[Advances and guidance in the treatment of drug-resistant epilepsy: a review by the Andalusian Epilepsy Society of the new drugs cenobamate, fenfluramine and cannabidiol]. / Avances y orientaciones en el tratamiento de la epilepsia farmacorresistente: revisión de los nuevos fármacos cenobamato, fenfluramina y cannabidiol por la Sociedad Andaluza de Epilepsia.

This review, conducted by the Andalusian Epilepsy Society, provides an update on recent advances in the treatment of drug-resistant epilepsy, focusing on three new anti-seizure drugs: cenobamate, fenfluramine and cannabidiol. These emerging drugs offer new therapeutic alternatives for patients with drug-resistant focal epilepsy, Dravet syndrome, and Lennox-Gastaut syndrome. The primary objective of this review is to provide healthcare professionals with an up-to-date overview of the efficacy, safety and potential clinical applications of these treatments, backed by the latest evidence. In addition to reviewing the available clinical evidence, the document addresses essential practical considerations for the implementation of these drugs in routine clinical practice, including aspects such as their dosage, drug interactions, and management of their side-effects. With this review, the Andalusian Epilepsy Society aims to contribute to improving the care for and quality of life of patients with drug-resistant epilepsy and their families.

TITLE: Avances y orientaciones en el tratamiento de la epilepsia farmacorresistente: revisión de los nuevos fármacos cenobamato, fenfluramina y cannabidiol por la Sociedad Andaluza de Epilepsia.Esta revisión, realizada por la Sociedad Andaluza de Epilepsia, proporciona una actualización sobre los avances recientes en el tratamiento de la epilepsia farmacorresistente y se enfoca en tres nuevos medicamentos anticrisis: cenobamato, fenfluramina y cannabidiol. Estos fármacos emergentes ofrecen nuevas opciones terapéuticas para pacientes con epilepsia focal farmacorresistente y síndromes como el de Dravet y el de Lennox-Gastaut. El objetivo principal de esta revisión es brindar a los profesionales de la salud un panorama actualizado sobre la eficacia, la seguridad y las posibles aplicaciones clínicas de estos tratamientos, respaldado por la evidencia más reciente. Además de revisar la evidencia clínica disponible, el documento aborda consideraciones prácticas esenciales para la implementación de estos fármacos en la práctica clínica diaria, incluyendo aspectos como la posología, la identificación de interacciones farmacológicas y la gestión de efectos secundarios. A través de esta revisión, la Sociedad Andaluza de Epilepsia trata de contribuir a mejorar la atención y la calidad de vida de los pacientes con epilepsia farmacorresistente y sus familias.

Direct and deferred sediment-transport events and seafloor disturbance induced by trawling in submarine canyons.

Bottom trawling on marine environments can drastically modify seafloor geomorphology and sedimentary dynamics not only on the fishing grounds but also in adjacent downslope regions, particularly in submarine canyons environments, which are hotspots of benthic biomass and productivity in the deep sea. When this type of fishery occurs along submarine canyon flanks, it can induce sediment gravity flows that descend along tributary gullies towards the main canyon axis. However, these flows had only been clearly identified in the Palamós Canyon, where they could be recorded synchronously with the passage of the trawling fleet. In this study we also recorded trawl-induced sediment gravity flows in the Blanes Canyon, both synchronously and asynchronously with the passage of trawlers. Increases in particulate matter fluxes in other trawled submarine canyons occurring in absence of natural triggering mechanisms, were not directly associated with bottom trawling because of the lack of direct synchronicity of these events with this human activity. Here we show, however, that the practice of bottom trawling along canyon flanks can not only resuspend and directly trigger sediment gravity flows, but they can also pile up disturbed sediment on steep areas, which can become unstable and collapse afterwards, asynchronically with the passage of trawlers. Our study provides evidence that sediment gravity flows in submarine canyons affected by bottom trawling, where the causal mechanisms are presently unidentified, may potentially be linked to instabilities in sediment originating from recurrent bottom trawling, which can precondition these events.

Long-Term Treatment with Alcaligenes faecalis A12C Improves Host Resistance to Pathogens in Septic Rats: Possible Contribution of Curdlan-Like Immune Trainer.

