Default mode network spatio-temporal electrophysiological signature and causal role in creativity.

The default mode network (DMN) is a widely distributed, intrinsic brain network thought to play a crucial role in internally-directed cognition. It subserves self-referential thinking, recollection of the past, mind wandering, and creativity. Knowledge about the electrophysiology underlying DMN activity is scarce, due to the difficulty to simultaneously record from multiple distant cortical areas with commonly-used techniques. The present study employs stereo-electroencephalography depth electrodes in 13 human patients undergoing monitoring for epilepsy, obtaining high spatiotemporal resolution neural recordings across multiple canonical DMN regions. Our results offer a rare insight into the temporal evolution and spatial origin of theta (4-8Hz) and gamma signals (30-70Hz) during two DMN-associated higher cognitive functions: mind-wandering and alternate uses. During the performance of these tasks, DMN activity is defined by a specific pattern of decreased theta coupled with increased gamma power. Critically, creativity and mind wandering engage the DMN with different dynamics: creativity recruits the DMN strongly during the covert search of ideas, while mind wandering displays the strongest modulation of DMN during the later recall of the train of thoughts. Theta band power modulations, predominantly occurring during mind wandering, do not show a predominant spatial origin within the DMN. In contrast, gamma power effects were similar for mind wandering and creativity and more strongly associated to lateral temporal nodes. Interfering with DMN activity through direct cortical stimulation within several DMN nodes caused a decrease in creativity, specifically reducing the originality of the alternate uses, without affecting creative fluency or mind wandering. These results suggest that DMN activity is flexibly modulated as a function of specific cognitive processes and supports its causal role in creative thinking. Our findings shed light on the neural constructs supporting creative cognition and provide causal evidence for the role of DMN in the generation of original connections among concepts.

[Diagnostic difficulties of isolated right ventricular myocardial infarction].

The article describes a case of isolated right ventricular myocardial infarction induced by proximal occlusion of the right coronary artery in a patient with the left type of heart blood supply. A specific feature of the case was detection of the McConnell's sign, which is considered characteristic of pulmonary artery thromboembolism.

Registry of Acute Myocardial Infarction. REGION-MI - Russian Registry of Acute Myocardial Infarction.

Aim      To study features of diagnosis and treatment of acute myocardial infarction (AMI) in Russian hospitals, results of the treatment, and early and late outcomes (6 and 12 months after AMI diagnosis); to evaluate the consistence of the treatment with clinical guidelines; and to evaluate patients' compliance with the treatment.Material and methods  The program was designed for 3 years, including 24 months for recruitment of patients to the study. The study will include 10, 000 patients hospitalized with a confirmed diagnosis (I21 according to ICD-10) of ST segment elevation acute myocardial infarction (MI) (STEMI) or non-ST segment elevation MI (NSTEMI) based on criteria of the European Society of Cardiology Guidelines on Forth Universal Definition of Myocardial Infarction (2018). The follow-up period was divided into three stages: observation during the stay in the hospital and at 6 and 12 months following inclusion into the registry. The primary endpoint included cardiac death, nonfatal MI during the hospitalization and after one-year follow-up. Secondary endpoints were 6-months and one-year incidence of repeated MI, heart failure, ischemic stroke, clinically significant hemorrhage, unscheduled revascularization after discharge from the hospital, and the proportion of patients who continue on statins, antiplatelet drugs, and drugs of other groups for 6 months and 1 year.Results The inclusion of patients into the registry started in 2020 and will continue for 24 months. By the time of the article publication (June, 2021), more than 2,000 patients will be included.Conclusion      REGION-MI (Russian rEGIstry Of acute myocardial iNfarction) is a multicenter, retrospective and prospective observational cohort study that excludes any interference with the clinical practice. Results of the registry will help to analyze a real picture of medical care provided to patients with myocardial infarction and to schedule ways to improve the situation.

