Potential Retinal Biomarkers in Alzheimer's Disease.

Alzheimer's disease (AD) represents a major diagnostic challenge, as early detection is crucial for effective intervention. This review examines the diagnostic challenges facing current AD evaluations and explores the emerging field of retinal alterations as early indicators. Recognizing the potential of the retina as a noninvasive window to the brain, we emphasize the importance of identifying retinal biomarkers in the early stages of AD. However, the examination of AD is not without its challenges, as the similarities shared with other retinal diseases introduce complexity in the search for AD-specific markers. In this review, we address the relevance of using the retina for the early diagnosis of AD and the complex challenges associated with the search for AD-specific retinal biomarkers. We provide a comprehensive overview of the current landscape and highlight avenues for progress in AD diagnosis by retinal examination.

Factores de riesgo en pacientes con diabetes mellitus tipo 2 con y sin hipertensión arterial. Lodana, Manabí-Ecuador

Introducción: la diabetes mellitus tipo 2 (DM2) y la hipertensión arterial (HTA) corresponden al grupo de enfermedades crónicas no transmisibles (ECNT) que se han presentado con mayor frecuencia a nivel mundial. Los pacientes que padecen DM2 con o sin HTA presentan estilos de vida poco saludables, que deben ser estudiados a través de instrumentos estandarizados. Objetivos: evaluar los factores de riesgo en pacientes con DM2 con y sin HTA que acuden al club de diabéticos del centro de salud del cantón Santa Ana en la parroquia de Lodana de la provincia de Manabí, Ecuador, en el período de octubre 2021 a marzo 2022. Metodología: se realizó un estudio observacional descriptivo, transversal. Se empleó un muestreo no probabilístico consecutivo obteniendo 44 pacientes que cumplían los criterios de inclusión. La muestra fue dividida en 2 grupos: 34 pacientes con DM2 y 10 pacientes con DM2 y HTA. A ambos grupos se les aplicó dos cuestionarios: uno sobre las características socio demográficas y el cuestionario IMEVID. Para el procesamiento y análisis de la información se elaboró una hoja de registro en Excel con la información obtenida de los cuestionarios aplicados. Los resultados fueron expresados en frecuencia relativa y porcentajes. Resultados: respecto a las características sociodemográficas se evidenció que en ambos grupos predominó el estado civil casado y la escolaridad primaria. En relación con la ocupación los pacientes del grupo DM2 manifestaron dedicarse a las labores del hogar y los pacientes del grupo DM2 y HTA son activos laboralmente. En cuanto al estilo de vida, se evaluaron las dimensiones correspondientes a nutrición, actividad física, tabaquismo, alcoholismo. Se obtuvieron resultados similares en ambos grupos estudiados. Conclusión: el estilo de vida llevado con mayor frecuencia en ambos grupos de pacientes es aquel relacionado a malos hábitos alimenticios y tendencias sedentarias.

Introduction: Type 2 diabetes mellitus (DM2) and arterial hypertension (HTA) correspond to the group of non-communicable chronic diseases (NCDs) that have occurred most frequently worldwide. Patients suffering from DM2 with or without AHT have unhealthy lifestyles, which must be studied using standardized instruments. Objective: To evaluate the risk factors in patients with DM2 with and without AHT who attend the diabetic club of the health center of the Santa Ana canton in the parish of Lodana in the province of Manabí, Ecuador, from October 2021 to March. 2022. Methodology: A descriptive, cross-sectional observational study was carried out. Consecutive non-probabilistic sampling was used, obtaining 44 patients who met the inclusion criteria. The sample was divided into 2 groups: 34 patients with DM2 and 10 patients with DM2 and HTA. Two questionnaires were applied to both groups: one on sociodemographic characteristics and the IMEVID questionnaire. For the processing and analysis of the information, a record sheet was prepared in Excel with the information obtained from the applied questionnaires. The results were expressed in relative frequency and percentages. Results: Regarding the sociodemographic characteristics, it was evidenced that in both groups the married marital status and primary schooling predominated. In relation to occupation, the patients of the DM2 group stated that they dedicated themselves to housework and the patients of the DM2 and HTA group were active at work. Regarding lifestyle, the dimensions corresponding to nutrition, physical activity, smoking, and alcoholism were evaluated. Similar results were obtained in both groups studied. Conclusion: The lifestyle followed most frequently in both groups of patients was that related to bad eating habits and sedentary tendencies.

