Brain Network Allostasis after Chronic Alcohol Drinking Is Characterized by Functional Dedifferentiation and Narrowing.

Alcohol use disorder (AUD) causes complex alterations in the brain that are poorly understood. The heterogeneity of drinking patterns and the high incidence of comorbid factors compromise mechanistic investigations in AUD patients. Here we used male Marchigian Sardinian alcohol-preferring (msP) rats, a well established animal model of chronic alcohol drinking, and a combination of longitudinal resting-state fMRI and manganese-enhanced MRI to provide objective measurements of brain connectivity and activity, respectively. We found that 1 month of chronic alcohol drinking changed the correlation between resting-state networks. The change was not homogeneous, resulting in the reorganization of pairwise interactions and a shift in the equilibrium of functional connections. We identified two fundamentally different forms of network reorganization. First is functional dedifferentiation, which is defined as a regional increase in neuronal activity and overall correlation, with a concomitant decrease in preferential connectivity between specific networks. Through this mechanism, occipital cortical areas lost their specific interaction with sensory-insular cortex, striatal, and sensorimotor networks. Second is functional narrowing, which is defined as an increase in neuronal activity and preferential connectivity between specific brain networks. Functional narrowing strengthened the interaction between striatal and prefrontocortical networks, involving the anterior insular, cingulate, orbitofrontal, prelimbic, and infralimbic cortices. Importantly, these two types of alterations persisted after alcohol discontinuation, suggesting that dedifferentiation and functional narrowing rendered persistent network states. Our results support the idea that chronic alcohol drinking, albeit at moderate intoxicating levels, induces an allostatic change in the brain functional connectivity that propagates into early abstinence.SIGNIFICANCE STATEMENT Excessive consumption of alcohol is positioned among the top five risk factors for disease and disability. Despite this priority, the transformations that the nervous system undergoes from an alcohol-naive state to a pathologic alcohol drinking are not well understood. In our study, we use an animal model with proven translational validity to study this transformation longitudinally. The results show that shortly after chronic alcohol consumption there is an increase in redundant activity shared by brain structures, and the specific communication shrinks to a set of pathways. This functional dedifferentiation and narrowing are not reversed immediately after alcohol withdrawal but persist during early abstinence. We causally link chronic alcohol drinking with an early and abstinence-persistent retuning of the functional equilibrium of the brain.

Neuroimaging reveals functionally distinct neuronal networks associated with high-level alcohol consumption in two genetic rat models.

Human imaging data suggest that the motivational processes associated with alcohol reward are reflected in the patterns of neural activation after alcohol or alcohol-related cues. In animal models of alcohol drinking, however, the changes in brain activation during voluntary alcohol ingestion are poorly known. In order to improve the translational utility of animal models, we examined alcohol-induced functional brain activation in Alko Alcohol (AA) and Marchigian-Sardinian alcohol-preferring (msP) rats that drink voluntarily high levels of alcohol, but exhibit widely different neurochemical and behavioral traits cosegregated with alcohol preference. Brain imaging was performed using manganese-enhanced MRI (MEMRI), which is based on accumulation of Mn2+ ions in activated neurons, allowing the identification of functional neuronal networks recruited during specific behaviors in awake animals during a subsequent imaging session under anesthesia. MEMRI was performed following 4 weeks of voluntary alcohol drinking, using water drinking as the control. Despite similar levels of alcohol drinking, strikingly different alcohol-induced neuronal activity patterns were observed in AA and msP rats. Overall, functional activation in the AA rats was more widespread, involving large cortical areas and subcortical structures, such as the bed nucleus of the stria terminalis, preoptic area, hypothalamus, periaqueductal grey, and substantia nigra. In the msP rats, however, alcohol-related activation was largely confined to prefrontal cortical regions and insular cortex, and olfactory areas. Overlapping areas of activation found in both rat lines included the nucleus accumbens, prelimbic, orbital, and insular cortex. In conclusion, our data reveal strikingly different brain circuits associated with alcohol drinking in two genetically different rat lines and suggest innately different motivational and behavioral processes driving alcohol drinking. These findings have important implications for the use of these lines in translational alcohol research.

