Drug-resistant epilepsy: Is there an overlooked association between drug resistant epilepsies and neuropsychiatric comorbidities?

Despite the introduction of several first-in-class antiseizure medications in the last 15 years and the recent generation of new hypotheses to explain the drug-resistant phenotype in epilepsy, the proportion of patients with refractory epilepsy remains apparently unchanged. Therefore, it is essential to provide new perspectives (or, perhaps, revive old perspectives) to develop more effective therapeutic interventions. Some of the complex comorbid disorders associated with epilepsy, which present similar rates of unresponsive patients and whose refractoriness is possibly mediated by similar causes, could provide keys to implement novel therapeutic interventions.

In Silico Screening Identification of Fatty Acids and Fatty Acid Derivatives with Antiseizure Activity: In Vitro and In Vivo Validation.

High fat diets have been used as complementary treatments for seizure disorders for more than a century. Moreover, many fatty acids and derivatives, including the broad-spectrum antiseizure medication valproic acid, have been explored and used as pharmacological agents to treat epilepsy. In this work, we have explored the anticonvulsant potential of a large library of fatty acids and fatty acid derivatives, the LIPID MAPS Structure Database, using structure-based virtual screening to assess their ability to block the voltage-gated sodium channel 1.

Young Plasma Rejuvenates Blood DNA Methylation Profile, Extends Mean Lifespan, and Improves Physical Appearance in Old Rats.

There is converging evidence that young blood conveys cells, vesicles, and molecules able to revitalize function and restore organ integrity in old individuals. We assessed the effects of young plasma on the lifespan, epigenetic age, and healthspan of old female rats. Beginning at 25.

Multifaceted and Other Insect-Related Fungi.

Since Agostino Bassi first isolated the fungal pathogenic agent of the white muscardine in insects (later named in his honor), and Ilya Mechnikov cultivated as a first approach to use fungi as pest control agents, many other entomopathogenic fungi have been studied over the last two centuries [...

Changes in Immune Response during Pig Gestation with a Focus on Cytokines.

Pigs have the highest percentage of embryonic death not associated with specific diseases of all livestock species, at 20-45%. During gestation processes, a series of complex alterations can arise, including embryonic migration and elongation, maternal immunological recognition of pregnancy, and embryonic competition for implantation sites and subsequent nutrition requirements and development. Immune cells and cytokines act as mediators between other molecules in highly complex interactions between various cell types.

A Combined Ligand- and Structure-Based Virtual Screening To Identify Novel NaV1.2 Blockers: In Vitro Patch Clamp Validation and In Vivo Anticonvulsant Activity.

Epilepsy is a neurological disorder characterized by recurrent seizures that arise from abnormal electrical activity in the brain. Voltage-gated sodium channels (NaVs), responsible for the initiation and propagation of action potentials in neurons, play a critical role in the pathogenesis of epilepsy. This study sought to discover potential anticonvulsant compounds that interact with NaVs, specifically, the brain subtype hNaV1.

Computer-Aided Drug Discovery and Design: Recent Advances and Future Prospects.

Computer-aided drug discovery and design involve the use of information technologies to identify and develop, on a rational ground, chemical compounds that align a set of desired physicochemical and biological properties. In its most common form, it involves the identification and/or modification of an active scaffold (or the combination of known active scaffolds), although de novo drug design from scratch is also possible. Traditionally, the drug discovery and design processes have focused on the molecular determinants of the interactions between drug candidates and their known or intended pharmacological target(s).

Long-Term Efficacy and Safety of Paliperidone 6-Month Formulation: An Open-Label 2-Year Extension of a 1-Year Double-Blind Study in Adult Participants With Schizophrenia.

Background: Paliperidone palmitate 6-month (PP6M) demonstrated noninferiority to paliperidone palmitate 3-month in preventing relapse in patients with schizophrenia in a phase 3 double-blind (DB) study (NCT03345342). Here, we report long-term efficacy and safety results from a 2-year single-arm, open-label extension (OLE; NCT04072575) of this DB study.

Methods: Participants who completed the DB study without relapse were enrolled and followed-up every 3 months up to 2 years.

