Prolonged Consumption of Sweetened Beverages Lastingly Deteriorates Cognitive Functions and Reward Processing in Mice.

We investigated the detrimental effects of chronic consumption of sweet or sweetened beverages in mice. We report that consumption of beverages containing small amounts of sucrose during several weeks impaired reward systems. This is evidenced by robust changes in the activation pattern of prefrontal brain regions associated with abnormal risk-taking and delayed establishment of decision-making strategy. Supporting these findings, we find that chronic consumption of low doses of artificial sweeteners such as saccharin disrupts brain regions' activity engaged in decision-making and reward processes. Consequently, this leads to the rapid development of inflexible decisions, particularly in a subset of vulnerable individuals. Our data also reveal that regular consumption, even at low doses, of sweet or sweeteners dramatically alters brain neurochemistry, i.e., dopamine content and turnover, and high cognitive functions, while sparing metabolic regulations. Our findings suggest that it would be relevant to focus on long-term consequences on the brain of sweet or sweetened beverages in humans, especially as they may go metabolically unnoticed.

Robustness of Random Forest-based gene selection methods.

BACKGROUND: Gene selection is an important part of microarray data analysis because it provides information that can lead to a better mechanistic understanding of an investigated phenomenon. At the same time, gene selection is very difficult because of the noisy nature of microarray data. As a consequence, gene selection is often performed with machine learning methods. The Random Forest method is particularly well suited for this purpose. In this work, four state-of-the-art Random Forest-based feature selection methods were compared in a gene selection context. The analysis focused on the stability of selection because, although it is necessary for determining the significance of results, it is often ignored in similar studies. RESULTS: The comparison of post-selection accuracy of a validation of Random Forest classifiers revealed that all investigated methods were equivalent in this context. However, the methods substantially differed with respect to the number of selected genes and the stability of selection. Of the analysed methods, the Boruta algorithm predicted the most genes as potentially important. CONCLUSIONS: The post-selection classifier error rate, which is a frequently used measure, was found to be a potentially deceptive measure of gene selection quality. When the number of consistently selected genes was considered, the Boruta algorithm was clearly the best. Although it was also the most computationally intensive method, the Boruta algorithm's computational demands could be reduced to levels comparable to those of other algorithms by replacing the Random Forest importance with a comparable measure from Random Ferns (a similar but simplified classifier). Despite their design assumptions, the minimal optimal selection methods, were found to select a high fraction of false positives.

Kendall transformation brings a robust categorical representation of ordinal data.

Kendall transformation is a conversion of an ordered feature into a vector of pairwise order relations between individual values. This way, it preserves ranking of observations and represents it in a categorical form. Such transformation allows for generalisation of methods requiring strictly categorical input, especially in the limit of small number of observations, when quantisation becomes problematic. In particular, many approaches of information theory can be directly applied to Kendall-transformed continuous data without relying on differential entropy or any additional parameters. Moreover, by filtering information to this contained in ranking, Kendall transformation leads to a better robustness at a reasonable cost of dropping sophisticated interactions which are anyhow unlikely to be correctly estimated. In bivariate analysis, Kendall transformation can be related to popular non-parametric methods, showing the soundness of the approach. The paper also demonstrates its efficiency in multivariate problems, as well as provides an example analysis of a real-world data.

Use of broad-spectrum antibiotics in children diagnosed with multisystem inflammatory syndrome temporarily associated with SARS-CoV-2 infection in Poland: the MOIS-CoR study.

OBJECTIVES: Multisystem inflammatory syndrome in children (MIS-C) is the result of an immune response triggered by a previous exposure to SARS-CoV-2. The clinical presentation of MIS-C overlaps with other life-threatening bacterial infections, in which antimicrobials are the mainstay therapy. The aim of study was to describe the use of antibiotics in children with MIS-C in Poland. METHODS: The analysis of 345 children reported from 42 Polish cities to the national MultiOrgan Inflammatory Syndromes COVID-19 Related Study (MOIS-CoR Study) from June 2020 to April 2021. RESULTS: At least one antibiotic was used in 310 (90%) children, mainly third-generation cephalosporin (251/310). Broad-spectrum antibiotics were used in 258 (75%) children and 224 (87%) received this treatment for more than 3 days. Concentrations of serum procalcitonin >2 µg/l and the presence of lower respiratory symptoms were associated with increased odds of receiving any antibiotic. CONCLUSION: Although bacterial infections in patients with MIS-C are uncommon, we show that MIS-C poses a challenge to clinicians who are faced with the decision to start, continue, or stop antimicrobial therapy. Antibiotic stewardship in patients with MIS-C should be improved to ensure that likely pathogens are treated and that antimicrobials are stopped when bacterial infections are excluded and the diagnosis of MIS-C is made.