Extracting orthogonal subject- and condition-specific signatures from fMRI data using whole-brain effective connectivity.

The study of brain communication based on fMRI data is often limited because such measurements are a mixture of session-to-session variability with subject- and condition-related information. Disentangling these contributions is crucial for real-life applications, in particular when only a few recording sessions are available. The present study aims to define a reliable standard for the extraction of multiple signatures from fMRI data, while verifying that they do not mix information about the different modalities (e.g., subjects and conditions such as tasks performed by them). In particular, condition-specific signatures should not be contaminated by subject-related information, since they aim to generalize over subjects. Practically, signatures correspond to subnetworks of directed interactions between brain regions (typically 100 covering the whole brain) supporting the subject and condition identification for single fMRI sessions. The key for robust prediction is using effective connectivity instead of functional connectivity. Our method demonstrates excellent generalization capabilities for subject identification in two datasets, using only a few sessions per subject as reference. Using another dataset with resting state and movie viewing, we show that the two signatures related to subjects and tasks correspond to distinct subnetworks, which are thus topologically orthogonal. Our results set solid foundations for applications tailored to individual subjects, such as clinical diagnostic.

Mortality and cardiovascular disease burden of uncontrolled diabetes in a registry-based cohort: the ESCARVAL-risk study.

BACKGROUND: Despite the epidemiological evidence about the relationship between diabetes, mortality and cardiovascular disease, information about the population impact of uncontrolled diabetes is scarce. We aimed to estimate the attributable risk associated with HbA1c levels for all-cause mortality and cardiovascular hospitalization. METHODS: Prospective study of subjects with diabetes mellitus using electronic health records from the universal public health system in the Valencian Community, Spain 2008-2012. We included 19,140 men and women aged 30 years or older with diabetes who underwent routine health examinations in primary care. RESULTS: A total of 11,003 (57%) patients had uncontrolled diabetes defined as HbA1c ≥6.5%, and, among those, 5325 participants had HbA1c ≥7.5%. During an average follow-up time of 3.3 years, 499 deaths, 912 hospitalizations for coronary heart disease (CHD) and 786 hospitalizations for stroke were recorded. We observed a linear and increasingly positive dose-response of HbA1c levels and CHD hospitalization. The relative risk for all-cause mortality and CHD and stroke hospitalization comparing patients with and without uncontrolled diabetes was 1.29 (95 CI 1.08,1.55), 1.38 (95 CI 1.20,1.59) and 1.05 (95 CI 0.91, 1.21), respectively. The population attributable risk (PAR) associated with uncontrolled diabetes was 13.6% (95% CI; 4.0-23.9) for all-cause mortality, 17.9% (95% CI; 10.5-25.2) for CHD and 2.7% (95% CI; - 5.5-10.8) for stroke hospitalization. CONCLUSIONS: In a large general-practice cohort of patients with diabetes, uncontrolled glucose levels were associated with a substantial mortality and cardiovascular disease burden.

[Anemia of chronic kidney disease: Protocol of study, management and referral to Nephrology]. / Anemia en la enfermedad renal crónica: protocolo de estudio, manejo y derivación a Nefrología.

The objective of this protocol is to know which test are needed to study an anaemia in a patient with chronic kidney disease, the differential diagnosis of renal anaemia, to know and correct other deficiency anaemias, and the criteria for referral to Nephrology or other specialties of the anaemic patient with chronic kidney disease.

Factors influencing pathological ankle-brachial index values along the chronic kidney disease spectrum: the NEFRONA study.

