Randomized Controlled Trial to Evaluate the Efficacy of Positive Mental Health Program for Adults: Study Protocol.

AIM: To evaluate the effectiveness of a positive mental health program for adults (PMHP) in the community. BACKGROUND: Positive mental health (PMH) can be seen as a construct represented by six factors (personal satisfaction, prosocial attitude, self-control, autonomy, problem resolution, and self-actualization, and interpersonal relationship skills) according to the Multifactorial Model for PMH. Although there are several interventions in promoting mental health, research on effective promotion of PMH for adults in the community with structured and validated programs of PMH is scarce. METHODS: This study protocol describes a randomized controlled trial (RCT) following a wait-list control design, aimed at evaluating the effectiveness of a PMHP in the community. This study was approved in June 2019 by the Ethics Committee. Participants will be recruited from the school community of teachers. Participants aged ≥ 18 years. The participants will be randomized 1:1 to either (a) an intervention group, which will integrate the PMHP, or (b) the standby control group. Three assessment moments for both groups will take place initial, after the intervention, and a follow-up of 3-6 months. The evaluation instruments will include a sociodemographic questionnaire, a PMH questionnaire, and a psychological vulnerability scale. CONCLUSION: The current study provides an innovative approach to PMH. Further, the study may demonstrate new interventions in PMH in the community, based on a program with systematized guidelines and sessions structured according to individual needs. It is expected that at the end of the program, the experimental group will increase the level of PMH. RELEVANCE TO CLINICAL PRACTICE: To allow future official implementation of the PMH program and the replication of the study in other professional groups as a promotion tool. NO PATIENT OR PUBLIC CONTRIBUTION: There was no funding to remunerate a participant for this study. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04600401. Registered on May 15, 2020.

Estilos de vida dos estudantes do ensino superior: Contributos para a promoção da saúde / Higher education students' lifestyles: Contributions to health promotion / Estilos de vida de los estudiantes de educación superior: Contribuciones a la promoción de la salud

Resumo Enquadramento: A transição para o ensino superior representa um período de mudança em que o jovem se depara com novas vivências, com implicações no seu estilo de vida. Objetivo: Identificar os domínios dos Estilos de vida dos estudantes do ensino superior que necessitam de intervenção. Metodologia: Estudo descritivo-correlacional, transversal, com uma amostra de 522 estudantes do ensino superior. Questionário de Estilos de Vida Fantástico. Análise estatística em IBM SPSS Statistics 25.0. Resultados: Mediana de idade 22 anos, 78,4% sexo feminino. Dos 522 estudantes, 17,8% excesso peso; 6,3 % obesidade; 14.4% portadores de doença crónica; 35,6% apresentaram Estilos de Vida Muito Bom e 20,1% Estilos de Vida Bom. Destacou-se pela negativa Comportamentos Saúde e Sexual (x-= 8,97/24), Trabalho/Tipo Personalidade (x-= 6,82/12). Há diferenças significativas no score global do questionário (U = 19785,00; p < 0,05) para estudantes as mulheres com melhor Estilo de Vida (x-= 89,16; DP = 12,75); e em função Ano do curso (H = 18,80; p < 0,01). Conclusão: A avaliação dos Estilos de Vida permitiu caraterizar os focos de intervenção e orientar intervenções de promoção da saúde.

Abstract Background: The transition to higher education is a period of change during which students have new experiences that influence their lifestyles. Objective: To identify the domains of higher education students' lifestyles that require intervention. Methodology: This cross-sectional descriptive correlational study was conducted with 522 higher education students. The Fantastic Lifestyle Assessment questionnaire was used, and statistical analysis was conducted using the IBM SPSS Statistics software - version 25.0. Results: The study participants had a median age of 22, and 78.4% were women. Of the 522 students in the sample, 17.8% were overweight and 6.3% were obese, 14.4% were diagnosed with a chronic disease, 35.6% had Very Good lifestyles, and 20.1% had Good lifestyles. The domains Health and sexual behavior (x-= 8.97/24) and Work/type of personality (x-= 6.82/12) obtained negative scores. Significant differences were found in the questionnaire's total score (U =19785.00; p < 0.05) when considering the variables Gender, with female students having better lifestyles (x-= 89.16; SD = 12.75) and Course year (H = 18.80; p < 0.01). Conclusion: Assessing higher education students' lifestyles offers the possibility to describe the intervention foci and guide the health promotion interventions.

