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1.
J Immunol ; 213(5): 619-627, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39037267

RESUMEN

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.


Asunto(s)
Linfocitos T CD8-positivos , Cromatina , Interferón gamma , Listeria monocytogenes , Sepsis , Animales , Ratones , Traslado Adoptivo , Linfocitos T CD8-positivos/inmunología , Cromatina/inmunología , Cromatina/metabolismo , Modelos Animales de Enfermedad , Interferón gamma/inmunología , Listeria monocytogenes/inmunología , Listeriosis/inmunología , Activación de Linfocitos/inmunología , Ratones Endogámicos C57BL , Sepsis/inmunología
2.
J Chromatogr A ; 1729: 465035, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-38851029

RESUMEN

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.


Asunto(s)
Hidróxidos , Leche , Tetraciclinas , Leche/química , Animales , Tetraciclinas/aislamiento & purificación , Tetraciclinas/análisis , Tetraciclinas/química , Hidróxidos/química , Adsorción , Microextracción en Fase Sólida/métodos , Antibacterianos/aislamiento & purificación , Antibacterianos/química , Antibacterianos/análisis , Dióxido de Silicio/química
3.
Rev. chil. neuro-psiquiatr ; Rev. chil. neuro-psiquiatr;62(1)2024.
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1559698

RESUMEN

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.

4.
Toxicon ; 230: 107172, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37211060

RESUMEN

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.


Asunto(s)
Plantas Medicinales , Picaduras de Escorpión , Venenos de Escorpión , Animales , Picaduras de Escorpión/tratamiento farmacológico , México , Extractos Vegetales/farmacología , Fitoterapia , Antivenenos/uso terapéutico , Venenos de Escorpión/farmacología , Escorpiones
5.
BMC Med Educ ; 23(1): 380, 2023 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-37226125

RESUMEN

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.


Asunto(s)
COVID-19 , Grupos de Población , Humanos , Niño , Adulto , Pandemias , COVID-19/epidemiología , Principios Morales , Desarrollo Moral
6.
Appl Radiat Isot ; 191: 110532, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36332425

RESUMEN

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.


Asunto(s)
Cuarzo , Rayos gamma , Temperatura
7.
Mol Med ; 28(1): 131, 2022 11 08.
Artículo en Inglés | MEDLINE | ID: mdl-36348276

RESUMEN

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.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , Adulto , Masculino , Humanos , Persona de Mediana Edad , Femenino , Bromuro de Piridostigmina/uso terapéutico , SARS-CoV-2 , Respiración Artificial , Inflamación , Resultado del Tratamiento
8.
BMC Med Educ ; 22(1): 568, 2022 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-35870920

RESUMEN

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.


Asunto(s)
Principios Morales , Estudiantes de Medicina , Adolescente , Adulto , Niño , Estudios Transversales , Humanos , Desarrollo Moral , Solución de Problemas
9.
Sci Rep ; 11(1): 8823, 2021 04 23.
Artículo en Inglés | MEDLINE | ID: mdl-33893363

RESUMEN

To describe fundus autofluorescence (FAF) patterns in premature infants and to determine whether FAF increases gradually with increasing post-gestational age. This was a cross-sectional, observational and descriptive case series. FAF images were obtained from patients screened for Retinopathy of Prematurity. The presence of the following hypo-autofluorescence areas/structures was graded and ranked: macular pigment (foveal centre), optic nerve head, peripapillary vessels/vascular arcade (PP/VA), and equatorial vessels (EqV). Ranks were attributed to the number of structures visualized from the posterior pole towards the periphery. The rank of FAF could then be analysed by Spearman's correlation against age. Additionally, patients were divided by age into group 1 (< 40 weeks of corrected gestational age (WCGA)) and group 2 (> 40 WCGA). Differences between groups were tested with the Mann-Whitney U test. Thirteen patients were analysed. The mean WCGA at examination was 47.85 weeks. Spearman's correlation showed a strong positive correlation (r = 0.714) (P = 0.006) of FAF and WCGA. The Mann-Whitney U test revealed that the PP/VA and EqV were significantly more visible at > 40 WCGA than at < 40 WCGA (8.0 [P = 0.016] and 7.5 [P = 0.03], respectively). Patterns of FAF are described for the first time in premature infants. FAF increases gradually with age and centrifugally from the posterior pole towards the equator in premature infants.


