Interaction between ATM and PARP-1 in response to DNA damage and sensitization of ATM deficient cells through PARP inhibition

ATM and PARP-1 are two of the most important players in the cell's response to DNA damage. PARP-1 and ATM recognize and bound to both single and double strand DNA breaks in response to different triggers. Here we report that ATM and PARP-1 form a molecular complex in vivo in undamaged cells and this association increases after gamma-irradiation. ATM is also modified by PARP-1 during DNA damage. We have also evaluated the impact of PARP-1 absence or inhibition on ATM-kinase activity and have found that while PARP-1 deficient cells display a defective ATM-kinase activity and reduced gamma-H2AX foci formation in response to gamma-irradiation, PARP inhibition on itself is able to activate ATM-kinase. PARP inhibition induced gamma H2AX foci accumulation, in an ATM-dependent manner. Inhibition of PARP also induces DNA double strand breaks which were dependent on the presence of ATM. As consequence ATM deficient cells display an increased sensitivity to PARP inhibition. In summary our results show that while PARP-1 is needed in the response of ATM to gamma irradiation, the inhibition of PARP induces DNA double strand breaks (which are resolved in and ATM-dependent pathway) and activates ATM kinase.

Prediction of postpartum depression using multilayer perceptrons and pruning.

OBJECTIVE. The main goal of this paper is to obtain a classification model based on feed-forward multilayer perceptrons in order to improve postpartum depression prediction during the 32 weeks after childbirth with a high sensitivity and specificity and to develop a tool to be integrated in a decision support system for clinicians. MATERIALS AND METHODS. Multilayer perceptrons were trained on data from 1397 women who had just given birth, from seven Spanish general hospitals, including clinical, environmental and genetic variables. A prospective cohort study was made just after delivery, at 8 weeks and at 32 weeks after delivery. The models were evaluated with the geometric mean of accuracies using a hold-out strategy. RESULTS. Multilayer perceptrons showed good performance (high sensitivity and specificity) as predictive models for postpartum depression. CONCLUSIONS. The use of these models in a decision support system can be clinically evaluated in future work. The analysis of the models by pruning leads to a qualitative interpretation of the influence of each variable in the interest of clinical protocols.

Sources of pre-analytical variations in yield of DNA extracted from blood samples: analysis of 50,000 DNA samples in EPIC.

The European Prospective Investigation into Cancer and nutrition (EPIC) is a long-term, multi-centric prospective study in Europe investigating the relationships between cancer and nutrition. This study has served as a basis for a number of Genome-Wide Association Studies (GWAS) and other types of genetic analyses. Over a period of 5 years, 52,256 EPIC DNA samples have been extracted using an automated DNA extraction platform. Here we have evaluated the pre-analytical factors affecting DNA yield, including anthropometric, epidemiological and technical factors such as center of subject recruitment, age, gender, body-mass index, disease case or control status, tobacco consumption, number of aliquots of buffy coat used for DNA extraction, extraction machine or procedure, DNA quantification method, degree of haemolysis and variations in the timing of sample processing. We show that the largest significant variations in DNA yield were observed with degree of haemolysis and with center of subject recruitment. Age, gender, body-mass index, cancer case or control status and tobacco consumption also significantly impacted DNA yield. Feedback from laboratories which have analyzed DNA with different SNP genotyping technologies demonstrate that the vast majority of samples (approximately 88%) performed adequately in different types of assays. To our knowledge this study is the largest to date to evaluate the sources of pre-analytical variations in DNA extracted from peripheral leucocytes. The results provide a strong evidence-based rationale for standardized recommendations on blood collection and processing protocols for large-scale genetic studies.

