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%.

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.

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.

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.

[Prevalence and relations of orthostatic hypotension in patients 80 years old and over from a primary care unit]. / Prevalencia y relaciones de la hipotensión ortostática en los pacientes de 80 o más años de edad de una unidad de atención primaria.

OBJECTIVE: To estimate the prevalence of orthostatic hypotension (OH) in patients 80 years old and over attending a primary care unit. To relate OH to the most prevalent pathologies and to the most used drugs. DESIGN: Transversal observational study. LOCATION: Primary care unit, Santiago de Compostela. PARTICIPANTS: Eighty one patients 80 years old or over representative of a primary care unit were recruited. Ten patients were excluded. MAIN MEASUREMENTS: Blood pressure was measured in decubitus and later in erect position first immediately after standing and then after 3 minutes. Diagnoses and active treatments were reviewed in the electronic clinical history and through an interview with the patient and caregiver. RESULTS: In 26.76% of patients the systolic blood pressure fell by 20mmHg or more and/or the diastolic blood pressure fell by 10mmHg in the instant following the postural shift. In 16.90% of patients the drop persisted after 3 minutes of standing from decubitus position. None of the patients was diagnosed with OH. The highest prevalence ratio was observed for diabetes mellitus (1.6; P=.412), not existing differences for arterial hypertension (P=.881). OH related in a statistically meaningful way to the use of renin angiotensin aldosterone system inhibitors (OR: 8.174, CI95%: 1.182-56.536); P=.033] and benzodiazepines (OR: 5.938, CI95%: 1.242-28.397; P=.026)]. CONCLUSION: OH had a prevalence of 16.90% among the elderly patients who had a consultation. Its connection with some drugs (renin angiotensin aldosterone system inhibitors and benzodiazepines) must be considered.

Current state and future of pediatric allergology in Europe: A road map.

The history of pediatric allergology (PA) in Europe is relatively youthful, dating back to 1984, when a small group of pediatricians founded the European Working Group on Pediatric Allergy and Immunology-later giving rise to ESPACI (European Society on Pediatric Allergology and Clinical Immunology). In 1990, the first dedicated journal, Pediatric Allergy and Immunology (PAI), was founded. There are striking differences across Europe, and even within European countries, in relation to the training pathways for doctors seeing children with allergic disease(s). In 2016, the EAACIClemens von Pirquet Foundation (CvP) organized and sponsored a workshop with the European Academy of Allergy and Clinical Immunology (EAACI) Pediatric Section. This collaboration focussed on the future of PA and specifically on education, research, and networking/ advocacy. The delegates representing many countries across Europe have endorsed the concept that optimal care of children with allergic diseases is delivered by pediatricians who have received dedicated training in allergy, or allergists who have received dedicated training in pediatrics. In order to meet the needs of children and families with allergic disease(s), the pediatric allergist is highly encouraged to develop several networks. Our challenge is to reinforce a clear strategic approach to scientific excellence to across our member base and to ensure and enhance the relevance of European pediatric research in allergy. With research opportunities in basic, translational, clinical, and epidemiologic trials, more trainees and trained specialists are needed and it is an exciting time to be a pediatric allergologist.

Rationale, design and preliminary results of the GALIPEMIAS study (prevalence and lipid control of familial dyslipidemia in Galicia, northwest Spain).

