Seizures Triggered by Systemic Administration of 4-Aminopyridine in Rats Lead to Acute Brain Glucose Hypometabolism, as Assessed by [F]FDG PET Neuroimaging.

4-aminopyridine (4-AP) is a non-selective blocker of voltage-dependent K channels used to improve walking in multiple sclerosis patients, and it may be useful in the treatment of cerebellar diseases. In animal models, 4-AP is used as a convulsant agent. When administered intrahippocampally, 4-AP induces acute local glucose hypermetabolism and significant brain damage, while i.

Haematopoietic gene therapy of non-conditioned patients with Fanconi anaemia-A: results from open-label phase 1/2 (FANCOLEN-1) and long-term clinical trials.

Background: Allogeneic haematopoietic stem-cell transplantation is the standard treatment for bone marrow failure (BMF) in patients with Fanconi anaemia, but transplantation-associated complications such as an increased incidence of subsequent cancer are frequent. The aim of this study was to evaluate the safety and efficacy of the infusion of autologous gene-corrected haematopoietic stem cells as an alternative therapy for these patients.

Methods: This was an open-label, investigator-initiated phase 1/2 clinical trial (FANCOLEN-1) and long-term follow-up trial (up to 7 years post-treatment) in Spain.

Dyadic Coping in Aging: Linking Self-Perceptions of Aging to Depression.

Negative self-perceptions of aging have been linked to poorer health and quality of life and predict significantly depressive symptomatology. The support provided by the partner may have an impact on the effects of self-perceptions of aging on depressive symptoms; a close relationship can go along with additional stress or resources and benefits. The present study analyzes the relationship between negative self-stereotypes and depressive symptomatology, considering positive and negative dyadic coping (DC) as moderator variables in this association.

Psychometric properties of the Partner Ambivalence Scale in middle-aged and older adults.

Objectives: Ambivalent feelings in a partner relationship, characterized by simultaneous positive and negative emotional experiences, can significantly influence individuals' mental health. Traditionally measured indirectly, this study introduces the Partner Ambivalence Scale (PAS), developed for directly capturing the complexity of ambivalent emotions. This study aimed to analyze the psychometric properties of the PAS, and assess the effects of ambivalent feelings on partner relationship quality and depressive symptomatology.

Astrocytic Ca activation by chemogenetics mitigates the effect of kainic acid-induced excitotoxicity on the hippocampus.

Astrocytes play a multifaceted role regulating brain glucose metabolism, ion homeostasis, neurotransmitters clearance, and water dynamics being essential in supporting synaptic function. Under different pathological conditions such as brain stroke, epilepsy, and neurodegenerative disorders, excitotoxicity plays a crucial role, however, the contribution of astrocytic activity in protecting neurons from excitotoxicity-induced damage is yet to be fully understood. In this work, we evaluated the effect of astrocytic activation by Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) on brain glucose metabolism in wild-type (WT) mice, and we investigated the effects of sustained astrocyte activation following an insult induced by intrahippocampal (iHPC) kainic acid (KA) injection using 2-deoxy-2-[F]-fluoro-D-glucose (F-FDG) positron emission tomography (PET) imaging, along with behavioral test, nuclear magnetic resonance (NMR) spectroscopy and histochemistry.

Effects of chronic treatment with metformin on brain glucose hypometabolism and central insulin actions in transgenic mice with tauopathy.

Brain glucose hypometabolism and insulin alterations are common features of many neurological diseases. Herein we sought to corroborate the brain glucose hypometabolism that develops with ageing in 12-months old Tau-VLW transgenic mice, a model of tauopathy, as well as to determine whether this model showed signs of altered peripheral glucose metabolism. Our results demonstrated that 12-old months Tau mice exhibited brain glucose hypometabolism as well as basal hyperglycemia, impaired glucose tolerance, hyperinsulinemia, and signs of insulin resistance.

Role of the mesenchymal stromal cells in bone marrow failure of Fanconi Anemia patients.

Introduction: Fanconi anemia (FA) is an inherited disorder characterized by bone marrow failure, congenital malformations, and predisposition to malignancies. Alterations in hematopoietic stem cells (HSC) have been reported, but little is known regarding the bone marrow (BM) stroma. Thus, the characterization of Mesenchymal Stromal Cells (MSC) would help to elucidate their involvement in the BM failure.

Profiles of Dementia Caregivers according to Psychosocial and Resource Variables. Importance of Kinship.

The present study aims to analyze the existence of different profiles in family caregivers of people with dementia according to psychosocial and resource variables. In addition, it aims to study whether there is a greater representation of each kinship group in each of the profiles and if there are differences in emotional distress among such profiles considering the kinship with the care-recipient. Participants 288 family dementia caregivers, divided into four kinship groups (wives, husbands, sons and daughters).

Choosing T-cell sources determines CAR-T cell activity in neuroblastoma.

