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Carcinoma-associated fibroblasts (CAFs) are highly accumulated in the tumor-surrounding stroma of primary epithelial ovarian cancer (OC). CAFs exert important functions for the vascularization, growth, and progression of OC cells. However, the origin of CAFs in primary OC had not yet been studied, and they were assumed to arise from the activation of resident fibroblasts. Here, we compared CAFs in the ovary to CAFs found in peritoneal metastases from patients with advanced OC. Our findings show that CAFs from primary tumors and peritoneal metastases share the expression of mesothelial markers. Therefore, similar to peritoneal carcinomatosis, CAFs in primary ovarian carcinomas may originate from mesothelial cells via a mesothelial-to-mesenchymal transition. The detection of mesothelial-derived CAFs in tumors confined to the ovary and identification of biomarkers could be the key to the early detection of OC and peritoneal spread.
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Whole-genome doubling (WGD) is a critical driver of tumor development and is linked to drug resistance and metastasis in solid malignancies. Here, we demonstrate that WGD is an ongoing mutational process in tumor evolution. Using single-cell whole-genome sequencing, we measured and modeled how WGD events are distributed across cellular populations within tumors and associated WGD dynamics with properties of genome diversification and phenotypic consequences of innate immunity. We studied WGD evolution in 65 high-grade serous ovarian cancer (HGSOC) tissue samples from 40 patients, yielding 29,481 tumor cell genomes. We found near-ubiquitous evidence of WGD as an ongoing mutational process promoting cell-cell diversity, high rates of chromosomal missegregation, and consequent micronucleation. Using a novel mutation-based WGD timing method, doubleTime , we delineated specific modes by which WGD can drive tumor evolution: (i) unitary evolutionary origin followed by significant diversification, (ii) independent WGD events on a pre-existing background of copy number diversity, and (iii) evolutionarily late clonal expansions of WGD populations. Additionally, through integrated single-cell RNA sequencing and high-resolution immunofluorescence microscopy, we found that inflammatory signaling and cGAS-STING pathway activation result from ongoing chromosomal instability and are restricted to tumors that remain predominantly diploid. This contrasted with predominantly WGD tumors, which exhibited significant quiescent and immunosuppressive phenotypic states. Together, these findings establish WGD as an evolutionarily 'active' mutational process that promotes evolvability and dysregulated immunity in late stage ovarian cancer.
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The shoots of Asparagus L. are consumed worldwide, although most species belonging to this genus have a restricted range, and several taxa remain unstudied. In this work, a total of four taxa from different locations were scrutinized and compared with cultivated A. officinalis. All shoots were screened for saponins via LC-MS, and in vitro antiproliferative activities against the HT-29 colorectal cancer cell line were assessed via the MTT assay. The total saponins (TS) contained in the crude extracts ranged from 710.0 (A. officinalis) to 1258.6 mg/100 g dw (A. acutifolius). The richness of the compounds detected in this work stands out; a total of 47 saponins have been detected and quantified in the edible parts (shoots) of five taxa of Asparagus. The structure of all the saponins found present skeletons of the furostane and spirostane type. In turn, the structures with a furostane skeleton are divided into unsaturated and dioxygenated types, both in the 20-22 position. The sum of dioscin and derivatives varied largely among the studied taxa, reaching the following percentages of TS: 27.11 (A. officinalis), 18.96 (A. aphyllus), 5.37 (A. acutifolius), and 0.59 (A. albus); while in A. horridus, this compound remains undetected. Aspachiosde A, D, and M varied largely among samples, while a total of seven aspaspirostanosides were characterized in the analyzed species. The hierarchical cluster analysis of the saponin profiles clearly separated the various taxa and demonstrated that the taxonomic position is more important than the place from which the samples were acquired. Thus, saponin profiles have chemotaxonomic significance in Asparagus taxa. The MTT assay showed dose- and time-dependent inhibitory effects of all saponins extracts on HT-29 cancer cells, and the strongest cell growth inhibition was exercised by A. albus and A. acutifolius (GI50 of 125 and 175 µg/mL). This work constitutes a whole approach to evaluating the saponins from the shoots of different Asparagus taxa and provides arguments for using them as functional foods.
