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The authors report ten cases of spontaneous intracerebellar haematoma diagnosed by computed tomography. They emphasize the role of CT scanning in the management of patients with cerebellar haemorrhage, while vertebral angiography excludes the presence of vascular malformations (aneurysms or angiomas). [ABSTRACT FROM AUTHOR]

Chromogranin A (CgA), a ∼ 49 kDa acidic secretory protein, is ubiquitously distributed in endocrine and neuroendocrine cells and neurons. As a propeptide, CgA is proteolytically cleaved to generate several peptides of biological importance, including pancreastatin (PST: hCgA 250 - 301 ), Vasostatin 1 (VS1: hCgA 1-76 ), and catestatin (CST: CgA 352 - 372 ). VS1 represents the most conserved fragment of CgA. A 20 amino acid domain within VS1 (CgA 47-66) exhibits potent antimicrobial and anti-inflammatory activities. Autism is known to be associated with inflammation. Therefore, we seek to test the hypothesis that VS1 modulates autism behaviors by reducing inflammation in the hippocampus. Treatment of C57BL/6 (B6) and BTBR (a mouse model of idiopathic autism) mice with VS1 revealed the following: BTBR mice showed a significant decrease in chamber time in the presence of a stranger or a novel object. Treatment with VS1 significantly increased chamber time in both cases, underscoring a crucial role for VS1 in improving behavioral deficits in BTBR mice. In contrast to chamber time, sniffing time in BTBR mice in the presence of a stranger was less compared to B6 control mice. VS1 did not improve this latter parameter. Surprisingly, sniffing time in BTBR mice in the presence of a novel object was comparable with B6 mice. Proinflammatory cytokines such as IL-6 and IL-1b, as well as other inflammatory markers, were elevated in BTBR mice, which were dramatically reduced after supplementation with VS1. Interestingly, even Beclin-1/p62, pAKT/AKT, and p-p70-S6K/p70-S6K ratios were notably reduced by VS1. We conclude that VS1 plays a crucial role in restoring autistic spectrum disorders (ASD) plausibly by attenuating neuroinflammation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction. The highest levels of childhood overweight and obesity in Latin America correspond to Argentina; this condition increases the risk of obesity, type 2 diabetes, cardiovascular and cerebrovascular diseases, and other conditions in adulthood. More than 25% of childhood and adolescent obesity are attributable to the consumption of sugar-sweetened beverages (SSBs). Our objective was to assess the disease and financial burden of SSB consumption among children and adolescents in Río Negro, the morbidity and mortality in adulthood, and the impact of reducing sugar consumption via the implementation of Law no. 27642 on the Promotion of Healthy Eating. Population and methods. We used a mathematical simulation model with a comparative risk assessment approach in the Río Negro population aged 0 to 17 years. The burden of obesity attributable to SSB consumption in the short and long term and direct medical costs were assessed. Results. The average consumption of SSBs was 348 mL/day; the prevalence of overweight and obesity was 16.6% and 11.6%, respectively. There were over 6600 cases of overweight in children and adolescents; while in adulthood, there were over 17 500 cases of overweight, 34 deaths attributable to SSBs, 3200 cases of diabetes, and over 4230 other health events. Direct medical costs were estimated at ARS 250 000 000 attributable to SSB consumption. Conclusion. The implementation of a comprehensive policy as established by Law no. 27642 on the Promotion of Healthy Eating in Río Negro would decrease 24% of overweight cases, morbidity, mortality, and associated medical costs., (Sociedad Argentina de Pediatría.)

Psychological flexibility has recently attracted the attention of researchers in the field of sleep disorders; therefore, in the study, psychological flexibility was evaluated as a predictor or factor related to the presence/severity of insomnia. We included 2218 individuals selected from the randomized-control trial for behavioural therapy for insomnia and cross-sectional studies, including 1797 individuals with insomnia and 421 controls without insomnia. All participants completed the DSM-5-based insomnia diagnosis interview, Insomnia Severity Index, Hospital Anxiety and Depression Scale, and Acceptance Action Questionnaire-II. Linear regression and multinomial logistic regression models were used. Sex, education, occupation, marital status, anxiety, depression and psychological inflexibility were possible predictors or factors associated with the severity of insomnia. Multivariate linear regression analysis demonstrated that sex (𝛽 = 0.88; t = 2.80; p = 0.005), depression (𝛽  = 0.41; t = 10.7; p < 0.001), anxiety (𝛽  = 0.58; t = 14.1; p < 0.001) and psychological inflexibility (𝛽  = 0.09; t = 5.07; p < 0.001) were predictors of insomnia. The results of the multinomial logistic regression demonstrate that, in comparison to the absence of insomnia, insomnia at all levels (mild, moderate and severe) was associated with sex, anxiety and depression. Psychological inflexibility was only associated with severe insomnia (odds ratio = 1.04). These findings are important from a public health perspective because behavioural strategies designed to treat insomnia with a focus on psychological flexibility are low-cost and may help improve sleep quality in adults with insomnia, which also influences mental health., (© 2024 European Sleep Research Society.)

