Prenatal risk factors and postnatal cannabis exposure: Assessing dual models of schizophrenia-like rodents.

Schizophrenia (SCZ) is a multifactorial neurodevelopmental disorder caused by genetic and environmental alterations, especially during prenatal stages. On the other hand, cannabis consumption in adolescence has been also linked to an increased risk of developing SCZ. The combination of both hits has been proposed as the dual hit hypothesis of SCZ. We systematically reviewed prenatal environmental alterations and cannabis consumption during adolescence that are associated with an increased risk of SCZ, following the PRISMA model. The analysis focused on dual animal models where the first hit is prenatal environmental exposure and the second hit consists of postnatal cannabis exposure. The articles were evaluated by three independent reviewers based on inclusion criteria. We extracted the first author´s name, year, model species, sex and analysis. The articles reported on dual murine models and their effects on weight, behavior, genetics, electrophysiology and brain structure and function. We conclude that the defects caused by the dual hits depend on the sex of the model, as well as type of hits.

A Neuroligin-1 mutation associated with Alzheimer's disease produces memory and age-dependent impairments in hippocampal plasticity.

Alzheimer's disease (AD) is characterized by memory impairments and age-dependent synapse loss. Experimental and clinical studies have shown decreased expression of the glutamatergic protein Neuroligin-1 (Nlgn1) in AD. However, the consequences of a sustained reduction of Nlgn1 are unknown. Here, we generated a knockin mouse that reproduces the NLGN1 Thr271fs mutation, identified in heterozygosis in a familial case of AD. We found that Nlgn1 Thr271fs mutation abolishes Nlgn1 expression in mouse brain. Importantly, heterozygous Nlgn1 Thr271fs mice showed delay-dependent amnesia for recognition memory. Electrophysiological recordings uncovered age-dependent impairments in basal synaptic transmission and long-term potentiation (LTP) in CA1 hippocampal neurons of heterozygous Nlgn1 Thr271fs mice. In contrast, homozygous Nlgn1 Thr271fs mice showed impaired fear-conditioning memory and normal basal synaptic transmission, suggesting unshared mechanisms for a partial or total loss of Nlgn1. These data suggest that decreased Nlgn1 may contribute to the synaptic and memory deficits in AD.

First Case of Abdominal and Tunica Vaginalis Multicystic Benign Mesothelioma: Management and Review of Literature.

Multicystic benign mesothelioma is a rare tumor that affects the serosa. Most cases present with peritoneal lesions exclusively. Some identified risk factors are chronic abdominal inflammation, woman of childbearing age, and asbestos exposure. The symptomatology is not specific and can delay the diagnosis. There are no guidelines for the treatment of this pathology. We describe one male patient with abdominal and tunica vaginalis localizations of multicystic benign mesothelioma. The diagnosis was suspected on imaging and confirmed with histological examination. The treatment on an expert center was complete cytoreduction surgery and HIPEC, but the patient had two recurrences during the 2-year of follow-up. This is the first case of simultaneous rare localizations of multicystic benign mesothelioma. No new risk factors were identified. The case underlines the importance of regular examination of all serosa localizations.

Telehealth Actions to Address COVID-19 in Latin American Countries.

Introduction: This study set out to examine the use of telehealth resources to tackle the coronavirus disease 2019 (COVID-19) pandemic in Latin America within the scope of national telehealth projects (NTPs). Methods: A qualitative study developed using ethnomethodology for appropriate understanding of how telehealth actions were carried out in practice during the COVID-19 pandemic within the scope of NTPs, in the following countries: Argentina, Colombia, Costa Rica, Ecuador, El Salvador, Guatemala, Honduras, Mexico, Peru, and Uruguay. The study was carried out from October to 2020 to March 2021. The number of participations in the discussion groups, formed by coordinating teams of NTPs, totaled 90. Results were described in the worksheet completed according to the script. Each country reviewed its respective data, three times on average, in an effort to clarify actions developed. Results: Three groups of countries were identified: (1) Countries with a telehealth background that used these resources to tackle COVID-19 and thereby refined telehealth activities. Countries with greater experience in NTP design, such as Mexico, Colombia, Peru, and Argentina, were able to use a wide range of telehealth activities to tackle the pandemic, with offers of teleconsultation, teleguidance, telemonitoring to patients, and training of health professionals; (2) Countries with some telehealth activities to address COVID-19. Uruguay, Ecuador, El Salvador, and Costa Rica; and (3) Countries with no evidence of telehealth resource use during the pandemic. Honduras and Guatemala. Discussion: Most NTPs in Latin America have improved their telehealth activities, contributing to address the COVID-19 pandemic in Latin America.

