high stability over time of both the photoluminescent signal intensity and the stability of the dispersions. The developed nanochemosensor was used to determine water in toluene with a detection limit of 8.5 × 10-4 M and a quantification limit of 2.4 × 10-3 M. The proposed system matches and even improves other methodologies for water determination in organic solvents; it has a low detection limit and a fast response time (almost instantaneous) and requires neither expensive material nor trained personnel. The results suggest a promising future for the development of a new sensing phase for moisture determination in lubricant base oil.

13.
J Clin Pharm Ther ; 47(12): 2020-2029, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35929568

RESUMEN

WHAT IS KNOWN AND OBJECTIVE: Immune-mediated inflammatory diseases (IMIDs) are a group of chronic and highly disabling diseases. The objective is to evaluate the satisfaction with the health care received by patients with the most prevalent IMIDs in Spain: inflammatory bowel disease (IBD), psoriasis (Ps) psoriatic arthritis (PsA), rheumatoid arthritis (RA) and spondyloarthropathies (SpAs), and to determine the factors that influence patient satisfaction. METHODS: This was an observational, cross-sectional, multicentre study in a real-world evidence context conducted in the Pharmacy Service in four hospital centres of the Community of Madrid that belong to the National Health System. The study included adult patients diagnosed with an IMID who had attended the Pharmacy Service at least three times. The patients were grouped according to the main IMID. Health care satisfaction was evaluated using the chronic patient experience assessment (IEXPAC) questionnaire. The responses to IEXPAC are grouped into three factors: productive interactions, new relational model and patient self-management, with a total score from 0 (worst) to 10 (best experience). Health-related quality of life (HRQoL) was also evaluated using the EQ-5D-5L questionnaire, and pharmacological adherence was evaluated through the Morisky-Green test. RESULTS AND DISCUSSION: A total of 578 patients were analysed (IBD = 25.3%; Ps = 19.7%; SpAs = 18.7%; RA = 18.5%; PsA = 17.8%). The mean age (SD) was 49.8 (12.3) years and 50.7% were male. The average score (SD) for the total IEXPAC sample was 6.6 (1.9). RA was the IMID with the lowest score, at 5.83 (2.0), significantly lower than the scores of Ps (SD) [7.01 (1.7); p = 0.003], IBD [6.83 (1, 9); p = 0.012] and SpAs [6.80 (1.6); p = 0.001]. Productive interactions (SD) [8.5 (1.8)] and patient self-management (SD) [7.3 (2.3)] were the factors with the highest scores, and the new relational model had the lowest score (SD) [3.2 (2.7)]. Male gender, a longer time interval between medication administrations and a higher HRQoL were correlated with better patient satisfaction. Current biological therapy (according to the Anatomical Chemical classification system) also had a significant influence; patients treated with tumour necrosis factor inhibitors and interleukin inhibitors showed greater satisfaction than those treated with selective immunosuppressants. WHAT IS NEW AND CONCLUSION: The IEXPAC results show high general satisfaction with care quality reported by patients with IMIDs treated in the Pharmacy Service. However, there are areas of improvement in care quality specially health professional-patient communication, such as increasing access to information, and promoting and facilitating relationships with patients in similar conditions.


Asunto(s)
Artritis Psoriásica , Artritis Reumatoide , Enfermedades Inflamatorias del Intestino , Adulto , Humanos , Masculino , Persona de Mediana Edad , Femenino , Calidad de Vida , Estudios Transversales , Agentes Inmunomoduladores , Artritis Reumatoide/tratamiento farmacológico , Hospitales
14.
J Antimicrob Chemother ; 76(6): 1539-1546, 2021 05 12.
Artículo en Inglés | MEDLINE | ID: mdl-33837406

RESUMEN

OBJECTIVES: To investigate if the addition of cloxacillin to vancomycin enhances the activity of both monotherapies for treating MSSA and MRSA experimental endocarditis (EE) in rabbits. METHODS: Vancomycin plus cloxacillin was compared with the respective monotherapies and daptomycin. In vitro time-kill studies were performed using standard (105 cfu) and high (108 cfu) inocula of five MRSA, one glycopeptide-intermediate (GISA) and five MSSA strains. One MSSA (MSSA-678) and one MRSA (MRSA-277) strain were selected to be used in the in vivo model. A human-like pharmacokinetics model was applied and the equivalents of cloxacillin 2 g/4 h IV and daptomycin 6 mg/kg/day IV were administered. To optimize vancomycin activity, dosage was adjusted to achieve an AUC/MIC ≥400. RESULTS: Daptomycin sterilized significantly more vegetations than cloxacillin (13/13, 100% versus 9/15, 60%; P = 0.02) and showed a trend of better activity than vancomycin (10/14, 71%; P = 0.09) and vancomycin plus cloxacillin (10/14, 71%; P = 0.09) against MSSA-678. Addition of cloxacillin to vancomycin (13/15, 87%) was significantly more effective than vancomycin (8/16, 50%; P = 0.05) and showed similar activity to daptomycin (13/18, 72%; P = 0.6) against MRSA-277. In all treatment arms, the bacterial isolates recovered from vegetations were re-tested and showed the same daptomycin susceptibility as the original strains. CONCLUSIONS: Vancomycin plus cloxacillin proved synergistic and bactericidal activity against MRSA. Daptomycin was the most efficacious option against MSSA and similar to vancomycin plus cloxacillin against MRSA. In settings with high MRSA prevalence, vancomycin plus cloxacillin might be a good alternative for empirical therapy of S. aureus IE.


