ABSTRACT
Sepsis is a complex condition of inflammatory and immune dysregulation, triggered by severe infection. In survivors, chronic inflammation and immune dysregulation linger, facilitating the emergence of infections. CD8 dysfunction contributes to immunosuppression in sepsis survivors. We devised an animal model that enabled us to identify and analyze CD8-intrinsic defects induced by sepsis. We adoptively transferred CD45.1 CD8 OT-I T cells into CD45.2 congenic mice and subjected them to cecal ligature and puncture, to induce abdominal sepsis. One month later, we isolated the transferred CD8 cells. Surface marker expression confirmed they had not been activated through the TCR. CD8 OT-I T cells isolated from septic (or sham-operated) mice were transferred to second recipients, which were challenged with OVA-expressing Listeria monocytogenes. We compared effector capacities between OT-I cells exposed to sepsis and control cells. Naive mice that received OT-I cells exposed to sepsis had higher bacterial burden and a shorter survival when challenged with OVA-expressing L. monocytogenes. OT-I cells isolated from septic mice produced less IFN-γ but had conserved activation, expansion potential, and cytotoxic function. We observed lower transcript levels of IFN-γ and of the long noncoding RNA Ifng-as1, a local regulator of the epigenetic landscape, in cells exposed to sepsis. Accordingly, local abundance of a histone modification characteristic of active promoter regions was reduced in sepsis-exposed CD8 T cells. Our results identify a mechanism through which inflammation in the context of sepsis affects CD8 T cell function intrinsically.
Subject(s)
CD8-Positive T-Lymphocytes , Chromatin , Interferon-gamma , Listeria monocytogenes , Sepsis , Animals , Sepsis/immunology , CD8-Positive T-Lymphocytes/immunology , Mice , Interferon-gamma/immunology , Chromatin/immunology , Chromatin/metabolism , Listeria monocytogenes/immunology , Mice, Inbred C57BL , Adoptive Transfer , Disease Models, Animal , Listeriosis/immunology , Lymphocyte Activation/immunologyABSTRACT
This work presents the development, synthesis, and application of a layered double hydroxide (LDH) coupled to magnetic particles for the removal of antibiotics as tetracyclines (TC´s): tetracycline (TC), chlortetracycline (CT), oxytetracycline (OT), and doxycycline (DT) from milk samples. The LDH synthesis conditions, reaction time (30-90 min), molar ratios Mg2+/Al3+ (7:1-1:7), interlayer anion (NO3-, Cl-, CO32-, and dodecyl sulphate (DS-)) were evaluated. Under synthesis conditions (reaction time of 30 min, Mg2+/Al3+ molar ratio of 7:1, and DS- as interlayer anion), the LDH was coupled in a magnetic solid phase microextraction (MSPµE) methodology. At the optimal extraction conditions (pH 6, 5 min of contact time, 10 mg of adsorbent), a removal percentage of 99.0 % was obtained for each tetracycline. FTIR, TGA, SEM, and adsorption isotherms were employed to characterize the optimal adsorbent. Each experiment was corroborated by large-volume sample stacking capillary electrophoresis (LVSS-CE). The adsorbent was applied directly to positive milk samples (previously tested) for TC´s removal.
Subject(s)
Hydroxides , Milk , Tetracyclines , Milk/chemistry , Animals , Tetracyclines/isolation & purification , Tetracyclines/analysis , Tetracyclines/chemistry , Hydroxides/chemistry , Adsorption , Solid Phase Microextraction/methods , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/analysis , Silicon Dioxide/chemistryABSTRACT
Introducción: La Enfermedad de Alzheimer (EA), es una patología neurodegenerativa progresiva que afecta la memoria y otras funciones cognitivas. Hasta ahora no existen tratamientos curativos ni modificadores de la enfermedad, por lo que el manejo está centrado en la prevención y en el tratamiento de factores que puedan contribuir a su evolución; las herramientas farmacológicas son escasas y tienen efectos modestos en la ralentización de la enfermedad. Se propone realizar una breve biografía de Oskar Fischer, describir el conflicto con Alois Alzheimer que se identifica en documentos científicos y mencionar los principales elementos de la teoría de Oskar Fischer. Método: Se realizó una revisión narrativa en las bases de datos Scielo, PubMed y Lilacs, con los términos "Oskar Fischer" y se encontró quince artículos publicados entre 1906 a 2023, los cuales fueron resumidos por los autores GS y NR. El artículo fue posteriormente revisado por los demás autores. Resultados: Se organizaron en secciones, partiendo con una breve biografía del autor, su interacción con Alois Alzheimer y un resumen de su teoría; lo descrito por Oskar Fischer en términos de las estructuras de placas y ovillos se considera como una de las principales teorías fisiopatológicas de la EA. Conclusiones: Oskar Fisher hizo un aporte invaluable y planteó conceptos clásicos con respecto a la EA, que, si bien no le valieron para ser reconocido en la posteridad, han permitido que en las investigaciones posteriores sea de gran importancia repensar estos conceptos e incluir otras posibilidades e hipótesis, para continuar en la profundización del conocimiento de la enfermedad.