Preserved blood-brain barrier and neurovascular coupling in female 5xFAD model of Alzheimer's disease.

Introduction: Dysfunction of the cerebral vasculature is considered one of the key components of Alzheimer's disease (AD), but the mechanisms affecting individual brain vessels are poorly understood. Methods: Here, using in vivo two-photon microscopy in superficial cortical layers and ex vivo imaging across brain regions, we characterized blood-brain barrier (BBB) function and neurovascular coupling (NVC) at the level of individual brain vessels in adult female 5xFAD mice, an aggressive amyloid-ß (Aß) model of AD. Results: We report a lack of abnormal increase in adsorptive-mediated transcytosis of albumin and preserved paracellular barrier for fibrinogen and small molecules despite an extensive load of Aß. Likewise, the NVC responses to somatosensory stimulation were preserved at all regulatory segments of the microvasculature: penetrating arterioles, precapillary sphincters, and capillaries. Lastly, the Aß plaques did not affect the density of capillary pericytes. Conclusion: Our findings provide direct evidence of preserved microvascular function in the 5xFAD mice and highlight the critical dependence of the experimental outcomes on the choice of preclinical models of AD. We propose that the presence of parenchymal Aß does not warrant BBB and NVC dysfunction and that the generalized view that microvascular impairment is inherent to Aß aggregation may need to be revised.

Effect of High-Pressure Treatments on the Properties of Food Packaging Materials with or without Antimicrobials.

The aim of this research work was the comparative study of the different properties of interest in the case of plastic materials for food use before and after being subjected to treatment by high hydrostatic pressure (HHP) as well as the impact of additivation with antimicrobials. This method of food preservation is currently on the rise and is of great interest because it is possible to extend the shelf life of many foods without the need for the use of additives or thermal processing, as is the case with other preservation methods currently used. The effects of HHP treatment (680 MPa for 8 min) on plastic materials commonly used in the food industry were studied. These materials, in sheet or film form, were polyethylene (PE), polyethylene terephthalate (PET), polystyrene (PS), multilayer polyethylene terephthalate-ethylene-vinyl alcohol copolymer-polyethylene (PET-EVOH-PE), multilayer polyethylene-polyethylene terephthalate (PE-PET), polyvinyl chloride aluminum (PVC-AL), and polylactic acid (PLA), which were provided by manufacturing companies in the sector. PE, PP, and PLA activated with tyrosol, zinc oxide, or zinc acetate were also tested. The phenomena and properties, such as overall migration, thermal behavior, oxygen barrier, and physical properties were analyzed before and after the process. The results show that the HHP process only slightly affected the properties of the materials. After pressurization, oxygen permeability increased greatly in PVC-AL (from 7.69 to 51.90) and decreased in PLA (from 8.77 to 3.60). The additivation of the materials caused a change in color and an increase in oxygen permeability. The additivated PE and PP showed migration values above the legal limit for certain simulants. The HHP treatment did not greatly affect the mechanical properties of the additivated materials. The main increases in the migration after HHP treatment were observed for PE activated with tyrosol or zinc oxide and for PS activated with zinc oxide. Activated PLA performed the best in the migration studies, irrespective of the HHP treatment. The results suggest that activated PLA could be used in HHP food processing as an inner antimicrobial layer in contact with the food packed in a container with the desired oxygen permeability barrier.

Prevention of Cell Death by Activation of Hydroxycarboxylic Acid Receptor 1 (GPR81) in Retinal Explants.

