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AIM: Understanding the molecular identity of human pluripotent stem cell (hPSC)-derived cardiac progenitors and mechanisms controlling their proliferation and differentiation, is valuable for developmental biology and regenerative medicine. METHODS AND RESULTS: Here we show that chemical modulation of Histone Acetyl Transferases (HATs; by IQ-1) and WNT (by CHIR99021), synergistically enable the transient and reversible block of directed cardiac differentiation progression on hPSCs. The resulting stabilized cardiovascular progenitors (SCPs) are characterized by ISL1pos/KI-67pos/NKX2-5neg expression. In the presence of the chemical inhibitors, SCPs maintain a proliferation quiescent state. Upon small molecules removal SCPs resume proliferation and concomitant NKX2-5 upregulation triggers cell-autonomous differentiation into cardiomyocytes. Directed differentiation of SCPs into the endothelial and smooth muscle lineages confirms their full developmental potential typical of bona fide cardiovascular progenitors. Single-cell RNAseq-based transcriptional profiling of our in vitro generated human SCPs notably reflects the dynamic cellular composition of E8.25-E9.25 posterior second heart field (pSHF) of mouse hearts, hallmarked by NR2F2 expression. Investigating molecular mechanisms of SCP stabilization, we found that the cell-autonomously regulated Retinoic Acid (RA) and BMP signaling is governing SCPs transition from quiescence towards proliferation and cell-autonomous differentiation, reminiscent of a niche-like behavior. CONCLUSION: The chemically defined and reversible nature our stabilization approach provides an unprecedented opportunity to dissect mechanisms of cardiovascular progenitors' specification and reveal their cellular and molecular properties.
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BACKGROUND: Rate control is the most commonly employed first-line management strategy for atrial fibrillation (AF) in patients with chronic kidney disease (CKD). Principal agents used to control heart rate (HR) include beta-blockers (BB) and nondihydropyridine calcium channel blockers (ND-CCB). However, there is a paucity of published studies of the differences between those drugs in CKD patients. HYPOTHESIS: The present study aimed to investigate the differences, in terms of hospitalizations due to a poor HR control, in patients with AF under a rate-control strategy according to glomerular filtration rate (GFR). METHODS: The study cohort included 2804 AF patients under rate-control regime (BB or ND-CCB) between January 2014 and April 2020. The end point, determined by competing risk regression, was hospitalizations for AF with rapid ventricular response (RVR), slow ventricular response (SVR), and need for pacemaker. RESULTS: On multivariate analysis, there were no statistical differences between ND-CCB and BB for subjects with GFR > 60 mL/min/1.73 m2 (subdistribution heart rate [sHR] 0.850, 95% confidence interval [CI]: 0.61-1.19; p = .442) and GFR 30-59 mL/min/1.73 m2 (sHR 1.242, 95% CI: 0.80-1.63; p = .333), while in patients with GFR < 30 mL/min/1.73 m2, ND-CCB therapy was associated with increased hospitalizations due to poor HR control (sHR 4.53, 95% CI: 1.19-17.18; p = .026). CONCLUSION: In patients with GFR ≥ 30 mL/min/1.73 m2, the choice of ND-CCB or BB had no impact on hospitalizations due to poor HR control, while in GFR < 30 mL/min/1.73 m2, a possible association was detected. The effects of these drugs on GFR < 30 mL/min/1.73 m2 would require further investigation.