Resumen Marco contextual: La transición a la enseñanza superior representa un periodo de cambio en el que los jóvenes se enfrentan a nuevas experiencias con implicaciones para su estilo de vida. Objetivo: Identificar los dominios de los estilos de vida de los estudiantes de enseñanza superior que necesitan intervención. Metodología: Estudio descriptivo-correlacional, transversal, muestra de 522 estudiantes de enseñanza superior. Cuestionario de estilos de vida Fantástico. Análisis estadístico en IBM SPSS Statistics 25.0. Resultados: Mediana de edad de 22 años, el 78,4% del sexo femenino. De los 522 estudiantes, el 17,8% con exceso de peso; el 6,3 % con obesidad; el 14.4% con una enfermedad crónica; el 35,6% presentó estilos de vida muy bueno, y el 20,1% estilos de vida bueno. Salud y comportamento sexual destacó negativamente (x-= 8,97/24), Trabajo/Tipo Personalidad (x-= 6,82/12). Existen diferencias significativas en la puntuación global del cuestionario (U = 19785,00; p < 0,05) para estudantes mujeres con un mejor estilo de vida (x-= 89,16; DP = 12,75) y dependiendo del año del curso (H = 18,80; p < 0,01). Conclusión: La evaluación de estilos de vida permitió caracterizar los focos de intervención y orientar las intervenciones de promoción de la salud.

Comparative Analysis of Cell Mixtures Deconvolution and Gene Signatures Generated for Blood, Immune and Cancer Cells.

In the last two decades, many detailed full transcriptomic studies on complex biological samples have been published and included in large gene expression repositories. These studies primarily provide a bulk expression signal for each sample, including multiple cell-types mixed within the global signal. The cellular heterogeneity in these mixtures does not allow the activity of specific genes in specific cell types to be identified. Therefore, inferring relative cellular composition is a very powerful tool to achieve a more accurate molecular profiling of complex biological samples. In recent decades, computational techniques have been developed to solve this problem by applying deconvolution methods, designed to decompose cell mixtures into their cellular components and calculate the relative proportions of these elements. Some of them only calculate the cell proportions (supervised methods), while other deconvolution algorithms can also identify the gene signatures specific for each cell type (unsupervised methods). In these work, five deconvolution methods (CIBERSORT, FARDEEP, DECONICA, LINSEED and ABIS) were implemented and used to analyze blood and immune cells, and also cancer cells, in complex mixture samples (using three bulk expression datasets). Our study provides three analytical tools (corrplots, cell-signature plots and bar-mixture plots) that allow a thorough comparative analysis of the cell mixture data. The work indicates that CIBERSORT is a robust method optimized for the identification of immune cell-types, but not as efficient in the identification of cancer cells. We also found that LINSEED is a very powerful unsupervised method that provides precise and specific gene signatures for each of the main immune cell types tested: neutrophils and monocytes (of the myeloid lineage), B-cells, NK cells and T-cells (of the lymphoid lineage), and also for cancer cells.

Identification of a gene expression signature associated with breast cancer survival and risk that improves clinical genomic platforms.

Motivation: Modern genomic technologies allow us to perform genome-wide analysis to find gene markers associated with the risk and survival in cancer patients. Accurate risk prediction and patient stratification based on robust gene signatures is a key path forward in personalized treatment and precision medicine. Several authors have proposed the identification of gene signatures to assign risk in patients with breast cancer (BRCA), and some of these signatures have been implemented within commercial platforms in the clinic, such as Oncotype and Prosigna. However, these platforms are black boxes in which the influence of selected genes as survival markers is unclear and where the risk scores provided cannot be clearly related to the standard clinicopathological tumor markers obtained by immunohistochemistry (IHC), which guide clinical and therapeutic decisions in breast cancer. Results: Here, we present a framework to discover a robust list of gene expression markers associated with survival that can be biologically interpreted in terms of the three main biomolecular factors (IHC clinical markers: ER, PR and HER2) that define clinical outcome in BRCA. To test and ensure the reproducibility of the results, we compiled and analyzed two independent datasets with a large number of tumor samples (1024 and 879) that include full genome-wide expression profiles and survival data. Using these two cohorts, we obtained a robust subset of gene survival markers that correlate well with the major IHC clinical markers used in breast cancer. The geneset of survival markers that we identify (which includes 34 genes) significantly improves the risk prediction provided by the genesets included in the commercial platforms: Oncotype (16 genes) and Prosigna (50 genes, i.e. PAM50). Furthermore, some of the genes identified have recently been proposed in the literature as new prognostic markers and may deserve more attention in current clinical trials to improve breast cancer risk prediction. Availability and implementation: All data integrated and analyzed in this research will be available on GitHub (https://github.com/jdelasrivas-lab/breastcancersurvsign), including the R scripts and protocols used for the analyses. Supplementary information: Supplementary data are available at Bioinformatics Advances online.

Dose and administration time of indocyanine green in near-infrared fluorescence cholangiography during laparoscopic cholecystectomy (DOTIG): study protocol for a randomised clinical trial.