This study used intra-hippocampal injections of Kainic Acid (KA) in Wistar rats to induce spontaneous recurrent seizures (SRS) after a 9-day latent period. A post-conditioning protocol with LPS, injected at the same site 72 h after the initial KA insult, was employed to trigger secondary competing processes. To evaluate the post-conditioning effect of LPS, 25 animals were divided into four groups: SAL-SAL (n = 6), KA-SAL (n = 6), SAL-LPS (n = 7), and KA-LPS (n = 6). SRS occurrence and seizure duration were quantified through video monitoring from days 9 to 17, along with other ictal behaviors, such as tail-chasing and wet-dog-shakes. Behavioral assessments revealed that the KA-LPS group had preserved sucrose preference and intact long-term memory in the object recognition test, indicating reduced depressive-like behavior and cognitive preservation compared to the KA-SAL group. The forced swim test showed increased depressive-like behavior in the SAL-LPS group, with LPS mitigating these effects in the KA group. The marble-burying test showed no significant differences among groups. Animals were euthanized on day 26, and hippocampal slices were analyzed using fluoro-jade staining for cell death and immunofluorescence staining for Iba-1 (microglia) and GFAP (astrocyte) labeling. The results support the hypothesis that epileptogenesis involves a cascade of plastic changes in neural networks and that precise, timely interventions can potentially interfere with this process., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The consumption of a high-fat diet (HFD) represents a risk factor for diseases such as obesity, diabetes, insulin resistance (IR), and different brain disorders. HFD-induced obesity is linked with systemic and neuroinflammation implicated in the pathogenesis of metabolic impairment and epilepsy. In this study, we studied the negative effects of HFD consumption (16 weeks) on absence epilepsy and behavior comorbidities in WAG/Rij rats, a well-validated idiopathic model of absence epilepsy and comorbidities. Moreover, we investigated how, by restoring a normocaloric diet (NCD; 12 weeks), epileptic seizures and neuropsychiatric comorbidities could improve. We found that the HFD group showed a worsening of absence seizures, aggravation of depressive-like behavior, and performance in learning and memory than the NCD group even in the absence of hyperglycemia and/or obesity. In addition, intestinal villus rupture, inflammatory infiltrate, and intestinal permeability alteration increased after prolonged HFD intake, which could prevent weight gain. Inflammatory protein levels were found higher in the colon of the HFD group than in the NCD group, and also in the cortex and hippocampus, regions involved in absence seizures and behavioral alterations. After replacing HFD with NCD, a reduction in absence seizures and behavioral alterations was observed, and this decrease was well correlated with an improvement in inflammatory pathways. In conclusion, HFD consumption is sufficient to disrupt gut integrity resulting in systemic and brain inflammation contributing to the worsening of absence epilepsy and its comorbidities also without obesity development. These alterations can be improved by switching back the diet to NCD., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Chronobiology is the scientific field focused on studying periodicity in biological processes. In mammals, most physiological variables exhibit circadian rhythmicity, such as metabolism, body temperature, locomotor activity, and sleep. The biological rhythmicity can be statistically evaluated by examining the time series and extracting parameters that correlate to the period of oscillation, its amplitude, phase displacement, and overall variability., New Method: We have developed a library called CircadiPy, which encapsulates methods for chronobiological analysis and data inspection, serving as an open-access toolkit for the analysis and interpretation of chronobiological data. The package was designed to be flexible, comprehensive and scalable in order to assist research dealing with processes affected or influenced by rhythmicity., Results: The results demonstrate the toolkit's capability to guide users in analyzing chronobiological data collected from various recording sources, while also providing precise parameters related to the circadian rhythmicity., Comparison With Existing Methods: The analysis methodology from this proposed library offers an opportunity to inspect and obtain chronobiological parameters in a straightforward and cost-free manner, in contrast to commercial tools., Conclusions: Moreover, being an open-source tool, it empowers the community with the opportunity to contribute with new functions, analysis methods, and graphical visualizations given the simplified computational method of time series data analysis using an easy and comprehensive pipeline within a single Python object., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marcio Flavio Dutra Moraes reports financial support was provided by Fundação de Amparo à Pesquisa do Estado de Minas Gerais. Paula Bargi-Souza reports financial support was provided by Fundação de Amparo à Pesquisa do Estado de Minas Gerais. Joao Pedro Carvalho-Moreira reports financial support was provided by Fundação de Amparo à Pesquisa do Estado de Minas Gerais. Marcio Flavio Dutra Moraes reports financial support was provided by Lemann Brazil Research Fund. Leonardo de Oliveira Guarnieri reports financial support was provided by Fundação de Amparo à Pesquisa do Estado de Minas Gerais. Marcio Flavio Dutra Moraes reports financial support was provided by Conselho Nacional de Desenvolvimento Científico e Tecnológico. Paula Bargi-Souza reports financial support was provided by Conselho Nacional de Desenvolvimento Científico e Tecnológico. Marcio Flavio Dutra Moraes reports financial support was provided by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The treatment of psoriasis has made considerable progress with biologicals, including tumor necrosis factor inhibitors, and recently, monoclonal antibodies inhibiting directly interleukin (IL) 17, IL-23, or both IL-12/23. Newer biologicals are directed to the interleukin pathway and appear to improve complete or near-complete clearance. The newer biologicals have also been shown to have an excellent safety profile. However, despite experience with patients having confirmed the results obtained in clinical trials, there are still few data on using the newer biologicals., Methods: The present active study aimed to prospectively evaluate safety profiles and persistence of some biologicals in a multicenter pharmacovigilance study, that enrolled 733 patients treated with a biologic drug in five Calabrian hospital units. Informative and treatment persistence evaluations with predictors for suspension and occurrence of adverse events (AEs) were executed. In particular, reasons for treatment discontinuation in our program take account of primary/secondary failure or development of an AE., Results: AEs occurred in 187/733 patients and serious AEs (SAEs) were identified in 5/733 patients. An number of 182/733 patients showed a primary/secondary inefficacy. The AEs and SAEs were described with adalimumab, infliximab, and etanercept but not with abatacept, brodalumab, tildrakizumab, golinumab, ixekizumab, guselkumab, risankizumab, secukinumab, and ustekinumab., Conclusions: Our analysis, although limited by a small sample size and a short-term follow-up period, offers suitable data on commonly used biological agents and their safety, interruption rate, and the attendance of SAEs. Real-world studies should be carried out to evaluate other safety interests.