[Clinical and angiopulmonographic association in pulmonary embolism].

AIM: To detect the effect of the feature of the pulmonary vascular obstruction on the clinical manifestations of pulmonary embolism (PE). MATERIALS AND METHODS: The 127 patients with PE were included in this study. PE verified with multidetector computed tomography with pulmonary angiography. Among them were 57 patients with high-risk PE, and 39 patients with intermediate-risk PE and 31 patients with low-risk PE. The pulmonary artery obstruction index and the obstruction level were determined. RESULTS: The mean values of the pulmonary artery obstruction index in high and intermediate risk patients were 42.5%, and in low risk patients 12.5% (p0.001). The trunk or main branches obstruction was in 80.7% of high-risk PE patients, the main or lobar branches obstruction in 92.3% of intermediate-risk patients and lobar or segmental branches obstruction in 93.5% of low-risk patients. Pulmonary infarction was detected in 89.2% of patients with the segmental branches obstruction and with another level of obstruction in 28.0% of patients only (p0.001). CONCLUSION: The hemodynamic disorder in pulmonary embolism associate with the pulmonary artery obstruction index of more than 30%. The development of obstructive shock is associated with the pulmonary artery trunk obstruction, and the development of pulmonary infarction associated with the segmental branches obstruction.

Right Ventricular Longitudinal Strain in Acute Pulmonary Embolism and Right Ventricular Myocardial Infarction in Patients with McConnell's Sign.

Aim      To study the right ventricular (RV) myocardial longitudinal systolic strain in patient with RV myocardial infarction (MI), and pulmonary embolism (PE) with and without McConnell' phenomenon.Material and methods  This study included 53 patients with PE (mean age, 59.0±15.1 years; men, 58.5 %) and 30 patients with RVMI (mean age, 61.8±10.9 years; men, 90 %). Longitudinal strain of basal, medial and apical segments of the RV free wall (RVFW) and the interventricular septum (IVS) was determined in the mode of two-dimensional speckle tracking. Ratio of the IVS apical strain to the RVFW strain (apical ratio) was calculated. Systolic excursion of the RVFW apical segment (apical excursion) was measured in the anatomical M-mode from the apical four-chamber view.Results The McConnell's sign was observed in 23 (43.4 %) of 53 patients with PE and in 16 (53.3 %) of 30 patients with RVMI (p>0.05). Irrespective of the cause for the RV damage, patients with the McConnell's sign had higher values of the apical ratio (1.69±0.50 vs. 0.95±0.22; p<0.001; cutoff point, 1.18) and apical excursion (7.9±1.7 vs. 2.6±1.4 mm; p<0.001; cutoff point, 5.0 mm). Apical excursion closely correlated with the value of apical ratio (r=0.65; p<0.001) but not with the RVFW apical segment strain (r= -0.07; p>0.05).Conclusion      Incidence of the McConnell's sign was similar in patients with PE and RVMI. McConnell's sign is based on a passive systolic shift of the RVFW apical segment, which develops during contraction of the IVS apical segment. The greater the ratio of IVS apical segment to RBFW global strain the greater the amplitude of this shift. With the ratio value of 1.18 or more, the systolic shift of RVFW apical segment was >5 mm, which was visually perceived as the McConnell's sign.

[On the Causes of Angina Pectoris in Patients With Pulmonary Embolism].

Objective Compare the distance between the pulmonary artery (PA) and the left coronary artery (LCA) using pulmonary angiography and the rate of detection of the signs of left ventricular myocardial ischemiain the first electrocardiogram (ECG) in pulmonary embolism (PE) patients with or without angina to detect possible causes of angina pectoris.Material and Methods Measurement of the minimum distance between the PA and LCA in multislice spiral computed tomography and analysis of the first ECG were performed in 55 PE patients. 15 (27.3%) patients had angina pectoris at the onset of the disease.Results Angina pectoris was observed in 14 (93.3%) of 15 patients with the distance between the PA andLCA less than 4.3 mm, and in one (2.5%) of 40 patients with the distance between these vessels equalto or exceeding the specified value (p<0.001). In the first ECG, the ST elevation in the aVR lead wasdetected in 10 (66.7%) patients with angina pectoris, and only in 3 (7.5%) patients without anginapectoris (p<0.001).Conclusions The findings suggest that angina pectoris in acute pulmonary embolism may be caused by compression of the LCA by the dilated PA.