Introduction: The clinical success of chimeric antigen receptor-modified T cells (CAR-T cells) for hematological malignancies has not been reproduced for solid tumors, partly due to the lack of cancer-type specific antigens. In this work, we used a novel combinatorial approach consisting of a versatile anti-FITC CAR-T effector cells plus an FITC-conjugated neuroblastoma (NB)-targeting linker, an FITC-conjugated monoclonal antibody (Dinutuximab) that recognizes GD2.

Methods: We compared cord blood (CB), and CD45RA-enriched peripheral blood leukapheresis product (45RA) as allogeneic sources of T cells, using peripheral blood (PB) as a control to choose the best condition for anti-FITC CAR-T production.

Inhibition of the AURKA/YAP1 axis is a promising therapeutic option for overcoming cetuximab resistance in colorectal cancer stem cells.

Background: Primary resistance to anti-EGFR therapies affects 40% of metastatic colorectal cancer patients harbouring wild-type RAS/RAF. YAP1 activation is associated with this resistance, prompting an investigation into AURKA's role in mediating YAP1 phosphorylation at Ser397, as observed in breast cancer.

Methods: We used transcriptomic analysis along with in vitro and in vivo models of RAS/RAF wild-type CRC to study YAP1 Ser397 phosphorylation as a potential biomarker for cetuximab resistance.

Mast Cell Activation Profile and TFH13 Detection Discriminate Food Anaphylaxis Versus Sensitization.

Background And Objective: The prevalence of food allergy (FA) has increased significantly, and the risk of developing anaphylaxis is unpredictable. Thus, discriminating between sensitized patients and those at risk of having a severe reaction is of utmost interest. To explore mast cell activation pattern and T follicular helper (TFH) 13 presence in sensitized and food anaphylaxis patients.

[Not Available].

Objetivo: Estimar la prevalencia del antecedente de vacunación en adultos de 20 a 59 años y mayores de 60 años mediante autorreporte. Material y métodos. Análisis de datos obtenidos de la Encuesta Nacional de Salud y Nutrición 2022 (Ensanut 2022).

[Not Available].

Objetivo: Estimar el porcentaje de infección respiratoria aguda (IRA) en menores de cinco años en las últimas dos semanas en México, de acuerdo con los datos de la Encuesta Nacional de Salud y Nutrición Continua 2022 (Ensanut Continua 2022). Material y métodos. Se analizaron datos de la Ensanut Continua 2022.

[Not Available].

Objetivo: Describir las coberturas de vacunación en 2022 en niñas, niños y en adolescentes, así como comparar las prevalencias observadas con los datos de la Encuesta Nacional de Salud y Nutrición 2021 (Ensanut 2021). Material y métodos. Análisis de datos obtenidos de la Ensanut 2022.

Resilience and family quality of life in parents of children with autism spectrum disorders.

Introduction: Resilience and quality of life (QOL) can involve a positive approach in group interventions for parents of children with autism spectrum disorders (ASD). This study aims to evaluate resilience and family QOL at the start of a psychoeducational group.

Methods: Cross-sectional assessment of resilience and family QOL used the Family Quality of Life Scale (ECVF) and 14-item Resilience Scale (RS-14).

Mexican Biobank advances population and medical genomics of diverse ancestries.

Latin America continues to be severely underrepresented in genomics research, and fine-scale genetic histories and complex trait architectures remain hidden owing to insufficient data. To fill this gap, the Mexican Biobank project genotyped 6,057 individuals from 898 rural and urban localities across all 32 states in Mexico at a resolution of 1.8 million genome-wide markers with linked complex trait and disease information creating a valuable nationwide genotype-phenotype database.

Demographic modeling of admixed Latin American populations from whole genomes.

Demographic models of Latin American populations often fail to fully capture their complex evolutionary history, which has been shaped by both recent admixture and deeper-in-time demographic events. To address this gap, we used high-coverage whole-genome data from Indigenous American ancestries in present-day Mexico and existing genomes from across Latin America to infer multiple demographic models that capture the impact of different timescales on genetic diversity. Our approach, which combines analyses of allele frequencies and ancestry tract length distributions, represents a significant improvement over current models in predicting patterns of genetic variation in admixed Latin American populations.

CD44 Modulates Cell Migration and Invasion in Ewing Sarcoma Cells.

The chimeric EWSR1::FLI1 transcription factor is the main oncogenic event in Ewing sarcoma. Recently, it has been proposed that EWSR1::FLI1 levels can fluctuate in Ewing sarcoma cells, giving rise to two cell populations. EWSR1::FLI1 cells present a migratory and invasive phenotype, while EWSR1::FLI1 cells are more proliferative.

A Single High Dose of Flufenamic Acid in Rats does not Reduce the Damage Associated with the Rat Lithium-Pilocarpine Model of Status Epilepticus but Leads to Deleterious Outcomes.

Background: Epilepsy is one of the most common neurologic diseases, and around 30% of all epilepsies, particularly the temporal lobe epilepsy (TLE), are highly refractory to current pharmacological treatments. Abnormal synchronic neuronal activity, brain glucose metabolism alterations, neurodegeneration and neuroinflammation are features of epilepsy. Further, neuroinflammation has been shown to contribute to dysregulation of neuronal excitability and the progression of epileptogenesis.