Objective: To assess the current Na levels in a variety of processed food groups and categories available in the Argentinean market to monitor compliance with the National Law and to compare the current Na content levels with the updated Pan American Health Organisation (PAHO) regional targets., Design: Observational cross-sectional study., Setting and Participants: Argentina. Data were collected during March 2022 in the city of Buenos Aires in two of the main supermarket chains. We carried out a systematic survey of pre-packaged food products available in the food supply assessing Na content as reported in nutrition information panels., Results: We surveyed 3997 food products, and the Na content of 760 and 2511 of them was compared with the maximum levels according to the Argentinean law and the regional targets, respectively. All food categories presented high variability of Na content. More than 90 % of the products included in the National Sodium Reduction Law were found to be compliant. Food groups with high median Na, such as meat and fish condiments, leavening flour and appetisers are not included in the National Law. In turn, comparisons with PAHO regional targets indicated that more than 50 % of the products were found to exceed the regional targets for Na., Conclusions: This evidence suggests that it is imperative to update the National Sodium Reduction Law based on regional public health standards, adding new food groups and setting more stringent legal targets.

Prolonged exposure to lead has been recognized as harmful to human health as it may cause neurotoxic effects including mitochondrial damage, apoptosis, excitotoxicity, and myelin formation alterations, among others. Numerous data have shown that consuming olive oil and its valuable components could reduce neurotoxicity and degenerative conditions. Olive oil is traditionally obtained from olive trees; this plant ( Olea europaea L.) is an evergreen fruit tree.In this manuscript, two extracts have been used and compared: the extract from the leaves of Olea europaea L. (OE) and the extract derived from OE but with a further sonication process (s-OE). Therefore, the objectives of this experimental work were as follows: 1) to generate an innovative extract; 2) to test both extracts on a model of neurotoxicity of human neurons induced following lead exposure; and 3) to study the mechanisms behind lead-induced neurotoxicity.The results showed that the mechanism involved in the neurotoxicity of lead included dysfunction of the cellular endoplasmic reticulum, which suffered oxidative damage. In addition, in all experiments, s-OE was more effective than OE, having greater and better effects against lead-induced damage and being dissolved in a smaller amount of EtOH, which promotes its sustainability., Competing Interests: The authors declare that they have no conflict of interest. The corresponding author declares that the manuscript was read, accepted, and submitted by all authors., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Temporal lobe epilepsy (TLE) represents the most common form of refractory focal epilepsy. The identification of innovative clinical biomarkers capable of categorizing patients with TLE, allowing for improved treatment and outcomes, still represents an unmet need. Circulating microRNAs (c-miRNAs) are short non-coding RNAs detectable in body fluids, which play crucial roles in the regulation of gene expression. Their characteristics, including extracellular stability, detectability through non-invasive methods, and responsiveness to pathological changes and/or therapeutic interventions, make them promising candidate biomarkers in various disease settings. Recent research has investigated c-miRNAs in various bodily fluids, including serum, plasma, and cerebrospinal fluid, of TLE patients. Despite some discrepancies in methodologies, cohort composition, and normalization strategies, a common dysregulated signature of c-miRNAs has emerged across different studies, providing the basis for using c-miRNAs as novel biomarkers for TLE patient management.

Growing epidemiological studies highlight a bi-directional relationship between depressive symptoms and diabetes mellitus. However, the detrimental impact of their co-existence on mental health suggests the need to treat this comorbidity as a separate entity rather than the two different pathologies. Herein, we characterized the peculiar mechanisms activated in mouse hippocampus from the concurrent development of hyperglycaemia, characterizing the different diabetes subtypes, and chronic stress, recognized as a possible factor predisposing to major depression. Our work demonstrates that kynurenine overproduction, leading to apoptosis in the hippocampus, is triggered in a different way depending on hyperglycaemia or chronic stress. Indeed, in the former, kynurenine appears produced by infiltered macrophages whereas, in the latter, peripheral kynurenine preferentially promotes resident microglia activation. In this scenario, QA, derived from kynurenine catabolism, appears a key mediator causing glutamatergic synapse dysfunction and apoptosis, thus contributing to brain atrophy. We demonstrated that the coexistence of hyperglycaemia and chronic stress worsened hippocampal damage through alternative mechanisms, such as GLUT-4 and BDNF down-expression, denoting mitochondrial dysfunction and apoptosis on one hand and evoking the compromission of neurogenesis on the other. Overall, in the degeneration of neurovascular unit, hyperglycaemia and chronic stress interacted each other as the partners of a "West Coast Swing" in which the leading role can be assumed alternatively by each partner of the dance. The comprehension of these mechanisms can open novel perspectives in the management of diabetic/depressed patients, but also in the understanding the pathogenesis of other neurodegenerative disease characterized by the compromission of hippocampal function., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Alzheimer's disease (AD) is a major global health problem today and is the most common form of dementia. AD is characterized by the formation of β-amyloid (Aβ) plaques and neurofibrillary clusters, leading to decreased brain acetylcholine levels in the brain. Another mechanism underlying the pathogenesis of AD is the abnormal phosphorylation of tau protein that accumulates at the level of neurofibrillary aggregates, and the areas most affected by this pathological process are usually the cholinergic neurons in cortical, subcortical, and hippocampal areas. These effects result in decreased cognitive function, brain atrophy, and neuronal death. Malnutrition and weight loss are the most frequent manifestations of AD, and these are also associated with greater cognitive decline. Several studies have confirmed that a balanced low-calorie diet and proper nutritional intake may be considered important factors in counteracting or slowing the progression of AD, whereas a high-fat or hypercholesterolemic diet predisposes to an increased risk of developing AD. Especially, fruits, vegetables, antioxidants, vitamins, polyunsaturated fatty acids, and micronutrients supplementation exert positive effects on aging-related changes in the brain due to their antioxidant, anti-inflammatory, and radical scavenging properties. The purpose of this review is to summarize some possible nutritional factors that may contribute to the progression or prevention of AD, understand the role that nutrition plays in the formation of Aβ plaques typical of this neurodegenerative disease, to identify some potential therapeutic strategies that may involve some natural compounds, in delaying the progression of the disease., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare. All co-authors have seen and agree with the contents of the manuscript. We certify that the submission is original work and is not under review at any other publication., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