BACKGROUND: One of the most severe complications in laparoscopic cholecystectomy (LC) is intraoperative bile duct injury (BDI). Despite its low incidence, the medical implications for the patient can be serious. Besides, BDI can also generate significant legal issues in healthcare. Different techniques have been described to reduce the incidence of this complication, and near-infrared fluorescence cholangiography with indocyanine green (NIRFC-ICG) is one of the latest additions. In spite of the great interest aroused by this procedure, there are currently great disparities in the usage or administration protocols of ICG. METHODS AND ANALYSIS: This is a randomised, multicentre, per-protocol analysis, open clinical trial with four arms. The estimated duration of the trial is 12 months. The aim of the study is to analyse whether there are differences between the dose and administration ICG intervals to obtain good-quality NIRFC during LC. The primary outcome is the degree of identification of critical biliary structures during LC. In addition, different factors will be analysed that may have an influence on the results of this technique. ETHICS AND DISSEMINATION: The trial will be conducted according to the recommendations for Clinical Trials in the Declaration of Helsinki Ethical Principles for Medical Research Involving Human Subjects and the recommendations of the Spanish Agency of Medicines and Medical Devices (AEMPs) for clinical trials. This trial was approved by the local institutional Ethics Committee and the AEMPs. The results of the study will be presented to the scientific community through publications, conferences or other means. EUDRACT NUMBER: 2022-000904-36. PROTOCOL VERSION: V.1.4, 2 June 2022 TRIAL REGISTRATION NUMBER: NCT05419947.

Systematic Evaluation of Antigenic Stimulation in Chronic Lymphocytic Leukemia: Humoral Immunity as Biomarkers for Disease Evolution.

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world. Studies of CLL antibody reactivity have shown differential targets to autoantigens and antimicrobial molecular motifs that support the current hypothesis of CLL pathogenesis. METHODS: In this study, we conducted a quantitative serum analysis of 7 immunoglobulins in CLL and monoclonal B-cell lymphocytosis (MBL) patients (bead-suspension protein arrays) and a serological profile (IgG and IgM) study of autoantibodies and antimicrobial antigens (protein microarrays). RESULTS: Significant differences in the IgA levels were observed according to disease progression and evolution as well as significant alterations in IgG1 according to IGHV mutational status. More representative IgG autoantibodies in the cohort were against nonmutagenic proteins and IgM autoantibodies were against vesicle proteins. Antimicrobial IgG and IgM were detected against microbes associated with respiratory tract infections. CONCLUSIONS: Quantitative differences in immunoglobulin serum levels could be potential biomarkers for disease progression. In the top 5 tumoral antigens, we detected autoantibodies (IgM and IgG) against proteins related to cell homeostasis and metabolism in the studied cohort. The top 5 microbial antigens were associated with respiratory and gastrointestinal infections; moreover, the subsets with better prognostics were characterized by a reactivation of Cytomegalovirus. The viral humoral response could be a potential prognosis biomarker for disease progression.

Exploring High-Throughput Immunoassays for Biomarker Validation in Rheumatic Diseases in the Context of the Human Proteome Project.

Rheumatic diseases are high prevalence pathologies with different etiology and evolution and low sensitivity in clinical diagnosis. Therefore, it is necessary to develop an early diagnosis method which allows personalized treatment, depending on the specific pathology. The biology/disease initiative, at Human Proteome Project, is an integrative approach to identify relevant proteins in the human proteome associated with pathologies. A previously reported literature data mining analysis, which identified proteins related to osteoarthritis (OA), rheumatoid arthritis (RA), and psoriatic arthritis (PSA) was used to establish a systematic prioritization of potential biomarkers candidates for further evaluation by functional proteomics studies. The aim was to study the protein profile of serum samples from patients with rheumatic diseases such as OA, RA, and PSA. To achieve this goal, customized antibody microarrays (containing 151 antibodies targeting 121 specific proteins) were used to identify biomarkers related to early and specific diagnosis in a screening of 960 serum samples (nondepleted) (OA, n = 480; RA, n = 192; PSA, n = 288). This functional proteomics screening has allowed the determination of a panel (30 serum proteins) as potential biomarkers for these rheumatic diseases, displaying receiver operating characteristics curves with area under the curve values of 80-90%.

Light, moderate and vigorous physical activities: New insights into a virtuous circle with happiness.

The study of the physical activity engagement (PA) has given rise to a relevant research agenda in a wide range of fields, such as its close relationship with subjective well-being, self-perceived health and social capital. Previous evidence has identified interrelationships among these variables, but without considering different levels of physical activity. We have thus considered three levels of activity: light (walking), moderate and vigorous. Structural Equation Modelling (SEM) is undertaken on data from Spain's National Health Survey in 2011-2012 to analyse these interrelationships. The SEM shows a simultaneous and bidirectional relationship between different levels of PA (moderate and vigorous activities) and happiness, with a more robust association stemming from happiness to PA than vice versa. This relationship is mediated through health. From a policy perspective, this implies a virtuous circle: involvement in different levels of PA increases happiness and self-perceived health, while happiness involves higher PA and subsequent positive increases in health and happiness. Nevertheless, this virtuous circle does not always run successfully when social capital is considered to mediate the relationship between PA and happiness, which might explain why it has proven to be very difficult for health policymakers to fight against inactivity and a sedentary lifestyle within a great part of the population.HighlightsWe investigate bidirectional interrelationships between different levels of physical activity (PA) and happiness.We consider the mediation role played by self-perceived health (SPH) and social capital.Our results highlight a network of association between different levels of PA, SPH, social capital and happiness.SPH positively mediates this relationship for any type of PA level, whereas social capital only mediates positively when vigorous PA is developed.From a health policy perspective, the simultaneity between PA levels and happiness implies a virtuous circle.