Physical activity is increased by a 12-week semiautomated telecoaching programme in patients with COPD: a multicentre randomised controlled trial.

RATIONALE: Reduced physical activity (PA) in patients with COPD is associated with a poor prognosis. Increasing PA is a key therapeutic target, but thus far few strategies have been found effective in this patient group. OBJECTIVES: To investigate the effectiveness of a 12-week semiautomated telecoaching intervention on PA in patients with COPD in a multicentre European randomised controlled trial. METHODS: 343 patients from six centres, encompassing a wide spectrum of disease severity, were randomly allocated to either a usual care group (UCG) or a telecoaching intervention group (IG) between June and December 2014. This 12-week intervention included an exercise booklet and a step counter providing feedback both directly and via a dedicated smartphone application. The latter provided an individualised daily activity goal (steps) revised weekly and text messages as well as allowing occasional telephone contacts with investigators. PA was measured using accelerometry during 1 week preceding randomisation and during week 12. Secondary outcomes included exercise capacity and health status. Analyses were based on modified intention to treat. MAIN RESULTS: Both groups were comparable at baseline in terms of factors influencing PA. At 12 weeks, the intervention yielded a between-group difference of mean, 95% CI (lower limit - upper limit; ll-ul) +1469, 95% CI (971 to 1965) steps/day and +10.4, 95% CI (6.1 to 14.7) min/day moderate PA; favouring the IG (all p≤0.001). The change in 6-min walk distance was significantly different (13.4, 95% CI (3.40 to 23.5) m, p<0.01), favouring the IG. In IG patients, an improvement could be observed in the functional state domain of the clinical COPD questionnaire (p=0.03) compared with UCG. Other health status outcomes did not differ. CONCLUSIONS: The amount and intensity of PA can be significantly increased in patients with COPD using a 12-week semiautomated telecoaching intervention including a step counter and an application installed on a smartphone. TRIAL REGISTRATION NUMBER: NCT02158065.

Comparative reactivity of serum samples from Argentinean HIV-infected patients with V3 peptides from subtype B or BF recombinants.

To analyze humoral cross-reactivity to V3 peptides from subtype B and BF recombinant forms, plasma samples from 50 HIV-1-infected patients were characterized by sequencing fragments of the env and pol genes. An in-house EIA was performed using peptides corresponding to the 15 central amino acids of the V3 loop of gp120 from subtypes B (MN, SF2) and F1 and a consensus peptide from Argentinean BF recombinants. No differences were found with respect to the infecting subtype, but significant differences were found among the peptides. Reactivity was higher against the MN and BF peptides in both groups infected with subtype B (n = 28) and BF (n = 22) recombinants than against subtype F1 and SF2 peptides.

Chronic endurance exercise induces quadriceps nitrosative stress in patients with severe COPD.

