ProphNet: a generic prioritization method through propagation of information.

BACKGROUND: Prioritization methods have become an useful tool for mining large amounts of data to suggest promising hypotheses in early research stages. Particularly, network-based prioritization tools use a network representation for the interactions between different biological entities to identify novel indirect relationships. However, current network-based prioritization tools are strongly tailored to specific domains of interest (e.g. gene-disease prioritization) and they do not allow to consider networks with more than two types of entities (e.g. genes and diseases). Therefore, the direct application of these methods to accomplish new prioritization tasks is limited. RESULTS: This work presents ProphNet, a generic network-based prioritization tool that allows to integrate an arbitrary number of interrelated biological entities to accomplish any prioritization task. We tested the performance of ProphNet in comparison with leading network-based prioritization methods, namely rcNet and DomainRBF, for gene-disease and domain-disease prioritization, respectively. The results obtained by ProphNet show a significant improvement in terms of sensitivity and specificity for both tasks. We also applied ProphNet to disease-gene prioritization on Alzheimer, Diabetes Mellitus Type 2 and Breast Cancer to validate the results and identify putative candidate genes involved in these diseases. CONCLUSIONS: ProphNet works on top of any heterogeneous network by integrating information of different types of biological entities to rank entities of a specific type according to their degree of relationship with a query set of entities of another type. Our method works by propagating information across data networks and measuring the correlation between the propagated values for a query and a target sets of entities. ProphNet is available at: http://genome2.ugr.es/prophnet. A Matlab implementation of the algorithm is also available at the website.

Evolution over a 15-year period of clinical characteristics and outcomes of critically ill patients with community-acquired bacteremia.

OBJECTIVE: In recent years, outcomes for critically ill patients with severe sepsis have improved; however, no data have been reported about the outcome of patients admitted for community-acquired bacteremia. We aimed to analyze the changes in the prevalence, characteristics, and outcome of critically ill patients with community-acquired bacteremia over the past 15 yrs. DESIGN: A secondary analysis of prospective cohort studies in critically ill patients in three annual periods (1993, 1998, and 2007). SETTING: Forty-seven ICUs at secondary and tertiary care hospitals. PATIENTS: All adults admitted to the participating ICUs with at least one true-positive blood culture finding within the first 48 hrs of admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 829 patients was diagnosed with community-acquired bacteremia during the study periods (148, 196, and 485 in the three periods). The prevalence density rate of community-acquired bacteremia increased from nine per 1000 ICU admissions in 1993 to 24.4 episodes per 1,000 ICU admissions in 2007 (p < 0.001). The prevalence of septic shock also increased from 4.6 episodes/1,000 admissions in 1993 to 14.6 episodes/1,000 admissions in 2007 (p < 0.001). Patients with community-acquired bacteremia were significantly older and had more comorbidities. No significant differences were observed in the presence of Gram-positive and Gram-negative micro-organisms among the three study periods. Mortality related to community-acquired bacteremia decreased over the three study periods: 42%, 32.2%, and 22.9% in 1993, 1998, and 2007, respectively (p < 0.01). The occurrence of septic shock and the number of comorbidities were independently associated with worse outcome. Appropriate antibiotic therapy and development of community-acquired bacteremia in 1998 and 2007 were independently associated with better survival. CONCLUSIONS: The prevalence of community-acquired bacteremia in ICU patients has increased. Despite a higher percentage of more severe and older patients, the mortality associated with community-acquired bacteremia decreased. Improved management of severe sepsis might explain the improvements in outcomes.

Genome-wide differential genetic profiling characterizes colorectal cancers with genetic instability and specific routes to HLA class I loss and immune escape.

