The Maremmano is an autochthonous Italian horse breed, which probably descended from the native horses of the Etruscans (VI century B.C.); the Studbook was acknowledged in 1980, and it includes 12 ...368 horses born from that year up to 2015. The aim of this study was to evaluate the effect of the selection program on the genetic variability of the Maremmano population; the analysis was performed using both the ‘Endog v 4.8’ program available at http://webs.ucm.es/info/prodanim/html/JP_Web.htm and in-house software on official pedigree data. Four Reference Populations were considered, and the most important one was the population of the 12 368 Maremmano horses officially registered in the National Studbook. The pedigree completeness of this population was very good because it was more than 90% at the third parental generation and more than 70% at the fifth generation; the pedigree traced back to a maximum of 10.50 generations with an average of 3.30 complete generations and 5.70 equivalent complete generations. The average generation interval was 10.65±4.72 years, with stallions used for longer periods than mares. The intervals ranged from 10.15±4.45 (mother–daughter) to 10.99±4.93 (father–daughter). The effective number of founders (fe) was 74 and the effective number of ancestors (fa) was 30 so that the ratio fe/fa was 2.47. The founder genome equivalents (fg) was 13.72 with a ratio fg/fe equal to 0.18. The mean of the genetic conservation index was 5.55±3.37, and it ranged from 0.81 to 21.32. The average inbreeding coefficient was 2.94%, with an increase of 0.1%/year, and the average relatedness coefficient was 5.52%. The effective population size (Ne) computed by an individual increase in inbreeding was 68.1±13.00; the Ne on equivalent generations was 42.00, and this value slightly increased to 42.20 when computed by Log regression on equivalent generations. The analysis confirmed the presence of seven traditional male lines. The percentage of Thoroughbred blood in the foals born in 2015 was 20.30% and has increased 0.21%/year since 1980; in particular, it increased more than twice (0.51%/year) until 1993 and afterwards slightly fluctuated. The pedigree analysis confirmed the completeness of genealogical information and the traditional importance that breeders gave to the male lines; although the genetic diversity of Maremmano seemed to be not endangered by the selection program, some effects on the population structure were found and a more scientific approach to genetic conservation should be incorporated in the selection plans.
OBJECTIVE:We aimed at investigating the influence of weight excess and traditional cardiovascular risk factors on vascular structure and function in a sample of obese children.
DESIGN AND ...METHOD:Overweight or obese children (BMI > 90th percentile for sex and age) included in this observational study underwent office and ambulatory BP measurements (ABPM) and the assessment of carotid intima-media thickness (cIMT), endothelial function by the Flow Mediated Dilation (FMD) technique, carotid distensibility (cDC) by ultrasounds and stiffness index (SI) by digital photopletismography.
RESULTS:Sixty-six obese and 4 overweight children were enrolled (age 11.5 ± 2.4 years; female n30). Carotid IMT directly correlated with 24h- and nighttime SBP; cDC showed inverse correlations with BMI and waist circumference and 24h-BP. Unexpectedly, SI resulted inversely related with several indexes of weight excess. Most of these correlations remained significant after adjustment for age, sex, BMI and BP. In a replication set of 40 obese children SI, but not Pulse Wave Velocity (PWV), was still inversely associated with BMI.
CONCLUSIONS:These data suggest that arterial structure and elasticity are negatively affected by weight excess and BP levels, even in childhood. Surprisingly, SI might not be a reliable marker of vascular stiffness in obese children, because this measure is probably confounded by other factors including vasodilation.
OBJECTIVE:Type 1 diabetes mellitus (T1DM) is associated with early development of atherosclerosis. The aim of this study was to measure some indices of vascular damage in a group of children and ...adolescents with T1DM and their relationship with haemodynamic and metabolic parameters.