AIMS: There is little information on the familial nature of dyslipidemias in the Spanish population. This knowledge could have potential diagnostic and treatment implications. The objective of the GALIPEMIAS study was to determine the prevalence of familial dyslipidemia in Galicia, as well as determine the degree of lipid control in the participants. Prevalence of atherosclerotic cardiovascular disease (ASCVD) was also estimated. This paper presents the design, methodology and selected preliminary results. METHODOLOGY: A cross-sectional study was performed in the population aged ≥18 years using cluster sampling and then random sampling. A sample of 1000 subjects was calculated and divided into three sequential phases with a specific methodology for each one. Phase I: selection of subjects from the general population and collection of informed consent documents; Phase II: collection of data from the digital clinical history to select subjects with dyslipidemia according to study criteria; Phase III: personal interview, blood analysis, family tree, and definitive diagnosis of dyslipidemia. Prevalence of different diseases and active medication was analysed. Corrected prevalence (to the reference population) of different risk factors and ASCVD was estimated. RESULTS: Phase I participation was 89.5%. We extracted complete information from 93% of the participants (Phase II). According to the study's own criteria, 56.5% (n = 527) of the participants had some form of dyslipidemia and almost 33.7% of them had familial dyslipidemia with autosomal dominant inherit pattern. The corrected prevalence of ASCVD was 5.1% (95% CI 3.1-7.2). CONCLUSIONS: Dyslipidemia was the most prevalent cardiovascular risk factor in our population with an autosomal dominant inheritance pattern in one out of every three dyslipidemia cases. Approximately, 5.1% of the sample population aged ≥18 has suffered an episode of ACVD.

Identification of expression patterns in the progression of disease stages by integration of transcriptomic data.

BACKGROUND: In the study of complex diseases using genome-wide expression data from clinical samples, a difficult case is the identification and mapping of the gene signatures associated to the stages that occur in the progression of a disease. The stages usually correspond to different subtypes or classes of the disease, and the difficulty to identify them often comes from patient heterogeneity and sample variability that can hide the biomedical relevant changes that characterize each stage, making standard differential analysis inadequate or inefficient. RESULTS: We propose a methodology to study diseases or disease stages ordered in a sequential manner (e.g. from early stages with good prognosis to more acute or serious stages associated to poor prognosis). The methodology is applied to diseases that have been studied obtaining genome-wide expression profiling of cohorts of patients at different stages. The approach allows searching for consistent expression patterns along the progression of the disease through two major steps: (i) identifying genes with increasing or decreasing trends in the progression of the disease; (ii) clustering the increasing/decreasing gene expression patterns using an unsupervised approach to reveal whether there are consistent patterns and find genes altered at specific disease stages. The first step is carried out using Gamma rank correlation to identify genes whose expression correlates with a categorical variable that represents the stages of the disease. The second step is done using a Self Organizing Map (SOM) to cluster the genes according to their progressive profiles and identify specific patterns. Both steps are done after normalization of the genomic data to allow the integration of multiple independent datasets. In order to validate the results and evaluate their consistency and biological relevance, the methodology is applied to datasets of three different diseases: myelodysplastic syndrome, colorectal cancer and Alzheimer's disease. A software script written in R, named genediseasePatterns, is provided to allow the use and application of the methodology. CONCLUSION: The method presented allows the analysis of the progression of complex and heterogeneous diseases that can be divided in pathological stages. It identifies gene groups whose expression patterns change along the advance of the disease, and it can be applied to different types of genomic data studying cohorts of patients in different states.

The Post-Ureteroscopic Lesion Scale (PULS): a multicenter video-based evaluation of inter-rater reliability.

PURPOSE: The Post-Ureteroscopic Lesion Scale (PULS) offers a simple grading system for the description of ureteral lesions after ureteroscopy. In this article, we present the results of a video-based multicenter evaluation of the inter-rater reliability of clinically important PULS grades 0-3. METHODS: Video sequences at the end of ureteroscopy (final passage) were recorded for 100 consecutive patients at a single institution and assessed by experienced urologists (n = 20) and senior residents (n = 17) at 19 international centers. The cohort included only patients with lesions grades 0-3 (with grades 2 and 3 subsumed as 2 + since distinction is defined by an extravasation of contrast medium in fluoroscopy). The gradings were evaluated for inter-rater reliability and in terms of simplicity, validity, comprehensibility, reproducibility, and usefulness. RESULTS: Overall, inter-rater reliability was high (Kendall's W = 0.69, p < 0.001) and was comparable between specialists (Kendall's W = 0.69, p < 0.001) and residents (Kendall's W = 0.71, p < 0.001). The matched ratings showed grade 0 in 43.0 % of patients and grades 1 or 2 + in 44.0 and 13.0 % of patients, respectively. Results of the questionnaires indicated a high degree of acceptance, with an overall rating of 1.76 (1.64-1.93 for different items, scale 1-6). CONCLUSIONS: Inter-rater reliability of the endoscopically assessable PULS was high among urologists with different levels of experience in different countries worldwide. The validated PULS system may be used for standardized reporting of ureteral lesions/injuries after ureteroscopy. In addition, PULS will enable more selective standardization of indications for postoperative DJ stenting based on the randomized controlled trials.