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Asparagus , Extractos Vegetales , Brotes de la Planta , Saponinas , Saponinas/farmacología , Saponinas/química , Humanos , Asparagus/química , Brotes de la Planta/química , Células HT29 , Extractos Vegetales/farmacología , Extractos Vegetales/química , Proliferación Celular/efectos de los fármacos , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/químicaRESUMEN
The search for new compounds with biocidal potential was carried out, focusing on the longipinenes 1-7 from the plant species Santolina viscosa Lag. Compounds 1, 2, and 5 showed remarkable molecular diversity when treated in acidic reaction conditions. Protonic, Lewis, and heterogeneous compounds were used in the treatment. Three main models of reaction have been observed: isomerization of the double bond (8-10); rearrangements to longibornane-based skeleton (11-15) and ring-opening to himachalane-based skeleton (16-18). Secolongibornane aldehydes 23 and 24 were obtained after epoxide opening under the same reaction conditions. The elucidation of the structures of the new compounds was carried out using spectroscopic data and was supported by computational theoretical calculations of 13C NMR spectra. Additionally, high-resolution mass spectrometry and single-crystal X-ray diffraction analysis were employed for certain compounds. Natural longipinenes 4-7, methyl esters 1-3 of corresponding natural carboxylic acids and the isomerized and derivatives compounds 8-19 exhibit moderate to high insecticidal activity against R. padi and M. persicae insects. Longipinene 5 shows potent inhibition against the root growth of the plants L. perenne and L. sativa, as well as compound 2 on the leaves of L. perenne. Furthermore, significant ixocidal and nematicidal activity was found for this latter compound.
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Insecticidas , Animales , Insecticidas/química , Insecticidas/farmacología , Catálisis , Estructura Molecular , Norbornanos/química , Norbornanos/farmacologíaRESUMEN
Introduction: Using a validated translational model that quantitatively predicts opioid-induced respiratory depression and cardiac arrest, we compared cardiac arrest events caused by synthetic opioids (fentanyl, carfentanil) following rescue by intranasal (IN) administration of the µ-opioid receptor antagonists naloxone and nalmefene. Methods: This translational model was originally developed by Mann et al. (Clin Pharmacol Ther 2022) to evaluate the effectiveness of intramuscular (IM) naloxone. We initially implemented this model using published codes, reproducing the effects reported by Mann et al. on the incidence of cardiac arrest events following intravenous doses of fentanyl and carfentanil as well as the reduction in cardiac arrest events following a standard 2 mg IM dose of naloxone. We then expanded the model in terms of pharmacokinetic and µ-opioid receptor binding parameters to simulate effects of 4 mg naloxone hydrochloride IN and 3 mg nalmefene hydrochloride IN, both FDA-approved for the treatment of opioid overdose. Model simulations were conducted to quantify the percentage of cardiac arrest in 2000 virtual patients in both the presence and absence of IN antagonist treatment. Results: Following simulated overdoses with both fentanyl and carfentanil in chronic opioid users, IN nalmefene produced a substantially greater reduction in the incidence of cardiac arrest compared to IN naloxone. For example, following a dose of fentanyl (1.63 mg) producing cardiac arrest in 52.1% (95% confidence interval, 47.3-56.8) of simulated patients, IN nalmefene reduced this rate to 2.2% (1.0-3.8) compared to 19.2% (15.5-23.3) for IN naloxone. Nalmefene also produced large and clinically meaningful reductions in the incidence of cardiac arrests in opioid naïve subjects. Across dosing scenarios, simultaneous administration of four doses of IN naloxone were needed to reduce the percentage of cardiac arrest events to levels that approached those produced by a single dose of IN nalmefene. Conclusion: Simulations using this validated translational model of opioid overdose demonstrate that a single dose of IN nalmefene produces clinically meaningful reductions in the incidence of cardiac arrest compared to IN naloxone following a synthetic opioid overdose. These findings are especially impactful in an era when >90% of all opioid overdose deaths are linked to synthetic opioids such as fentanyl.