Asunto(s)
Fluorescencia , Fondo de Ojo , Estudios Transversales , Humanos , Recién Nacido , Recien Nacido Prematuro , Lipofuscina/metabolismo , Epitelio Pigmentado de la Retina/metabolismo
10.
Epidemiol Infect ; 149: e109, 2021 04 29.
Artículo en Inglés | MEDLINE | ID: mdl-33913410

RESUMEN

Conflicting results have been obtained through meta-analyses for the role of obesity as a risk factor for adverse outcomes in patients with coronavirus disease-2019 (COVID-19), possibly due to the inclusion of predominantly multimorbid patients with severe COVID-19. Here, we aimed to study obesity alone or in combination with other comorbidities as a risk factor for short-term all-cause mortality and other adverse outcomes in Mexican patients evaluated for suspected COVID-19 in ambulatory units and hospitals in Mexico. We performed a retrospective observational analysis in a national cohort of 71 103 patients from all 32 states of Mexico from the National COVID-19 Epidemiological Surveillance Study. Two statistical models were applied through Cox regression to create survival models and logistic regression models to determine risk of death, hospitalisation, invasive mechanical ventilation, pneumonia and admission to an intensive care unit, conferred by obesity and other comorbidities (diabetes mellitus (DM), chronic obstructive pulmonary disease, asthma, immunosuppression, hypertension, cardiovascular disease and chronic kidney disease). Models were adjusted for other risk factors. From 24 February to 26 April 2020, 71 103 patients were evaluated for suspected COVID-19; 15 529 (21.8%) had a positive test for SARS-CoV-2; 46 960 (66.1%), negative and 8614 (12.1%), pending results. Obesity alone increased adjusted mortality risk in positive patients (hazard ratio (HR) = 2.7, 95% confidence interval (CI) 2.04-2.98), but not in negative and pending-result patients. Obesity combined with other comorbidities further increased risk of death (DM: HR = 2.79, 95% CI 2.04-3.80; immunosuppression: HR = 5.06, 95% CI 2.26-11.41; hypertension: HR = 2.30, 95% CI 1.77-3.01) and other adverse outcomes. In conclusion, obesity is a strong risk factor for short-term mortality and critical illness in Mexican patients with COVID-19; risk increases when obesity is present with other comorbidities.


Asunto(s)
COVID-19/mortalidad , Obesidad/complicaciones , Adulto , COVID-19/complicaciones , COVID-19/epidemiología , Estudios de Cohortes , Femenino , Humanos , Masculino , México/epidemiología , Persona de Mediana Edad , Obesidad/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Adulto Joven
11.
Mult Scler ; 27(11): 1695-1705, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-33300840

RESUMEN

BACKGROUND: Regulatory CD4+ T cells (Tregs) exhibit functional alterations in patients with multiple sclerosis (MS). Transforming growth factor (TGF)-ß is a key regulator of Treg development and function. OBJECTIVE: The objective of this study is to determine whether the expression of functionally relevant TGF-ß-regulated molecules is altered in Tregs from patients with MS. METHODS: Expression of nine Treg markers was analyzed by multi-color flow cytometry in CD4+ T cells and Treg subpopulations of 31 untreated MS patients and age- and sex-matched healthy donors (HDs). Correlations between Treg marker expression and clinical variables were sought. RESULTS: Expression of the transcription factor Helios, which defines thymic-derived Tregs, was decreased in this Treg subpopulation. The frequency of peripherally generated Tregs was increased in patients with MS, particularly in patients with progressive MS. Low frequencies of thymic-derived Tregs were associated with magnetic resonance imaging (MRI) lesion-burden and a high relapse rate. Four surface markers associated with TGF-ß signaling (ABCA1, BTLA, DNAM-1, and GARP) were differentially expressed on Tregs from patients with MS and HDs. Expression levels of CD73, CD103, ABCA1, and PAR2 showed strong correlations with disease severity. CONCLUSION: We have identified novel markers abnormally expressed on Tregs from patients with MS that could detect patients with severe disease.


