Supplemental fibrinogen restores thrombus formation in cardiopulmonary bypass-induced platelet dysfunction ex vivo.

BACKGROUND: Major cardiac surgery related blood loss is associated with increased postoperative morbidity and mortality. Platelet dysfunction is believed to contribute to post-cardiopulmonary bypass (CPB)-induced microvascular bleeding. We hypothesised that moderately hypothermic CPB induces platelet dysfunction and that supplemental fibrinogen can restore in vitro thrombus formation. METHODS: Blood from 18 patients, undergoing first-time elective isolated aortic valve surgery was drawn before CPB, 30 min after initiation of CPB, and after CPB and protamine administration, respectively. Platelet aggregation was quantified by optical aggregometry, platelet activation by flow-cytometric detection of platelet surface expression of P-selectin, annexin V, and activated glycoprotein IIb/IIIa, thrombus formation under flow and effect of supplemental fibrinogen (4 mg ml-1) on in vitro thrombogenesis. RESULTS: Post-CPB adenosine-diphosphate and TRAP-6-induced aggregation decreased by 40% and 10% of pre-CPB levels, respectively (P<0.0001). Although CPB did not change glycoprotein IIb/IIIa receptor expression, it increased the percentage of unstimulated P-selectin (1.2% vs 7%, P<0.01) positive cells and annexin V mean fluorescence intensity (15.5 vs 17.2, P<0.05), but decreased percentage of stimulated P-selectin (52% vs 26%, P<0.01) positive cells and annexin V mean fluorescence intensity (508 vs 325, P<0.05). Thrombus area decreased from 6820 before CPB to 5230 after CPB (P<0.05, arbitrary units [a.u.]). Supplemental fibrinogen increased thrombus formation to 20 324 and 11 367 a.u. before CPB and after CPB, respectively (P<0.001), thereby restoring post-CPB thrombus area to levels comparable with or higher than pre-CPB baseline. CONCLUSIONS: Single valve surgery using moderately hypothermic CPB induces partial platelet dysfunction. Thrombus formation was restored in an experimental study design by ex vivo supplementation of fibrinogen.

Albumin of People with Diabetes Mellitus Is More Reduced at Low HbA1c.

Oxidative stress is involved in the development, progression, and complications of diabetes mellitus (DM). Oxidative modification of human serum albumin's cysteine-34 is a marker for oxidative stress-related pathological conditions. We aimed to evaluate the redox state of albumin in patients with DM to investigate possible correlations with age, diabetes duration, and disease control status. Plasma aliquots were collected from 52 participants (26 type 1 and 26 type 2 DM). Patients were divided into two groups according to their glycated hemoglobin levels less than or equal to and greater than 58 mmol/L. Albumin redox state was assessed with high-performance liquid chromatography by fractionating it into human mercaptalbumin (HMA) and human nonmercaptalbumin 1 and 2 (HNA1 and HNA2). Albumin redox fractions were differently related to the age of study participants. In age-matched T1DM and T2DM groups, the albumin redox state was essentially the same. Irreversibly oxidized HNA2 was positively correlated with diabetes duration, especially in the T1DM group. HNA was increased in people with an increased HbA1c (>58 mmol/mol). Our results support the hypothesis that oxidative stress plays a crucial role in DM pathogenesis and emphasize the importance of diabetes control on systemic oxidative burden.

Humoral immune response to COVID-19 vaccination in diabetes is age-dependent but independent of type of diabetes and glycaemic control: The prospective COVAC-DM cohort study.