AIM: We compared the expression of genes related to inflammatory and cytotoxic functions between MSI and MSS (HLA-class I-negative and HLA-class I-positive) colorectal cancers (CRCs), seeking evidence of differences in inflammatory mediators and cytotoxic T-cell responses. Twenty-two CRCs were divided into three study groups as a function of HLA class I expression and MSI phenotype: 8 MSI tumours, 6 MSS/HLA- tumours and 6 MSS/HLA+ tumours (controls). FINDINGS: A first comparison between eight MSI and six MSS/HLA-positive (control) cancers, based on microarray analysis on an Affymetrix(®) HG-U133-Plus-PM plate, identified 1974 differentially expressed genes (P < 0.05). We grouped genes in Gene Ontology functional categories: apoptotic programme (72 genes, P = 5.5·10(-3)), leucocyte activation (43 genes, P = 1.8·10(-5)), T-cell activation (24 genes, P = 6.3·10(-4)), inflammatory response (40 genes, 2.3·10(-2)) and cytokine production (10 genes, P = 1.9·10(-2)). Real-time PCR and immunohistochemical evaluation were used to validate the data, finding that increased mRNA levels of pro-inflammatory cytokines and cytotoxic mediators were associated with greater infiltration by CD8+T lymphocytes in the MSI group (P < 0.001). Finally, HLA-class I-negative tumours were not grouped together but rather in accordance with features of the gene expression profile of MSI or MSS tumours. As expected, genes associated with antigen processing machinery and MHC class I molecules (TAP2, B2m) were downregulated in MSS/HLA-class I-negative CRCs (n = 6) in comparison to controls. CONCLUSIONS: In conclusion, microarray and immunohistochemical data may be useful to comprehensively assess tumour-host interactions and differentiate MSI from MSS cancers. The two types of tumour, MSI/HLA-class I-negative and MSS/HLA-class I-negative, showed marked differences in the composition and intensity of infiltrating leucocytes, suggesting that their immune escape strategies involve distinct pathways.

Acceleration of the DNA methylation clock among lynch syndrome-associated mutation carriers.

BACKGROUND: DNA methylation (DNAm) age metrics have been widely accepted as an epigenetic biomarker for biological aging and disease. The purpose of this study is to assess whether or not individuals carrying Lynch Syndrome-associated mutations are affected in their rate of biological aging, as measured by the epigenetic clock. METHODS: Genome-wide bisulfite DNA sequencing data were generated using DNA from CD4 + T-cells obtained from peripheral blood using 27 patient samples from Lynch syndrome families. Horvath's DNAm age model based on penalized linear regression was applied to estimate DNAm age from patient samples with distinct clinical and genetic characteristics to investigate cancer mutation-related aging effects. RESULTS: Both Lynch mutation carriers and controls exhibited high variability in their estimated DNAm age, but regression analysis showed steeper slope for the Lynch mutation carriers. Remarkably, six Lynch Syndrome-associated mutation carriers showed a strong correlation to the control group, and two sisters carrying Lynch Syndrome-associated mutations, with no significant difference in lifestyle and similar chronological age, were assigned very different DNAm age. CONCLUSIONS: Future studies will be required to explore, in larger patient populations, whether specific epigenetic age acceleration is predictive of time-to-cancer development, treatment response, and survival. Epigenetic clock DNAm metrics may be affected by the presence of cancer mutations in the germline, and thus show promise of potential clinical utility for stratified surveillance strategies based on the relative risk for imminent emergence of tumor lesions in otherwise healthy Lynch Syndrome-associated mutation carriers.

Latin American consensus: children born small for gestational age.

BACKGROUND: Children born small for gestational age (SGA) experience higher rates of morbidity and mortality than those born appropriate for gestational age. In Latin America, identification and optimal management of children born SGA is a critical issue. Leading experts in pediatric endocrinology throughout Latin America established working groups in order to discuss key challenges regarding the evaluation and management of children born SGA and ultimately develop a consensus statement. DISCUSSION: SGA is defined as a birth weight and/or birth length greater than 2 standard deviations (SD) below the population reference mean for gestational age. SGA refers to body size and implies length-weight reference data in a geographical population whose ethnicity is known and specific to this group. Ideally, each country/region within Latin America should establish its own standards and make relevant updates. SGA children should be evaluated with standardized measures by trained personnel every 3 months during year 1 and every 6 months during year 2. Those without catch-up growth within the first 6 months of life need further evaluation, as do children whose weight is ≤ -2 SD at age 2 years. Growth hormone treatment can begin in SGA children > 2 years with short stature (< -2.0 SD) and a growth velocity < 25th percentile for their age, and should continue until final height (a growth velocity below 2 cm/year or a bone age of > 14 years for girls and > 16 years for boys) is reached. Blood glucose, thyroid function, HbA1c, and insulin-like growth factor-1 (IGF-1) should be monitored once a year. Monitoring insulin changes from baseline and surrogates of insulin sensitivity is essential. Reduced fetal growth followed by excessive postnatal catch-up in height, and particularly in weight, should be closely monitored. In both sexes, gonadal function should be monitored especially during puberty. SUMMARY: Children born SGA should be carefully followed by a multidisciplinary group that includes perinatologists, pediatricians, nutritionists, and pediatric endocrinologists since 10% to 15% will continue to have weight and height deficiency through development and may benefit from growth hormone treatment. Standards/guidelines should be developed on a country/region basis throughout Latin America.