Asunto(s)
Esclerosis Múltiple , Linfocitos T Reguladores , Células Cultivadas , Citometría de Flujo , Regulación de la Expresión Génica , Humanos
12.
BMC Infect Dis ; 20(1): 765, 2020 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-33066761

RESUMEN

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the causative agent of coronavirus disease 2019 (COVID-19), may lead to severe systemic inflammatory response, pulmonary damage, and even acute respiratory distress syndrome (ARDS). This in turn may result in respiratory failure and in death. Experimentally, acetylcholine (ACh) modulates the acute inflammatory response, a neuro-immune mechanism known as the inflammatory reflex. Recent clinical evidence suggest that electrical and chemical stimulation of the inflammatory reflex may reduce the burden of inflammation in chronic inflammatory diseases. Pyridostigmine (PDG), an ACh-esterase inhibitor (i-ACh-e), increases the half-life of endogenous ACh, therefore mimicking the inflammatory reflex. This clinical trial is aimed at evaluating if add-on of PDG leads to a decrease of invasive mechanical ventilation and death among patients with severe COVID-19. METHODS: A parallel-group, multicenter, randomized, double-blinded, placebo-controlled, phase 2/3 clinical trial to test the efficacy of pyridostigmine bromide 60 mg/day P.O. to reduce the need for invasive mechanical ventilation and mortality in hospitalized patients with severe COVID-19. DISCUSSION: This study will provide preliminary evidence of whether or not -by decreasing systemic inflammation- add-on PDG can improve clinical outcomes in patients with severe COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov NCT04343963 (registered on April 14, 2020).


Asunto(s)
Inhibidores de la Colinesterasa/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Bromuro de Piridostigmina/uso terapéutico , Adulto , Betacoronavirus/patogenicidad , COVID-19 , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/fisiopatología , Humanos , Inflamación , Pulmón/efectos de los fármacos , Pulmón/patología , Pulmón/fisiopatología , Pandemias , Neumonía Viral/mortalidad , Neumonía Viral/patología , Neumonía Viral/fisiopatología , Respiración Artificial , SARS-CoV-2
13.
Brain Sci ; 10(9)2020 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-32933015

RESUMEN

Temporal lobe epilepsy (TLE), the most common type of focal epilepsy, affects learning and memory; these effects are thought to emerge from changes in synaptic plasticity. Levetiracetam (LEV) is a widely used antiepileptic drug that is also associated with the reversal of cognitive dysfunction. The long-lasting effect of LEV treatment and its participation in synaptic plasticity have not been explored in early chronic epilepsy. Therefore, through the measurement of evoked field potentials, this study aimed to comprehensively identify the alterations in the excitability and the short-term (depression/facilitation) and long-term synaptic plasticity (long-term potentiation, LTP) of the dentate gyrus of the hippocampus in a lithium-pilocarpine rat model of TLE, as well as their possible restoration by LEV (1 week; 300 mg/kg/day). TLE increased the population spike (PS) amplitude (input/output curve); interestingly, LEV treatment partially reduced this hyperexcitability. Furthermore, TLE augmented synaptic depression, suppressed paired-pulse facilitation, and reduced PS-LTP; however, LEV did not alleviate such alterations. Conversely, the excitatory postsynaptic potential (EPSP)-LTP of TLE rats was comparable to that of control rats and was decreased by LEV. LEV caused a long-lasting attenuation of basal hyperexcitability but did not restore impaired synaptic plasticity in the early chronic phase of TLE.

14.
J Clin Invest ; 130(11): 5989-6004, 2020 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-32750040

RESUMEN

How T cells integrate environmental cues into signals that limit the magnitude and length of immune responses is poorly understood. Here, we provide data that demonstrate that B55ß, a regulatory subunit of protein phosphatase 2A, represents a molecular link between cytokine concentration and apoptosis in activated CD8+ T cells. Through the modulation of AKT, B55ß induced the expression of the proapoptotic molecule Hrk in response to cytokine withdrawal. Accordingly, B55ß and Hrk were both required for in vivo and in vitro contraction of activated CD8+ lymphocytes. We show that this process plays a role during clonal contraction, establishment of immune memory, and preservation of peripheral tolerance. This regulatory pathway may represent an unexplored opportunity to end unwanted immune responses or to promote immune memory.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Memoria Inmunológica , Proteína Fosfatasa 2/inmunología , Animales , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/inmunología , Ratones , Ratones Transgénicos , Neuropéptidos/genética , Neuropéptidos/inmunología , Proteína Fosfatasa 2/genética , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/inmunología
15.
J Am Mosq Control Assoc ; 36(1): 16-21, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32497478