AIMS: To investigate the seroconversion following first and second COVID-19 vaccination in people with type 1 and type 2 diabetes in relation to glycaemic control prior to vaccination and to analyse the response in comparison to individuals without diabetes. MATERIALS AND METHODS: This prospective, multicentre cohort study analysed people with type 1 and type 2 diabetes and a glycated haemoglobin level ≤58 mmol/mol (7.5%) or >58 mmol/mol (7.5%), respectively, and healthy controls. Roche's Elecsys anti-SARS-CoV-2 S immunoassay targeting the receptor-binding domain was used to quantify anti-spike protein antibodies 7 to 14 days after the first and 14 to 21 days after the second vaccination. RESULTS: A total of 86 healthy controls were enrolled in the study, as well as 161 participants with diabetes, of whom 150 (75 with type 1 diabetes and 75 with type 2 diabetes) were eligible for the analysis. After the first vaccination, only 52.7% of participants in the type 1 diabetes group and 48.0% of those in the type 2 diabetes group showed antibody levels above the cut-off for positivity. Antibody levels after the second vaccination were similar in participants with type 1 diabetes, participants with type 2 diabetes and healthy controls after adjusting for age, sex and multiple testing (P > 0.05). Age (r = -0.45, P < 0.001) and glomerular filtration rate (r = 0.28, P = 0.001) were significantly associated with antibody response. CONCLUSIONS: Anti-SARS-CoV-2 S receptor-binding domain antibody levels after the second vaccination were comparable in healthy controls and in participants with type 1 and type 2 diabetes, irrespective of glycaemic control. Age and renal function correlated significantly with the extent of antibody levels.

Redox State of Human Serum Albumin in Multiple Sclerosis: A Pilot Study.

Like in many other pathologies, oxidative stress is involved in the development of neurodegenerative disorders. Human serum albumin (HSA) is the main protein in different body fluids including cerebrospinal fluid (CSF). By its redox state in terms of cysteine-34, albumin serves as marker for oxidative burden. We aimed to evaluate the redox state of HSA in patients with multiple sclerosis in serum and CSF in comparison to controls to identify possible correlations with disease activity and severity. Samples were stored at -70 °C until analysis by HPLC for the determination of albumin redox state in terms of the fractions of human mercaptalbumin (HMA), human nonmercaptalbumin1 (HNA1), and human nonmercaptalbumin2 (HNA2). Albumin in CSF showed significantly higher fractions of the reduced form HMA and decreased HNA1 and HNA2. There was no difference between albumin redox states in serum of patients and controls. In CSF of patients HNA2 showed a trend to higher fractions compared to controls. Albumin redox state in serum was associated with physical disability in remission while albumin redox state in CSF was related to disease activity. Thus, albumin redox state in serum and CSF of patients in relation to disease condition merits further investigation.

COVID-19 and its effects on endothelium in HIV-positive patients in sub-Saharan Africa: Cardiometabolic risk, thrombosis and vascular function (ENDOCOVID STUDY).

BACKGROUND: COVID-19 has affected almost every country in the world, especially in terms of health system capacity and economic burden. People from sub-Saharan Africa (SSA) often face interaction between human immunodeficiency virus (HIV) infection and non-communicable diseases such as cardiovascular disease. Role of HIV infection and anti-retroviral treatment (ART) in altered cardiovascular risk is questionable and there is still need to further carry out research in this field. However, thus far it is unclear, what impact the COVID-19 co-infection in people living with HIV (PLHIV), with or without therapy will have. The ENDOCOVID project aims to investigate whether and how HIV-infection in COVID-19 patients modulates the time course of the disease, alters cardiovascular risk, and changes vascular endothelial function and coagulation parameters/ thrombosis risk. METHODS: A total of 1026 patients will be included into this study. Cardiovascular research PLHIV with (n = 114 in each of the three recruiting centers) - or without - ART (n = 114 in each of the three recruiting centers) with COVID-19 and HIV-negative with COVID-19 (n = 114 in each of the three recruiting centers) will be carried out via clinical and biochemical measurements for cardiovascular risk factors and biomarkers of cardiovascular disease (CVD). Vascular and endothelial function will be measured by brachial artery flow-mediated dilatation (FMD), carotid intima-media thickness (IMT) assessments, and retinal blood vessel analyses, along with vascular endothelial biomarkers and cogualation markers. The correlation between HIV-infection in COVID-19 PLHIV with or without ART and its role in enhancement of cardiovascular risk and endothelial dysfunction will be assessed at admission, weekly, at discharge and, 4 weeks post-discharge (if possible). IMPACT OF PROJECT: The ENDOCOVID project aims to evaluate in the long-term the cardiovascular risk and vascular endothelial function in PLHIV thus revealing an important transitional cardiovascular phenotype in COVID-19. The study was registered under clinicaltrials.gov (NCT04709302).

