Merger of Visible Light-Driven Chiral Organocatalysis and Continuous Flow Chemistry: An Accelerated and Scalable Access into Enantioselective α-Alkylation of Aldehydes.

The electron donor-acceptor complex-enabled asymmetric photochemical alkylation strategy holds potential to attain elusive chiral α-alkylated aldehydes without an external photoredox catalyst. The photosensitizer-free conditions are beneficial concerning process costs and sustainability. However, lengthy organocatalyst preparation steps as well as limited productivity and difficult scalability render the current approaches unsuitable for synthesis on enlarged scales. Inspired by these limitations, a protocol was developed for the enantioselective α-alkylation of aldehydes based on the synergistic combination of visible light-driven asymmetric organocatalysis and a controlled continuous flow reaction environment. With the aim to reduce process costs, a commercially available chiral catalyst has been exploited to achieve photosensitizer-free enantioselective α-alkylations using phenacyl bromide derivates as alkylating agents. As a result of elaborate optimization and process development, the present flow strategy furnishes an accelerated and inherently scalable entry into enantioenriched α-alkylated aldehydes including a chiral key intermediate of the antirheumatic esonarimod.

Accurate response selection and inhibition in healthy aging: An event-related potential study.

Inhibitory control is thought to be critical for appropriate response selection in an ever-changing environment and to decline with age. However, experimental paradigms (e.g., go/no-go) confound stimulus frequency with demands to respond or inhibit responding. The present study eliminated that confound by using a modified go/no-go task controlling for stimulus frequency differences (using frequent-go, infrequent-go, and infrequent no-go types of stimuli) in healthy older and young adults. Event-related potential (ERP) components related to detection of response conflict (N2) and response evaluation (P3) were also examined. Behaviorally, older and young adults were sensitive to stimulus frequencies indicated by significant slowing for the infrequent-go compared with the frequent-go stimuli observed in both groups. Furthermore, older adults were characterized by reduced commission errors and overall slowing, suggesting that they could take advantage of their slower performance. Increase of N2 amplitude was evident for correctly inhibited no-go stimuli in both groups. In contrast, no-go stimulus-related increase in P3 amplitude could be observed only in the young. Stimulus frequency-related ERP amplitude differences were not significant either in the young or in the older adults. These results suggest preserved behavioral control over inappropriate responses in older adults and indicate that efficient response inhibition is related to compensatory mechanisms. The age-related decrease in the P3 amplitude suggests that the evaluation of response inhibition (a) could be independent of the detection of response conflict and (b) supports the notion of strategic differences in performance with age. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

The Outcome of Status Epilepticus and Long-Term Follow-Up.

Objective: This study was to investigate the outcome of status epilepticus (SE) associated with antiepileptic therapy during SE and in follow-up period, risk factors including age, co-morbidities, pre-existing epilepsy, and etiology in the East-Hungarian region. Methods: A prospective cross-sectional database was compiled from outpatient files between 2013 and 2017. Follow-up ended on 30.06.2018. Results: One hundred and thirty five episodes (male: 68, 50.4%) were evaluated, mean age and follow-up time being 64.1 ± 13.9 years and 39.9 ± 14.2 months, respectively. Of the 89 patients with pre-existing epilepsy, 34 failed to visit the outpatient unit regularly. Case fatality rate was 25.2% and 31 patients (30.7%) died after discharge due to co-morbidities; their mean survival time was 10.44 ± 8 months. Focal, generalized and combined type epilepsies were diagnosed in 67 patients (49.6%), 47 patients (34.8%), and 21 patients (15.6%) of SE, respectively. Nine patients had non-convulsive SE (NCSE). Mean seizure-free period was 6.8 ± 6.9 months. Patients taking carbamazepine (20.9%; OR: 0.37, 95%CI: 0.16-0.82; p = 0.018), levetiracetam (27.5%; OR: 0.51, 95%CI: 0.27-0.97; p = 0.041), or valproate (11.1%; OR: 0.18, 95%CI: 0.05-0.61; p = 0.0043) were expected to achieve seizure freedom after SE. The worst outcome was linked to advanced age, etiology, new onset status epilepticus, NCSE, and focal status epilepsy. Conclusion: This study highlights the importance of regular care and patient follow-up.

Balanced assessment systems revisited.