Background: The ankle-brachial index (ABI) is widely used to diagnose subclinical peripheral artery disease (PAD) in the general population, but data assessing its prevalence and related factors in different chronic kidney disease (CKD) stages are scarce. The aim of this study is to evaluate the prevalence and associated factors of pathological ABI values in CKD patients. Methods: NEFRONA is a multicentre prospective project that included 2445 CKD patients from 81 centres and 559 non-CKD subjects from 9 primary care centres across Spain. A trained team collected clinical and laboratory data, performed vascular ultrasounds and measured the ABI. Results: PAD prevalence was higher in CKD than in controls (28.0 versus 12.3%, P < 0.001). Prevalence increased in more advanced CKD stages, due to more patients with an ABI ≥1.4, rather than ≤0.9. Diabetes was the only factor predicting both pathological values in all CKD stages. Age, female sex, carotid plaques, higher carotid intima-media thickness, higher high-sensitivity C-reactive protein (hsCRP) and triglycerides, and lower 25-hydroxi-vitamin D were independently associated with an ABI ≤0.9. Higher phosphate and hsCRP, lower low-density lipoprotein (LDL)-cholesterol and dialysis were associated with an ABI ≥1.4. A stratified analysis showed different associated factors in each CKD stage, with phosphate being especially important in earlier CKD, and LDL-cholesterol being an independent predictor only in Sage 5D CKD. Conclusions: Asymptomatic PAD is very prevalent in all CKD stages, but factors related to a low or high pathological ABI differ, revealing different pathogenic pathways. Diabetes, dyslipidaemia, inflammation and mineral-bone disorders play a role in the appearance of PAD in CKD.

Inflammatory status and uricaemia determine HDL-cholesterol levels in hypertensive adults over 65: an analysis of the FAPRES register.

In inflammatory disease, the levels of high-density lipoprotein cholesterol (HDL-C) decrease, and the composition of HLD-C changes. Data from the "non-inflammatory" general population indicate the presence of the same phenomenon, albeit to a smaller extent. Levels of uricaemia contribute to the overall inflammatory state of patients. The aim of this study was to analyse the association between inflammatory state, levels of uricaemia, and levels of HLD-C in a hypertensive Spanish population aged 65 or older. This was a retrospective analysis of the FAPRES database. We compared lipid levels [HDL-C, low-density lipoprotein cholesterol (LDL-C), total cholesterol, and triglycerides] in terciles of patients according to their leukocyte counts and uricaemia. When we observed statistically significant differences at a 95% confidence level, we constructed a multivariable linear regression model to adjust for possible confounders. We analysed 860 patients (52.7% women) with a mean age of 72.9 years (±5.8). Participants in the highest tercile for leukocytes or uricaemia presented with significantly lower levels of HDL-C and higher levels of triglycerides, but there was no difference in total cholesterol or LDL-C. The multivariable analysis confirmed an independent and inverse association between HDL-C and both leukocytes (ß = -0.001, p = 0.025) and uricaemia (ß = -1.054, p = 0037) as well as an independent, direct association between triglycerides and both leukocytes (ß = 0.004, p = 0.049), and uricaemia (ß = 8.411, p = 0.003). In hypertensive adults aged 65 or older, inflammatory state, and uricaemia independently operate to decrease HDL-C-these findings confirm those described in studies in people with inflammatory disease. This phenomenon could help to define a proatherogenic profile in people without inflammatory disease.

[Management of patients with dyslipidaemia in Spain. The Cardio Right Care Control of cardiovascular risk project]. / Manejo del paciente con dislipidemia en España. Proyecto Cardio Right Care Control del Riesgo Cardiovascular.

