Improving motor imagery through a mirror box for BCI users.

The aim of this study was to evaluate mirror visual feedback (MVF) as a training tool for brain-computer interface (BCI) users. This is because approximately 20-30% of subjects require more training to operate a BCI system using motor imagery. Electroencephalograms (EEGs) were recorded from 18 healthy subjects, using event-related desynchronization (ERD) to observe the responses during the movement or movement intention of the hand for the conditions of control, imagination, and the MVF with the mirror box. We constituted two groups: group 1: control, imagination, and MVF; group 2: control, MVF, and imagination. There were significant differences in imagination conditions between groups using MVF before or after imagination (right-hand, P = 0.0403; left-hand, P = 0.00939). The illusion of movement through MVF is not possible in all subjects, but even in those cases, we found an increase in imagination when the subject used the MVF previously. The increase in the r2s of imagination in the right and left hands suggests cross-learning. The increase in motor imagery recorded with EEG after MVF suggests that the mirror box made it easier to imagine movements. Our results provide evidence that the MVF could be used as a training tool to improve motor imagery.NEW & NOTEWORTHY The increase in motor imagery recorded with EEG after MVF (mirror visual feedback) suggests that the mirror box made it easier to imagine movements. Our results demonstrate that MVF could be used as a training tool to improve motor imagery.

Miettinen and Nurminen score statistics revisited.

It is commonly necessary to perform inferences on the difference, ratio, and odds ratio of two proportions p1 and p2 based on two independent samples. For this purpose, the most common asymptotic statistics are based on the score statistics (S-type statistics). As these do not correct the bias of the estimator of the product pi (1-pi), Miettinen and Nurminen proposed the MN-type statistics, which consist of multiplying the statistics S by (N-1)/N, where N is the sum of the two sample sizes. This paper demonstrates that the factor (N-1)/N is only correct in the case of the test of equality of two proportions, providing the estimation of the correct factor (AU-type statistics) and the minimum value of the same (AUM-type statistics). Moreover, this paper assesses the performance of the four-type statistics mentioned (S, MN, AU and AUM) in one and two-tailed tests, and for each of the three parameters cited (d, R and OR). We found that the AUM-type statistics are the best, followed by the MN type (whose performance was most similar to that of AU-type). Finally, this paper also provides the correct factors when the data are from a multinomial distribution, with the novelty that the MN and AU statistics are similar in the case of the test for the odds ratio.

Unbiased Phosphoproteome Mining Reveals New Functional Sites of Metabolite-Derived PTMs Involved in MASLD Development.

Post-translational modifications (PTMs) of proteins are paramount in health and disease. Phosphoproteome analysis by enrichment techniques is becoming increasingly attractive for biomedical research. Recent findings show co-enrichment of other phosphate-containing biologically relevant PTMs, but these results were obtained by closed searches focused on the modifications sought. Open searches are a breakthrough in high-throughput PTM analysis (OS-PTM), identifying practically all PTMs detectable by mass spectrometry, even unknown ones, with their modified sites, in a hypothesis-free and deep manner. Here we reanalyze liver phosphoproteome by OS-PTM, demonstrating its extremely complex nature. We found extensive Lys glycerophosphorylations (pgK), as well as modification with glycerylphosphorylethanolamine on Glu (gpetE) and flavin mononucleotide on His (fmnH). The functionality of these metabolite-derived PTMs is demonstrated during metabolic dysfunction-associated steatotic liver disease (MASLD) development in mice. MASLD elicits specific alterations in pgK, epgE and fmnH in the liver, mainly on glycolytic enzymes and mitochondrial proteins, suggesting an increase in glycolysis and mitochondrial ATP production from the early insulin-resistant stages. Thus, we show new possible mechanisms based on metabolite-derived PTMs leading to intrahepatic lipid accumulation during MASLD development and reinforce phosphoproteome enrichment as a valuable tool with which to study the functional implications of a variety of low-abundant phosphate-containing PTMs in cell physiology.

Ageing alters the lipid sensing process in the hypothalamus of Wistar rats. Effect of food restriction.