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Antagonistas Adrenérgicos beta , Fibrilación Atrial , Bloqueadores de los Canales de Calcio , Tasa de Filtración Glomerular , Frecuencia Cardíaca , Insuficiencia Renal Crónica , Humanos , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/fisiopatología , Femenino , Masculino , Bloqueadores de los Canales de Calcio/uso terapéutico , Antagonistas Adrenérgicos beta/uso terapéutico , Tasa de Filtración Glomerular/efectos de los fármacos , Anciano , Frecuencia Cardíaca/efectos de los fármacos , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Estudios Retrospectivos , Resultado del Tratamiento , Persona de Mediana Edad , Hospitalización/estadística & datos numéricos , Riñón/fisiopatología , Factores de Riesgo , Estudios de SeguimientoRESUMEN
OBJECTIVE: To develop and evaluate the efficacy of WS Biotin, a novel water-soluble form of D-Biotin, for cosmetic use. METHODS: A new encapsulated form of D-Biotin was developed with the purpose of improving the water solubility of biotin. This novel form of encapsulated biotin was characterized by its physicochemical properties: particle size, D-Biotin content and solubility in water. Also, proliferation and gene expression in vitro tests in cell culture were performed to evaluate its effectiveness in promoting hair growth, an ELISA test was conducted for hair keratinization and skin lightening property was tested by analysing the intracellular melanin content. RESULTS: The developed WS Biotin microcapsules exhibit a particle size range of 2-30 µm with D-Biotin content of ~50% (w/w). The water solubility of WS Biotin was found to be 20-fold greater than free biotin. The obtained in vitro results indicated that WS Biotin enhances the expression of hair-related keratins in hair follicle keratinocytes, as well as the expression of hair growth-promoting genes in dermal papilla cells. Moreover, the melanin content in UVA-exposed epidermal melanocytes was reduced upon exposure to WS Biotin. CONCLUSION: In this work, a novel form of encapsulated biotin, WS Biotin, was developed in order to improve the water solubility of free biotin and was found to be effective for cosmetic use in both hair and skin applications.
OBJECTIF: Développer et évaluer l'efficacité de la WS Biotin, une nouvelle forme hydrosoluble de D-biotine, à usage cosmétique. MÉTHODES: Une nouveau format gélules de D-biotine a été développé dans le but d'améliorer la propriété d'hydrosolubilité de la biotine. Ce nouveau format de gélules de biotine a été caractérisé pour ses propriétés physicochimiques : taille des particules, teneur en D-biotine et solubilité dans l'eau. En outre, des tests in vitro de prolifération et d'expression génique en culture cellulaire ont été réalisés pour évaluer son efficacité à favoriser la croissance des cheveux, un test ELISA a été réalisé pour la kératinisation des cheveux et la propriété d'éclaircissement de la peau a été testée en analysant la teneur en mélanine intracellulaire. RÉSULTATS: Les microgélules de WS Biotin développées présentent une plage de tailles de particules de 2 à 30 micromètres avec une teneur en biotine D d'environ 50 % (p/p). L'hydrosolubilité de WS Biotin s'est avérée 20 fois plus élevée que celle de la biotine libre. Les résultats in vitro obtenus ont indiqué que WS Biotin améliorait l'expression des kératines capillaires dans les kératinocytes des follicules pileux, ainsi que l'expression des gènes favorisant la croissance dans les cellules papillaires dermiques. En outre, la teneur en mélanine dans les mélanocytes épidermiques exposés aux UVA a été réduite lors de l'exposition à WS Biotin. CONCLUSION: Dans ce travail, une nouvelle forme de biotine en gélule, WS Biotin, a été développée afin d'améliorer l'hydrosolubilité de la biotine libre et s'est avérée efficace pour une utilisation cosmétique dans les applications capillaires et cutanées.
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Biotina , Melaninas , Biotina/farmacología , Biotina/metabolismo , Melaninas/metabolismo , Solubilidad , Cabello , Piel , Folículo PilosoRESUMEN
Iliac vein compression syndrome (IVCS) is defined as extrinsic compression of the left common iliac vein (LCIV) between the overlying right common iliac artery and the lumbar vertebra. The most severe complication is phlegmasia cerulea dolens (PCD), a medical emergency that requires quick intervention to prevent irreversible limb ischemia. This article reports the case of a patient with PCD as the first manifestation of IVCS. The treatment included embolectomy and fasciotomy. Bilateral femoral iliac axis phlebography and cavography were performed 48 hours after the procedure. The IVCS was identified, and balloon predilatation of the lesions followed by implantation of self-expanding stents from the confluence of the LCIV with the inferior vena cava to the middle portion of the left external iliac vein was performed. Postprocedure phlebography demonstrated satisfactory final results, and a 12-month follow-up image showed patent stents and minimal intimal hyperplasia.
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Iliac vein compression syndrome (IVCS) is defined as extrinsic compression of the left common iliac vein (LCIV) between the overlying right common iliac artery and the lumbar vertebra. The most severe complication is phlegmasia cerulea dolens (PCD), a medical emergency that requires quick intervention to prevent irreversible limb ischemia. This article reports the case of a patient with PCD as the first manifestation of IVCS. The treatment included embolectomy and fasciotomy. Bilateral femoral iliac axis phlebography and cavography were performed 48 hours after the procedure. The IVCS was identified, and balloon predilatation of the lesions followed by implantation of self-expanding stents from the confluence of the LCIV with the inferior vena cava to the middle portion of the left external iliac vein was performed. Postprocedure phlebography demonstrated satisfactory final results, and a 12-month follow-up image showed patent stents and minimal intimal hyperplasia.