OBJECTIVE: To ascertain the opinion of physicians about diagnostic criteria, control targets, control rates, and therapeutic approach of patients with dyslipidaemia in Spain. METHODS: A specific questionnaire was created about diagnostic criteria, control targets, control rates, lipid lowering therapies, and therapeutic inertia in patients with dyslipidaemia. Physicians completed the questionnaire online during a 4-month period. RESULTS: A total of 959 questionnaires were collected from all over Spain. The most frequent scale to stratify cardiovascular risk is SCORE (54.9%), and guidelines from the European Society of Cardiology are the most common guidelines used (50.5%). The majority of patients are on primary prevention (57.7%), and 31.4% have a high-very high cardiovascular risk. More than 70% of investigators considered that the target among patients at very high risk and those in secondary prevention is an LDL cholesterol < 70 mg/dL. It is considered by 60.0% and 66.4% of investigators that their patients on primary and secondary prevention, respectively, achieve control targets. Statins are the most common lipid lowering drugs used, followed by ezetimibe. In the majority of cases, when a patient is not adequately controlled with statins, there is an increase in the dose or a change to another statin. Poor adherence to treatment and therapeutic inertia are the main reasons for poor LDL cholesterol control. CONCLUSIONS: The Cardio Right Care CVR Control project allows those aspects to be identified, as well as areas of improvement in patients with dyslipidaemia in Spain.

Rationale and methods of the cardiometabolic Valencian study (Escarval-Risk) for validation of risk scales in Mediterranean patients with hypertension, diabetes or dyslipidemia.

BACKGROUND: The Escarval-Risk study aims to validate cardiovascular risk scales in patients with hypertension, diabetes or dyslipidemia living in the Valencia Community, a European Mediterranean region, based on data from an electronic health recording system comparing predicted events with observed during 5 years follow-up study. METHODS/DESIGN: A cohort prospective 5 years follow-up study has been designed including 25000 patients with hypertension, diabetes and/or dyslipidemia attended in usual clinical practice. All information is registered in a unique electronic health recording system (ABUCASIS) that is the usual way to register clinical practice in the Valencian Health System (primary and secondary care). The system covers about 95% of population (near 5 million people). The system is linked with database of mortality register, hospital withdrawals, prescriptions and assurance databases in which each individual have a unique identification number. Diagnoses in clinical practice are always registered based on IDC-9. Occurrence of CV disease was the main outcomes of interest. Risk survival analysis methods will be applied to estimate the cumulative incidence of developing CV events over time. DISCUSSION: The Escarval-Risk study will provide information to validate different cardiovascular risk scales in patients with hypertension, diabetes or dyslipidemia from a low risk Mediterranean Region, the Valencia Community.

Twenty-four-hour ambulatory heart rate and organ damage in primary hypertension.

BACKGROUND: The relationship between basal heart rate (HR) and the occurrence of myocardial ischemia, sudden death, cardiovascular mortality have been described. Therefore, further studies are warranted to evaluate the behaviour of heart rate in different scenarios. We sought to determine whether ambulatory heart rate is associated with the presence of target organ damage (TOD) in hypertensive patients. PATIENTS AND METHODS: Crossectional study of essential hypertensive patients in whom a twenty-four hour ambulatory blood pressure monitoring (ABPM) was performed. The relationship between TOD and 24 hour ambulatory heart rate (HR) was analyzed. RESULTS: Five hundred and sixty-six patients with arterial hypertension were included (55.8% male, mean age 59.9 +/- 14.2 years). 15% were smokers, 62.2% had dyslipidemia, 18.4% diabetes mellitus. Heart rate values were higher during activity as compared to the resting period (72.8 vs 63.3 bpm, p < 0.001). Heart rate, in both periods, was not associated with the presence of TOD. Nevertheless, the patients with nocturnal HR > or = 65 bpm have high risk and a high prevalence of TOD. This relationship was also present in multivariate analysis (HR 2.41; CI 95% 1.41-4.11; p=0.001). CONCLUSION: An elevated nocturnal HR, > or = 65 bpm, obtained with ABPM registry, is associated with the presence of TOD in hypertensive patients. ABPM is a powerful tool for hypertensive patients not only to monitor BP control but also to obtain information on HR which may provide additional information about current and future cardiovascular risk.

Model-based whole-brain effective connectivity to study distributed cognition in health and disease.

