Prophylactic treatment with the c-Abl inhibitor, neurotinib, diminishes neuronal damage and the convulsive state in pilocarpine-induced mice.

The molecular mechanisms underlying seizure generation remain elusive, yet they are crucial for developing effective treatments for epilepsy. The current study shows that inhibiting c-Abl tyrosine kinase prevents apoptosis, reduces dendritic spine loss, and maintains N-methyl-d-aspartate (NMDA) receptor subunit 2B (NR2B) phosphorylated in in vitro models of excitotoxicity. Pilocarpine-induced status epilepticus (SE) in mice promotes c-Abl phosphorylation, and disrupting c-Abl activity leads to fewer seizures, increases latency toward SE, and improved animal survival. Currently, clinically used c-Abl inhibitors are non-selective and have poor brain penetration. The allosteric c-Abl inhibitor, neurotinib, used here has favorable potency, selectivity, pharmacokinetics, and vastly improved brain penetration. Neurotinib-administered mice have fewer seizures and improved survival following pilocarpine-SE induction. Our findings reveal c-Abl kinase activation as a key factor in ictogenesis and highlight the impact of its inhibition in preventing the insurgence of epileptic-like seizures in rodents and humans.

Advances and challenges in the diagnosis and management of left ventricular noncompaction in adults: A literature review.

In the realm of cardiovascular health, isolated left ventricular noncompaction (LVNC) stands out for its distinct morphological features and the clinical challenges it presents, particularly in adults. This literature review explores the intricacies of LVNC, aiming to unravel its epidemiological spread, diagnostic hurdles, and therapeutic strategies. Despite technological advancements in cardiac imaging that have improved the recognition of LVNC, a significant gap persists alongside a fragmented understanding of its pathogenesis. The studies scrutinized reveal a broad spectrum of prevalence rates influenced by diverse diagnostic tools and demographic variables. This variation underscores the complexity of accurately identifying LVNC and the resultant implications for clinical management. The review succinctly addresses the need for precise guidelines to navigate the diagnosis of LVNC and outlines the imperative for tailored clinical management approaches that cater to the wide array of patient presentations, from asymptomatic cases to those with severe cardiac dysfunction. By highlighting the critical gaps in current literature-namely the absence of standardized diagnostic criteria and a comprehensive pathogenic model-the review sets the stage for future research directions. These endeavors are essential for enhancing diagnostic accuracy, refining management protocols, and ultimately improving patient outcomes in this complex subset of cardiomyopathy, thus contributing significantly to the advancement of cardiovascular medicine.

Education's impact on primary care dentists' confidence in treating patients with special health care needs.

INTRODUCTION: Special care dentistry (SCD) is still developing in XX. This study aimed to clarify whether primary care dentists are treating patients with special health care needs (SHCN), to know if they have had previous education on SCD (on an undergraduate or postgraduate level), whether their training level impacts their confidence when treating patients with SHCN, and to assess their opinion on SCD as a relevant topic in undergraduate education. METHODS: A survey was answered by 149 primary care dentists working for the National Health Service of the XX region in XX, including information on their daily clinical practice, undergraduate, and postgraduate training in SCD, and their opinions on them. RESULTS: Most interviewees would like to complement their training and believed that SCD should be formally incorporated into undergraduate programs. There was a significant association between confidence in treating patients with SHCN and the rating of their undergraduate training, and between confidence and the number of hours of continuous development courses. CONCLUSION: Most primary care dentists treat patients with SHCN regularly. Therefore, including training in the undergraduate curriculum and afterward becomes necessary to increase their confidence when facing this challenging group of patients.

Microplastics in water, feed and tissues of European seabass reared in a recirculation aquaculture system (RAS).