RESUMEN

Commercial aerosolized insecticides can be implemented as a community-based approach to targeted indoor residual spraying against Aedes aegypti, but their efficacy on pyrethroid-resistant mosquitoes has not yet been evaluated. Two commercial aerosolized products (H24 Poder Fulminante Ultra Eficaz®, carbamate, and Baygon Ultra Verde®, pyrethroid) were sprayed on common indoor surfaces e.g., cement, plywood, and cloth, and tested for their residual efficacy on susceptible and field-derived pyrethroid-resistant Ae. aegypti strains using the WHO cone bioassays. Overall, ≥80% 24-h mortality was observed for both products for at least 4 wk regardless of the mosquito strain or surface type used. H24 Poder Fulminante Ultra Eficaz showed the highest residual potency, sustaining >80% mortality for 7-wk posttreatment regardless of mosquito strain and surface type. For Baygon Ultra Verde, the mean mortality of female Ae. aegypti remained >80% for a shorter period (4-6 wk). Nonpyrethroid commercial aerosolized formulations can provide a lasting residual effect indoors compatible with the need for rapid and lasting mosquito control during outbreaks and may be suitable for community-based targeted indoor residual spraying.


Asunto(s)
Aedes , Carbamatos , Insecticidas , Control de Mosquitos , Piretrinas , Animales , Femenino , México , Residuos de Plaguicidas
16.
Sensors (Basel) ; 20(10)2020 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-32429400

RESUMEN

This paper proposes a teleophthalmology support system in which we use algorithms of object detection and semantic segmentation, such as faster region-based CNN (FR-CNN) and SegNet, based on several CNN architectures such as: Vgg16, MobileNet, AlexNet, etc. These are used to segment and analyze the principal anatomical elements, such as optic disc (OD), region of interest (ROI) composed by the macular region, real retinal region, and vessels. Unlike the conventional retinal image quality assessment system, the proposed system provides some possible reasons about the low-quality image to support the operator of an ophthalmoscope and patient to acquire and transmit a better-quality image to central eye hospital for its diagnosis. The proposed system consists of four steps: OD detection, OD quality analysis, obstruction detection of the region of interest (ROI), and vessel segmentation. For the OD detection, artefacts and vessel segmentation, the FR-CNN and SegNet are used, while for the OD quality analysis, we use transfer learning. The proposed system provides accuracies of 0.93 for the OD detection, 0.86 for OD image quality, 1.0 for artefact detection, and 0.98 for vessel segmentation. As the global performance metric, the kappa-based agreement score between ophthalmologist and the proposed system is calculated, which is higher than the score between ophthalmologist and general practitioner.


Asunto(s)
Oftalmología , Disco Óptico , Telemedicina , Algoritmos , Humanos , Retina
17.
Graefes Arch Clin Exp Ophthalmol ; 258(4): 767-772, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31953595

RESUMEN

PURPOSE: To provide a diagnostic algorithm of recurrence and treatment failure after intravitreal bevacizumab (IVB) injection for retinopathy of prematurity type 1 (ROP1) and the stepwise therapeutic approach for both conditions. METHODS: Retrospective chart review of all patients diagnosed with ROP1 initially treated with IVB in 6 tertiary referral centers of Toluca and Mexico City from 2005 to 2017. Treatment failure was defined as persistence or progression of neovascularization, elevation of the ridge, worsening of plus disease, or retinal crunch within the first week after treatment. Recurrence was defined as the new appearance of plus disease, an elevated ridge, or pathological new vessels after an initial regression of ROP following treatment. Therapy was observation, switch of anti-VEGF agent, retinal photocoagulation, vitrectomy, or a combination of two or more, depending on the severity of findings. RESULTS: A total of 672 patients who received intravitreal bevacizumab injection for ROP1 treatment were included. Of these, 2.5% (17 patients) failed to treatment, 6.8% (46 patients) developed a recurrence for ROP, and 5.5% (37 patients) carried a misdiagnosis of recurrence and were diagnosed with other than ROP1 after examination. Based on the severity of findings, patients with recurrence or treatment failure were further treated by observation, repeat anti-VEGF intravitreal injection (bevacizumab or other), laser photocoagulation, vitrectomy, or a combination of these. Based on the treatment results, a therapeutic algorithm was created. CONCLUSIONS: Intravitreal injection of anti-VEGFs for the treatment of ROP warrants close follow-up as some of these patients may have treatment failure or recurrence of the disease. It is crucial to differentiate between them to avoid a misdiagnosis and offer the correct treatment. We propose a novel algorithm for the follow-up and treatment approach of ROP1 following initial treatment with IVB. This algorithm offers a summary of our recommendations based on a large case series of ROP1 patients. It is meant to grow and expand as more clinical evidence becomes available.


