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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection triggers activation of the NLRP3 inflammasome, which promotes inflammation and aggravates severe COVID-19. Here, we report that SARS-CoV-2 induces upregulation and activation of human caspase-4/CASP4 (mouse caspase-11/CASP11), and this process contributes to NLRP3 activation. In vivo infections performed in transgenic hACE2 humanized mice, deficient or sufficient for Casp11, indicate that hACE2 Casp11-/- mice were protected from disease development, with the increased pulmonary parenchymal area, reduced clinical score of the disease, and reduced mortality. Assessing human samples from fatal cases of COVID-19, we found that CASP4 was expressed in patient lungs and correlated with the expression of inflammasome components and inflammatory mediators, including CASP1, IL1B, IL18, and IL6. Collectively, our data establish that CASP4/11 promotes NLRP3 activation and disease pathology, revealing a possible target for therapeutic interventions for COVID-19.
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COVID-19 , Inflamasomas , Ratones , Animales , Humanos , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Macrófagos/metabolismo , COVID-19/metabolismo , SARS-CoV-2/metabolismo , Ratones TransgénicosRESUMEN
Historically, eating disorders (EDs) have been conceptualized from a female-centric lens. However, consistent research demonstrates that EDs afflict individuals across the gender spectrum, including cismales and gender-diverse individuals. Despite this evidence, a consensus regarding gender-sensitive assessment practices, theoretical formulations, and treatment considerations has yet to be established. The present review briefly summarizes research to date on the presentation of EDs in cismales and gender-diverse individuals, suggests appropriate assessment and treatment practices, and offers recommendations for gender-inclusive ED treatment. To effectively serve patients with EDs across the gender spectrum, more research is needed to validate gender-sensitive assessment tools, comprehensively study ED pathology within gender-representative samples, and conduct randomized controlled trials that serve cismales and gender-diverse patients. In doing so, clinicians and researchers may better detect EDs across the gender spectrum and implement gender-appropriate, evidence-based interventions, thereby reducing impairment and mortality related to EDs for all patients.
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Microchemical sensors and catalytic reactors make use of gases during adsorption in specific ways on selected materials. Fine-tuning is normally achieved by morphological control and material doping. The latter relates surface properties to the electronic structure of the bulk, and this suggests the possibility of electronic control. Although unusual for catalytic surfaces, such phenomena are sometimes reported for microsensors, but with little understanding of the underlying mechanisms. Herein, direct observation of the electroadsorptive effect by a combination of X-ray photoelectron spectroscopy and conductivity analysis on nanometre-thick semiconductor films on buried control electrodes is reported. For the SnO2/NO2 model system, NO3 surface species, which normally decay at the latest within minutes, can be kept stable for 1.5 h with a high coverage of 15% under appropriate electric fields. This includes uncharged states, too, and implies that nanoelectronic structures provide control over the predominant adsorbate conformation on exterior surfaces and thus opens the field for chemically reactive interfaces with in situ tunability.
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Cervical cancer (CC) is the fourth most common cancer in women worldwide, with more than 500,000 new cases each year and a mortality rate of around 55%. Over 80% of these deaths occur in developing countries. The most important risk factor for CC is persistent infection by a sexually transmitted virus, the human papillomavirus (HPV). Conventional treatments to eradicate this type of cancer are accompanied by high rates of resistance and a large number of side effects. Hence, it is crucial to devise novel effective therapeutic strategies. In recent years, an increasing number of studies have aimed to develop immunotherapeutic methods for treating cancer. However, these strategies have not proven to be effective enough to combat CC. This means there is a need to investigate immune molecular targets. An adaptive immune response against cancer has been described in seven key stages or steps defined as the cancer-immunity cycle (CIC). The CIC begins with the release of antigens by tumor cells and ends with their destruction by cytotoxic T-cells. In this paper, we discuss several molecular alterations found in each stage of the CIC of CC. In addition, we analyze the evidence discovered, the molecular mechanisms and their relationship with variables such as histological subtype and HPV infection, as well as their potential impact for adopting novel immunotherapeutic approaches.
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Novel manganese oxide particles with complex morphologies and different nanostructures (i.e., spherical/lamellar) were synthesized by initial preparation of a coordination complex of manganese with 1,4,7,10-tetraazacyclododecane (cyclen), followed by characterization of the nanostructured oxide as a catalytic material for ethanol oxidation. The samples present a bulk gamma-MnO2 structure although X-ray photoelectron spectroscopy analysis reveals that their surfaces have different chemical compositions. Some of these nanostructured particles show high catalytic activities for ethanol oxidation enabling a decrease of the reaction temperature by more than 80 degrees C as compared with traditional MnO2 particles. The high catalytic activity of the particles depends on their morphology and a relationship between morphology and specific area was established. It is proposed that these novel nanostructured manganese oxide particles may be highly active in the catalytic oxidation of other volatile organic compounds (VOCs) opening up their further development for environmental applications.