BACKGROUND: Although exercise training has beneficial effects on skeletal muscle bioenergetics and exercise performance in patients with severe chronic obstructive pulmonary disease (COPD), it may also be associated with increased quadriceps oxidative and nitrosative stress. The aim of this study was to explore quadriceps oxidative and nitrosative stress in patients with severe COPD, both before and after a 3 week endurance exercise programme, and to identify the nature of the oxidatively modified proteins. METHODS: Reactive carbonyls, hydroxynonenal-protein adducts, antioxidant enzymes, nitric oxide synthase (NOS) and 3-nitrotyrosine levels were determined in the quadriceps (pre- and post-exercise) of 15 patients with severe COPD and seven healthy controls using immunoblotting (one- and two-dimensional electrophoresis), activity assays and mass spectrometry. RESULTS: At baseline, muscle levels of reactive carbonyls, which were negatively associated with muscle strength and exercise tolerance, were significantly higher in patients than in controls. Moreover, baseline hydroxynonenal-protein adducts, superoxide dismutase activity, inducible NOS and 3-nitrotyrosine immunoreactivity levels were also significantly increased in the quadriceps of patients compared with controls. In patients, chronic exercise induced a significant rise in inducible NOS levels and a fourfold increase in protein nitration. Chronic endurance exercise induced tyrosine nitration of muscle enolase 3beta, aldolase A, triosephosphate isomerase, creatine kinase, carbonic anhydrase III, myoglobin and uracil DNA glycosylase in the quadriceps of patients, while contractile protein alpha-1 actin was nitrated only in patients exhibiting muscle loss (post hoc analysis). Superoxide dismutase activity increased after the exercise programme only in controls. CONCLUSIONS: In severe COPD, chronic endurance exercise induces increased tyrosine nitration of quadriceps proteins involved in glycolysis, energy distribution, carbon dioxide hydration, muscle oxygen transfer, DNA repair and contractile function in patients exhibiting systemic effects of the disease.

Genetic variants of microsomal epoxide hydrolase and glutamate-cysteine ligase in COPD.

The genetic factors that contribute to the development of chronic obstructive pulmonary disease (COPD) are poorly understood. Many candidate genes have been proposed, including enzymes that protect the lung against oxidative stress, such as microsomal epoxide hydrolase (EPHX1) and glutamate-cysteine ligase (GCL). To date, most reported findings have been for EPHX1, particularly in relation to functional variants associated with fast and slow metabolism of epoxide intermediates. The present study aimed to identify any association of variation in these genes with COPD susceptibility or severity. In total, 1,017 white COPD patients and 912 nondiseased age and sex matched smoking controls were genotyped for six single nucleotide polymorphisms (SNPs) in EPHX1 (including the fast and slow variants and associated haplotypes), and eight SNPs in the two genes encoding GCL. GCL is a rate-limiting enzyme in the synthesis of glutathione, a major contributor to anti-oxidant protection in the lung. No association of variation was found in EPHX1 or GCL with susceptibility to COPD or disease severity. This is the largest reported study to date and is well powered to detect associations that have been previously suggested. The current data indicate that these genetic variants are unlikely to be related to susceptibility or disease severity in white chronic obstructive pulmonary disease patients.

Value of chest radiography in phenotyping chronic obstructive pulmonary disease.

The objectives of the present study were to reappraise chest radiography for the diagnosis of emphysema, using computed tomography (CT) as the reference standard, and to establish whether or not chest radiography is useful for phenotyping chronic obstructive pulmonary disease (COPD). Patients (n = 154) who had undergone posteroanterior and lateral chest radiography and CT for diagnostic purposes were studied. CT data were scored for emphysema using the picture-grading method. Chest radiographs were examined independently by five raters using four criteria for emphysema that had been validated against lung pathology. These criteria were then used to assess the prevalence of emphysema in 458 COPD patients. Patients with and without evidence of emphysema were compared with regard to age, sex, smoking history, body mass index (BMI), forced expiratory volume in one second (FEV(1)), diffusing capacity of the lung for carbon monoxide (D(L,CO)) and health status. Chest radiography yielded a sensitivity of 90% and a specificity of 98% for emphysema. Of the 458 COPD patients, 245 showed radiological evidence of emphysema. Emphysemic patients had a significantly lower BMI, FEV(1) and D(L,CO), greater restriction of physical activity and worse quality of life than nonemphysemic patients. There was no difference across the two groups with regard to age, sex or smoking history. Chest radiography is a simple means of diagnosing moderate-to-severe emphysema. It is useful in phenotyping chronic obstructive pulmonary disease and may aid physicians in their choice of treatment.