Consumo de cannabis, grau de risco e policonsumos numa amostra de adultos portugueses / Cannabis use, risk grade, and polydrug use in Portuguese adults / Consumo de cannabis, grado de riesgo y policonsumo en una muestra de adultos portugueses

Resumo Enquadramento: O Observatório Europeu da Droga e da Toxicodependência refere um crescente número de utentes em tratamento por consumo de opiáceos e cannabis. Em Portugal, foram identificadas 72 mortes induzidas por drogas na faixa etária entre os 15 e os 64 anos. Objetivos: Caracterizar, numa amostra de adultos portugueses, os consumos de cannabis, o grau de risco e os policonsumos. Metodologia: Estudo quantitativo, descritivo, correlacional e transversal, com utilização do Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). Resultados: Os resultados revelam frequências de consumo mais elevadas que os estudos epidemiológicos de âmbito nacional para todas as substâncias (com exceção do álcool). O consumo de cannabis é maioritariamente de baixo risco, mas há consumo nocivo e provável dependência. O policonsumo existe, principalmente da cannabis com o álcool e tabaco. Conclusão: O consumo de cannabis aumentou nos últimos anos. Há associação do consumo de cannabis com outras substâncias e há uma relativização dos problemas associados à utilização da cannabis, apesar de a avaliação do grau de risco apontar noutro sentido.

Abstract Background: The European Monitoring Centre for Drugs and Drug Addiction reports an increasing number of patients in treatment for opioid and cannabis use. In Portugal, 72 drug-induced deaths were identified in the 15-64 age group. Objectives: To characterize cannabis use, risk grade, and polydrug use in Portuguese adults. Methodology: Quantitative, descriptive, correlational, and cross-sectional study, using the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). Results: The results reveal higher frequencies of consumption than nationwide epidemiological studies for all substances (except alcohol). Cannabis use is mostly low risk, but there is harmful use and probable dependence. Polydrug use exists, mainly of cannabis with alcohol and tobacco. Conclusion: Cannabis use has increased in recent years; there is an association of cannabis use with other substances; problems associated with cannabis use are relativized, despite the risk assessment pointing in another direction.

Resumen Marco contextual: El European Monitoring Centre for Drugs and Drug Addiction informa de un número creciente de usuarios en tratamiento por consumo de opioides y cannabis. En Portugal, se identificaron 72 muertes inducidas por drogas en el grupo de edad de 15 a 64 años. Objetivos: Caracterizar, en una muestra de adultos portugueses, el consumo de cannabis, el grado de riesgo y el policonsumo. Metodología: Estudio cualitativo, descriptivo, correlacional y transversal, para el cual se utilizó el Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). Resultados: Los resultados muestran frecuencias de consumo superiores a las de los estudios epidemiológicos nacionales para todas las sustancias (excepto el alcohol). El consumo de cannabis es mayoritariamente de bajo riesgo, pero existe un consumo perjudicial y una probable dependencia. Existe policonsumo, principalmente de cannabis con alcohol y tabaco. Conclusión: El consumo de cannabis ha aumentado en los últimos años. Este consumo se asocia a otras sustancias y hay una relativización de los problemas asociados al consumo de cannabis, aunque la evaluación de riesgos apunta en otra dirección.

Unravelling soluble immune checkpoints in chronic lymphocytic leukemia: Physiological immunomodulators or immune dysfunction.

Chronic lymphocytic leukemia (CLL) is a lymphoid neoplasm characterized by the accumulation of mature B cells. The diagnosis is established by the detection of monoclonal B lymphocytes in peripheral blood, even in early stages [monoclonal B-cell lymphocytosis (MBLhi)], and its clinical course is highly heterogeneous. In fact, there are well-characterized multiple prognostic factors that are also related to the observed genetic heterogenicity, such as immunoglobulin heavy chain variable region (IGHV) mutational status, del17p, and TP53 mutations, among others. Moreover, a dysregulation of the immune system (innate and adaptive immunity) has been observed in CLL patients, with strong impact on immune surveillance and consequently on the onset, evolution, and therapy response. In addition, the tumor microenvironment is highly complex and heterogeneous (i.e., matrix, fibroblast, endothelial cells, and immune cells), playing a critical role in the evolution of CLL. In this study, a quantitative profile of 103 proteins (cytokines, chemokines, growth/regulatory factors, immune checkpoints, and soluble receptors) in 67 serum samples (57 CLL and 10 MBLhi) has been systematically evaluated. Also, differential profiles of soluble immune factors that discriminate between MBLhi and CLL (sCD47, sCD27, sTIMD-4, sIL-2R, and sULBP-1), disease progression (sCD48, sCD27, sArginase-1, sLAG-3, IL-4, and sIL-2R), or among profiles correlated with other prognostic factors, such as IGHV mutational status (CXCL11/I-TAC, CXCL10/IP-10, sHEVM, and sLAG-3), were deciphered. These results pave the way to explore the role of soluble immune checkpoints as a promising source of biomarkers in CLL, to provide novel insights into the immune suppression process and/or dysfunction, mostly on T cells, in combination with cellular balance disruption and microenvironment polarization leading to tumor escape.

