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Animals with complex nervous systems demand sleep for memory consolidation and synaptic remodeling. Here, we show that, although the Caenorhabditis elegans nervous system has a limited number of neurons, sleep is necessary for both processes. In addition, it is unclear if, in any system, sleep collaborates with experience to alter synapses between specific neurons and whether this ultimately affects behavior. C. elegans neurons have defined connections and well-described contributions to behavior. We show that spaced odor-training and post-training sleep induce long-term memory. Memory consolidation, but not acquisition, requires a pair of interneurons, the AIYs, which play a role in odor-seeking behavior. In worms that consolidate memory, both sleep and odor conditioning are required to diminish inhibitory synaptic connections between the AWC chemosensory neurons and the AIYs. Thus, we demonstrate in a living organism that sleep is required for events immediately after training that drive memory consolidation and alter synaptic structures.
Assuntos
Caenorhabditis elegans , Odorantes , Animais , Caenorhabditis elegans/fisiologia , Olfato , Sono/fisiologia , Sinapses/fisiologiaRESUMO
Phage-displayed immunoprecipitation sequencing (PhIP-seq) has enabled high-throughput profiling of human antibody repertoires. However, a comprehensive overview of environmental and genetic determinants shaping human adaptive immunity is lacking. In this study, we investigated the effects of genetic, environmental, and intrinsic factors on the variation in human antibody repertoires. We characterized serological antibody repertoires against 344,000 peptides using PhIP-seq libraries from a wide range of microbial and environmental antigens in 1,443 participants from a population cohort. We detected individual-specificity, temporal consistency, and co-housing similarities in antibody repertoires. Genetic analyses showed the involvement of the HLA, IGHV, and FUT2 gene regions in antibody-bound peptide reactivity. Furthermore, we uncovered associations between phenotypic factors (including age, cell counts, sex, smoking behavior, and allergies, among others) and particular antibody-bound peptides. Our results indicate that human antibody epitope repertoires are shaped by both genetics and environmental exposures and highlight specific signatures of distinct phenotypes and genotypes.
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Anticorpos , Bacteriófagos , Humanos , Antígenos , Epitopos/genética , PeptídeosRESUMO
Although the impact of host genetics on gut microbial diversity and the abundance of specific taxa is well established1-6, little is known about how host genetics regulates the genetic diversity of gut microorganisms. Here we conducted a meta-analysis of associations between human genetic variation and gut microbial structural variation in 9,015 individuals from four Dutch cohorts. Strikingly, the presence rate of a structural variation segment in Faecalibacterium prausnitzii that harbours an N-acetylgalactosamine (GalNAc) utilization gene cluster is higher in individuals who secrete the type A oligosaccharide antigen terminating in GalNAc, a feature that is jointly determined by human ABO and FUT2 genotypes, and we could replicate this association in a Tanzanian cohort. In vitro experiments demonstrated that GalNAc can be used as the sole carbohydrate source for F. prausnitzii strains that carry the GalNAc-metabolizing pathway. Further in silico and in vitro studies demonstrated that other ABO-associated species can also utilize GalNAc, particularly Collinsella aerofaciens. The GalNAc utilization genes are also associated with the host's cardiometabolic health, particularly in individuals with mucosal A-antigen. Together, the findings of our study demonstrate that genetic associations across the human genome and bacterial metagenome can provide functional insights into the reciprocal host-microbiome relationship.
