Risk of left atrial appendage thrombus in older patients with atrial fibrillation.

Introduction: We aimed to compare the prevalence of left atrial appendage (LAA) thrombus and its predictors between old and young patients with atrial fibrillation (AF). Material and methods: The study included 1970 patients aged ≥ 65 (n = 822 (41.7%)) and < 65 (n = 1148 (58.3%)) referred for AF cardioversion or ablation preceded by transoesophageal echocardiography (TEE). Results: Oral anticoagulation (OAC) was prescribed in 799 (97.2%) patients aged ≥ 65 years and in 1054 (91.8%) of those aged < 65 years (p < 0.001). In patients treated with OAC, those aged ≥ 65 years less often received vitamin K antagonist (VKA) (267 (33.4%) vs. 416 (39.5%)) and more often non-VKA-OAC (NOAC) (532 (66.6%) vs. 638 (60.5%), p = 0.008, p = 0.008) compared to patients < 65 years. On TEE, LAA thrombus was more often observed in patients aged ≥ 65 years than those aged < 65 years (63 (7.7%) vs. 46 (4.0%), p < 0.001), with an absolute but not statistically significant difference between patients aged 65-74 and ≥ 75 years (47 (7.3%) vs. 16 (8.8%), p = 0.528). In patients aged ≥ 65 years, there was no difference in the prevalence of LAA thrombus between patients treated with VKA and NOAC, in contrast to patients aged < 65 years, in whom such a difference was observed (27 (6.5%) vs. 16 (2.5%), p = 0.002). In multivariate logistic regression, predictors of LAA thrombus in both age groups were older age, non-paroxysmal AF, and heart failure, whereas only in patients aged < 65 years - VKA use, and in those aged ≥ 65 years - lower glomerular filtration rate and platelet count. Conclusions: Despite OAC use, older patients with AF remain at high risk of LAA thrombus formation. Older age, non-paroxysmal AF, and heart failure are predictors of LAA thrombus, irrespective of age.

Novel IL2RG Gene Mutation in One of Dizygotic Twins Causing Profound Changes of Receptor Structure.

In this study, we report a 4-month-old boy with T-B+NK- severe combined immunodeficiency (SCID) due to a novel mutation in exon 2 of IL2RG, the gene encoding the interleukin (IL) common gamma chain (γc) of the cytokine receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. The patient was born from a twin pregnancy. He manifested recurrent infections of the gastrointestinal tract, whereas his twin brother was asymptomatic with no immune defects. In order to evaluate the effect of this unreported variant on the protein structure, a structural modeling process was performed showing prominent biochemical alterations of the protein features, including molecular weight, isoelectric charge, and possible changes to its secondary and tertiary structure.

Risk of left atrial appendage thrombus in patients with atrial fibrillation and chronic kidney disease.

BACKGROUND: Atrial fibrillation (AF) and chronic kidney disease (CKD) are associated with an increased risk of ischemic stroke. The aim of this study was to compare the clinical characteristics, the incidence of left atrial appendage (LAA) thrombus and its predictors, and spontaneous echo contrast (SEC) in a population of patients with AF depending on estimated glomerular filtration rate (eGFR) values. METHODS: This study included 1962 patients who underwent transesophageal echocardiographic examination prior to cardioversion or ablation in the years 2014-2018 in three cardiac centers. RESULTS: More than a quarter of AF patients had decreased eGFR (< 60 mL/min/1.73 m2) and were characterized as a high-risk population, with more comorbidities, higher thromboembolic and bleeding risk compared to those with normal renal function. Oral anticoagulation (OAC) was prescribed in 97% and 93% of patients with decreased and normal eGFR, respectively, with a higher prevalence of prescribed non-vitamin K antagonist oral anticoagulants (NOACs). The incidence of LAA thrombus (24%, 9% and 4%) and SEC (25%, 25% and 19%) increases simultaneously with a decrease in eGFR (< 30, 30-59 and ≥ 60 mL/min/1.73 m2, respectively). Among patients prescribed reduced doses of NOAC, those with decreased eGFR were more often observed with LAA thrombus (10% vs. 2.5%). Non-paroxysmal AF, heart failure and previous bleeding were predictors of LAA thrombus, irrespective of eGFR value. CKD was the predictor of LAA thrombus in all patients including those with non-paroxysmal AF, males, without diabetes, without hypertension and with CHA2DS2-VASc < 2. CONCLUSIONS: Despite OAC, patients with concomitant AF and CKD remain at high risk for LAA thrombus formation.