Plastic particles (PLs) are ubiquitous in aquatic ecosystems, and aquaculture production is susceptible to contamination from external or endogenous sources. This study investigated PL presence in water, fish feed and body sites of 55 European seabass produced in a recirculating aquaculture system (RAS). Fish morphometric parameters and health status biomarkers were determined. A total of 372 PLs were recovered from water (37.2 PL/L), 118 PLs from feed (3.9 PL/g), and 422 from seabass (0.7 PL/g fish; all body sites analysed). All 55 specimens had PLs in at least two of the four body sites analysed. Concentrations were higher in the gastrointestinal tract (GIT; 1.0 PL/g) and gills (0.8 PL/g) than in the liver (0.8 PL/g) and muscle (0.4 PL/g). PL concentration in GIT was significantly higher than in muscle. Black, blue, and transparent fibres made of man-made cellulose/rayon and polyethylene terephthalate were the most common PLs in water and seabass, while black fragments of phenoxy resin were the most common in feed. The levels of polymers linked to RAS components (polyethylene, polypropylene, and polyvinyl chloride) were low, suggesting a limited contribution to the overall PL levels found in water and/or fish. The mean PL size recovered from GIT (930 µm) and gills (1047 µm) was significantly larger than those found in the liver (647 µm) and dorsal muscle (425 µm). Considering all body sites, PLs bioconcentrated in seabass (BCFFish >1), but their bioaccumulation did not occur (BAFFish <1). No significant differences were observed in oxidative stress biomarkers between fish with low (<7) and high (≥7) PL numbers. These findings suggest that fish produced in RAS are mainly exposed to MPs through water and feed. Further monitoring under commercial conditions and risk assessment are warranted to identify potential threats to fish and human health and define mitigating measures.

c-Abl tyrosine kinase down-regulation as target for memory improvement in Alzheimer's disease.

Background: Growing evidence suggests that the non-receptor tyrosine kinase, c-Abl, plays a significant role in the pathogenesis of Alzheimer's disease (AD). Here, we analyzed the effect of c-Abl on the cognitive performance decline of APPSwe/PSEN1ΔE9 (APP/PS1) mouse model for AD. Methods: We used the conditional genetic ablation of c-Abl in the brain (c-Abl-KO) and pharmacological treatment with neurotinib, a novel allosteric c-Abl inhibitor with high brain penetrance, imbued in rodent's chow. Results: We found that APP/PS1/c-Abl-KO mice and APP/PS1 neurotinib-fed mice had improved performance in hippocampus-dependent tasks. In the object location and Barnes-maze tests, they recognized the displaced object and learned the location of the escape hole faster than APP/PS1 mice. Also, APP/PS1 neurotinib-fed mice required fewer trials to reach the learning criterion in the memory flexibility test. Accordingly, c-Abl absence and inhibition caused fewer amyloid plaques, reduced astrogliosis, and preserved neurons in the hippocampus. Discussion: Our results further validate c-Abl as a target for AD, and the neurotinib, a novel c-Abl inhibitor, as a suitable preclinical candidate for AD therapies.

Política pública en cuidados paliativos y sus implicaciones sobre servicios, opioides y educación en Colombia / Public policy on palliative care and its implications for services, opioids, and education in Colombia

Introducción: El desarrollo de cuidados paliativos exige la intervención de múltiples dimensiones de salud pública, incluyendo la disponibilidad de servicios de salud, medicamentos esenciales y programas educativos. En Colombia se han realizado diversos cambios en las políticas públicas para promover la atención de personas con necesidades paliativas. Objetivo: Evaluar empíricamente las políticas públicas, existentes en cuidados paliativos y sus implicaciones sobre disponibilidad de servicios, opioides y programas educativos en los años 2010 ­ 2019 en Colombia. Materiales y métodos: Se diseñó un estudio mixto exploratorio secuencial en tres fases: identificación de indicadores empíricos de políticas nacionales, diagnostico situacional de cuidados paliativos y evaluación cualitativa de los resultados de la implementación de políticas en siete nodos territoriales de Colombia. Resultados: Se revisaron siete normas obteniendo 12 indicadores empíricos para la evaluación, seis de ellos no contaban con fuentes de información. El diagnostico nacional evidencia un aumento gradual de servicios y consumo de opioides en los años hito del desarrollo de políticas. 44 profesionales de cuidados paliativos perciben un efecto positivo de las políticas públicas en el consumo de opioides y bajos resultados para el dominio de servicios y educación Conclusiones: Existe una relación positiva entre políticas públicas y consumo de opioides, una relación cuantitativa positiva para servicios de cuidados paliativos y una relación cuanticualitativa negativa para programas educativos, lo que denota un bajo estatus operativo de las políticas construidas para mejorar el dolor y sufrimiento asociado a la enfermedad crónica avanzada.