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The dataset contains RGB and depth version video frames of various hand movements captured with the Intel RealSense Depth Camera D435. The camera has two channels for collecting both RGB and depth frames at the same time. A large dataset is created for accurate classification of hand gestures under complex backgrounds. The dataset is made up of 29718 frames from RGB and depth versions corresponding to various hand gestures from different people collected at different time instances with complex backgrounds. Hand movements corresponding to scroll-right, scroll-left, scroll-up, scroll-down, zoom-in, and zoom-out are included in the data. Each sequence has data of 40 frames, and there is a total of 662 sequences corresponding to each gesture in the dataset. To capture all the variations in the dataset, the hand is oriented in various ways while capturing.
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Natural illumination has an important place in home automation applications. Among other advantages, it contributes to better visual health, energy savings, and lower CO2 emissions. Therefore, it is important to measure illuminance in the most accurate and cost-effective way. This work compares several low-cost commercial sensors (VEML 7700, TSL2591, and OPT3001) with a professional one (ML-020S-O), all of them installed outdoors. In addition, a platform based on the Internet of Things technology was designed and deployed as a centralized point of data collection and processing. Summer months have been chosen for the comparison. This is the most adverse situation for low-cost sensors since they are designed for indoor use, and their operating range is lower than the maximum reached by sunlight. The solar illuminance was recorded every minute. As expected, the obtained bias depends on the solar height. This can reach 60% in the worst circumstances, although most of the time, its value stays below 40%. The positive side lies in the good precision of the recordings. This systematic deviation makes it susceptible to mathematical correction. Therefore, the incorporation of more sensors and data that can help the global improvement of the precision and accuracy of this low-cost system is left as a future line of improvement.
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Benchmarking , Internet de las Cosas , Dióxido de CarbonoRESUMEN
Well-designed approaches to ecological restoration can benefit nature and society. This is particularly the case in tropical agroecosystems, where restoration can provide substantial socioecological benefits at relatively low costs. To successfully restore tropical agroecosystems and maximise benefits, initiatives must begin by considering 'who' should be involved in and benefit from restoration, and 'what', 'where', and 'how' restoration should occur. Based on collective experience of restoring tropical agroecosystems worldwide, we present nine actions to guide future restoration of these systems, supported by case studies that demonstrate our actions being used successfully in practice and highlighting cases where poorly designed restoration has been damaging. We call for increased restoration activity in tropical agroecosystems during the current UN Decade on Ecosystem Restoration.
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Conservación de los Recursos Naturales , EcosistemaRESUMEN
INTRODUCTION: Some important factors influencing and maintaining unhealthy habits are food advertising and products accessibility. In order to develop and support recommendations, an analysis of the available evidence on the impact of food advertising on the health of children and adolescents has been carried out. METHODS: Literature review of systematic reviews and meta-analyses published up to January 2022 for the term "food advertising" that analyzed the impact of food advertising on weight, body mass index (BMI), adiposity, dietary intake, behavior toward the advertised product, its purchase or consumption in children and adolescents. RESULTS: Twenty-one systematic reviews fulfilled the inclusion criteria, including a total of 490 primary studies, 5 of which also contained a meta-analysis. The vast majority of the primary studies evaluate intermediate effects, related to the behavior of children and adolescents in relation to advertised products and their consumption. There is great variety in terms of the type of advertising and effects studied. Most of the studies agree that there is an association between food advertising and effect analyzed, being more evident in children under 12 years of age and in obese children. Most recent systematic reviews are focused on online advertising, noticing the negative effects especially in adolescents. CONCLUSIONS: Children and adolescents are a particularly vulnerable population to food advertising strategies. Despite the difficulty to demonstrate an independent effect, there is evidence of an association between food advertising and childhood and adolescents' behavior respect to the announced products, and the increase of consumption at short-term. In Spain unhealthy product advertising are still very common in the media and in the children and adolescent's online environment. The Nutrition and Breastfeeding Committee of the Spanish Association of Pediatrics supports the need for regulation and limitation of unhealthy food advertising, covering all media and marketing strategies.
