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The concept of exposome covers all the exposures an individual suffers from conception to death, which can be partially assessed through the monitoring of human biofluids. In there, target analytical approaches tend to focus on a limited set of xenobiotics, whereas exposomic studies need broad scopes in search of a full understanding. Given the issue, suspect and non-target screening are feasible alternatives. However, adequate sample preparation procedures should minimize interferences without significantly reducing the number of xenobiotics. Within this context, the present article aims to describe comprehensive sample preparation procedures for suspect or non-target screening of organic xenobiotics in several human biofluids, all coupled to unified separation and detection conditions based on ultra-high performance liquid chromatography-high resolution tandem mass spectrometry (UHPLCHRMS/MS). The referred biofluids consist of human urine, breast milk, saliva and ovarian follicular fluid. • Analytical methods for untargeted analysis of a wide range of xenobiotics in human biofluids are fully described in order to ensure reproducibility. • The sample preparation procedures balance selectivity and sensitivity. • Unified analysis conditions allow simultaneous analysis of diverse biofluids.

As a contribution to the forthcoming 500th anniversary of the publication of Margaret Roper (née More)’s A Devout Treatise (1524-2024), the purpose of this article is to make a survey of her written production (public and private), including those works that were preserved as well as those others that were written but have been lost. The trial and death of Thomas More necessarily resulted in the loss of documents and writings, not only by More but by his daughter too. Sixteenth-century biographies of Thomas More are the main source of information about his daughter Margaret (1505-1544) and her written production. These early biographers were clearly concerned with the promotion of the figure of More, but they did not let pass the opportunity to ponder and testify to the scholarly excellence of his eldest daughter. This is particularly the case of Nicholas Harpsfield (1557) and, more especially, Thomas Stapleton (1588). Cresacre More’s biography of More (Douai, 1631), even though in general terms it offers no original information, has also been used in this study. Another important corpus of information is the epistolary writings of Margaret and her father, as well as of Erasmus. Various other documents subject to recent literary criticism are also consulted.

Space resource utilisation is opening a new space era. The scientific proof of the presence of water ice on the south pole of the Moon, the recent advances in oxygen extraction from lunar regolith, and its use as a material to build shelters are positioning the Moon, again, at the centre of important space programs. These worldwide programs, led by ARTEMIS, expect robotics to be the disrupting technology enabling humankind’s next giant leap. However, Moon robots require a high level of autonomy to perform lunar exploration tasks more efficiently without being constantly controlled from Earth. Furthermore, having more than one robotic system will increase the resilience and robustness of the global system, improving its success rate, as well as providing additional redundancy. This paper introduces the Resilient Exploration and Lunar Mapping System, developed with a scalable architecture for semi-autonomous lunar mapping. It leverages Visual Simultaneous Localization and Mapping techniques on multiple rovers to map large lunar environments. Several resilience mechanisms are implemented, such as two-agent redundancy, delay invariant communications, a multi-master architecture different control modes. This study presents the experimental results of REALMS with two robots and its potential to be scaled to a larger number of robots, increasing the map coverage and system redundancy. The system’s performance is verified and validated in a lunar analogue facility, and a larger lunar environment during the European Space Agency (ESA)-European Space Resources Innovation Centre Space Resources Challenge. The results of the different experiments show the efficiency of REALMS and the benefits of using semi-autonomous systems.

AbstractThe development of effective combined anti-retroviral therapy (cART) led to a significant reduction in the death rate associated with human immunodeficiency virus type 1 (HIV-1) infection. However, recent studies indicate that considerably more than 50% of all HIV-1 infected patients develop HIV-1-associated neurocognitive disorder (HAND). Microglia are the foremost cells infected by HIV-1 in the central nervous system (CNS), and so, are also likely to contribute to the neurotoxicity observed in HAND. The activation of microglia induces the release of pro-inflammatory markers and altered secretion of cytokines, chemokines, secondary messengers, and reactive oxygen species (ROS) which activate signalling pathways that initiate neuroinflammation. In turn, ROS and inflammation also play critical roles in HAND. However, more efforts are required to understand the physiology of microglia and the processes involved in their activation in order to better understand the how HIV-1-infected microglia are involved in the development of HAND. In this review, we summarize the current state of knowledge about the involvement of oxidative stress mechanisms and role of HIV-induced ROS in the development of HAND. We also examine the academic literature regarding crucial HIV-1 pathogenicity factors implicated in neurotoxicity and inflammation in order to identify molecular pathways that could serve as potential therapeutic targets for treatment of this disease.KEY MESSAGESNeuroinflammation and excitotoxicity mechanisms are crucial in the pathogenesis of HAND.CNS infiltration by HIV-1 and immune cells through the blood brain barrier is a key process involved in the pathogenicity of HAND.Factors including calcium dysregulation and autophagy are the main challenges involved in HAND.