Introduction: Alzheimer's disease (AD) is a progressive neurodegenerative pathology that affects memory and other cognitive functions. Until now, there are no curative or disease-modifying treatments, so management is focused on prevention and treatment of factors that may contribute to its evolution; pharmacological tools are scarce and have modest effects in slowing the disease. It is proposed to make a brief biography of Oskar Fischer, describe the conflict with Alois Alzheimer that is identified in scientific documents and mention the main elements of Oskar Fischer's theory. Method: A narrative review was carried out in the Scielo, PubMed and Lilacs databases, with the terms "Oskar Fischer" and fifteen articles published between 1906 and 2023 were found, which were summarized by the authors GS and NR. The article was subsequently reviewed by the other authors. Results: They were organized in sections, starting with a brief biography of the author, his interaction with Alois Alzheimer and a summary of his theory; what was described by Oskar Fischer in terms of the structures of plaques and tangles is considered one of the main pathophysiological theories of AD. Conclusions: Oskar Fisher made an invaluable contribution and raised classic concepts regarding AD, which, although they did not earn him recognition in posterity, have allowed subsequent research to be of great importance to rethink these concepts and include other possibilities and hypotheses, to continue deepening the knowledge of the disease.
ABSTRACT
BACKGROUND AND PURPOSE: The nucleus basalis of Meynert is a key subcortical structure that is important in arousal and cognition and has been explored as a deep brain stimulation target but is difficult to study due to its small size, variability among patients, and lack of contrast on 3T MR imaging. Thus, our goal was to establish and evaluate a deep learning network for automatic, accurate, and patient-specific segmentations with 3T MR imaging. MATERIALS AND METHODS: Patient-specific segmentations can be produced manually; however, the nucleus basalis of Meynert is difficult to accurately segment on 3T MR imaging, with 7T being preferred. Thus, paired 3T and 7T MR imaging data sets of 21 healthy subjects were obtained. A test data set of 6 subjects was completely withheld. The nucleus was expertly segmented on 7T, providing accurate labels for the paired 3T MR imaging. An external data set of 14 patients with temporal lobe epilepsy was used to test the model on brains with neurologic disorders. A 3D-Unet convolutional neural network was constructed, and a 5-fold cross-validation was performed. RESULTS: The novel segmentation model demonstrated significantly improved Dice coefficients over the standard probabilistic atlas for both healthy subjects (mean, 0.68 [SD, 0.10] versus 0.45 [SD, 0.11], P = .002, t test) and patients (0.64 [SD, 0.10] versus 0.37 [SD, 0.22], P < .001). Additionally, the model demonstrated significantly decreased centroid distance in patients (1.18 [SD, 0.43] mm, 3.09 [SD, 2.56] mm, P = .007). CONCLUSIONS: We developed the first model, to our knowledge, for automatic and accurate patient-specific segmentation of the nucleus basalis of Meynert. This model may enable further study into the nucleus, impacting new treatments such as deep brain stimulation.