To date, the complex pathological interactions between renal and cardiovascular systems represent a real global epidemic in both developed and developing countries. In this context, renovascular hypertension (RVH) remains among the most prevalent, but also potentially reversible, risk factor for numerous reno-cardiac diseases in humans and pets. Here, we investigated the anti-inflammatory and reno-cardiac protective effects of a polyphenol-rich fraction of bergamot (BPF) in an experimental model of hypertension induced by unilateral renal artery ligation. Adult male Wistar rats underwent unilateral renal artery ligation and treatment with deoxycorticosterone acetate (DOCA) (20 mg/kg, s.c.), twice a week for a period of 4 weeks, and 1% sodium chloride (NaCl) water (n = 10). A subgroup of hypertensive rats received BPF (100 mg/kg/day for 28 consecutive days, n = 10) by gavage. Another group of animals was treated with a sub-cutaneous injection of vehicle (that served as control, n = 8). Unilateral renal artery ligation followed by treatment with DOCA and 1% NaCl water resulted in a significant increase in mean arterial blood pressure (MAP; p< 0.05. vs CTRL) which strongly increased the resistive index (RI; p<0.05 vs CTRL) of contralateral renal artery flow and kidney volume after 4 weeks (p<0.001 vs CTRL). Renal dysfunction also led to a dysfunction of cardiac tissue strain associated with overt dyssynchrony in cardiac wall motion when compared to CTRL group, as shown by the increased time-to-peak (T2P; p<0.05) and the decreased whole peak capacity (Pk; p<0.01) in displacement and strain rate (p<0.05, respectively) in longitudinal motion. Consequently, the hearts of RAL DOCA-Salt rats showed a larger time delay between the fastest and the lowest region (Maximum Opposite Wall Delay-MOWD) when compared to CTRL group (p<0.05 in displacement and p <0.01 in strain rate). Furthermore, a significant increase in the levels of the circulating pro-inflammatory cytokines and chemokines (p< 0.05 for IL-12(40), p< 0.01 for GM-CSF, KC, IL-13, and TNF- α) and in the NGAL expression of the ligated kidney (p< 0.001) was observed compared to CTRL group. Interestingly, this pathological condition is prevented by BPF treatment. In particular, BPF treatment prevents the increase of blood pressure in RAL DOCA-Salt rats (p< 0.05) and exerts a protective effect on the volume of the contralateral kidney (p <0.01). Moreover, BPF ameliorates cardiac tissue strain dysfunction by increasing Pk in displacement (p <0.01) and reducing the T2P in strain rate motion (p<0.05). These latter effects significantly improve MOWD (p <0.05) preventing the overt dyssynchrony in cardiac wall motion. Finally, the reno-cardiac protective effect of BPF was associated with a significant reduction in serum level of some pro-inflammatory cytokines and chemokines (p<0.05 for KC and IL-12(40), p<0.01 for GM-CSF, IL-13, and TNF- α) restoring physiological levels of renal neutrophil gelatinase-associated lipocalin (NGAL, p<0.05) protein of the tethered kidney. In conclusion, the present results show, for the first time, that BPF promotes an efficient renovascular protection preventing the progression of inflammation and reno-cardiac damage. Overall, these data point to a potential clinical and veterinary role of dietary supplementation with the polyphenol-rich fraction of citrus bergamot in counteracting hypertension-induced reno-cardiac syndrome., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof. Vincenzo Mollace reports financial support was provided by Italian Ministry of Research. Prof. Vincenzo Mollace reports financial support was provided by Region of Calabria., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Introduction: Cardiovascular diseases (CVDs) are the most important cause of premature death and disability worldwide. Environmental degradation and cardiovascular diseases are two keys to health challenges, characterized by a constant evolution in an industrialized world that exploits natural resources regardless of the consequences for health. The etiological risk factors of CVDs are widely known and include dyslipidemia, obesity, diabetes, and chronic cigarette consumption. However, one component that is often underestimated is exposure to heavy metals. The biological perspective explains that different metals play different roles. They are therefore classified into essential heavy metals, which are present in organisms where they perform important vital functions, especially in various physiological processes, or non-essential heavy metals, with a no biological role but, nonetheless, remain in the environment in which they are absorbed. Although both types of metal ions are many times chemically similar and can bind to the same biological ligands, the attention given today to nonessential metals in several eukaryotic species is starting to raise strong concerns due to an exponential increase in their concentrations. The aim of this systematic review was to assess possible correlations between exposure to nonessential heavy metals and increased incidence of cardiovascular disease, reporting the results of studies published in the last 5 years through March 2023., Methods: The studies includes reviews retrieved from PubMed, Medline, Embase, and Web of Science databases, in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement and following the PICO (Population Intervention Comparison Outcome Population) framework., Results: Eight reviews, including a total of 153 studies, were identified. Seven of these review enlighted the association between CVDs and non-essential heavy metals chronic exposure., Discussion: It is evident that exposure to heavy metals represent a risk factor for CVDs onset. However, further studies are needed to better understand the effects caused by these metals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Nucera, Serra, Caminiti, Ruga, Passacatini, Macrì, Scarano, Maiuolo, Bulotta, Mollace, Bosco, Guarnieri, Oppedisano, Ilari, Muscoli, Palma and Mollace.)