[Analysis of factors affecting circulation in the territory of internal carotid artery in arterial hypertension].

AIM: To assess carotid blood flow in healthy subjects and hypertensive patients, to specify prognostic significance of factors affecting carotid circulation with use of a multivariate analysis. MATERIAL AND METHODS: Clinical examination, ultrasonic dopplerography of the internal carotid arteries (ICA), echocardiography, tests for blood lipids were performed in 132 subjects (114 patients with arterial hypertension of stage I--III, 18 normotensive subjects). RESULTS: The role of age, blood pressure, blood lipids was essential both for initial and stenotic changes in ICA territory. Smoking was also an important factor. Moreover, impairment of carotid circulation correlated with progressive decline of myocardial function in the presence of coronary artery disease.

Mitochondrial dysfunction in COPD patients with low body mass index.

Patients with chronic obstructive pulmonary disease (COPD) show abnormal adaptations of skeletal muscle redox status after exercise training. Increased skeletal muscle oxidative stress in COPD patients may prompt mitochondrial dysfunction. The present study explores the association between body composition and mitochondrial respiration in seven COPD patients with low body mass index (BMI(L)), eight COPD patients with normal body mass index (BMI(N)) and seven healthy controls. All of them underwent a vastus lateralis biopsy in which muscle structure, in vitro mitochondrial respiratory function, uncoupling protein 3 (UCP3) mRNA expression and glutathione levels in both isolated mitochondria and the whole muscle were determined. Mitochondrial respiratory function (assessed by acceptor control ratio (ACR)) was impaired in BMI(L) (2.2+/-0.6) compared with both BMI(N) (5.3+/-1.3) and controls (8.2+/-1.3). ACR significantly correlated with arterial oxygen tension and with muscle endurance but it showed a negative association with exercise-induced increase in blood lactate levels. UCP3 mRNA expression was reduced in BMI(L) patients. In conclusion, chronic obstructive pulmonary disease patients with low body mass index show electron transport chain dysfunction, which may contribute to low muscle endurance in the current subgroup of patients.

Viral reactivation and pseudotype production in an in vitro superinfection system with two different strains of HIV-1.

Viral production and variability of HIV-1 is normally high in vivo causing the necessary conditions for cellular superinfection. In order to evaluate the superinfection dynamics in vitro, H9HTLVIIIB cell line was superinfected with HIVMN. Superinfected cells showed nearly 50% cell mortality at day 1 post-superinfection (ps), which increased significantly up to day 4 ps. Superinfecting genome was detectable until day 10 ps. The superinfecting strain was found in the supernatant only on day 1 ps, but was recovered up to day 4 ps by coculture with non-infected cells. The existing strain (HIVHXB2) was recovered throughout the studied period. Pseudotype formation by the HIVHXB2 genome and envelope proteins of the superinfecting strain (HIVMN) was observed from day 1 to 6 ps. Viral production was increased by 1.7 LOG in superinfected cells from day 1 ps. Both viral production increase and pseudotype formation could be relevant for HIV pathogenesis in vivo.

Evaluación de la tolerancia al ejercicio en pacientes con EPOC. Prueba de marcha de 6 minutos / Evaluation exercise tolerance in COPD patients: the 6-minute walking test

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Formoterol protects against platelet-activating factor-induced effects in asthma.