Influence of Type of Filler and Bitumen on the Mechanical Performance of Asphalt Mortars.

This article presents a new methodology of analysis based on a fast-running experimental procedure to characterise the mechanical response of asphalt mortars in terms of stiffness, ductility, and fatigue resistance. This was achieved using the DMA (Dynamic Mechanical Analyser) three-point bending configuration. The study was carried out by considering the employment of different types of fillers such cement and CaCO3 and different types of binders such as conventional asphalt binder (B35/50) or modifided polymer-modified bitumen (PMB 25/55-65). From the results of this study, the filler was found to have a greater influence on the stiffness and ductility of the asphalt material, while bitumen had a higher effect on the fatigue life of the asphalt mortar. Fatigue life was observed to increase with the use of a polymer-modified binder, while a lower degree of permanent deformation and higher bearing capacity achieved by the use of cement instead of calcium carbonate as active fillers.

Reelin Alterations, Behavioral Phenotypes, and Brain Anomalies in Schizophrenia: A Systematic Review of Insights From Rodent Models.

Reelin is an extracellular matrix glycoprotein reduced in brain regions (the prefrontal cortex and the hippocampus) of patients with schizophrenia. There are diverse rodent models of schizophrenia that mimic patient symptoms based on various causal theories; however, likely shared reelin alterations have not yet been systematically assessed in those models. A systematic review of the literature was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) model. Articles focused on psychotic disorders or schizophrenia and their relationship with reelin in rodent models were selected. Data (first author, publication year, results, both open field and prepulse inhibition test results, and type of reelin alteration) were extracted in duplicate by two independent reviewers. The 37 reviewed articles reported about various schizophrenia models and their reelin alterations, brain morphology, and behavioral defects. We conclude that reelin is an altered preclinical biomarker common to all models included, mainly prenatal or genetic models, and a key protein in schizophrenia disease, making the reelin signaling pathway in prenatal stages a target of special interest for future preclinical and clinical studies. All models presented at least one of the four described reelin alteration types. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021210568], identifier [CRD42021210568].

Survival capacity of Arcobacter butzleri at different incubation temperatures in drinking water

Arcobacter represents a zoonotic emerging pathogen with increasing importance for public health and drinking water has been cited as a major risk factor for its dissemination. The aim of this work was to evaluate the survival capacity of Arcobacter in different water matrixes stored at different temperatures. Three different water matrixes were used, including potable water with a chlorine concentration of 0,5 mg/mL, non-chlorinated water and non-chlorinated water added with an 11% of organic matter. Each matrix was inoculated in a 1/10 proportion with 103 and 105 Arcobacter pools, divided into 4 different subsamples, in order to be incubated at 0°C, 5°C, 12 °C and 25°C by up to 15 days. The presence of Arcobacter in each matrix was determined on days 1, 3, 5, 7, 9, 11, 13 and 15. Results obtained show that this bacterium can survive in all the water matrixes evaluated, regardless of the presence or not of residual disinfecting agent. Also, the amount of CFU/mL inoculated in water correlates with the number of bacteria that can survive on it, and that incubation temperature has a significant effect over the bacterial survival.

Selective expression of the neurexin substrate for presenilin in the adult forebrain causes deficits in associative memory and presynaptic plasticity.