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Background: The methods previously proposed in the literature to assess patients with rotator cuff related shoulder pain, based on special orthopedic tests to precisely identify the structure causing the shoulder symptoms have been recently challenged. This opens the possibility of a different way of physical examination. Objective: To analyze the differences in shoulder range of motion, strength and thoracic kyphosis between rotator cuff related shoulder pain patients and an asymptomatic group. Method: The protocol of the present research was registered in the International Prospective Register of Systematic Review (PROSPERO) (registration number CRD42021258924). Database search of observational studies was conducted in MEDLINE, EMBASE, WOS and CINHAL until July 2023, which assessed shoulder or neck neuro-musculoskeletal non-invasive physical examination compared to an asymptomatic group. Two investigators assessed eligibility and study quality. The Newcastle Ottawa Scale was used to evaluate the methodology quality. Results: Eight studies (N = 604) were selected for the quantitative analysis. Meta-analysis showed statistical differences with large effect for shoulder flexion (I2 = 91.7%, p < 0.01, HG = -1.30), external rotation (I2 = 83.2%, p < 0.01, HG = -1.16) and internal rotation range of motion (I2 = 0%, p < 0.01, HG = -1.32). Regarding to shoulder strength; only internal rotation strength showed statistical differences with small effect (I2 = 42.8%, p < 0.05, HG = -0.3). Conclusions: There is moderate to strong evidence that patients with rotator cuff related shoulder pain present less shoulder flexion, internal and external rotation range of motion and less internal rotation strength than asymptomatic individuals.
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Fuerza Muscular , Rango del Movimiento Articular , Manguito de los Rotadores , Dolor de Hombro , Humanos , Rango del Movimiento Articular/fisiología , Dolor de Hombro/fisiopatología , Manguito de los Rotadores/fisiopatología , Fuerza Muscular/fisiología , Lesiones del Manguito de los Rotadores/fisiopatología , Articulación del Hombro/fisiopatología , Cifosis/fisiopatologíaRESUMEN
INTRODUCTION: Condoms and combined oral contraceptive pills are widely used in Spain with high failure rates. Long-Acting Reversible Contraceptive (LARC) methods offer better efficacy and adherence and reduce unintended pregnancies (UP) compared with short-acting reversible contraceptive (SARC) methods. OBJECTIVE: To assess the cost-effectiveness of LNG-IUS 52 mg (Mirena®) versus other LARC for contraception in Spain. MATERIALS AND METHODS: A Markov model with annual cycles and an eight-year time horizon was developed from the Spanish national healthcare system (NHS) perspective, considering costs for contraceptive method acquisition, health care resources (HCR) and UP. Effectiveness was based on failure and discontinuation rates. Sensitivity analyses were performed to test the model's robustness. RESULTS: LNG-IUS 52 mg (Mirena®) resulted in lower costs and fewer UP versus LNG-IUS 13.5 mg (Jaydess®), Implant (Implanon®) and Copper IUD. LNG-IUS 52 mg (Levosert®) prevented the same UP events at a higher cost. LNG-IUS 19.5 mg (Kyleena®) was the most effective option, due to a lower discontinuation rate. CONCLUSIONS: LNG-IUS 52 mg (Mirena®) is the least costly LARC, driven by lower acquisition costs and reduced HCR utilisation. Increasing LNG-IUS 52 mg (Mirena®) uptake in contraception could generate further cost savings for the Spanish NHS and reduce economic burden of UP.
Levonorgestrel-releasing intrauterine system (LNG-IUS; Mirena®) is an effective and cost-saving long-acting reversible contraceptive (LARC) method compared with other similar methods in Spain over an eight-year time horizon, and Kyleena® was the most effective option.