DESIGN AND METHOD:In a cross-sectional study, peripheral (pSBP/pDBP) and central systolic and diastolic blood pressure (cSBP/cDPB), carotid intima media thickness (cIMT) and carotid distensibility (cDC), pulse wave velocity (PWV) were measured using ultrasound and the SphygmoCor XCel device. Metabolic parameters, including triglycerides, LDL and HDL-cholesterol, were measured and glycated haemoglobin (HbA1c; average of the last two years) was calculated.
RESULTS:126 subjects with T1DM (61 females and 65 males, mean age 15.9 ± 2.6 years) followed at the Paediatric Diabetology Unit of Verona were evaluated at the Vascular Laboratory of the General Medicine & Hypertension Unit. Eighteen per cent of the sample had cDC under the 5th percentiles and 60% had cIMT higher than the 95th percentiles per sex and height. Both cSBP and pSBP were positively correlated with BMI (respectively r = 0.404; p < 0.0001 and r = 0.279; p < 0.01). A significant correlation between cSBP and all the measures of vascular damage was foundcDC (r = −0.410; p < 0.0001), PWV (r = 0.447; p < 0.0001), cIMT (r = 0.227; p < 0.01). The duration of diabetes, LDL-cholesterol and the average HbA1c were not correlated to any vascular phenotype. In linear regression analysis, after adjustment for all metabolic and anthropometric parameters, central SBP remained independently associated with subclinical carotid damage (for cIMT β = 0.002; p = 0.023; for cDC β = −0.343; p = 0.003) and PWV (β = 0.025; p < 0.001) whereas LDL-cholesterol with cIMT (β = 0.001; p < 0.05) and PWV (β = 0.025; p < 0.01).
CONCLUSIONS:Subclinical vascular damages are present in a high proportion of children and adolescents with T1DM. cSBP, more than pBP, is independently associated with indexes of vascular subclinical atherosclerosis, suggesting a pivotal role of blood pressure homeostasis, along with LDL-cholesterol, in determining vascular damage even during childhood and adolescence in patients with T1DM.
OBJECTIVE:Epoxyeicosatrienoic acids (EETs) act as vasodilators activating high conductance calcium-operated potassium (K) channels (Kca1.1, also named BK, MAXI-K). We found expression of MAXI-K ...channel in platelets. The present study aimed at defining its functionality in platelet using an in vitro model of platelet thrombosis.
DESIGN AND METHOD:We tested the effects of 5 μmol/L 11,12-EET and the pharmacological modulation of MAXI-K channel (agonists5 and 20 μmol/L BMS 191011, 5 μmol/L NS1619, 5 μmol/L NS11021). Platelet rich plasma was used to assess adhesion-induced thrombi formation under flow by microfluidics technology with collagen-coated microchips mimicking arterial blood flow. The kinetic of platelet responses to scalar doses of 0.3–10 μmol/L ADP, 0.05–2 μmol/L U46619 0.5–10 μg/mL collagen was determined by paired analysis using Born aggregometry. Flow-cytometry was used to analyse the expression of active fibrinogen receptor and P-selectin in stimulated platelets. The effects of 100 μmol/L aspirin and 1 μmol/L ticagrelor were also assessed.
RESULTS:In vitro thrombi formation was halved (expressed as platelet-covered area) by pre-treatment with either 11,12-EET (−45 ± 11%, n = 5, P < 0.001 vs control, Mean ± SD), aspirin (−66 ± 8%, n = 4, P < 0.001) or ticagrelor (−55 ± 8%, n = 4, P < 0.001). Similar results were obtained using BMS 5 μmol/L (−54 ± 17%, n = 6, P < 0.001), NS1619 (−50 ± 19%, n = 9, P < 0.001), NS11021 (−60 ± 21%, n = 6, P < 0.001). The addition of 20 μmol/L BMS191011 prior to platelet aggregation (EC502.67 μmol/L, 95%CI0.97–7.29, n = 36) significantly shifted to the right the dose response-curve to ADP (EC500.91 μmol/L, 0.43–1.92, n = 36). Platelet aggregation was further blunted by the addition of aspirin to BMS191011 (EC506.18 μmol/L, 2.11–18.09, n = 36). U46619- and collagen-induced aggregation was not altered. ADP-induced activation of the fibrinogen receptor (−48 ± 14% to −62 ± 10%, n = 7, P < 0.05) and P-selectin expression (−37 ± 15% to −41 ± 13%, n = 7, P < 0.01) were blunted by the activators of MAXI-K channel.