A tendency to worse course of multisystem inflammatory syndrome in children with obesity: MultiOrgan Inflammatory Syndromes COVID-19 related study.

Background: A new disease entity called multisystem inflammatory syndrome in children (MIS-C) is a rare consequence of COVID-19 infection. The pathophysiology and risk factors of MIS-C are still unclear, and the clinical manifestation ranges from milder forms to cases needing intensive care unit treatment. Based on available data, obesity is linked to pro-inflammatory stimulation. Moreover, several studies showed that obesity could play a role in COVID-19 severity and its comorbidities among the adult and children's populations. This study aimed to investigate the influence of overweightedness/obesity in childhood for the course of MIS-C in Poland. Methods: This study presented data from the national MultiOrgan Inflammatory Syndromes COVID-19 Related Study (MOIS-CoR) collected between 4 March 2020 and 20 February 2021. Of the 371 patients that met the Polish MIS-C criteria, 306 were included for further analysis. Results: Children who are obese (OB with body mass index (BMI) ≥95th percentile) and overweight (OV with BMI ≥85th percentile but <95th percentile) (28 and 49 patients, respectively) represented 25.1% (n=77) of all recruited patients. Complete recovery at the time of discharge presented in 93% of normal body weight (NW) participants and 90% of OV children (p>0.05). Among OB children, 76% recovered fully, which differed from the NW group (p=0.01). Calculated odds ratio (OR) of incomplete recovery for OB children was 4.2. Irrespective of body weight, there were no differences (p>0.05) in the length of hospitalization and the duration of symptoms (for OB, 13 and 16.5 days; for OV and NW, 10 and 14 days, respectively), as well as in the frequency of cardiovascular abnormalities, necessity of oxygen therapy (OB, 26.9%; OV, 23.9%; and NW, 20.7%), and intravenous immunoglobulin and glucocorticosteroid (GCS) treatment. Conclusion: The higher risk of incomplete recovery and observed tendency toward a worsening course of MIS-C in patients with obesity suggest the need for further studies to confirm and understand our findings.

Relaying Aversive Ultrasonic Alarm Calls Depends on Previous Experience. Empathy, Social Buffering, or Panic?

Ultrasonic vocalizations are among the oldest evolutionarily forms of animal communication. In order to study the communication patterns in an aversive social situation, we used a behavioral model in which one animal, the observer, is witnessing as his cagemate, the demonstrator, is experiencing a series of mild electrical foot shocks. We studied the effect of the foot shock experience on the observer and the influence of a warning sound (emitted shortly before the shock) on USV communication. These experiments revealed that such a warning seems to increase the arousal level, which differentiates the responses depending on previous experience. This can be identified by the emission of characteristic, short 22 kHz calls of a duration below 100 ms. Two rats emitted calls that overlapped in time. Analysis of these overlaps revealed that in 'warned' pairs with a naive observer, 22 kHz calls were mixed with 50 kHz calls. This fact, combined with a high fraction of very high-pitched 50 kHz calls (over 75 kHz), suggests the presence of the phenomenon of social buffering. Pure 22 kHz overlaps were mostly found in 'warned' pairs with an experienced observer, suggesting a possible fear contagion with distress sharing. The results show the importance of dividing 22 kHz calls into long and short categories.

Distinct characteristics of multisystem inflammatory syndrome in children in Poland.

During the winter months of 2020/2021 a wave of multisystem inflammatory syndrome in children (MIS-C) emerged in Poland. We present the results of a nationwide register aiming to capture and characterise MIS-C with a focus on severity determinants. The first MIS-C wave in Poland was notably high, hence our analysis involved 274 children. The group was 62.8% boys, with a median age of 8.8 years. Besides one Asian, all were White. Overall, the disease course was not as severe as in previous reports, however. Pediatric intensive care treatment was required for merely 23 (8.4%) of children, who were older and exhibited a distinguished clinical picture at hospital admission. We have also identified sex-dependent differences; teenage boys more often had cardiac involvement (decreased ejection fraction in 25.9% vs. 14.7%) and fulfilled macrophage activation syndrome definition (31.0% vs. 15.2%). Among all boys, those hospitalized in pediatric intensive care unit were significantly older (median 11.2 vs. 9.1 years). Henceforth, while ethnicity and sex may affect MIS-C phenotype, management protocols might be not universally applicable, and should rather be adjusted to the specific population.

Social deprivation substantially changes multi-structural neurotransmitter signature of social interaction: Glutamate concentration in amygdala and VTA as a key factor in social encounter-induced 50-kHz ultrasonic vocalization.