Modelo de estadios de cambio: compatibilidad con relatos biográficos de mujeres que sufren violencia doméstica

This study aims to analyze the adjustment of women, victims of intimate partner violence, by applying the Prochaska and Di Clemente Stages of Change Model. An interpretative qualitative study was made in 35 domestic violence victims women detected in primary care, women who recognized their relationship as abusive (perceived maltreatment). This is a multicentric study, with participation of six health centers of Malaga city. Biographical Narration technique by audio-recorded and transcribed interview was used; about this, thematic analysis adjustment to Transtheoretic Model phases was applied. ATLAS-TI 5.0 program was used for codification. Precontemplative, maintenance and ending stages were more represented while action phases were poorly mentioned. Main phases characteristics were: "blindness" and inexplicability in precontemplative stage; pros / cons analysis in contemplative phase; making decisions difficulty in action phases; suffering and going ahead purpose in maintenance stage, and determination and analysis capacity in the ending stage. Keys for intervention according to the phase of the process were offered.

Social inequalities and mortality in Europe-results from a large multi-national cohort

BACKGROUND Socio-economic inequalities in mortality are observed at the country level in both North America and Europe. The purpose of this work is to investigate the contribution of specific risk factors to social inequalities in cause-specific mortality using a large multi-country cohort of Europeans. METHODS A total of 3,456,689 person/years follow-up of the European Prospective Investigation into Cancer and Nutrition (EPIC) was analysed. Educational level of subjects coming from 9 European countries was recorded as proxy for socio-economic status (SES). Cox proportional hazard model's with a step-wise inclusion of explanatory variables were used to explore the association between SES and mortality; a Relative Index of Inequality (RII) was calculated as measure of relative inequality. RESULTS Total mortality among men with the highest education level is reduced by 43% compared to men with the lowest (HR 0.57, 95% C.I. 0.52-0.61); among women by 29% (HR 0.71, 95% C.I. 0.64-0.78). The risk reduction was attenuated by 7% in men and 3% in women by the introduction of smoking and to a lesser extent (2% in men and 3% in women) by introducing body mass index and additional explanatory variables (alcohol consumption, leisure physical activity, fruit and vegetable intake) (3% in men and 5% in women). Social inequalities were highly statistically significant for all causes of death examined in men. In women, social inequalities were less strong, but statistically significant for all causes of death except for cancer-related mortality and injuries. DISCUSSION In this European study, substantial social inequalities in mortality among European men and women which cannot be fully explained away by accounting for known common risk factors for chronic diseases are reported.

Common variants of the liver fatty acid binding protein gene influence the risk of type 2 diabetes and insulin resistance in Spanish population

SUMMARY The main objective was to evaluate the association between SNPs and haplotypes of the FABP1-4 genes and type 2 diabetes, as well as its interaction with fat intake, in one general Spanish population. The association was replicated in a second population in which HOMA index was also evaluated. METHODS 1217 unrelated individuals were selected from a population-based study [Hortega study: 605 women; mean age 54 y; 7.8% with type 2 diabetes]. The replication population included 805 subjects from Segovia, a neighboring region of Spain (446 females; mean age 52 y; 10.3% with type 2 diabetes). DM2 mellitus was defined in a similar way in both studies. Fifteen SNPs previously associated with metabolic traits or with potential influence in the gene expression within the FABP1-4 genes were genotyped with SNPlex and tested. Age, sex and BMI were used as covariates in the logistic regression model. RESULTS One polymorphism (rs2197076) and two haplotypes of the FABP-1 showed a strong association with the risk of DM2 in the original population. This association was further confirmed in the second population as well as in the pooled sample. None of the other analyzed variants in FABP2, FABP3 and FABP4 genes were associated. There was not a formal interaction between rs2197076 and fat intake. A significant association between the rs2197076 and the haplotypes of the FABP1 and HOMA-IR was also present in the replication population. CONCLUSIONS The study supports the role of common variants of the FABP-1 gene in the development of type 2 diabetes in Caucasians.

DRB1*03:01 haplotypes: differential contribution to multiple sclerosis risk and specific association with the presence of intrathecal IgM bands.