Presenilins (PS) form the active subunit of the gamma-secretase complex, which mediates the proteolytic clearance of a broad variety of type-I plasma membrane proteins. Loss-of-function mutations in PSEN1/2 genes are the leading cause of familial Alzheimer's disease (fAD). However, the PS/gamma-secretase substrates relevant for the neuronal deficits associated with a loss of PS function are not completely known. The members of the neurexin (Nrxn) family of presynaptic plasma membrane proteins are candidates to mediate aspects of the synaptic and memory deficits associated with a loss of PS function. Previous work has shown that fAD-linked PS mutants or inactivation of PS by genetic and pharmacological approaches failed to clear Nrxn C-terminal fragments (NrxnCTF), leading to its abnormal accumulation at presynaptic terminals. Here, we generated transgenic mice that selectively recreate the presynaptic accumulation of NrxnCTF in adult forebrain neurons, leaving unaltered the function of PS/gamma-secretase complex towards other substrates. Behavioral characterization identified selective impairments in NrxnCTF mice, including decreased fear-conditioning memory. Electrophysiological recordings in medial prefrontal cortex-basolateral amygdala (mPFC-BLA) of behaving mice showed normal synaptic transmission and uncovered specific defects in synaptic facilitation. These data functionally link the accumulation of NrxnCTF with defects in associative memory and short-term synaptic plasticity, pointing at impaired clearance of NrxnCTF as a new mediator in AD.

Assessment of the adequacy of mobile applications for disaster reduction.

Natural events continue to take a heavy toll on human lives. Added to this are the challenge of dynamic at-risk settings, uncertainty, and increasing threats, which demand holistic, flexible, and quickly adaptable solutions. In this context, mobile applications are strongly emerging as communication tools that can assist in disaster reduction. Yet, these have not been sufficiently evaluated. In view of this, the aim of this research is to evaluate the adequacy of mobile applications in disaster risk reduction in reference to some of the deadliest natural events. To this purpose, a two-part methodology is developed. Firstly, a random sample of applications is evaluated and contrasted with the literature. Secondly, the viability of mobile applications is determined based on the Digital Application Potential Index proposed by the authors, cross-referenced in Geographical Information Systems with the WorldRiskIndex. The results show that most mobile applications limit their coverage range to only one stage of Disaster Risk Management (DRM) and one type of hazard event, failing to address systemic risk and hampering the scale-up of humanitarian response. For these to become adequate and wide-reaching, strong policies to promote reliability, transparency, and citizen empowerment would be required. The policies establishing the use of mobile applications as a viable tool for DRM must consider reducing the prices of internet connectivity while increasing educational levels, on top of language translation. At this point, the adoption of mobile applications is unable to ensure DRM communication, especially in countries with higher-risk levels, requiring these to be complemented with auxiliary tools.

Características sociodemográficas, clínicas y familiares de pacientes con trastornos mentales de una unidad médica familiar / Sociodemographic, clinical and family characteristics of patients with mental disorders in a family medical unit

RESUMEN: Objetivo: Determinar las características epidemiológicas, clínicas y familiares de los pacientes con trastornos mentales adscritos a una unidad de medicina familiar (UMF) mexicana. Material y métodos: Estudio prospectivo, transversal, observacional, descriptivo, sobre 164 pacientes adscritos a una UMF mexicana, elegidos por muestreo no probabilístico que cumplieron criterios de selección: mayores de 18 años, con trastorno mental, sin impedimento físico o cognitivo. Resultados: Se presentaron 51 hombres y 113 mujeres con edad promedio de 48,6 años; 57% con más de un trastorno mental; los más frecuentes fueron depresión y ansiedad. En escolaridad sobresale licenciatura; 16% reportaron intento de suicidio, 42% tiene más de 6 años diagnosticado. El 64,6% recibe psicoterapia y farmacología; el 18% fue hospitalizado a causa de sus trastornos, gran parte de ellos entre 1 y 4 semanas y 38% tiene algún familiar con algún trastorno mental, Las comorbilidades más frecuentes fueron Hipertensión, obesidad, diabetes mellitus, dislipidemia y artrosis. Los tipos de familia más frecuentes son: nuclear o nuclear simple, con núcleo integrado y núcleo no integrado; subsisten principalmente de los servicios; viven con niveles 1 y 2 de pobreza familiar; son modernas y urbanas en mayor número. Conclusiones: las características sociodemográficas, clínicas y familiares de los pacientes con trastornos mentales adscritos a una unidad de medicina familiar (UMF) mexicana son en su mayoría mujeres, en adultez media, que cursan con más de un trastorno mental (ansiedad y depresión), tratadas con fármacos y psicoterapia, además cursaban con hipertensión, y pertenecen a familias de tipo nuclear simple, de núcleo integrado y núcleo no; subsisten por servicios; viven con niveles 1 y 2 de pobreza familiar, son modernas y urbanas.