Introduction: Palliative care development requires the intervention of multiple dimensions of public health, including the availability of health services, essential medicines, and educational programs. In Colombia, several changes have been made in public policy to promote the care of people with palliative needs. Objective: To empirically evaluate existing public policies on palliative care and their implications for the availability of services, opioids, and educational programs during the years 2010 to 2019 in Colombia. Materials and methods: A mixed sequential exploratory study was designed in three phases: identification of empirical indicators of national policies, palliative care situational diagnosis, and qualitative assessment of the results of policy implementation in seven regional nodes in Colombia. Results: Seven standards were reviewed, yielding 12 empirical indicators for assessment, six of which had no sources of information. The national diagnosis shows a gradual increase in services and opioid use during the landmark years of policy development. Forty-four palliative care professionals perceive a positive effect of public policy on opioid use and low outcomes for service and education domains. Conclusions: There is a positive relationship between public policy and opioid use, a positive quantitative relationship with palliative care services, and a negative quantitative-qualitative relationship with educational programs. This indicates a low operational status of policies designed to alleviate the pain and suffering associated with advanced chronic diseases.

Introdução: O desenvolvimento dos cuidados paliativos requer a intervenção de múltiplas dimensões da saúde pública, incluindo a disponibilidade de serviços de saúde, medicamentos essenciais e programas educativos. Na Colômbia, várias mudanças foram feitas nas políticas públicas para promover o cuidado de pessoas com necessidades paliativas. Objetivo: Avaliar empiricamente as políticas públicas existentes em cuidados paliativos e suas implicações na disponibilidade de serviços, opioides e programas educacionais nos anos 2010 - 2019 na Colômbia. Materiais e métodos: Desenhou-se um estudo misto exploratório sequencial em três fases: identificação de indicadores empíricos de políticas nacionais, diagnóstico situacional de cuidados paliativos e avaliação qualitativa dos resultados da implementação de políticas em sete nodos territoriais da Colômbia. Resultados: Sete normas foram revisadas, obtendo-se 12 indicadores empíricos para avaliação, seis delas não possuíam fontes de informação. O diagnóstico nacional mostra um aumento gradual nos serviços e consumo de opioides nos anos marcantes do desenvolvimento de políticas. 44 profissionais de cuidados paliativos percebem efeito positivo das políticas públicas sobre o consumo de opioides e resultados baixos para o domínio serviços e educação Conclusões: Existe relação positiva entre políticas públicas e consumo de opioides, relação quantitativa positiva para serviços de cuidados paliativos e negativa relação quantitativo-qualitativa para programas educativos, o que denota um baixo status operacional das políticas destinadas a melhorar a dor e o sofrimento associados à doença crônica avançada.

Comparison of Two Tuberculosis Infection Tests in a South American Tertiary Hospital: STANDARD F TB-Feron FIA vs. QIAreachTM QuantiFERON-TB.

INTRODUCTION: Tuberculosis (TB) is one of the most prevalent respiratory diseases in the world. In 2020 there were at least 9.9 million new infections, with 1.5 million deaths. Approximately 10% of people infected with Mycobacterium tuberculosis develop the disease during the first 2 to 5 years after infection. In South America, the diagnosis of Latent Tuberculosis Infections (LTBI) continues to be performed through the Mantoux tuberculin skin test (TST). OBJECTIVE: The objective of our study was to compare the sensitivity of a new immunofluorescence IGRA test against a widely available IGRA kit on the market. MATERIAL AND METHOD: Close contact with infectious TB patients, HIV patients, or immunocompromised for another cause were recruited. Two interferon-gamma release assay (IGRA) diagnostic kits were used and compared with TST. RESULTS: 76 patients were recruited, 93.42% were Chilean nationality, and 98.68% of the patients did not have immunosuppression. The sensitivity of the new technique was 88.89%, and the specificity was 92.50% in the study population compared to the IGRA previously used. In the subgroup older than 36 years, the sensitivity was 95.65%, and the specificity was 89.47%. CONCLUSION: IGRA techniques are a new resource in clinical laboratories to make an accurate diagnosis of LTBI in the region of the Americas. In our population, the greatest benefit of this new IGRA would be observed in people over 36 years of age, where the sensitivity of the technique was like that of the currently available test.

c-Abl kinase at the crossroads of healthy synaptic remodeling and synaptic dysfunction in neurodegenerative diseases.