In Patients With Obesity, the Number of Adipose Tissue Mast Cells Is Significantly Lower in Subjects With Type 2 Diabetes.

Type 2 diabetes (T2D) is a rising global health problem mainly caused by obesity and a sedentary lifestyle. In healthy individuals, white adipose tissue (WAT) has a relevant homeostatic role in glucose metabolism, energy storage, and endocrine signaling. Mast cells contribute to these functions promoting WAT angiogenesis and adipogenesis. In patients with T2D, inflammation dramatically impacts WAT functioning, which results in the recruitment of several leukocytes, including monocytes, that enhance this inflammation. Accordingly, the macrophages population rises as the WAT inflammation increases during the T2D status worsening. Since mast cell progenitors cannot arrive at WAT, the amount of WAT mast cells depends on how the new microenvironment affects progenitor and differentiated mast cells. Here, we employed a flow cytometry-based approach to analyze the number of mast cells from omental white adipose tissue (o-WAT) and subcutaneous white adipose tissue (s-WAT) in a cohort of 100 patients with obesity. Additionally, we measured the number of mast cell progenitors in a subcohort of 15 patients. The cohort was divided in three groups: non-T2D, pre-T2D, and T2D. Importantly, patients with T2D have a mild condition (HbA1c <7%). The number of mast cells and mast cell progenitors was lower in patients with T2D in both o-WAT and s-WAT in comparison to subjects from the pre-T2D and non-T2D groups. In the case of mast cells in o-WAT, there were statistically significant differences between non-T2D and T2D groups (p = 0.0031), together with pre-T2D and T2D groups (p=0.0097). However, in s-WAT, the differences are only between non-T2D and T2D groups (p=0.047). These differences have been obtained with patients with a mild T2D condition. Therefore, little changes in T2D status have a huge impact on the number of mast cells in WAT, especially in o-WAT. Due to the importance of mast cells in WAT physiology, their decrease can reduce the capacity of WAT, especially o-WAT, to store lipids and cause hypoxic cell deaths that will trigger inflammation.

An intuitionistic approach to scoring DNA sequences against transcription factor binding site motifs.

BACKGROUND: Transcription factors (TFs) control transcription by binding to specific regions of DNA called transcription factor binding sites (TFBSs). The identification of TFBSs is a crucial problem in computational biology and includes the subtask of predicting the location of known TFBS motifs in a given DNA sequence. It has previously been shown that, when scoring matches to known TFBS motifs, interdependencies between positions within a motif should be taken into account. However, this remains a challenging task owing to the fact that sequences similar to those of known TFBSs can occur by chance with a relatively high frequency. Here we present a new method for matching sequences to TFBS motifs based on intuitionistic fuzzy sets (IFS) theory, an approach that has been shown to be particularly appropriate for tackling problems that embody a high degree of uncertainty. RESULTS: We propose SCintuit, a new scoring method for measuring sequence-motif affinity based on IFS theory. Unlike existing methods that consider dependencies between positions, SCintuit is designed to prevent overestimation of less conserved positions of TFBSs. For a given pair of bases, SCintuit is computed not only as a function of their combined probability of occurrence, but also taking into account the individual importance of each single base at its corresponding position. We used SCintuit to identify known TFBSs in DNA sequences. Our method provides excellent results when dealing with both synthetic and real data, outperforming the sensitivity and the specificity of two existing methods in all the experiments we performed. CONCLUSIONS: The results show that SCintuit improves the prediction quality for TFs of the existing approaches without compromising sensitivity. In addition, we show how SCintuit can be successfully applied to real research problems. In this study the reliability of the IFS theory for motif discovery tasks is proven.

FISim: a new similarity measure between transcription factor binding sites based on the fuzzy integral.