Asunto(s)
Daptomicina , Endocarditis Bacteriana , Endocarditis , Staphylococcus aureus Resistente a Meticilina , Animales , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Cloxacilina , Endocarditis/tratamiento farmacológico , Endocarditis Bacteriana/tratamiento farmacológico , Meticilina/farmacología , Resistencia a la Meticilina , Pruebas de Sensibilidad Microbiana , Conejos , Staphylococcus aureus , Vancomicina
15.
Exp Dermatol ; 30(5): 717-722, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33523531

RESUMEN

Characterization of patients, surgery procedures and the risk factors for dermatofibrosarcoma protuberans (DFSP) recurrences is poorly defined. In this study, we aimed to describe the demographics, tumor characteristics and interventions of DFSP treated with Mohs micrographic surgery (MSS) to determine the rate and risk factors for recurrence. Data were collected from REGESMOHS, a nationwide prospective cohort study of patients treated with MMS in Spain. From July 2013 to February 2020, 163 patients with DFSP who underwent MMS were included. DFSP was mostly located on trunk and extremities. Recurrent tumors had deeper tumor invasion and required higher number of MMS stages. Paraffin MMS was the most frequently used technique. Overall recurrence rate was 0.97 cases/100 person-years (95% IC = 0.36-2.57). No differences were found in epidemiological, tumor, surgery characteristics or surgical technique (frozen or paraffin MMS [p = 0.6641]) in terms of recurrence. Median follow-up time was 28.6 months with 414 patient-years of follow-up. In conclusion, we found an overall low recurrence rate of DFSP treated with MMS. None of the studied risk factors, including MMS techniques, was associated with higher risk for recurrence.


Asunto(s)
Dermatofibrosarcoma/cirugía , Procedimientos Quirúrgicos Dermatologicos/métodos , Cirugía de Mohs/métodos , Sistema de Registros , Neoplasias Cutáneas/cirugía , Dermatofibrosarcoma/patología , Humanos , Invasividad Neoplásica , Estudios Prospectivos , Factores de Riesgo , Neoplasias Cutáneas/patología
16.
Crit Rev Food Sci Nutr ; 61(9): 1470-1489, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32370550

RESUMEN

Bioactive peptides derived from food protein sources have been widely studied in the last years, and scientific researchers have been proving their role in human health, beyond their nutritional value. Several bioactivities have been attributed to these peptides, such as immunomodulatory, antimicrobial, antioxidant, antihypertensive, and opioid. Among them, metal-binding capacity has gained prominence. Mineral chelating peptides have shown potential to be applied in food products so as to decrease mineral deficiencies since peptide-metal complexes could enhance their bioavailability. Furthermore, many studies have been investigating their potential to decrease the Fe pro-oxidant effect by forming a stable structure with the metal and avoiding its interaction with other food constituents. These complexes can be formed during gastrointestinal digestion or can be synthesized prior to intake, with the aim to protect the mineral through the gastrointestinal tract. This review addresses: (i) the amino acid residues for metal-binding peptides and their main protein sources, (ii) peptide-metal complexation prior to or during gastrointestinal digestion, (iii) the function of metal (especially Fe, Ca, and Zn)-binding peptides on the metal bioavailability and (iv) their reactivity and possible pro-oxidant and side effects.


Asunto(s)
Complejos de Coordinación , Disponibilidad Biológica , Humanos , Minerales , Péptidos , Especies Reactivas de Oxígeno
17.
Acta Derm Venereol ; 101(11): adv00602, 2021 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-34694418