Platelet-activating factor (PAF) is an inflammatory mediator that provokes neutropaenia, bronchoconstriction and gas exchange defects due to exudation of bulk plasma within the airways. While the inhibitory effects of short-acting beta2-agonists on PAF-induced disturbances have been consistently shown, those of long-acting beta2-agonists are less convincing. To further explore the mechanisms involved in PAF challenge in asthma, 12 patients (forced expiratory volume in one second, 90 +/- 4% predicted) were investigated 2 h after inhaled formoterol (18 microg), in a double-blind, placebo-controlled, crossover design following PAF (18 microg) inhalation. Compared with the placebo, at 5 min, premedication with formoterol reduced PAF-induced cough and dyspnoea, and attenuated increased respiratory system resistance (by 67%) and arterial deoxygenation (by 50%). Likewise, ventilation-perfusion (V'A/Q') inequality improved, as reflected by the dispersion of pulmonary blood flow (by 63%) and an overall index of V'A/Q' heterogeneity (by 71%). In contrast, PAF-induced facial flushing, neutropaenia and subsequent rebound neutrophilia remained unchanged. The improvement in gas exchange abnormalities shown after platelet-activating factor in patients with asthma pretreated with formoterol at the recommended clinical dose may reflect, in addition to its class effects, an anti-exudative effect of formoterol in the airways.

Modeling and evaluation of respiratory and muscle pattern during hypercapnic stimulus.

Understanding the respiratory control system and the ventilatory pattern under hypercapnic stimulus is important to interpret the acute exacerbation of COPD and the condition of patients connected to mechanical ventilation. The purpose of this study is the analysis of respiratory and muscle parameters in order to obtain the most sensitive and characteristic of different levels of hypercapnic stimulus. Parameters defined and calculated from pressure signals show the highest variations with the increment of stimulus. Other ones like exhaled ventilation or ratios between respiratory parameters are more influenced by hypercapnia than tidal volume, respiratory frequency or even end tidal CO2. Muscle parameters from electromyographic signals of three respiratory muscles are calculated in time and frequency domain. In spite of greater variability between subjects, the most interesting muscles because of their activation with higher stimulus are in the following order: diaphragm, sternomastoid and genioglossus. Moreover, a model of respiratory control system is evaluated in order to predict and simulate appropriately this ventilatory stimulus. In spite of scattered real data, they are compared with simulation results obtained by the model and predicted by means of a specific respiratory optimization.

Increased tumour necrosis factor-alpha plasma levels during moderate-intensity exercise in COPD patients.

Post-training downregulation of muscle tumour necrosis factor (TNF)-alpha messenger ribonucleic acid (mRNA) expression and decrease in cellular TNF-alpha levels have been reported in the elderly. It is hypothesised that chronic obstructive pulmonary disease (COPD) patients may not show these adaptations due to their reduced ability to increase muscle antioxidant capacity with training. Eleven COPD patients (forced expiratory volume in one second 40 +/- 4.4% of the predicted value) and six age-matched controls were studied. Pre- and post-training levels of TNF-alpha, soluble TNF receptors (sTNFRs: sTNFR55 and sTNFR75) and interleukin (IL)-6 in plasma at rest and during exercise and vastus lateralis TNF-alpha mRNA were examined. Moderate-intensity constant-work-rate exercise (11 min at 40% of pretraining peak work-rate) increased pretraining plasma TNF-alpha levels in COPD patients (from 17 +/- 3.2 to 23 +/- 2.7 pg x mL(-1); p<0.005) but not in controls (from 19 +/- 4.6 to 19 +/- 3.2 pg x mL(-1)). No changes were observed in sTNFRs or IL-6 levels. After 8 weeks' endurance training, moderate-intensity exercise increased plasma TNF-alpha levels similarly to pretraining (from 16 +/- 3 to 21 +/- 4 pg x mL(-1); p<0.01). Pretraining muscle TNF-alpha mRNA expression was significantly higher in COPD patients than in controls (29.3 +/- 13.9 versus 5.0 +/- 1.5 TNF-alpha/18S ribonucleic acid, respectively), but no changes were observed after exercise or training. It is concluded that moderate-intensity exercise abnormally increases plasma tumour necrosis factor-alpha levels in chronic obstructive pulmonary disease patients without exercise-induced upregulation of the tumour necrosis factor-alpha gene in skeletal muscle.