BACKGROUND: Regulatory motifs describe sets of related transcription factor binding sites (TFBSs) and can be represented as position frequency matrices (PFMs). De novo identification of TFBSs is a crucial problem in computational biology which includes the issue of comparing putative motifs with one another and with motifs that are already known. The relative importance of each nucleotide within a given position in the PFMs should be considered in order to compute PFM similarities. Furthermore, biological data are inherently noisy and imprecise. Fuzzy set theory is particularly suitable for modeling imprecise data, whereas fuzzy integrals are highly appropriate for representing the interaction among different information sources. RESULTS: We propose FISim, a new similarity measure between PFMs, based on the fuzzy integral of the distance of the nucleotides with respect to the information content of the positions. Unlike existing methods, FISim is designed to consider the higher contribution of better conserved positions to the binding affinity. FISim provides excellent results when dealing with sets of randomly generated motifs, and outperforms the remaining methods when handling real datasets of related motifs. Furthermore, we propose a new cluster methodology based on kernel theory together with FISim to obtain groups of related motifs potentially bound by the same TFs, providing more robust results than existing approaches. CONCLUSION: FISim corrects a design flaw of the most popular methods, whose measures favour similarity of low information content positions. We use our measure to successfully identify motifs that describe binding sites for the same TF and to solve real-life problems. In this study the reliability of fuzzy technology for motif comparison tasks is proven.

Usefulness of the "Candida score" for discriminating between Candida colonization and invasive candidiasis in non-neutropenic critically ill patients: a prospective multicenter study.

OBJECTIVE: To assess the usefulness of the "Candida score" (CS) for discriminating between Candida species colonization and invasive candidiasis (IC) in non-neutropenic critically ill patients. A rate of IC <5% in patients with CS <3 was the primary end point. DESIGN: Prospective, cohort, observational study. SETTING: Thirty-six medical-surgical intensive care units of Spain, Argentina, and France. PATIENTS: A total of 1,107 non-neutropenic adult intensive care unit patients admitted for at least 7 days between April 2006 and June 2007. MEASUREMENTS AND MAIN RESULTS: Clinical data, surveillance cultures for fungal growth, and serum levels of (1-3)-beta-d-glucan and anti-Candida antibodies (in a subset of patients) were recorded. The CS was calculated as follows (variables coded as absent = 0, present = 1): total parenteral nutrition x1, plus surgery x1, plus multifocal Candida colonization x1, plus severe sepsis x2. A CS >or=3 accurately selected patients at high risk for IC. The colonization index was registered if >or=0.5. The rate of IC was 2.3% (95% confidence interval [CI] 1.06-3.54) among patients with CS <3, with a linear association between increasing values of CS and IC rate (p 7 days, with a CS <3 and not receiving antifungal treatment, the rate of IC was <5%. Therefore, IC is highly improbable if a Candida-colonized non-neutropenic critically ill patient has a CS <3.

Fuzzy association rules for biological data analysis: a case study on yeast.

BACKGROUND: Last years' mapping of diverse genomes has generated huge amounts of biological data which are currently dispersed through many databases. Integration of the information available in the various databases is required to unveil possible associations relating already known data. Biological data are often imprecise and noisy. Fuzzy set theory is specially suitable to model imprecise data while association rules are very appropriate to integrate heterogeneous data. RESULTS: In this work we propose a novel fuzzy methodology based on a fuzzy association rule mining method for biological knowledge extraction. We apply this methodology over a yeast genome dataset containing heterogeneous information regarding structural and functional genome features. A number of association rules have been found, many of them agreeing with previous research in the area. In addition, a comparison between crisp and fuzzy results proves the fuzzy associations to be more reliable than crisp ones. CONCLUSION: An integrative approach as the one carried out in this work can unveil significant knowledge which is currently hidden and dispersed through the existing biological databases. It is shown that fuzzy association rules can model this knowledge in an intuitive way by using linguistic labels and few easy-understandable parameters.

ProphTools: general prioritization tools for heterogeneous biological networks.

Background: Networks have been proven effective representations for the analysis of biological data. As such, there exist multiple methods to extract knowledge from biological networks. However, these approaches usually limit their scope to a single biological entity type of interest or they lack the flexibility to analyze user-defined data. Results: We developed ProphTools, a flexible open-source command-line tool that performs prioritization on a heterogeneous network. ProphTools prioritization combines a Flow Propagation algorithm similar to a Random Walk with Restarts and a weighted propagation method. A flexible model for the representation of a heterogeneous network allows the user to define a prioritization problem involving an arbitrary number of entity types and their interconnections. Furthermore, ProphTools provides functionality to perform cross-validation tests, allowing users to select the best network configuration for a given problem. ProphTools core prioritization methodology has already been proven effective in gene-disease prioritization and drug repositioning. Here we make ProphTools available to the scientific community as flexible, open-source software and perform a new proof-of-concept case study on long noncoding RNAs (lncRNAs) to disease prioritization. Conclusions: ProphTools is robust prioritization software that provides the flexibility not present in other state-of-the-art network analysis approaches, enabling researchers to perform prioritization tasks on any user-defined heterogeneous network. Furthermore, the application to lncRNA-disease prioritization shows that ProphTools can reach the performance levels of ad hoc prioritization tools without losing its generality.