Clinical studies documented that cenobamate (CNB) has a marked efficacy compared to other antiseizure medications (ASMs) in reducing focal seizures. To date, different aspects of CNB need to be clarified, including its efficacy against generalized seizures. Similarly, the pattern of drug-drug interactions between CNB and other ASMs also compels further investigation. This study aimed to detect the role of CNB on generalized seizures using the DBA/2 mouse model. We have also studied the effects of an adjunctive CNB treatment on the antiseizure properties of some ASMs against reflex seizures. The effects of this adjunctive treatment on motor performance, body temperature, and brain levels of ASMs were also evaluated. CNB was able to antagonize seizures in DBA/2 mice. CNB, at 5 mg/kg, enhanced the antiseizure activity of ASMs, such as diazepam, clobazam, levetiracetam, perampanel, phenobarbital, topiramate, and valproate. No synergistic effects were observed when CNB was co-administered with some Na + channel blockers. The increase in antiseizure activity was associated with a comparable intensification in motor impairment; however, the therapeutic index of combined treatment of ASMs with CNB was more favorable than the combination with vehicle except for carbamazepine, phenytoin, and oxcarbazepine. Since CNB did not significantly influence the brain levels of the ASMs studied, we suggest that pharmacokinetic interactions seem not probable. Overall, this study shows the ability of CNB to counteract generalized reflex seizures in mice. Moreover, our data documented an evident synergistic antiseizure effect for the combination of CNB with ASMs including phenobarbital, benzodiazepines, valproate, perampanel, topiramate, and levetiracetam., Competing Interests: Declaration of competing interest Every author declare that no financial support or compensation has been received from any individual or corporate entity for research or professional service and there are no personal financial holdings that could be perceived as constituting a potential conflict of interest. Ethical guidelines were followed for animal experimentation. The contents of the manuscript have not been previously published elsewhere neither are under submission., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Chronic consumption of hyperpalatable and hypercaloric foods has been pointed out as a factor associated with cognitive decline and memory impairment in obesity. In this context, the integration between peripheral and central inflammation may play a significant role in the negative effects of an obesogenic environment on memory. However, little is known about how obesity-related peripheral inflammation affects specific neurotransmission systems involved with memory regulation. Here, we test the hypothesis that chronic exposure to a highly palatable diet may cause neuroinflammation, glutamatergic dysfunction, and memory impairment. For that, we exposed C57BL/6J mice to a high sugar and butter diet (HSB) for 12 weeks, and we investigated its effects on behavior, glial reactivity, blood-brain barrier permeability, pro-inflammatory features, glutamatergic alterations, plasticity, and fractalkine-CX3CR1 axis. Our results revealed that HSB diet induced a decrease in memory reconsolidation and extinction, as well as an increase in hippocampal glutamate levels. Although our data indicated a peripheral pro-inflammatory profile, we did not observe hippocampal neuroinflammatory features. Furthermore, we also observed that the HSB diet increased hippocampal fractalkine levels, a key chemokine associated with neuroprotection and inflammatory regulation. Then, we hypothesized that the elevation on glutamate levels may saturate synaptic communication, partially limiting plasticity, whereas fractalkine levels increase as a strategy to decrease glutamatergic damage., (© 2023. Springer Nature Limited.)

Salvia rosmarinus Spenn. is a native Mediterranean shrub belonging to the Lamiaceae family and is well-known as a flavoring and spicing agent. In addition to its classical use, it has drawn attention because its biological activities, due particularly to the presence of polyphenols, including carnosic acid and rosmarinic acid, and phenolic diterpenes as carnosol. In this study, the aerial part of rosemary was extracted with a hydroalcoholic solution through maceration, followed by ultrasound sonication, to obtain a terpenoids-rich Salvia rosmarinus extract (TR Sr E) and a polyphenols-rich Salvia rosmarinus extract (PR Sr E). After phytochemical characterization, both extracts were investigated for their antioxidant activity through a classical assay and with electron paramagnetic resonance (EPR) for their DPPH and hydroxyl radicals scavenging. Finally, their potential beneficial effects to reduce lipid accumulation in an in vitro model of NAFLD were evaluated.

Epilepsy is a chronic neurological disease characterized by abnormal brain activity, which results in repeated spontaneous seizures. Sudden unexpected death in epilepsy (SUDEP) is the leading cause of seizure-related premature death, particularly in drug-resistant epilepsy patients. The etiology of SUDEP is a structural injury to the brain that is not fully understood, but it is frequently associated with poorly controlled and repeated generalized tonic-clonic seizures (GTCSs) that cause cardiorespiratory and autonomic dysfunctions, indicating the involvement of the brainstem. Both respiratory and cardiac abnormalities have been observed in SUDEP, but not much progress has been made in their prevention. Owing to the complexity of SUDEP, experimental animal models have been used to investigate cardiac and/or respiratory dysregulation due to or associated with epileptic seizures that may contribute to death in humans. Numerous rodent models, especially mouse models, have been developed to better understand epilepsy and SUDEP physiopathology. This review synthesizes the current knowledge about dilute brown agouti coat color (DBA/2) mice as a possible SUDEP model because respiratory arrest (RA) and sudden death induced by audiogenic generalized seizures (AGSs) have been observed in these animals. Respiratory/cardiac dysfunction, brainstem arousal system dysfunction, and alteration of the neurotransmitter systems, which are observed in human SUDEP, have also been observed in these mice. In particular, serotonin (5-HT) alteration and adenosine neurotransmission appear to contribute to not only the pathophysiological mechanisms of medication but also seizure-related respiratory dysfunctions in this animal model. These neurotransmitter systems could be the relevant targets for medication development for chronic epilepsy and SUDEP prevention. We reviewed data on AGSs in DBA/2 mice and the relevance of this model of generalized tonic-clonic epilepsy to human SUDEP. Furthermore, the advantages of using this strain prone to AGSs for the identification of possible new therapeutic targets and treatment options have also been assessed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bosco, Guarnieri, Leo, Tallarico, Gallelli, Rania, Citraro and De Sarro.)