BACKGROUND: Progressive retinal ganglion cell (RGC) dysfunction and death are common characteristics of retinal neurodegenerative diseases. Recently, hydroxycarboxylic acid receptor 1 (HCA1R, GPR81) was identified as a key modulator of mitochondrial function and cell survival. Thus, we aimed to test whether activation of HCA1R with 3,5-Dihydroxybenzoic acid (DHBA) also promotes RGC survival and improves energy metabolism in mouse retinas. METHODS: Retinal explants were treated with 5 mM of the HCA1R agonist, 3,5-DHBA, for 2, 4, 24, and 72 h. Additionally, explants were also treated with 15 mM of L-glutamate to induce toxicity. Tissue survival was assessed through lactate dehydrogenase (LDH) viability assays. RGC survival was measured through immunohistochemical (IHC) staining. Total ATP levels were quantified through bioluminescence assays. Energy metabolism was investigated through stable isotope labeling and gas chromatography-mass spectrometry (GC-MS). Lactate and nitric oxide levels were measured through colorimetric assays. RESULTS: HCA1R activation with 3,5-DHBAincreased retinal explant survival. During glutamate-induced death, 3,5-DHBA treatment also increased survival. IHC analysis revealed that 3,5-DHBA treatment promoted RGC survival in retinal wholemounts. 3,5-DHBA treatment also enhanced ATP levels in retinal explants, whereas lactate levels decreased. No effects on glucose metabolism were observed, but small changes in lactate metabolism were found. Nitric oxide levels remained unaltered in response to 3,5-DHBA treatment. CONCLUSION: The present study reveals that activation of HCA1R with 3,5-DHBA treatment has a neuroprotective effect specifically on RGCs and on glutamate-induced retinal degeneration. Hence, HCA1R agonist administration may be a potential new strategy for rescuing RGCs, ultimately preventing visual disability.

Proteomic phenotype of cerebral organoids derived from autism spectrum disorder patients reveal disrupted energy metabolism, cellular components, and biological processes.

The way in which brain morphology and proteome are remodeled during embryonal development, and how they are linked to the cellular metabolism, could be a key for elucidating the pathological mechanisms of certain neurodevelopmental disorders. Cerebral organoids derived from autism spectrum disorder (ASD) patients were generated to capture critical time-points in the neuronal development, and metabolism and protein expression were investigated. The early stages of development, when neurogenesis commences (day in vitro 39), appeared to be a critical timepoint in pathogenesis. In the first month of development, increased size in ASD-derived organoids were detected in comparison to the controls. The size of the organoids correlates with the number of proliferating cells (Ki-67 positive cells). A significant difference in energy metabolism and proteome phenotype was also observed in ASD organoids at this time point, specifically, prevalence of glycolysis over oxidative phosphorylation, decreased ATP production and mitochondrial respiratory chain activity, differently expressed cell adhesion proteins, cell cycle (spindle formation), cytoskeleton, and several transcription factors. Finally, ASD patients and controls derived organoids were clustered based on a differential expression of ten proteins-heat shock protein 27 (hsp27) phospho Ser 15, Pyk (FAK2), Elk-1, Rac1/cdc42, S6 ribosomal protein phospho Ser 240/Ser 244, Ha-ras, mTOR (FRAP) phospho Ser 2448, PKCα, FoxO3a, Src family phospho Tyr 416-at day 39 which could be defined as potential biomarkers and further investigated for potential drug development.

Decreased Glucose Metabolism and Glutamine Synthesis in the Retina of a Transgenic Mouse Model of Alzheimer's Disease.