Introducción: como consecuencia del aislamiento social asociado al COVID-19, la depresión y la ansiedad son dos de los trastornos afectivos más frecuentes en el adulto mayor. Objetivo: determinar la relación entre depresión y ansiedad con el aislamiento social en adultos mayores en una clínica de primer nivel de atención. Material y métodos: se llevó a cabo un estudio observacional descriptivo de corte transversal en pacientes de 65 años en adelante, de ambos sexos, en aislamiento social debido al confinamiento. Se aplicó un cuestionario validado para el diagnóstico de ansiedad y depresión, así como otro con preguntas sobre el aislamiento social y sobre variables sociodemográficas. Se utilizaron las pruebas estadísticas U de Mann-Whitney y Kruskall Wallis, con nivel de significancia de 0.05. Programa SPSS. Versión 26. Resultados: se incluyeron 286 adultos mayores, con promedio de edad de 70.6 años, 54.2 % pertenecían al sexo femenino. Con relación al aislamiento social, 73.4 % refirieron falta de relación con sus amigos. El promedio del puntaje del cuestionario fue de 45.06 (IC95%: 43.4 % - 46.6 %). Solamente el 25.3 % no presentó ni ansiedad, ni depresión, y en 51.1 % se identificó algún tipo de depresión. Respecto al aislamiento social y su relación con ansiedad y depresión; se obtuvo significancia estadística en todas las preguntas. Conclusión: el aislamiento social de los adultos mayores debido al confinamiento por el SARS-CoV2, se relacionó con significancia estadística tanto con la ansiedad como con la depresión, sin dejar de remarcar que en 75% de los pacientes se presentó alguna de las dos condiciones.

Antecedentes: Existe consenso en que la cesárea ha sido fundamental en la disminución de la morbimortalidad materno-infantil, sin embargo, desde 1985 expertos consultados por la Organización Mundial de la Salud (OMS), concluyeron que la tasa ideal de cesáreas debe oscilar entre el 10 y el 15%. La proporción real actual supera ampliamente lo recomendado. El último informe de la Organización para la Cooperación y el Desarrollo Económicos (OCDE), publicado en enero de 2019, señala a Chile en el tercer lugar con mayor porcentaje de cesáreas. Este dato es preocupante, ya que el exceso de intervenciones quirúrgicas vs. parto normal se asocia a un aumento de la morbimortalidad materna y a un mayor riesgo para el recién nacido. Objetivo: Revisar los porcentajes de cesáreas en las muertes maternas, tanto en establecimientos públicos como privados de la región de Los Lagos, Chile, y detectar si existe una asociación entre cesáreas y mortalidad materna. Resultados: Se puede apreciar una relación entre las cesáreas y las muertes maternas.

Abstract Background The microorganism present in breast milk, added to other factors, determine the colonization of infants. The objective of the present study is to evaluate the safety, tolerance and effects of the consumption of a milk formula during the first year of life that is supplemented with L. fermentum CECT5716 or Bifidobacterium breve CECT7263, two strains originally isolated from breast milk. Methods A randomized, double blind, controlled, parallel group study including healthy, formula-fed infants was conducted. Two hundred and thirty-six 1-month-old infants were selected and randomly divided into three study groups according to a randomization list. Infants in the control group received a standard powdered infant formula until 12 months of age. Infants in the probiotic groups received the same infant formula but supplemented with L. fermentum CECT5716 Lc40 or B. breve CECT7263. Main outcome was weigh-gain of infants as safety marker. Results One hundred and eighty-nine infants completed the eleven months of intervention (61 in control group, 65 in Lf group and 63 in Bb group). The growth of infants in the three groups was consistent with standards. No significant differences were observed in the main outcome, weight-gain (Control group: 5.77 Kg ± 0.95, Lf group: 5.77 Kg ± 1.31, Bb group: 5.58 Kg ± 1.10; p = 0.527). The three milk formulae were well tolerated, and no adverse effects were related to the consumption of any of the formula. Infants receiving B. breve CECT7263 had a 1.7 times lower risk of crying than the control group (OR = 0.569, CI 95% 0.568–0.571; p = 0.001). On the other hand, the incidence of diarrhoea in infants receiving the formula supplemented with L. fermentum CECT5716 was a 44% lower than in infants receiving the control formula (p = 0.014). The consumption of this Lactobacillus strain also reduced the duration of diarrhoea by 2.5 days versus control group (p = 0.044). Conclusions The addition of L. fermentum CECT5716 Lc40 or B. breve CECT7263, two probiotic strains naturally found in breast milk, to infant formulae is safe and induces beneficial effects on the health of infants. Trial registration The trial was retrospectively registered in the US Library of Medicine (www.clinicaltrial.gov) with the number NCT03204630. Registered 11 August 2016.