Alzheimer's disease (AD) and epilepsy are common neurological disorders in the elderly. A bi-directional link between these neurological diseases has been reported, with patients with either condition carrying almost a two-fold risk of contracting the other compared to healthy subjects. AD/epilepsy adversely affects patients' quality of life and represents a severe public health problem. Thus, identifying the relationship between epilepsy and AD represents an ongoing challenge and continuing need. Seizures in AD patients are often unrecognized because they are often nonconvulsive and sometimes mimic some behavioral symptoms of AD. Regarding this, it has been hypothesized that epileptogenesis and neurodegeneration share common underlying mechanisms. Targeted treatment to decrease epileptiform activity could represent a valuable strategy for delaying the neurodegenerative process and related cognitive impairment. Several preclinical studies have shown that some antiseizure medications (ASMs) targeting abnormal network hyperexcitability may change the natural progression of AD. However, to date, no guidelines are available for managing seizures in AD patients because of the paucity of randomized clinical trials sufficient for answering the correlated questions. Future AD clinical studies are mandatory to update clinicians about the symptomatic treatment of seizures in AD patients and recognize whether ASM therapy could change the natural progression of the disease, thereby rescuing cognitive performance.

Neurodegenerative diseases (NDs) affect millions of people worldwide, and to date, Alzheimer's and Parkinson's diseases are the most common NDs. Of the many risk factors for neurodegeneration, the aging process has the most significant impact, to the extent that it is tempting to consider neurodegenerative disease as a manifestation of accelerated aging. However, genetic and environmental factors determine the course of neurodegenerative disease progression. It has been proposed that environmental stimuli influence neuroplasticity. Some clinical studies have shown that healthy lifestyles and the administration of nutraceuticals containing bioactive molecules possessing antioxidant and anti-inflammatory properties have a preventive impact or mitigate symptoms in previously diagnosed patients. Despite ongoing research efforts, the therapies currently used for the treatment of NDs provide only marginal therapeutic benefits; therefore, the focus is now directly on the search for natural products that could be valuable tools in combating these diseases, including the natural compound Andrographis paniculata (Ap) and its main constituent, andrographolide (Andro). Preclinical studies have shown that the aqueous extract of Ap can modulate neuroinflammatory and neurodegenerative responses, reducing inflammatory markers and oxidative stress in various NDs. Therefore, in this review, we will focus on the molecular mechanisms by which Ap and Andro can modulate the processes of neurodegeneration and neuroinflammation, which are significant causes of neuronal death and cognitive decline.

Background: Riluzole (RLZ) has demonstrated neuroprotective effects in several neurological disorders. These neuroprotective effects seem to be mainly due to its ability to inhibit the excitatory glutamatergic neurotransmission, acting on different targets located both at the presynaptic and postsynaptic levels., Methods: In the present study, we evaluated the effects of Riluzole (RLZ) against limbic seizures, induced by AMPA, kainate, and NMDA receptor agonists in Sprague-Dawley rats, and in a well-validated genetic model of absence epilepsy, the WAG/Rij rat. Furthermore, in this latter model, we also studied the effect of RLZ in co-administration with the competitive NMDA receptor antagonist, CPP, or the non-competitive AMPA receptor antagonist, THIQ-10c, on spike-wave discharges (SWDs) in WAG/Rij rats, to understand the potential involvement of AMPA and NMDA receptors in the anti-absence effect of RLZ., Results: In Sprague-Dawley rats, RLZ pretreatment significantly reduced the limbic seizure severity induced by glutamatergic agonists, suggesting an antagonism of RLZ mainly on NMDA rather than non-NMDA receptors. RLZ also reduced SWD parameters in WAG/Rij rats. Interestingly, the co-administration of RLZ with CPP did not increase the anti-absence activity of RLZ in this model, advocating a competitive effect on the NMDA receptor. In contrast, the co-administration of RLZ with THIQ-10c induced an additive effect against absence seizure in WAG/Rij rats., Conclusions: these results suggest that the antiepileptic effects of RLZ, in both seizure models, can be mainly due to the antagonism of the NMDA glutamatergic receptors.

Social cues are valuable sensorial stimuli to the acquisition and retrieval of contextual memories. Here, we asked whether the valence of social cues would impact the formation of contextual memories. Adult male C57/BL6 mice were exposed to either conditioned place preference (CPP) or avoidance (CPA). As positive stimuli we used social interaction with a female (IF), while interaction with a male CD1 mice (IM) was used as negative stimulus. Contextual memory was tested 24 h and 7 days after conditioning. Aggressive behavior of CD1, as well as interaction with the female were quantified along the conditioning sessions. IM, but not IF, was salient enough to induce contextual memory estimated by the difference between the time in the conditioned context during test and habituation. Next, we chose two odors with innate behavioral responses and opposite valence to narrow down the sociability to one of its sensorial sources of information - the olfaction. We used urine from females in proestrus (U) and 2,4,5-trimethyl thiazoline (TMT), a predator odor. TMT decreased and U increased the time in the conditioned context during the test performed 24 h and 7 days after conditioning. Taken together, our results suggest that contextual memories conditioned to social encounters are difficult to stablish in mice, specially the one with positive valence. On the other hand, using odors with ecological relevance is a promising strategy to study long-term contextual memories with opposite valences. Ultimately, the behavioral protocol proposed here offers the advantage of studying contextual memories with opposite valences using unconditioned stimulus from the same sensorial category such as olfaction., (Copyright © 2023 Elsevier B.V. All rights reserved.)