Curdlan, a ß-1,3/1,6-glucan found in Alcaligenes faecalis (A. faecalis) wall, activates innate and humoral immunity. The aim of this study is to evaluate whether pretreated rats with A. faecalis A12C could prevent sepsis disturbances and identify the immunomodulatory mechanisms involved. Experiments occurred in two stages: a survival study with 16 rats randomly divided into septic (SC) (n = 8) and septic pretreated (SA) (n = 8) groups and 45 rats divided into four groups: healthy (AGUSAN) (n = 9), septic (AGUIC) (n = 13), septic pretreated (AGUIA) (n = 14), and healthy pretreated (AGUSTO) (n = 9). Sepsis was induced by cecal ligation and puncture after 30 days of A. faecalis A12C pretreatment or without. SA group had a higher survival rate of 58% vs. 16% for SC group (P < 0.05). Overall, AGUIA showed better status than AGUIC (P < 0.01). Higher monocytosis was found in AGUIA and AGUSTO vs. AGUIC and AGUSAN, respectively (P < 0.05). A gradual increase in curdlan fecal concentration was observed in AGUIA during pretreatment. Fecal concentrations of Escherichia coli significantly decreased in AGUIA and AGUSTO. Bacterial load in urine, peritoneal lavage fluid (PLF), and bronchoalveolar lavage fluid (BALF) decreased (P < 0.05) in AGUIA vs. AGUIC. Finally, lower inflammation was observed in serum, BALF, and PLF, with reduced IL-6, IL-10, IL-1ß, and TNF-α, along with less damage in lungs and peritoneum in AGUIA vs. AGUIC. These findings suggest the connection between curdlan-produced by A. faecalis A12C-with the immune system and the reduction in severity of experimental sepsis.

Relationship between iron deficiency and expression of genes involved in iron metabolism in human myocardium and skeletal muscle.

BACKGROUND: Iron deficiency (ID) is associated with adverse prognosis in patients with heart failure. This study aims to investigate the relationship between ID and expression of genes involved in iron metabolism in human myocardium and skeletal muscle, focusing on Transferrin 1 receptor (TfR1), the main pathway of cellular iron uptake. METHODS: Patients undergoing elective CABG were assessed prior to surgery with echocardiography and serum iron parameters. Core needle biopsies were collected from the left and right ventricle (LV, RV), the right atrium and intercostal skeletal muscle (SM). Gene expression analyses were done by mRNA sequencing. RESULTS: Of 69 patients (median age 69 years, 91% men), 28% had ID. 26% had HFrEF, 25% had HFpEF physiology according to echocardiographic findings and NT-proBNP levels, and 49% had normal LV function. The expression of TfR1 was increased in patients with ID compared to patients without ID in ventricular tissue (p = 0.04) and in intercostal SM (p = 0.01). The increase in TfR1 expression in LV and RV was more pronounced when analysing patients with absolute ID (S-Ferritin<100 µg/L). Analysing the correlation between various iron parameters, S-Ferritin levels showed the strongest correlation with TfR1 expression. There was no correlation with NT-proBNP levels and no difference in TfR1 expression between different HF phenotypes. CONCLUSIONS: In patients undergoing elective CABG we found an association between ID and increased TfR1 expression in myocardium regardless of LV function, indicating physiologically upregulated TfR1 expression in the presence of ID to restore intracellular iron needs. CLINICAL TRIAL REGISTRATION: Clinicaltrials.govNCT03671122.

Basophil activation test as alternative method to CAP-inhibition in patients with double sensitization to vespid venoms.

Most patients with Hymenoptera venom allergy (HVA) to vespid venoms present double sensitization by specific IgE (sIgE)-mediated cross-reactivity. Thus, it is mandatory could discriminate between a true double and primary sensitization to implement an accurate venom-specific immunotherapy (VIT). To date, CAP-inhibition is the reference method in the diagnosis of cross-reactivity in double sensitized patients to vespid venoms, being the results obtained with the component resolved diagnostics (CRD) conflicting. For this, we have studied in a cohort of double sensitized patients to Vespula vulgaris (VV) and Polistes dominulus (PD) venoms (n = 40) the diagnostic accuracy of CRD using the CAP-inhibition as reference method, as well as to investigate whether basophil activation test (BAT) is an alternative method for inconclusive results obtained by CAP-inhibition. CAP-inhibition showed a sensitivity of 59.46 % in view of the indeterminate results; most patients had true double sensitization (54.5 %), followed by single sensitization to PD (27.27 %) and VV (18.18 %) venoms. CRD based on rVes v 5/rPol d 5 (or vice versa) ratio as well as whole extracts I3/I77 (or vice versa) ratio (specific IgE-I3 to VV/specific IgE-I77 to PD) showed a low diagnostic accuracy (AUC = 0.504, p = 0.974; AUC = 0.35, p = 0.235; respectively). BAT was determined in parallel with CAP-inhibition in 12 patients, presented higher sensitivity than CAP-inhibition (p = 0.021) and a positive agreement of 71.43 %. Likewise it was able to identify 100% of inconclusive results, showing a specificity of 83.3 %. Therefore, CRD is not a suitable method to distinguish monosensitization and BAT appears to be an appropriate method resolving indeterminate results from the gold standard method.