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Bactérias , Microbioma Gastrointestinal , Interações entre Hospedeiro e Microrganismos , Metagenoma , Humanos , Acetilgalactosamina/metabolismo , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Estudos de Coortes , Simulação por Computador , Faecalibacterium prausnitzii/genética , Microbioma Gastrointestinal/genética , Genoma Humano/genética , Genótipo , Interações entre Hospedeiro e Microrganismos/genética , Técnicas In Vitro , Metagenoma/genética , Família Multigênica , Países Baixos , TanzâniaRESUMO
In bacteria, mutations lead to the evolution of antibiotic resistance, which is one of the main public health problems of the twenty-first century. Therefore, determining which cellular processes most frequently contribute to mutagenesis, especially in cells that have not been exposed to exogenous DNA damage, is critical. Here, we show that endogenous oxidative stress is a key driver of mutagenesis and the subsequent development of antibiotic resistance. This is the case for all classes of antibiotics and highly divergent species tested, including patient-derived strains. We show that the transcription-coupled repair pathway, which uses the nucleotide excision repair proteins (TC-NER), is responsible for endogenous oxidative stress-dependent mutagenesis and subsequent evolution. This suggests that a majority of mutations arise through transcription-associated processes rather than the replication fork. In addition to determining that the NER proteins play a critical role in mutagenesis and evolution, we also identify the DNA polymerases responsible for this process. Our data strongly suggest that cooperation between three different mutagenic DNA polymerases, likely at the last step of TC-NER, is responsible for mutagenesis and evolution. Overall, our work identifies a highly conserved pathway that drives mutagenesis due to endogenous oxidative stress, which has broad implications for all diseases of evolution, including antibiotic resistance development.
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Reparo do DNA , Estresse Oxidativo , Humanos , Reparo do DNA/genética , Mutagênese , Estresse Oxidativo/genética , Dano ao DNA/genética , DNA Polimerase Dirigida por DNA/genética , BactériasRESUMO
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main Protease (Mpro) is an enzyme that cleaves viral polyproteins translated from the viral genome and is critical for viral replication. Mpro is a target for anti-SARS-CoV-2 drug development, and multiple Mpro crystals complexed with competitive inhibitors have been reported. In this study, we aimed to develop an Mpro consensus pharmacophore as a tool to expand the search for inhibitors. We generated a consensus model by aligning and summarizing pharmacophoric points from 152 bioactive conformers of SARS-CoV-2 Mpro inhibitors. Validation against a library of conformers from a subset of ligands showed that our model retrieved poses that reproduced the crystal-binding mode in 77% of the cases. Using models derived from a consensus pharmacophore, we screened >340 million compounds. Pharmacophore-matching and chemoinformatics analyses identified new potential Mpro inhibitors. The candidate compounds were chemically dissimilar to the reference set, and among them, demonstrating the relevance of our model. We evaluated the effect of 16 candidates on Mpro enzymatic activity finding that seven have inhibitory activity. Three compounds (1, 4, and 5) had IC50 values in the midmicromolar range. The Mpro consensus pharmacophore reported herein can be used to identify compounds with improved activity and novel chemical scaffolds against Mpro. The method developed for its generation is provided as an open-access code (https://github.com/AngelRuizMoreno/ConcensusPharmacophore) and can be applied to other pharmacological targets.
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COVID-19 , SARS-CoV-2 , Humanos , Bibliotecas de Moléculas Pequenas/farmacologia , Farmacóforo , Consenso , Proteínas não Estruturais Virais/química , Inibidores de Proteases/farmacologia , Inibidores de Proteases/química , Simulação de Acoplamento Molecular , Antivirais/farmacologia , Antivirais/químicaRESUMO
Here, the unresolved question of why single-chain nanoparticles (SCNPs) prepared from a weak polyelectrolyte (PE) precursor can be synthesized on a large is addresses, unlike SCNPs obtained from an equivalent neutral (nonamphiphilic) polymer precursor. The combination of the standard elastic single-chain nanoparticles (ESN) model -developed for neutral chains- with the classical scaling theory of PE solutions provides the key. Essentially, the long-range repulsion between electrostatic blobs in a weak PE precursor restricts the cross-linking process during SCNPs formation to the interior of each blob. Consequently, the maximum concentration at which PE-SCNPs can be prepared without interchain cross-linking is not determined by the full size of the PE precursor but, instead, by the smaller size of its electrostatic blobs. Therefore, PE-SCNPs can be synthesized up to a critical concentration where electrostatic blobs from different chains touch each other. This concentration can be 30 times higher than that for non-PE polymer precursors. Upon progressive dilution, the size of PE-SCNPs synthesized in concentrated solution increases until it reaches the bigger size of PE-SCNPs prepared under highly diluted conditions. PE-SCNPs do not adopt a globular conformation either in concentrated or in diluted solution. It shows that the main model predictions agree with experimental results.