In 2014, balanced assessment systems (BAS) were proposed as a resource-conscious, 'fit-for-purpose' form of health technology assessment for middle-income countries which lack resources and competences necessary for resource-intensive health technology assessment models. BAS has undergone extensive policy debate in the period since its publication but it has not been critically assessed in a structured form yet. This article aims to describe both the contributions and the weak spots of the original framework and to reflect on them with the intention of further developing the model.

Age-dependent characteristics of feedback evaluation related to monetary gains and losses.

Monitoring the consequences of actions is of crucial importance in order to optimize behavior to the challenges of the environment. Recently the age-related aspects of this fundamentally important cognitive processing have been brought into the focus of investigation since behavioral monitoring and related control mechanisms are widely known to be affected by aging. Processing of feedback stimuli is a core mechanism for rapid evaluation of the functionally significant aspects of outcome, guiding behavior towards avoidance or approach. The aim of the present study was to analyze the age-related alterations in the most prominent electrophysiological correlates of feedback processing, the feedback-related negativity (FRN) and the P3 event-related potential components, using a two-choice-single-outcome gambling task with two amounts of monetary stakes. In terms of behavioral indices higher proportion of risky choices was observed after loss than after gain events in both groups. In the young the FRN component was found to be an indicator of the goodness of outcome (loss or gain), and the P3 showed a complex picture of feedback evaluation with selective sensitivity to large amount of gain. In contrast, in the elderly group outcome valence had no effect on the amplitude of the FRN, and the P3 was also insensitive of the complex outcome properties. As the ERP-correlates of feedback processing are not as pronounced in the elderly, it is suggested that normal aging is accompanied by an alteration of the neural mechanisms signaling the most salient feedback stimulus properties.

Age-related characteristics of risky decision-making and progressive expectation formation.

During daily encounters, it is inevitable that people take risks. Investigating the sequential processing of risk hazards involve expectation formation about outcome contingencies. The present study aimed to explore risk behavior and its neural correlates in sequences of decision making, particularly in old age, which represents a critical period regarding risk-taking propensity. The Balloon Analogue Risk Task was used in an electrophysiological setting with young and elderly age groups. During the task each additional pump on a virtual balloon increased the likelihood of a balloon burst but also increased the chance to collect more reward. Event-related potentials associated with rewarding feedback were analyzed based on the forthcoming decisions (whether to continue or to stop) in order to differentiate between states of expectation towards gain or loss. In the young, the reward positivity ERP component increased as a function of reward contingencies with the largest amplitude for rewarding feedback followed by the decision to stop. In the elderly, however, reward positivity did not reflect the effect of reward structure. Behavioral indices of risk-taking propensity suggest that the performance of the young and the elderly were dissociable only with respect to response times: The elderly was characterized by hesitation and more deliberative decision making throughout the experiment. These findings signify that sequential tracking of outcome contingencies has a key role in cost-efficient action planning and progressive expectation formation.

[ELECTROPHYSIOLOGIC ANALYSIS OF MENTAL ARITHMETIC TASK BY THE "MINIMUM SPANNING TREE" METHOD]. / ARITMETIKAI FELADAT ELEKTROFIZIOLÓGIAI ELEMZÉSE A "MINIMÁLIS FESZÍTO FÁK" MÓDSZERÉVEL.

GOALS: In the present study basic arithmetic induced rearrangements in functional connections of the brain were investigated by using graph theoretical analysis what becomes increasingly important both in theoretical neuroscience and also in clinical investigations. RESEARCH QUESTIONS: During mental arithmetic operations (working) memory plays an important role, but there are only a few studies in which an attempt was made to separate this effect from the process of arithmetic operations themselves. The goal of our study was to separate the neural networks involved in cognitive functions. METHODS: As an attempt to clarify this issue the graph-theoretical "minimal spanning tree" method was used for the analysis of EEG recorded during task performance. The effects of passive viewing, number recognition and mental arithmetic on PLI based minimal spanning trees (MST) were investigated on the EEG in young adults (adding task: 17 subjects; passive viewing and number recognition: 16 subjects) in the θ (4-8 Hz) frequency band. RESULTS: Occipital task relevant synchronization was found by using the different methods, probably related to the effect of visual stimulation. With respect to diameter, eccentricity and fraction of leafs different task-related changes were found. DISCUSSION: It was shown that the task related changes of various graph indices are capable to identify networks behind the various relevant dominant functions. Thus the "minimal spanning tree" method is suitable for the analysis of the reorganization of the brain with respect to cognitive functions.

