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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., (Copyright © 2022 the authors.)

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., (© 2019 Massachusetts Institute of Technology.)

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., (Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

The Rubinstein-Taybi Syndrome (RSTS) is a congenital disease that affects brain development causing severe cognitive deficits. In most cases the disease is associated with dominant mutations in the gene encoding the CREB binding protein (CBP). In this work, we present the first quantitative analysis of brain abnormalities in a mouse model of RSTS using magnetic resonance imaging (MRI) and two novel self-developed automated algorithms for image volumetric analysis. Our results quantitatively confirm key syndromic features observed in RSTS patients, such as reductions in brain size (-16.31%, p < 0.05), white matter volume (-16.00%, p < 0.05), and corpus callosum (-12.40%, p < 0.05). Furthermore, they provide new insight into the developmental origin of the disease. By comparing brain tissues in a region by region basis between cbp(+/-) and cbp(+/+) littermates, we found that cbp haploinsufficiency is specifically associated with significant reductions in prosencephalic tissue, such us in the olfactory bulb and neocortex, whereas regions evolved from the embryonic rhombencephalon were spared. Despite the large volume reductions, the proportion between gray-, white-matter and cerebrospinal fluid were conserved, suggesting a role of CBP in brain size regulation. The commonalities with holoprosencephaly and arhinencephaly conditions suggest the inclusion of RSTS in the family of neuronal migration disorders.

Neurons are able to express long-lasting and activity-dependent modulations of their synapses. This plastic property supports memory and conveys an extraordinary adaptive value, because it allows an individual to learn from, and respond to, changes in the environment. Molecular and physiological changes at the cellular level as well as network interactions are required in order to encode a pattern of synaptic activity into a long-term memory. While the cellular mechanisms linking synaptic plasticity to memory have been intensively studied, those regulating network interactions have received less attention. Combining high-resolution fMRI and in vivo electrophysiology in rats, we have previously reported a functional remodelling of long-range hippocampal networks induced by long-term potentiation (LTP) of synaptic plasticity in the perforant pathway. Here, we present new results demonstrating an increased bilateral coupling in the hippocampus specifically supported by the mossy cell commissural/associational pathway in response to LTP. This fMRI-measured increase in bilateral connectivity is accompanied by potentiation of the corresponding polysynaptically evoked commissural potential in the contralateral dentate gyrus and depression of the inactive convergent commissural pathway to the ipsilateral dentate. We review these and previous findings in the broader context of memory consolidation.

Aim: To determine whether there are gender differences in the epidemiological profile of atrial fibrillation (AF) and to characterise the clinical, biochemical, and therapeutic factors associated with AF., Methods: Each investigator (primary care physicians or physicians based in hospital units for hypertension treatment) recruited the first 3 patients with an age of ≥ 65 years and a clinical diagnosis of hypertension (ambulatory blood pressure monitoring and an electrocardiogram, were performed) on the first working day of the week for 5 wk and identified those individuals with atrial fibrillation. A binary logistic regression was performed, including all of the variables that were significant in the univariate analysis, to establish the variables that were associated with the presence of arrhythmia., Results: A total of 1028 patients were included in the study, with a mean age of 72.8 ± 5.8 years. Of these patients, 47.3% were male, 9% were smokers, 27.6% were diabetics, 48.3% had dyslipidaemia, 10.9% had angina, and 6.5% had experienced a myocardial infarction. Regarding gender differences, the men exhibited a larger waist circumference, a lower body mass index, less obesity, and a more extensive history of diabetes, smoking, ischaemic heart disease, kidney failure, peripheral arterial disease and carotid disease than the women. There were no differences, however, in the prevalence of AF between the men and the women (11.5% vs 9.2%, respectively; P = no significant). Regarding treatment, the women received antiplatelet agents and diuretics less frequently, but there were no other differences in the use of antihypertensive and antithrombotic therapies. In the multivariate analysis, AF in the total study population was associated with age, alcohol consumption, the presence of heart disease, and decreased glomerular filtration. In the women, AF was associated with all of the factors included in the overall analysis, as well as the presence of left ventricle hypertrophy. In contrast, in the men, the only risk factors associated with AF were age, the presence of heart disease and alcohol consumption., Conclusion: In patients with hypertension over 65 years of age, there are relevant gender differences in the factors associated with AF.

The SCORE table indiscriminately recommends the use of total cholesterol (SCORE-TC) or atherogenic index (SCORE-AI) for calculating cardiovascular (CV) risk. We evaluated reliability and agreement between both methods and the clinical implications for the identification of high CV risk. Observational study (n=8942) in a 40- to 65-year-old population. Spearman's Rho correlation was 0.987 (P<.001), the agreement intraclass correlation coefficient was 0.671 (IC 95% 0.413-0.796; with Bland-Altman's method, the average of the differences between models was 0.74. Kappa index was poor, 0.297 (P<.001) and positive specific agreement was 0.31. Discrepancies fitted individuals with high CV risk with SCORE-TC and not-high with SCORE-AI (4.7%) and 5.8% (n=518) of individuals were classified as high-risk according to SCORE-TC versus 1.1% (n=95) according to SCORE-AI. Poor agreement was found between SCORE-TC and SCORE-IA for identification of high cardiovascular risk individuals., (Copyright © 2010 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.)