Visual changes are some of the earliest symptoms that patients with Alzheimer's disease (AD) experience. Pathophysiological processes such as amyloid-ß plaque formation, vascular changes, neuroinflammation, and loss of retinal ganglion cells (RGCs) have been detected in the retina of AD patients and animal models. However, little is known about the molecular processes that underlie retinal neurodegeneration in AD. The cellular architecture and constant sensory activity of the retina impose high metabolic demands. We thus hypothesized that energy metabolism might be compromised in the AD retina similarly to what has been observed in the AD brain. To address this question, we explored cellular alterations and retinal metabolic activity in the 5 × FAD mouse model of AD. We used 8-month-old female 5 × FAD mice, in which the AD-related pathology has been shown to be apparent. We observed that RGC density is selectively affected in the retina of 5 × FAD mice. To map retinal metabolic activity, we incubated isolated retinal tissue with [U-13C] glucose and analyzed tissue extracts by gas chromatography-mass spectrometry. We found that the retinas of 5 × FAD mice exhibit glucose hypometabolism. Moreover, we detected decreased glutamine synthesis in 5 × FAD retinas but no changes in the expression of markers of Müller glia, the main glial cell type responsible for glutamate uptake and glutamine synthesis in the retina. These findings suggest that AD presents with metabolic alterations not only in the brain but also in the retina that may be detrimental to RGC activity and survival, potentially leading to the visual impairments that AD patients suffer.

A conserved ATG2 binding site in WIPI4 and yeast Hsv2 is disrupted by mutations causing ß-propeller protein-associated neurodegeneration.

PROPPINs are phosphoinositide-binding ß-propeller proteins that mediate membrane recruitment of other proteins and are involved in different membrane remodeling processes. The main role of PROPPINs is their function in autophagy, where they act at different steps in phagophore formation. The human PROPPIN WIPI4 (WDR45) forms a complex with ATG2 involved in phagophore elongation, and mutations in this gene cause ß-propeller protein-associated neurodegeneration (BPAN). The yeast functional counterpart of WIPI4 is Atg18, although its closest sequence homolog is another member of the PROPPIN family, Hsv2, whose function remains largely undefined. Here, we provide evidence that Hsv2, like WIPI4 and Atg18, interacts with Atg2. We show that Hsv2 and a pool of Atg2 colocalize on endosomes under basal conditions and at the pre-autophagosomal structure (PAS) upon autophagy induction. We further show that Hsv2 drives the recruitment of Atg2 to endosomes while Atg2 mediates Hsv2 recruitment to the PAS. HSV2 overexpression results in mis-sorting and secretion of carboxypeptidase CPY, suggesting that the endosomal function of this protein is related to the endosome-to-Golgi recycling pathway. Furthermore, we show that the Atg2 binding site is conserved in Hsv2 and WIPI4 but not in Atg18. Notably, two WIPI4 residues involved in ATG2 binding are mutated in patients with BPAN, and there is a correlation between the inhibitory effect of these mutations on ATG2 binding and the severity of the disease.

Neuronal Loss of the Glutamate Transporter GLT-1 Promotes Excitotoxic Injury in the Hippocampus.

GLT-1, the major glutamate transporter in the mammalian central nervous system, is expressed in presynaptic terminals that use glutamate as a neurotransmitter, in addition to astrocytes. It is widely assumed that glutamate homeostasis is regulated primarily by glutamate transporters expressed in astrocytes, leaving the function of GLT-1 in neurons relatively unexplored. We generated conditional GLT-1 knockout (KO) mouse lines to understand the cell-specific functions of GLT-1. We found that stimulus-evoked field extracellular postsynaptic potentials (fEPSPs) recorded in the CA1 region of the hippocampus were normal in the astrocytic GLT-1 KO but were reduced and often absent in the neuronal GLT-1 KO at 40 weeks. The failure of fEPSP generation in the neuronal GLT-1 KO was also observed in slices from 20 weeks old mice but not consistently from 10 weeks old mice. Using an extracellular FRET-based glutamate sensor, we found no difference in stimulus-evoked glutamate accumulation in the neuronal GLT-1 KO, suggesting a postsynaptic cause of the transmission failure. We hypothesized that excitotoxicity underlies the failure of functional recovery of slices from the neuronal GLT-1 KO. Consistent with this hypothesis, the non-competitive NMDA receptor antagonist MK801, when present in the ACSF during the recovery period following cutting of slices, promoted full restoration of fEPSP generation. The inclusion of an enzymatic glutamate scavenging system in the ACSF conferred partial protection. Excitotoxicity might be due to excess release or accumulation of excitatory amino acids, or to metabolic perturbation resulting in increased vulnerability to NMDA receptor activation. Previous studies have demonstrated a defect in the utilization of glutamate by synaptic mitochondria and aspartate production in the synGLT-1 KO in vivo, and we found evidence for similar metabolic perturbations in the slice preparation. In addition, mitochondrial cristae density was higher in synaptic mitochondria in the CA1 region in 20-25 weeks old synGLT-1 KO mice in the CA1 region, suggesting compensation for loss of axon terminal GLT-1 by increased mitochondrial efficiency. These data suggest that GLT-1 expressed in presynaptic terminals serves an important role in the regulation of vulnerability to excitotoxicity, and this regulation may be related to the metabolic role of GLT-1 expressed in glutamatergic axon terminals.