ABSTRACT: Objective: To determine the epidemiological, clinical and family characteristics of patients with mental disorders assigned to a Mexican family medicine unit (FMU). Material and methods: Prospective, cross-sectional, observational, descriptive study of 164 patients assigned to a Mexican FMU, chosen by non-probabilistic evidence that they met the selection criteria: older than 18 years, with mental disorder, without physical or cognitive impairment. Results: 51 men and 113 women with a mean age of 48.6 years were presented; 57% with more than one mental disorder; the most frequent were depression and anxiety. In schooling overselling bachelor's degree; 16% reported attempted suicide, 42% have been diagnosed for more than 6 years. 64.6% receive psychotherapy and pharmacology; 18% were hospitalized due to their disorders, most of them between 1 and 4 weeks and 38% have a family member with a mental disorder. The most frequent comorbidities were hypertension, obesity, diabetes mellitus, dyslipidemia and osteoarthritis. The most frequent types of family are: nuclear or simple nuclear, with integrated nucleus and non-integrated nucleus; they subsist mainly on services; they live with levels 1 and 2 of family poverty; are modern and urban in greater number. Conclusions: the epidemiological, clinical and family characteristics of patients with mental disorders assigned to a Mexican family medicine unit (FMU) are mostly women, in middle adulthood, who attend more than a mental disorder (anxiety and depression), treated with drugs and psychotherapy, also had hypertension, and belong to families of simple nuclear type and non-integrated nucleus; subsist on services; they live with levels 1 and 2 of family poverty, they are modern and urban.

Non-productive angiogenesis disassembles Aß plaque-associated blood vessels.

The human Alzheimer's disease (AD) brain accumulates angiogenic markers but paradoxically, the cerebral microvasculature is reduced around Aß plaques. Here we demonstrate that angiogenesis is started near Aß plaques in both AD mouse models and human AD samples. However, endothelial cells express the molecular signature of non-productive angiogenesis (NPA) and accumulate, around Aß plaques, a tip cell marker and IB4 reactive vascular anomalies with reduced NOTCH activity. Notably, NPA induction by endothelial loss of presenilin, whose mutations cause familial AD and which activity has been shown to decrease with age, produced a similar vascular phenotype in the absence of Aß pathology. We also show that Aß plaque-associated NPA locally disassembles blood vessels, leaving behind vascular scars, and that microglial phagocytosis contributes to the local loss of endothelial cells. These results define the role of NPA and microglia in local blood vessel disassembly and highlight the vascular component of presenilin loss of function in AD.

Aripiprazole as a Candidate Treatment of COVID-19 Identified Through Genomic Analysis.

Background: Antipsychotics modulate expression of inflammatory cytokines and inducible inflammatory enzymes. Elopiprazole (a phenylpiperazine antipsychotic drug in phase 1) has been characterized as a therapeutic drug to treat SARS-CoV-2 infection in a repurposing study. We aim to investigate the potential effects of aripiprazole (an FDA approved phenylpiperazine) on COVID-19-related immunological parameters. Methods: Differential gene expression profiles of non-COVID-19 vs. COVID-19 RNA-Seq samples (CRA002390 project in GSA database) and drug-naïve patients with non-affective psychosis at baseline and after three months of aripiprazole treatment were identified. An integrative transcriptomic analyses of aripiprazole effects on differentially expressed genes in COVID-19 patients was performed. Findings: 82 out the 377 genes (21.7%) with expression significantly altered by aripiprazole have also their expression altered in COVID-19 patients and in 93.9% of these genes their expression is reverted by aripiprazole. The number of common genes with expression altered in both analyses is significantly higher than expected (Fisher's Exact Test, two tail; p value = 3.2e-11). 11 KEGG pathways were significantly enriched with genes with altered expression both in COVID-19 patients and aripiprazole medicated non-affective psychosis patients (p adj<0.05). The most significant pathways were associated to immune responses and mechanisms of hyperinflammation-driven pathology (i.e.,"inflammatory bowel disease (IBD)" (the most significant pathway with a p adj of 0.00021), "Th1 and Th2 cell differentiation" and "B cell receptor signaling pathway") that have been also associated with COVID19 clinical outcome. Interpretation: This exploratory investigation may provide further support to the notion that a protective effect is exerted by aripiprazole (phenylpiperazine) by modulating the expression of genes that have shown to be altered in COVID-19 patients. Along with many ongoing studies and clinical trials, repurposing available medications could be of use in countering SARS-CoV-2 infection, but require further studies and trials.