Blood pressure values and depression in hypertensive individuals at high cardiovascular risk.

BACKGROUND: Hypertension and depression are both important risk factors for cardiovascular diseases. Nevertheless, the association of blood pressure on and depression has not been completely established. This study aims to analyze whether depression may influence the control of blood pressure in hypertensive individuals at high cardiovascular risk. METHODS: Cross-sectional study, embedded within the PREDIMED clinical trial, of 5954 hypertensive patients with high cardiovascular risk factor profiles. The relationship between blood pressure control and depression was analyzed. A multivariate analysis (logistic and log-linear regression), adjusting for potential confounders (socio-demographic factors, body mass index, lifestyle, diabetes, dyslipidemia, and antihypertensive treatment), was performed. RESULTS: Depressive patients, with and without antidepressant treatment, had better blood pressure control (OR: 1.28, CI 95%: 1.06-1.55, and OR: 1.30, CI 95%: 1.03-1.65, respectively) than non-depressive ones. Regarding blood pressure levels, systolic blood pressure values (mmHg) were found to be lower in both treated and untreated depressive patients (Log coefficient Beta: -1.59, 95% CI: -0.50 to -2.69 and Log coefficient Beta: -3.49, 95% CI: -2.10 to -4.87, respectively). CONCLUSIONS: Among hypertensive patients at high cardiovascular risk, the control of blood pressure was better in those diagnosed with depression. TRIAL REGISTRATION: Unique identifier: ISRCTN35739639.

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.

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.

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.

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.

Combined analysis of genome-wide expression and copy number profiles to identify key altered genomic regions in cancer.

BACKGROUND: Analysis of DNA copy number alterations and gene expression changes in human samples have been used to find potential target genes in complex diseases. Recent studies have combined these two types of data using different strategies, but focusing on finding gene-based relationships. However, it has been proposed that these data can be used to identify key genomic regions, which may enclose causal genes under the assumption that disease-associated gene expression changes are caused by genomic alterations.

[The scientific entertainer in primary health care]. / La animación científica en atención primaria.

The scientific method is capable of being applied in primary care. In this article we defend the role of the "scientific entertainer "as strategic and necessary in achieving this goal. The task has to include playful and light-hearted content. We explore some words in English that may help us to understand the concept of "scientific entertainer" from a semantic point of view (showman, master of ceremonies, entrepreneur, go-between) also in Spanish language (counsellor, mediator, methodologist) and finally in Latin and Greek (tripalium, negotium, chronos, kairos). We define the clinical, manager or research health-worker who is skilled in primary care as a "primarylogist".

Drug administration guides in dysphagia.

BACKGROUND: Patients with dysphagia are more likely to suffer medication administration errors than those without swallowing difficulties. AIM: To evaluate the use of individualised medication administration guides (I-MAGs) for patients with dysphagia on one stroke ward over six months. METHOD: A specialist pharmacist in dysphagia designed a software package supported with data on national guidelines on administering medicines to this group, which enabled the pharmacist to create I-MAGs. Once the pilot was completed, a questionnaire was given to all nurses, pharmacists and speech and language therapists who had used the guides. RESULTS: Of 26 health professionals approached, 19 returned questionnaires. Eight (62%) nurses felt more confident in their practice when I-MAGs were in place. CONCLUSION: I-MAGs were well received and supported individualised care. However, they needed additional pharmacist input and greater nursing time. Research to determine the guides' cost-effectiveness is needed.

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.

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.

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.