Our ability to learn and remember depends on the active formation, remodeling, and elimination of synapses. Thus, the development and growth of synapses as well as their weakening and elimination are essential for neuronal rewiring. The structural reorganization of synaptic complexes, changes in actin cytoskeleton and organelle dynamics, as well as modulation of gene expression, determine synaptic plasticity. It has been proposed that dysregulation of these key synaptic homeostatic processes underlies the synaptic dysfunction observed in many neurodegenerative diseases. Much is known about downstream signaling of activated N-methyl-D-aspartate and α-amino-3-hydroxy-5-methyl-4-isoazolepropionate receptors; however, other signaling pathways can also contribute to synaptic plasticity and long-lasting changes in learning and memory. The non-receptor tyrosine kinase c-Abl (ABL1) is a key signal transducer of intra and extracellular signals, and it shuttles between the cytoplasm and the nucleus. This review focuses on c-Abl and its synaptic and neuronal functions. Here, we discuss the evidence showing that the activation of c-Abl can be detrimental to neurons, promoting the development of neurodegenerative diseases. Nevertheless, c-Abl activity seems to be in a pivotal balance between healthy synaptic plasticity, regulating dendritic spines remodeling and gene expression after cognitive training, and synaptic dysfunction and loss in neurodegenerative diseases. Thus, c-Abl genetic ablation not only improves learning and memory and modulates the brain genetic program of trained mice, but its absence provides dendritic spines resiliency against damage. Therefore, the present review has been designed to elucidate the common links between c-Abl regulation of structural changes that involve the actin cytoskeleton and organelles dynamics, and the transcriptional program activated during synaptic plasticity. By summarizing the recent discoveries on c-Abl functions, we aim to provide an overview of how its inhibition could be a potentially fruitful treatment to improve degenerative outcomes and delay memory loss.

Amyloid ß-Peptide Causes the Permanent Activation of CaMKIIα through Its Oxidation.

Alzheimer's disease (AD) is characterised by the presence of extracellular amyloid plaques in the brain. They are composed of aggregated amyloid beta-peptide (Aß) misfolded into beta-sheets which are the cause of the AD memory impairment and dementia. Memory depends on the hippocampal formation and maintenance of synapses by long-term potentiation (LTP), whose main steps are the activation of NMDA receptors, the phosphorylation of CaMKIIα and the nuclear translocation of the transcription factor CREB. It is known that Aß oligomers (oAß) induce synaptic loss and impair the formation of new synapses. Here, we have studied the effects of oAß on CaMKIIα. We found that oAß produce reactive oxygen species (ROS), that induce CaMKIIα oxidation in human neuroblastoma cells as we assayed by western blot and immunofluorescence. Moreover, this oxidized isoform is significantly present in brain samples from AD patients. We found that the oxidized CaMKIIα is active independently of the binding to calcium/calmodulin, and that CaMKIIα phosphorylation is mutually exclusive with CaMKIIα oxidation as revealed by immunoprecipitation and western blot. An in silico modelling of the enzyme was also performed to demonstrate that oxidation induces an activated state of CaMKIIα. In brains from AD transgenic models of mice and in primary cultures of murine hippocampal neurons, we demonstrated that the oxidation of CaMKIIα induces the phosphorylation of CREB and its translocation to the nucleus to promote the transcription of ARC and BDNF. Our data suggests that CaMKIIα oxidation would be a pro-survival mechanism that is triggered when a noxious stimulus challenges neurons as do oAß.

Identification of Exoenzymes Secreted by Entomopathogenic Fungus Beauveria pseudobassiana RGM 2184 and Their Effect on the Degradation of Cocoons and Pupae of Quarantine Pest Lobesia botrana.