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A Gram-stain-negative bacterial strain designated Be4T, belonging to the genus Acidovorax, was isolated from mining porewaters sampled in uranium mill tailings repository sites, located in Bellezane, near Bessines-sur-Gartempe (Limousin, France). Cells were facultative anaerobic, rod-shaped, non-endospore-forming and motile with flagella. The mean cell size was 1.25-1.31 µm long and 0.70-0.73 µm wide. Colonies were light yellow, opaque, circular, convex with smooth margins, and 1-2 mm in diameter. Growth occurs at 4-37 °C and between pH 5.5-9.0. It differed from its phylogenetically related strains by phenotypic and physiological characteristics such as growth at 4 °C, presence of acid phosphatase, naphthol-AS-BI-phosphohydrolase and ß-glucosidase enzymatic activities, and fermentation of l-xylose and esculin. The major fatty acids were C16:0, C16:1 ω7c/C16:1 ω6c, C17:0 cyclo and C18:1 ω7c. Phylogenetic analysis based on 16S rRNA and 938 core genes, confirmed its placement within the genus Acidovorax as a novel species. Strain Be4T showed highest 16S rRNA sequence similarity to Acidovorax antarcticus (98.2 %), Acidovorax radicis (97.9 %), Acidovorax temperans (97.8 %) and Acidovorax facilis (97.7 %). The genome of strain Be4T is 5,041,667 bp size with a DNA G + C content of 65.15 %. By automatic annotation numerous sequences involved in the interaction with metals/metalloids including some genes related to Se uptake and selenite resistance were detected in its genome. The average nucleotide identity (ANI) values calculated from whole genome sequences between strain Be4T and the most closely related strains A. radicis and A. facilis were below the threshold value of 95 %. Thus, the data from the phylogenetic, physiological, biochemical, and genomic analyses clearly indicates that strain Be4T represents a novel species with the suggested name Acidovorax bellezanensis sp. nov. The type strain is Acidovorax bellezanensis Be4T (=DSM116209T = CECT30865T). This novel species, due to its unique isolation source, genomic analysis, and preliminary laboratory tests where it was able to reduce toxic Se(IV) to less harmful Se(0) in the form of nanoparticles, holds great potential for further investigation in bioremediation, particularly concerning Se.
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One of the major challenges for edu-communication research is to analyze the influence of social media on young and adolescent users. This article examines the evaluation of gender inequalities - real and symbolic - in the consumption of social networks such as YouTube and Instagram among young people. Within the framework of a Research & Development & innovation (R&D + i) project, it presents a discursive-theoretical analysis of how young users of social media perceive the presence and representation of gender on social media and whether such digital representations can be associated with an empowering gender perspective. This study presents results from 14 focus groups (N = 83), composed of students aged 12 to 18, drawn from three Spanish Autonomous Communities (Catalonia, the Balearic Islands and the Basque Country). The results show that gender issues arise in participants' conversations, especially among female participants, who perceive the importance of physical appearance on platforms such as Instagram and TikTok. Female participants feel more pressure in terms of appearance and dress compared to male participants. Among male participants there are more expressions of self-affirmation and more mentions related to fun and social prestige. Both male and female participants express concern about the impact of that pressure on younger girls. The influence of social media on self-image is more evident among female participants, who make frequent mention of the importance of self-esteem in relation to beauty standards and exposure to idealized body images. Notably, there were no comments by male participants that acknowledge any influence of social media on their self-image. The findings are in line with existing research and taken as a whole gives rise to concern as to the gender disparities observed in the use of social media, which do not constitute a picture of female empowerment. This research underlines the importance of promoting a respectful and equitable environment in relation to gender equality within digital spaces. Thus, this study provides support for the need to develop and implement edu-communicative initiatives to foster critical thinking around the influence of social media in this context and the evaluation of the impact of such initiatives in future research.