Evaluation of Whole-Cell and Acellular Pertussis Vaccines in the Context of Long-Term Herd Immunity.

After the pertussis vaccine had been introduced in the 1940s and was shown to be very successful in reducing the morbidity and mortality associated with the disease, the possibility of improving both vaccine composition and vaccination schedules has become the subject of continuous interest. As a result, we are witnessing a considerable heterogeneity in pertussis vaccination policies, which remains beyond universal consensus. Many pertussis-related deaths still occur in low- and middle-income countries; however, these deaths are attributable to gaps in vaccination coverage and limited access to healthcare in these countries, rather than to the poor efficacy of the first generation of pertussis vaccine consisting in inactivated and detoxified whole cell pathogen (wP).

Constitutive activity of the dopamine (D ) receptor, highly expressed in CA1 hippocampal neurons, selectively reduces Ca 3.2 and Ca 3.3 currents.

Background And Purpose: Ca 3.1-3 currents differentially contribute to neuronal firing patterns. Ca 3 are regulated by G protein-coupled receptors (GPCRs) activity, but information about Ca 3 as targets of the constitutive activity of GPCRs is scarce.

Prediabetes is more than a pre-disease: additional evidences supporting the importance of its early diagnosis and appropriate treatment.

Aim: To identify Prediabetes (PreD) as early and serious diabetes step using clinical-biochemical characteristics in the population of the Primary Prevention Diabetes Buenos Aires (PPDBA) study.

Methods: PPDBA Study evaluated benefits of adopting healthy lifestyles to prevent T2D. It recruited people 45-75 years of age with PreD (impaired fasting glycaemia [IFG], impaired glucose tolerance [IGT] or both, American Diabetes Association criteria), using an opportunistic approach.

Identification of New Carbonic Anhydrase VII Inhibitors by Structure-Based Virtual Screening.

Human carbonic anhydrase VII (hCA VII) constitutes a promising molecular target for the treatment of epileptic seizures and other central nervous system disorders due to its almost exclusive expression in neurons. Achieving isoform selectivity is one of the main challenges for the discovery of new hCA inhibitors, since nonspecific inhibition may lead to tolerance and side effects. In the present work, we report the development of a molecular docking protocol based on AutoDock4 for the search of new hCA VII inhibitors by virtual screening.

Effects of an intraoral device (IOD) on electromyographic activity on the masseter and temporal muscles in Class III patients.

Objective: Class III malocclusion is characterized by a loss of vertical dimension associated with muscle imbalance. The present study was designed to determine electromyographic amplitude changes in temporal (T) and masseter (M) at rest and during clenching in Class III patients treated with an intraoral device (IOD) over a 24-hour period for 30 days with transcutaneous electrical nerve stimulation (TENS).

Methods: Twelve patients with Class III (mean age 27.

Age-related loss of recognition memory and its correlation with hippocampal and perirhinal cortex changes in female Sprague Dawley rats.

Ageing is associated with impaired performance in recognition memory, a process that consists of the discrimination of familiar and novel stimuli. Previous studies have shown the impact of ageing on object recognition memories. However, the early stages of memory impairment remain unknown.

Hippocampal DNA Methylation, Epigenetic Age, and Spatial Memory Performance in Young and Old Rats.

In humans and rats, aging is associated with a progressive deterioration of spatial learning and memory. These functional alterations are correlated with morphological and molecular changes in the hippocampus. Here, we assessed age-related changes in DNA methylation (DNAm) landscape in the rat hippocampus and the correlation of spatial memory with hippocampal DNAm age in 2.

iRaPCA and SOMoC: Development and Validation of Web Applications for New Approaches for the Clustering of Small Molecules.

The clustering of small molecules implies the organization of a group of chemical structures into smaller subgroups with similar features. Clustering has important applications to sample chemical datasets or libraries in a representative manner (e.g.

Can the Introduction of Different Olive Cakes Affect the Carcass, Meat and Fat Quality of Bísaro Pork?