Psychosocial Crowding Stress-Induced Changes in Synaptic Transmission and Glutamate Receptor Expression in the Rat Frontal Cortex.

This study demonstrates how exposure to psychosocial crowding stress (CS) for 3, 7, and 14 days affects glutamate synapse functioning and signal transduction in the frontal cortex (FC) of rats. CS effects on synaptic activity were evaluated in FC slices of the primary motor cortex (M1) by measuring field potential (FP) amplitude, paired-pulse ratio (PPR), and long-term potentiation (LTP). Protein expression of GluA1, GluN2B mGluR1a/5, VGLUT1, and VGLUT2 was assessed in FC by western blot. The body's response to CS was evaluated by measuring body weight and the plasma level of plasma corticosterone (CORT), adrenocorticotropic hormone (ACTH), and interleukin 1 beta (IL1B). CS 3 14d increased FP and attenuated LTP in M1, while PPR was augmented in CS 14d. The expression of GluA1, GluN2B, and mGluR1a/5 was up-regulated in CS 3d and downregulated in CS 14d. VGLUTs expression tended to increase in CS 7d. The failure to blunt the effects of chronic CS on FP and LTP in M1 suggests the impairment of habituation mechanisms by psychosocial stressors. PPR augmented by chronic CS with increased VGLUTs level in the CS 7d indicates that prolonged CS exposure changed presynaptic signaling within the FC. The CS bidirectional profile of changes in glutamate receptors' expression seems to be a common mechanism evoked by stress in the FC.

Insulin Resistance in Adults with Type 1 Diabetes is Associated with Lower Vitamin D Serum Concentration.

AIM: Type 1 diabetes mellitus (T1DM) is a disease characterized by an absolute deficiency of endogenous insulin secretion. Insulin resistance (IR) may develop among patients with T1DM. Vitamin D deficiency was reported to be a risk factor in the development of IR. The aim of the study was to assess the relationship between serum concentrations of 25-hydroxyvitamin D (25(OH)D) and IR among patients with T1DM. METHODS: The test group consisted of 110 adult patients [males=65 (59%)] with T1DM. Participants were recruited in Poland between 1st October and 30th April in 2015/2016 and 2016/2017. VD serum level was assessed by ELISA array. IR was assessed by estimated Glucose Disposal Rate (eGDR). RESULTS: In the study group 21 (19%) patients were recognized as IR according to eGDR cut-offs (<7.5 mg/kg/min), 52 (47.3%) patients had VD deficiency (25(OH)D<20 ng/ml), 16 (14.5%) patients had 25(OH)D<10 ng/ml. Only 6 (5%) participants reported VD supplementation. Patients with IR, according to eGDR cut-off revealed significantly lower 25(OH)D serum level 15.7 (9.2-28.4) vs. 22.1 (13.0-38.4) ng/ml; p=0.04 as compared to patients without IR. R Spearman analysis found a positive relationship between VD and eGDR (Rs=0.27; p<0.01). Logistic regression analysis revealed significant relationship between the presence of IR and VD serum level/presence of 25(OH)D serum level below 10 ng/ml, both models adjusted to sex, age, BMI, LDL and triglycerides, accordingly (OR=0.95, CI: 0.90-0.99; p=0.04) and (OR=4.19, CI: 1.04-16.93; p=0.04). CONCLUSION: The serum concentration of Vitamin D is negatively associated with insulin resistance in patients with T1DM and may have clinical implications.

Non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation in secondary stroke and systemic embolism prevention.