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Background: Existing criteria for predicting patient survival from immunotherapy are primarily centered on the PD-L1 status of patients. We tested the hypothesis that noninvasively captured baseline whole-lung radiomics features from CT images, baseline clinical parameters, combined with advanced machine learning approaches, can help to build models of patient survival that compare favorably with PD-L1 status for predicting 'less-than-median-survival risk' in the metastatic NSCLC setting for patients on durvalumab. With a total of 1062 patients, inclusive of model training and validation, this is the largest such study yet. Methods: To ensure a sufficient sample size, we combined data from treatment arms of three metastatic NSCLC studies. About 80% of this data was used for model training, and the remainder was held-out for validation. We first trained two independent models; Model-C trained to predict survival using clinical data; and Model-R trained to predict survival using whole-lung radiomics features. Finally, we created Model-C+R which leveraged both clinical and radiomics features. Results: The classification accuracy (for median survival) of Model-C, Model-R, and Model-C+R was 63%, 55%, and 68% respectively. Sensitivity analysis of survival prediction across different training and validation cohorts showed concordance indices ([95 percentile]) of 0.64 ([0.63, 0.65]), 0.60 ([0.59, 0.60]), and 0.66 ([0.65,0.67]), respectively. We additionally evaluated generalization of these models on a comparable cohort of 144 patients from an independent study, demonstrating classification accuracies of 65%, 62%, and 72% respectively. Conclusion: Machine Learning models combining baseline whole-lung CT radiomic and clinical features may be a useful tool for patient selection in immunotherapy. Further validation through prospective studies is needed.
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Anticuerpos Monoclonales , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Tomografía Computarizada por Rayos X , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/patología , Masculino , Femenino , Tomografía Computarizada por Rayos X/métodos , Anticuerpos Monoclonales/uso terapéutico , Persona de Mediana Edad , Anciano , Aprendizaje Automático , Medición de Riesgo , Antineoplásicos Inmunológicos/uso terapéutico , Pronóstico , Antígeno B7-H1 , RadiómicaRESUMEN
The extent of cell-to-cell variation in tumor mitochondrial DNA (mtDNA) copy number and genotype, and the phenotypic and evolutionary consequences of such variation, are poorly characterized. Here we use amplification-free single-cell whole-genome sequencing (Direct Library Prep (DLP+)) to simultaneously assay mtDNA copy number and nuclear DNA (nuDNA) in 72,275 single cells derived from immortalized cell lines, patient-derived xenografts and primary human tumors. Cells typically contained thousands of mtDNA copies, but variation in mtDNA copy number was extensive and strongly associated with cell size. Pervasive whole-genome doubling events in nuDNA associated with stoichiometrically balanced adaptations in mtDNA copy number, implying that mtDNA-to-nuDNA ratio, rather than mtDNA copy number itself, mediated downstream phenotypes. Finally, multimodal analysis of DLP+ and single-cell RNA sequencing identified both somatic loss-of-function and germline noncoding variants in mtDNA linked to heteroplasmy-dependent changes in mtDNA copy number and mitochondrial transcription, revealing phenotypic adaptations to disrupted nuclear/mitochondrial balance.
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Núcleo Celular , Variaciones en el Número de Copia de ADN , ADN Mitocondrial , Genoma Mitocondrial , Neoplasias , Análisis de la Célula Individual , Humanos , ADN Mitocondrial/genética , Análisis de la Célula Individual/métodos , Variaciones en el Número de Copia de ADN/genética , Núcleo Celular/genética , Neoplasias/genética , Neoplasias/patología , Línea Celular Tumoral , Animales , Mitocondrias/genética , Secuenciación Completa del Genoma/métodos , Ratones , Heteroplasmia/genéticaRESUMEN
PURPOSE: The aim of this study was to analyse the complications and problems associated with the use of an experimental prototype designed for the prevention of parastomal hernia (PSH), one of the most frequent complications in ostomates. METHODS: A single-centre, non-comparative, proof-of-concept interventional pilot study of an experimental prototype designed to be used in conjunction with an abdominal compression binder to prevent PSH was conducted. The "Ostomy Fixation Device for Hernia Prevention" (patent P201531826) is a semi-rigid ostomy protector, to be used in conjunction with a compression binder. It is designed to adapt to the dimensions of standard ostomy bags from different brands and serves to transmit, in a localised manner, the support coming from the compression binder in the peristomal area without putting pressure on the collection bag. The main outcome measures were efficacy, safety, and patient-users' opinion/perception. RESULTS: Ten patients were studied for 12 months. Mean age was 61 years (± 11.59), 70% (7) were male, 80% (8) ostomised for colorectal cancer, 90% (9) underwent planned surgery and 80% (8) had a colostomy. EFFICACY: the incidence of HPE was 10% (1). SAFETY: no participant experienced pain, discomfort, itching, stinging, leakage, pouch detachment, allergy to components, or injury to the stoma or peristomal skin due to rubbing or pressure. 90% (n = 9) were considered "very satisfied" or "satisfied" with the device. CONCLUSIONS: An innovative device designed in collaboration between healthcare professionals and end-users has been shown to be safe and effective in reducing PSH in the group of ostomates studied.