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Publicidad , Obesidad Infantil , Adolescente , Lactancia Materna , Niño , Femenino , Humanos , Metaanálisis como Asunto , Obesidad Infantil/prevención & control , Revisiones Sistemáticas como Asunto , TelevisiónRESUMEN
Limited data exists to show the correlation of (tumour protein 53) TP53 mutation detected by Next generation sequencing (NGS) and the presence/absence of deletions of 17p13 detected by FISH. The study which is the largest series to date includes 2332 CLL patients referred for analysis of del(17p) by FISH and TP53 mutations by NGS before treatment. Using a 10% variant allele frequency (VAF) threshold, cases were segregated into high burden mutations (≥10%) and low burden mutations (<10%). TP53 aberrations (17p [del(17p)] and/or TP53 mutation) were detected in 320/2332 patients (13.7%). Using NGS analysis, 429 TP53 mutations were identified in 303 patients (13%). Of these 238 (79%) and 65 (21%) were cases with high burden and low burden mutations respectively. In our cohort, 2012 cases did not demonstrate a TP53 aberration (86.3%). A total of 159 cases showed TP53 mutations in the absence of del(17p) (49/159 with low burden TP53 mutations) and 144 cases had both TP53 mutation and del(17p) (16/144 with low burden mutations). Only 17/2332 (0.7%) cases demonstrated del(17p) with no TP53 mutation. Validated NGS protocols should be used in clinical decision making to avoid missing low-burden TP53 mutations and can detect the vast majority of TP53 aberrations.
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Introducción: Diversos estudios sugieren que el personal sanitario, que realiza guardias de 24h y turnos de noche, sigue una alimentación poco saludable. Una situación que afecta directamente a su calidad de vida y que puede repercutir en la calidad de la atención a los pacientes. Objetivo: Valorar el grado de adherencia a la Dieta Mediterránea y la adecuada ingesta de nutrientes de residentes de medicina del Hospital Universitario Reina Sofía de Córdoba que realizan guardias de 24h. Métodos: Estudio transversal con una muestra de 35 residentes de medicina. Se empleó una aplicación diseñada específicamente para el estudio (App eFoodDiary) para recoger información de dos cuestionarios de adherencia a la Dieta Mediterránea y el registro diario de alimentos durante el día de guardia de 24h, el día anterior y posterior. Se aplicó el Modelo Lineal General Multivariante (MLGM) a las puntuaciones obtenidas por ambos test (PrediMed y MedLife) y un estudio de correlación entre las puntuaciones de ambos cuestionarios (curvas ROC). Para la valoración nutricional se realizó un estudio estadístico de los %IDR del día completo y por tomas a través del MLGM. Resultados: Los resultados muestran una adherencia baja a la Dieta Mediterránea de los participantes (71%). Respecto a la valoración nutricional, los resultados denotan una ingesta de energía inferior a la recomendada y una dieta poco equilibrada a nivel de nutrientes, resaltando una ingesta superior a la recomendada de proteínas y ácidos grasos saturados, y un déficit de ingesta de hierro entre las mujeres (p<0.001). Durante las guardias de 24h se observa una mayor ingesta de energía, carbohidratos, vitamina A y B6. Conclusión: El bajo porcentaje de personal residente de medicina que sigue una dieta saludable y adecuada a sus necesidades nutricionales, evidencia la importancia de incorporar programas que mejoren la alimentación de este colectivo.(AU)
ntroduction: Various studies suggest that health person-nel, who carryout 24-hour shifts and nightshifts, follow an un-healthy diet. A situation that directly affects their quality oflife and that can affect the quality of patientcare. Objective: To assess the degree of adherence to theMediterranean Diet and nutritional status of the medical residents of the Reina Sofia de Córdoba University Hospital whocarry out 24-hour shifts. Methods: Cross-sectional study with a sample of 35 med-ical residents. An application designed specifically for thestudy (App eFoodDiary) was used to collect information fromtwo questionnaires of adherence to the Mediterranean Dietand the daily food record of the day on duty, the previous andthe subsequent one. The Multivariate General Linear Model(MLGM) was applied to the scores obtained by both tests(PrediMed and MedLife) and a correlation study between thescores of both questionnaires (ROC curves). For the nutri-tional assessment, a statistical study of the% RDI of the fullday and by doses was carried out through the MLGM. Results: The results show a low adherence to the Medite -rranean Diet of the participants (71%). Regarding the nutri-tional assessment, the results denote an energy intake lowerthan recommended and a diet that is not very balanced interms of nutrients, highlighting an intake higher than the rec-ommended protein and saturated fatty acids, and a deficit ofiron intake among the women (p <0.001). During the 24-hourshifts, a higher intake of energy, carbohydrates, vitamin A andB6 is observed. Conclusion: The low percentage of medical residents whofollow a healthy diet appropriate to their nutritional needs,shows the importance of incorporating programs that improvethe diet of this group.(AU)