Deciphering Biomarkers for Leptomeningeal Metastasis in Malignant Hemopathies (Lymphoma/Leukemia) Patients by Comprehensive Multipronged Proteomics Characterization of Cerebrospinal Fluid.

In the present work, leptomeningeal disease, a very destructive form of systemic cancer, was characterized from several proteomics points of view. This pathology involves the invasion of the leptomeninges by malignant tumor cells. The tumor spreads to the central nervous system through the cerebrospinal fluid (CSF) and has a very grim prognosis; the average life expectancy of patients who suffer it does not exceed 3 months. The early diagnosis of leptomeningeal disease is a challenge because, in most of the cases, it is an asymptomatic pathology. When the symptoms are clear, the disease is already in the very advanced stages and life expectancy is low. Consequently, there is a pressing need to determine useful CSF proteins to help in the diagnosis and/or prognosis of this disease. For this purpose, a systematic and exhaustive proteomics characterization of CSF by multipronged proteomics approaches was performed to determine different protein profiles as potential biomarkers. Proteins such as PTPRC, SERPINC1, sCD44, sCD14, ANPEP, SPP1, FCGR1A, C9, sCD19, and sCD34, among others, and their functional analysis, reveals that most of them are linked to the pathology and are not detected on normal CSF. Finally, a panel of biomarkers was verified by a prediction model for leptomeningeal disease, showing new insights into the research for potential biomarkers that are easy to translate into the clinic for the diagnosis of this devastating disease.

Biophysical controls over fire regime properties in Central Portugal.

The concept of fire regime can be used to describe, with different degrees of complexity, the spatial and temporal patterns of fires and their effects within a given area and over a given period. In this work, we explore the relations between fire regime and a set of potential biophysical controls at a local scale, for 972 civil parishes in central Portugal. The fire regime was characterized with reference to a 44-year period (1975-2018) using three properties: cumulative percentage of parish area burned, area-weighted total number of wildfires, and the Gini concentration index of burned area over time. Potential control variables included topography, seasonal temperature and rainfall, and land use/land cover type and patch fragmentation. Ordinal logistic regression was used to model the relations between the fire regime properties and the potential control factors. Results show that the fire regime properties have important spatial contrasts within the study area, and that land use/land cover distribution, spring rainfall and summer temperatures are the major controls over their variability. The percentage of each parish occupied by shrubland and spontaneous herbaceous vegetation is the single most important factor influencing cumulative percentage of parish area burned and the Gini concentration index of burned area, whereas spring rainfall is the foremost factor regarding area-weighted total number of wildfires. Along with the role of spring rainfall in promoting fuel availability later in the year, our results highlight the importance of the speed of regrowth of shrubland and spontaneous herbaceous vegetation after burning, pointing out the need of tailoring fuel management strategies to the properties of each parish.

Tracking the Antibody Immunome in Sporadic Colorectal Cancer by Using Antigen Self-Assembled Protein Arrays.

Sporadic Colorectal Cancer (sCRC) is the third leading cause of cancer death in the Western world, and the sCRC patients presenting with synchronic metastasis have the poorest prognosis. Genetic alterations accumulated in sCRC tumor cells translate into mutated proteins and/or abnormal protein expression levels, which contribute to the development of sCRC. Then, the tumor-associated proteins (TAAs) might induce the production of auto-antibodies (aAb) via humoral immune response. Here, Nucleic Acid Programmable Protein Arrays (NAPPArray) are employed to identify aAb in plasma samples from a set of 50 sCRC patients compared to seven healthy donors. Our goal was to establish a systematic workflow based on NAPPArray to define differential aAb profiles between healthy individuals and sCRC patients as well as between non-metastatic (n = 38) and metastatic (n = 12) sCRC, in order to gain insight into the role of the humoral immune system in controlling the development and progression of sCRC. Our results showed aAb profile based on 141 TAA including TAAs associated with biological cellular processes altered in genesis and progress of sCRC (e.g., FSCN1, VTI2 and RPS28) that discriminated healthy donors vs. sCRC patients. In addition, the potential capacity of discrimination (between non-metastatic vs. metastatic sCRC) of 7 TAAs (USP5, ML4, MARCKSL1, CKMT1B, HMOX2, VTI2, TP53) have been analyzed individually in an independent cohort of sCRC patients, where two of them (VTI2 and TP53) were validated (AUC ~75%). In turn, these findings provided novel insights into the immunome of sCRC, in combination with transcriptomics profiles and protein antigenicity characterizations, wich might lead to the identification of novel sCRC biomarkers that might be of clinical utility for early diagnosis of the tumor. These results explore the immunomic analysis as potent source for biomarkers with diagnostic and prognostic value in CRC. Additional prospective studies in larger series of patients are required to confirm the clinical utility of these novel sCRC immunomic biomarkers.