CONCLUSIONS:Activation of the MAXI-K channel by 11,12-EET and all the tested synthetic compounds is associated with reduced sensitivity to ADP and reduced thrombus generation through the inhibition of the amplificatory phase of platelet activation. The present results reveal new mechanisms of platelet activation and suggest that targeting MAXI-K might be of potential pharmacological interest for the prevention of atherothrombosis.
OBJECTIVE:Dietary and circulating fatty acids (FA) and desaturases activity, involved in FA metabolism, are associated with metabolic and cardiovascular disorders. In particular, a lower delta-5 ...desaturase activity (D5D) in contrast to a higher delta-6 desaturase (D6D) and stearoyl-CoA desaturase (SCD-16; the enzyme that metabolizes palmitic (PA) to palmitoleic acid (PtA)) activities were related to obesity and metabolic disorders.
DESIGN AND METHOD:FA profile was determined on whole blood drop in 244 children (50.2 % females; mean age 8.6 ± 0.72 years) participating in a school-based cross-sectional study. The possible associations between individual FA and desaturases activity (evaluated as product:precursor ratios) with indices of adiposity and blood pressure (BP) was investigated.
RESULTS:Omega-3 Index, marker of long-term eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) dietary intake, was low (3.9 ± 0.88 %). DHA inversely correlated with BMI and waist/height ratio, whereas oleic acid, PA and individual omega-6 PUFAs were not associated with either obesity or BP, except for a direct correlation of dihomo-gamma-linoleic acid (DGLA) with some indices of adiposity. PtA, an omega-7 FA, was directly associated with adiposity (BMIr = 0.408, p < 0.01; waist circumferencer = 0.368, p < 0.01; fat massr = 0.402, p < 0.01) and BP (Systolicr = 0.203, p < 0.01; Diastolicr = 0.167, p < 0.01). D5D inversely correlated with waist circumference, D6D directly with waist/height ratio and SCD-16 directly with most adiposity indices and BP. Children with excess weight (BMI > 85th percentile) showed higher concentrations of PA, PtA and a higher SCD-16 activity compared to normal-weight children. In the excess-weight group PA directly correlated with some anthropometric measurements and PtA confirmed the direct association with obesity and BP. Even SCD-16 directly correlated with anthropometric features and BP. Caucasian children (66.8%) had higher D6D activity than non-Caucasians (33.2%), and in Caucasians D6D directly correlated with obesity. In this subgroup PA, PtA and SCD-16 directly correlated with anthropometric characteristics and BP.
CONCLUSIONS:PtA and SCD-16 directly correlated with indices of adiposity and BP, especially in obese children. D6D activity is likely influenced by ethnicity, showing an apparent harmful effect especially in Caucasians.
OBJECTIVE:Since childhood, unhealthy dietary habits could trigger the onset of cardiovascular risk factors, such as obesity and hypertension. Aim of this school-based study was to identify the ...possible relation between dietary patterns, physical activity and anthropometric, hemodynamic (blood pressure, BP; pulse wave velocity, PWV) and gluco-lipid parameters.
DESIGN AND METHOD:A validated Food Frequency Questionnaire (FFQ) and a validated questionnaire assessing the degree of physical activity (PAQ-C) were administered to children attending the 3rd and 4th class of 4 primary schools. Children responded with the aid of their parents and a dedicated dietitian. From FFQ, composed by 15 categories for a total of 61 foods, nutritional content in term of energy and macro-nutrients intake was extrapolated. Also dietary patterns obtained by Principal Component Analysis (PCA) were identified. Metabolic Equivalent of Task (MET) were computed for each child from IPAQ.