BACKGROUND: Oral anticoagulants (OAC) are recommended in all patients with atrial fibrillation (AF) after thromboembolic events without contraindications. It is hypothesized herein, that the majority of patients with AF after thromboembolic events receive OAC and the presence of specific factors, predisposes the use of non-vitamin K antagonist oral anticoagulants (NOACs). METHODS: This is a retrospective study, encompassing patients with AF hospitalized in a reference cardiology center over the years 2014-2017. Thromboembolic events were defined as: ischemic stroke, transient ischemic attack and systemic embolism. Inclusion criteria were the following: diagnosis of non-valvular AF at discharge from hospital, hospitalization not resulting in death. RESULTS: Among 2834 hospitalized patients with AF, a history of thromboembolic events was identified in 347 (12.2%) patients. In the group studied, of 347 patients with AF after a thromboembolic event, 322 (92.8%) received OAC, including 133 patients on vitamin K antagonist (41.3% of patients on OAC) and 189 patients on NOACs (58.7% of patients on OAC). Among patients treated with NOACs the majority were on dabigatran (116 patients, 61.4%), followed by rivaroxaban (54 patients, 28.6%), and apixaban (19 patients, 10%). Multivariate logistic regression analysis demonstrated that the presence of arterial hypertension reduced the chance for NOACs use (odds ratio [OR] 0.4, 95% confidence interval [CI] 0.2-0.9, p = 0.04) and left atrial size ≤ 40 mm was a factor increasing the chance for the use of NOACs (OR 2.5, 95% CI 1.1-5.8, p = 0.03). CONCLUSIONS: Nearly all hospitalized patients with AF received OAC in the secondary prevention of thromboembolic complications. NOACs were used for secondary prevention of stroke among patients with AF in patients with fewer comorbidities.

Left Atrial Appendage Thrombus Formation Despite Continuous Non-Vitamin K Antagonist Oral Anticoagulant Therapy in Atrial Fibrillation Patients Undergoing Electrical Cardioversion or Catheter Ablation: A Comparison of Dabigatran and Rivaroxaban.

Left atrial appendage thrombus (LAAT) may be detected by transesophageal echocardiography (TOE) in patients with atrial fibrillation (AF) despite continuous anticoagulation therapy. We examined the factors predisposing to LAAT in patients treated with the anticoagulants dabigatran and rivaroxaban. We retrospectively evaluated 1,256 AF patients from three centres who underwent TOE before electrical cardioversion (n = 611, 51.4%) or catheter ablation (n = 645, 48.6%) from January 2013 to December 2019 and had been on at least three weeks of continuous dabigatran (n = 603, 48%) or rivaroxaban (n = 653, 52%) therapy. Preprocedural TOE diagnosed LAAT in 51 patients (4.1%), including 30 patients (5%) treated with dabigatran and 21 patients (3.2%) treated with rivaroxaban (p=0.1145). In multivariate logistic regression, predictors of LAAT in patients treated with dabigatran were non-paroxysmal AF (vs. paroxysmal AF) (OR = 6.2, p=0.015), heart failure (OR = 3.22, p=0.003), and a eGFR <60 ml/min/1.73 m2 (OR = 2.65, p=0.012); the predictors in patients treated with rivaroxaban were non-paroxysmal AF (vs. paroxysmal AF) (OR = 5.73, p=0.0221) and heart failure (OR = 3.19, p=0.116). In ROC analysis of the dabigatran group, the area under the curve (AUC) for the CHA2DS2-VASc-RAF score was significantly higher (0.78) than those for the CHADS2, CHA2DS2-VASc, and R2CHADS2 scores (0.67, 0.70, and 0.72, respectively). In the rivaroxaban group, the CHA2DS2-VASc-RAF score also performed significantly better (AUC of 0.77) than the CHADS2, CHA2DS2-VASc, and R2CHADS2 scores (AUC of 0.66, 0.64, and 0.67, respectively). The risk of LAAT was the same for patients in both treatment groups. In all patients, non-paroxysmal AF or heart failure, and in patients treated with dabigatran an eGFR <60 ml/min/1.73 m2, were independent predictors of LAAT. The new CHA2DS2-VASc-RAF scale had the highest predictive value for LAAT in the entire study population.

Prevalence and risk factors of left atrial thrombus in patients with atrial fibrillation and lower class (IIa) recommendation to anticoagulants.