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BACKGROUND: The CROM instrument is widely used clinically and in research to measure neck range of motion. However, its measurement proprieties during the assessment of protraction and retraction movements were not examined so far. OBJECTIVE: To analyse the intra- and inter-rater reliability, the concurrent validity of the CROM for measuring head posture, retraction and protraction in healthy subjects. METHODS: Thirty-three asymptomatic subjects were recruited and assigned in a random order to one of two raters. After a 10-min break, they were examined by a second rater (Assessment 1). After a 30-min break, both raters repeated the examination (Assessment 2). The examination consisted of measuring the head posture, maximum head protraction and maximum retraction. Each movement was repeated 3 times and measured simultaneously with the CROM and with a 3D capture system laboratory. RESULTS: The intra-rater reliability of the CROM was excellent for both raters for head posture and all head movements (ICC>0.9, 95% CI: 0.82-0.99, p < 0.01). The inter-rater reliability was excellent for head posture (ICC>0.95, 95% CI: 0.92-0.98, p < 0.01) and good-to-excellent for all movements at both time-points (ICC = 0.73-0.98, 95%CI: 0.45-0.99, p < 0.01). The validity analysis showed moderate-to-strong correlation between instruments for the head posture and head movements [(r) = -0.47 to -0.78), 95% CI: 0.99 to -0.24, p < 0.01]. CONCLUSION: The CROM instrument has good-to-excellent reliability and adequate validity for measuring cervical position and displacement in the sagittal plane.
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Postura , Rango del Movimiento Articular , Humanos , Masculino , Femenino , Adulto , Postura/fisiología , Reproducibilidad de los Resultados , Rango del Movimiento Articular/fisiología , Cabeza/fisiología , Movimientos de la Cabeza/fisiología , Cuello/fisiología , Variaciones Dependientes del Observador , Voluntarios Sanos , Adulto JovenRESUMEN
Cancer development is characterized by chromosomal instability, manifesting in frequent occurrences of different genomic alteration mechanisms ranging in extent and impact. Mathematical modeling can help evaluate the role of each mutational process during tumor progression, however existing frameworks can only capture certain aspects of chromosomal instability (CIN). We present CINner, a mathematical framework for modeling genomic diversity and selection during tumor evolution. The main advantage of CINner is its flexibility to incorporate many genomic events that directly impact cellular fitness, from driver gene mutations to copy number alterations (CNAs), including focal amplifications and deletions, missegregations and whole-genome duplication (WGD). We apply CINner to find chromosome-arm selection parameters that drive tumorigenesis in the absence of WGD in chromosomally stable cancer types. We found that the selection parameters predict WGD prevalence among different chromosomally unstable tumors, hinting that the selective advantage of WGD cells hinges on their tolerance for aneuploidy and escape from nullisomy. Direct application of CINner to model the WGD proportion and fraction of genome altered (FGA) further uncovers the increase in CNA probabilities associated with WGD in each cancer type. CINner can also be utilized to study chromosomally stable cancer types, by applying a selection model based on driver gene mutations and focal amplifications or deletions. Finally, we used CINner to analyze the impact of CNA probabilities, chromosome selection parameters, tumor growth dynamics and population size on cancer fitness and heterogeneity. We expect that CINner will provide a powerful modeling tool for the oncology community to quantify the impact of newly uncovered genomic alteration mechanisms on shaping tumor progression and adaptation.