RESULTS:hree-hundred and nine children between 8 and 11 years participated (74,8% response rate) of whose 302 (97,7%) children compiled the FFQ. Significant correlations were found between“junk food” intake and BMI (rs = 0.141, p < 0.05), diastolic BP (rs = 0.114, p < 0.05); PWV (rs = 0.155, p < 0.001), triglycerides (rs = 0.150, p < 0.05); meat intake and diastolic BP (rs = 0.124, p < 0.05); vegetables intake and Z-score of diastolic BP (rs = −0.115, p < 0.05); “animal fats” intake and cholesterol (rs = 0.165, p < 0.05). PCA identifies three dietary patternsone characterized by junk food, meat, sweet, cereals and tubers; one composed by fruits, vegetables and fish and legumes and one characterized by eggs. No significant correlation was found between physical activity and the analyzed parameters.
CONCLUSIONS:The significant correlation between some categories of food and anthropometric, vascular and gluco-lipid parameters in 8-11y children suggests that it is important to begin early with politics to prevent the onset of overt cardiovascular risk factors.
OBJECTIVE:Treatment of obstructive sleep apnoea (OSA) has been shown to reduce blood pressure (BP). However, the effect size is modest and treatment of OSA is not recommended as the only treatment ...target when treating hypertension. Despite the limited effect of continuous positive airway pressure (CPAP) therapy on BP, it is likely that certain phenotypes of OSA patients respond better to CPAP than others. The aim of the present systematic review and meta-analysis was to identify potential predictors for BP response in patients with OSA undergoing CPAP treatment.(Figure is included in full-text article.)
DESIGN AND METHOD:A systematic search was conducted in three databases (MEDLINE, Embase and Web of Science) using terms exploring three domains (obstructive sleep apnoea, CPAP, clinical trial) based on the following inclusion criteriai) randomised controlled clinical trials published between January 1st 1960 to December 31st 2017 including a reasonable control group; iii) OSA diagnosis using polysomnography; iv) age >18 years; v) OSA severity of at least 5 AHI/h. The random effect model was fitted to estimate the pooled BP reductions calculated as the difference between the BP change (end-treatment minus baseline) in the CPAP and control group. Moreover, the original estimates have been stratified according to selected patient characteristics.
RESULTS:Out of 2445 articles, 59 RCTs were included (n = 7,329 subjects) comparing CPAP with control groups. CPAP was associated with a net reduction in systolic BP of −2.12 (95% CI −2.82 to −1.42) mmHg and in diastolic BP of −1.97 (95% CI −2.46 to −1.48) mmHg, favouring treatment of OSA using CPAP (both p-values < 0.001). The subgroup analysis showed that systolic BP reduction was greater in subjects younger than 60 years (−2.88 fro age 40–50, −2.78 for age 50–60 and −0.61 for age more than 60 years, p = 0.007) and in patients with controlled BP at baseline versus uncontrolled BP (−1.45 vs −4.14, p = 0.002) (Figure 1).
CONCLUSIONS:Younger patients (< 60 years) with uncontrolled blood pressure at baseline are more likely to experience significant BP reductions with CPAP therapy. Phenotypisation of specific cohorts of patients can guide clinicians to target OSA treatment and help to optimise patients’ cardiovascular risk.
The Marchigiana is famous for its large body size and favorable dressing percentage. A myostatin (MSTN) gene mutation (a G to T transversion) was identified in the breed. The homozygote "GG" yields a ..."normal" phenotype, the homozygote "TT" yields a double muscled body shape but sometimes causes survival problems, and the heterozygote genotype produces an extremely muscled body without defects. In practice, Marchigiana "TT" homozygotes are culled from reproduction, but the heterozygotes are chosen as sires. The objective of this study was to assess genes involved in Marchigiana muscle development to improve selection procedures. The effects of the MSTN and myogenic factor 5 (MYF5) genes on the growth and muscle traits in the Marchigiana breed were assessed. The effects of MSTN together with the genotype of the causative mutation (g.874G > T) and the effects of the two SNP in the promoter were studied (g.-371T > A and g.-805G > C). The SNP effects were evaluated in a comparison between the means of the several genotypes or for the average gene substitution and dominance effect. Two hundred forty-nine bullocks were evaluated using a performance test. At the beginning and end of the trial, the animals were weighed and their bodies were measured every 21 d up to 12 mo of age. In addition to these observations, morphological scores and the BLUP indices were estimated at the end of the performance test. The obtained results suggested that the MSTN g.874G > T and MYF5 SNP could be considered in the selection program of the Marchigiana breed. A MSTN g.874G > T genotyping service for the breeders could help to avoid the "TT" genotype and to select for the "GT" genotype. The "AA" MYF5 SNP genotype could also be selected for even if good muscle development yields a certain size reduction.