BACKGROUND: Oral anticoagulation therapy (OAT) prevents ischaemic incidents in patients with atrial fibrillation (AF). CHA2DS2-VASc risk score of ≥2 points in men and ≥3 in women is a class I indication for OAT. OAT should also be considered as a prevention of thromboembolism in AF men with a CHA2DS2-VASc score of 1 point and women with 2 points, but the class of recommendation is lower (IIa). This study aims to assess the occurrence of left atrial appendage thrombus (LAAT) and risk factors of its formation in patients with lower class recommendation to oral antiocoagulation treatment. METHODS: The study group consisted of 1,858 patients: 555 patients with class IIa indication to OAT (IIa group) and 1,303 patients with class I indication as a control group (I group). Patients were admitted to three cardiology departments. All subjects underwent transoesophageal echocardiography. RESULTS: The incidence of LAAT was comparable in both IIa and I group: LAAT was confirmed in 30 (5.4%) subjects of IIa group and in 77 (5.9%) of I group. The prevalence of LAAT in IIa group was higher on treatment with VKAs (in comparison to NOACs) (8.4% vs. 3.4%, P=0.010), and lower in case of paroxysmal AF (in comparison to non-paroxysmal AF) (2.4% vs. 9.8%, P=0.0002). Multivariate logistic regression revealed the following variables as the independent predictors of LAAT in IIa group: treatment with VKAs (OR 2.99, 95% CI: 1.33-6.69; P=0.007), paroxysmal AF (OR 0.26, 95% CI: 0.11-0.62; P=0.002) and eGFR <60 mL/min/1.73 m2 (OR 3.19, 95% CI: 1.42-7.16; P=0.005). CONCLUSIONS: The prevalence of LAAT in AF patients with lower class (IIa) recommendation to anticoagulants was comparable to higher (I). Treatment with VKAs, along with non-paroxysmal type of AF and eGFR <60 mL/min/1.72 m2 were identified as the strongest predictors of LAAT in IIa group.

Cardiovascular risk in patients with plaque psoriasis and psoriatic arthritis without a clinically overt cardiovascular disease: the role of endothelial progenitor cells.

Psoriasis is an autoimmune, chronic disease determined by environmental and genetic factors. The occurrence of psoriasis is accompanied by metabolic diseases, cardiovascular diseases (CVD) and depression, disturbances on interpersonal interactions and a tendency towards social isolation. Regardless of the form of psoriasis and the severity of the disease, early arterial lesions are recorded in arterial vessels of patients. Nevertheless, the chance of CVD is higher in the population of patients with severe psoriasis than in patients with mild to moderate psoriasis. The correlation between the presence of atherosclerotic plaque and psoriatic plaque is partially explained by: (1) a similar inflammatory pathway - via the T helper cells, (2) impaired angiogenesis, and (3) endothelial dysfunction. In the considered tests, the diagnostic tools used showed a reduced level of endothelial progenitor cells in the circulation of patients with psoriasis. Endogenous angiopoietin stimulation in patients with psoriasis leads to deterioration of endothelial regeneration, atherosclerosis which secondarily contributes to the progression of heart failure. Clinical and experimental data confirm the potential of immunomodulatory methods to combat both autoimmune and cardiovascular diseases through the use of immunosuppressive drugs. Full understanding of the way in which CVD develops in patients with autoimmune diseases would enable the implementation of targeted cell therapy allowing the quality and life expectancy of patients to be improved. Modern cellular diagnostic tools allow the use of highly specific biomarkers, which in the near future will enable a reduction in morbidity and mortality due to CVD.

Stroke prevention and guideline adherent antithrombotic treatment in elderly patients with atrial fibrillation: A real-world experience.