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Humanos , España , Urgencias Médicas , Dieta Mediterránea , Ingestión de Alimentos , Nutrientes , Personal de Salud , 24439 , Nutrición, Alimentación y Dieta , Dieta Saludable , Estudios Transversales , 52503 , DietéticaRESUMEN
Spectral hole burning has been employed for decades to study various amorphous solids and proteins. Triplet states and respective transient holes were incorporated into theoretical models and software simulating nonphotochemical spectral hole burning (NPHB) and including all relevant distributions, in particular the distribution of the angle between the electric field of light E and transient dipole moment of the chromophore µ. The presence of a chlorophyll a triplet state with a lifetime of several milliseconds explains the slowdown of NPHB (on the depth vs illumination dose scale) with the increase of the light intensity, as well as larger hole depths observed in weak probe beam experiments, compared to those deduced from the hole growth kinetics (HGK) measurements (signal collected at a fixed wavelength while a stronger burning beam is on) in cytochrome b6f and chemically modified LH2. We also considered the solvent deuteration effects on triplet lifetime and concluded that both triplet states and local heating likely play a role in slowing down the HGK with increasing burn intensity.
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Clorofila , Proteínas , Clorofila A , Cinética , SolventesRESUMEN
In this paper, we will review the dietary allowances of these fatty acids in the paediatric population, and also the indications in different pathologies within the field of pediatric gastroenterology. Finally, we will try to explain the reasons that may justify the difficulty in translating good results in experimental studies to the usual clinical practice. This "good results" may be too little to be detected or there may be other causes but misinterpreted as effects of DHA.
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Ácidos Docosahexaenoicos , Gastroenterología , Niño , Suplementos Dietéticos , Ácidos Docosahexaenoicos/uso terapéutico , HumanosRESUMEN
We formulate a controlled system of ordinary differential equations, with vaccination and lockdown interventions as controls, to simulate the mitigation of COVID-19. The performance of the controls is measured through a cost functional involving vaccination and lockdown costs as well as the burden of COVID19 quantified in DALYs. We calibrate parameters with data from Mexico City and Valle de Mexico. By using differential evolution, we minimize the cost functional subject to the controlled system and find optimal policies that are constant in time intervals of a given size. The main advantage of these policies relies on its practical implementation since the health authority has to make only a finite number of different decisions. Our methodology to find optimal policies is relatively general, allowing changes in the dynamics, the cost functional, or the frequency the policymaker changes actions.
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OBJECTIVE: Long-term survival of patients who undergo surgical resection of isolated adrenal metastasis instead of nonsurgical treatment has shown higher values than those described for stage IVA. The primary endpoint was to evaluate overall survival (OS) of patients with single adrenal metastasis from non-small cell lung cancer (NSCLC), who underwent surgical treatment. The secondary endpoint was to evaluate and compare the OS and disease-free survival (DFS) according to: pathological lung tumour size, histology, lymph node involvement, type of metastasis at the time of diagnosis and laterality of the metastasis according to the primary lung tumour. METHODS: From August 2007 to March 2020, 13 patients with isolated adrenal gland metastasis were identified. We performed a descriptive observational study including patients with diagnosed single adrenal gland metastasis of resectable primary lung cancer and no history of other malignant disease. Clinical data obtained included patient demographics, metastases characteristics, laterality of the metastasis, time between surgeries, length of follow-up, survival status, pathological lung tumour size, histology and lymph node involvement. The variables analysed were OS and DFS. RESULTS: Median global OS was 31.9 months (interquartile range (IQR), 19.1-51.4). The 2- and 5-year OS estimated was 54% (95% CI: 29.5%-77.4%) and 36% (95% CI: 13.4%-68.1%), respectively. In patients with NSCLC without mediastinal lymph node involvement, we obtain a median OS of 40 months (IQR, 27.4-51.4) and a 2- and 5-year OS estimated of 75% (95% CI: 43.2%-92.2%) and 50% (95% CI: 18.7%-81.2%), respectively. Recurrence was detected in five patients with a median DFS of 11.9 months (IQR, 6-34.2). CONCLUSION: The resection of the adrenal metastasis should be considered if the primary lung cancer is resectable. Presence of mediastinal lymph node involvement should be ruled out through invasive staging of the mediastinum before performing adrenal and lung surgery. Proper selection of patients who would benefit from surgery is essential to obtain better survival results.
