Age-related changes in EEG coherence

Background and purpose Coherence changes can reflect the pathophysiological processes involved in human ageing. We conducted a retrospective population study that sought to analyze the age-related changes in EEG coherence in a group of 17,722 healthy professional drivers. Materials and methods The EEGs were obtained using a standard 10–20 electrode configuration on the scalp. The recordings from 19 scalp electrodes were taken while the participants’ eyes were closed. The linear correlations between the age and coherence were estimated by linear regression analysis. Results Our results showed a significant decrease in coherence with age in the theta and alpha bands, and there was an increasing coherence with the beta bands. The most prominent changes occurred in the alpha bands. The delta bands contained movement artefacts, which most likely do not change with age. Conclusions The age-related EEG desynchrony can be partly explained by the age-related reduction of cortical connectivity. Higher frequencies of oscillations require less cortical area of high coherence. These findings explain why the lowest average coherence values were observed in the beta and sigma bands, as well as why the beta bands show borderline statistical significance and the sigma bands show non-significance. The age-dependent decrease in coherence may influence the estimation of age-related changes in EEG energy due to phase cancellation

PPI Long Term Use: Risk of Neurological Adverse Events?

The purpose of this review study is to reveal a potential threat of one type of such widely used and freely distributed drugs, which are proton pump inhibitors that might be the cause of the onset of both dementia and depression. The authors performed a literature review of available studies on the research topic describing the adverse effect of proton pum inhibitors (PPIs) (omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, pantoprazole, dexrabeprazole, ilaprazole). For a long time, PPIs were considered to be completely safe drug substances for both short and long-term use. In recent years, there have been a few contradictory studis of absolute safety, especially in patients, who have long been using PPIs. At this time when depression and dementia are rising in the population, this is a very worrying fact that needs to be highlighted, and which needs to be carefully studied and evaluated, ideally trying to prevent it. The findings of most research studies described in this review indicate that there is a direct association between the onset of dementia and depression on one side and the long-term use of PPIs on the other

Alzheimer's disease and its treatment costs: case study in the Czech Republic

This paper deals with the analysis of the costs, applied, for example, when treating specific diseases – an important aid in prioritizing the process of resource allocation. In our review, the specific disease is dementia caused by Alzheimer’s disease. This paper aims to provide more information on the partial costs per patient that are calculated according to the aggregated data from publicly available sources as well as from the results of authors’ own investigation. The University Hospital in Hradec Králové and the General Health Insurance Company of the Czech Republic participated in this research. The elementary research objective was to compare the costs per patient diagnosed early onset, to those of the patient diagnosed later. The Czech Republic lacks information regarding dementia. Therefore, these issues require attention. The methods used in this paper included time series analyses, methods of direct questioning, interviews with experts, and analyses of medical documentation. These methods were combined to exploit their particular advantages and to ensure the issues discussed, were covered. The investigation showed that the underpinning of patients with Alzheimer’s disease at early onset is advantageous from an economic perspective, because the cost of outpatient care is much lower compared with that of inpatient care. The international comparisons of the volume of care provided should be approached with great caution. These are based solely on the facts of various expert estimates and are not usually supported by hard data. Yet, they still illustrate the overall view of our ability to take care of people with dementia. According to experts, care in the Czech Republic significantly lags behind the rest of developed Europe. While services are provided to 26% of people with dementia in Germany and 50% in France, the experts estimate that services are provided to only 10% of the population in the Czech Republic. If we were to offer a similar volume of services in the Czech Republic, to the same extent as the average in Europe, we would have to triple the existing capacities

Nitrendipine and Dementia: Forgotten Positive Facts?