Patients aged ≥75 years with the diagnosis of atrial fibrillation (AF) are at a higher risk of stroke and, according to recent recommendations, should receive oral anticoagulant (OAC) therapy. This study aimed to assess the recommended prophylactic antithrombotic therapy among patients with AF aged ≥ 75 years and its compliance with current guidelines. We also aimed to identify predisposing factors associated with the administration of non-vitamin K antagonist oral anticoagulants (NOACs) in elderly patients with AF.This was a retrospective, single-center observational study. Patients with AF aged ≥75 years hospitalized at a reference cardiology center from 2014 to 2017 were included in the analysis.Among the 1236 eligible patients (43.4% male; mean age, 82 years), OACs were recommended in 90.1% of cases. Of these, 59.8% of patients used NOACs and 40.2% used vitamin K antagonists. Additionally, 3.3% of patients received antiplatelet (AP) therapy and 2.5% were administered low molecular weight heparin. Only 4.5% of patients did not receive any anticoagulant treatment. The majority (89.9%) of patients received relevant prophylactic antithrombotic therapy according to current guidelines; only 1.4% were overtreated and 8.7% were undertreated. The significant predictors of NOAC therapy among patients treated with anticoagulants were non-permanent AF (odds ratio [OR] = 1.68, 95% confidence interval [CI] = 1.30-2.18, P = .0001), age-by 5 years (OR = 1.33, 95% CI = 1.16-1.52, P = .0001), and glomerular filtration rate-by 5 units (OR = 1.06, 95% CI = 1.02-1.10, P = .0066).A high percentage of AF patients aged ≥75 years receive OACs, mainly NOACs. Most patients are treated according to the current guidelines; under treatment is primarily observed in patients receiving AP therapy. Non-permanent AF, age, and preservation of renal function are significant predictors of NOAC use.

Does the CHA2DS2-VASc scale sufficiently predict the risk of left atrial appendage thrombus in patients with diagnosed atrial fibrillation treated with non-vitamin K oral anticoagulants?

The CHA2DS2-VASc scale does not include potential risk factors for left atrial appendage thrombus (LAAT) formation such as a form of atrial fibrillation (AF) and impaired kidney function. The real risk of thromboembolic complications in AF patients is still unclear as well as an optimal anticoagulant treatment in males with a CHA2DS2-VASc score of 1 and females with a CHA2DS2-VASc score of 2.The aim of this study was to compare the predictive value of the CHA2DS2-VASc scale and other scales to estimate the risk of LAAT formation in AF patients treated with non-vitamin K oral anticoagulants (NOACs) and to assess the prevalence of thrombi in patients at intermediate risk of stroke.The observational study included consecutive patients with a diagnosis of non-valvular AF treated with NOACs, admitted to 3 high-reference institutions between 2013 and 2018. All individuals underwent transoesophageal echocardiography before cardioversion or ablation.Out of 1163 enrolled AF patients (62.1% male, mean age 62 years) the LAAT had been detected in 50 individuals (4.3%). Among patients with LAAT, 1 patient (2.0%) was classified as a low-risk category, 9 (18.0%) were at intermediate-risk, and 40 (80.0%) were at high risk of thromboembolic complications according to CHA2DS2-VASc scale. All patients were treated with NOACs: 51.0% rivaroxaban, 47.1% dabigatran, and 1.9% apixaban.Patients at intermediate stroke-risk with detected LAAT had higher R2CHADS2 score (2.1 ±â€Š1.2 vs 1.2 ±â€Š0.8, P = .007), higher CHA2DS2-VASc-RAF score (6.4 ±â€Š4.4 vs 3.7 ±â€Š2.6, P = .027) and more often had an estimated glomerular filtration rate below 56 mL/min/1.73 m (44.4% vs 13.2%, P = .026) compared to patients without LAAT. The receiver operating characteristics revealed that the CHA2DS2-VASc-RAF scale had better predictive ability to distinguish between patients with and without LAAT in the study group than CHA2DS2-VASc (P = .0006), CHADS2 (P = .0006) and R2CHADS2 scale (P = .0140).The CHA2DS2-VASc scale should be supplemented with an assessment of renal function and form of AF to improve stroke risk estimation. The application of additional scales to estimate the risk of LAAT might be especially useful among males with a CHA2DS2-VASc score of 1 and females with a CHA2DS2-VASc score of 2.

Left Ventricular Ejection Fraction Is Associated with the Risk of Thrombus in the Left Atrial Appendage in Patients with Atrial Fibrillation.