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The sterile alpha motif and histidine-aspartic domain-containing protein 1 (SAMHD1) has been demonstrated to predict the response to high-dose cytarabine consolidation treatment in acute myeloid leukemia patients. Here, we evaluated SAMHD1 as potential biomarker for the response to high-dose cytarabine in mantle cell lymphoma (MCL) patients. We quantified SAMHD1 protein expression and determined the mutation status in patients of the MCL Younger and Elderly trials (n = 189), who had received high-dose cytarabine- or fludarabine-based polychemotherapy. Additionally, we quantified SAMHD1 expression in B cell lymphoma cell lines and exposed them to cytarabine, fludarabine, and clinically relevant combinations. Across both trials investigated, SAMHD1 mutations had a frequency of 7.1% (n = 13) and did not significantly affect the failure-free survival (FFS, P = .47). In patients treated with high-dose cytarabine- or fludarabine-containing regimes, SAMHD1 expression was not significantly associated with FFS or complete remission rate. SAMHD1 expression in B cell lymphoma cell lines, however, inversely correlated with their in vitro response to cytarabine as single agent (R = .65, P = .0065). This correlation could be reversed by combining cytarabine with other chemotherapeutics, such as oxaliplatin and vincristine, similar to the treatment regime of the MCL Younger trial. We conclude that this might explain why we did not observe a significant association between SAMHD1 protein expression and the outcome of MCL patients upon cytarabine-based treatment.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Biomarcadores de Tumor/genética , Resistencia a Antineoplásicos/genética , Linfoma de Células B/tratamiento farmacológico , Linfoma de Células del Manto/tratamiento farmacológico , Proteína 1 que Contiene Dominios SAM y HD/genética , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Línea Celular Tumoral , Ciclofosfamida/farmacología , Ciclofosfamida/uso terapéutico , Citarabina/farmacología , Citarabina/uso terapéutico , Análisis Mutacional de ADN , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Resistencia a Antineoplásicos/efectos de los fármacos , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Linfoma de Células B/genética , Linfoma de Células B/patología , Linfoma de Células del Manto/genética , Linfoma de Células del Manto/mortalidad , Masculino , Persona de Mediana Edad , Mutación , Oxaliplatino/farmacología , Oxaliplatino/uso terapéutico , Prednisona/farmacología , Prednisona/uso terapéutico , Cultivo Primario de Células , Rituximab/farmacología , Rituximab/uso terapéutico , Análisis de Matrices Tisulares , Vidarabina/análogos & derivados , Vidarabina/farmacología , Vidarabina/uso terapéutico , Vincristina/farmacología , Vincristina/uso terapéuticoRESUMEN
BackgroundCardiac sequelae of past SARS-CoV-2 infection are still poorly documented. We conducted a cross-sectional study in health-care workers to report evidence of pericarditis and myocarditis after SARS-CoV-2 infection. MethodsWe studied 139 health-care workers with confirmed past SARS-CoV-2 infection (103 diagnosed by RT-PCR and 36 by serology). Participants underwent clinical assessment, electrocardiography, laboratory tests including immune cell profiling and cardiac magnetic resonance (CMR). Pericarditis was diagnosed when classical criteria were present, and the diagnosis of myocarditis was based on the updated CMR Lake-Louise-Criteria. ResultsMedian age was 52 years (IQR 41-57), 100 (72%) were women, and 23 (16%) were previously hospitalized for Covid-19 pneumonia. At examination (10.4 [9.3-11.0] weeks after infection-like symptoms), all participants presented hemodynamic stability. Chest pain, dyspnoea or palpitations were observed in 58 (42%) participants; electrocardiographic abnormalities in 69 (50%); NT-pro-BNP was elevated in 11 (8%); troponin in 1 (1%); and CMR abnormalities in 104 (75%). Isolated pericarditis was diagnosed in 4 (3%) participants, myopericarditis in 15 (11%) and isolated myocarditis in 36 (26%). Participants diagnosed by RT-PCR were more likely to still present symptoms than participants diagnosed by serology (73 [71%] vs 18 [50%]; p=0.027); nonetheless, the prevalence of pericarditis or myocarditis was high in both groups (44 [43%] vs 11 [31%]; p=0.238). Most participants (101 [73%]) showed altered immune cell counts in blood, particularly decreased eosinophil (37 [27%]; p<0.001) and increased CD4-CD8-/loT{beta}-cell numbers (24 [17%]; p<0.001). Pericarditis was associated with elevated CD4-CD8-/loT{beta}-cell numbers (p=0.011), while