Dietary magnesium intake can affect mechanical properties of rat carotid artery

The purpose of the present study was to determine the effects of Mg deficiency and supplementation on the mechanical properties of the rat common carotid artery. The internal diameter and intra-arterial pressure of carotid artery were measured continuously using an echo-tracking device. Systolic, diastolic and mean intra-arterial pressures were not significantly different in Mg-deficient, -supplemented or control rats. Histological examination showed a larger cross-sectional area, increased intima-media thickness and a greater media:lumen value in carotid artery of Mg-deficient rats, indicating that Mg deficiency may directly stimulate growth and/or proliferation of arterial wall components. In addition, we observed a negative linear relationship between intima-media thickness and plasma Mg concentration, suggesting that increased Mg intake may counteract arterial wall hypertrophy. Neither Mg deficiency nor supplementation modified the arterial distensibility v. intra-arterial pressure curve or the Einc v. wall stress curve, indicating that dietary Mg intake did not modify wall stiffness in young rats. At mean intra-arterial pressure, the stress and Einc values were, however, significantly lower in Mg-deficient rats (P<0·05 in both cases); this finding could be related to the alteration in the geometry of the carotid artery. In conclusion, these findings suggest that Mg deficiency modifies the mechanical properties of the common carotid artery in young rats. Since Mg deficiency is considered a risk factor, these mechanical alterations could contribute to the development of atherosclerosis, hypertension and cardiovascular disease

Clinical Experience With Angiotensin II Receptor Antagonists

This series of studies was designed to assess in normal volunteers the relationships between various doses (5, 10, 20, 40, 80, and 120 mg) of the orally active angiotensin II antagonist losartan (DuP 753, MK-954) and their inhibitory effect on the pressure response to a given bolus of angiotensin I or II. It was found that the maximal inhibitory effect was reached with a dose of 80 mg. The minimal dose necessary for maximal efficacy would therefore be expected to be between 40 and 80 mg. The effect lasted for more than 24 h and was related almost exclusively to the circulating levels of the active metabolite EXP3174. It remains to be demonstrated in hypertensive patients that the same dose relationship holds for the antihypertensive effect, but preliminary data already suggest that this is the case. Am J Hypertens 1992;5:243S-246

How reliable are left ventricular ejection fraction cut offs assessed by echocardiography for clinical decision making in patients with heart failure?

We aimed to study the potential influence of the variability in the assessment of echocardiographically measured left ventricular ejection fraction (LVEF) on indications for the implantation of internal cardioverter defibrillator and/or cardiac resynchronization devices in heart failure patients. TIME-CHF was a multicenter trial comparing NT-BNP versus symptom-guided therapy in patients aged ≥60years. Patients had their LVEF assessed at the recruiting centre using visual assessment, the area-length or biplane Simpson's method. Echocardiographic data were transferred to the study core-lab for re-assessment. Re-assessment in the core-lab was done with biplane Simpson's method, and included an appraisal of image quality. 413 patients had the LVEF analyzed at the recruiting centre and at the core lab. Image quality was optimal in 191 and suboptimal in 222. Overall, the correlation between LVEF at the recruiting centres and at the core-lab was good, independent of image quality (R²=0.62). However, when a LVEF≤30% or ≥30% was used as a cut-off, about 20% of all patients would have been re-assigned to having either a LVEF above or below the cut-off, this proportion was not significantly influenced by image quality. We conclude that correlation between LVEF assessed by different centres based on the same ultrasound data is good, regardless of image quality. However, one fifth of patients would have been re-assigned to a different category when using the clinically important cut-off of 30

Alcohol and cannabis consumption in patients with inflammatory bowel disease: prevalence, pattern of consumption and impact on the disease.

OBJECTIVES OF THE STUDY There is little guidance regarding the impact of alcohol and cannabis on the clinical course of inflammatory bowel disease. The aim of this study was to assess the prevalence, sociodemographic characteristics and impact of alcohol and cannabis use on the clinical course of the disease. METHODS We performed an analysis of prospectively collected data within the Swiss Inflammatory Bowel Disease Cohort Study with yearly follow-ups and substance-specific questionnaires. We analyzed the prevalence of use, the profile of users at risk for addiction and the impact of alcohol and cannabis on the course of the disease. RESULTS We collected data of 2828 patients included between 2006 and 2018 and analyzed it according to their completion of specific surveys on alcohol and cannabis use. The prevalence of patient-reported active use was 41.3% for alcohol and 6% for cannabis. Heavy drinkers were over-represented among retired, married smokers receiving mostly aminosalicylates and less immunosuppression. In ulcerative colitis patients, low-to-moderate drinking was associated with less extensive disease. Cannabis users were often students with ileal Crohn's disease. CONCLUSION A significant proportion of patients with inflammatory bowel disease consume alcohol or cannabis. Heavy alcohol consumption is most likely in male smokers >50 years, whereas young men with ileal disease rather use cannabis

Baraitser-Winter cerebrofrontofacial syndrome: Delineation of the spectrum in 42 cases