Background
SARS- CoV-2 virus has had dramatic consequences worldwide being able to cause acute respiratory distress syndrome (ARDS), massive thrombosis and pulmonary embolism and, finally, patients’ ...death. In COVID-19 infection, platelets have a procoagulant phenotype that can cause thrombosis in the pulmonary and systemic vascular network. Aspirin is a well-known anti-platelet drug widely used for the prevention of cardiovascular events and systematic reviews suggest a possible benefit of low-dose aspirin (LDA) use in the prevention and treatment of ARDS in patients with COVID-19 infection. However, several studies are available in the literature which do not support any benefits and no association with the patients’ outcome. Therefore, currently available data are inconclusive.
Materials and patients
Data from the nationwide cohort multicenter study of the Italian Society of Internal Medicine (SIMI) were analyzed. We conducted a propensity score-matched cohort analysis to investigate the impact of chronic assumption of LDA on mortality of adult COVID-19 patients admitted in Internal Medicine Units (IMU). Data from 3044 COVID-19 patients who referred to 41 Italian hospitals between February 3rd to May 8th 2020 were analyzed. A propensity score-matched analysis was conducted using the following variables: age, sex, hypertension, hyperlipidemia diabetes, atrial fibrillation, cerebrovascular disease, COPD, CKD and stratified upon LDA usage, excluding anticoagulant treatment. After matching, 380 patients were included in the final analysis (190 in LDA group and 190 in no-LDA group).
Results
66.2% were male, median age was 77 70–83. 34.8% of the population died during the hospitalization. Cardiovascular diseases were not significantly different between the groups. After comparison of LDA and no-LDA subgroups, we didn’t record a significant difference in mortality rate (35.7% vs 33.7%) duration of hospital stay and ICU admission. In a logistic regression model, age (OR 1.05; 95% CI 1.01–1.09), FiO2 (OR 1.024; 95% CI 1.03–1.04) and days between symptoms onset and hospitalization (OR 0.93; 95% CI 0.87–0.99) were the only variables independently associated with death
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Summary
We explored the expression and cell type distribution of cannabinoid receptors type 1 (CB1) and cannabinoid receptors type 2 (CB2) in the mandibular glands of pigs in relation to different ...physical forms of the diet. Thirty‐two crossbred growing pigs (ages 5–6 weeks) were randomly allotted to four experimental groups (eight pigs/group) and fed four different physical types of the same diet for 4 weeks: finely ground pellet (FP), coarsely ground meal (CM), coarsely ground pellet (CP) and coarsely ground extruded (CE) with dMEAN of 0.46, 0.88, 0.84 and 0.66 mm respectively. At the end of the feeding trial, the pigs were euthanized and the mandibular gland was collected after dissection. By immunohistochemistry, positive signals for CB1 were found in the cytoplasm of duct epithelial cells of pigs fed CP, FP and CE diets and in the serous cells of mixed acini in pigs fed the coarser CM diet. Positive signals for CB2 were detected in duct epithelial cells and in neurons of ganglia close to major secretory ducts of all pigs. The differential expression and localization of these receptors in response to variable chewing activity due to the type of diet suggest that endocannabinoids may influence the functional activity of the mandibular gland by modifying qualitative and/or quantitative aspects of salivary secretion.