participants diagnosed with myopericarditis or myocarditis had lower (p<0.05) plasmacytoid dendritic cell, NK-cell and plasma cell counts and lower anti-SARS-CoV-2-IgG antibody levels (p=0.027). ConclusionsPericarditis and myocarditis with clinical stability are frequent long after SARS-CoV-2 infection, even in presently asymptomatic subjects. These observations will probably apply to the general population infected and may indicate that cardiac sequelae might occur late in association with an altered (delayed) innate and adaptative immune response. The trial is registered with ClinicalTrials.gov, number NCT04413071 Research in contextO_ST_ABSEvidence before this studyC_ST_ABSVery little evidence exists describing long cardiac sequelae after SARS-CoV-2 infection. Although pericarditis and myocarditis are the two most frequent cardiac manifestations observed after a viral infection, as of May 13, 2020, the peer-reviewed literature was limited to isolated case reports of myocarditis and pericarditis during the COVID-19 hospitalization phase and to a retrospective observation in 26 recovered patients with COVID-19 pneumonia presenting cardiac complaints during hospitalization, revealing the presence of myocardial oedema in 14 (54%) patients and late gadolinium enhancement in 8 (31%) patients. These small size case series, limited to hospitalized RT-PCR patients with COVID-19 pneumonia, are insufficient to generalize conclusions about the true prevalence of pericardial and myocardial long involvement after SARS-CoV-2 infection. In addition, no study has investigated the immunological consequences of SARS-CoV-2 infection in the settings of pericarditis and myocarditis. Added value of this studyTo our knowledge, this is the largest cohort of subjects (N=139) --even for other common viruses-- with clinical, electrocardiographic, laboratory and CMR imaging evaluations, to assess pericardial and myocardial involvements after SARS-CoV-2 infection. The strength of this study is the addition of non-hospitalized participants and also the inclusion of participants diagnosed of past SARS-CoV-2 infection through serology. Contrary to previous studies, women are well represented. We found a prevalence of pericarditis or myocarditis up to 40% cases; pericarditis coexisted with some degree of concurrent myocardial inflammation in 11% cases. Study participants who were previously hospitalized for COVID-19 pneumonia and patients who received antiviral (hydroxychloroquine, lopinavir-ritonavir) or anti-inflammatory (high-dose glucocorticoids and anti-interleukin treatments) treatments, and who were on chronic drug treatment with statins, were less likely to develop pericarditis or myocarditis. The clinical assessment of the participants showed clinical stability without any patient presenting severe pericardial effusion, heart failure or left ventricular dysfunction. We provide new data on seropositive subjects; although RT-PCR participants were more likely to still present symptoms than participants diagnosed by serology, the prevalence of pericarditis, myocarditis or myocarditis, almost three months after the initial viral prodrome, was high in both groups. In-depth investigation of the distribution of multiple major and minor populations of immune cells in blood showed high frequency of altered immune profiles after SARS-CoV-2 infection. The altered immune cell profiles identified partially mimic abnormalities previously reported during active infection together with others described here for the first time, with unique patterns associated with pericardial and/or myocardial injury. Nonetheless, we also described altered immune profiles in participants without pericardial and myocardial manifestations. Whether these later alterations are due to persistence of tissue damage in other organs affected by SARS-CoV-2, such as the lung, or they reflect normal post-infection immune recovery mechanisms, remains to be investigated. Implications of all the available evidenceAt present, there is much interest in the long-term sequelae of COVID-19. It is intriguing that pericarditis and myocarditis were observed so long after SARS-CoV-2 infection and also in some presently asymptomatic subjects, in association with notably altered immune cell profiles in blood. These observations will probably apply to the general population infected and may indicate that cardiac sequelae might occur late, paving the way for a better understanding the immune mechanisms involved. Thus, our study may have health-care consequences given the widespread diagnosis of SARS-CoV-2 infection in population-based seroprevalence studies.