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Etanol/química , Óxido de Magnesio/química , Nanopartículas del Metal , Catálisis , Cristalografía por Rayos X , Microscopía Electrónica de Rastreo , Oxidación-Reducción , Espectroscopía de FotoelectronesRESUMEN
INTRODUCTION: SARS-CoV-2 infection can produce endothelial injury and microvascular damage, one cause of the multiorgan failure associated with COVID-19. Cerebrovascular endothelial damage increases the risk of stroke in COVID-19 patients, which makes prompt diagnosis important. Endothelial dysfunction can be evaluated by using transcranial Doppler ultrasound to study cerebral hemodynamic reserve, but there are few of these studies in patients with COVID-19, and the technique is not included in COVID-19 action and follow-up guidelines nationally or internationally. OBJECTIVE: Estimate baseline cerebral hemodynamic patterns, cerebral hemodynamic reserve, and breath-holding index in recovered COVID-19 patients. METHOD: We conducted an exploratory study in 51 people; 27 men and 24 women 20-78 years of age, divided into two groups. One group comprised 25 recovered COVID-19 patients, following clinical and epidemiological discharge, who suffered differing degrees of disease severity, and who had no neurological symptoms or disease at the time they were incorporated into the study. The second group comprised 26 people who had not been diagnosed with COVID-19 and who tested negative by RT-PCR at the time of study enrollment. Recovered patients were further divided into two groups: those who had been asymptomatic or had mild disease, and those who had severe or critical disease. We performed transcranial Doppler ultrasounds to obtain baseline and post-apnea tests of cerebral hemodynamic patterns to evaluate cerebral hemodynamic reserve and breath-holding indices. We characterized the recovered patient group and the control group through simple descriptive statistics (means and standard deviations). RESULTS: There were no measurable differences in baseline cerebral hemodynamics between the groups. However, cerebral hemodynamic reserve and breath-holding index were lower in those who had COVID-19 than among control participants (19.9% vs. 36.8% and 0.7 vs. 1.2 respectively). These variables were similar for patients who had asymptomatic or mild disease (19.9% vs.19.8%) and for those who had severe or critical disease (0.7 vs. 0.7). CONCLUSIONS: Patients recovered from SARS-CoV-2 infection showed decreased cerebral hemodynamic reserve and breath-holding index regardless of the disease's clinical severity or presence of neurological symptoms. These abnormalities may be associated with endothelial damage caused by COVID-19. It would be useful to include transcranial Doppler ultrasound in evaluation and follow-up protocols for patients with COVID-19.
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COVID-19 , Cuba , Femenino , Hemodinámica , Humanos , Masculino , SARS-CoV-2 , Ultrasonografía Doppler TranscranealRESUMEN
Background: In COVID-19, EGFR production is upregulated in the alveolar epithelial cells. EGFR overexpression further activates STAT-3 and increases lung pathology. The EGFR pathway is also one of the major nodes in pulmonary fibrosis. Methods: Nimotuzumab, a humanized anti-EGFR antibody, was used to treat three patients with severe or moderate COVID-19. The antibody was administered in combination with other drugs included in the national COVID-19 protocol. Results: Nimotuzumab was well tolerated. IL-6 decreased from the first antibody infusion. Clinical symptoms significantly improved after nimotuzumab administration, and the CT scans at discharge showed major resolution of the lung lesions and no signs of fibrosis. Conclusion: Safe anti-EGFR antibodies like nimotuzumab may modulate COVID-19-associated hyperinflammation and prevent fibrosis. Clinical Trial Registration: RPCEC00000369 (RPCEC rpcec.sld.cu).
Lay abstract Background: In COVID-19, the protein EGFR is overactive in the infected lung cells. Methods: Nimotuzumab, an anti-EGFR antibody, was used to treat three patients with severe or moderate COVID-19. The antibody was administered in combination with other drugs included in the national COVID-19 protocol. Results: Nimotuzumab was safe. The most important inflammatory markers decreased from the first administration. The patients' clinical symptoms and imaging results improved significantly. Conclusion: Anti-EGFR antibodies like nimotuzumab may contribute to the recovery of COVID-19 patients without long-term consequences.
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A set of poly(propylene) composites containing different amounts of copper nanoparticles (CNP) were prepared by the melt mixed method and their antimicrobial behavior was quantitatively studied. The time needed to reduce the bacteria to 50% dropped to half with only 1 v/v % of CNP, compared to the polymer without CNP. After 4 h, this composite killed more than 99.9% of the bacteria. The biocide kinetics can be controlled by the nanofiller content; composites with CNP concentrations higher than 10 v/v % eliminated 99% of the bacteria in less than 2 h. X-ray photoelectron spectroscopy did not detect CNP at the surface, therefore the biocide behavior was attributed to copper in the bulk of the composite.