RESUMEN

Randomized studies to assess the efficacy of Mohs micrographic surgery in basal cell and squamous cell carcinomas are limited by methodological and ethical issues and a lack of long follow-up periods. This study presents the "real-life" results of a nationwide 7-years cohort on basal cell carcinoma and squamous cell carcinoma treated with Mohs micrographic surgery. A prospective cohort was conducted in 22 Spanish centres (from July 2013 to February 2020) and a multivariate analysis, including characteristics of patients, tumours, surgeries and follow-up, was performed. A total of 4,402 patients followed up for 12,111 patient-years for basal cell carcinoma, and 371 patients with 915 patient-years of follow-up for squamous cell carcinoma were recruited. Risk factors for recurrence included age, non-primary tumours and more stages or unfinished surgeries for both tumours, and immunosuppression for squamous cell carcinoma. Incidence rates of recurrence were 1.3 per 100 person-years for basal cell carcinoma (95% confidence interval 1.1-1.5) and 4.5 for squamous cell carcinoma (95% confidence interval 3.3-6.1), being constant over time (0-5 years). In conclusion, follow-up strategies should be equally intense for at least the first 5 years, with special attention paid to squamous cell carcinoma (especially in immunosuppressed patients), elderly patients, non-primary tumours, and those procedures requiring more stages, or unfinished surgeries.


Asunto(s)
Carcinoma Basocelular , Carcinoma de Células Escamosas , Neoplasias Cutáneas , Anciano , Carcinoma Basocelular/epidemiología , Carcinoma Basocelular/cirugía , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/cirugía , Humanos , Cirugía de Mohs , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/cirugía , Estudios Prospectivos , Sistema de Registros , Factores de Riesgo , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/cirugía
18.
J Dairy Res ; 88(2): 205-209, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-34075866

RESUMEN

In this research communication we describe the composition of fatty acids (FA) present in the milk of the Nordestina donkey breed, and how they differ during lactation. Milk samples were taken from 24 multiparous lactating Nordestina donkeys that grazed the Caatinga, comprising 5 animals at each of around 30, 60 and 90 d in milk (DIM) and a further 9 animals ranging from 120 to 180 DIM. The milk fat content was analysed by mid infrared spectroscopy and the FA profile by gas chromatography. The milk fat percentage ranged from 0.45 to 0.61%. The main FA found in milk were 16:0 and 18:1c9. These did not differ among DIM classes and comprised 23% and 25% of total FA. Notably, the α-Linolenic acid (18:3 n-3) was the third most abundant FA and differed (P < 0.05) with DIM, being lowest in the 30 and 60 DIM samples (around 10.7% of total FA) and highest in the 60 and 90 DIM classes (around 14.6% of total FA). The low-fat content and the FA profile of the donkey milk gives it potential as a functional ingredient, which could help to preserve the commercial viability of the Nordestina donkey breed.


Asunto(s)
Equidae , Ácidos Grasos/análisis , Leche/química , Animales , Brasil , Dieta/veterinaria , Femenino , Lactancia , Especificidad de la Especie , Factores de Tiempo , Ácido alfa-Linolénico/análisis
19.
J Therm Biol ; 100: 103004, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34503771

RESUMEN

Thermal responses in cicadas have been studied for many years. The minimum flight temperature (MFT) does not show the same relationship to habitat and behavior as other thermal responses. We measured live mass, wing length, wingspan, wing area and wing loading in an attempt to correlate these morphological parameters to the MFT. We analyzed both intraspecific (in Magicicada cassinii (Fisher, 1852)) and interspecific relationships of the wing morphology and the ability of the cicadas to fly in a large number of North American cicada taxa (n=119). A total of 109 species and 10 subspecies from 17 genera, six tribes, and three subfamilies including all major North American habitats were studied. Analyses show that wing morphology (wing length, wingspan, wing area and wing loading) scales to body size as predicted by geometric similarity (all P<0.0001) for all species and wing area and wing loading (both P<0.0001) in M. cassinii. Mass (P=0.0105), wing length (P=0.0006), wingspan (P=0.0006), wing area (P=0.0055), and wing loading (P=0.0455) all demonstrate a significant correlation to MFT between species, as would be predicted by aerodynamic theory, but not within species. However, the low correlation coefficients suggest the flight system has minimal influence on the MFT of cicadas. Specific physiological adaptations appear to be responsible for the between species variability in MFT rather than being the result of modifications to the flight system morphology.


Asunto(s)
Temperatura Corporal , Vuelo Animal , Hemípteros/fisiología , Adaptación Fisiológica , Animales , Hemípteros/anatomía & histología
20.
Molecules ; 26(16)2021 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-34443408

RESUMEN

Complex wastewater matrices present a major environmental concern. Besides the biodegradable organics, they may contain a great variety of toxic chemicals, heavy metals, and other xenobiotics. The electrochemically activated persulfate process, an efficient way to generate sulfate radicals, has been widely applied to the degradation of such complex effluents with very good results. This review presents the fundamentals of the electro-persulfate processes, highlighting the advantages and limitations, followed by an exhaustive evaluation on the application of this process for the treatment of complex industrial effluents. An overview of the main relevant experimental parameters/details and their influence on the organic load removal is presented and discussed, having in mind the application of these technologies at an industrial scale. Finally, the future perspectives for the application of the electro-persulfate processes in the treatment of complex wastewater matrices is outlined.

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