Introduction and Objectives: Age and arterial hypertension are two of the main factors associated with atrial fibrillation and an increased risk of embolism. The objective of this study was to determine the prevalence of atrial fibrillation and the extent of antithrombotic use in hypertensive patients aged ≥65 years in the Spanish region of Valencia., Methods: Each study investigator enrolled the first three hypertensive patients aged ≥65 years who came for a consultation on the first day of each week for 5 weeks. Each patient's risk factors, history of cardiovascular disease, CHADS(2) score and medical treatment were noted and an ECG was recorded. Data were analyzed centrally. A patient was regarded as having atrial fibrillation if it was observable on the ECG or reported in medical records., Results: The study included 1,028 hypertensive patients with a mean age of 72.8 years. Overall, 10.3% had atrial fibrillation: in 6.7%, it was observable on the ECG while 3.6% were in sinus rhythm but had a history of the condition. Factors associated with atrial fibrillation were age, alcohol intake, structural heart disease and glomerular filtration rate. In total, 76.2% of patients with ECG evidence of atrial fibrillation and a CHADS(2) score >1 were taking anticoagulants compared with 41.7% of those who had a history of the condition but were currently in sinus rhythm., Conclusions: The prevalence of atrial fibrillation in our group of hypertensives was 10.3%; in 1.7%, it was previously undiagnosed. Antithrombotic use was high in patients with current atrial fibrillation, but lower in those who had experienced an episode previously., (Copyright © 2010 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.)

Introduction and Objectives: Age and arterial hypertension are two of the main factors associated with atrial fibrillation and an increased risk of embolism. The objective of this study was to determine the prevalence of atrial fibrillation and the extent of antithrombotic use in hypertensive patients aged >or=65 years in the Spanish region of Valencia., Methods: Each study investigator enrolled the first three hypertensive patients aged >or=65 years who came for a consultation on the first day of each week for 5 weeks. Each patient's risk factors, history of cardiovascular disease, CHADS2 score and medical treatment were noted and an ECG was recorded. Data were analyzed centrally. A patient was regarded as having atrial fibrillation if it was observable on the ECG or reported in medical records., Results: The study included 1,028 hypertensive patients with a mean age of 72.8 years. Overall, 10.3% had atrial fibrillation: in 6.7%, it was observable on the ECG while 3.6% were in sinus rhythm but had a history of the condition. Factors associated with atrial fibrillation were age, alcohol intake, structural heart disease and glomerular filtration rate. In total, 76.2% of patients with ECG evidence of atrial fibrillation and a CHADS2 score >1 were taking anticoagulants compared with 41.7% of those who had a history of the condition but were currently in sinus rhythm., Conclusions: The prevalence of atrial fibrillation in our group of hypertensives was 10.3%; in 1.7%, it was previously undiagnosed. Antithrombotic use was high in patients with current atrial fibrillation, but lower in those who had experienced an episode previously.

Objective: The aim of this study is to evaluate the effect of trimetazidine (TMZ) on myocardial systolic dysfunction resulting from an isolated episode of induced coronary ischemia., Methods: In a double-blinded randomized design we studied 13 mongrel anesthetized dogs of either sex (6 of them treated with oral TMZ previously). The anterior descending coronary artery was totally occluded during 15 minutes followed by 60 minutes of reperfusion. Global and regional cardiac variables were recorded in control and ischemic areas., Results: There were no significant differences between TMZ and placebo series with respect to global cardiac function variables. Both series showed no significant variations in global variables during the ischemia-reperfusion process. The shortening fraction in the ischemic area fell significantly during the ischemic period in both TMZ and placebo series reaching dyskinetic values. Myocardial contractility dysfunction persisted after 60 minutes of reperfusion in both series with no significant differences (41% vs 50% placebo)., Conclusions: Contrary to shorter and repeated occlusion periods, myocardial contractility recovery after a complete episode of ischemia did not show significant differences between TMZ-treated and placebo series.

Introduction and Objectives: The need for more specific, more sensitive and earlier biochemical markers of acute myocardial infarction, has led to the development of alternative methods to CK-MB). The aim of this work is to assess the usefulness of TnT measurement, in comparison with other markers for detecting transitory ischemic processes without necrosis in some experimental models., Methods: The plasma levels of Troponine T, CK, CK-MB and adenosine were assessed as markers of ischemic myocardial injury. Two protocols were used: in Series I and II very brief (2 min ischemia with 3-min reperfusion) repeated (20 episodes) ischemias were induced, while Series III involved a single 15-min ischemia with a 60-min reperfusion. In Series I the coronary occlusor was placed close to the anterior descending coronary artery (AD); in Series II and III it was placed distally in the AD. Blood samples were taken from the peripheral vein (PVB) and corresponding coronary segment vein; in a basal situation, during ischemia, upon reperfusion, after 24 hours, and after 5 and 10 days. The plasma levels of adenosine, troponine T, CK and CK-MB as well as general and regional function parameters were measured., Results: In Series I we observed hypokinesis that lasted 10 days, reaching its maximum on days 4-5. In Series II and III regional function was restored by 24 hours. CK and CK-MB showed similar behaviour; they rose significantly when the chest was opened (p < 0.05) reaching the highest value at 24 hours in all the series. Adenosine rose significantly only during reperfusion (p < 0.05). Troponine T increased after ischemia but not before, remained high for 5 days in all series (PVB)., Conclusions: Troponine T rises in absence of necrosis, preferably when the ischemia is longer.