Comparison between conventional and chemomechanical approaches for the removal of carious dentin: an in vitro study.

The present study aimed to evaluate the efficiency, effectiveness, and biocompatibility of two agents used for the chemomechanical removal of carious dentin. Sixty extracted carious human teeth were treated with a conventional bur (CBG) or chemomechanical agents - Papacarie Duo (PG) and Brix 3000 (BG). Treatment efficiency and effectiveness were assessed by the working time for carious dentin removal and Knoop microhardness values, respectively. Human pulp fibroblasts (FP6) were used to evaluate cytotoxicity by incorporating MTT dye, and genotoxicity was evaluated with the micronuclei test. The carious tissue was removed in a shorter time with CBG (median = 54.0 seconds) than the time required for chemomechanical agents (p = 0.0001). However, the time was shorter for Brix 3000 (BG) than that for Papacarie Duo (PG), showing mean values of 85.0 and 110.5 seconds, respectively. Regarding microhardness testing, all approaches tested were effective (p < 0.05). The final mean microhardness values were 48.54 ± 16.31 KHN, 43.23 ± 13.26 KHN, and 47.63 ± 22.40 KHN for PG, BG, and CBG, respectively. PG decreased cell viability compared to that of BG, but it presented no genotoxicity. Brix 3000 may be a good option for chemomechanical dentin caries removal due to its reduced removal time and lower cytotoxicity compared to the other treatment options.

Fracturas de pelvis con hematoma retroperitoneal asociado: tiempo hasta la angioembolización y resultados / Pelvic fractures with associated retroperitoneal hematoma: time until angioembolization and results

Introducción: El tratamiento de las fracturas de pelvis con hematoma retroperitoneal (HRP) es controvertido. Especialmente la necesidad de angioembolización (AE) cuando no hay extravasación de contraste (EC) en la tomografía computarizada (TC) o angiografía. Otro aspecto relevante es el retraso hasta la misma. Nuestro objetivo ha sido determinar si existen diferencias en el tiempo hasta la AE entre los pacientes admitidos durante el horario laboral y los admitidos fuera del mismo y durante los fines de semana y festivos. Nuestra hipótesis era que la angiografía y AE serían más frecuentes en el horario laboral, y el tiempo hasta las mismas sería superior fuera del horario laboral habitual, con una mortalidad mayor en este grupo para una gravedad global similar. Un objetivo secundario ha sido valorar la correlación entre EC en la TC y la angiografía. Métodos: Análisis retrospectivo de 2 cohortes de pacientes con HRP por fractura de pelvis. Se estudia la realización de angiografía dividiendo a los pacientes según su hora de llegada a lo largo de un periodo de 24 años (grupo A: horario laboral, y grupo B: fuera del mismo). La indicación de angiografía y AE fue realizada por la guardia de cirugía general, en consenso con el radiólogo intervencionista. Se han analizado variables demográficas, mecanismo lesivo, lesiones asociadas, gravedad fisiológica y anatómica, EC en la TC y la angiografía, necesidad de AE, estancia en unidad de cuidados intensivos (UCI) y mortalidad. Resultados: Se admitió a 104 pacientes con diagnóstico de HRP por fractura pélvica. Se realizó angiografía, con AE en 63 casos (61%). Los grupos eran comparables en las variables analizadas. En el 70% de los pacientes del grupo A se realizó angiografía, frente al 57% del grupo B, sin diferencias en tiempo hasta la AE. Se demostró EC en la TC en 53 de los 96 pacientes en los que se hizo, lo que se confirmó mediante angiografía en el 85%. No hubo diferencias estadísticamente significativas de mortalidad entre ambos grupos. Conclusiones: Se demuestra un tiempo corto entre la admisión en Urgencias y la AE, sin relación con el momento del ingreso durante el día, y una buena correlación entre la EC en la TC y la angiografía