Ultrasonic vocalizations are important for coordinating social behavior in rats. Examination of the neurochemical mechanisms that govern social behavior and ultrasonic vocalization emission is crucial for understanding the social impairments that occur in many neuropsychiatric disorders. To elucidate neurochemical changes in the brain structures related to social behavior and their mutual relationships, we conducted three-phase experiment. Neurochemicals were measured in the following behavioral situations: without social encounter, with short social encounter, with long social encounter in isolated and non-isolated rats. The aims of this study were to: (1) extract the most important neurotransmitters and their metabolites that are involved in social encounter-induced emission of 50 kHz calls; (2) to elucidate mutual relationships among the neurochemical changes in the selected, six brain structures, and analyze compound relationships by step analysis; (3) create a model of all-to-all neurotransmitter correlations; (4) find the neurochemical basis of 50-kHz USVs emission during social encounter. Our behavioral and neurochemical analysis indicated that social encounter was a triggering factor of the glutamatergic neurotransmission in the ventral tegmental area (VTA), hippocampus, and amygdala; serotonergic neurotransmission in the NAcc, CPu, and amygdala; the dopaminergic neurotransmission in the caudate putamen (CPu) and hippocampus; GABAergic neurotransmission in the hippocampus and VTA. Social encounter-induced 50-kHz USVs were bound up with changes in glutamate in amygdala and VTA, glycine in the amygdala, VTA, hippocampus, nucleus accumbens and CPu, and dopamine metabolites in VTA and CPu.

Inter-individual differences in serotonin and glutamate co-transmission reflect differentiation in context-induced conditioned 50-kHz USVs response after morphine withdrawal.

A growing body of research provides compelling evidence that in rats 50-kHz USVs are a form of expression of positive emotions. Context-induced 50-kHz USVs emission is variable among rats, indicating individual differences in contextual response bound up with pharmacological reward. The aims of this study were to: extract the most important neurotransmitters related to context-induced conditioned 50-kHz USVs response; find biological basis of existing inter-individual differences in context-induced conditioned 50-kHz USVs response; create a model of all-to-all neurotransmitters correlations. The data collected here confirms that re-exposure to the context of morphine administration after the withdrawal period increases the level of 50-kHz USVs and this contextual response is associated with elevated serotonin concentrations in amygdala, hippocampus and mPFC and with increased Glu/Gln ratio in nucleus accumbens. The concentration of serotonin increases simultaneously in amygdala, nucleus accumbens and hippocampus. Moreover, 5-HT concentration in amygdala is bound up with glutamate level in this structure as well as in hippocampus. Furthermore, Glu/Gln ratio in nucleus accumbens has strong associations with Glu/Gln ratio simultaneously in VTA, amygdala, striatum and hippocampus. All-to-all-analysis indicate that concentration of glutamate in hippocampus is proportional to glutamate in VTA and GABA concentration in the hippocampus. We have also demonstrated that Glu/GABA ratio in VTA and amygdala was elevated after post withdrawal re-exposure to the pharmacological reward paired context. Presented analysis indicates a strong correlation between serotonergic and glutamatergic systems in context-induced conditioned response. The strength of this co-transmission correlates with the number of 50-kHz USVs emitted in response to morphine-paired context.

Non-parametric analysis of neurochemical effects and Arc expression in amphetamine-induced 50-kHz ultrasonic vocalization.

A number of studies have identified the importance of dopaminergic, opioid, serotonergic, noradrenergic and glutamatergic neurotransmission in amphetamine-induced "50-kHz" ultrasonic vocalizations (USVs). Amphetamine became a topic of interest for many researchers interested in USVs due to its ability to induce 50-kHz USVs. To date, it has been difficult to identify the neurotransmitters responsible for this phenomenon. The aim of this study was to determine the following: (i) concentrations of neurotransmitters in selected structures of the rat brain after re-exposure of the rats to amphetamine administration; (ii) changes in Arc in the medial prefrontal cortex, striatum, nucleus accumbens core and shell, hippocampus, amygdala and ventral tegmental area; and (iii) a biological basis for differences in 50-kHz USV emissions in response to amphetamine administration. Re-exposure to amphetamine increased 50-kHz USVs. This parameter do not correlate with distance covered by the investigated animals. An increased concentration of noradrenaline in the nucleus accumbens (NAcc) strongly correlated with the number of 50-kHz USVs. We found that NAcc noradrenaline concentrations negatively correlated with the concentration of dopamine and dopamine metabolites and positively correlated with the concentration of GABA and 5-HIAA (serotonin metabolite) in this structure. We have also identified a positive correlation between striatal 3-MT (dopamine metabolite) concentrations and Arc expression in the hippocampal DG as well as a negative correlation between the concentration of GABA in the amygdala and Arc expression in the central amygdala. Thus, the relationship between the emission of 50-kHz USVs and the neurochemical changes that occur after re-exposure to amphetamine indicates cross-talk between NA, DA, 5-HT and GABA neurotransmission in the NAcc.