BACKGROUND Multiple sclerosis (MS) is a multifactorial disease with a genetic basis. The strongest associations with the disease lie in the Human Leukocyte Antigen (HLA) region. However, except for the DRB1*15:01 allele, the main risk factor associated to MS so far, no consistent effect has been described for any other variant. One example is HLA-DRB1*03:01, with a heterogeneous effect across populations and studies. We postulate that those discrepancies could be due to differences in the diverse haplotypes bearing that allele. Thus, we aimed at studying the association of DRB1*03:01 with MS susceptibility considering this allele globally and stratified by haplotypes. We also evaluated the association with the presence of oligoclonal IgM bands against myelin lipids (OCMB) in cerebrospinal fluid. METHODS Genotyping of HLA-B, -DRB1 and -DQA1 was performed in 1068 MS patients and 624 ethnically matched healthy controls. One hundred and thirty-nine MS patients were classified according to the presence (M+, 58 patients)/absence (M-, 81 patients) of OCMB. Comparisons between groups (MS patients vs. controls and M+ vs. M-) were performed with the chi-square test or the Fisher exact test. RESULTS Association of DRB1*03:01 with MS susceptibility was observed but with different haplotypic contribution, being the ancestral haplotype (AH) 18.2 the one causing the highest risk. Comparisons between M+, M- and controls showed that the AH 18.2 was affecting only M+ individuals, conferring a risk similar to that caused by DRB1*15:01. CONCLUSIONS The diverse DRB1*03:01-containing haplotypes contribute with different risk to MS susceptibility. The AH 18.2 causes the highest risk and affects only to individuals showing OCMB.

Del artículo de revisión a la recomendación profesional: La uniformación y material de protección individual para los equipos del ámbito prehospitalario de urgencias y emergencias

The Spanish Society of Nursing Emergency (SEEUE) has several lines documentaries that can be consulted on its web page and that have been spread through various publications: Statutes, scientific recommendations, professional recommendations, statements and allegations, grounds for nursing emergency, guarantees and rules, documents of interest and legislation. Set this that composed the regulatory environment, legal and recommendations which society poses to the collective nurse from the area of the emergency, as well as the rest of actors associated with urgent assistance (institutional and administratively) and through what has been the work of conceptualization and definition in our area the past few years. Part of this documentation offer possibilities for scientific endorsement and professional and invites to continue building knowledge and evidence. It is in this sense in which this work can and should be defined from a literature review approach and under the scheme of "review article". The working Group in Primary Care (PC) of the SEEUE, decided to build a Professional Recommendation (PR) in one of the areas of "uncertainty/variability" in the employment context and historical demand of nurses and other emergency care team on security issues: "The uniform and personal protective equipment for professional teams on prehospital emergency areas”.

Continuidad De Cuidados y Comunicación interniveles entre equipos de emergencias sanitarias y Atención Primaria.

The gradual incorporation of the nurses to the extrahospital emergency teams give them a holistic aspect in the field of care. And this is not possible without addressing the possibility of continuity of care and communication with other levels of care. All efforts in this regard and made speeches themselves as nursing, "Refer" (Nic 8100) and "Exchange of information on health care" (Nic 7960), is the conceptual framework of this work, which objetives are to quantify and exposing the proceedings in this line taken by the nurses of emergency team.

Prescripción enfermera en el contexto de las urgencias y emergencia

The area of the urgencies and emergencies, assisted from all levels and care settings raises, if possible, patterns of work and ways that collaboration between professionals and teamwork make nurse prescription, often pharmacological, a legislative needs in response to increased scientific evidence and through internationally accepted performance algorithms. Enabling the nurse to act according to these concepts and beyond any "doubt and suspicion" of illegality. Taking a consensus necessary training and development and according to professional specialization and differentiation in this area and as arguments to remove any doubt still remains the subject without enclosing any sense and in many sectors.