Introduction: Two areas of controversy in the management of bleeding pelvic fractures are the need to perform angioembolization (AE) in patients with a retroperitoneal hematoma (RPH) but no contrast extravasation (CE) on Computerized Tomography (CT) and/or angiography, and the delay to AE. Our main objective was to assess whether there had been differences in the percentage and delay to AE between patients admitted on weekdays versus off-hours (weekends and admission after 3pm) at our hospital. Our hypothesis was that angiography and AE would be more frequent on weekdays, and the time delay would be longer during off-hours, with a higher mortality in this latter group for a similar overall severity. A secondary objective was to assess the correlation between CE on CT scan and angiography. Methods: Retrospective review of two cohorts of patients with RPH from a pelvic fracture during a period of 24 years. Patients were divided depending on the time of arrival (Group A: weekdays, and Group B: off-hours). The decision to perform angiography and AE was made by the general surgeons on call, in consensus with the interventional radiologist. We analyzed demographics, mechanism of injury, associated injuries, physiologic and anatomic trauma scores, CE on CT scan, need of AE, Intensive Care Unit (ICU) stay and mortality. Results: 104 patients were admitted with RPH from a pelvic fracture. We performed AE in 63 cases (61%). The groups were comparable in the variables analyzed. In 70% of patients in group A, angiography was done, vs 57% in group B, with the same median time delay. CE on CT scan was seen in 53 out of 96 patients and confirmed by angiography in 45 (85%) of them. No significant differences were found in mortality between the two groups. Conclusions: There was a short delay from admission to AE, even during off-hours, and a good correlation of CE on CT scan and angiography

Pelvic fractures with associated retroperitoneal hematoma: time until angioembolization and results. / Fracturas de pelvis con hematoma retroperitoneal asociado: tiempo hasta la angioembolización y resultados.

INTRODUCTION: Two areas of controversy in the management of bleeding pelvic fractures are the need to perform angioembolization (AE) in patients with a retroperitoneal hematoma (RPH) but no contrast extravasation (CE) on Computerized Tomography (CT) and/or angiography, and the delay to AE. Our main objective was to assess whether there had been differences in the percentage and delay to AE between patients admitted on weekdays versus off-hours (weekends and admission after 3pm) at our hospital. Our hypothesis was that angiography and AE would be more frequent on weekdays, and the time delay would be longer during off-hours, with a higher mortality in this latter group for a similar overall severity. A secondary objective was to assess the correlation between CE on CT scan and angiography. METHODS: Retrospective review of two cohorts of patients with RPH from a pelvic fracture during a period of 24 years. Patients were divided depending on the time of arrival (Group A: weekdays, and Group B: off-hours). The decision to perform angiography and AE was made by the general surgeons on call, in consensus with the interventional radiologist. We analyzed demographics, mechanism of injury, associated injuries, physiologic and anatomic trauma scores, CE on CT scan, need of AE, Intensive Care Unit (ICU) stay and mortality. RESULTS: 104 patients were admitted with RPH from a pelvic fracture. We performed AE in 63 cases (61%). The groups were comparable in the variables analyzed. In 70% of patients in group A, angiography was done, vs 57% in group B, with the same median time delay. CE on CT scan was seen in 53 out of 96 patients and confirmed by angiography in 45 (85%) of them. No significant differences were found in mortality between the two groups. CONCLUSIONS: There was a short delay from admission to AE, even during off-hours, and a good correlation of CE on CT scan and angiography.

Evaluating the reliability of specific and global methods to assess the phenolic content of virgin olive oil: Do they drive to equivalent results?