Complex IV subunit isoform COX6A2 protects fast-spiking interneurons from oxidative stress and supports their function.

Parvalbumin-positive (PV+ ) fast-spiking interneurons are essential to control the firing activity of principal neuron ensembles, thereby regulating cognitive processes. The high firing frequency activity of PV+ interneurons imposes high-energy demands on their metabolism that must be supplied by distinctive machinery for energy generation. Exploring single-cell transcriptomic data for the mouse cortex, we identified a metabolism-associated gene with highly restricted expression to PV+ interneurons: Cox6a2, which codes for an isoform of a cytochrome c oxidase subunit. Cox6a2 deletion in mice disrupts perineuronal nets and enhances oxidative stress in PV+ interneurons, which in turn impairs the maturation of their morphological and functional properties. Such dramatic effects were likely due to an essential role of COX6A2 in energy balance of PV+ interneurons, underscored by a decrease in the ATP-to-ADP ratio in Cox6a2-/- PV+ interneurons. Energy disbalance and aberrant maturation likely hinder the integration of PV+ interneurons into cortical neuronal circuits, leading to behavioral alterations in mice. Additionally, in a human patient bearing mutations in COX6A2, we found a potential association of the mutations with mental/neurological abnormalities.

Staphylococcus aureus induces cell-surface expression of immune stimulatory NKG2D ligands on human monocytes.

Staphylococcus aureus is among the leading causes of bacterial infections worldwide. The pathogenicity and establishment of S. aureus infections are tightly linked to its ability to modulate host immunity. Persistent infections are often associated with mutant staphylococcal strains that have decreased susceptibility to antibiotics; however, little is known about how these mutations influence bacterial interaction with the host immune system. Here, we discovered that clinical S. aureus isolates activate human monocytes, leading to cell-surface expression of immune stimulatory natural killer group 2D (NKG2D) ligands on the monocytes. We found that expression of the NKG2D ligand ULBP2 (UL16-binding protein 2) is associated with bacterial degradability and phagolysosomal activity. Moreover, S. aureus-induced ULBP2 expression was linked to altered host cell metabolism, including increased cytoplasmic (iso)citrate levels, reduced glycolytic flux, and functional mitochondrial activity. Interestingly, we found that the ability of S. aureus to induce ULBP2 and proinflammatory cytokines in human monocytes depends on a functional ClpP protease in S. aureus These findings indicate that S. aureus activates ULBP2 in human monocytes through immunometabolic mechanisms and reveal that clpP inactivation may function as a potential immune evasion mechanism. Our results provide critical insight into the interplay between the host immune system and S. aureus that has evolved under the dual selective pressure of host immune responses and antibiotic treatment. Our discovery of an immune stimulatory pathway consisting of human monocyte-based defense against S. aureus suggests that targeting the NKG2D pathway holds potential for managing persistent staphylococcal infections.