Recepción, clasificación según escala Manchester y atención sanitaria inicial al paciente que acude a un Dispositivo de Cuidados Críticos y Urgencias (DCCU) con motivo de consulta “Diabetes”: Posibilidad de intervención finalista de la enfermera en la consulta de triage (Triage Avanzado) ante la hipoglucemia. Colaboración multidisciplinar y criterios de derivación

The Andalusian Public Health System (SSPA) is considering the last time an attempt urgent process management through triage consultation, both hospital and primary care environment and tables situations in which the nurse responsible for these consultations can carry out a final statement of which only she is directly responsible through their independent intervention and referral (Triage Advanced). Pose, at once and consistently to the idea of teamwork, where they can be the limits to that intervention finalist and the circuits to follow. This paper proposes a definition line of one of those situations through triage concepts universally tested, and takes full advantage of advanced practice profile offered by nurses Device Critical Care (DCCU) of the SSPA and any the emerging legal and regulatory framework in terms of standardized collaborative prescription, us know legitimate receivers. This work stems from the vision of professionals and our contribution to that line of institutional work that must be consensus.

Paciente transferido desde Equipo Móvil de Dispositivo de Cuidados Críticos y Urgencias (EM DCCU) a sistema de helitransporte sanitario (HEMS): Guía de actuación

Assistance and transfer of critical patients often takes place in an environment in which the medium response time, playing against an appropriate and definitive treatment at a center useful. The relationship in this sense arises between the resources of the level of primary care and the medical helicopter transport system (HEMS), is caused by the need to shorten those response times and referral in areas where initial care is taken to DCCU out by, despite being timedependent pathology that requires a fast transfer can not be offered by them with the possibility of optimization. The support in this sense of HEMS is essential: The knowledge of the environment and the establishment of policy guidance are necessary.

Toma de decisiones en Enfermería de Urgencias, Emergencias y Catástrofes: Márgenes de Autonomía y Responsabilidad

Fear of achieving higher levels of nurse autonomy must be overcome for a new environment of relationships, change, communication and respect within the multidisciplinary team. The progressive achievement of new skills, the handling of evidence and the implementation of models and ways of working based on the nursing process, through encouraged training courses into the company and by the possibility of resource management in line and technology, foster as the ideal setting for Emergency Nursing, Emergency and Disaster acquires its own identity and development.

Continuidad de cuidados de enfermería a través de un protocolo asistencial de transferencia

The creation and establishment within the healthcare team of the Primary Healthcare Centre of Baena of a Protocol and Procedures for healthcare that provides a communication tool for nurses enabled the healthcare team to develop a dynamic circuit and at the same time communication with nurses of the Critical Care and Emergency Team (DCCU) assigned to that centre. The created work environment for healthcare included Case Management Nurse, Primary Healthcare Nurse and Critical Care and Emergency Nurse. Thus, nursing assessment and actions for programmed and urgent healthcare, provided the first contact with DCCU nurses and reoriented them for the proposed healthcare plan for the patients, in addition to communicate with the rest of the healthcare team. This article presents the results of continuous nurse healthcare over nine months, applying this protocol.

Guía para el desarrollo de Programas de intercambio de Jeringuillas (PIJ) desde la consulta de triage de los Dispositivos de Cuidados Críticos y Urgencias (DCCU)

There are exceptional situations where emergency services are required Primary Care in the application of material used by drug-dependent patients, being the response to this demand is something that many of the cases, to individual discretion and the randomness and variability every situation leads to an answer. It calls for a response commensurate to public services and preventive health philosophy in most cases will be carried out by the nurse to perform assistance Devices Critical Care (DCCU), often this first contact these patients and slots at the supply of resources diminishes the possibilities of acquisition of such material to them. That is why, and in the absence in this area of patient safety and professional, a workflow model and according to the prevailing philosophy of working in primary care in terms of prevention policies and recruitment of patients concerned, this project raises guidance for the development of a needle exchange program from the triage consultations DCCU.