Despite the huge number of different published methodologies, there is an open debate regarding which one is the most convenient analytical strategy for the determination of phenolic compounds from virgin olive oils. Diverse technical issues together with the disparity of criteria regarding results expression cause a lot of confusion. Herewith, a systematic comparison between specific (a powerful and LC-MS method) and global methodologies (the Folin-Ciocalteau (FC) colorimetric assay, the International Olive Council (IOC) method and hydrolysis plus HPLC-DAD) has been carried out. Thus, these strategies have been applied to the analysis of 50 extra virgin olive oils (covering all the possible quantitative ranges of these substances). This is the first time in which the individual LC-MS quantification of so many phenolic substances is included in this kind of comprehensive comparison. The outcomes of all the strategies have been thoroughly confronted and their equivalence (or divergence) has been carefully evaluated, establishing possible correspondence factors. The LC-MS individual determination with the pure standard of every analyte represented the ideal situation; when only the commercially available standards were used, a drastic change was observed in the absolute concentrations of oleuropein derivatives (in terms of hydroxytyrosol). Total phenolic content (summing individual levels) proved to be higher (1.9-3.0 times when data was expressed in mg/kg) than the values given by the three non-specific methods (with R2 from 0.84 to 0.90). In any case, the IOC method, the FC assay and the hydrolysis approach could be considered as feasible strategies when a global value is pursued. Good correlations between their results were found (R2 > 0.89), with the following equivalence factors: FC(mg caffeic acid/kg) ≈ 0.60 IOC(mg TY/kg); IOC(mg TY/kg) ≈ 1.27 Sum acid hydrolysis(mg TY+HTY/kg); FC(mg HTY/kg) ≈ 1.04 Sum acid hydrolysis(mg TY+HTY/kg).

Proteolytic Processing of Neurexins by Presenilins Sustains Synaptic Vesicle Release.

Proteolytic processing of synaptic adhesion components can accommodate the function of synapses to activity-dependent changes. The adhesion system formed by neurexins (Nrxns) and neuroligins (Nlgns) bidirectionally orchestrate the function of presynaptic and postsynaptic terminals. Previous studies have shown that presenilins (PS), components of the gamma-secretase complex frequently mutated in familial Alzheimer's disease, clear from glutamatergic terminals the accumulation of Nrxn C-terminal fragments (Nrxn-CTF) generated by ectodomain shedding. Here, we characterized the synaptic consequences of the proteolytic processing of Nrxns in cultured hippocampal neurons from mice and rats of both sexes. We show that activation of presynaptic Nrxns with postsynaptic Nlgn1 or inhibition of ectodomain shedding in axonal Nrxn1-ß increases presynaptic release at individual terminals, likely reflecting an increase in the number of functional release sites. Importantly, inactivation of PS inhibits presynaptic release downstream of Nrxn activation, leaving synaptic vesicle recruitment unaltered. Glutamate-receptor signaling initiates the activity-dependent generation of Nrxn-CTF, which accumulate at presynaptic terminals lacking PS function. The sole expression of Nrxn-CTF decreases presynaptic release and calcium flux, recapitulating the deficits due to loss of PS function. Our data indicate that inhibition of Nrxn processing by PS is deleterious to glutamatergic function.SIGNIFICANCE STATEMENT To gain insight into the role of presenilins (PS) in excitatory synaptic function, we address the relevance of the proteolytic processing of presynaptic neurexins (Nrxns) in glutamatergic differentiation. Using synaptic fluorescence probes in cultured hippocampal neurons, we report that trans-synaptic activation of Nrxns produces a robust increase in presynaptic calcium levels and neurotransmitter release at individual glutamatergic terminals by a mechanism that depends on normal PS activity. Abnormal accumulation of Nrxn C-terminal fragments resulting from impaired PS activity inhibits presynaptic calcium signal and neurotransmitter release, assigning synaptic defects to Nrxns as a specific PS substrate. These data may provide links into how loss of PS activity inhibits glutamatergic synaptic function in Alzheimer's disease patients.

Chronic stress alters the expression levels of longevity-related genes in the rat hippocampus.

The molecular mechanisms underlying the negative effects of psychological stress on cellular stress during aging and neurodegenerative diseases are poorly understood. The main objective of this study was to test the effect of chronic psychological stress, and the consequent increase of circulating glucocorticoids, on several hippocampal genes involved in longevity. Sirtuin-1, p53, thioredoxin-interacting protein, and heat shock protein 70 were studied at the mRNA and protein levels in stressed and non-stressed animals. Stress treatment for 10 days decreased sirtuin-1 and heat shock protein 70 levels, but increased levels of p53, thioredoxin-interacting protein and the NADPH oxidase enzyme. Examination of protein expression following two months of stress treatment indicated that sirtuin-1 remained depressed. In contrast, an increase was observed for thioredoxin-interacting protein, heat shock protein 70, p53 and the NADPH oxidase enzyme. The effect of stress was reversed by mifepristone, a glucocorticoid receptor antagonist. These data suggest that chronic stress could contribute to aging in the hippocampus.