Asunto(s)
Algoritmos , Bevacizumab/administración & dosificación , Retinopatía de la Prematuridad/tratamiento farmacológico , Inhibidores de la Angiogénesis/administración & dosificación , Femenino , Estudios de Seguimiento , Edad Gestacional , Humanos , Recién Nacido , Inyecciones Intravítreas , Coagulación con Láser/métodos , Masculino , Recurrencia , Retina/patología , Retinopatía de la Prematuridad/diagnóstico , Retinopatía de la Prematuridad/cirugía , Estudios Retrospectivos , Insuficiencia del Tratamiento , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores
19.
Rev Chilena Infectol ; 36(3): 318-330, 2019 Jun.
Artículo en Español | MEDLINE | ID: mdl-31859751

RESUMEN

BACKGROUND: Since the incorporation of antiretroviral therapy (ART) HIV has become a chronic condition, improving survival and allowing children with the virus to come in better conditions to adolescence, where they are faced with a series of changes, among them, to sexual awakening. AIM: To explore the main beliefs, perceptions and experiences in sexuality of a group of adolescents with HIV infection acquired through vertical transmission. METHODS: A qualitative research was carried out with exploratory and descriptive scope. Semi-structured interviews were applied to 28 adolescents, under control in hospitals in Santiago and Valparaíso, with HIV infection. The analysis was carried out according to the Grounded Theory. RESULTS: There was a lack of sexual education and a vision that focuses on risks, such as sexually transmissible infections or teenage pregnancy. There are fears about the possibility of rejection by others and of transmitting the virus to the couple or the children and they are invaded by feelings of shame and anger. CONCLUSION: It is important to train health professionals who work with this group, because they are identified as a reliable source of information and education.


Asunto(s)
Conducta del Adolescente/psicología , Infecciones por VIH/transmisión , Conocimientos, Actitudes y Práctica en Salud , Transmisión Vertical de Enfermedad Infecciosa , Conducta Sexual/psicología , Adolescente , Adulto , Niño , Cultura , Femenino , Infecciones por VIH/psicología , Humanos , Acontecimientos que Cambian la Vida , Masculino , Percepción , Educación Sexual , Factores Socioeconómicos , Encuestas y Cuestionarios , Adulto Joven
20.
Rev. cir. (Impr.) ; 71(5): 446-449, oct. 2019. ilus
Artículo en Español | LILACS | ID: biblio-1058299

RESUMEN

Resumen Introducción: Los aneurismas infecciosos constituyen una patología poco frecuente y se caracterizan por presentar infección de la pared del vaso implicado. El mejor tratamiento no está definitivamente establecido. Objetivo: Describir un caso de aneurisma infeccioso con manejo endovascular. Caso clínico: Presentamos un paciente de sexo masculino de 75 años que ingresa por cuadro compatible con abdomen agudo y que en el posoperatorio se pesquisa un aneurisma infeccioso del tronco celíaco, el cual se trata mediante una endoprótesis y manejo antibiótico. Discusión: El manejo tradicional del aneurisma infeccioso es la cirugía abierta que incluye la extirpación o exclusión del aneurisma y de su tejido perivascular infectado, pero conlleva gran morbimortalidad. Conclusión: El aneurisma infeccioso puede ser manejado de forma mínimamente invasiva con técnica endovascular, con baja morbilidad inmediata, pero con resultados a largo plazo aun no concluyentes.


Introduction: Infectious aneurysms are a rare disease and are characterized by infection of the involved vessel wall. The best treatment is definitely not established. Aim: To describe a case of infectious aneurysm with endovascular management. Case report: We present a 75-year-old male patient admitted to a table compatible with acute abdomen and that an infectious aneurysm of the celiac trunk is investigated in the postoperative period, treated with an endoprosthesis and antibiotic management. Discussion: The traditional management of the infectious aneurysm is open surgery that includes the removal or exclusion of the aneurysm and its infected perivascular tissue, but it leads to great morbidity and mortality. Conclusion: The infectious aneurysm can be managed minimally invasively with endovascular technique, with immediate low morbidity, but with long-term results that are still inconclusive.


Asunto(s)
Humanos , Masculino , Anciano , Aneurisma Infectado/diagnóstico , Aneurisma Infectado/terapia , Procedimientos Endovasculares/métodos , Absceso Hepático/complicaciones , Prótesis e Implantes , Angiografía , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Procedimientos Quirúrgicos Mínimamente Invasivos , Abdomen Agudo/etiología , Absceso Hepático/diagnóstico
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