Neuroimaging techniques are now widely used to study human cognition. The functional associations between brain areas have become a standard proxy to describe how cognitive processes are distributed across the brain network. Among the many analysis tools available, dynamic models of brain activity have been developed to overcome the limitations of original connectivity measures such as functional connectivity. This goes in line with the many efforts devoted to the assessment of directional interactions between brain areas from the observed neuroimaging activity. This opinion article provides an overview of our model-based whole-brain effective connectivity to analyze fMRI data, while discussing the pros and cons of our approach with respect to other established approaches. Our framework relies on the multivariate Ornstein-Uhlenbeck (MOU) process and is thus referred to as MOU-EC. Once tuned, the model provides a directed connectivity estimate that reflects the dynamical state of BOLD activity, which can be used to explore cognition. We illustrate this approach using two applications on task-evoked fMRI data. First, as a connectivity measure, MOU-EC can be used to extract biomarkers for task-specific brain coordination, understood as the patterns of areas exchanging information. The multivariate nature of connectivity measures raises several challenges for whole-brain analysis, for which machine-learning tools present some advantages over statistical testing. Second, we show how to interpret changes in MOU-EC connections in a collective and model-based manner, bridging with network analysis. Our framework provides a comprehensive set of tools that open exciting perspectives to study distributed cognition, as well as neuropathologies.

Recommendations to improve lipid control. Consensus document of the Spanish Society of Cardiology.

T***he current control of low-density lipoprotein cholesterol among patients with atherosclerotic cardiovascular disease is very low and this is associated with an increase of cardiovascular outcomes. In addition, the latter this happens, the risk will be greater. This is mainly due to an insufficient use of the lipid-lowering therapy currently available. In fact, with current treatments (statins, ezetimibe and PCSK9 inhibitors), the majority of patients in secondary prevention should achieve low-density lipoprotein cholesterol goals. For these reasons, in this manuscript promoted by the Spanish Society of Cardiology we propose three simple and feasible decision-making algorithms that include the majority of clinical scenarios among patients with ischemic heart disease, with the double aim of attaining therapeutic goals in the majority of patients as soon as possible; in secondary prevention the magnitude of the benefit is risk- and time-dependent.

SEA/SEMERGEN consensus document 2019: Dietary recommendations in the prevention of cardiovascular disease. / Documento de consenso SEA/SEMERGEN 2019. Recomendaciones dietéticas en la prevención cardiovascular.

The current paradigm in the nutrition sciences states that the basic nutritional unit is not the nutrients, but the foods that contain them (oils, nuts, dairy products, eggs, red or processed meats, etc.). These act as a food matrix in which the different nutrients synergistically or antagonistically modulate their effects on the various metabolic pathways determining health and disease. Food is not based on nutrients or isolated foods but on complex mixtures of one and the other that are part of a specific food pattern, a concept that has been targeted as the most pertinent to evaluate the associations between nutrition and health or disease. This document presents a summary of the available evidence on the relationship between different foods and cardiovascular health, and offers simple recommendations to be implemented in the dietary advice offered by the health professional.

[SEA/SEMERGEN consensus document 2019: Dietary recommendations in the prevention of cardiovascular disease]. / Documento de consenso SEA/SEMERGEN 2019. Recomendaciones dietéticas en la prevención cardiovascular.

The current paradigm in the nutrition sciences states that the basic nutritional unit is not the nutrients, but the foods that contain them (oils, nuts, dairy products, eggs, red or processed meats, etc.). These act as a food matrix in which the different nutrients synergistically or antagonistically modulate their effects on the various metabolic pathways determining health and disease. Food is not based on nutrients or isolated foods but on complex mixtures of one and the other that are part of a specific food pattern, a concept that has been targeted as the most pertinent to evaluate the associations between nutrition and health or disease. This document presents a summary of the available evidence on the relationship between different foods and cardiovascular health, and offers simple recommendations to be implemented in the dietary advice offered by the health professional.