INTRODUCTION: Lipids regulate a wide range of biological processes. The mechanisms by which fatty acids (FA) and its metabolites influence the hypothalamic regulation of energy homeostasis have been highly studied. However, the effect of ageing and food restriction (FR) on this process is unknown. METHODS: Herein, we analyzed the gene expression, protein and phosphorylation levels of hypothalamic enzymes and transcription factors related to lipid metabolism. Experiments were performed in male Wistar rats of 3-, 8- and 24-month-old Wistar rats fed ad libitum (AL), as ageing model. Besides, 5- and 21-month-old rats were subjected to a moderate FR protocol (equivalent to ≈ 80% of normal food intake) for three months before the sacrifice. RESULTS: Aged Wistar rats showed a situation of chronic lipid excess as a result of an increase in de novo FA synthesis and FA levels that reach the brain, contributing likely to the development of central leptin and insulin resistance. We observe a hypothalamic downregulation of AMP-activated protein kinase (AMPK) and stearoyl-CoA desaturase (SCD1) and an increase of carnitine palmitoyltransferase-1c (CPT1c) expression. DISCUSSION: Our results suggest an impairment in the physiological lipid sensing system of aged Wistar rats, which would alter the balance of the intracellular mobilization and trafficking of lipids between the mitochondria and the Endoplasmic Reticulum (ER) in the hypothalamus, leading probably to the development of neurolipotoxicity in aged rats. Lastly, FR can only partially restore this imbalance.Schematic representation of the fate of LCFA-CoA in the hypothalamus of young and old rats. Blood circulating LCFAs in young Wistar rats reach the hypothalamus, where they are esterified to LCFA-CoA. Into glial cells or neurons, LCFA-CoA are driven to mitochondria (CPT1a) or ER (CPT1c) where could be desaturated by SDC1 and, thereby, converted into structural and signaling unsaturated lipids as oleic acid, related with neuronal myelinization and differentiation. However, the excess of LCFA that reach to the hypothalamus in old animals, could generate an increase in LCFA-CoA, which together with an increase in CPT1c levels, could favor the capture of LCFA-CoA to the ER. The decrease in the levels of SCD1 in old rats would decrease FA unsaturation degree that could trigger lipotoxicity process and neurodegeneration, both related to the development of neurodegenerative diseases linked to age.

Leptin, Acting at Central Level, Increases FGF21 Expression in White Adipose Tissue via PPARß/δ.

The altered function of adipose tissue can result in obesity, insulin resistance, and its metabolic complications. Leptin, acting on the central nervous system, modifies the composition and function of adipose tissue. To date, the molecular changes that occur in epididymal white adipose tissue (eWAT) during chronic leptin treatment are not fully understood. Herein we aimed to address whether PPARß/δ could mediate the metabolic actions induced by leptin in eWAT. To this end, male 3-month-old Wistar rats, infused intracerebroventricularly (icv) with leptin (0.2 µg/day) for 7 days, were daily co-treated intraperitoneally (ip) without or with the specific PPARß/δ receptor antagonist GSK0660 (1 mg/kg/day). In parallel, we also administered GSK0660 to control rats fed ad libitum without leptin infusion. Leptin, acting at central level, prevented the starvation-induced increase in circulating levels of FGF21, while induced markedly the endogenous expression of FGF21 and browning markers of eWAT. Interestingly, GSK0660 abolished the anorectic effects induced by icv leptin leading to increased visceral fat mass and reduced browning capacity. In addition, the pharmacological inhibition of PPARß/δ alters the immunomodulatory actions of central leptin on eWAT. In summary, our results demonstrate that PPARß/δ is involved in the up-regulation of FGF21 expression induced by leptin in visceral adipose tissue.

Two-tailed asymptotic inferences for the odds ratio in cross-sectional studies: evaluation of fifteen old and new methods of inference.