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Pre-exposure prophylaxis (PrEP) is a highly effective method for preventing HIV acquisition and plays a crucial role in the Ending the HIV Epidemic in the US initiative. However, there are various barriers that hinder the access and uptake of PrEP among Latino sexual minority men (SMM) at individual, interpersonal, and cultural levels. While the significance of cultural factors in designing and implementing HIV prevention programs for Latino populations has been consistently emphasized in the literature and prioritized by the Centers for Disease Control and Prevention, few studies have directly integrated these cultural factors into their programs. Our study aimed to investigate the potential influence of siblings in promoting the utilization of PrEP for HIV prevention, an area that has received limited attention. We conducted interviews with 31 pairs of siblings between December 2020 and January 2021, which were held in either English or Spanish and lasted approximately 45-60 min. The data were analyzed using a deductive thematic content analysis approach. The interviews revealed several key themes and categories, including: (1) Sibling support for coming out; (2) Types of support that siblings provide to each other for behavior change; (3) Sibling support for PrEP; and (4) The impact of the study interview on the quality of the sibling relationships. Our findings indicated that siblings were willing to provide support for PrEP in various ways, ranging from emotional support for brothers who may be concerned about potential rejection to practical support such as transportation or financial assistance. These results have significant implications for the design of HIV prevention interventions for Latinos. Incorporating siblings or other extended family members into these interventions can facilitate communication between siblings and their brothers, ultimately encouraging the use of PrEP or similar prevention methods. By considering the unique dynamics and support systems within Latino communities, researchers can develop more effective strategies to promote HIV prevention and support the well-being of Latino SMM.
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Infecções por HIV , Hispânico ou Latino , Minorias Sexuais e de Gênero , Irmãos , Humanos , Masculino , Hispânico ou Latino/psicologia , Hispânico ou Latino/estatística & dados numéricos , Adulto , Minorias Sexuais e de Gênero/psicologia , Infecções por HIV/prevenção & controle , Irmãos/psicologia , Profilaxia Pré-Exposição/estatística & dados numéricos , Saúde Sexual , Comportamento Sexual/psicologia , Pessoa de Meia-Idade , Adulto JovemRESUMO
Mountain ranges generate clouds, precipitation, and perennial streamflow for water supplies, but the role of forest cover in mountain hydrometeorology and cloud formation is not well understood. In the Luquillo Experimental Forest of Puerto Rico, mountains are immersed in clouds nightly, providing a steady precipitation source to support the tropical forest ecosystems and human uses. A severe drought in 2015 and the removal of forest canopy (defoliation) by Hurricane Maria in 2017 created natural experiments to examine interactions between the living forest and hydroclimatic processes. These unprecedented land-based observations over 4.5 y revealed that the orographic cloud system was highly responsive to local land-surface moisture and energy balances moderated by the forest. Cloud layer thickness and immersion frequency on the mountain slope correlated with antecedent rainfall, linking recycled terrestrial moisture to the formation of mountain clouds; and cloud-base altitude rose during drought stress and posthurricane defoliation. Changes in diurnal cycles of temperature and vapor-pressure deficit and an increase in sensible versus latent heat flux quantified local meteorological response to forest disturbances. Temperature and water vapor anomalies along the mountain slope persisted for at least 12 mo posthurricane, showing that understory recovery did not replace intact forest canopy function. In many similar settings around the world, prolonged drought, increasing temperatures, and deforestation could affect orographic cloud precipitation and the humans and ecosystems that depend on it.