The role of astrocytes in seizure generation: insights from a novel in vitro seizure model based on mitochondrial dysfunction.

Approximately one-quarter of patients with mitochondrial disease experience epilepsy. Their epilepsy is often severe and resistant towards conventional antiepileptic drugs. Despite the severity of this epilepsy, there are currently no animal models available to provide a mechanistic understanding of mitochondrial epilepsy. We conducted neuropathological studies on patients with mitochondrial epilepsy and found the involvement of the astrocytic compartment. As a proof of concept, we developed a novel brain slice model of mitochondrial epilepsy by the application of an astrocytic-specific aconitase inhibitor, fluorocitrate, concomitant with mitochondrial respiratory inhibitors, rotenone and potassium cyanide. The model was robust and exhibited both face and predictive validity. We then used the model to assess the role that astrocytes play in seizure generation and demonstrated the involvement of the GABA-glutamate-glutamine cycle. Notably, glutamine appears to be an important intermediary molecule between the neuronal and astrocytic compartment in the regulation of GABAergic inhibitory tone. Finally, we found that a deficiency in glutamine synthetase is an important pathogenic process for seizure generation in both the brain slice model and the human neuropathological study. Our study describes the first model for mitochondrial epilepsy and provides a mechanistic insight into how astrocytes drive seizure generation in mitochondrial epilepsy.

Generation of a set of isogenic, gene-edited iPSC lines homozygous for all main APOE variants and an APOE knock-out line.

Alzheimer's disease (AD) is the most frequent neurodegenerative disease amongst the elderly. The SNPs rs429358 and rs7412 in the APOE gene are the most common risk factor for sporadic AD, and there are three different alleles commonly referred to as APOE-ε2, APOE-ε3 and APOE-ε4. Induced pluripotent stem cells (iPSCs) hold great promise to model AD as such cells can be differentiated in vitro to the required cell type. Here we report the use of CRISPR/Cas9 technology employed on iPSCs from a healthy individual with an APOE-ε3/ε4 genotype to obtain isogenic APOE-ε2/ε2, APOE-ε3/ε3, APOE-ε4/ε4 lines as well as an APOE-knock-out line.

Estudio descriptivo de opinión de estudiantes y docente referente a la ejecución del trabajo en equipo y el manejo de las emociones en un escenario de simulación clínica de alta fidelidad / Descriptive study of student and teacher opinion regarding the execution of team work and the management of emotions in a scenario of high fidelity clinical simulation

INTRODUCCIÓN: Los cuidados de enfermería requieren que el profesional de hoy además de contar con un sustento teórico, obtenga competencias que le permitan entregar cuidados humanizados. Ante esto, es necesario buscar metodologías de aprendizaje que favorezcan el desarrollo de habilidades no técnicas, por lo cual se plantea si la simulación clínica permite a los estudiantes lograr estas competencias, buscando evidenciar la ejecución del trabajo en equipo y el manejo de las emociones por medio de un escenario de simulación clínica de alta fidelidad. METODOLOGÍA: El estudio fue de carácter cuantitativo, descriptivo. Para la obtención de los datos se requirió elaborar un instrumento el cual fue validado por validez aparente, y por grupo de expertos, previo a su aplicación, que fue ejecutada término de una sesión de simulación clínica, los datos obtenidos se analizaron por medio de porcentajes. RESULTADOS: En relación al trabajo en equipo, se obtienen niveles de acuerdo por sobre el 80% en la ejecución de la habilidad, según la opinión de los estudiantes y el docente, siendo el docente quien entrega un menor porcentaje de acuerdo. Referente al manejo de emociones se observa que en ambos grupos (estudiantes y docente) entregan niveles de acuerdo por sobre el 60% en la ejecución de la habilidad, siendo el docente quien entrega un menor porcentaje de acuerdo. Estos resultados abren una puerta, a como la simulación clínica permite la ejecución de las habilidades no técnicas, las cuales en la actualidad son fundamentales en la formación profesional.