Frontal midline theta connectivity is related to efficiency of WM maintenance and is affected by aging.

Representations in working memory (WM) are temporary, but can be refreshed for longer periods of time through maintenance mechanisms, thereby establishing their availability for subsequent memory tests. Frontal brain regions supporting WM maintenance operations undergo anatomical and functional changes with advancing age, leading to age related decline of memory functions. The present study focused on age-related functional connectivity changes of the frontal midline (FM) cortex in the theta band (4-8 Hz), related to WM maintenance. In the visual delayed-match-to-sample WM task young (18-26 years, N=20) and elderly (60-71 years N=16) adults had to memorize sample stimuli consisting of 3 or 5 items while 33 channel EEG recording was performed. The phase lag index was used to quantify connectivity strength between cortical regions. The low and high memory demanding WM maintenance periods were classified based on whether they were successfully maintained (remembered) or unsuccessfully maintained (unrecognized later). In the elderly reduced connectivity strength of FM brain region and decreased performance were observed. The connectivity strength between FM and posterior sensory cortices was shown to be sensitive to both increased memory demands and memory performance regardless of age. The coupling of frontal regions (midline and lateral) and FM-temporal cortices characterized successfully maintained trials and declined with advancing age. The findings provide evidence that a FM neural circuit of theta oscillations that serves a possible basis of active maintenance process is especially vulnerable to aging.

EEG network connectivity changes in mild cognitive impairment - Preliminary results.

Resting state EEGs were compared between patients with amnestic subtype of mild cognitive impairment (aMCI) and matched elderly controls at two times over a one year period. The study aimed at investigating the role of functional connectivity between and within different brain regions in relation to the progression of cognitive deficit in MCI. The EEG was recorded in two sessions during eyes closed and eyes open resting conditions. Functional brain connectivity was investigated based on the measurement of phase synchronization in different frequency bands. Delta and theta synchronization characteristics indicated decreased level of local and large-scale connectivity in the patients within the frontal, between the frontal and temporal, and frontal and parietal brain areas which was more pronounced 1year later. As a consequence of opening the eyes connectivity in the alpha1 band within the parietal lobe decreased compared to the eyes closed condition but only in the control group. The lack of alpha1 band reactivity following eye opening could reliably differentiate patients from controls. Our preliminary results support the notion that the functional disconnection between distant brain areas is a characteristic feature of MCI, and may prove to be predictive in terms of the progression of this condition.

[Spectral, phase-synchronization, and graph theoretical EEG changes related to mental arithmetics]. / Számolási teljesítmeny spektrális, fázisszinkronizációs és gráfelméleti EEG-jellemzoi.

During mental arithmetic operations working memory plays an important role, but there are only few studies in which an attempt was made to separate this effect from the process of arithmetics per se. In this study the effects of arithmetic on the EEG of young adults (14 participants, six of them women, mean age 21.57 years, SD: 2.62) was investigated during a subtraction task in the theta (4-8 Hz) frequency band. Besides the power density spectrum analysis phase synchrony based on recently developed graph theoretical methods were used and strength of local connections (cluster coefficient; C) and global interconnectedness of network (characteristic path length; L) were determined. Before the arithmetic task passive viewing (control situation) and a number recognition paradigms were used. During the arithmetic task compared to the control situation significantly increasing phase synchrony and C values were found. L was significantly shorter (F(2, 26) = 818.77, p < 0.0001) only during the arithmetic task: this fact and the former two results imply that the network topology shifted towards the "small world" direction. Our findings concerning regional differences confirm those reported earlier in the literature: compared to the control condition significant task-related increase was found in C values in the parietal areas [more explicitly in the left side, (F(1, 13) = 7.2020, p = 0.0188)], which probably corresponds to stronger local connections and more synchronized (sub)networks. During the task condition significantly increased 0 band power; (F(1, 13) = 7.9708, p = 0.01447 and decreased L values were found in the left frontal region compared to the right side (F(1, 13) = 6.0734, p = 0.0284), which can also be interpreted as an indicator of optimized network topology of information processing.

Persistence with statin therapy in Hungary.