Beauveria pseudobassiana RGM 2184 has shown 80% maximum efficacy against the pest Lobesia botrana in the autumn and winter seasons. This suggests that the strain possesses an interesting battery of enzymes that are cold-adapted to penetrate the thick and hydrophobic cocoon of L. botrana. In this study, screening of the proteolytic, lipolytic, and chitinolytic activity of enzyme extracts secreted by the RGM 2184 strain was carried out in various culture media. The enzyme extracts with the highest activity were subjected to zymography and mass spectrometry. These analyses allowed the identification of two proteases, two lipases, and three chitinases. Comparative analysis indicated that the degree of similarity between these enzymes was substantially reduced when the highest degree of taxonomic relatedness between RGM 2184 and the entomopathogenic fungus strain was at the family level. These results suggest that there is a wide variety of exoenzymes in entomopathogenic fungi species belonging to the order Hypocreales. On the other hand, exoenzyme extract exposure of cocoons and pupae of L. botrana provoked damage at 10 °C. Additionally, an analysis of the amino acid composition of the RGM 2184 exoenzyme grouped them close to the cold-adapted protein cluster. These results support the use of this strain to control pests in autumn and winter. Additionally, these antecedents can form a scaffold for the future characterization of these exoenzymes along with the optimization of the strain's biocontrol ability by overexpressing them.

Effects of testosterone therapy in adult males with hypogonadism and T2DM: A meta-analysis and systematic review.

BACKGROUND AND AIMS: Testosterone supplementation therapy (TST) is a longstanding treatment for hypogonadal men with type 2 diabetes mellitus (T2DM), even though the benefits of TST are variable among trials. This meta-analysis was done to determine the specific role of TST in hypogonadal men with T2DM. METHODS: PubMed, Embase, and Google Scholar were queried to discover eligible randomized controlled trials (RCTs) and observational studies. To quantify the specific effects of TST, we estimated pooled mean differences (MDs) and relative risks with 95% confidence intervals (CIs). RESULTS: Our meta-analysis included 1596 hypogonadal T2DM subjects from 12 randomized controlled trials and one observational study. TST can significantly enhance glycemic control compared to placebo by decreasing homeostatic model assessment of insulin resistance (WMD = -1.55 [-2.65, -0.45]; p = 0.26; I2 = 20.2%), fasting glucose (WMD = -0.35 [-0.79, 0.10]; p = 0.07; I2 = 69.7%), fasting insulin (WMD = -2.88 [-6.12, 0.36]; p = In addition, TST can decrease cholesterol (WMD = -0.28 [-0.47, -0.09] p = 0.0008; I2 = 91%) and triglyceride (WMD = -0.23 [-0.43, -0.03] p = 0.03; I2 = 79.2%). Furthermore, Testosterone therapy is related to a significant rise in total testosterone levels (WMD = 5.08 [2.90, 7.26] p = 0.0002; I2 = 92.9%). Pooling of free testosterone levels indicated a larger increase in the patients who got TST than placebo (WMD = 81.21 [23.87, 138.54] p = 0.07; I2 = 70%). CONCLUSION: Our findings suggested that TST can enhance glycemic control and hormone levels and reduce total cholesterol, triglyceride, LDL cholesterol whereas increase HDL cholesterol in hypogonadal T2DM patients. Therefore, in these patients, we propose TST alongside anti-diabetic treatment.

Alpinone: A positive regulator molecule of immune antiviral response in Atlantic salmon kidney cells.