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While most testicular germ cell tumours (TGCTs) exhibit exquisite sensitivity to platinum chemotherapy, ~10% are platinum resistant. To gain insight into the underlying mechanisms, we undertake whole exome sequencing and copy number analysis in 40 tumours from 26 cases with platinum-resistant TGCT, and combine this with published genomic data on an additional 624 TGCTs. We integrate analyses for driver mutations, mutational burden, global, arm-level and focal copy number (CN) events, and SNV and CN signatures. Albeit preliminary and observational in nature, these analyses provide support for a possible mechanistic link between early driver mutations in RAS and KIT and the widespread copy number events by which TGCT is characterised.
Asunto(s)
Resistencia a Antineoplásicos/efectos de los fármacos , Genómica/métodos , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Platino (Metal)/uso terapéutico , Neoplasias Testiculares/tratamiento farmacológico , Variaciones en el Número de Copia de ADN , Predisposición Genética a la Enfermedad/genética , Humanos , Masculino , Mutación , Neoplasias de Células Germinales y Embrionarias/genética , Neoplasias de Células Germinales y Embrionarias/metabolismo , Compuestos Organoplatinos/uso terapéutico , Proteínas Proto-Oncogénicas c-kit/genética , Proteínas Proto-Oncogénicas c-kit/metabolismo , Transducción de Señal/genética , Neoplasias Testiculares/genética , Neoplasias Testiculares/metabolismo , Secuenciación del Exoma/métodos , Proteínas ras/genética , Proteínas ras/metabolismoRESUMEN
BACKGROUND: In order to investigate the combination effect of anticancer drugs and X-ray irradiation on neurotoxic side-effects (neurotoxicity), a method that provides homogeneously X-ray-irradiated cells was newly established. MATERIALS AND METHODS: PC12 cell suspension was irradiated by X-ray (0.5 Gy) in serum-supplemented medium, immediately inoculated into 96-microwell plates and incubated overnight. The medium was replaced with fresh serum-depleted medium containing 50 ng/ml nerve growth factor to induce differentiation toward nerve-like cells with characteristic neurites according to the overlay method without changing the medium. The differentiated cells were treated by anticancer drugs as well as antioxidants, oxaliplatin or bortezomib, and the viable cell number was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. RESULTS: Antioxidants and anticancer drugs were cytotoxic to differentiating PC12 cells. Combination of anticancer drugs and X-ray irradiation slightly reduced cell viability. CONCLUSION: The present 'population irradiation method' may be useful for the investigation of the combination effect of X-ray irradiation and any pharmaceutical drug.
Asunto(s)
Antineoplásicos/efectos adversos , Sistema Nervioso/efectos de los fármacos , Radiación Ionizante , Rayos X , Animales , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Biomarcadores , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Inmunohistoquímica , Ratones , Fosforilación , Transducción de Señal/efectos de los fármacosRESUMEN
OBJECTIVE: to assess the epidemiological profile of patients undergoing exploratory trauma laparotomy based on severity and prognosis criteria, and to determine the predictive accuracy of trauma scoring systems in terms of morbidity and mortality. METHODS: retrospective cohort study and review of medical records of patients undergoing exploratory laparotomy for blunt or penetrating trauma at the Hospital de Pronto Socorro de Porto Alegre, from November 2015 to November 2019. Demographic data, mechanism of injury, associated injuries, physiological (RTS and Shock Index), anatomical (ISS, NISS and ATI) and combined (TRISS and NTRISS) trauma scores, intraoperative findings, postoperative complications, length of stay and outcomes. RESULTS: 506 patients were included in the analysis. The mean age was 31 ± 13 years, with the majority being males (91.3%). Penetrating trauma was the most common mechanism of injury (86.2%), predominantly by firearms. The average RTS at hospital admission was 7.5 ± 0.7. The mean ISS and NISS was 16.5 ± 10.1 and 22.3 ± 13.6, respectively. The probability of survival estimated by TRISS was 95.5%, and by NTRISS 93%. The incidence of postoperative complications was 39.7% and the overall mortality was 12.8%. The most accurate score for predicting mortality was the NTRISS (88.5%), followed by TRISS, NISS and ISS. CONCLUSION: the study confirms the applicability of trauma scores in the studied population. The NTRISS seems to be the best predictor of morbidity and mortality.