Baraitser-Winter, Fryns-Aftimos and cerebrofrontofacial syndrome types 1 and 3 have recently been associated with heterozygous gain-of-function mutations in one of the two ubiquitous cytoplasmic actin-encoding genes ACTB and ACTG1 that encode β- and γ-actins. We present detailed phenotypic descriptions and neuroimaging on 36 patients analyzed by our group and six cases from the literature with a molecularly proven actinopathy (9 ACTG1 and 33 ACTB). The major clinical anomalies are striking dysmorphic facial features with hypertelorism, broad nose with large tip and prominent root, congenital non-myopathic ptosis, ridged metopic suture and arched eyebrows. Iris or retinal coloboma is present in many cases, as is sensorineural deafness. Cleft lip and palate, hallux duplex, congenital heart defects and renal tract anomalies are seen in some cases. Microcephaly may develop with time. Nearly all patients with ACTG1 mutations, and around 60% of those with ACTB mutations have some degree of pachygyria with anteroposterior severity gradient, rarely lissencephaly or neuronal heterotopia. Reduction of shoulder girdle muscle bulk and progressive joint stiffness is common. Early muscular involvement, occasionally with congenital arthrogryposis, may be present. Progressive, severe dystonia was seen in one family. Intellectual disability and epilepsy are variable in severity and largely correlate with CNS anomalies. One patient developed acute lymphocytic leukemia, and another a cutaneous lymphoma, indicating that actinopathies may be cancer-predisposing disorders. Considering the multifaceted role of actins in cell physiology, we hypothesize that some clinical manifestations may be partially mutation specific. Baraitser-Winter cerebrofrontofacial syndrome is our suggested designation for this clinical entity

Solve-RD: systematic pan-European data sharing and collaborative analysis to solve rare diseases.

For the first time in Europe hundreds of rare disease (RD) experts team up to actively share and jointly analyse existing patient\u27s data. Solve-RD is a Horizon 2020-supported EU flagship project bringing together \u3e300 clinicians, scientists, and patient representatives of 51 sites from 15 countries. Solve-RD is built upon a core group of four European Reference Networks (ERNs; ERN-ITHACA, ERN-RND, ERN-Euro NMD, ERN-GENTURIS) which annually see more than 270,000 RD patients with respective pathologies. The main ambition is to solve unsolved rare diseases for which a molecular cause is not yet known. This is achieved through an innovative clinical research environment that introduces novel ways to organise expertise and data. Two major approaches are being pursued (i) massive data re-analysis of \u3e19,000 unsolved rare disease patients and (ii) novel combined -omics approaches. The minimum requirement to be eligible for the analysis activities is an inconclusive exome that can be shared with controlled access. The first preliminary data re-analysis has already diagnosed 255 cases form 8393 exomes/genome datasets. This unprecedented degree of collaboration focused on sharing of data and expertise shall identify many new disease genes and enable diagnosis of many so far undiagnosed patients from all over Europe

Acute coronary syndromes and acute heart failure:a diagnostic dilemma and high-risk combination. A statement from the Acute Heart Failure Committee of the Heart Failure Association of the European Society of Cardiology

Acute coronary syndrome is a precipitant of acute heart failure in a substantial proportion of cases, and the presence of both conditions is associated with a higher risk of short-term mortality compared to acute coronary syndrome alone. The diagnosis of acute coronary syndrome in the setting of acute heart failure can be challenging. Patients may present with atypical or absent chest pain, electrocardiograms can be confounded by pre-existing abnormalities, and cardiac biomarkers are frequently elevated in patients with chronic or acute heart failure, independently of acute coronary syndrome. It is important to distinguish transient or limited myocardial injury from primary myocardial infarction due to vascular events in patients presenting with acute heart failure. This paper outlines various clinical scenarios to help differentiate between these conditions and aims to provide clinicians with tools to aid in the recognition of acute coronary syndrome as a cause of acute heart failure. Interpretation of electrocardiogram and biomarker findings, and imaging techniques that may be helpful in the diagnostic work-up are described. Guidelines recommend an immediate invasive strategy for patients with acute heart failure and acute coronary syndrome, regardless of electrocardiographic or biomarker findings. Pharmacological management of patients with acute coronary syndrome and acute heart failure should follow guidelines for each of these syndromes, with priority given to time-sensitive therapies for both. Studies conducted specifically in patients with the combination of acute coronary syndrome and acute heart failure are needed to better define the management of these patients

Ventilatory Chaos Is Impaired in Carotid Atherosclerosis

Ventilatory chaos is strongly linked to the activity of central pattern generators, alone or influenced by respiratory or cardiovascular afferents. We hypothesized that carotid atherosclerosis should alter ventilatory chaos through baroreflex and autonomic nervous system dysfunctions. Chaotic dynamics of inspiratory flow was prospectively evaluated in 75 subjects undergoing carotid ultrasonography: 27 with severe carotid stenosis (>70%), 23 with moderate stenosis (<70%), and 25 controls. Chaos was characterized by the noise titration method, the correlation dimension and the largest Lyapunov exponent. Baroreflex sensitivity was estimated in the frequency domain. In the control group, 92% of the time series exhibit nonlinear deterministic chaos with positive noise limit, whereas only 68% had a positive noise limit value in the stenoses groups. Ventilatory chaos was impaired in the groups with carotid stenoses, with significant parallel decrease in the noise limit value, correlation dimension and largest Lyapunov exponent, as compared to controls. In multiple regression models, the percentage of carotid stenosis was the best in predicting the correlation dimension (p<0.001, adjusted R2: 0.35) and largest Lyapunov exponent (p<0.001, adjusted R2: 0.6). Baroreflex sensitivity also predicted the correlation dimension values (p = 0.05), and the LLE (p = 0.08). Plaque removal after carotid surgery reversed the loss of ventilatory complexity. To conclude, ventilatory chaos is impaired in carotid atherosclerosis. These findings depend on the severity of the stenosis, its localization, plaque surface and morphology features, and is independently associated with baroreflex sensitivity reduction. These findings should help to understand the determinants of ventilatory complexity and breathing control in pathological conditions