Alpinone is a flavonoid obtained from the resinous exudate of Heliotropium huascoense. This flavonoid shows antiviral activity against the infectious salmon anemia virus (ISAV), which causes severe disease in farmed Atlantic salmon. Here, we aim to elucidate mechanisms underlying the antiviral effects of the flavonoid. In this regard, we evaluated whether Alpinone can act upregulating the pattern-recognition receptor genes, i.e., the RIG-I-like, TLR3, and TLR9 genes, and the genes of the downstream signaling pathways. Transcriptional expression of the genes was analyzed using real-time PCR after 8, 24, and 48 h treatment of salmon kidney adherent cells with 15 µg/mL of Alpinone. First, we showed that Alpinone induced IFNa expression in the kidney adherent cells, indicating that this type of salmon cells is in part responsible for the effects previously reported in vivo. Upregulation of the IFN-induced myxovirus resistance (Mx) gene was also observed in the head kidney cells in response to the treatment. Overexpression reached a maximum level at 24 h post-treatment. Interestingly, Alpinone also induced upregulation of the cytosolic receptors of ssRNA, named Retinoic acid-inducible gene I (RIG-I) and Melanoma Differentiation-Associated protein 5 (MDA5), but there were no effects on the transcriptional expression of the TLR3 and TLR9 endosomal receptors. In addition, Alpinone upregulated the expression of genes encoding the main components of the RIG-I/MDA5 signaling pathways, such as the mitochondrial antiviral-signaling protein (MAVS), TNF Receptor Associated Factor 3 (TRAF3), TANK-binding kinase 1 (TBK1), I-kappaB kinase ε (IKKε), the transcription factors IRF-3, and IRF7. The increased expression of all these genes is consistent with the upregulation of IFNa and Mx mRNAs. Because BX795 completely prevents Alpinone-dependent upregulation of IFNa and IRF3, the flavonoid targets seem to be upstream of the kinases TBK1 and IKKε. Altogether, this study contributes to elucidating the mechanisms involved in Alpinone antiviral activity in fish. Alpinone can be used to counteract virus mechanisms of evasion where the onset of interferon-mediated response is prevented or delayed.

c-Abl regulates a synaptic plasticity-related transcriptional program involved in memory and learning.

Memory consolidation requires activation of a gene expression program that allows de novo protein synthesis. But the molecular mechanisms that favour or restrict that program are poorly understood. The kinase c-Abl can modulate gene expression through transcription factors and chromatin modifiers. Here, we show that c-Abl ablation in the brain improves learning acquisition and memory consolidation in mice. Its absence also affects gene expression profiles in the mouse hippocampus. We found that genes involved in synaptic plasticity and actin cytoskeleton dynamics, such as Arp2 and Thorase, are up-regulated at the mRNA and protein levels in trained c-Abl KO mice and by a chemical-LTP stimulus. Trained c-Abl KO mice also show that dendritic spines are larger than in wild-type mice and present at a higher density. These results indicate that c-Abl kinase is an important part of the mechanism that limits or restricts signalling of relevant gene programs involved in morphological and functional spine changes upon neuronal stimulation.

Complicaciones por infección de Covid-19 en mujeres embarazadas y neonatos en el año 2020 / Complications from Covid-19 infection in pregnant women and neonates in the year 2020

La infección por Covid-19, se ha convertido en una emergencia en salud pública, a casi un año de su aparición ha dejado millones de muertos, el binomio materno-fetal es vulnerable ante este riesgo y la atención a este grupo, es un servicio esencial que requiere de apego a medidas de prevención, y desigualdad económica; el acceso y la capacidad de los servicios de salud son trascendentes en esta pandemia. Objetivo: Describir las complicaciones y sintomatología principal relacionadas con infección por Covid-19 en mujeres embarazadas y neonatos a nivel mundial y número de casos reportados en México. Metodología: Se realizó una revisión sistemática en Cochrane, MEDLINE, PubMed, NCBI, Scielo y Google Scholar. páginas de la OMS, Secretaria de Salud de México, (FEMECOG), 3 libros acerca de Coronavirus, 2020, información para la determinación de la morbimortalidad materno fetal y sintomatología por infección COVID-19 de diciembre, 2019 a julio, 2020; en cuanto a la epidemiología mexicana se revisaron fuentes actualizadas de octubre de 2020. Resultados: Las mujeres embarazadas con infección por Covid-19 tienen alto riesgo de experimentar complicaciones obstétricas y neonatales: aborto espontáneo, parto pretérmino, restricción del crecimiento intrauterino, ingreso a unidad de cuidados intensivos, necesidad de ventilación mecánica y neumonia. En la infección por Covid-19 las características clínicas más comunes fueron fiebre, tos y fatiga. Hasta el 18 de octubre del 2020 se han registrado un total de 6,761 embarazadas y/o puérperas y 1387 recién nacidos positivos confirmados a Covid-19 en México. Conclusión: La comorbilidad en embarazadas es determinante en la evolución, comportamiento y complicaciones de la infección por Covid-19 y las medidas de prevención ineficientes, de continuar así, los resultados serán indudablemente negativos.(AU)