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Processos Climáticos , Florestas , Folhas de Planta/fisiologia , Estresse Fisiológico , Ciclo Hidrológico , Altitude , Clima TropicalRESUMO
BACKGROUND: Precise preoperative localization of liver tumors facilitates successful surgical procedures, Intraoperative ultrasonography is a sensitive imaging modality. However, the presence of small non-palpable isoechoic intraparenchymal lesions may be challenging intraoperatively. METHODOLOGY AND MATERIAL DESCRIPTION: Onyx® is a non-adhesive liquid agent comprised of ethylene-vinyl alcohol usually used dissolved in dimethyl-sulfoxide and suspended micronized tantalum powder to provide contrast for visualization under fluoroscopy and ultrasonography and a macroscopic black shape. This embolization material has been increasingly used for the embolization of intracranial arteriovenous malformations. We present the novel application of Onyx® on liver surgery. CURRENT STATUS: We present the case of a female, 55 years-old, whose medical history revealed an elective sigmoidectomy (pT3N1a). After 17 months of follow up, by PET-CT scan, the patient was diagnosed of a small intraparenchymal hypo-attenuated 13 mm tumor located at segment V consistent with metachronous colorectal liver metastasis. Open metastasectomy was performed, ultrasonography-guided Onyx® infusion was delivered the day after, intraoperative ultrasonography showed a palpable hyperechoic material with a posterior acoustic shadowing artifact around the lesion. Onyx® is a promising new tool, without any previous application on liver surgery, feasible with advantages in small not palpable intraparenchymal liver lesions.
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Embolização Terapêutica , Neoplasias Hepáticas , Feminino , Humanos , Pessoa de Meia-Idade , Embolização Terapêutica/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Polivinil/uso terapêutico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Resultado do TratamentoRESUMO
Transcription factors (TFs) regulate gene expression by binding to specific sequences on DNA through their DNA-binding domain (DBD), a universal process. This update conveys information about the diverse roles of TFs, focusing on the NACs (NAM-ATAF-CUC), in regulating target-gene expression and influencing various aspects of plant biology. NAC TFs appeared before the emergence of land plants. The NAC family constitutes a diverse group of plant-specific TFs found in mosses, conifers, monocots, and eudicots. This update discusses the evolutionary origins of plant NAC genes/proteins from green algae to their crucial roles in plant development and stress response across various plant species. From mosses and lycophytes to various angiosperms, the number of NAC proteins increases significantly, suggesting a gradual evolution from basal streptophytic green algae. NAC TFs play a critical role in enhancing abiotic stress tolerance, with their function conserved in angiosperms. Furthermore, the modular organization of NACs, their dimeric function, and their localization within cellular compartments contribute to their functional versatility and complexity. While most NAC TFs are nuclear-localized and active, a subset is found in other cellular compartments, indicating inactive forms until specific cues trigger their translocation to the nucleus. Additionally, it highlights their involvement in endoplasmic reticulum (ER) stress-induced programmed cell death (PCD) by activating the vacuolar processing enzyme (VPE) gene. Moreover, this update provides a comprehensive overview of the diverse roles of NAC TFs in plants, including their participation in ER stress responses, leaf senescence (LS), and growth and development. Notably, NACs exhibit correlations with various phytohormones (i.e., ABA, GAs, CK, IAA, JA, and SA), and several NAC genes are inducible by them, influencing a broad spectrum of biological processes. The study of the spatiotemporal expression patterns provides insights into when and where specific NAC genes are active, shedding light on their metabolic contributions. Likewise, this review emphasizes the significance of NAC TFs in transcriptional modules, seed reserve accumulation, and regulation of seed dormancy and germination. Overall, it effectively communicates the intricate and essential functions of NAC TFs in plant biology. Finally, from an evolutionary standpoint, a phylogenetic analysis suggests that it is highly probable that the WRKY family is evolutionarily older than the NAC family.