Right ventricular end-systolic remodeling index in the assessment of pediatric pulmonary arterial hypertension. The European Pediatric Pulmonary Vascular Disease Network (EPPVDN).

BACKGROUND: Echocardiographic determination of the right ventricular end-systolic remodeling index (RVES RI) has clinical value for the assessment of pulmonary hypertension (PH) in adults. We aim to determine RVES RI values in pediatric PH and to correlate RVES RI data with echocardiographic variables and NYHA functional class (FC). METHODS: Prospective echocardiography study in 49 children with PH. The 49 matched control subjects were chosen from 123 healthy children used to construct pediatric normal reference values. The associations with invasive hemodynamic variables were also investigated in a validation cohort of 12 PH children and matched controls. RESULTS: RVES RI was increased in children with PH vs. healthy controls (1.45 ± 0.16 vs. 1.16 ± 0.06; p < 0.01; confirmed in the validation cohort). RVES RI was associated with invasive hemodynamic variables, i.e. the mean pulmonary artery pressure. RVES RI values increased with worsening NYHA-FC. The highest RVES RI values were observed in PH children with NYHA FC 3 (1.60 ± 0.12). CONCLUSIONS: RVES RI is a useful indicator of RV remodeling and dilation in the setting of increased RV pressure load, especially when the degree of regurgitation of the tricuspid and pulmonary valves is insufficient to numerically estimate RV systolic pressure and mPAP, due to incomplete Doppler envelopes.

Increased tissue factor activity promotes thrombin generation at type 1 diabetes onset in children.

OBJECTIVE: In type 1 diabetes (T1D), a prothrombotic status due to elevated coagulation factors coincides with metabolic derailment. In a previous study, we discovered altered thrombin generation profiles in children with T1D. These alterations are potentially most pronounced at T1D onset and ameliorated after insulin treatment. We tested this hypothesis in a longitudinal study, measuring thrombin generation together with coagulation parameters in children at T1D onset and during follow-up. MATERIALS AND METHODS: Twenty-three children (12 female, age: 9.4 [2.7-17.3] years; median [range]) were tested at T1D onset and after long-term insulin treatment. Thrombin generation was measured using calibrated automated thrombography. Tissue factor (TF) activity and tissue factor pathway inhibitor (TFPI) activity were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: A procoagulant shift was observed in thrombin generation traces at T1D onset compared to follow-up (time to peak: 5.67 [4.11-7.67] min vs 6.39 [4.89-10.44] min, P < .001). These alterations at T1D onset coincided with increased TF activity (5.18 [0.01-12.97] pmol/L vs 2.67 [0.04-10.41] pmol/L, P < .05) and increased TFPI activity (0.051 [0.038-0.074] U/mL vs 0.035 [0.026-0.056] U/mL, P < .05). CONCLUSION: The procoagulant shift in thrombin generation at T1D onset is a result of increased TF activity, but this effect is partially counterbalanced by increased TFPI levels. Elevated TF and TFPI levels hint to a fragile hemostatic balance at the endothelial lining of blood vessels. Additional prothrombotic stimuli may tip over this balance explaining the increased thrombotic risk of children with T1D.

Calculation of HAS-BLED Score Is Useful for Early Identification of Venous Thromboembolism Patients at High Risk for Major Bleeding Events: A Prospective Outpatients Cohort Study.

The aim of this study was prospective evaluation of the performance of the HAS-BLED score in predicting major bleeding complications in a real-world outpatient cohort, during long-term anticoagulation for venous thromboembolism (VTE), treated with a broad spectrum of anticoagulants. We analyzed 111 outpatients objectively diagnosed with VTE and treated long-term with various anticoagulants. Patients were grouped in three cohorts based on the anticoagulant regimen. Calculation of the HAS-BLED score and documentation of bleeding events were performed every 6 months for 1 year. Patients with a HAS-BLED score ≥ 3 had an increased risk for major bleeding events (odds ratio [OR]: 13.05, 95% confidence interval [CI]: 0.96-692.58, p = 0.028) and a trend to higher risk for minor bleeding events as well (OR: 2.25, 95% CI: 0.87-5.85, p = 0.091) when compared with patients with a HAS-BLED score < 3.This indicates that a HAS-BLED score ≥ 3 allows for identification of patients with VTE on long-term anticoagulation at an increased risk for major bleeding events, irrespective of the anticoagulant agent used.