Acciones educativas de la familia con el escolar durante el confinamiento por la COVID-19 / Family educational actions with schoolers during COVID-19 confinement

Introducción: El confinamiento por la COVID-19 ha generado un desafío en la crianza de los escolares. Objetivo: Examinar el desempeño de acciones educativas de la familia con el escolar durante el confinamiento por la COVID-19. Métodos: Investigación descriptiva, muestreo no probabilístico,112 familias. que cumplían aislamiento social en la comunidad Ramón López Peña, San Cristóbal, Artemisa en 2020. Instrumento utilizado: Escala de acciones educativas de la familia con el escolar durante el confinamiento por la COVID-19, construida y validada por los investigadores con alfa de Cronbach= 0,970). Resultados: Las acciones educativas: cumplir los horarios de alimentación y sueño (70,6 por ciento), distribuir los roles en el cuidado del menor (70,6 por ciento), apoyo emocional (70,6 por ciento), apoyar con las teleclases (70,6 por ciento), siempre se realizaron por las familias con desempeño favorable. Las acciones: ayudar a recuperarse de una emoción negativa (72,7 por ciento), alejar al escolar de las preocupaciones y tensiones del hogar (72,7 por ciento), explicar si no entiende los contenidos o buscar ayuda (72,7 por ciento), casi nunca fueron realizadas por las familias con desempeño desfavorable. Conclusiones: La mayoría de las familias presentaron desempeño favorable de acciones educativas. La dimensión Cuidados del menor fue la mejor expresada. Enseñar al escolar las medidas higiénicas de protección; brindar información a los escolares sobre cómo protegerse; enseñar y practicar formas de saludar y de mantenerse conectados con seres queridos y amigos, fueron las acciones educativas más realizadas por ambos grupos de familia. La complejidad del aprendizaje en casa y el manejo afectivo del niño requieren especial atención(AU)

Introduction: COVID-19 confinement has created a challenge in raising schoolers. Objective: Examine the performance of educational actions of the family with the school during the confinement by COVID-19. Methods: Descriptive research, non-probabilistic sampling, 112 families who complied with social isolation in Ramón López Peña community, San Cristobal, Artemisa province in 2020. Instrument used: Scale of educational actions of the family with school children during confinement by COVID-19, built and validated by researchers with Cronbach´s alpha = 0.970. Results: Educational actions as meeting food and sleep schedules (70.6 percent), distributing roles in child care (70.6 percent), emotional support (70.6 percent), supporting with teleclasses (70.6 percent) were always carried out by families with favorable performance. Actions like helping to recover from negative emotions (72.7 percent), keeping the schooler away from household concerns and tensions (72.7 percent), explaining whether they don't understand the contents or looking for help (72.7 percent) were almost never made by families with unfavorable performance. Conclusions: Most families had a favorable performance in educational actions. The Child Care dimension was the best performed one. Teaching the schoolchildren the hygienic protective measures, provide information to schoolchildren on how to protect themselves, teaching and practicing ways to greet and stay connected with loved ones and friends were the most performed educational actions by both family groups. The complexity of home learning and the child's affective management require special attention(AU)

[Postsurgery meningitis by Staphylococcus aureus: comparison between methicillin-sensitive and resistant strains]. / Estudio comparativo de la meningitis posquirúrgica por Staphylococcus aureus sensible y resistente a meticilina.

BACKGROUND AND OBJECTIVE: In recent years, meningitis caused by methicillin-resistant S. aureus has increased. This study was undertaken to compare the clinical characteristics and prognosis of methicillin-resistant S. aureus (MRSA) postneurosurgical meningitis and methicillin-sensible S. aureus (MSSA) postneurosurgical meningitis. PATIENTS AND METHODS: Twenty-five episodes of postneurosurgical meningitis due to S. aureus (13 methicillin-resistant strains) seen during a ten-year period were retrospectively reviewed. RESULTS: Most common underlying diseases were: intracerebral hemorrhage (50% of MRSA patients and 46% of MSSA patients) and neoplasm (53% of MRSA patients and 33% of MSSA patients). Eleven patients (6 of them with MRSA infection) had received antibiotic treatment previously. Thirteen patients were carriers of intraventricular catheters (8 with MRSA infection), 5 wore a ventriculoperitoneal shunt (4 with infections by MSSA), 5 cases had a CSF leakage (4 with infections by MRSA), and one patient with infection by MSSA wore an epidural catheter. Fifteen patients were cured (7 with MRSA infection), and 8 died due to the infection (27% with MSSA infection and 38% with MRSA infection). CONCLUSIONS: The prognosis of postneurosurgical meningitis by S. aureus does not depend on the presence of resistance to methicillin. Nowadays, the intravenous administration of vancomycin is the treatment of choice in MRSA meningitis.