INTRODUCTION: Persistence with lipid-lowering drug therapy by cardiovascular patients in Hungary has not been studied previously. This study was designed to determine the rate with which Hungarian patients with hyperlipidemia persist in taking lipid-lowering agents, and to compare this with rates reported from other countries. MATERIAL AND METHODS: This was a retrospective study that utilized data from the Institutional Database of the National Health Insurance Fund to analyze persistence rates with statins and ezetimibe. The study included data for patients who started lipid-lowering therapy between January 1, 2007, and March 31, 2009. Variables included type of lipid-lowering therapy, year of therapy start, and patient age. Main outcome measures were medians of persistence in months, percentages of patients persisting in therapy for 6 and 12 months, and Kaplan-Meier persistence plots. RESULTS: The percentage of patients who persisted with overall statin therapy was 46% after 1 month, 40.3% after 2 months, 27% after 6 months, and 20.1% after 12 months. Persistence was slightly greater for statin therapy started during 2008 than during 2007. Older patients were more persistent with therapy than younger patients. Persistence with the combination of ezetimibe-statin therapy was greater than with statin or ezetimibe monotherapy. CONCLUSIONS: Persistence with statin therapy by patients in Hungary was low compared with other countries. Low persistence may have negated potential clinical benefits of long-term statin therapy.

EEG synchronization characteristics of functional connectivity and complex network properties of memory maintenance in the delta and theta frequency bands.

Task-dependent changes of nonlinear-linear synchronization features and graph theoretical properties of the delta and theta frequencies were analyzed in the present EEG study that were related to episodic memory maintenance processes. Synchronization was found to increase with respect to both the delta and theta bands within the frontal and parietal areas and also between these regions. Results of graph theoretical analysis indicated a task-related shift towards small-world network topology in the theta band.

[Ageing and arithmetic performance--electrophysiological complexity-, and graph theoretical characteristics]. / Oregedés és számolási teljesítmény: az EEG spektrális, komplexitás- és hálózatjellemzoi.

During the course of ageing the decline of cognitive performance, including attention and working memory processes--essential for arithmetic procedures--is well known. For the investigation of the neuronal mechanisms of these processes the application of methods capable of taking into account the high complexity of the nervous system, the role of nonlinear processes and network-properties of its constituents are necessary. As for the latter the recently realized small world network characteristics representing optimal conditions for information processing may be of particular importance. In the present study the spectral, complexity-, and network characteristics of the EEG recorded during performing an arithmetic task in a group of young (n=32, mean age 22.0 yrs) and elderly (n=19, mean age: 66.7 yrs) was analyzed. Heart rate and behavioral measures (number of mistakes, reaction time) were also investigated. The alpha2 band decreased in the young, while the delta band increased in the elderly in the task condition. The increased Omega-complexity observed in the elderly is probably caused by reduced interneuronal connectivity. "Small-world" network characteristics were found in the beta and delta bands although in the elderly the topology was closer to a random pattern. In the task condition the network features of the elderly subjects shifted more towards the small world pattern than those seen in the young indicating that for the elderly the mobilized effort for task completion was higher. In spite of this, the level of performance and the heart rate change observed in the elderly was lower than that seen in the young. The application of complexity-, and graph theoretical analysis appears to be a promising tool for the investigation of diseases of the nervous system characterized by diffuse pathology as in the case of as various types of dementias.

Age-dependent features of EEG-reactivity--spectral, complexity, and network characteristics.

Our goal was to measure indices characterizing EEG-reactivity in young and elderly subjects. It was hypothesized that EEG-reactivity as reflected by different measures would be lower in the elderly. In two age groups (young: N= 23, mean age = 21.5 +/- 2.2 years; old: N= 25, mean age = 66.9 +/- 3.6 years) absolute frequency spectra, Omega-complexity, synchronization likelihood and network properties (clustering coefficient and characteristic path length) of the EEG were analyzed in the delta, theta, alpha1, alpha2, beta1 and beta2 frequency bands occurring as a result of eyes opening. Absolute spectral power was higher in the young in the delta, alpha1 and alpha2 bands in the posterior area. The alpha1 peak frequency decreased following eyes opening in the young, while no change was observed in the elderly. Omega-complexity was higher in the elderly especially in the frontal area and increased following eyes opening. Values of the clustering coefficient, path length and that of the "small-world index" decreased as a result of eyes opening, the latter in the fast frequency range. The results suggest reduced reactivity in the elderly as shown by frequency spectra and decreased level of integrative activity particularly in the frontal area probably as a result of reduced interneuronal processing capacity. Indices of network characteristics reveal a shift towards more random topology especially in the beta frequencies caused by eyes opening.