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Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Sementes , Fatores de Transcrição , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Sementes/genética , Sementes/crescimento & desenvolvimento , Sementes/metabolismo , Família Multigênica , Evolução Molecular , Estresse Fisiológico , Filogenia , Plantas/genética , Plantas/metabolismoRESUMO
A T-cell-independent (TI) pathway activated by microbiota results in the generation of low-affinity homeostatic IgA with a critical role in intestinal homeostasis. Moderate aerobic exercise (MAE) provides a beneficial impact on intestinal immunity, but the action of MAE on TI-IgA generation under senescence conditions is unknown. This study aimed to determine the effects of long-term MAE on TI-IgA production in young (3 month old) BALB/c mice exercised until adulthood (6 months) or aging (24 months). Lamina propria (LP) from the small intestine was obtained to determine B cell and plasma cell sub-populations by flow cytometry and molecular factors related to class switch recombination [Thymic Stromal Lymphopoietin (TSLP), A Proliferation-Inducing Ligand (APRIL), B Cell Activating Factor (BAFF), inducible nitric oxide synthase (iNOS), and retinal dehydrogenase (RDH)] and the synthesis of IgA [α-chain, interleukin (IL)-6, IL-21, and Growth Factor-ß (TGF-ß)]; and epithelial cells evaluated IgA transitosis [polymeric immunoglobulin receptor (pIgR), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-4] by the RT-qPCR technique. The results were compared with data obtained from sedentary age-matched mice. Statistical analysis was computed with ANOVA, and p < 0.05 was considered to be a statistically significant difference. Under senescence conditions, MAE promoted the B cell and IgA+ B cells and APRIL, which may improve the intestinal response and ameliorate the inflammatory environment associated presumably with the downmodulation of pro-inflammatory mediators involved in the upmodulation of pIgR expression. Data suggested that MAE improved IgA and downmodulate the cytokine pro-inflammatory expression favoring homeostatic conditions in aging.
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Envelhecimento , Homeostase , Imunoglobulina A , Camundongos Endogâmicos BALB C , Condicionamento Físico Animal , Animais , Imunoglobulina A/metabolismo , Imunoglobulina A/imunologia , Camundongos , Envelhecimento/imunologia , Citocinas/metabolismo , Linfócitos B/imunologia , Linfócitos B/metabolismo , Fator Ativador de Células B/metabolismo , Fator Ativador de Células B/genética , Mucosa Intestinal/metabolismo , Mucosa Intestinal/imunologia , Intestino Delgado/imunologia , Intestino Delgado/metabolismo , Masculino , Plasmócitos/imunologia , Plasmócitos/metabolismo , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genéticaRESUMO
Metformin is the most widely known anti-hyperglycemic, officially acquired by the USA government in 1995 and in 2001 it became the most prescribed treatment for type II diabetes. But how did it become the must-use drug for this disease in such a short period of time? it all started with traditional medicine, by using a plant known as "goat's rue" for the reduction of blood glucose levels. Its use arose in 1918 and evolved to the metformin synthesis in laboratories a couple of years later, using very rudimentary methods which involved melting and strong heating. Thus, a first synthetic route that allowed the preparation of the initial metformin derivates was established. Some of these resulted toxics, and others outperformed the metformin, reducing the blood glucose levels in such efficient way. Nevertheless, the risk and documented cases of lactic acidosis increased with metformin derivatives like buformin and phenformin. Recently, metformin has been widely studied, and it has been associated and tested in the treatment of type II diabetes, cancer, polycystic ovarian syndrome, cell differentiation to oligodendrocytes, reduction of oxidative stress in cells, weight reduction, as anti-inflammatory and even in the recent COVID-19 disease. Herein we briefly review and analyze the history, synthesis, and biological applications of metformin and its derivates.