DrugNet: network-based drug-disease prioritization by integrating heterogeneous data.

OBJECTIVE: Computational drug repositioning can lead to a considerable reduction in cost and time in any drug development process. Recent approaches have addressed the network-based nature of biological information for performing complex prioritization tasks. In this work, we propose a new methodology based on heterogeneous network prioritization that can aid researchers in the drug repositioning process. METHODS: We have developed DrugNet, a new methodology for drug-disease and disease-drug prioritization. Our approach is based on a network-based prioritization method called ProphNet which has recently been developed by the authors. ProphNet is able to integrate data from complex networks involving a wide range of types of elements and interactions. In this work, we built a network of interconnected drugs, proteins and diseases and applied DrugNet to different types of tests for drug repositioning. RESULTS: We tested the performance of our approach on different validation tests, including cross validation and tests based on real clinical trials. DrugNet achieved a mean AUC value of 0.9552±0.0015 in 5-fold cross validation tests, and a mean AUC value of 0.8364 for tests based on recent clinical trials (phases 0-4) not present in our data. These results suggest that DrugNet could be very useful for discovering new drug uses. We also studied specific cases of particular interest, proving the benefits of heterogeneous data integration in this problem. CONCLUSIONS: Our methodology suggests that new drugs can be repositioned by generating ranked lists of drugs based on a given disease query or vice versa. Our study shows that the simultaneous integration of information about diseases, drugs and targets can lead to a significant improvement in drug repositioning tasks. DrugNet is available as a web tool from http://genome2.ugr.es/drugnet/ (accessed 23.09.14). Matlab source code is also available on the website.

Vulnerabilidad al estrés en pacientes adultos hipertensos / Vulnerability to the stress in hypertensive adult patients

RESUMEN Introducción: En la hipertensión, el estrés constituye un factor sicosocial de riesgo. Objetivo: establecer la relación entre vulnerabilidad al estrés con variables sociodemográficas y clínicas en pacientes hipertensos adultos del Policlínico Santa Cruz. Métodos: Estudio descriptivo, transversal. El universo lo conformaron 65 hipertensos, diagnosticados de enero a junio del 2019. La muestra intencional fue de 58 hipertensos. Para la recogida de información se emplearon: la Historia Clínica Individual y familiar y el Test de Vulnerabilidad al Estrés. Resultados: Predominio del 70,7 % de hipertensos en la tercera subetapa de la adultez, supremacía femenina (69,0 %); la mayoría con secundaria básica terminada (36,2 %); casados (44,8 %) y trabajadores estatales (51,7 %); predominaron los fumadores (81 %); prevaleció la hipertensión arterial grado II (69 %) y dieron cumplimiento al tratamiento el 53,4 %. La mayoría presentó vulnerabilidad al estrés (65,5%); mejor representado en la tercera subetapa de la adultez (81,6 %), mujeres (63,2 %), con secundaria básica terminada (39,5 %), casados (42,1 %), trabajador estatal (55,3 %), fumadores (76,3 %), con hipertensión arterial grado II el 76,3 %; cumplieron el tratamiento siempre el 55,3 %; presentaron nivel vulnerable al estrés el 68,4 % de los hipertensos. Existió asociación entre el nivel seriamente vulnerable al estrés y la escolaridad primaria (p= 0,007). La mayoría de los hipertensos presentaron vulnerabilidad al estrés. El nivel vulnerable al estrés predominó; mejor representado en la tercera subetapa de la adultez, en las mujeres, los fumadores, los hipertensos grado II y los que siempre cumplían con el tratamiento. Existió asociación entre el nivel seriamente vulnerable al estrés y la escolaridad primaria.