A balanced diet, rich in fruits and vegetables and ensuring the intake of natural products, has been shown to reduce or prevent the occurrence of many chronic diseases. However, the choice to consume large quantities of fruits and vegetables leads to an increase in the amount of waste, which can cause an alteration in environmental sustainability. To date, the concept of a "byproduct" has evolved, now being understood as a waste product from which it is still possible obtain useful compounds. Byproducts in the agricultural sector are a rich source of bioactive compounds, capable of possessing a second life, decreasing the amount of waste products, the disposal costs, and environmental pollution. A promising and well-known citrus of the Mediterranean diet is the bergamot ( Citrus bergamia , Risso et Poiteau). The composition of bergamot is known, and the rich presence of phenolic compounds and essential oils has justified the countless beneficial properties found, including anti-inflammatory, antioxidant, anti-cholesterolemic, and protective activity for the immune system, heart failure, and coronary heart diseases. The industrial processing of bergamot fruits leads to the formation of bergamot juice and bergamot oil. The solid residues, referred to as "pastazzo", are normally used as feed for livestock or pectin production. The fiber of bergamot (BF) can be obtained from pastazzo and could exert an interesting effect thanks to its content of polyphenols. The aims of this work were twofold: (a) to have more information (composition, polyphenol and flavonoid content, antioxidant activity, etc.) on BF powder and (b) to verify the effects of BF on an in vitro model of neurotoxicity induced by treatment with amyloid beta protein (Aβ). In particular, a study of cell lines was carried out on both neurons and oligodendrocytes, to measure the involvement of the glia and compare it with that of the neurons. The results obtained showed that BF powder contains polyphenols and flavonoids and that it is able to exercise an antioxidant property. Moreover, BF exerts a protective action on the damage induced by treatment with Aβ, and this defense is found in experiments on the cell viability, on the accumulation of reactive oxygen species, on the involvement of the expression of caspase-3, and on necrotic or apoptotic death. In all these results, oligodendrocytes were always more sensitive and fragile than neurons. Further experiments are needed, and if this trend is confirmed, BF could be used in AD; at the same time, it could help to avoid the accumulation of waste products.

Background: Sleep problems are known to compound the negative effects of other health issues, such as eating disorders and the associated behavior of binge eating. Previous studies suggested associations between binge eating and sleep problems, but the strength of the relationship is unknown., Methods: We conducted a systematic review with meta-analyses examining the relationship between binge eating and sleep parameters. We searched for studies in Scopus, PubMed, and PsycInfo. The quality of evidence, including risk of bias, was assessed with adaptations of the Newcastle-Ottawa Scale and the Joanna Briggs Institute Critical Appraisal Checklist for Quasi-Experimental Studies, depending on study design. Data was synthesized as the difference in sleep between people who did or did not have binge eating., Results: Thirty-one reports of studies met our eligibility criteria. Results are presented in 12 meta-analyses. In the 7 reports of studies (with 4448 participants) that assessed poor overall sleep quality, we found poorer overall sleep quality in people with binge eating compared to people without binge eating, with a standardized mean difference of 0.77 (95% confidence interval [CI] 0.61-0.92; P < 0.001), which is a large effect size. In addition, we found evidence that people with binge eating had significantly greater hypersomnia/daytime sleepiness (7 reports of studies with 4370 participants), insomnia (5 reports of studies with 12,733 participants), and difficulty falling asleep (3 reports of studies with 4089 participants) compared to people without binge eating, with moderate effect sizes (standardized mean differences of 0.57-0.66)., Conclusions: People with binge eating exhibit poorer overall sleep quality compared to people without binge eating, and may also exhibit greater hypersomnia/daytime sleepiness, insomnia, and difficulty falling asleep. It is recommended that healthcare professionals routinely screen for poor overall sleep quality when treating people with binge eating-and address sleep difficulties when present., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Skeletal muscle atrophy is a condition characterized by a loss of muscle mass and muscle strength caused by an imbalance between protein synthesis and protein degradation. Muscle atrophy is often associated with a loss of bone mass manifesting as osteoporosis. The aim of this study was to evaluate if chronic constriction injury (CCI) of the sciatic nerve in rats can be a valid model to study muscle atrophy and consequent osteoporosis. Body weight and body composition were assessed weekly. Magnetic resonance imaging (MRI) was performed on day zero before ligation and day 28 before sacrifice. Catabolic markers were assessed via Western blot and Quantitative Real-time PCR. After the sacrifice, a morphological analysis of the gastrocnemius muscle and Micro-Computed Tomography (Micro-CT) on the tibia bone were performed. Rats that underwent CCI had a lower body weight increase on day 28 compared to the naive group of rats ( p < 0.001). Increases in lean body mass and fat mass were also significantly lower in the CCI group ( p < 0.001). The weight of skeletal muscles was found to be significantly lower in the ipsilateral hindlimb compared to that of contralateral muscles; furthermore, the cross-sectional area of muscle fibers decreased significantly in the ipsilateral gastrocnemius. The CCI of the sciatic nerve induced a statistically significant increase in autophagic and UPS (Ubiquitin Proteasome System) markers and a statistically significant increase in Pax-7 (Paired Box-7) expression. Micro-CT showed a statistically significant decrease in the bone parameters of the ipsilateral tibial bone. Chronic nerve constriction appeared to be a valid model for inducing the condition of muscle atrophy, also causing changes in bone microstructure and leading to osteoporosis. Therefore, sciatic nerve constriction could be a valid approach to study muscle-bone crosstalk and to identify new strategies to prevent osteosarcopenia., Competing Interests: The authors have no conflicts of interest to declare. All co-authors have seen and agreed with the contents of the manuscript. We certify that this submission is an original work and is not under review at any other publication.