Anemia of chronic kidney disease: Protocol of study, management and referral to Nephrology. / Anemia en la enfermedad renal crónica: protocolo de estudio, manejo y derivación a Nefrología.

The objective of this protocol is to know which test are needed to study an anaemia in a patient with chronic kidney disease, the differential diagnosis of renal anaemia, to know and correct other deficiency anaemias, and the criteria for referral to Nephrology or other specialties of the anaemic patient with chronic kidney disease.

Consensus document for the use of the Polypill in the secondary prevention of cardiovascular disease. / Documento de consenso del uso clínico de la Polypill en la prevención secundaria del riesgo cardiovascular.

Cardiovascular disease is a chronic disorder which is usually already at an advanced stage when the first symptoms develop. The fact that the initial clinical presentation can be lethal or highly incapacitating emphasizes the need for primary and secondary prevention. It is estimated that the ratio of patients with good adherence to secondary prevention of cardiovascular disease is low and also decreases gradually over time. The Polypill for secondary prevention of cardiovascular disease is the first fixed-dose combination therapy of salicylic acid, atorvastatin and ramipril approved in Spain. The purpose of this consensus document was to define and recommend, through the evidence available in the literature and clinical expert opinion, the impact of treatment adherence in the secondary prevention of cardiovascular disease and the use of the Polypill in daily clinical practice as part of a global strategy including adjustments in patient lifestyle. A RAND/UCLA methodology based on scientific evidence, as well as the collective judgment and clinical expertise of an expert panel was used for this assessment. As a result, a final report of recommendations on the impact of the lack of adherence to treatment of secondary prevention of cardiovascular disease and the effect of using a Polypill in adherence of patients was produced. The recommendations included in this document have been addressed to all those specialists, cardiologists, internists and primary care physicians with competence in prescribing and monitoring patients with high and very high cardiovascular risks.

[Use of the CHADS2 score as a predictor of the risk of mortality in hypertensive patients. The FAPRES study]. / Uso de la escala CHADS2 como predictor de riesgo de mortalidad en pacientes hipertensos. El estudio FAPRES.

FOUNDATIONS AND AIM: The aim of this study is to analyze the CHADS2 score as a marker of the risk of mortality in hypertensive patients, with and without the presence of atrial fibrillation. METHODS: We included 1,003 hypertensive patients≥65 years. Risk factors, and CHADS2 score were recorded among other factors, as well as clinical follow-up of number and type of deaths. RESULTS: Mean age was 72.8±5.8 years, and 47.5% were men. During follow-up there were 41 deaths, 20 were of cardiovascular origin. Patients with higher CHADS2 had a higher mortality: 1.5% CHADS2=1; 4.7% in CHADS2=2; 9.1% in CHADS2=3, and 7.8% in CHADS2≥4. CONCLUSIONS: The CHADS2 score can be a clinical instrument of easy application to identify hypertensive patients with a high risk of mortality.

Renal function and attributable risk of death and cardiovascular hospitalization in patients with cardiovascular risk factors from a registry-based cohort: the Estudio Cardiovascular Valencia-risk study.