Various asymptotic methods of obtaining a confidence interval (CI) for the odds ratio (OR) have been proposed. Surprisingly, insofar as we know, the behavior of these methods has not been evaluated for data proceeding from a cross-sectional study (multinomial sampling), but only for data that originate in a prospective or retrospective study (two independent binomials sampling). The paper evaluates 15 different methods (10 classic ones and 5 new ones). Because the CI is obtained by inversion in θ of the two-tailed test for H0(θ): OR =[Formula: see text] (null hypothesis), this paper evaluates the tests for various values of θ, more than the CIs that are obtained. The following statements are valid only for the two-tailed inferences based on 20 ≤ n ≤ 200 and 0.05≤ OR≤20, since these are the limitations of the study. The two best methods are the classic Cornfield chi-squared method for 0.2≤ OR≤5 and, in other cases, the new method of Sterne for chi-squared; but the adjusted likelihood ratio method is a good alternative to the two previous methods, especially to the first when the sample size is large. The three methods require iterative calculations to obtain the CI. If one is looking for methods that are simple to apply (that is, ones that admit a simple, explicit solution), the best option is the Gart logit method for 1/3≤ OR≤3 and, if in other cases, the Agresti logit method. The Cornfield chi-squared and Gart logit methods should not be used outside the specified interval OR. The paper also selects the best methods for realizing the classic independence test (θ = 1).

One-tailed asymptotic inferences for the difference of proportions: Analysis of 97 methods of inference.

Two-tailed asymptotic inferences for the difference d = p2 - p1 with independent proportions have been widely studied in the literature. Nevertheless, the case of one tail has received less attention, despite its great practical importance (superiority studies and noninferiority studies). This paper assesses 97 methods to make these inferences (test and confidence intervals [CIs]), although it also alludes to many others. The conclusions obtained are (1) the optimal method in general (and particularly for errors α = 1% and 5%) is based on arcsine transformation, with the maximum likelihood estimator restricted to the null hypothesis and increasing the successes and failures by 3/8; (2) the optimal method for α = 10% is a modification of the classic model of Peskun; (3) a more simple and acceptable option for large sample sizes and values of d not near to ±1 is the classic method of Peskun; and (4) in the particular case of the superiority and inferiority tests, the optimal method is the classic Wald method (with continuity correction) when the successes and failures are increased by one. We additionally select the optimal methods to make compatible the conclusions of the homogeneity test and the CI for d, both for one tail and for two (methods which are related to arcsine transformation and the Wald method).

Correlates of out-of-pocket and catastrophic health expenditures in Tanzania: results from a national household survey.

BACKGROUND: Inequality in health services access and utilization are influenced by out-of-pocket health expenditures in many low and middle-income countries (LMICs). Various antecedents such as social factors, poor health and economic factors are proposed to direct the choice of health care service use and incurring out-of-pocket payments. We investigated the association of these factors with out-of-pocket health expenditures among the adult and older population in the United Republic of Tanzania. We also investigated the prevalence and associated determinants contributing to household catastrophic health expenditures. METHODS: We accessed the data of a multistage stratified random sample of 7279 adult participants, aged between 18 and 59 years, as well as 1018 participants aged above 60 years, from the first round of the Tanzania National Panel survey. We employed multiple generalized linear and logistic regression models to evaluate the correlates of out-of-pocket as well as catastrophic health expenditures, accounting for the complex sample design effects. RESULTS: Increasing age, female gender, obesity and functional disability increased the adults' out-of-pocket health expenditures significantly, while functional disability and visits to traditional healers increased the out-of-pocket health expenditures in older participants. Adult participants, who lacked formal education or worked as manual laborers earned significantly less (p < 0.001) and spent less on health (p < 0.001), despite having higher levels of disability. Large household size, household head's occupation as a manual laborer, household member with chronic illness, domestic violence against women and traditional healer's visits were significantly associated with high catastrophic health expenditures. CONCLUSION: We observed that the prevalence of inequalities in socioeconomic factors played a significant role in determining the nature of both out-of-pocket and catastrophic health expenditures. We propose that investment in social welfare programs and strengthening the social security mechanisms could reduce the financial burden in United Republic of Tanzania.

Central leptin signaling deficiency induced by leptin receptor antagonist leads to hypothalamic proteomic remodeling.