ABSTRACT Introduction: In the hypertension, the stress constitutes a psychosocial risk factor. Objective: To establish the relation between vulnerability to the stress with socio-demographics and clinical variables in adult hypertensive patients of the General hospital Santa Cruz. Methods: Descriptive, transverse study. The universe was constituted of 65 hypertensive patients, diagnosed from January until June, 2019. The intentional sample was 58 hypertensive patients. For the information collection, it was used: the Individual and familiar Case history and the Test of Vulnerability to the Stress. Results: Predominance 70.7 % of hypertensive patients in the third sub-stage of the adulthood, feminine supremacy (69.0 %); the majority with secondary school finished (36.2 %); married (44.8 %) and state workpeople (51.7 %); there prevailed the smokers (81 %); the arterial hypertension grade II prevailed (69 %) and they fulfilled the treatment 53.4 %. The majority presented vulnerability to the stress (65.5 %); better represented in the third sub-stage of the adulthood (81.6 %), women (63.2 %), with secondary school finished (39.5 %), married (42.1 %), state worker (55.3 %), smokers (76.3 %), with arterial hypertension grade II 76.3 %; they always fulfilled the treatment 55.3 %; they presented vulnerable level to the stress 68.4 % of the hypertensive patients. Association existed between the level seriously vulnerably to the stress and the primary schooling (p = 0.007). Discussion: Most of the hypertensive patients presented vulnerability to the stress. The vulnerable level to the stress prevailed; better represented in the third sub-stage of the adulthood, in the women, the smokers, hypertensive grade II and those who were always fulfilled with the treatment. Association existed between the level seriously vulnerably to the stress and the primary schooling.

Differences in the deflation limb of the pressure-volume curves in acute respiratory distress syndrome from pulmonary and extrapulmonary origin.

OBJECTIVE: To assess the differences in the deflation pressure-volume (PV) curves between acute respiratory distress syndrome from pulmonary (ARDSp) and extrapulmonary (ARDSe) origin. DESIGN: . Prospective study. SETTING: Twenty-bed intensive care unit in an university hospital. PATIENTS: Ten patients within the first 24 h from meeting ARDS criteria, classified as ARDSp or ARDSe in a clinical basis. INTERVENTIONS: A deflation PV curve was recorded by means of decreasing steps of continuous positive airway pressure (CPAP) from 35 to 0 cmH(2)O. RESULTS: The simultaneous recording of pressure at the airway opening (Pao), esophageal pressure (Pes) and volumes (V) allows us to trace the Pao-V, Pes-V and transpulmonary pressure (Ptp)-V curves. These data were fitted to a sigmoid model and ARDSp and ARDSe groups were compared. ARDSp has lower lung compliance and higher chest wall compliance than ARDSe (35.9+/-11.3 vs. 77.2+/-50.6 and 199.6+/-44.4 vs. 125.5+/-16.5 ml/cmH(2)O, respectively, P<0.05). The Pao-V curve in ARDSp is shifted down and right with respect to ARDSe. The Ptp-V curve shows a similar displacement. The Pes-V curve in the ARDSp group is, however, shifted to the left. When relative values (percentage to the maximum volume achieved at 35 cmH(2)O) are considered, these differences persist, but, in the Ptp-V curves, are only significant in the low-pressure range. CONCLUSIONS: Differences between ARDSp and ARDSe PV curves are present all along the pressure axis and are related to differences not only in the Pes-V curve, but also in the Ptp-V curve.

Early antibiotic treatment (prophylaxis) of septic complications in severe acute necrotizing pancreatitis: a prospective, randomized, multicenter study comparing two regimens with imipenem-cilastatin.

OBJECTIVE: We compared two imipenem regimens for prevention of septic complications in patients with severe acute necrotizing pancreatitis (ANP). DESIGN AND SETTING: Prospective, randomized open clinical trial involving intensive care units of 14 Spanish Hospitals. PARTICIPANTS: 92 patients with ANP. INTERVENTIONS: Imipenem/cilastatin was administered at 500 mg four times daily starting at the time of diagnosis of ANP, within the first 96 h from the onset of symptoms. Patients were randomized to receive antibiotic prophylaxis either for 14 days (group 1) or at least for 14 days and as long as major systemic complications of the disease persisted (group 2). RESULTS: Antibiotic was maintained in group 2 for 19.7+/-10.9 days. The incidence of infected pancreatic necrosis, pancreatic abscess, and extrapancreatic infections was 11%, 17%, and 28% in group 1 and 17.4%, 13%, and 35% in group 2 (n.s.). Pancreatic or extrapancreatic infection by Candida albicans occurred in 7% and 22% of patients. Global mortality was 18.5% (10.9% secondary to septic complications), without differences between groups. In patients with persisting systemic complications at day 14 mortality was almost always secondary to septic complications and decreased from 25% (group 1) to 8.8% (group 2) by maintaining antibiotic prophylaxis. CONCLUSIONS: Compared to a 14-day imipenem prophylaxis, a longer antibiotic administration in patients with ANP is not associated with a reduction in the incidence of septic complications of the disease. However, prolonged imipenem administration in patients with persisting systemic complications tends to reduce mortality in ANP compared to a 14-days regimen.