Sustainable application of pecan nutshell waste: Greener synthesis of Pd-based nanocatalysts for electro-oxidation of methanol.

Palladium-based electrocatalysts are widely used in alkaline direct alcohol fuel cells. The synthesis and characterization of carbon-supported bimetallic nanoparticles (NP) of AuPd and AgPd is described using pecan nutshell extract (Carya illinoinensis) which serves as both, reducing and the stabilizing agent. This environmentally friendly route generates bimetallic NP for a wide range of applications, including electrocatalysis; since particularly AuPd NP proved to be a potentially suitable electrode material for alkaline direct methanol fuel cells. The electrocatalytic activity of these nanomaterials was comparable to commercially available Pd/C 1% in the electro-oxidation of methanol in alkaline media.

Hipotiroidismo subclínico en una muestra oportunista de la población de Castilla y León / Prevalence and clinical characteristics of subclinical hypothyroidism in an opportunistic sample in the population of Castile-León (Spain)

Objetivo: Describir la distribución de los valores de la hormona estimulante del tiroides (TSH) y estimar la prevalencia de hipotiroidismo subclínico en la población adulta de Castilla y León. Material y método: Estudio observacional en 45 consultas de medicina de familia de Castilla y León seleccionadas de manera oportunista. Se determinó la TSH en sueros, recogidos por cualquier motivo, de personas ≥35 años de edad. Se realizó análisis de confirmación, incluyendo la tiroxina libre y los anticuerpos antitiroperoxidasa. Resultados: Se realizaron 3957 análisis. El 63,4% eran mujeres. La edad media fue de 61,5 años. La mediana de los valores de TSH fue de 2,3 ¿UI/mL (2, ¿UI/mL en mujeres y 2,1 ¿UI/mL en hombres), con tendencia ascendente con la edad. Los valores de TSH son mayores en los hipotiroidismos subclínicos desconocidos o sin tratamiento que en los tratados. Los valores más bajos se observan en los sujetos eutiroideos. La prevalencia de hipotiroidismo subclínico fue del 9,2% (intervalo de confianza del 95%: 8,3-10,2); en las mujeres fue el triple que en los hombres (12,4% frente a 3,7%) y aumenta con la edad, con un máximo del 16,9% en las mujeres de 45 a 64 años. Conclusiones: La prevalencia estimada de hipotiroidismo subclínico es alta, en los límites superiores reflejados en la literatura. La posibilidad de progresión a hipotiroidismo manifiesto, así como la asociación con diversas enfermedades y factores de riesgo, aconsejan una gestión adecuada de su diagnóstico y tratamiento (AU)

Objective: To describe the distribution of thyroid-stimulating hormone (TSH) values and to estimate the prevalence of subclinical hypothyroidism in the adult population of Castile and León (Spain). Method: An observational study was conducted in an opportunistic sample of 45 primary care centers in Castile and León. TSH was determined in people aged ≥35 years that attended a primary care physician and had a blood test for any reason. Confirmatory analysis included free thyroxine and anti-thyroid peroxidase antibody determination. Results: A total of 3957 analyses were carried out, 63% in women. The mean age was 61.5 years. The median TSH value was 2.3 ¿IU/mL (2.5 ¿IU/mL in women and 2.1 ¿IU/mL in men), with a rising trend with age. TSH values were higher in undiagnosed or untreated subclinical hypothyroidism than in patients under treatment. The lowest levels were found in euthyroidism. The prevalence of subclinical hypothyroidism was 9.2% (95%CI: 8.3-10.2), and hypothyroidism was three times higher in women than in men (12.4% versus 3.7%). Hypothyroidism increased with age, reaching a peak of 16.9% in women aged 45 to 64 years. Conclusions: The prevalence of subclinical hypothyroidism in our sample was high and in the upper limits of values found in previous studies. Proper diagnosis and treatment are important because of the risk of progression to hypothyroidism and the association with multiple diseases and other risk factors (AU)