Right Ventricular Outflow Tract (RVOT) Changes in Children with an Atrial Septal Defect: Focus on RVOT Velocity Time Integral, RVOT Diameter, and RVOT Systolic Excursion.

OBJECTIVE: Aim of the study was to determine the influence of right heart volume overload in children with atrial septal defect (ASD) on right ventricular outflow tract (RVOT) variables. METHODS: A prospective study was conducted in 115 children (age range: 2 days-18.1 years) with a moderate to large ASD. We determined effects of age, body length (BL), body weight (BW), and body surface area (BSA) on the variables RVOT diameter, RVOT velocity time integral (VTI), and RVOT systolic excursion (SE), and tested the predictive value of published normal values for age, BW, BL, and BSA in our ASD patients. RESULTS: In our pediatric ASD patients, the age-specific RVOT diameter (z-score: +2.2, 95% CI: 2.0-2.4, P < 0.001) was significantly increased compared to normal values with 54% of our ASD patients having a z-score >2.0. The age-specific RVOT VTI z-score (z-score: +3.6, 95% CI: 3.2-3.9, P < 0.001) was significantly increased compared to normal values with 81% of our ASD patients having a z-score >2.0. The age-specific RVOT SE z-score was not increased but slightly lower compared to normal values (z-score: -0.5, 95% CI: -0.7 to -0.3, P < 0.001) with 3% of our ASD patients having a z-score >2.0 while 12% of the patients had a z-score <-2. CONCLUSION: In our study population, we show the RVOT VTI and diameter to be relevant predictors in identifying an enlarged RVOT size and flow in children with moderate to large ASD.

Significant decrease of subcutaneous body fat during tube-weaning from enteral feeding.

BACKGROUND: The aim of this paper was to evaluate anthropometry and subcutaneous body fat on long-term enterally-fed children during tube weaning through a prospective cohort study with a pre-post-test design. METHODS: The LIPOMETER, an optical device, was used to measure the thickness of subcutaneous adipose tissue (SAT) layers (in mm). The specification of 15 evenly-distributed body sites allows for a precise measurement of subcutaneous body fat distribution, known as subcutaneous adipose tissue topography (SAT-Top). Anthropometry and SAT-Top were determined in long-term enterally fed children in the pre- and post-tube weaning phase of a 3-week tube weaning program. The results of the SAT-Top measurements are presented on three levels: 15 body sites, four body regions and SAT-total. RESULTS: The sample size consisted of 30 long-term tube-fed children (13 girls and 17 boys). Both sexes demonstrated a clear decrease of anthropometry and subcutaneous body fat during tube weaning. Girls lost -26.1 mm, -30.7%, (P=0.002) of their initial fat mass and boys -12.5 mm, -18.4%, (P<0.001). In general, girls had thicker SAT layers in all SAT-Top measurements and a higher reduction of subcutaneous body fat during the intervention. At the end of the tube weaning program girls and boys demonstrated similar results of subcutaneous body fat on the three observed levels: 15 body sites, four body regions and SAT-total. Upon discharge, total subcutaneous body fat of girls and boys was 58.9 mm and 55.5 mm, respectively. CONCLUSION: This study presents a basic documentation of changes in anthropometry and subcutaneous body fat during tube weaning and could potentially be used to help create guidelines for safe tube weaning.

Bed rest does not induce hypercoagulability.