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COVID-19 , Diabetes Mellitus Tipo 2 , Metformina , Humanos , Metformina/farmacologia , Metformina/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , GlicemiaRESUMO
BACKGROUND: Although sex differences in anaesthetic sensitivity have been reported, what underlies these differences is unknown. In rodents, one source of variability in females is the oestrous cycle. Here we test the hypothesis that the oestrous cycle impacts emergence from general anaesthesia. METHODS: Time to emergence was measured after isoflurane (2 vol% for 1 h), sevoflurane (3 vol% for 20 min), dexmedetomidine (50 µg kg-1 i.v., infused over 10 min), or propofol (10 mg kg-1 i.v. bolus) during proestrus, oestrus, early dioestrus, and late dioestrus in female Sprague-Dawley rats (n=24). EEG recordings were taken during each test for power spectral analysis. Serum was analysed for 17ß-oestradiol and progesterone concentrations. The effect of oestrous cycle stage on return of righting latency was assessed using a mixed model. The association between righting latency and serum hormone concentration was tested by linear regression. Mean arterial blood pressure and arterial blood gases were assessed in a subset of rats after dexmedetomidine and compared in a mixed model. RESULTS: Oestrous cycle did not affect righting latency after isoflurane, sevoflurane, or propofol. When in the early dioestrus stage, rats emerged more rapidly from dexmedetomidine than in the proestrus (P=0.0042) or late dioestrus (P=0.0230) stage and showed reduced overall power in frontal EEG spectra 30 min after dexmedetomidine (P=0.0049). 17ß-Oestradiol and progesterone serum concentrations did not correlate with righting latency. Oestrous cycle did not affect mean arterial blood pressure or blood gases during dexmedetomidine. CONCLUSIONS: In female rats, the oestrous cycle significantly impacts emergence from dexmedetomidine-induced unconsciousness. However, 17ß-oestradiol and progesterone serum concentrations do not correlate with the observed changes.
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Dexmedetomidina , Isoflurano , Propofol , Ratos , Feminino , Masculino , Animais , Propofol/farmacologia , Sevoflurano/farmacologia , Isoflurano/farmacologia , Dexmedetomidina/farmacologia , Progesterona/farmacologia , Ratos Sprague-Dawley , Anestesia Geral , Estradiol/farmacologia , GasesRESUMO
BACKGROUND: Textbook outcome (TO) is a multidimensional quality management tool that uses a set of traditional surgical measures to reflect an "ideal" surgical result for a particular pathology. The aim of the present study is to record the rate of TO in patients undergoing elective surgery for colon cancer (CC). MATERIAL AND METHODS: Retrospective study of all patients undergoing scheduled CC surgery at a Spanish university hospital from September 2012 to August 2016. Patients with rectal cancer were excluded. The variables included in the definition of TO were: R0 resection, number of isolated nodes ≥ 12, no Clavien-Dindo ≥ IIIa complications, no prolonged stay, no readmissions, and no mortality in the first 30 days. The main objective of this study is to analyse the achievement of TO in these patients and to assess the relationship between TO and overall and disease-free survival. RESULTS: Five hundred and sixty-four patients were included in the study. TO was achieved in 49.8%. The sample had a mean age of 69 ± 11 years, and 60% were male. Female sex (OR 1.61; 95% CI 2.30-1.13), T3 and T4 classification (OR 2.50, 95% CI 4.59-1.36, and OR 2.55, 95% CI 5.21-1.24 respectively) and laparoscopic approach (OR 1.53, 95% CI 2.33-1.00) were independent factors that were significantly associated with achieving a TO. Patients who achieved TO had higher overall survival (p = 0.008) than those who did not. However, with regard to disease-free survival, no statistically significant differences were found (p = 0.303). CONCLUSION: TO is a useful, easy-to-interpret management tool for measuring oncological results and for predicting patient survival.
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Carcinoma , Neoplasias do Colo , Laparoscopia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Resultado do Tratamento , Estudos Retrospectivos , Laparoscopia/métodos , Neoplasias do Colo/patologia , Carcinoma/cirurgiaRESUMO
Proteostasis dysfunction and activation of the unfolded protein response (UPR) are characteristic of all major neurodegenerative diseases. Nevertheless, although the UPR and proteostasis dysfunction has been studied in great detail in model organisms like yeast and mammalian cell lines, it has not yet been examined in neurons. In this study, we applied a viral vector-mediated expression of a reporter protein based on a UPR transcription factor, ATF4, and time-lapse fluorescent microscopy to elucidate how mouse primary neurons respond to pharmacological and genetic perturbations to neuronal proteostasis. In in vitro models of endoplasmic reticulum (ER) stress and proteasome inhibition, we used the ATF4 reporter to reveal the time course of the neuronal stress response relative to neurite degeneration and asynchronous cell death. We showed how potential neurodegenerative disease co-factors, ER stress and mutant α-synuclein overexpression, impacted neuronal stress response and overall cellular health. This work therefore introduces a viral vector-based reporter that yields a quantifiable readout suitable for non-cell destructive kinetic monitoring of proteostasis dysfunction in neurons by harnessing ATF4 signaling as part of the UPR activation.