A Gene Signature Derived from the Loss of CDKN1A (p21) Is Associated with CMS4 Colorectal Cancer.

The epithelial-mesenchymal transition (EMT) is associated with tumor aggressiveness and increased invasion, migration, metastasis, angiogenesis, and drug resistance. Although the HCT116 p21-/- cell line is well known for its EMT-associated phenotype, with high Vimentin and low E-cadherin protein levels, the gene signature of this rather intermediate EMT-like cell line has not been determined so far. In this work, we present a robust molecular and bioinformatics analysis, to reveal the associated gene expression profile and its correlation with different types of colorectal cancer tumors. We compared the quantitative signature obtained with the NanoString platform with the expression profiles of colorectal cancer (CRC) Consensus Molecular Subtypes (CMS) as identified, and validated the results in a large independent cohort of human tumor samples. The expression signature derived from the p21-/- cells showed consistent and reliable numbers of upregulated and downregulated genes, as evaluated with two machine learning methods against the four CRC subtypes (i.e., CMS1, 2, 3, and 4). High concordance was found between the upregulated gene signature of HCT116 p21-/- cells and the signature of the CMS4 mesenchymal subtype. At the same time, the upregulated gene signature of the native HCT116 cells was similar to that of CMS1. Using a multivariate Cox regression model to analyze the survival data in the CRC tumor cohort, we selected genes that have a predictive risk power (with a significant gene risk incidence score). A set of genes of the mesenchymal signature was proven to be significantly associated with poor survival, specifically in the CMS4 CRC human cohort. We suggest that the gene signature of HCT116 p21-/- cells could be a suitable metric for mechanistic studies regarding the CMS4 signature and its functional consequences in CRC. Moreover, this model could help to discover the molecular mechanisms of intermediate EMT, which is known to be associated with extraordinarily high stemness and drug resistance.

Factors that affect health-care workers' practices of medication administration to aged care residents with swallowing difficulties: An Australia-wide survey study.

OBJECTIVES: To understand the barriers and facilitators of medication administration to aged care residents with swallowing difficulties. METHODS: Health-care workers in aged care facilities across Australia involved in medication administration to residents completed an online survey. RESULTS: Of 355 respondents, 90.9% reported 'everyday' encounters with residents with swallowing difficulties and 94.1% modified medications to facilitate administration. Time constraints (63.4%) and workload (69.0%) were common barriers. Only 39.0% believed swallowing abilities are considered at the prescribing stage. Pill size (95.8%), polypharmacy (75.2%) and lack of alternative formulations (74.9%) contributed to these challenges. Support from other health-care professionals (91.5%) and training (85.9%) were the most favoured facilitators. CONCLUSION: Health-care workers are faced with various challenges when caring for residents with swallowing difficulties. Promoting multidisciplinary collaborations, provision of training and medication review services, and improving skill mix and staffing composition in aged care facilities are needed to address these challenges.

Patterns of sports involvement in Spain.

AbstractIn a context of a rise in physical inactivity, this paper aims to provide new insights about the relationship between different forms of sport engagements and their correlates, analysing, for the first time, both active and passive sport involvement for a large sample of individuals. Applying the cluster technique, we identify four different segments of sports involvement among the Spanish population: non-sporty, exclusively practitioner, balanced practitioner, and basically spectator. Also, we develop a multinomial logit model to analyse the main sociodemographic, physical, and sports features that could increase the individual sport involvement, from the non-sporty segment, which assembles the highest number of individuals, to the other clusters. Most of the variables under analysis show a different impact on sport involvement: some of them stimulate active participation (e.g. being member of private sport clubs), whereas others mainly encourage sport attendance (e.g. readers and listeners of sport news, children in the household), and other variables boost sport engagement in general (e.g. being male, educational level, health status, e-sports). The results may have significant implications in terms of developing a general perspective about sport engagement, including both active and passive participation. Particularly, our findings suggest that active and passive sport engagement do not seem to be negatively associated and they can coexist at different levels.

Is Passive Sport Engagement Positively Associated with Happiness?