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Introduction: Axial spondyloarthritis (axSpA) is a heterogeneous disease that can be represented by radiographic axSpA (r-axSpA) and non-radiographic axSpA (nr-axSpA). This study aimed to evaluate the relationship between the markers of inflammation and bone turnover in r-axSpA patients and nr-axSpA patients. Methods: A cross-sectional study included 29 r-axSpA patients, 10 nr-axSpA patients, and 20 controls matched for age and sex. Plasma markers related to bone remodeling such as human procollagen type 1 N-terminal propeptide (P1NP), sclerostin, tartrate-resistant acid phosphatase 5b (TRACP5b), receptor activator of nuclear factor kappa B ligand (RANKL), and osteoprotegerin (OPG) were measured by an ELISA kit. A panel of 92 inflammatory molecules was analyzed by proximity extension assay. Results: R-axSpA patients had decreased plasma levels of P1NP, a marker of bone formation, compared to controls. In addition, r-axSpA patients exhibited decreased plasma levels of sclerostin, an anti-anabolic bone hormone, which would not explain the co-existence of decreased plasma P1NP concentration; however, sclerostin levels could also be influenced by inflammatory processes. Plasma markers of osteoclast activity were similar in all groups. Regarding inflammation-related molecules, nr-axSpA patients showed increased levels of serum interleukin 13 (IL13) as compared with both r-axSpA patients and controls, which may participate in the prevention of inflammation. On the other hand, r-axSpA patients had higher levels of pro-inflammatory molecules compared to controls (i.e., IL6, Oncostatin M, and TNF receptor superfamily member 9). Correlation analysis showed that sclerostin was inversely associated with IL6 and Oncostatin M among others. Conclusion: Altogether, different inflammatory profiles may play a role in the development of the skeletal features in axSpA patients particularly related to decreased bone formation. The relationship between sclerostin and inflammation and the protective actions of IL13 could be of relevance in the axSpA pathology, which is a topic for further investigation.
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Espondiloartritis Axial no Radiográfica , Humanos , Oncostatina M , Estudios Transversales , Interleucina-13 , Interleucina-6 , Inflamación/diagnóstico por imagen , BiomarcadoresRESUMEN
There is evidence that healthcare can be executed differentially depending on the gender of patients, researchers, and clinicians. The aim was to analyze the possible existence of nursing gender differences in pain management produced by arterial puncture for blood gas analysis. A cross-sectional, multicenter study designed was conducted in Castilla-la Mancha (Spain). Variables of interest were collected from nurses in the public health system of a European region through a questionnaire. Data were collected for four months; the primary outcome was the use of any intervention to reduce pain and the explanatory variable was the nurse's gender. Bivariate analysis was carried out to assess associations between gender and pain-reducing interventions and a multivariate model was created with those factors that were relevant using logistic regression. A significantly higher proportion of men reported using some form of intervention (45% vs. 30%) and had more specific training (45.9% vs. 32.4%). The adjusted probability of using pain-reducing interventions by men was 71% higher than women. Thus, we found gender differences in the management of pain caused by arterial punctures performed by nurses as the main healthcare providers.
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Interstitial carbon-doped RuO2 catalyst with the newly reported ruthenium oxycarbonate phase is a key component for low-temperature CO2 methanation. However, a crucial factor is the stability of interstitial carbon atoms, which can cause catalyst deactivation when removed during the reaction. In this work, the stabilization mechanism of the ruthenium oxycarbonate active phase under reaction conditions is studied by combining advanced operando spectroscopic tools with catalytic studies. Three sequential processes: carbon diffusion, metal oxide reduction, and decomposition of the oxycarbonate phase and their influence by the reaction conditions, are discussed. We present how the reaction variables and catalyst composition can promote carbon diffusion, stabilizing the oxycarbonate catalytically active phase under steady-state reaction conditions and maintaining catalyst activity and stability over long operation times. In addition, insights into the reaction mechanism and a detailed analysis of the catalyst composition that identifies an adequate balance between the two phases, i.e., ruthenium oxycarbonate and ruthenium metal, are provided to ensure an optimum catalytic behavior.