Interaction Control and Bright Solitons in Coherently Coupled Bose-Einstein Condensates.

We demonstrate fast control of the interatomic interactions in a Bose-Einstein condensate by coherently coupling two atomic states with intra- and interstate scattering lengths of opposite signs. We measure the elastic and inelastic scattering properties of the system and find good agreement with a theoretical model describing the interactions between dressed states. In the attractive regime, we observe the formation of bright solitons formed by dressed-state atoms. Finally, we study the response of the system to an interaction quench from repulsive to attractive values, and observe how the resulting modulational instability develops into a bright soliton train.

Genomic landscape and immune-related gene expression profiling of epithelial ovarian cancer after neoadjuvant chemotherapy.

Platinum-based neoadjuvant chemotherapy followed by interval debulking surgery is an accepted treatment for patients with stage III or IV epithelial ovarian cancer who are not suitable for primary debulking surgery. The identification of suitable adjuvant treatments in these patients is an unmet need. Here, we explore potential genomic characteristics (mutational and immune-associated expression profiles) in a series of patients undergoing neoadjuvant chemotherapy. Tumor samples from biopsy and interval debulking surgery were analyzed for mutational landscape and immune profiling, together with detailed immunohistochemistry using different immune cell markers, and correlated with clinicopathological characteristics and potential response to neoadjuvant chemotherapy. No major differences in the mutational landscape were observed in paired biopsy and surgery samples. Genomic loss of heterozygosity was found to be higher in patients with total/near-total tumor response. The immune gene expression profile after neoadjuvant chemotherapy revealed activation of several immune regulation-related pathways in patients with no/minimal or partial response. In parallel, neoadjuvant therapy caused a significant increase of tumor-infiltrating lymphocyte population abundance, primarily due to an augmentation of the CD8+ T cell population. Remarkably, these changes occurred irrespective of potential homologous recombination defects, such as those associated with BRCA1/2 mutations. Our study strengthens the use of loss of heterozygosity as a biomarker of homologous repair deficiency. The changes of immune states during neoadjuvant chemotherapy reveal the dynamic nature of tumor-host immune interactions and suggest the potential use of immune checkpoint inhibitors or their combination with poly-ADP polymerase inhibitors in high stage and grade epithelial ovarian cancer patients undergoing neoadjuvant therapy.

Monitorización neurofisiológica intraoperatoria en cirugía de columna / Neurophisiologic monitoring in spinal surgery

The most feared complication in spinal surgeries is damage to the spinal cord due to inadvertent compression or interference in the blood supply with the consequent motor and/or sensory déficit. Intraoperative physiological surveillance reduces the risk of generating direct damage or due to hypoxia, helping in the early detection of complications. Publications in the Pubmed database are reviewed.

La complicación más temida en las cirugías de columna es el daño de la médula espinal por una compresión inadvertida o interferencia en el aporte sanguíneo con el consiguiente déficit motor y/o sensitivo. La vigilancia fisiológica intra operatoria disminuye el riesgo de generar daño directo o por hipoxia, ayudando en la detección temprana de las complicaciones. Se revisan publicaciones en base de datos Pubmed.

Gestational nutrient restriction under extensive grazing conditions: Effects on muscle characteristics and meat quality in heavy lambs.

We evaluated maternal undernutrition effects induced by a lower natural pasture allowance (gestation days 30-143) on histological-biochemical and meat traits in muscles Semitendinosus, cranial Gluteobiceps and Supraspinatus from 200-day old male and female lambs. Maternal undernutrition increased oxidative and reduced glycolytic fibers in all muscles (P ≤ 0.01). Maternal undernutrition reduced the diameter of glycolytic fibers in the cranial Gluteobiceps of exclusively female lambs (P = 0.05) and reduced the diameter of oxidative fibers in the Supraspinatus of exclusively male lambs (P = 0.02). Maternal undernutrition increased lipid content in the Supraspinatus of females (P = 0.001), reduced lactate content (P = 0.03) and WB shear force (P = 0.02) in the Semitendinosus of females, and increased cooking losses in the Semitendinosus of males (P = 0.0069). In conclusion, gestational nutrient restriction induced fetal programming effects on muscle characteristics of lambs. Moreover, our study demonstrates that maternal undernutrition influences muscle and meat characteristics in a sex and muscle-dependent way.