Treatment of pregnant rats with oleoyl-estrone slows down pup fat deposition after weaning

BACKGROUND: In rats, oral oleoyl-estrone (OE) decreases food intake and body lipid content. The aim of this study was to determine whether OE treatment affects the energy metabolism of pregnant rats and eventually, of their pups; i.e. changes in normal growth patterns and the onset of obesity after weaning. METHODS: Pregnant Wistar rats were treated with daily intragastric gavages of OE in 0.2 ml sunflower oil from days 11 to 21 of pregnancy (i.e. 10 nmol oleoyl-estrone/g/day). Control animals received only the vehicle. Plasma and hormone metabolites were determined together with variations in cellularity of adipose tissue. RESULTS: Treatment decreased food intake and lowered weight gain during late pregnancy, mainly because of reduced adipose tissue accumulation in different sites. OE-treated pregnant rats' metabolic pattern after delivery was similar to that of controls. Neonates from OE-treated rats weighed the same as those from controls. They also maintained the same growth rate up to weaning, but pups from OE-treated rats slowed their growth rate afterwards, despite only limited differences in metabolite concentrations. CONCLUSION: The OE influences on pup growth can be partially buffered by maternal lipid mobilization during the second half of pregnancy. This maternal metabolic "imprinting" may condition the eventual accumulation of adipose tissue after weaning, and its effects can affect the regulation of body weight up to adulthood

Comprehensive cross-platform comparison of methods for non-invasive EGFR mutation testing: results of the RING observational trial

Several platforms for noninvasive EGFR testing are currently used in the clinical setting with sensitivities ranging from 30% to 100%. Prospective studies evaluating agreement and sources for discordant results remain lacking. Herein, seven methodologies including two next-generation sequencing (NGS)-based methods, three high-sensitivity PCR-based platforms, and two FDA-approved methods were compared using 72 plasma samples, from EGFR-mutant non-small-cell lung cancer (NSCLC) patients progressing on a first-line tyrosine kinase inhibitor (TKI). NGS platforms as well as high-sensitivity PCR-based methodologies showed excellent agreement for EGFR-sensitizing mutations (K = 0.80–0.89) and substantial agreement for T790M testing (K = 0.77 and 0.68, respectively). Mutant allele frequencies (MAFs) obtained by different quantitative methods showed an excellent reproducibility (intraclass correlation coefficients 0.86–0.98). Among other technical factors, discordant calls mostly occurred at mutant allele frequencies (MAFs) ≤ 0.5%. Agreement significantly improved when discarding samples with MAF ≤ 0.5%. EGFR mutations were detected at significantly lower MAFs in patients with brain metastases, suggesting that these patients risk for a false-positive result. Our results support the use of liquid biopsies for noninvasive EGFR testing and highlight the need to systematically report MAFs

Defining Optimal Conditions for Tumor Extracellular Vesicle DNA Extraction for Mutation Profiling

(1) Background: Extracellular vesicles (EVs) have emerged as crucial players in the communication between cells in both physiological and pathological scenarios. The functions of EVs are strongly determined by their molecular content, which includes all bioactive molecules, such as proteins, lipids, RNA, and, as more recently described, double-stranded DNA. It has been shown that in oncological settings DNA associated with EVs (EV-DNA) is representative of the genome of parental cells and that it reflects the mutational status of the tumor, gaining much attention as a promising source of biomarker mutant DNA. However, one of the challenges in studies of EV-DNA is the lack of standardization of protocols for the DNA extraction from EVs, as well as ways to assess quality control, which hinders its future implementation in clinics. (2) Methods: We performed a comprehensive comparison of commonly used approaches for EV-DNA extraction by assessing DNA quantity, quality, and suitability for downstream analyses. (3) Results: We here established strategic points to consider for EV-DNA preparation for mutational analyses, including qPCR and NGS. (4) Conclusions: We put in place a workflow that can be applied for the detection of clinically relevant mutations in the EV-DNA of cancer patients

Functionality and Quality of Life with Parkinson’s Disease after Use of a Dynamic Upper Limb Orthosis: A Pilot Study

Parkinson’s disease (PD) is a chronic, neurodegenerative movement disorder, whose symptoms have a negative impact on quality of life and functionality. Although its main treatment is pharmacological, non-pharmacological aids such as the dynamic elastomeric fabric orthosis (DEFO) merit an evaluation. Our objective is to assess the DEFO in upper limb (UL) functional mobility and in the quality of life of PD patients. A total of 40 patients with PD participated in a randomized controlled crossover study, and were assigned to a control group (CG) and to an experimental group (EG). Both groups used the DEFO for two months, the experimental group the first two months of the study and the control group the last two. Motor variables were measured in the ON and OFF states at the baseline assessment and at two months. Differences from the baseline assessment were observed in some motor items of the Kinesia assessment, such as rest tremor, amplitude, rhythm or alternating movements in the ON and OFF states with and without orthosis. No differences were found in the unified Parkinson’s disease rating scale (UPDRS) or the PD quality-of-life questionnaire. The DEFO improves some motor aspects of the UL in PD patients but this does not translate to the amelioration of the standard of functional and quality-of-life scales

Comprehensive cross-platform comparison of methods for non-invasive EGFR mutation testing : results of the RING observational trial.