AIMS: Leptin irresponsiveness, which is often associated with obesity, can have significant impacts on the hypothalamic proteome of individuals, including those who are lean. While mounting evidence on leptin irresponsiveness has focused on obese individuals, understanding the early molecular and proteomic changes associated with deficient hypothalamic leptin signaling in lean individuals is essential for early intervention and prevention of metabolic disorders. Leptin receptor antagonists block the binding of leptin to its receptors, potentially reducing its effects and used in cases where excessive leptin activity might be harmful. MATERIALS AND METHODS: In this work, we blocked the central actions of leptin in lean male adult Wistar rat by chronically administering intracerebroventricularly the superactive leptin receptor antagonist (SLA) (D23L/L39A/D40A/F41A) and investigated its impact on the hypothalamic proteome using label-free sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) for quantitative proteomics. KEY FINDINGS: Our results show an accumulation of proteins involved in mRNA processing, mRNA stability, and translation in the hypothalamus of SLA-treated rats. Conversely, hypothalamic leptin signaling deficiency reduces the representation of proteins implicated in energy metabolism, neural circuitry, and neurotransmitter release. SIGNIFICANCE: The alterations in the adult rat hypothalamic proteome contribute to dysregulate appetite, metabolism, and energy balance, which are key factors in the development and progression of obesity and related metabolic disorders. Additionally, using bioinformatic analysis, we identified a series of transcription factors that are potentially involved in the upstream regulatory mechanisms responsible for the observed signature.

Assessment of Classical and Non-Classical Quantitative Electroencephalographic Measures in Patients with Substance Use Disorders.

Background: People diagnosed with substance use disorders (SUDs) are at risk for impairment of brain function and structure. However, physicians still do not have any clinical biomarker of brain impairment that helps diagnose or treat these patients when needed. The most common method to study these patients is the classical electroencephalographic (EEG) analyses of absolute and relative powers, but this has limited individual clinical applicability. Other non-classical measures such as frequency band ratios and entropy show promise in these patients. Therefore, there is a need to expand the use of quantitative (q)EEG beyond classical measures in clinical populations. Our aim is to assess a group of classical and non-classical qEEG measures in a population with SUDs. Methods: We selected 56 non-medicated and drug-free adult patients (30 males) diagnosed with SUDs and admitted to Rehabilitation Clinics. According to qualitative EEG findings, patients were divided into four groups. We estimated the absolute and relative powers and calculated the entropy, and the alpha/(delta + theta) ratio. Results: Our findings showed a significant variability of absolute and relative powers among patients with SUDs. We also observed a decrease in the EEG-based entropy index and alpha/(theta + delta) ratio, mainly in posterior regions, in the patients with abnormal qualitative EEG. Conclusions: Our findings support the view that the power spectrum is not a reliable biomarker on an individual level. Thus, we suggest shifting the approach from the power spectrum toward other potential methods and designs that may offer greater clinical possibilities.

Health care utilization by immigrants in Italy.

Healthcare utilization studies show how well documented disparities between migrants and non-migrants. Reducing such disparities is a major goal in European countries. However, healthcare utilization among Italian immigrants is under-studied. The objective of this study is to explore differences in healthcare use between immigrant and native Italians. Cross-sectional study using the latest available (2004/2005) Italian Health Conditions Survey. We estimated separate hurdle binomial negative regression models for GP, specialist, and telephone consultations and a logit model for emergency room (ER) use. We used logistic regression and zero-truncated negative binomial regression to model the zero (contact decision) and count processes (frequency decisions) respectively. Adjusting for risk factors, immigrants are significantly less likely to use healthcare services with 2.4 and 2.7 % lower utilization probability for specialist and telephone consultations, respectively. First- and second-generation immigrants' probability for specialist and telephone contact is significantly lower than natives'. Immigrants, ceteris paribus, have a much higher probability of using ERs than natives (0.7 %). First-generation immigrants show a higher probability of visiting ERs (1 %). GP visits show no significant difference. In conclusion Italian immigrants are much less likely to use specialist healthcare and medical telephone consultations than natives but more likely to use ERs. Hence, we report an over-use of ERs and under-utilization of preventive care among immigrants. We recommend improved health policies for immigrants: promotion of better information dissemination among them, simplification of organizational procedures, better communications between providers and immigrants, and an increased supply of health services for the most disadvantaged populations.