Lithium has shown the capacity to: a) inhibit the replication of several types of viruses, some of which are similar to the SARS-CoV-2 virus, b) increase the immune response by reducing lymphopenia, and c) reduce inflammation by preventing or reducing the cytokine storm. In the present study, we have treated six patients with severe COVID-19 infection with lithium carbonate. We found that lithium carbonate significantly reduced plasma reactive C-Protein levels, increased lymphocyte numbers and decreased the neutrophil-lymphocyte ratio, improving both inflammatory activity and the immune response in these patients. We propose that lithium carbonate may deserve a place in the treatment against COVID-19.

Antecedentes: Se analiza la evolución de la actividad de donación cadavérica de órganos y de la realización de trasplantes de órganos sólidos en México de 2007 a 2018. Método: Se recolectó y ordenó la información de donación cadavérica y de trasplante de órganos en México en ese período. Cuando no hubo información completa de 2018, se consideró la de 2017. Las principales fuentes de información fueron The Global Observatory on Donation and Transplantation y el Centro Nacional de Trasplantes de la Secretaría de Salud de México. Resultados: 1) La tasa de donación cadavérica de México en 2007 fue de 3.2 donaciones por millón de población (pmp), y en 2017 fue de 3.94 pmp (incremento del 23.1%). La tasa de 2017 está muy por debajo de la media reportada para América Latina (9.5 pmp). 2) El número de pacientes en espera de trasplante de un órgano sólido pasó de 4,993 en 2007 a 15,448 en 2018 (incremento del 309%). 3) En 2017, México reportó tener 255 centros autorizados para trasplante renal, más que cualquier país en el mundo. Para el caso de otros órganos, como hígado, corazón, pulmón y páncreas, México es el país que tiene más centros autorizados en América Latina. Conclusión: La evolución de las cifras de donación cadavérica y de trasplante de órganos sólidos en el período de estudio explica una escasez cada vez mayor de órganos para trasplante en México, a pesar de una aparente gran capacidad instalada. El sistema nacional de donación y trasplante de órganos es ineficaz e ineficiente.

This is a case of a patient affected by Cushing syndrome that was admitted at the hospital due to hormonal problems. He had presented psychiatric symptoms that were mistakenly considered not directly connected to the pathology causing the clinical condition, but a mere psychological reaction to it.

Abstract Background The pattern of serotonin transporter clustering on the plasma membrane of lymphocytes extracted from human whole blood samples has been identified as a putative biomarker of therapeutic efficacy in major depression. Here we evaluated the possibility of performing a similar analysis using blood smears obtained from rats, and from control human subjects and depression patients. We hypothesized that we could optimize a protocol to make the analysis of serotonin protein clustering in blood smears comparable to the analysis of serotonin protein clustering using isolated lymphocytes. Results Our data indicate that blood smears require a longer fixation time and longer times of incubation with primary and secondary antibodies. In addition, one needs to optimize the image analysis settings for the analysis of smears. When these steps are followed, the quantitative analysis of both the number and size of serotonin transporter clusters on the plasma membrane of lymphocytes is similar using both blood smears and isolated lymphocytes. Conclusions The development of this novel protocol will greatly facilitate the collection of appropriate samples by eliminating the necessity and cost of specialized personnel for drawing blood samples, and by being a less invasive procedure. Therefore, this protocol will help us advance the validation of membrane protein clustering in lymphocytes as a biomarker of therapeutic efficacy in major depression, and bring it closer to its clinical application.