Abstract Several platforms for noninvasive EGFR testing are currently used in the clinical setting with sensitivities ranging from 30% to 100%. Prospective studies evaluating agreement and sources for discordant results remain lacking. Herein, seven methodologies including two next-generation sequencing (NGS)-based methods, three high-sensitivity PCR-based platforms, and two FDA-approved methods were compared using 72 plasma samples, from EGFR-mutant non-small-cell lung cancer (NSCLC) patients progressing on a first-line tyrosine kinase inhibitor (TKI). NGS platforms as well as high-sensitivity PCR-based methodologies showed excellent agreement for EGFR-sensitizing mutations (K = 0.80-0.89) and substantial agreement for T790M testing (K = 0.77 and 0.68, respectively). Mutant allele frequencies (MAFs) obtained by different quantitative methods showed an excellent reproducibility (intraclass correlation coefficients 0.86-0.98). Among other technical factors, discordant calls mostly occurred at mutant allele frequencies (MAFs) ≤ 0.5%. Agreement significantly improved when discarding samples with MAF ≤ 0.5%. EGFR mutations were detected at significantly lower MAFs in patients with brain metastases, suggesting that these patients risk for a false-positive result. Our results support the use of liquid biopsies for noninvasive EGFR testing and highlight the need to systematically report MAFs. Keywords: NGS; circulating free DNA; epidermal growth factor receptor; non-small-cell lung cancer; osimertinib; tyrosine kinase inhibitor

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

EstuPlan: Methodology for the development of creativity in the resolution of scientific and social problems

[EN] Creative thinking is necessary to generate novel ideas and solve problems. "EstuPlan" is a methodology in which knowledge and creativity converge for the resolution of scientific problems with social projection. It is a training programme that integrates teachers, laboratory technicians and PhD students, master and undergraduate students which form working groups for the development of projects. Projects have a broad and essential scope and projection in terms of environmental problems, sustainable use of natural resources, food, health, biotechnology or biomedicine. The results show the success of this significant learning methodology using tools to develop creativity in responding to scientific and social demand for problem-solving to transfer academic knowledge to different professional environments. Bioplastics, Second Life of Coffee, LimBio, Algae oils, Ecomers, Caring for the life of your crop and Hate to Deforestate are currently being developed.Astudillo Calderón, S.; De Díez De La Torre, L.; García Companys, M.; Ortega Pérez, N.; Rodríguez Martínez, V.; Alzahrani, S.; Alonso Valenzuela, R.... (2019). EstuPlan: Methodology for the development of creativity in the resolution of scientific and social problems. En HEAD'19. 5th International Conference on Higher Education Advances. Editorial Universitat Politècnica de València. 711-717. https://doi.org/10.4995/HEAD19.2019.9205OCS71171

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Best Practice Guide for Positive Parenting. A resource for practitioners working with families

[spa] El modo en que se concibe el ejercicio de la parentalidad ha cambiado sustancialmente en nuestra sociedad. Ello no sólo se debe a la gran variedad de formas familiares y diversidad de culturas que conviven actualmente en su seno, sino también a un cambio conceptual que afecta al núcleo básico de la tarea parental. Nos referimos a la necesidad de sustituir el concepto de autoridad parental, centrado únicamente en la necesidad de lograr metas de obediencia y disciplina en los hijos e hijas, por otro más complejo y demandante como es el concepto de responsabilidad parental. Según este concepto, la cuestión clave no es si las figuras parentales deben ejercer la autoridad para que sus hijos/as les obedezcan, sino cómo ejercerla de modo responsable para que se preserven los derechos de los mismos, sin menoscabar los de padres y madres, y se fomenten sus capacidades críticas y de participación en el proceso de socialización, al mismo tiempo que se promueve progresivamente su autonomía y contribución a la vida comunitaria. Ante este cambio cualitativo en la manera de entender las responsabilidades parentales, se alzan muchas voces de desánimo entre los propios padres y madres, quienes en ocasiones se ven impotentes en su tarea al no saber cómo actuar para lograr metas educativas tan complejas y sentir, al mismo tiempo, que están perdiendo capacidades de control sobre sus hijos e hijas. En otras ocasiones, el desánimo y el estrés ante la tarea parental no surge por no saber llevarla a cabo sino por no poder hacerlo adecuadamente debido a la situación de la persona que educa en solitario o en pareja sin contar con redes de apoyo apropiadas. Esto crea situaciones límite que repercuten negativamente en todos y cada uno de los miembros de la familia, especialmente en los más vulnerables.[eng] Our conception of what parenting should look like has changed considerably in our society. This is due not only to the large variety of family structures and the diversity of cultures that currently co-exist in our society, but also to a shift in mindset that touches the very heart of the parenting task. This can be expressed as the need to replace the concept of parental authority, which focuses solely on meeting aims related to the child’s obedience and discipline, with the much more complex and demanding concept of parental responsibility. Here, the key question is not whether the parent figure should exert the necessary authority to ensure a child’s obedience. Rather, it is about how this authority can be exerted responsibly in a way that protects the child’s rights - without of course neglecting the mother’s and father’s rights - and that fosters the child’s skills in critical thinking and participation in the socialisation process, while at the same time progressively fostering the child’s autonomy and contribution to community life. There has been much concern expressed in response to this qualitative shift in how a parent’s responsibilities are viewed, including amongst mothers and fathers themselves. Parents often feel powerless to act, as they do not know how to achieve such complex parenting goals, and feel like they are losing control over their children. Other times, feelings of discouragement and stress arise not because parents do not how to go about the task of parenting, but rather because they find themselves unable to do so, as may be the case for single parents or couples raising children without the necessary support networks. This can lead to extreme situations which can have a negative impact on the entire family, and especially its most vulnerable members

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group