Subject(s)
Basal Nucleus of Meynert , Deep Learning , Humans , Magnetic Resonance Imaging/methods , Brain , CognitionABSTRACT
BACKGROUND: Kohlberg's theory of moral development asserts that people progress through different stages of moral reasoning as their cognitive abilities and social interactions mature. Individuals at the lowest stage of moral reasoning (preconventional stage) judge moral issues based on self-interest, those with a medium stage (conventional stage) judge them based on compliance with rules and norms, and those at the highest stage (postconventional stage) judge moral issues based on universal principles and shared ideals. Upon attaining adulthood, it can be considered that there is stability in the stage of individuals' moral development; however, the effect of a global population crisis such as the one experienced in March 2020, when the World Health Organization (WHO) declared the COVID-19 pandemic, is unknown. The purpose of this study was to evaluate the changes in the moral reasoning of pediatric residents before and after one year of the COVID-19 pandemic and compare them with a general population group. METHODS: This is a naturalistic quasi-experimental study conducted with two groups, one comprised 47 pediatric residents of a tertiary hospital converted into a COVID hospital during the pandemic and another group comprised 47 beneficiaries of a family clinic who were not health workers. The defining issues test (DIT) was applied to the 94 participants during March 2020, before the pandemic initiated in Mexico, and later during March 2021. To assess intragroup changes, the McNemar-Bowker and Wilcoxon tests were used. RESULTS: Pediatric residents showed higher baseline stages of moral reasoning: 53% in the postconventional group compared to the general population group (7%). In the preconventional group, 23% were residents and 64% belonged to the general population. In the second measurement, one year after the start of the pandemic, the group of residents had a significant decrease of 13 points in the P index, unlike the general population group in which a decrease of 3 points was observed. This decrease however, did not equalize baseline stages. Pediatric residents remained 10 points higher than the general population group. Moral reasoning stages were associated with age and educational stage. CONCLUSIONS: After a year of the COVID-19 pandemic, we found a decrease in the stage of moral reasoning development in pediatric residents of a hospital converted for the care of patients with COVID-19, while it remained stable in the general population group. Physicians showed higher stages of moral reasoning at baseline than the general population.
Subject(s)
COVID-19 , Population Groups , Humans , Child , Adult , Pandemics , COVID-19/epidemiology , Morals , Moral DevelopmentABSTRACT
Scorpion sting envenomation is a major public health in Mexico. Rural communities rarely have antivenoms in the health centers, therefore, the people commonly resort to using medicinal plants to treat the symptoms of envenoming caused by scorpion venom, but this knowledge has not yet been reported in detail. In this review, we carry out a review of the medicinal plants used in Mexico against scorpion stings. PubMed, Google, Science Direct, and the Digital Library of Mexican Traditional Medicine (DLMTM) were used to collect data. The results showed the use of at least 48 medicinal plants distributed in 26 families, where Fabaceae (14.6%), Lamiaceae (10.4%), and Asteraceae (10.4%) have the maximum representation. The application of leaves (32%) was preferred followed by roots (20%), stem (17.3%), flowers (16%), and bark (8%). In addition, the most common method of use to treat scorpion stings is decoction (32.5%). The oral and topical routes of administration have similar percentages of use. In vitro and in vivo studies of Aristolochia elegans, Bouvardia ternifolia, and Mimosa tenuiflora were found, which showed an antagonistic effect on the contraction of the ileum caused by the venom of C. limpidus, likewise, they increased the LD50 of said venom and even B. ternofila showed reduced albumin extravasation. The results of these studies demonstrate the promising use of medicinal plants for future pharmacological applications; nevertheless, validation, bioactive compound isolation and toxicity studies are necessary to support and improve therapeutics.