INTRODUCTION: Atrial fibrillation (AF) is associated with high risk of ischemic stroke. The most frequent thrombus location in AF is the left atrial appendage (LAA). Transthoracic echocardiography (TTE) is a basic diagnostic examination in patients (pts) with AF. OBJECTIVES: To analyse the relations between basic echocardiographic features, well-established stroke risk factors, type of AF, and anticoagulation therapy with the incidence of left atrial appendage thrombus (LAAT). Patients and Methods. The study group consisted of 768 pts with AF (mean age, 63 years), admitted to three high-reference cardiology departments. Five hundred and twenty-three pts were treated with non-vitamin K antagonist oral anticoagulants (NOACs) and 227 (30%) with vitamin K antagonists (VKAs). The subjects underwent TTE and transesophageal echocardiography (TEE) before cardioversion or ablation. RESULTS: LAAT was significantly more frequent in pts with reduced left ventricular ejection fraction (LVEF): in 10.6% (7 pts) with LVEF < 40% and in 9.0% (9 pts) with LVEF 40-49%, while only in 5.5% (33 pts) with LVEF > 50%. Compared to pts without LAAT, those with LAAT presented with lower LVEF and higher left atrial diameter (LAD). Multivariate logistic regression revealed the following variables as independent predictors of LAAT: previous bleeding, treatment with VKA, and LVEF. CONCLUSION: LAAT is related to lower LVEF and higher LAD. LVEF is one of the independent predictors of LAAT. Even in the case of adequate anticoagulant therapy, it might be prudent to consider TEE before cardioversion or ablation in patients with low LVEF and LA enlargement, especially in the coexistence of other thromboembolic risk factors.

Thrombus in the left atrial appendage in patients with atrial fibrillation treated with non-vitamin K antagonist oral anticoagulants in clinical practice-A multicenter registry.

BACKGROUND: The prevalence and predictors of left atrial appendage thrombus (LAAT) in patients with non-valvular atrial fibrillation (AF) who have been treated with non-vitamin K antagonist oral anticoagulants (NOACs) are not well defined. We aimed to assess the occurrence and predictors of LAAT on transesophageal echocardiography (TOE) in patients with non-valvular AF treated with NOACs for at least 3 weeks. METHODS: Consecutive patients with non-valvular AF who underwent TOE before catheter ablation or electrical cardioversion in three high-reference centers between 2014 and 2018 were included. Patients on apixaban were excluded from the study due to low numbers in this category. All patients received NOACs for at least 3 weeks before TOE. RESULTS: A total of 1148 patients (female, 38.1%; mean age, 62.1 years) referred to our centers for catheter ablation of AF (52.1%) or electrical cardioversion (47.9%) were included. Patients were on rivaroxaban (51.9%) or dabigatran (48.1%). Preprocedural TOE revealed LAAT in 4.4% of all patients. Multivariable logistic regression analysis showed the CHA2DS2-VASc score ≥2 points (OR = 2.11; 95% CI, 1.15-3.88; P = .0161), non-paroxysmal AF (OR = 6.30; 95% CI, 2.22-17.91; P = .0005), and GFR <60 mL/min/1.73 m2 (OR = 2.05; 95% CI, 1.14-3.67; P = .0160) were independent predictors of LAAT in patients treated with NOACs. CONCLUSIONS: In non-valvular AF patients treated with NOACs, the prevalence of LAAT was 4.4% before electrical cardioversion or ablation. In addition to the CHA2DS2-VASc score, the type of AF and renal function should be considered in the stratification of thromboembolism risk in AF patients and qualification for a preprocedural TOE.

Differential susceptibility of human neural progenitors and neurons to ischaemic injury.

BACKGROUND: Neuroprotection for stroke has shown great promise but has had little translational success. Developing drugs for humans logically requires human tissue evaluation. Human embryonic stem cell (hESC)-derived neuronal cultures at different developmental stages were subject to oxygen glucose deprivation (OGD) to determine how developing maturity altered response to ischemic injury. METHODS: H9 hESCs were induced by Noggin to generate neural progenitors (NPs) and highly arbourised structurally complex neurons. They were both subjected to OGD or OGD with reoxygenation (OGD-R) for 1-6 h.Outcome was assessed by measures of cell death, survival and morphology. RESULTS: NPs did not die after OGD but experienced progressive loss of metabolic activity. Highly arbourised neurons showed minimal cell death initially but 44 % and 78 % died after 4 and 6 h OGD. Metabolic dysfunction was greater in these more mature neurons (∼70 %) than in NPs and evident after 1 h OGD, before detection of neuronal death at 4 h. OGD-R salvaged metabolic activity but not cell death in mature neurons. In NPs there was little metabolic salvage and cell death was induced (50 % and 65 % at 4 and 6 h OGD-R, respectively). CONCLUSIONS: Highly arbourised neurons are more sensitive to ischaemic injury than NPs which did however develop marked vulnerability to prolonged injury with reoxygenation. These observations imply that therapeutic potential may be highly dependent of the developmental state of the neurons we aim to protect.