BACKGROUND: Nurses, nowadays, required a theoretical framework and competences that allow having a human care. For this reason, it is necessary to explore learning approaches that develop in nursing student's soft skills. There are evidences that show that high fidelity simulation trainingis a useful methodology at the management of moods and teamwork in nursing students. METHOD: Descriptive and quantitative method was used, a questionnaire were design and validated by experts that were applied after participants ended high fidelity simulation training. Descriptive statistics methods such as percent were used to compare students and teachers opinions regards execution of competences and skills. RESULTS: The opinion about work in team were similar between teachers and students, however, there were differences opinions about moods management in the high definition training. These results open a window on how clinical simulation as a methodology allows the execution of non-technical skills, which are currently relevant for nursing education.

Sintomatología depresiva en el post parto y factores psicosociales asociados / Postpartum depressive symptomatology and its associated psychosocial factors

Introducción: La sintomatología depresiva en el postparto impacta negativamente en el sistema familiar. En México existe poca investigación al respecto por ello es primordial su estudio. Objetivo: Conocer la frecuencia de sintomatología depresiva postparto y los factores psicosociales que se le asocian. Material y métodos. Se entrevistaron 154 mujeres con 0 a 12 meses de postparto que acudieron a dos hospitales públicos de un estado del noreste México. Se aplicó el Cuestionario de Depresión Postparto de Edimburgo (EPDS) para medir la sintomatología depresiva y un Cuestionario de Factores Psicosociales diseñado por los investigadores. Resultados. El 16% de la muestra presentó sintomatología depresiva. Los factores que se le asociaron fueron estado civil de unión libre, familiar con depresión, tristeza en embarazo, acontecimiento vital estresante en embarazo, consumo de alcohol en embarazo, ansiedad, consumo de alcohol actual, insatisfacción con los cambios corporales, percibir mayor atención de la familia al bebé y haber experimentado tristeza en embarazos anteriores. Conclusiones. Existen factores psicosociales que se asocian a sintomatología depresiva en el postparto que es de relevancia conocer en la atención primaria con el fin de crear estrategias preventivas en las instituciones de salud.

Background. Postpartum depressive symptomatology has a negative impact on the nuclear family. Research on this topic is scarce in Mexico, therefore conducting more studies in this field is of upmost importance. Objective. Finding out the frequency of postpartum depressive symptomatology and its associated psychosocial factors. Material and methods. 154 women at 0-12 months postpartum that attended two public hospitals in a northeast state of the Mexico were interviewed. They answered the Edinburgh Postpartum Depression Scale (EPDS), measuring depressive symptomatology, and a Psychosocial Factors questionnaire designed by the researchers. Results. 16% of women in the cohort presented depressive symptomatology. The factors associated were out-of-wedlock cohabitation, having relatives that suffer from depression, feelings of sadness during pregnancy, stressful life event during pregnancy, alcohol consumption during pregnancy, anxiety, current alcohol consumption, dissatisfaction regarding body changes caused by pregnancy, feeling that family attention is focused on the baby and having feelings of sadness during previous pregnancies. Conclusions. There are psychosocial factors that are associated to postpartum depressive symptomatology, which should be taken into consideration to create preventive strategies in health institutes.

Effect of the Anti-depressant Sertraline, the Novel Anti-seizure Drug Vinpocetine and Several Conventional Antiepileptic Drugs on the Epileptiform EEG Activity Induced by 4-Aminopyridine.