Technological knowledge progress: Were famous laws almost correct in developing and emerging economies?

Do the famous laws of the motion of technological progress like the Moore's Law, Wright's Law, Goddard's Law, and their derivatives explain the technological knowledge progress of developing and emerging economies? The aim of this paper is to investigate that question. For that purpose, we rationalize an existing framework (Nagy et al. 2013) and employ it on a panel data set of 66 developing and emerging market economies over the 1995-2017 period. Empirical evidence is mixed. Some of the results confirm a positive relationship between technological knowledge progress and the progress of time. Other instances indicate that the slow rate of learning delays the doubling time by 18 years. Yet other results predict that this group of countries will double its rate of progress in 4-5 years. The explanatory power varies across the laws, with most laws suggesting acceptance of the hypotheses that the included variables affect the technological knowledge progress while others recommending that we "do not accept" the hypothesis that in-situ scale and hence cumulative GDP per capita explain the technological knowledge progress of these countries. Practical policy implications, which this group of countries can use to assess and address constraints to the technological knowledge progress, are also discussed.

Acceptability by End-users of a Standardized Structured Format for Reporting EEG.

The report of the electroencephalogram (EEG) results has traditionally been made using free-text formats with a huge variation in descriptions due to several factors. Recently, the International Federation of Clinical Neurophysiology (IFCN) endorsed the use of the Standardized Computer-based Organized Reporting of EEG (SCORE). This system has many advantages, but only some concerns have been investigated so far. This study aimed to assess the end-users acceptability of this proposed EEG report format. A 16-item electronic survey was sent to physicians who use EEG services of a medical diagnosis clinic. Physicians had been receiving the EEG reports in free-text formats from the same three board-certified electroencephalographers for the past three years. In January 2019, the report changed to the SCORE format. The survey assessed five main topics: physician information and historical use of EEG; personal preferences; comparative aspects of the formats; impact of the new format on clinical decision-making; and satisfaction. Thirty-two of 52 have responded to the survey (61%). On average, 81% of the responders have received enough reports with the new format to reliably complete the survey. Every responder prefers the standardized compared to the free-text format. Twenty-five responders like the inclusion of the head model, and interestingly, five suggest including another legend to differentiate "slow activity" from "other abnormal activity". Virtually all responders would recommend the new format, but one-third read only the conclusion. Our findings suggest high acceptability of this standardized report format. Despite the limitations of this study, we hope these findings contribute to the improvement and expansion of standardized EEG reporting systems.

Electro-optical Study of the Anomalous Rotational Diffusion in Polymer Solutions.

Brownian diffusion of spherical nanoparticles is usually exploited to ascertain the rheological properties of complex media. However, the behavior of the tracer particles is affected by a number of phenomena linked to the interplay between the dynamics of the particles and polymer coils. For this reason, the characteristic lengths of the dispersed entities, depletion phenomena, and the presence of sticking conditions have been observed to affect the translational diffusion of the probes. On the other hand, the retardation effect of the host fluid on the rotational diffusion of nonspherical particles is less understood. We explore the possibility of studying this phenomenon by analyzing the electro-orientation of the particles in different scenarios in which we vary the ratio between the particle and polymer characteristic size, and the geometry of the particles, including both elongated and oblate shapes. We find that the Stokes-Einstein relation only applies if the radius of gyration of the polymer is much shorter than the particle size and when some repulsive interaction between both is present.

Grape seed extract supplementation modulates hepatic lipid metabolism in rats. Implication of PPARß/δ.