Subject(s)
Plants, Medicinal , Scorpion Stings , Scorpion Venoms , Animals , Scorpion Stings/drug therapy , Mexico , Plant Extracts/pharmacology , Phytotherapy , Antivenins/therapeutic use , Scorpion Venoms/pharmacology , ScorpionsABSTRACT
La encefalomielitis diseminada aguda es una enfermedad inflamatoria-desmielinizante inmunomediada que suele manifestarse tras una infección o vacunación en niños en edad escolar. Típicamente presenta una fase prodrómica con un cuadro pseudogripal seguida de una fase con clínica muy variada, pudiendo aparecer alteraciones neurooftalmológicas como oftalmoplejía o neuritis óptica.La etiología es variada, incluyendo enfermedades tumorales, vasculares, infecciosas, inflamatorias y desmielinizantes. El diagnóstico se basa en la historia clínica y en las características de la resonancia magnética cerebral, prueba de imagen de elección. El estudio del líquido cefalorraquídeo puede servir de ayuda en la orientación del cuadro clínico.El pronóstico es favorable, con excelente respuesta a los corticoides e inmunoglobulinas y con mínimas secuelas a largo plazo en la mayoría de los casos.Presentamos el caso de un varón de 8años con enfermedad desmielinizante aguda por adenovirus cuya manifestación fue un síndrome del ocho y medio. (AU)
Acute disseminated encephalomyelitis is an immune mediated inflammatory-demyelinizing disease that usually manifests after infection or vaccination in school-age children. It typically presents a prodromal phase with flu-like symptoms, followed by a phase with varied clinical symptoms, neuro-ophthalmological alterations such as ophthalmoplegia or optic neuritis may occur.The differential diagnosis includes tumor, vascular, infectious, inflammatory and demyelinating diseases. Diagnosis is based on the clinical history and the characteristics of brain magnetic resonance imaging, the gold standard test. The study of the cerebrospinal fluid can help to guide the clinical picture.The prognosis is favorable, with an excellent response to corticosteroids and immunoglobulins, with minimal long-term sequelae in most cases.We report the case of an 8-year-old male with acute demyelinating disease due to adenovirus whose manifestation was an eight-and-a-half syndrome. (AU)
Subject(s)
Humans , Male , Child , Encephalomyelitis, Acute Disseminated/diagnosis , Encephalomyelitis, Acute Disseminated/virology , Ophthalmoplegia/virology , Adenoviridae Infections/complications , Tomography, X-Ray Computed , Magnetic Resonance Imaging , SyndromeABSTRACT
Acute disseminated encephalomyelitis is an immune mediated inflammatory-demyelinizing disease that usually manifests after infection or vaccination in school-age children. It typically presents a prodromal phase with flu-like symptoms, followed by a phase with varied clinical symptoms, neuro-ophthalmological alterations such as ophthalmoplegia or optic neuritis may occur. The differential diagnosis includes tumor, vascular, infectious, inflammatory and demyelinating diseases. Diagnosis is based on the clinical history and the characteristics of brain magnetic resonance imaging, the gold standard test. The study of the cerebrospinal fluid can help to guide the clinical picture. The prognosis is favorable, with an excellent response to corticosteroids and immunoglobulins, with minimal long-term sequelae in most cases. We report the case of an 8-year-old male with acute demyelinating disease due to adenovirus whose manifestation was an eight-and-a-half syndrome.
Subject(s)
Adenoviridae Infections , Encephalomyelitis, Acute Disseminated , Encephalomyelitis , Male , Child , Humans , Encephalomyelitis, Acute Disseminated/diagnostic imaging , Encephalomyelitis, Acute Disseminated/etiology , Adenoviridae , Brain/pathology , Magnetic Resonance Imaging/methods , Encephalomyelitis/pathologyABSTRACT
This work reports on the thermoluminescence (TL) properties and detection of contaminating minerals isolated from Mexican cocoa beans irradiated with gamma radiation and stored for 4 years. Contaminating minerals isolated from cocoa beans consisting of quartz, diopside, plagioclase, albite, and iron oxide with irregular and rectangular grains and average length of 135 µm. Cocoa beans are detected as irradiated even after 4 years of storage using the shape and maximum temperature of the TL glow curve of contaminating minerals. The TL properties of dose-response, and fading of minerals were also analysed. The TL dose-response is linear from 5 to 100 Gy, supra-linear between 250 and 1000 Gy, and sub-linear above 1500 Gy. Based on the TL1/TL2 ratio the minerals are identified as irradiated from 250 Gy to 4500 Gy in the dose-response test and after different storage times in the darkness at room temperature. A continuum trap distribution can be associated with the TL glow curve of minerals using the Tm-Tstop method. First order kinetic peaks were used in the Glow Curve Deconvolution of natural and irradiated (1 and 10 kGy) TL curves.