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PURPOSE: Body dissatisfaction in transgender youth (TY) may increase the risk for eating disorders. This is the first study using the Eating Disorders Examination Questionnaire (EDE-Q) to assess for eating disorder psychopathology in TY. METHODS: Youth aged 13-22 years (n = 106) presenting to a gender clinic from January 2018 to January 2019 completed the EDE-Q and answered questions on weight manipulation for gender-affirming purposes. RESULTS: Respondents identified as transmasculine (61%), transfeminine (28%), or nonbinary (11%). Mean age was 16.5 years (standard deviation = 2.0), mean weight was 119.9% median body mass index (standard deviation = 32.9), and 32% were on hormonal therapy. Of the participants, 15% had elevated EDE-Q scores. Most (63%) disclosed weight manipulation for gender-affirming purposes, with 11% of assigned females doing so for menstrual suppression. These behaviors had poor concordance with elevated EDE-Q scores (κ = .137 and .148). CONCLUSIONS: Disordered eating behaviors are relatively common among TY. Further studies are needed to validate the EDE-Q in TY and establish meaningful cutoff score values.
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Insatisfacción Corporal/psicología , Trastornos de Alimentación y de la Ingestión de Alimentos/fisiopatología , Tamizaje Masivo , Personas Transgénero , Adolescente , Femenino , Humanos , Masculino , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
Eating disorders are one of the most common chronic conditions in adolescents. The clinical symptoms can mimic those of other chronic diseases including gastrointestinal and endocrine disorders. However, an eating disorder can coexist with another chronic disease, making the diagnosis and management of both conditions challenging. This Review describes what is known about eating disorders in adolescents with chronic gastrointestinal and endocrine diseases, focusing on coeliac disease, inflammatory bowel disease, diabetes, and thyroid disorders. The prevalence and onset of each condition during adolescence is discussed, followed by a description of the associations among the conditions and eating disorders. We also discuss management challenges posed by the coexistence of the two conditions. When both diseases coexist, a multidisciplinary approach is often needed to address the additional complexities posed.
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Enfermedad Celíaca/fisiopatología , Diabetes Mellitus/fisiopatología , Trastornos de Alimentación y de la Ingestión de Alimentos/fisiopatología , Enfermedades Inflamatorias del Intestino/fisiopatología , Enfermedades de la Tiroides/fisiopatología , Adolescente , Adulto , Enfermedad Celíaca/complicaciones , Enfermedad Celíaca/diagnóstico , Diabetes Mellitus/diagnóstico , Trastornos de Alimentación y de la Ingestión de Alimentos/complicaciones , Trastornos de Alimentación y de la Ingestión de Alimentos/diagnóstico , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/diagnóstico , Masculino , Enfermedades de la Tiroides/complicaciones , Enfermedades de la Tiroides/diagnóstico , Adulto JovenRESUMEN
BACKGROUND: Fibroepithelial polyps (FEPs) are benign tumors, of possibly hormone-dependent nature, found in the vulvovaginal region of women of reproductive age. CASE: A 15-year-old adolescent girl, receiving hormonal contraceptive therapy, who presented with multiple vulvar masses with histopathology consistent with FEP. SUMMARY AND CONCLUSION: The spectrum of the morphology of FEPs might make their diagnosis challenging. We describe a rare presentation of vulvar FEPs in an adolescent girl receiving hormonal contraceptive therapy.
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Neoplasias Fibroepiteliales/patología , Vulva/patología , Neoplasias de la Vulva/patología , Adolescente , Femenino , Humanos , Neoplasias Fibroepiteliales/cirugía , Pólipos/diagnóstico , Neoplasias de la Vulva/cirugíaRESUMEN
Local polarization of a magnetic layer, a well-known method for storing information, has found its place in numerous applications such as the popular magnetic drawing board toy or the widespread credit cards and computer hard drives. Here we experimentally show that a similar principle can be applied for imprinting the trajectory of quantum units of flux (vortices), travelling in a superconducting film (Nb), into a soft magnetic layer of permalloy (Py). In full analogy with the magnetic drawing board, vortices act as tiny magnetic scribers leaving a wake of polarized magnetic media in the Py board. The mutual interaction between superconducting vortices and ferromagnetic domains has been investigated by the magneto-optical imaging technique. For thick Py layers, the stripe magnetic domain pattern guides both the smooth magnetic flux penetration as well as the abrupt vortex avalanches in the Nb film. It is however in thin Py layers without stripe domains where superconducting vortices leave the clearest imprints of locally polarized magnetic moment along their paths. In all cases, we observe that the flux is delayed at the border of the magnetic layer. Our findings open the quest for optimizing magnetic recording of superconducting vortex trajectories.