The Covid-19 infection has become a public health emergency, almost a year after its appearance it has left millions of deaths, the maternal-fetal pairing is vulnerable to this risk and care for this group is a service essential that requires adherence to prevention measures, and economic inequality; the access and capacity of health services are transcendent in this pandemic. Objective: Describe the complications and main symptoms related to Covid-19 infection in pregnant women and neonates worldwide and the number of cases reported in Mexico. Methodology: A systematic review was performed in Cochrane, MEDLINE, PubMed, NCBI, Scielo, and Google Scholar. pages of the WHO, Secretary of Health of Mexico, (FEMECOG), 3 books about Coronavirus, 2020, information for the determination of fetal maternal morbidity and mortality and symptoms due to COVID-19 infection from December 19, 2019 to July, 2020 Regarding Mexican epidemiology, updated sources from October 2020 were reviewed. Results: Pregnant women with Covid-19 infection are at high risk of experiencing obstetric and neonatal complications: miscarriage, preterm delivery, intrauterine growth restriction, admission to the intensive care unit, need for mechanical ventilation and pneumonia. In Covid-19 infection, the most common clinical characteristics were fever, cough, and fatigue. Until October 18, 2020, a total of 6,761 pregnant and / or postpartum women and 1,387 positive newborns confirmed to Covid-19 have been registered in Mexico. Conclusion: Comorbidity in pregnant women is a determining factor in the evolution, behavior and complications of Covid-19 infection and inefficient prevention measures, if this continues, the results will undoubtedly be negative.(AU)

Isolation of Nuclei from Mammalian Cells and Tissues for Single-Nucleus Molecular Profiling.

Both single-cell RNA sequencing (scRNAseq) and single-nucleus RNA sequencing (snRNAseq) can be used to characterize the transcriptional profile of individual cells, and based on these transcriptional profiles, help define cell type distribution in mixed cell populations. However, scRNAseq analyses are confounded if some of the cells are large (>50 µm) or if some of cells adhere more tightly to some adjacent cells than to others. Further, single cell isolation for scRNAseq requires fresh tissue, which may not be available for human or animal model tissues. Additionally, the current enzymatic and mechanical methods for single-cell dissociation can lead to stress-induced transcriptional artifacts. Nuclei for snRNAseq, on the other hand, can be isolated from any cell, regardless of size, and from either fresh or frozen tissues, and compared to whole cells, they are more resistant to mechanical pressures and appear not to exhibit as many cell isolation-based transcriptional artifacts. Here, we describe a time- and cost-effective procedure to isolate nuclei from mammalian cells and tissues. The protocol incorporates steps to mechanically disrupt samples to release nuclei. Compared to conventional nuclei isolation protocols, the approach described here increases overall efficiency, eliminates risk of contaminant exposure, and reduces volumes of expensive reagents. A series of RNA quality control checks are also incorporated to ensure success and reduce costs of subsequent snRNAseq experiments. Nuclei isolated by this procedure can be separated on the 10× Genomics Chromium system for either snRNAseq and/or Single-Nucleus ATAC-Seq (snATAC-Seq), and is also compatible with other single cell platforms. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Sample preparation and quality control check via RNA Isolation and Analysis Basic Protocol 2: Nuclei Isolation.

Evaluation of the Antiviral Activity against Infectious Pancreatic Necrosis Virus (IPNV) of a Copper (I) Homoleptic Complex with a Coumarin as Ligand.