Subject(s)
Quartz , Gamma Rays , TemperatureABSTRACT
BACKGROUND: Respiratory failure in severe coronavirus disease 2019 (COVID-19) is associated with a severe inflammatory response. Acetylcholine (ACh) reduces systemic inflammation in experimental bacterial and viral infections. Pyridostigmine increases the half-life of endogenous ACh, potentially reducing systemic inflammation. We aimed to determine if pyridostigmine decreases a composite outcome of invasive mechanical ventilation (IMV) and death in adult patients with severe COVID-19. METHODS: We performed a double-blinded, placebo-controlled, phase 2/3 randomized controlled trial of oral pyridostigmine (60 mg/day) or placebo as add-on therapy in adult patients admitted due to confirmed severe COVID-19 not requiring IMV at enrollment. The primary outcome was a composite of IMV or death by day 28. Secondary outcomes included reduction of inflammatory markers and circulating cytokines, and 90-day mortality. Adverse events (AEs) related to study treatment were documented and described. RESULTS: We recruited 188 participants (94 per group); 112 (59.6%) were men; the median (IQR) age was 52 (44-64) years. The study was terminated early due to a significant reduction in the primary outcome in the treatment arm and increased difficulty with recruitment. The primary outcome occurred in 22 (23.4%) participants in the placebo group vs. 11 (11.7%) in the pyridostigmine group (hazard ratio, 0.47, 95% confidence interval 0.24-0.9; P = 0.03). This effect was driven by a reduction in mortality (19 vs. 8 deaths, respectively). CONCLUSION: Our data indicate that adding pyridostigmine to standard care reduces mortality among patients hospitalized for severe COVID-19.
Subject(s)
COVID-19 Drug Treatment , Adult , Male , Humans , Middle Aged , Female , Pyridostigmine Bromide/therapeutic use , SARS-CoV-2 , Respiration, Artificial , Inflammation , Treatment OutcomeABSTRACT
The validity of one-dimensional (1D) models for liquid columns (capillary jets, liquid bridges, and other similar systems) for predicting the dynamics of their breakup into drops is studied when viscosity is not relevant. These models assume a simplified radial dependence, which in turn is supported by the premise that the system is slender enough. However, even though the latter hypothesis does not seem to be fulfilled when the system gets close to breakup, 1D models continue to describe its evolution surprisingly well. Our numerical simulations of a liquid jet confirm this good behavior, even when the liquid jet becomes a sequence of incipient drops joined by filaments. A dynamic definition of the slenderness allows computing the stage until which the liquid jet can be considered slender from the standpoint of 1D models. Beyond that point, a detailed numerical study of mass and energy reveals that the action that each incipient main drop suffers from the two adjacent filaments becomes barely significant. Thus, the drop can be considered to oscillate almost freely, while the filaments remain nearly static. To explain how the 1D models can predict the evolution of a so scarcely slender system as a droplet, we compare the linear modal analysis of the Lee, Cosserat and parabolic 1D models for an inviscid free drop with the 3D analysis in cylindrical coordinates. The frequencies of the oscillation modes with lowest index, the most relevant ones arising from the breakup, are in general well predicted. This happens when the radial dependence of both pressure and axial velocity assumed in 1D models reasonably fit the corresponding 3D exact results. The Cosserat model (and even more the parabolic one) performs better than the Lee model.