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Doenças Neurodegenerativas , Deficiências na Proteostase , Animais , Estresse do Retículo Endoplasmático/fisiologia , Mamíferos , Camundongos , Doenças Neurodegenerativas/metabolismo , Neurônios/metabolismo , Deficiências na Proteostase/metabolismo , Resposta a Proteínas não DobradasRESUMO
Background: New era of cardiac surgery aims to provide an enhanced postoperative recovery through the implementation of every step of the process. Thus, perfusion strategy should adopt evidence-based measures to reduce the impact of cardiopulmonary bypass (CPB). Hematic Antegrade Repriming (HAR) provides a standardized procedure combining several measures to reduce haemodilutional priming to 300 mL. Once the safety of the procedure in terms of embolic release has been proven, the evaluation of its beneficial effects in terms of transfusion and ICU stay should be assessed to determine if could be considered for inclusion in Enhanced Recovery After Cardiac Surgery (ERACS) programs. Methods: Two retrospective and non-randomized cohorts of high-risk patients, with similar characteristics, were assessed with a propensity score matching model. The treatment group (HG) (n = 225) received the HAR. A historical cohort, exposed to conventional priming with 1350 mL of crystalloid confirmed the control group (CG) (n = 210). Results: Exposure to any transfusion was lower in treated (66.75% vs. 6.88%, p < 0.01). Prolonged mechanical ventilation (>10 h) (26.51% vs. 12.62%; p < 0.01) and extended ICU stay (>2 d) (47.47% vs. 31.19%; p < 0.01) were fewer for treated. HAR did not increase early morbidity and mortality. Related savings varied from 581 to 2741.94 $/patient, depending on if direct or global expenses were considered. Discussion: By reducing the gaseous and crystalloid emboli during CPB initiation, HAR seems to have a beneficial impact on recovery and reduces the overall transfusion until discharge, leading to significant cost savings per process. Due to the preliminary and retrospective nature of the research and its limitations, our findings should be validated by future prospective and randomized studies.
Assuntos
Transfusão de Sangue , Ponte Cardiopulmonar , Recuperação Pós-Cirúrgica Melhorada , Humanos , Transfusão de Sangue/métodos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Ponte Cardiopulmonar/efeitos adversos , Ponte Cardiopulmonar/métodos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Structural Health Monitoring (SHM) systems allow three types of diagnostic tasks to be performed, namely damage identification, loads monitoring, and damage prognosis. Only if all three tasks are correctly fulfilled can the useful remaining life of a structure be estimated credibly. This paper deals with the second task and aimed to extend state-of-the-art in load identification, by demonstrating that it is feasible to achieve it through the analysis of response signals captured with high-speed three-dimensional Digital Image Correlation (HS 3D-DIC). The efficacy of the proposed procedure is demonstrated experimentally on a frame structure under broadband vibration excitation. Full-field vibration displacement signals are captured with the use of two high-speed cameras and processed with 3D-DIC. Loads are identified with two different algorithms based on inverting the Frequency Response Function (FRF) matrix and modal filtration (MF). The paper discusses both methods providing their theoretical background and experimental performance.