BACKGROUND: Although there is no direct evidence, it is generally believed that bed rest shifts the haemostatic system towards hypercoagulability; thus, immobilized patients are commonly treated with anticoagulants. We therefore aimed to investigate whether long-term bed rest actually leads to an elevated risk for thromboembolic events. MATERIALS AND METHODS: Eleven healthy men were enrolled in our study (bed rest campaign in MEDES Clinique d'Investigation, Toulouse, France). Besides various standard laboratory methods, we used calibrated automated thrombography (CAT) and thrombelastometry (TEM). Activation of samples with minute amounts of relipidated tissue factor allowed sensitive detection of hyper- or hypocoagulable states. RESULTS: CAT and TEM values were not indicative of bed rest-induced hypercoagulability. On the contrary, several parameters were indicative of a tendency towards a hypocoagulable state. Peak and thrombin formation velocity (VELINDEX) were significantly decreased during bed rest compared to baseline. Coagulation times were significantly increased and alpha angles were significantly decreased, indicating attenuated clot formation. Moreover, F1 + 2 and thrombin/antithrombin complex (TAT) values were significantly decreased during bed rest, indicating suppressed coagulation activation. FVII plasma levels were also significantly decreased during the first week of bed rest. CONCLUSIONS: Our data indicate that the re-ambulation period is associated with a tendency towards hypercoagulability: ttPeak and StartTail were significantly shorter, Peak and VELINDEX were significantly higher compared to baseline. Moreover, plasma levels of F1 + 2, TAT, FVII and FVIII were significantly higher compared to baseline. The results from our study suggest that bed rest by itself is not associated with hypercoagulable states in healthy subjects.

Longitudinal systolic left ventricular function in preterm and term neonates: reference values of the mitral annular plane systolic excursion (MAPSE) and calculation of z-scores.

The mitral annular plane systolic excursion (MAPSE) is a quick and reliable echocardiographic tool for assessing longitudinal left ventricular (LV) systolic function in children and adults. Because this parameter is affected by the LV longitudinal dimension, pediatric and adult normal values are not suitable for preterm and term neonates. A prospective study investigated a large group of preterm and term neonates [gestational age (GA), 26/0-6 to 40/0-6; birth weight (BW), 670-4,140 g]. The growth- and BW-related changes in MAPSE were determined to establish normal z-score values for preterm and term neonates. The MAPSE ranged from a mean of 0.36 ± 0.05 cm in preterm neonates with a GA of 26/0-6 to 0.56 ± 0.08 cm in term neonates with a GA of 40/0-6. The findings showed MAPSE, GA, and BW to be moderately correlated. Pearson's correlation coefficient was 0.56 for GA (MAPSE; p < 0.001) and 0.58 for BW (MAPSE; p < 0.001). The normal MAPSE values did not differ significantly between females and males (p = 0.946). The absolute values and z-scores of normal MAPSE values in healthy preterm and term neonates within the first 48 h of life were calculated, and percentile charts were established. Determination of LV function using MAPSE might be useful for vulnerable infants for whom a prolonged examination is inappropriate and for neonates with suboptimal visualization of the endocardium.

Right Ventricular Outflow Tract Velocity Time Integral Determination in 570 Healthy Children and in 52 Pediatric Atrial Septal Defect Patients.

Determination of the right ventricular outflow tract velocity time integral (RVOT VTI) is an important part of the noninvasive investigation of pulmonary blood flow in adults; however, age-related pediatric reference data are lacking. We examined growth-related changes of RVOT VTI values in children and the predictive value of RVOT VTI values in identifying enhanced pulmonary blood flow in children with secundum type atrial septal defect (ASD). A prospective study was conducted in a group of 570 healthy children and 52 children with a moderate-sized to large ASD. We determined the effects of age, body length (BL), body weight (BW), and body surface area (BSA) on RVOT VTI values. The predictive value of normal values stratified for age, BW, BL, and BSA was tested in our 52 ASD children. RVOT VTI values ranged from mean 9.7 ± 1.2 cm in neonates to 23.3 ± 2.7 cm in children with 18 years of age and showed a positive correlation with age, BL, BSA, and BW. In our population, RVOT VTI z-scores showed a high specificity for detecting ASD patients (>97 %) with sensitivity up to 71 %. We provide normal ranges and calculated z-scores of pediatric RVOT VTI values. Normal RVOT VTI z-scores might be additional predictors in identifying increased pulmonary blood flow in patients with ASD.