Seizures are accompanied by an exacerbated activation of cerebral ion channels. 4-aminopyridine (4-AP) is a pro-convulsive agent which mechanism of action involves activation of Na(+) and Ca(2+) channels, and several antiepileptic drugs control seizures by reducing these channels permeability. The antidepressant, sertraline, and the anti-seizure drug vinpocetine are effective inhibitors of cerebral presynaptic Na(+) channels. Here the effectiveness of these compounds to prevent the epileptiform EEG activity induced by 4-AP was compared with the effectiveness of seven conventional antiepileptic drugs. For this purpose, EEG recordings before and at three intervals within the next 30 min following 4-AP (2.5 mg/kg, i.p.) were taken in anesthetized animals; and the EEG-highest peak amplitude values (HPAV) calculated. In control animals, the marked increase in the EEG-HPAV observed near 20 min following 4-AP reached its maximum at 30 min. Results show that this epileptiform EEG activity induced by 4-AP is prevented by sertraline and vinpocetine at a dose of 2.5 mg/kg, and by carbamazepine, phenytoin, lamotrigine and oxcarbazepine at a higher dose (25 mg/kg). In contrast, topiramate (25 mg/kg), valproate (100 mg/kg) and levetiracetam (100 mg/kg) failed to prevent the epileptiform EEG activity induced by 4-AP. It is concluded that 4-AP is a useful tool to elicit the mechanism of action of anti-seizure drugs at clinical meaningful doses. The particular efficacy of sertraline and vinpocetine to prevent seizures induced by 4-AP is explained by their high effectiveness to reduce brain presynaptic Na(+) and Ca(2+) channels permeability.

A new approach for automated liquid-liquid extraction in a sequential injection manifold.

A new approach for the implementation of liquid-liquid extraction in a sequential injection manifold is presented. The manifold consists of two syringe pumps and one multi-position valve. The use of a 30 % MeOH/H2O (v/v) solution as the carrier, with isobutanol as the extractant, made it possible to avoid the problems associated with the different affinities of the organic and aqueous phases for Teflon tubing, and the formation of bubbles. The suitability of the proposed method was demonstrated by the determination of thiamine in pharmaceutical preparations and dietary supplements. Detection and quantification limits were estimated as 9 and 30 µg L(-1), respectively. The repeatability was lower than 3 % and the intermediate precision (3 d) was lower than 7 %. The sample throughput was 14 samples per h. The results were in agreement with a high-performance liquid chromatography-electrospray/mass spectrometry reference method.

Role of histaminergic system in blood-brain barrier dysfunction associated with neurological disorders.

Blood-brain barrier (BBB) disruption has been associated with several acute and chronic brain disorders such as Alzheimer's disease, Parkinson's disease and epilepsy. This represents a critical situation because damaged integrity of the BBB is related to the influx of immune mediators, plasma proteins and other outside elements from blood to the central nervous system (CNS) that may trigger a cascade of events that leads to neuroinflammation. In this review, evidence that mast cells and the release of factors such as histamine play an important role in the neuroinflammatory process associated with brain disorders such as Alzheimer's disease, Parkinson's disease and epilepsy is presented.

The membrane-spanning 4-domains, subfamily A (MS4A) gene cluster contains a common variant associated with Alzheimer's disease.

BACKGROUND: In order to identify novel loci associated with Alzheimer's disease (AD), we conducted a genome-wide association study (GWAS) in the Spanish population. METHODS: We genotyped 1,128 individuals using the Affymetrix Nsp I 250K chip. A sample of 327 sporadic AD patients and 801 controls with unknown cognitive status from the Spanish general population were included in our initial study. To increase the power of the study, we combined our results with those of four other public GWAS datasets by applying identical quality control filters and the same imputation methods, which were then analyzed with a global meta-GWAS. A replication sample with 2,200 sporadic AD patients and 2,301 controls was genotyped to confirm our GWAS findings. RESULTS: Meta-analysis of our data and independent replication datasets allowed us to confirm a novel genome-wide significant association of AD with the membrane-spanning 4-domains subfamily A (MS4A) gene cluster (rs1562990, P = 4.40E-11, odds ratio = 0.88, 95% confidence interval 0.85 to 0.91, n = 10,181 cases and 14,341 controls). CONCLUSIONS: Our results underscore the importance of international efforts combining GWAS datasets to isolate genetic loci for complex diseases.