Eye health is crucial, and the onset of diseases can reduce vision and affect the quality of life of patients. The main causes of progressive and irreversible vision loss include various pathologies, such as cataracts, ocular atrophy, corneal opacity, age-related macular degeneration, uncorrected refractive error, posterior capsular opacification, uveitis, glaucoma, diabetic retinopathy, retinal detachment, undetermined disease and other disorders involving oxidative stress and inflammation. The eyes are constantly exposed to the external environment and, for this reason, must be protected from damage from the outside. Many drugs, including cortisonics and antinflammatory drugs have widely been used to counteract eye disorders. However, recent advances have been obtained via supplementation with natural antioxidants and nutraceuticals for patients. In particular, evidence has accumulated that polyphenols (mostly deriving from Citrus Bergamia) represent a reliable source of antioxidants able to counteract oxidative stress accompanying early stages of eye diseases. Luteolin in particular has been found to protect photoreceptors, thereby improving vision in many disease states. Moreover, a consistent anti-inflammatory response was found to occur when curcumin is used alone or in combination with other nutraceuticals. Additionally, Coenzyme Q10 has been demonstrated to produce a consistent effect in reducing ocular pressure, thereby leading to protection in patients undergoing glaucoma. Finally, both grape seed extract, rich in anthocyanosides, and polynsatured fatty acids seem to contribute to the prevention of retinal disorders. Thus, a combination of nutraceuticals and antioxidants may represent the right solution for a multi-action activity in eye protection, in association with current drug therapies, and this will be of potential interest in early stages of eye disorders.

Objectives: To identify the front-of-package scheme-Multiple Traffic Light (MTL), Nutri-Score (NS), and black octagon Warning System (WS)-most effective in reducing purchase intention and perceived product healthfulness of drinking yogurts, cookies and cheese spreads, and to assess the joint influence of nutrient claims on the effects., Methods: Randomized-controlled experiment. A within-subjects factorial design was used to evaluate the influence of three independent factors on perceived product healthfulness and purchase intention. A total of 704 adults in Argentina were shown three mock-up products and asked to indicate which product they would buy choosing between pairs of products from different categories and to rate product healthfulness on a 7-point Likert scale., Results: The WS was the most effective in reducing purchase intention in drinking yogurts (OR:0.16, 95%CI: 0.09;0.28), cookies (OR:0.10, 95%CI: 0.05;0.18) and cheese spreads (OR:0.10, 95%CI: 0.05;0.18), and the perception of healthfulness (WS Mean score 3,63 vs No label 4,24, p<0.001), regardless of the participants' gender, age, and level of education. NS was inefficacious in reducing product healthfulness perception, while MTL had significantly increased how healthful the product was perceived (p<0.001). Nutrient claims increased purchase intention and perception of healthfulness, thus reducing the effectiveness of front-of-package labels (p<0.001)., Conclusions: In line with growing evidence, our findings support that WS perform better than NS and MTL in reducing purchase intention and healthfulness perception of products with excessive amounts of critical nutrients associated with the greatest burden of diseases. Front-of-package WS are expected to facilitate the population in Argentina to make healthier decisions.

Diabetes is a complex chronic disease, and among the affected patients, cardiovascular disease (CVD)is the most common cause of death. Consequently, the evidence for the cardiovascular benefit of glycaemic control may reduce long-term CVD rates. Over the years, multiple pharmacological approaches aimed at controlling blood glucose levels were unable to significantly reduce diabetes-related cardiovascular events. In this view, a therapeutic strategy combining SGLT2 inhibitors and plant extracts might represent a promising solution. Indeed, countering the main cardiometabolic risk factor using plant extracts could potentiate the cardioprotective action of SGLT2 inhibitors. This review highlights the main molecular mechanisms underlying these beneficial effects that could contribute to the better management of diabetic patients.

Ferula communis L. ( F. communis ) belongs to the Apiaceae family and is a herbaceous plant with various pharmaceutical properties, due to the different contents of bioactive compounds extracted mainly from its roots, as well as its leaves and rhizome. To date, this plant extract has demonstrated estrogenic, anti-inflammatory, antiproliferative, cytotoxic, antimicrobial and anti-neoplastic properties. Its estrogenic activity is justified by the presence of ferutinin, an ester of a sesquiterpenic alcohol that acts as an agonist for estrogen receptors, with a chemical formula equal to C 22 H 3 O 4 . The component present in F. communis responsible for the toxicity of the plant is ferulenol, a prenylated coumarin with the chemical formula C 24 H 30 O 3 . This compound is capable of inducing mortality via its strong anti-coagulant properties, leading to a lethal hemorrhagic syndrome, ferulosis, in animals that feed on a chemotype of F. communis containing a high amount of ferulenol. The removal of the component ferulenol makes extracts of Ferula non-toxic. In fact, the remaining prenylated coumarins are not present in concentrations sufficient to induce toxicity. The intake of high concentrations of the extract of this plant leads a double dose-dependent effect that is typical of sesquiterpenes such as ferutinin. Here, we assessed the cytotoxicity and the estrogenic properties of the F. communis phytocomplex obtained through extraction using a mixture of acetone and water. Among the active constituents of F. communis , the identification of ferutinin and ferulenol was performed using HPLC. The effects of the extract were evaluated, following the removal of ferulenol, on three cell lines: human breast cancer MCF-7, human cervical cancer HeLa and human osteoblastic sarcoma Saos-2. The choice of these cell lines was justified by the need to mimic certain processes which may occur in vivo and which are estrogen-dependent. The obtained results demonstrated that F. communis extract, in addition to possessing an estrogenic-like property, showed a dose-dependent effect. Low concentrations (0.1-0.8 μM) demonstrated a hyperproliferative effect, whereas higher concentrations (1.6-50 μM) were toxic. Therefore, this extract could be an excellent candidate to make up for a reduction or lack of estrogen., Competing Interests: The authors declare no conflicts of interest.