BACKGROUND: Previous empirical evidence has shown the positive relationship between happiness or subjective well-being (SWB) and sport participation. Nevertheless, passive sport participation has traditionally been ignored as a correlate with happiness. METHODS: Based on a sample of 1,632 Spanish people, one ordered probit model and three extended ordered probit models with an ordinal endogenous covariate technique and robust standard errors were applied. RESULTS: We find that different forms of passive sport participation-such as frequency of attending sporting events and a set of other forms of passive sports participation such as watching sports on TV, listening to sports programmes, reading sports news, and talking to others about sports-are positively associated with happiness. CONCLUSIONS: The results indicate that passive sport participation generally appears to have a closer relationship with individual happiness than active sport participation and emphasise the role played by some forms of sport participation as a source of relational goods. This current research extends the field's understanding of sport participation and happiness, including passive participation, and the relevance of social interactions to account for this association. Finally, the relational aspect of different forms of sport participation offers new implications for the analysis of sport engagement and happiness.

Factors affecting Australian aged care facility workers in administering oral medication to residents with swallowing difficulties.

Swallowing difficulties are common in older people and can complicate the administration of oral medications. The aim of this study was to explore factors affecting healthcare workers in their practices of oral medication administration to aged care residents with swallowing difficulties. A purposeful sample of 17 healthcare workers composed of clinical/care managers, registered nurses (RNs), enrolled nurses (ENs), and assistants in nursing (AINs) from three aged care facilities in Queensland, Australia participated in semi-structured interviews. Leximancer was used for quantitative content analysis. The responses centered on three main factors. Participants discussed workprocess-related factors including time, workload, and stress and frustrations resulting from work processes. Medication-related factors included strategies to facilitate medication administration, uncertainties around modifying medications, availability/cost of alternatives, multidisciplinary medication management, prescribing considerations, and polypharmacy. Resident-related factors were discussed around individualized needs of residents especially those with dementia-associated swallowing difficulties. Ideas differed among the four groups of participants. Managers discussed workprocess-related factors pertaining to staff and facility. RNs focused on how clinical aspects of the medication practices were affected by work processes. ENs were task-oriented and their responses focused on work processes. AIN responses centered on reliance on RNs in performing medication tasks. The findings suggest that healthcare workers' practices of medication administration to residents with swallowing difficulties are affected by various factors associated with work processes, medications, and resident characteristics. Although these factors affect all levels of healthcare workers, the needs of each group vary depending on their level of training and responsibilities.

Appropriateness of oral dosage form modification for aged care residents: a video-recorded observational study.

Background Dosage forms of oral medications are frequently modified in aged care facilities by crushing/splitting tablets or opening capsules to facilitate medication administration for residents with swallowing difficulties. These practices pose safety concerns including the risk of adverse events resulting from loss of dose during transfer and alteration in the rate of absorption. Objective To identify the incidence, methods, and appropriateness of oral dosage form modification practices in aged care facilities. Setting A purposive sample of four urban and regional aged care facilities in Queensland, Australia. Method The processes of modification of oral dosage forms were observed and video-recorded using an action camera placed on medication trolleys. Each video was then reviewed and the details of the medication modification processes were recorded in a data collection form. The appropriateness of the practices of dosage form modification was evaluated against existing national guideline (Australian Don't Rush to Crush Handbook). Deviations from the instructions in the guideline were considered as inappropriate practice. Main outcome measure Incidence and characteristics of inappropriate modification of oral dosage forms. Results Oral dosage forms were modified in 25.7% of 810 observed medications. The most common methods of dosage form modification included crushing tablets with a manual crushing device (71.6%), cutting/splitting tablets (20.2%), and opening capsules (4.3%). According to the national guideline, 12.5% of the modification instances were inappropriate. Inappropriate practices were commonly associated with the suboptimal methods of medication preparation where medications were unsuitably modified, mixed, spilled, or incompletely dosed. Conclusion The modification of oral dosage forms seems a common practice in aged care facilities in Queensland. However, some of these modifications do not comply with the requirements of good practice according to existing guidelines. Healthcare workers in aged care facilities need to be supported and upskilled with effective training to promote the best and safest practices of ODF modification.

Trends of caesarean delivery from 2008 to 2017, Mexico.

Caesarean delivery rates in Mexico are among the highest in the world. Given heightened public and professional awareness of this problem and the updated 2014 national guidelines to reduce the frequency of caesarean delivery, we analysed trends in caesarean delivery by type of facility in Mexico from 2008 to 2017. We obtained birth-certificate data from the Mexican General Directorate for Health Information and grouped the total number of vaginal and caesarean deliveries into five categories of facility: health-ministry hospitals; private hospitals; government employment-based insurance hospitals; military hospitals; and other facilities. Delivery rates were calculated for each category nationally and for each state. On average, 2 114 630 (95% confidence interval, CI: 2 061 487-2 167 773) live births occurred nationally each year between 2008 and 2017. Of these births, 53.5% (1 130 570; 95% CI: 1 108 068-1 153 072) were vaginal deliveries, and 45.3% (957 105; 95% CI: 922 936-991 274) were caesarean deliveries, with little variation over time. During the study period, the number of live births increased by 4.4% (from 1 978 380 to 2 064 507). The vaginal delivery rate decreased from 54.8% (1 083 331/1 978 380) to 52.9% (1 091 958/2 064 507), giving a relative percentage decrease in the rate of 3.5%. The caesarean delivery rate increased from 43.9% (869 018/1 978 380) to 45.5% (940 206/2 064 507), giving a relative percentage increase in the rate of 3.7%. The biggest change in delivery rates was in private-sector hospitals. Since 2014, rates of caesarean delivery have fallen slightly in all sectors, but they remain high at 45.5%. Policies with appropriate interventions are needed to reduce the caesarean delivery rate in Mexico, particularly in private-sector hospitals.