Nowadays, there are about 50 million people suffering from dementia worldwide. In 2030, it is expected that there will be 82 million people living with dementia and in 2050, their number should reach 152 million. This increase in the number of people with dementia results in significant social and economic problems. Therefore, researchers attempt to reduce risk factors causing the development of dementia such as high blood pressure. Epidemiological studies have shown that hypertension increases the risk of dementia at an older age. It can, therefore, be assumed that hypertension therapy will reduce the risk of dementia. However, previous clinical studies have shown that the efficacy of different antihypertensive drugs differs in this respect. The drug group that appears to be the most effective in these analyses is calcium channel blockers (CCBs). The most significant preventive efficacy in terms of protection against dementia has been demonstrated with nitrendipine. Its use is, therefore, particularly advantageous in elderly patients with systolic hypertension who are at high risk of dementia. The purpose of this study is to restore the discussion on the prevention of vascular dementia and Alzheimer’s dementia with nitrendipine in indicated hypertonic patients. The authors performed a literature search of available sources describing the issue of dementia, hypertension and its treatment with nitrendipine. In addition, they made a comparison and evaluation of relevant findings. The results of the detected research studies indicate that nitrendipine is able to reduce the incidence of dementia [Alzheimer’s disease (AD), vascular and mixed] by 55%. The treatment of 1,000 patients with nitrendipine for 5 years may prevent 20 cases of dementia. However, what has not yet been explained is the temporal link between hypertension and dementia due to the long-time intervals between hypertension and the development of dementia

Delayed-Release Dimethyl Fumarate Safety and Efficacy in Pediatric Patients With Relapsing-Remitting Multiple Sclerosis

Background: Pediatric multiple sclerosis (MS) is rare: only 1.5-5% of MS cases are diagnosed before 18 years of age, and data on disease-modifying therapies (DMTs) for pediatric MS are limited. The CONNECTED study assessed the long-term safety and efficacy of treatment with delayed-release dimethyl fumarate (DMF), an oral MS DMT, in pediatric patients with MS. Methods: CONNECTED is the 96-week extension to FOCUS, a 24-week phase 2 study of patients aged 13-17 years;participants received DMF 240 mg twice daily. Endpoints included (primary) incidence of adverse events (AEs), serious AEs, and DMF discontinuations due to an AE, and (secondary) T2 hyperintense lesion incidence by magnetic resonance imaging and annualized relapse rate (ARR). Results: Twenty participants [median (range) age, 17 (14-18) years;65% female] who completed FOCUS enrolled into CONNECTED;17 (85%) completed CONNECTED. Eighteen participants (90%) experienced AEs: the most frequent was flushing (25%). None experienced infections or fever related to low lymphocyte counts. Three participants experienced four serious AEs;none led to DMF discontinuation. Twelve of 17 participants (71%) had no new/newly enlarged T2 lesions from weeks 16-24, two (12%) had one, and one each (6%) had two, three, or five or more lesions [median (range), 0 (0-6)]. Over the full 120-week treatment period, ARR was 0.2, an 84.5% relative reduction (n = 20;95% confidence interval: 66.8-92.8;p < 0.0001) vs. the year before DMF initiation. Conclusions: The long-term safety and efficacy observed in CONNECTED was consistent with adults, suggesting pediatric and adolescent patients with MS might benefit from DMF treatment

Venous Thromboembolism as an Adverse Effect During Treatment With Olanzapine: A Case Series

Objective: Venous thromboembolism (VTE) is a serious multifactorial disorder. Patients with severe mental illness have a higher risk of developing the condition compared to the general population.Methods: We observed 10 cases of VTE in patients with mental illness who were treated with the antipsychotic drug olanzapine. The diagnosis of VTE was made at the University Hospital Hradec Kralove (UH HK) from 2004 to 2013. VTE was objectively determined by imaging techniques (duplex ultrasonography, CT angiography) and laboratory tests (D-dimer). The average age was 46 years. The clinical manifestation of VTE was deep vein thrombosis in nine cases, including one case of simultaneous pulmonary embolism and one case of a concurrent ischemic cerebrovascular accident (iCVA). None of our patients had a history of malignant disease, trauma, or surgery.Results: Apart from antipsychotic medication, all the patients had clinical or laboratory risk factors for VTE. The most frequent clinical risk factors were obesity (n = 7) and smoking (n = 6). The most frequent laboratory risk factors were increased levels of FVIII (n = 4), mild hyperhomocysteinemia (n = 3), and factor V Leiden mutation (n = 2). VTE developed within 3 months after antipsychotic drug initiation in three patients and within 6 months in three patients.Conclusion: Olanzapine can be considered a precipitating factor for VTE formation. When olanzapine is administered, we need to monitor for clinical signs and symptoms of VTE, especially when other risk factors are present