The Influence of Inulin on the Retention of Polyphenolic Compounds during the Drying of Blackcurrant Juice.

In blackcurrant juice powders made using freeze-, vacuum-, and spray-drying methods, 19 polyphenolic compounds were identified: anthocyanins (6), (+)-catechin, flavonols (8), and phenolic acids (4). The highest content of identified polyphenols was noted after vacuum drying at 90 °C, which was connected with the thermally induced release of (+)-catechin. Drying at this temperature also increased the formation of the Maillard reaction/caramelization product, hydroxymethyl-l-furfural, when inulin was added. The higher the vacuum drying temperature was, the stronger the degradation of anthocyanins was. Inulin was a better protectant of anthocyanins than maltodextrin, except during vacuum drying at 90 °C, which probably triggered inulin's participation in the formation of hydroxymethyl-l-furfural (HMF), thus limiting its capability to protect anthocyanins. Flavonols and phenolic acids were best retained after vacuum drying at 50 °C. Carrier selection affected only slightly, whereas carrier concentration did not affect, the content of flavonols and phenolic acids. The quality of fruit juice powders should be considered taking into account a broad spectrum of factors, including the initial composition of the material subjected to drying, the drying parameters, the carrier type and concentration, and the interactions that occur during the thermal treatment of fruit juices.

Qualitative and Quantitative Evaluation of Heat-Induced Changes in Polyphenols and Antioxidant Capacity in Prunus domestica L. By-products.

Plum pomace, an agro-industrial waste product has received attention due to the worldwide popularity of plums. During convection, the content of flavan-3-ols decrease, except drying at 90 °C, whereas the content of i.e., chlorogenic, 3-p- and 4-p-coumaroylquinic acids, quercetin rutinoside, and galactoside was observed to increase along with the increase in process temperature. The highest content of all identified polyphenols was found in plum pomace powders obtained using a combination of convective at 90 °C and microwave vacuum drying (MVD) at 120 W, whereas the highest retention of the group consisted of phenolic acids, flavonols, and anthocyanins was noted when CD 70 °C/MVD 120 W was used, pointing to a strong influence of the type of polyphenols on their changes caused by drying. The correlations between TEAC ABTS and the sum of flavonoids (r = 0.634) and anthocyanins (r = 0.704) were established. The multiple regression analysis showed that polyphenol content was more strongly affected by drying time than by maximum temperature, whereas antioxidant capacity was more influenced by maximum temperature of sample than by drying time.

Chronic Isolation Stress Affects Subsequent Crowding Stress-Induced Brain Nitric Oxide Synthase (NOS) Isoforms and Hypothalamic-Pituitary-Adrenal (HPA) Axis Responses.

The nitric oxide (NO) pathway in the brain is involved in response to psychosocial stressors. The aim of this study was to elucidate the role of nNOS and iNOS in the prefrontal cortex (PFC), hippocampus (HIP), and hypothalamus (HYPO) during social isolation stress (IS), social crowding stress (CS), and a combined IS + CS. In the PFC, 3 days of CS increased iNOS but not nNOS protein level. In the HIP and HYPO, the levels of nNOS and iNOS significantly increased after 3 days of CS. In the PFC, IS alone (11 days) enhanced iNOS protein level following 3 days of CS and increased nNOS level in the HIP and HYPO after 14 days of CS. By contrast, in the HIP, IS abolished the subsequent CS-induced increase in nNOS in the HIP and strongly elevated iNOS level after 7 days of CS. In the HYPO, prior IS inhibited nNOS protein level induced by subsequent CS for 3 days, but increased nNOS protein level after longer exposure times to CS. Isolation stress strongly upregulated plasma interleukin-1ß (IL-1ß) and adrenocorticotropic hormone (ACTH) levels while corticosterone (CORT) level declined. We show that the modulatory action of the NO pathway and ACTH/CORT adaptation to chronic social isolation stress is dependent on the brain structure and nature and duration of the stressor. Our results indicate that isolation is a robust natural stressor in social animals; it enhances the NO pathway in the PFC and abolishes subsequent social CS-induced NOS responses in the HIP and HYPO.