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OBJECTIVE: To design, develop and validate a new tool, called NEUMOBACT, to evaluate critical care nurses' knowledge and skills in ventilator-associated pneumonia (VAP) and catheter-related bacteraemia (CRB) prevention through simulation scenarios involving central venous catheter (CVC), endotracheal suctioning (ETS) and mechanically ventilated patient care (PC) stations. BACKGROUND: Simulation-based training is an excellent way for nurses to learn prevention measures in VAP and CRB. DESIGN: Descriptive metric study to develop NEUMOBACT and analyse its content and face validity that followed the COSMIN Study Design checklist for patient-reported outcome measurement instruments. METHODS: The first version was developed with the content of training modules in use at the time (NEUMOBACT-1). Delphi rounds were used to assess item relevance with experts in VAP and CRB prevention measures, resulting in NEUMOBACT-2. Experts in simulation methods then assessed feasibility, resulting in NEUMOBACT-3. Finally, a pilot test was conducted among 30 intensive care unit (ICU) nurses to assess the applicability of the evaluation tool in clinical practice. RESULTS: Seven national experts in VAP and CRB prevention and seven national simulation experts participated in the analysis to assess the relevance and feasibility of each item, respectively. After two Delphi rounds with infection experts, four Delphi rounds with simulation experts, and pilot testing with 30 ICU nurses, the NEUMOBACT-FINAL tool consisted of 17, 26 and 21 items, respectively, for CVC, ETS and PC. CONCLUSION: NEUMOBACT-FINAL is useful and valid for assessing ICU nurses' knowledge and skills in VAP and CRB prevention, acquired through simulation. RELEVANCE FOR CLINICAL PRACTICE: Our validated and clinically tested tool could facilitate the transfer of ICU nurses' knowledge and skills learning in VAP and CRB prevention to critically ill patients, decreasing infection rates and, therefore, improving patient safety. PATIENT OR PUBLIC CONTRIBUTION: Experts participated in the Delphi rounds and nurses in the pilot test.
Asunto(s)
Lista de Verificación , Enfermería de Cuidados Críticos , Neumonía Asociada al Ventilador , Humanos , Enfermería de Cuidados Críticos/normas , Enfermería de Cuidados Críticos/educación , Enfermería de Cuidados Críticos/métodos , Neumonía Asociada al Ventilador/prevención & control , Neumonía Asociada al Ventilador/enfermería , Técnica Delphi , Competencia Clínica/estadística & datos numéricos , Competencia Clínica/normas , Femenino , Entrenamiento Simulado/métodos , Masculino , Adulto , Control de Infecciones/métodos , Control de Infecciones/normas , Infecciones Relacionadas con Catéteres/prevención & control , Infecciones Relacionadas con Catéteres/enfermería , Personal de Enfermería en Hospital/educación , Unidades de Cuidados IntensivosRESUMEN
Our objective was to know the COVID-19 vaccination coverage in multiple sclerosis (MS) patients and its factors associated. A retrospective cohort study was carried out. Patients seen at the MS unit of the University Clinical Hospital of Zaragoza between 2017 and 2021 were included. Variables were obtained by reviewing the specialized and primary care records. Associations between receiving COVID-19 full primo-vaccination, as well as one booster dose since autumn 2022, and the other variables were analyzed using bivariate analysis and multiple logistic regression models. Of the 359 included patients, 90.3% received the COVID-19 full primo-vaccination. Having been born in Spain (aOR = 3.40) and having received the 2020-2021 influenza vaccine (aOR = 6.77) were associated with receiving the COVID-19 full primo-vaccination. Vaccination with a COVID-19 booster dose was detected in 141 patients (39.3%). Sex (man) (aOR = 2.36), age (60 years or over) (aOR = 6.82), type of MS (Primary Progressive/Secondary Progressive) (aOR = 3.94), and having received the 2022-2023 influenza vaccine (aOR = 27.54) were associated with receiving such a booster dose. The COVID-19 booster dose was administered at the same time as the 2022-2023 influenza vaccine in 57.8% (67/116) of the patients vaccinated with both vaccines. The COVID-19 full primo-vaccination coverage is higher than in other countries. However, the decrease in vaccination coverage with the booster dose makes it necessary to develop strategies to improve it that are not limited to administering the flu vaccine together with the COVID-19 booster dose. Such strategies should be in focus, especially for women under 60 years of age.