Hypothyroidism Exacerbates Thrombophilia in Female Rats Fed with a High Fat Diet.

Clotting abnormalities are discussed both in the context with thyroid dysfunctions and obesity caused by a high fat diet. This study aimed to investigate the impact of hypo-, or hyperthyroidism on the endogenous thrombin potential (ETP), a master indicator of clotting activation, on Sprague Dawley rats fed a normal or high fat diet. Female Sprague Dawley rats (n = 66) were grouped into normal diet (ND; n = 30) and high-fat diet (HFD; n = 36) groups and subdivided into controls, hypothyroid and hyperthyroid groups, induced through propylthiouracil or triiodothyronine (T3) treatment, respectively. After 12 weeks of treatment ETP, body weight and food intake were analyzed. Successfully induced thyroid dysfunction was shown by T3 levels, both under normal and high fat diet. Thyroid dysfunction was accompanied by changes in calorie intake and body weight. In detail, compared to euthyroid controls, hypothyroid rats showed significantly increased-and hyperthyroid animals significantly decreased-ETP levels. High fat diet potentiated these effects in both directions. In summary, we are the first to show that hypothyroidism and high fat diet potentiate the thrombotic capacity of the clotting system in Sprague Dawley rats. This effect may be relevant for cardiovascular disease where thyroid function is poorly understood as a pathological contributor in the context of clotting activity and obesogenic nutrition.

Subcutaneous Adipose Tissue Topography in Long-Term Enterally Fed Children and Healthy Controls.

In the context of enteral feeding in children the influence on growth and the question of fat resorption is of great interest. We, therefore, measured the thickness of subcutaneous body fat in a sample of long-term enterally fed toddlers and healthy controls. In 33 long-term enterally fed toddlers (10 girls, 23 boys) and 275 healthy controls (128 girls, 147 boys) subcutaneous body fat was measured by means) of the optical device Lipometer. All participants were divided into three age groups (infants, toddlers and children). The height (p=0. 014, -11.7 cm, -12.5%) and weight (p=0.012, -3.0 kg, -21.9%) of long-term enterally fed female toddlers were significantly lower than healthy controls, while male enterally fed toddlers had lower values in all anthropometric measures compared to healthy controls: height (p=0.003, -8.0 cm, -8.4%), weight (p<0.001, -3.5 kg, -24.8%), BMI (p=0.004, -1.3 BMI), Z-score BMI (p=0.001, -1.2 Z-score BMI), upper arm circumference (p<0.001, -1.6 cm, -10.1%) and waist circumference (p<0.001, -6.2 cm, -12.5%). Tube fed toddlers showed a similar body fat distribution when compared to healthy controls, but demonstrated significantly lower values of anthropometric measurements. The results indicate that long-term enterally fed children have ample fat stores but lack physical development.

Caliper vs. Lipometer--Comparing Two Methods of Subcutaneous Body Fat Measurement by Bland-Altman Diagrams.

Skinfold Calipers are widely used to obtain subcutaneous adipose tissue thickness because of its non-invasive, simple and inexpensive technique. Nevertheless, Caliper skinfold thicknesses have the disadvantage of measuring compressed adipose tissue and double layers of skin, which might reduce the precision of these results. In contrast, the computerized optical device Lipometer was developed to permit a quick, precise and non-invasive determination of non-compressed mono layers of subcutaneous adipose tissue thickness. In the present paper we investigate the hypothesis that Caliper skinfold thicknesses are significantly different from subcutaneous adipose tissue thicknesses in mm, which can be measured by Lipometer. Caliper and Lipometer results were obtained from 371 Estonian boys aged between 9.0 and 12.8 years. Measurements were performed at six different body sites: triceps, biceps, upper back, upper abdomen, hip and front thigh. Caliper measurements were systematically higher than Lipometer results in a range between 1.2 mm (hip) and 11.08 mm (front thigh). The limits of agreement analysis provided intervals from 7.5 mm (biceps) up to 30.14 mm (front thigh). Comparing Caliper and Lipometer results very low measurement agreement was found. The two methods provided very poor interchangeability.