The present study aimed to evaluate the effect of the inclusion of different olive cakes in the diet of Bísaro pigs on the carcass, meat and fat. The carcasses of 40 animals fed a diet with five treatments (T1—Basic diet and commercial feed; T2—Basic diet + 10% crude olive cake; T3—Basic diet + 10% olive cake, two phases; T4—Basic diet + 10% exhausted olive cake; T5—Basic diet + 10% exhausted olive cake + 1% olive oil) were used to study the effect on carcass traits, physicochemical meat quality and lipid composition of meat and backfat. There were no significant differences between treatments for the conformation measurements performed, except for the length at the seventh and last rib (p < 0.

GHSR controls food deprivation-induced activation of CRF neurons of the hypothalamic paraventricular nucleus in a LEAP2-dependent manner.

Objective: Prolonged fasting is a major challenge for living organisms. An appropriate metabolic response to food deprivation requires the activation of the corticotropin-releasing factor-producing neurons of the hypothalamic paraventricular nucleus (PVH neurons), which are a part of the hypothalamic-pituitary-adrenal axis (HPA), as well as the growth hormone secretagogue receptor (GHSR) signaling, whose activity is up- or down-regulated, respectively, by the hormones ghrelin and the liver-expressed antimicrobial peptide 2 (LEAP2). Since ghrelin treatment potently up-regulates the HPA axis, we studied the role of GHSR in mediating food deprivation-induced activation of the PVH neurons in mice.

The Eco-Physiological Role of in a Changing World.

Among the bloom-forming cyanobacteria, is one of the most harmful species [...

Ghrelin treatment induces rapid and delayed increments of food intake: a heuristic model to explain ghrelin's orexigenic effects.

Ghrelin is a stomach-derived peptide hormone with salient roles in the regulation of energy balance and metabolism. Notably, ghrelin is recognized as the most powerful known circulating orexigenic hormone. Here, we systematically investigated the effects of ghrelin on energy homeostasis and found that ghrelin primarily induces a biphasic effect on food intake that has indirect consequences on energy expenditure and nutrient partitioning.

Circulating ghrelin crosses the blood-cerebrospinal fluid barrier via growth hormone secretagogue receptor dependent and independent mechanisms.

Ghrelin is a peptide hormone mainly secreted from gastrointestinal tract that acts via the growth hormone secretagogue receptor (GHSR), which is highly expressed in the brain. Strikingly, the accessibility of ghrelin to the brain seems to be limited and restricted to few brain areas. Previous studies in mice have shown that ghrelin can access the brain via the blood-cerebrospinal fluid (CSF) barrier, an interface constituted by the choroid plexus and the hypothalamic tanycytes.

LEAP2 Impairs the Capability of the Growth Hormone Secretagogue Receptor to Regulate the Dopamine 2 Receptor Signaling.

The growth hormone secretagogue receptor (GHSR) signals in response to ghrelin, but also acts via ligand-independent mechanisms that include either constitutive activation or interaction with other G protein-coupled receptors, such as the dopamine 2 receptor (D2R). A key target of GHSR in neurons is voltage-gated calcium channels type 2.2 (Ca2.

Therapeutic potential of glial cell line-derived neurotrophic factor and cell reprogramming for hippocampal-related neurological disorders.

Hippocampus serves as a pivotal role in cognitive and emotional processes, as well as in the regulation of the hypothalamus-pituitary axis. It is known to undergo mild neurodegenerative changes during normal aging and severe atrophy in Alzheimer's disease. Furthermore, dysregulation in the hippocampal function leads to epilepsy and mood disorders.

Insulin-like growth factor 1 gene transfer for sporadic Alzheimer's disease: New evidence for trophic factor mediated hippocampal neuronal and synaptic recovery-based behavior improvement.

Sporadic Alzheimer's disease (sAD) is the most prevalent neurodegenerative disorder with no cure. Patients typically suffer from cognitive impairment imprinted by irreversible neocortex and hippocampal degeneration with overt synaptic and neuron dysfunction. Insulin-like growth factor 1 (IGF1) has proven to be a potent neuroprotective molecule in animal models of age-related neurodegeneration.