Abstract Background A 12-week, double-blind, parallel, multi-center randomized controlled trial in 316 adult patients with major depressive disorder (MDD) was conducted to evaluate the effectiveness of pharmacogenetic (PGx) testing for drug therapy guidance. Methods Patients with a CGI-S ≥ 4 and requiring antidepressant medication de novo or changes in their medication regime were recruited at 18 Spanish public hospitals, genotyped with a commercial PGx panel (Neuropharmagen®), and randomized to PGx-guided treatment (n = 155) or treatment as usual (TAU, control group, n = 161), using a computer-generated random list that locked or unlocked psychiatrist access to the results of the PGx panel depending on group allocation. The primary endpoint was the proportion of patients achieving a sustained response (Patient Global Impression of Improvement, PGI-I ≤ 2) within the 12-week follow-up. Patients and interviewers collecting the PGI-I ratings were blinded to group allocation. Between-group differences were evaluated using χ2-test or t-test, as per data type. Results Two hundred eighty patients were available for analysis at the end of the 12-week follow-up (PGx n = 136, TAU n = 144). A difference in sustained response within the study period (primary outcome) was not observed (38.5% vs 34.4%, p = 0.4735; OR = 1.19 [95%CI 0.74-1.92]), but the PGx-guided treatment group had a higher responder rate compared to TAU at 12 weeks (47.8% vs 36.1%, p = 0.0476; OR = 1.62 [95%CI 1.00-2.61]), and this difference increased after removing subjects in the PGx-guided group when clinicians explicitly reported not to follow the test recommendations (51.3% vs 36.1%, p = 0.0135; OR = 1.86 [95%CI 1.13-3.05]). Effects were more consistent in patients with 1–3 failed drug trials. In subjects reporting side effects burden at baseline, odds of achieving a better tolerability (Frequency, Intensity and Burden of Side Effects Rating Burden subscore ≤2) were higher in the PGx-guided group than in controls at 6 weeks and maintained at 12 weeks (68.5% vs 51.4%, p = 0.0260; OR = 2.06 [95%CI 1.09-3.89]). Conclusions PGx-guided treatment resulted in significant improvement of MDD patient’s response at 12 weeks, dependent on the number of previously failed medication trials, but not on sustained response during the study period. Burden of side effects was also significantly reduced. Trial registration European Clinical Trials Database 2013-002228-18 , registration date September 16, 2013; ClinicalTrials.gov NCT02529462 , retrospectively registered: August 19, 2015.

Abstract Regulation of biological processes occurs through complex, synergistic mechanisms. In this study, we discovered the synergistic orchestration of multiple mechanisms regulating the normal and diseased state (age related macular degeneration, AMD) in the retina. We uncovered gene networks with overlapping feedback loops that are modulated by nuclear hormone receptors (NHR), miRNAs, and epigenetic factors. We utilized a comprehensive filtering and pathway analysis strategy comparing miRNA and microarray data between three mouse models and human donor eyes (normal and AMD). The mouse models lack key NHRS (Nr2e3, RORA) or epigenetic (Ezh2) factors. Fifty-four total miRNAs were differentially expressed, potentially targeting over 150 genes in 18 major representative networks including angiogenesis, metabolism, and immunity. We identified sixty-eight genes and 5 miRNAS directly regulated by NR2E3 and/or RORA. After a comprehensive analysis, we discovered multimodal regulation by miRNA, NHRs, and epigenetic factors of three miRNAs (miR-466, miR1187, and miR-710) and two genes (Ell2 and Entpd1) that are also associated with AMD. These studies provide insight into the complex, dynamic modulation of gene networks as well as their impact on human disease, and provide novel data for the development of innovative and more effective therapeutics.

There is an utmost necessity of developing novel biomarkers of depression that result in a more efficacious use of current antidepressant drugs. The present report reviews and discusses a recent series of experiments that focused on analysis of membrane protein clustering in peripheral lymphocytes as putative biomarkers of therapeutic efficacy for major depressive disorder. This review recapitulates how the ideas were originated, and the main findings demonstrated that analysis of serotonin transporter and serotonin 2 A receptor clustering in peripheral lymphocytes of naïve depression patients resulted in a discrimination of two subpopulations of depressed patients that showed a differential response upon 8 weeks of antidepressant treatment. The paper also reviews the usefulness of animal models of depression for an initial evaluation of membrane protein clustering in lymphocytes, which provides a screening tool to determine additional proteins to be further evaluated in depression patients. Finally, the present review provides a brief discussion of the general field of biomarkers of depression in relation to therapeutic outcomes and suggests additional ideas to provide extra value to the reviewed studies.

Currently, the automotive industry has made great advances in the incorporation of materials such as carbon fiber in high-performance cars. One of the main problems of these vehicles is warming, which is generated inside due to the heat transfer produced by solar radiation falling on the car, mainly on the roof. This research proposes the preparation of a composite material containing henequen natural fiber as a thermal barrier to be used as the roof of the car. In this research, 35 different laminates of 5 layers were prepared, combining carbon fiber, henequen natural fiber, fiberglass, and additives such as resin + Al2O3 or resin + Al. Reference samples were taken from stainless steel and one reference sample was extracted from the roof of the car. Considering the solar radiation and the heat transfer mechanisms, the temperature of the surface exposed to solar radiation was determined. The thermal conductivity of the 37 samples was determined, and the experimental results showed that the thermal conductivity of the steel with which the roof of the car is manufactured was 13.43 W·m−1·K−1 and that of the proposed laminate was 5.22 W·m−1·K−1, achieving a decrease in the thermal conductivity by 61.13%. Using the temperature and thermal conductivity data, the simulation (ANSYS) of the thermal system was performed. The results showed that the temperature inside the car with the carbon steel, which is currently used to manufacture high-performance cars, would be 62.34°C, whereas that inside the car with the proposed laminate would be 44.96°C, achieving a thermal barrier that allows a temperature difference of 17.38°C.