Subject(s)
COVID-19 , Vaccines , Humans , SARS-CoV-2 , COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , Antibodies, Viral , VaccinationABSTRACT
BACKGROUND: Reasoning and moral action are necessary to resolve day-to-day moral conflicts, and there are certain professions where a greater moral character is expected, e.g., medicine. Thus, it is desirable that medical students develop skills in this field. Some studies have evaluated the level of moral reasoning among medical students; however, there are no comparative studies involving other types of populations. Therefore, the objective of this study was to compare the moral reasoning among medical graduates with that of a group of young graduates with other degrees and of a group of nonprofessional adults. METHODS: An exploratory cross-sectional study was conducted. Pediatric residents and pediatric subspecialty residents at a pediatric hospital were invited to participate, forming the group of "medical graduates". A group of young people from a social program and students with a master's degree in a science from the same pediatric hospital were also invited to participate, comprising the group of "graduates with other degrees". Finally, a group of beneficiaries of a family clinic was invited to participate, which we categorized as "nonprofessionals". To evaluate the differences in moral reasoning between these 3 groups, we applied the Defining Issues Test (DIT), a moral reasoning questionnaire designed by James Rest using Kohlberg's theory of moral development. RESULTS: The moral reasoning of 237 subjects-88 from the "medical graduates" group, 82 from the "graduates with other degrees" group and 67 from the "nonprofessionals" group- was evaluated. We found differences in the profiles of moral development of the groups. The profile of the "nonprofessionals" showed a very high predominance of subjects at the preconventional level, 70%, but only 4.5% at the postconventional level. Among the "medical graduates", we observed 37.5% at the preconventional level and 34% at the postconventional level (X2 p < 0.001); this group had the highest percentage in this category. This large difference could be because the differences in the ages and socioeducational levels of nonprofessionals are much wider than those among medical graduates. However, significant differences were also found when the profiles of medical graduates were compared with those of graduates with other degrees, since the latter demonstrated 56% at the preconventional level and 18% at the postconventional level (X2 test, p = 0.02). CONCLUSIONS: Significant differences were found in moral reasoning among the groups that we evaluated. Among the group of medical graduates, there was a higher percentage of subjects at the postconventional level than among the group of graduates with other degrees and a much higher percentage than among the group of nonprofessionals. Our conclusions give the first evidence that studying medicine seems to influence the development of moral reasoning in its students. Therefore, we consider it relevant to develop educational strategies where the student is involved in simulated but realistic decision-making situations, where there are moral dilemmas to resolve from their early years of training.
Subject(s)
Morals , Students, Medical , Adolescent , Adult , Child , Cross-Sectional Studies , Humans , Moral Development , Problem SolvingABSTRACT
INTRODUCTION: This study aimed to identify the impact of the COVID-19 pandemic upon radiography education across Latin American countries. METHODS: A survey containing 20 questions was circulated to radiography students, across 13 universities in 11 countries of Latin America using Google Forms. The survey contained open and closed questions. Answers were analysed with descriptive statistics and the methodology of interpretative phenomenological analysis for the open answers. RESULTS: Of the 1310 responses only 23.9% (n = 313) of students reported attending clinical placements and from this cohort only 8.9% (n = 28) became infected with COVID-19. In response to how the pandemic had impacted upon the students' academic progression, the most common topic in the open answers was "Concerns about the lack of clinical training", mentioned by 629 students. Students in middle and later years of their radiography education expressed the greatest concern about future clinical placements. Almost all radiography students (95.2%/n = 1247) indicated that their main concerns regarding COVID-19 infection while undertaking clinical placements was in relation to the risk of infecting their families as most students stated they cohabited with relatives (86.6%/n = 1134). CONCLUSION: Compared to European findings co-habitation trends increased anxiety related to infection and impacted their mental health. Students expressed concern about the quality of education they were receiving during the pandemic and access to resources to facilitate on-line learning was inadequate. Socio-economic and internet connectivity factors specific to Latin America were identified and these issues need to be addressed if on-line education is required in the future. IMPLICATIONS FOR PRACTICE: The COVID-19 pandemic has impacted Latin America and this study identifies the implications for radiography students related to their clinical and academic training and highlights factors which require consideration to support radiography students as the pandemic continues.
Subject(s)
COVID-19 , COVID-19/epidemiology , Humans , Latin America/epidemiology , Pandemics , Students/psychology , UniversitiesABSTRACT
BACKGROUND: Uveal melanoma (UM) and conjunctival melanoma (CM) are distinct entities with different etiologies and genetic background. We present a case of an atypical subconjunctival melanoma arising from a blue nevus. PATIENTS AND METHODS: A 61-year-old female presented with a partially melanocytic epibulbar mass with surrounding episcleral pigmented spots. The lesion was detached from the overlying conjunctiva without an intraocular component. Excisional biopsy revealed a predominantly epithelioid melanoma, that was suggested to be metastasic, although there was no evidence of a primary melanoma elsewhere. RESULTS: Molecular analysis identified GNAQ and BAP1 pathogenic variants, which strongly suggested the diagnosis as a primary epibulbar melanoma arising from episcleral blue nevus. CONCLUSION: This case demonstrates the value of tumor molecular analysis using Next Generation Sequencing (NGS) for differentiating the origin of an unusually located ocular melanoma.