Reference values of the mitral annular peak systolic velocity (Sm) in 690 healthy pediatric patients, calculation of Z-score values, and comparison to the mitral annular Plane systolic excursion (MAPSE).

BACKGROUND: The mitral annular peak systolic velocity (Sm) is an echocardiographic measurement using tissue Doppler imaging to assess longitudinal left ventricular (LV) systolic function in children and adults. We determined growth-related changes in Sm to establish reference values for the entire pediatric age group. METHODS AND RESULTS: A prospective study was conducted in a group of 690 healthy pediatric patients (age: 1 day-18 years). We determined the effects of age, sex, and body surface area (BSA) on the Sm values. Regression analysis was used to estimate Sm from age, BSA, and sex. In addition, a correlation of normal Sm with normal age-matched values of the M-mode parameter mitral annular plane systolic excursion (MAPSE) was measured. The Sm ranged from a mean of 5.8 cm/sec (Z-score ±2: 3.6-8.0 cm/sec) in the newborn to 11.8 cm/sec (Z-score ±2: 8.5-15.1 cm/sec) in the 18-year-old adolescent. The Sm values showed a positive correlation with age and BSA with a nonlinear course. There was no significant difference in Sm values between females and males. A significant correlation was found between Sm and MAPSE values. CONCLUSION: Z-scores of Sm values were calculated and percentile charts were established to serve as reference data in patients with congenital heart diseases.

Supplementation with a juice powder concentrate and exercise decrease oxidation and inflammation, and improve the microcirculation in obese women: randomised controlled trial data.

Obesity and sedentary lifestyle are associated with increased oxidative stress, inflammation and vessel dysfunction. Previous research has shown that an encapsulated fruit/berry/vegetable juice powder (FBV) supplement or controlled exercise training improve the markers of redox biology, low-grade inflammation and circulation. The aim of the present study was to assess the effects of 8 weeks of supplementation with FBV or placebo, and a single bout of controlled walking on the markers of oxidation, inflammation and skin capillary microcirculation in forty-two obese pre-menopausal women (41 (SD 5) years, non-smokers and BMI 34·5 (SD 3·8) kg/m(2)) using a randomised, double-blind, placebo-controlled design. All assessments were made before and after 8 weeks of capsule supplementation, and pre- and post-30 min of controlled treadmill walking at 70 % of VO2max. Venous blood was collected for the determination of carbonyl proteins (CP), oxidised LDL (ox-LDL), total oxidation status (TOS) of lipids, malondialdehyde, TNF-α and IL-6. Capillary blood flow, O2 saturation of Hb (SO2Hb) and the relative concentration of Hb (rHb) were assessed at a 2 mm skin depth. Following 8 weeks of supplementation, compared with placebo, the FBV group had a significant (P< 0·05) reduction in CP, ox-LDL, TOS and TNF-α, and a significant increase in blood flow, SO2Hb and rHb. Independent of supplementation, moderate exercise significantly increased blood flow and rHb, with a trend towards increased SO2Hb. Compared with placebo, 8 weeks of supplementation with FBV decreased the markers of systemic oxidation and inflammation. Both FBV supplementation and a single walking bout improved the markers of the microcirculation in these obese women.

Polyphenols' Impact on Selected Biomarkers of Brain Aging in Healthy Middle-Aged and Elderly Subjects: A Review of Clinical Trials.

With a constantly growing elderly population, incidences of neurodegenerative diseases are also rising and are expected to further increase over the next years, while costing health systems across the world trillions of dollars. Therefore, biomarkers to detect manifestations of brain aging early and interventions to slow down its pace are of great interest. In the last years, the importance of the neurotrophins brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the context of cognitive function and the aging brain has increased, besides the already well-established amyloid-beta (Aß) and tau plaques. Due to their wide range of beneficial health effects as well as their antioxidant and anti-inflammatory properties, a class of secondary plant-metabolites, the so-called polyphenols, gained increasing attention. In this review, we discuss the roles of BDNF, Aß, NGF, and tau proteins as biomarkers of brain aging and the effect of dietary polyphenol interventions on these biomarkers, assessed via blood analysis, magnetic resonance imaging (MRI), and positron emission tomography (PET).