Naïve depression patients show alterations in serotonin transporter (SERT) and serotonin 2A (5HT2A) receptor clustering in peripheral lymphocytes, and these alterations have been proposed as a biomarker of therapeutic efficacy in major depression. Repeated corticosterone (CORT) induces a consistent depression-like phenotype and has been widely used as an animal model to study neurobiological alterations underlying the depressive symptoms. In this experiment, we used the CORT paradigm to evaluate whether depression-like behavior is associated with similar changes in the pattern of SERT and 5HT2A membrane protein clustering as those observed in depression patients. We also analyzed the clustering of other proteins expressed in lipid rafts in lymphocytes. Rats received daily CORT or vehicle injections for 21 consecutive days. Afterward they underwent the forced swim test to evaluate depression-like behavior, and isolated lymphocytes were analyzed by immunocytochemistry coupled to image-analysis to study clustering parameters of the SERT, 5HT2A receptor, dopamine transporter (DAT), Beta2 adrenergic receptor (β2AR), NMDA 2B receptor (NR2B), Pannexin 1 (Pnx1), and prion cellular protein (PrPc). Our results showed that CORT increases the size of protein clusters for all proteins with the exception of β 2AR, which is decreased. CORT also increased the number of clusters for Pnx1 and PrPc only. Overall, these results indicate that alterations in SERT and 5HT2A protein clustering in naïve depression patients are paralleled by changes seen in an animal model of depression. The CORT paradigm may be a useful screen for examining additional proteins in lymphocytes as a preliminary step prior to their analysis as biomarkers of depression in human blood samples.

The placement of immediate implants in the posterior sector is a widespread procedure where the success and survival rates are similar to those of traditional protocols. It has several anatomical challenges, such as the presence of interradicular bone septa that hinder a correct three-dimensional positioning of the implant and may compromise primary stability and/or cause damage of neighboring structures. The aim of this article is to present the treatment and the one-year clinical follow-up of a patient who received immediate implant placement using an interradicular bone-drilling technique before the molar extraction.

Introduction: diabetes mellitus type 2 (DM2) is a silent disease that affects up to 20% of our population and of it, up to 50% do not know that it suffers. This disease is associated with a high prevalence of risk factors such as overweight, obesity and physical inactivity. Frequently, DM2 is diagnosed late and sometimes generates a large number of associated complications that could be avoided.

Following the extraction of oil for biodiesel production, oilseed press cakes are high in fat. As the dietary supplementation of fat is currently considered the most promising strategy of consistently depressing methanogenesis, it follows that oilseed press cakes may have a similar potential for CH4 abatement. As such, this study aimed to characterise the nutritive value of several oilseed press cakes, glycerine and soybean meal (SBM) and to examine their effects on in vitro ruminal fermentation, digestion kinetics and CH4 production. Moringa press oil seeds exhibited the greatest in sacco effective degradability (ED) of DM and CP (p

Background: Obesity and the metabolic syndrome affect a considerable segment of the population worldwide, including health professionals. In fact, several studies have reported that physicians tend to have more cardiovascular risk factors than their patients. The present cross-sectional study assessed whether the Health Sciences students had a healthier lifestyle, thus could have a more preventive attitude towards chronic diseases than the general population. Materials and methods: Students of the medical-biological areas were surveyed by answering a questionnaire about familiar cardiovascular risk factors, personal smoking, alcohol drinking, dietary and exercise habits. Blood pressure was also measured, along with weight, height, and abdominal circumference. Results: 23.4% of the participants were overweight and 10% obese. Parental obesity was the most frequent risk factor, followed by social drinking and smoking. We found high consumption of animal derived foods, breakfast-like cereals, pastries, white bread and sweetened beverages; while low intake of fruit and vegetables were reported. More than half the sample reported to practice very little or no exercise at all. Discussion and conclusions: We found similar or even higher rates of risk factors than the average population, that may eventually lead to the development of chronic cardiometabolic diseases. Thus we can infer that biomedical education is inefficient in inducing healthy lifestyles among biomedical students, which could have impact in their future practice as they will most probable become obese health-professionals, thus fail to effectively treat their own patients.