The aquatic infectious pancreatic necrosis virus (IPNV) causes a severe disease in farmed salmonid fish that generates great economic losses in the aquaculture industry. In the search for new tools to control the disease, in this paper we show the results obtained from the evaluation of the antiviral effect of [Cu(NN1)2](ClO4) Cu(I) complex, synthesized in our laboratory, where the NN1 ligand is a synthetic derivate of the natural compound coumarin. This complex demonstrated antiviral activity against IPNV at 5.0 and 15.0 µg/mL causing a decrease viral load 99.0% and 99.5%, respectively. The Molecular Docking studies carried out showed that the copper complex would interact with the VP2 protein, specifically in the S domain, altering the process of entry of the virus into the host cell.

Modulation of Escherichia coli Translation by the Specific Inactivation of tRNAGly Under Oxidative Stress.

Bacterial oxidative stress responses are generally controlled by transcription factors that modulate the synthesis of RNAs with the aid of some sRNAs that control the stability, and in some cases the translation, of specific mRNAs. Here, we report that oxidative stress additionally leads to inactivation of tRNAGly in Escherichia coli, inducing a series of physiological changes. The observed inactivation of tRNAGly correlated with altered efficiency of translation of Gly codons, suggesting a possible mechanism of translational control of gene expression under oxidative stress. Changes in translation also depended on the availability of glycine, revealing a mechanism whereby bacteria modulate the response to oxidative stress according to the prevailing metabolic state of the cells.

Amyloid Beta-Peptide Increases BACE1 Translation through the Phosphorylation of the Eukaryotic Initiation Factor-2α.

Alzheimer's disease (AD) is tightly linked to oxidative stress since amyloid beta-peptide (Aß) aggregates generate free radicals. Moreover, the aggregation of Aß is increased by oxidative stress, and the neurotoxicity induced by the oligomers and fibrils is in part mediated by free radicals. Interestingly, it has been reported that oxidative stress can also induce BACE1 transcription and expression. BACE1 is the key enzyme in the cleavage of the amyloid precursor protein to produce Aß, and the expression of this enzyme has been previously shown to be enhanced in the brains of Alzheimer's patients. Here, we have found that BACE1 expression is increased in the hippocampi from AD patients at both the early (Braak stage II) and late (Braak stage VI) stages of the disease as studied by immunohistochemistry and western blot. To address the role of Aß and oxidative stress in the regulation of BACE1 expression, we have analyzed the effect of subtoxic concentrations of Aß oligomers (0.25 µM) and H2O2 (10 mM) on a human neuroblastoma cell line. Firstly, our results show that Aß oligomers and H2O2 induce an increase of BACE1 mRNA as we studied by qPCR. Regarding BACE1 translation, it is dependent on the phosphorylation of the eukaryotic initiation factor 2α (eIF2α), since BACE1 mRNA bears a 5'UTR that avoids its translation under basal conditions. BACE1 5'UTR contains four upstream initiating codons (uAUGs), and its translation is activated when eIF2α is phosphorylated. Consistently, we have obtained that Aß oligomers and H2O2 increase the levels of BACE1 and p-eIF2α assayed by western blot and confocal microscopy. Our results suggest that Aß oligomers increase BACE1 translation by phosphorylating eIF2α in a process that involves oxidative stress and conforms a pathophysiological loop, where the Aß once aggregated favors its own production continuously by the increase in BACE1 expression as observed in AD patients.

Genotoxic stress triggers the activation of IRE1α-dependent RNA decay to modulate the DNA damage response.

The molecular connections between homeostatic systems that maintain both genome integrity and proteostasis are poorly understood. Here we identify the selective activation of the unfolded protein response transducer IRE1α under genotoxic stress to modulate repair programs and sustain cell survival. DNA damage engages IRE1α signaling in the absence of an endoplasmic reticulum (ER) stress signature, leading to the exclusive activation of regulated IRE1α-dependent decay (RIDD) without activating its canonical output mediated by the transcription factor XBP1. IRE1α endoribonuclease activity controls the stability of mRNAs involved in the DNA damage response, impacting DNA repair, cell cycle arrest and apoptosis. The activation of the c-Abl kinase by DNA damage triggers the oligomerization of IRE1α to catalyze RIDD. The protective role of IRE1α under genotoxic stress is conserved in fly and mouse. Altogether, our results uncover an important intersection between the molecular pathways that sustain genome stability and proteostasis.