The acute effect of low-dose alcohol on working memory during mental arithmetic: I. Behavioral measures and EEG theta band spectral characteristics.

OBJECTIVE AND HYPOTHESIS: Task-related EEG changes were studied during the performance of a mental arithmetic task, as influenced by low alcohol dosages with the presumption that even "social" drinking may have detrimental effect. METHODS: A mental arithmetic task was used in which addition and working memory effort was required. EEG spectra with an emphasis on the theta band, error rate and reaction time were analyzed in 5 (control, task, placebo-task, low-dose task [0.2 g/kg alcohol], high-dose task [0.4 g/kg alcohol]) conditions. Blood alcohol concentrations were measured. RESULTS: Reaction time was shortest in the placebo condition. No significant alcohol effect was seen for error rate. Task-related significant theta power increase was observed especially in the frontal area and in the left hemisphere which was reversed, although not in a significant way, by alcohol. CONCLUSION: No detrimental alcohol effect was seen on behavioral indices of task performance. However, the ethanol-induced moderate reduction of the task-related frontally dominant theta increase, probably corresponding to working memory demand, is a modest but clear electrophysiological sign of alcohol effect in this low-dose range.

The acute effect of low-dose alcohol on working memory during mental arithmetic: II. Changes of nonlinear and linear EEG-complexity in the theta band, heart rate and electrodermal activity.

OBJECTIVE AND HYPOTHESIS: Nonlinear and linear methods of EEG-complexity analysis and autonomic measures were used to characterize processes accompanying performance in a mental arithmetic task challenged by low ("social") alcohol doses. It was expected that alcohol in such doses will dampen changes of task-related EEG-synchronization in the theta band, and those of heart rate and electrodermal activity (EDA). METHODS: In the mental arithmetic task addition and working memory, effort was required. The EEG, ECG and EDA were recorded in 5 conditions: task, placebo-task, low dose-task (0.2 g/kg alcohol), high dose-task (0.4 g/kg alcohol). Omega-complexity and synchronization likelihood (SL) were computed of the theta band of the EEG. RESULTS: Task-related decrease of the Omega-complexity and increase of the SL was found in the theta frequency band. Following alcohol consumption, these changes did not develop as seen especially for SL in the anterior area, although the significant effects were elicited by task performance. Conspicuous task-evoked increases were observed for ECG and EDA which were even more enhanced by alcohol. CONCLUSIONS: Task-induced significant changes of the Omega-complexity and that of SL indicate increased synchrony in the theta band, probably corresponding to working memory effort. Both of these measures proved to be sensitive for the effect of low alcohol dose although these alcohol-elicited changes were not statistically significant. Task-induced heart rate and EDA increases were further intensified by alcohol probably indicating its activating effect on these autonomic measures in the dose range studied.

Spectral characteristics and linear-nonlinear synchronization changes of different EEG frequency bands during the CNV.

During the CNV recorded in a simple auditory working memory task, task-specific decrease of the relative delta band and a transient increase of the absolute theta band were seen, accompanied by an increase of the absolute alpha1 and alpha2 bands in the posterior region. The decreased delta power probably corresponds to increased task-evoked arousal, whereas the transient theta power increase corresponds to working memory demand and possibly to the orienting response. The increased alpha1 and alpha2 power may be a manifestation of a top-down mechanism revealing control over the execution of a response. The area-specific, task-related, and frequency-dependent changes of EEG complexity measures indicate frontally increasing complexity during the early part of the CNV in the beta frequency bands, which underscores the importance of this region in the mechanisms of anticipatory behavior.

Quantitative EEG in early Alzheimer's disease patients - power spectrum and complexity features.

The goal of this study was to investigate the EEG signs of early stage Alzheimer's disease (AD) by conventional analyses and by methods quantifying linear and nonlinear EEG-complexity. The EEG was recorded in 12 mild AD patients and in an age-matched healthy control group (24 subjects) in both eyes open and eyes closed conditions. Frequency spectra, Omega-complexity and Synchronization likelihood were calculated on the data. In the patients a significant decrease of the relative alpha and increase of the theta power were found. Remarkably increased Omega-complexity and lower Synchronization likelihood were observed in AD in the 0.5-25 Hz frequency ranges. It is concluded that both spectral- and EEG-complexity changes can be found already in the early stage of AD in a wide frequency range. Application of conventional EEG analysis methods in combination with quantification of EEG-complexity may improve the chances of early diagnosis of AD.