BACKGROUND: Information about the attributable risk associated with renal dysfunction in patients with cardiovascular risk factors is lacking. OBJECTIVE: We aimed to estimate the attributable risk associated with chronic kidney disease Epidemiology Collaboration-estimated glomerular filtration rate (eGFR), for all-cause mortality, and cardiovascular hospitalization. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of study participants with cardiovascular risk factors in 2008-2012. We included 52 007 cardiovascular disease-free men and women aged 30 years or older with hypertension, diabetes, or dyslipidemia, who underwent routine health examinations in primary care. RESULTS: A total of 6639 (12.8%) patients had eGFR below 60 ml/min per 1.73 m and among them 1782 (3.4%) had 45 ml/min per 1.73 m or lower. During an average follow-up time of 3.2 years, 54.12 deaths, 99.98 coronary heart disease (CHD) hospitalizations, and 90.64 stroke hospitalizations/10 000 person-years were recorded. The population attributable risks associated with having a GFR lower than 60 ml/min per 1.73 m were 6.9% (95% confidence interval = 2.07, 10.65) for all-cause mortality, 6.8% (4.3, 9.4) for CHD hospitalization, and 4.1% (1.02, 7.00) for stroke hospitalization. Participants with increasing number of cardiovascular risk factors displayed increasing population attributable risks associated to a GFR less than 60 ml/min per 1.73 m for all-cause mortality and CHD (P heterogeneity 0.002 and 0.05, respectively). CONCLUSION: In a large general practice cohort of patients with cardiovascular disease risk factors, decreasing eGFR levels were associated with additional attributed risk of mortality and cardiovascular disease. Our findings underscore that intensified efforts are needed to reduce the cardiovascular disease burden associated to chronic kidney disease.

Impact of hypertension on mortality and cardiovascular disease burden in patients with cardiovascular risk factors from a general practice setting: the ESCARVAL-risk study.

OBJECTIVE: To estimate the attributable risk associated to hypertension for all-cause mortality and cardiovascular hospitalization endpoints in a prospective study of patients with at least one cardiovascular risk factors participating in the Estudio Cardiovascular Valencia-risk project, we also evaluated the attributable risk associated with other risk factors and risk factor clustering. METHODS: Prospective electronic health recording-based study in a Mediterranean population that included 52 007 cardiovascular disease-free men and women aged 30 years or older (mean age 62.6 year) with hypertension (79.0%), diabetes mellitus (37.3%), or dyslipidemia (88.2%), who underwent routine health examinations. All-cause mortality and hospitalization records for coronary heart disease (CHD) or stroke were collected. RESULTS: During an average follow-up time of 3.2 years, 928 deaths and 1682 and 1529 hospitalizations for CHD and stroke, respectively, were recorded. In both men and women, hypertension significantly increased the multiadjusted rates of death and CHD and stroke hospitalizations. Hypertension was associated with a substantial amount of avoidable deaths both in men and women, population attributable risks were 41.81 (95% confidence interval 28.02, 53.24)% and 37.84 (5.74, 61.51)%, respectively. Similarly, the population attributable risk of hospitalization for CHD and stroke associated to hypertension was among the highest in both the sexes as compared with the impact of the other main cardiovascular risk factors. Increasing cardiovascular risk factors clustering was associated with increasing burden of disease. CONCLUSION: Our results highlight the relevance of hypertension as main risk factor for mortality and cardiovascular events in a real-life setting. Although our data support the ongoing need of cardiovascular risk factors prevention, intensified actions for primary prevention of hypertension show potential to largely reduce the burden of cardiovascular disease.

Neurosurgery planning in rodents using a magnetic resonance imaging assisted framework to target experimentally defined networks.

BACKGROUND AND OBJECTIVE: Meaningful targeting of brain structures is required in a number of experimental designs in neuroscience. Current technological developments as high density electrode arrays for parallel electrophysiological recordings and optogenetic tools that allow fine control of activity in specific cell populations provide powerful tools to investigate brain physio-pathology. However, to extract the maximum yield from these fine developments, increased precision, reproducibility and cost-efficiency in experimental procedures is also required. METHODS: We introduce here a framework based on magnetic resonance imaging (MRI) and digitized brain atlases to produce customizable 3D-environments for brain navigation. It allows the use of individualized anatomical and/or functional information from multiple MRI modalities to assist experimental neurosurgery planning and in vivo tissue processing. RESULTS: As a proof of concept we show three examples of experimental designs facilitated by the presented framework, with extraordinary applicability in neuroscience. CONCLUSIONS: The obtained results illustrate its feasibility for identifying and selecting functionally and/or anatomically connected neuronal population in vivo and directing electrode implantations to targeted nodes in the intricate system of brain networks.