Atrial fibrillation type and renal dysfunction as important predictors of left atrial thrombus.

OBJECTIVE: We aimed to identify predictors of left atrial appendage (LAA) thrombus in patients with atrial fibrillation (AF) and to enhance the prognostic value of the CHA2DS2-VASc score. METHODS: Derivation cohort included 1033 consecutive AF patients referred for catheter ablation or direct current cardioversion, in whom transoesophageal echocardiography (TOE) was performed prior to the procedure. Logistic regression analysis was used to identify predictors of LAA thrombus on TOE. Receiver operating characteristic (ROC) curves were constructed to compare the newly developed score with the CHA2DS2 and CHA2DS2-VASc scores in the derivation and the validation (n=320) cohort. RESULTS: On TOE, LAA thrombus was present in 59 (5.7%) patients in the derivation cohort. Aside from variables encompassed by the CHA2DS2-VASc score, LAA thrombus predictors included AF type (persistent/'permanent' vs paroxysmal) and renal dysfunction. These predictors were incorporated into the CHA2DS2-VASc score. In ROC analysis, area under the curve (AUC) for the new score (CHA2DS2-VASc-RAF score) was significantly higher (0.81) than those for the CHA2DS2 and CHA2DS2-VASc scores (0.71 and 0.70, respectively). In the validation cohort, the CHA2DS2-VASc-RAF score also performed significantly better (AUC of 0.88) than the CHA2DS2 and CHA2DS2-VASc scores (AUC of 0.63 and 0.60, respectively). CONCLUSION: In real-world AF patients with majority on oral anticoagulation, LAA thrombus was found in approximately 6%. Two variables not included in the CHA2DS2-VASc score (AF type and renal dysfunction) proved strong, independent predictors of LAA thrombus and might improve thromboembolic risk stratification.

Sexual Dysfunction Is a More Common Problem in Young Women with Type 1 Diabetes than in Healthy Women.

The aim of the study was to analyze the relationship between the presence of type 1 diabetes and sexual dysfunction among young women. The study group consisted of 230 women, including 70 healthy and 160 with diabetes mellitus type 1 (DM1). All the participants voluntarily filled anonymous questionnaire. The results regarding sexual function were obtained using a Female Sexual Function Index (FSFI) questionnaire. Statistical analysis was performed for sexually active people. In the study group, 180 women declared sexual activity: 62 healthy (88%) and 118 with DM1 (82.5%). Women with DM1 in comparison with healthy women were older, had higher BMI, weight, and had more pack-years of cigarette smoking. Women with DM1 had lower results in FSFI and more often achieved scores below the clinical cutoff point. In a multiple linear regression model, the presence of diabetes predicted lower FSFI results. DM1 is independently associated with the presence of impaired sexual function. Sexual dysfunctions are more common among young women with DM1 than in healthy controls. The relationship is significant despite of the age, duration of diabetes, body weight, and presence of angiopathy.

Deposition of mullite in peatlands of southern Poland: Implications for recording large-scale industrial processes.

Mullite, a pure aluminosilicate (Al6Si2O13), is a rare natural rock component, known for centuries as a very resistant ceramic material. It is also a common waste product of high-temperature coal combustion that is emitted in quantity from coal-based power stations. The occurrence of mullite in two Sphagnum-dominated peatlands located near the Upper Silesia industrial region in southern Poland is described. For the first time, a complete record of mullite deposition in the peat profiles has been obtained by XRD analyses of ashed peat samples. The mullite distribution is compared with records of Hg, Pb and Cu. While mullite is supplied during high temperature processes only, Cu, Pb and Hg show more complex pattern of distribution. Both peat profiles contain elevated amounts of mullite in the time span between ca 1950-1990 with a maximum content in ca 1980. The first appearance (∼1900) of mullite is indicative of the beginning of energy production in coal-based power plants in the region. Mullite is proposed here as an indicator of industrialization in geological records. It is resistant to post-depositional processes, emitted globally, and restricted to large-scale industry.