Les taux d'accouchements par césarienne au Mexique sont parmi les plus élevés au monde. Au vu de la sensibilisation accrue de la population et des professionnels à ce problème et de la mise à jour des directives nationales de 2014 visant à diminuer la fréquence des accouchements par césarienne, nous avons analysé l'évolution des accouchements par césarienne selon le type d'établissement entre 2008 et 2017 au Mexique. Nous avons obtenu des données issues d'actes de naissance auprès de la Direction générale mexicaine des informations sur la santé et regroupé le nombre total d'accouchements par voie basse et par césarienne en cinq catégories d'établissement: hôpitaux relevant du ministère de la Santé, hôpitaux publics, hôpitaux relevant de l'assurance liée à l'emploi public, hôpitaux militaires et autres établissements. Les taux d'accouchements ont été calculés pour chaque catégorie à l'échelle nationale et pour chaque État. En moyenne, 2 114 630 (intervalle de confiance, IC, à 95%: 2 061 487-2 167 773) naissances vivantes ont eu lieu chaque année entre 2008 et 2017 à l'échelle nationale. Parmi ces naissances, 53,5% (1 130 570; IC à 95%: 1 108 068-1 153 072) étaient des accouchements par voie basse, et 45,3% (957 105; IC à 95%: 922 936-991 274) étaient des accouchements par césarienne, avec peu de variations dans le temps. Au cours de la période étudiée, le nombre de naissances vivantes a augmenté de 4,4% (de 1 978 380 à 2 064 507). Le taux d'accouchements par voie basse est passé de 54,8% (1 083 331/1 978 380) à 52,9% (1 091 958/2 064 507), ce qui correspond à une diminution relative du taux de 3,5%. Le taux d'accouchements par césarienne est passé de 43,9% (869 018/1 978 380) à 45,5% (940 206/2 064 507), ce qui correspond à une augmentation relative du taux de 3,7%. Le changement le plus important concernant les taux d'accouchements a été constaté dans les hôpitaux du secteur privé. Depuis 2014, les taux d'accouchements par césarienne ont légèrement diminué dans tous les secteurs, mais demeurent élevés (45,5%). Des politiques et des interventions appropriées sont nécessaires pour réduire le taux d'accouchements par césarienne aux Mexique, en particulier dans les hôpitaux de secteur privé.

Las tasas de parto por cesárea en México están entre las más altas del mundo. Dada la creciente concienciación pública y profesional sobre este problema y las directrices nacionales actualizadas de 2014 para reducir la frecuencia de los partos por cesárea, se analizaron las tendencias de los partos por cesárea según el tipo de establecimiento en México entre 2008 y 2017. Se obtuvieron datos de los certificados de nacimiento de la Dirección General de Información Sanitaria de México y se agrupó el número total de partos vaginales y por cesárea en cinco categorías de establecimientos: hospitales del ministerio de salud pública, hospitales privados, hospitales gubernamentales para asegurados por empleo, hospitales militares y otras instalaciones. Se calcularon los índices de partos para cada categoría a nivel nacional y según cada estado. De media, 2 114 630 (intervalo de confianza, IC, del 95 %: 2 061 487­2 167 773) nacimientos vivos se produjeron a nivel nacional al año entre 2008 y 2017. De estos nacimientos, el 53,5 % (1 130 570; IC del 95 %: 1 108 068­1 153 072) fueron partos vaginales y el 45,3 % (957 105; IC del 95 %: 922 936­991 274) fueron partos por cesárea, con poca variación a lo largo del tiempo. Durante el periodo de estudio, el número de nacidos vivos aumentó un 4,4 % (de 1 978 380 a 2 064 507). La tasa de partos vaginales disminuyó del 54,8 % (1 083 331/1 978 380) al 52,9 % (1 091 958/2 064 507), lo que supone una disminución porcentual relativa de la tasa del 3,5 %. La tasa de partos por cesárea aumentó del 43,9 % (869 018/1 978 380) al 45,5 % (940 206/2 064 507), lo que representa un aumento porcentual relativo de la tasa del 3,7 %. El mayor cambio en las tasas de partos se produjo en los hospitales del sector privado. Desde 2014, las tasas de parto por cesárea se han reducido ligeramente en todos los sectores, pero siguen siendo elevadas (45,5 %). Se necesitan políticas con intervenciones apropiadas para reducir la tasa de partos por cesárea en México, especialmente en los hospitales del sector privado.