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Algoritmos , Imageamento Tridimensional , Imageamento Tridimensional/métodos , Vibração , EletrocardiografiaRESUMO
BACKGROUND: Odontogenic deep neck infections remain a common condition that presents a challenging issue due to the complex involvement of the neck and adjacent structures and its potential life-threatening risk. Periapical infection of the second or third molar with spread to the submandibular and parapharyngeal spaces is the most commonly observed scenario. However, the time of dental extraction of the infection focus remains controversial. The aim of this study is to provide an overview of the epidemiology, clinical and radiological features, and management in patients diagnosed with ODNI and to identify the role of early dental extraction on patient outcomes and recovery. MATERIAL AND METHODS: This retrospective study included patients over 18 years old with a diagnosis of ODNI who were admitted to the University Hospital "Dr Jose Eleuterio Gonzalez" from January 2017 to January 2022. ODNI diagnosis was based on clinical and radiological evidence of the disease supplemented by dental and maxillofacial evaluation for an odontogenic aetiology. RESULTS: A total of 68 patients were included in the study. The patients' mean age was 40.96 ± 14.9. Diabetes mellitus was the most common comorbidity. The submandibular space was the most common deep neck space involved (n=59, 86.8%). Mediastinitis, marginal nerve injury and orocervical fistula were observed in 7.5% of patients, with no fatality in this series. A delay of >3 days for dental extraction of the involved tooth was associated with an increased rate of mediastinitis (n=3, 100%, p= 0.022), number of surgical interventions (1.45 ± 0.61, p= 0.006), ICU stay (n=8, 40%, p= 0.019), and ICU length of stay (0.85 ± 0.8, p= 0.001). CONCLUSIONS: Expedited management with surgical drainage and intravenous antibiotic treatment, along with early extraction of the involved tooth, is mandatory.
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Mediastinite , Humanos , Adulto , Pessoa de Meia-Idade , Adolescente , Estudos Retrospectivos , Mediastinite/diagnóstico , Mediastinite/tratamento farmacológico , Mediastinite/etiologia , Pescoço , Hospitalização , Antibacterianos/uso terapêuticoRESUMO
Critical thinking is identified as a key educational outcome in higher education curricula; however, it is not trivial to support students in building this multifaceted skill. In this study, we evaluated a brief online learning intervention focusing on informal fallacy identification, a hallmark critical-thinking skill. The intervention used a bite-sized video learning approach, which has been shown to promote student engagement. Video-based learning was implemented within a precision teaching (PT) framework, which modulates the exposure of individual learners to the learning material to enable them to build 'fluency' in the targeted skills. In one of the learning conditions, PT was applied synergistically with domain-general problem-based training to support generalisation. The intervention consisted of two learning episodes and was administered to three groups (learning conditions) of 19 participants each: a PT fluency-based training group; a PT + group, where PT was combined with problem-based training; and a self-directed learning control group. All three groups showed comparable improvements in fallacy identification on taught (post-episode tests) and unseen materials (post-intervention assessment), with lower-scoring participants showing higher gains than high-scoring participants. The results of the knowledge retention tests a week later were also comparable between groups. Importantly, in the domain-general fallacy-identification assessment (post-intervention), the two PT groups showed higher improvements than the control group. These findings suggest that the integration of bite-sized video learning technologies with PT can improve students' critical-thinking skills. Furthermore, PT, on its own or combined with problem-based training, can improve their skill to generalise learning to novel contexts. We discuss the educational implications of our findings.
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The purpose of the current study was to identify biopsychosocial factors associated with depressive symptoms among Hispanic women aged ≥50 years. Cross-sectional data related to 10 biological, psychological, and social factors were analyzed. Center for Epidemiologic Studies Depression Scale scores suggested that 32% of the sample had depressive symptoms. Self-esteem, self-perception of health status, income, and chronic pain had statistically significant associations with depressive symptoms. A logistic regression analysis showed that increasing self-esteem scores were associated with decreases in the likelihood of having depressive symptoms. Findings underscore that depression is associated with biological, psychological, and social factors. Culturally tailored interventions that aim at targeting these factors may have an impact on Hispanic women's depression and overall well-being. [Journal of Psychosocial Nursing and Mental Health Services, 61(11), 32-42.].