In mammals, the liver is involved in nutrient metabolism and in the regulation of lipid and glucose homeostasis. Multiple studies have described improvements in liver disorders after regular consumption of grape seed extract (GSE). GSE prevents or ameliorates hepatic metabolic dysfunction through AMPK activation, which reduces hepatic lipogenesis while enhancing hepatic lipid oxidation. However, the involvement of ChREBPß and PPARß/δ in these effects has not been fully elucidated. We aim to demonstrate that chronic consumption of GSE at low doses (25 mg kg-1 body weight per day) produces beneficial effects on hepatic glucose and lipid metabolism in young lean Wistar rats and that part of these effects involve ChREBPß inactivation and PPARß/δ activation. In our study, increased concentrations of structurally related (-)-(epi)catechin metabolites and 5-carbon ring fission metabolites were found in the serum of GSE-supplemented rats parallel with the reduction in triglycerides and leptin levels, hepatic cholesterol content and visceral adiposity. GSE supplementation inactivates ChREBP and GSK-3ß, which has been linked to improvements in hepatic lipid and glucose metabolism. Furthermore, the consumption of GSE promotes the expression of Pparß/δ, as well as Pgc-1α and Acox-1, which control hepatic lipid oxidation. Interestingly, pharmacological inhibition of PPARß/δ slowed the induction of Pgc-1α and Acox-1, as well as the activation of AMPK triggered by GSE consumption. Our data suggest that PPARß/δ activation is involved in the metabolic reprogramming effects of chronic GSE consumption in young rats, by modulating, at least, part of the transcriptional programs that maintain hepatic and systemic fuel homeostasis.

Yield of Sleep Deprivation EEG in Suspected Epilepsy. A Retrospective Study.

Background. Sleep is an activation procedure and is considered the most potent and best-documented modulator of seizures and interictal epileptiform discharges (IEDs) on electroencephalogram (EEG). The precise role of sleep deprivation in the diagnostic process of epilepsy has not been fully clarified after more than 50 years of use. Sleep deprivation is a procedure that is accompanied by discomfort for patients and their families. Therefore, an accurate indication according to each patient-specific characteristic is needed. This study aims to assess the effectiveness of sleep deprivation EEG in the diagnostic process of patients with suspected epilepsy in our center. Methods. We included patients with a first unprovoked seizure and patients with paroxysmal events suspecting seizures who underwent a sleep deprivation EEG (sdEEG) or routine EEG (rEEG). All patients were subsequently classified with confirmed epilepsy or not. Results. We included 460 patients. The group with sdEEG consisted of 115 patients, while the group with rEEG comprised 345 patients. In the sdEEG group, 19 patients (17%) were confirmed with epilepsy, of which 17 presented interictal epileptiform discharges (IEDs). For the rEEG group, 66 patients (19%) were confirmed with epilepsy, of which 63 presented IEDs. The difference was not statistically significant. Conclusion. Our study failed to find a difference in the yield of sleep deprivation versus routine EEG in patients with epilepsy, but there are many significant confounders/sample biases that limit the generalizability of the findings, particularly to the majority of adult practices.

S-resistin inhibits adipocyte differentiation and increases TNFalpha expression and secretion in 3T3-L1 cells.

S-resistin is a non-secretable resistin spliced variant described in white adipose tissue from Wistar rats. Since resistin has been implicated in adipogenesis regulation, here we have investigated the possible role of this new isoform in this process. For that, we have studied the adipocyte development in 3T3-L1 pre-adipocyte cell line stably expressing s-resistin and resistin. Both isoforms are able to restrain 3T3-L1 pre-adipocyte differentiation though affecting differently the expression pattern of pro-adipogenic transcription factors such CCAAT/enhancer binding proteins alpha and beta (C/EBPalpha and C/EBPbeta) and peroxisome proliferator-activated receptor gamma (PPARgamma), as well of proteins implicated in lipid metabolism such perilipin, fatty acid synthase (FAS), adipocyte lipid binding protein (ALBP/aP2) and carnitine palmitoyltransferase1 (CPT1). Likewise, both resistin isoforms impair insulin-stimulated glucose transport by decreasing glucose transport 4 (GLUT4) expression but to a different degree. In addition, s-resistin expressing 3T3-L1 cells display other remarkable differences. Thus, in these cells, endogenous resistin expression falls down while tumor necrosis factor alpha (TNFalpha) and interleukine 6 (IL-6) productions are increased along differentiation. These findings indicate that s-resistin isoform also impairs adipocyte differentiation affecting the expression pattern of key pro-adipogenic transcription factors and insulin sensitivity. Additionally, s-resistin may play a role in inflammatory processes.