[Enterococcal infections in critically ill patients admitted to ICU]. / Infección por enterococo en pacientes críticos ingresados en la UCI.

BACKGROUND AND OBJECTIVE: To determine the frequency of infections caused by Enterococcus spp. in critically ill patients admitted to ICUs in Spain and to describe the clinical features and outcome of those patients in whom this pathogen was isolated. PATIENTS AND METHOD: Prospective, observational, multicenter study. Patients admitted to the ICUs who participated in the National Surveillance Study of Nosocomial Infections (ENVIN) from 1997 to 2001 were included. Patients were classified as infected by Enterococcus spp., infected by other pathogens, and without nosocomial infection (non-infected). RESULTS: Of 21,972 patients, 2,177 (9.9%) had acquired 3,490 nosocomial infections during their stay in the ICU. In 223 patients (10.2%), 239 episodes of infections in which one of the causative pathogen was Enterococcus spp. were identified (cumulative incidence 1.1 episodes of Enterococcus spp. infection per 100 patients). Enterococcus spp. accounted for urinary infection in 14.3% of cases and secondary bacteremia in 12.2% especially those related with abdominal infection (20%) and soft tissue infection (21.4%). Predominant species was E. faecalis in 197 isolates (82.4%). After multivariate analysis, variables significantly associated with infection caused by Enterococcus spp. included: age (odds ratio [OR]=1.13; 95% confidence interval [CI], 1.01-1.25); APACHE II score (OR=1.19; CI 95%, 1.07-1.32); and length of ICU stay (OR=1.02; CI 95%, 1.01-1.03). There were no differences in the overall ICU mortality rate between patients with Enterococcus spp. infection (31.8%) and those with infection caused by other pathogens (31.8%), although in both cases the mortality rate was significantly higher than in non-infected patients (11.1%). CONCLUSIONS: Enterococcus spp. was present in 10.2% patients with ICU-acquired infection. Infection by Enterococcus spp. mainly occurred in the form of urinary tract infection and secondary bacteremia, mainly related to abdominal and soft tissue infections. E. faecalis predominated in all foci. There were no differences in mortality between patients with Enterococcus spp. infection and patients with infection caused by other pathogens.

CisMiner: genome-wide in-silico cis-regulatory module prediction by fuzzy itemset mining.

Eukaryotic gene control regions are known to be spread throughout non-coding DNA sequences which may appear distant from the gene promoter. Transcription factors are proteins that coordinately bind to these regions at transcription factor binding sites to regulate gene expression. Several tools allow to detect significant co-occurrences of closely located binding sites (cis-regulatory modules, CRMs). However, these tools present at least one of the following limitations: 1) scope limited to promoter or conserved regions of the genome; 2) do not allow to identify combinations involving more than two motifs; 3) require prior information about target motifs. In this work we present CisMiner, a novel methodology to detect putative CRMs by means of a fuzzy itemset mining approach able to operate at genome-wide scale. CisMiner allows to perform a blind search of CRMs without any prior information about target CRMs nor limitation in the number of motifs. CisMiner tackles the combinatorial complexity of genome-wide cis-regulatory module extraction using a natural representation of motif combinations as itemsets and applying the Top-Down Fuzzy Frequent- Pattern Tree algorithm to identify significant itemsets. Fuzzy technology allows CisMiner to better handle the imprecision and noise inherent to regulatory processes. Results obtained for a set of well-known binding sites in the S. cerevisiae genome show that our method yields highly reliable predictions. Furthermore, CisMiner was also applied to putative in-silico predicted transcription factor binding sites to identify significant combinations in S. cerevisiae and D. melanogaster, proving that our approach can be further applied genome-wide to more complex genomes. CisMiner is freely accesible at: http://genome2.ugr.es/cisminer. CisMiner can be queried for the results presented in this work and can also perform a customized cis-regulatory module prediction on a query set of transcription factor binding sites provided by the user.