Binocular video head impulse test: Normative data study

IntroductionThe video head impulse test (vHIT) evaluates the vestibulo-ocular reflex (VOR). It’s usually recorded from only one eye. Newer vHIT devices allow a binocular quantification of the VOR.Purpose (Aim)To investigate the advantages of simultaneously recorded binocular vHIT (bvHIT) to detect the differences between the VOR gains of the adducting and the abducting eye, to define the most precise VOR measure, and to assess gaze dys/conjugacy. We aimed to establish normative values for bvHIT adducting/abducting eye VOR gains and to introduce the VOR dysconjugacy ratio (vorDR) between adducting and abducting eyes for bvHIT.MethodsWe enrolled 44 healthy adult participants in a cross-sectional, prospective study using a repeated-measures design to assess test–retest reliability. A binocular EyeSeeCam Sci 2 device was used to simultaneously record bvHIT from both eyes during impulsive head stimulation in the horizontal plane.ResultsPooled bvHIT retest gains of the adducting eye significantly exceeded those of the abducting eye (mean (SD): 1.08 (SD = 0.06), 0.95 (SD = 0.06), respectively). Both adduction and abduction gains showed similar variability, suggesting comparable precision and therefore equal suitability for VOR asymmetry assessment. The pooled vorDR here introduced to bvHIT was 1.13 (SD = 0.05). The test–retest repeatability coefficient was 0.06.ConclusionOur study provides normative values reflecting the conjugacy of eye movement responses to horizontal bvHIT in healthy participants. The results were similar to a previous study using the gold-standard scleral search coil, which also reported greater VOR gains in the adducting than in the abducting eye. In analogy to the analysis of saccade conjugacy, we propose the use of a novel bvHIT dysconjugacy ratio to assess dys/conjugacy of VOR-induced eye movements. In addition, to accurately assess VOR asymmetry, and to avoid directional gain preponderance between adduction and abduction VOR-induced eye movements leading to monocular vHIT bias, we recommend using a binocular ductional VOR asymmetry index that compares the VOR gains of only the abduction or only the adduction movements of both eyes

Ligand-Based Virtual Screening, Molecular Docking, Molecular Dynamics, and MM-PBSA Calculations towards the Identification of Potential Novel Ricin Inhibitors.

Ricin is a toxin found in the castor seeds and listed as a chemical weapon by the Chemical Weapons Convention (CWC) due to its high toxicity combined with the easiness of obtention and lack of available antidotes. The relatively frequent episodes of usage or attempting to use ricin in terrorist attacks reinforce the urge to develop an antidote for this toxin. In this sense, we selected in this work the current RTA (ricin catalytic subunit) inhibitor with the best experimental performance, as a reference molecule for virtual screening in the PubChem database. The selected molecules were then evaluated through docking studies, followed by drug-likeness investigation, molecular dynamics simulations and Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) calculations. In every step, the selection of molecules was mainly based on their ability to occupy both the active and secondary sites of RTA, which are located right next to each other, but are not simultaneously occupied by the current RTA inhibitors. Results show that the three PubChem compounds 18309602, 18498053, and 136023163 presented better overall results than the reference molecule itself, showing up as new hits for the RTA inhibition, and encouraging further experimental evaluation