Oxidative stress is tightly regulated by cytochrome c phosphorylation and respirasome factors in mitochondria

Respiratory cytochrome c has been found to be phosphorylated at tyrosine 97 in the postischemic brain upon neuroprotective insulin treatment, but how such posttranslational modification affects mitochondrial metabolism is unclear. Here, we report the structural features and functional behavior of a phosphomimetic cytochrome c mutant, which was generated by site-specific incorporation at position 97 of p-carboxymethyl-l-phenylalanine using the evolved tRNA synthetase method. We found that the point mutation does not alter the overall folding and heme environment of cytochrome c, but significantly affects the entire oxidative phosphorylation process. In fact, the electron donation rate of the mutant heme protein to cytochrome c oxidase, or complex IV, within respiratory supercomplexes was higher than that of the wild-type species, in agreement with the observed decrease in reactive oxygen species production. Direct contact of cytochrome c with the respiratory supercomplex factor HIGD1A (hypoxia-inducible domain family member 1A) is reported here, with the mutant heme protein exhibiting a lower affinity than the wild-type species. Interestingly, phosphomimetic cytochrome c also exhibited a lower caspase-3 activation activity. Altogether, these findings yield a better understanding of the molecular basis for mitochondrial metabolism in acute diseases, such as brain ischemia, and thus could allow the use of phosphomimetic cytochrome c as a neuroprotector with therapeutic applications.España, Junta de Andalucía BIO-198España MINECO BFU2015-71017/BM

Predictors of mortality and poor outcome in cancer patients with E. faecium bloodstream infection

Background. To analyze predictors of mortality and poor outcome in cancer patients diagnosed with E. faecium bloodstream infection. Methods. Demographic, clinical and microbiological data were collected (January 1998-June 2011). Results. After multivariate analysis, presence of a urinary catheter was associated with a worse 7-day prognosis, and higher mortality at discharge. A high Charlson index was also associated with higher 7-day mortality. Conclusion. Presence of a urinary catheter was associated with poor 7-day prognosis and higher mortality at discharge in the present series.Fundamento. Analizar los predictores de mortalidad y mal pronóstico en el paciente oncológico diagnosticado de bacteriemia por E. faecium. Métodos. Se analizaron datos demográficos, clínicos y microbiológicos (Enero 1998-Junio 2011). Resultados. El análisis multivariable demostró que la presencia de una sonda urinaria se asoció a mal pronóstico a los 7 días y alta mortalidad del paciente al final del estudio. Un índice de Charlson elevado se asoció a un aumento en la mortalidad a los 7 días. Conclusión. En nuestro estudio, la presencia de sonda urinaria se asoció con mal pronóstico del paciente a los 7 días y aumento de la mortalidad

Porcine proliferative enteropathy by Lawsonia intracellularis and coinfection with Trichuris suis and Balantidium coli in a pig in Uruguay

La enteropatía proliferativa porcina (EPP) es una enfermedad infecciosa transmisible, ampliamente difundida mundialmente, de gran importancia económica, causada por Lawsonia intracellularis. El objetivo del presente trabajo es describir un caso de EPP por L. intracellularis en coinfección con Trichuris suis y Balantidium coli en Uruguay. La enfermedad se diagnosticó en octubre de 2015 en una piara de 130 lechones cruza de hasta 3 meses de edad. La incidencia acumulada en 30 días fue de 14% (18/130) y la letalidad de 83% (15/18). Los animales afectados presentaron diarrea profusa, deshidratación, adelgazamiento progresivo y debilidad, con evolución a muerte tras un curso clínico de 10 días. Macroscópicamente en un cerdo necropsiado, se observó engrosamiento de la mucosa con aspecto cerebroide en la última porción del íleon, y en el ciego y el colon. El intestino grueso presentó además una membrana fibrinonecrótica difusamente adherida a la mucosa, donde se identificaron ejemplares de Trichuris suis. Microscópicamente, había hiperplasia de las criptas y glándulas intestinales, que se observaron elongadas, ramificadas y con marcada reducción del número de células caliciformes en el íleon y el ciego. Había múltiples áreas de necrosis superficial y ulceración con numerosos protozoarios morfológicamente compatibles con trofozoitos de Balantidium coli adheridos a la superficie necrótica en el ciego. La identificación intralesional de L. intracellularis se realizó mediante las técnicas de Warthin-Starry e inmunohistoquímica. Lawsonia intracellularis debe ser considerada un diagnóstico etiológico diferencial en porcinos con diarrea y enteropatía en Uruguay.Porcine proliferative enteropathy (PPE) is an economically important, transmissible infectious disease of worldwide distribution caused by Lawsonia intracellularis. The objective of this report is to describe a case of PPE caused by L. intracellularis in coinfection with Trichuris suis and Balantidium coli in Uruguay. The disease was diagnosed in October 2015 in a herd of 130 crossbred grower pigs up to 3 months of age. The cumulative incidence was 14% (18/130) and a lethality rate 83% (15/18). Affected animals presented profuse diarrhea, ill thrift and weakness, with progression to death after a clinical course of 10 days. At necropsy of one pig, the terminal segment of the ileum, cecum and colon showed thickening of the mucosa and irregular folds in a cerebriform pattern. In the cecum and proximal colon, there was also a diffuse fibrinonecrotic membrane attached to the mucosa with embedded specimens of Trichuris suis. Microscopic lesions were characterized by crypt and gland hyperplasia with branching and depletion of goblet cells in the ileum and cecum. Multiple areas of superficial necrosis and ulceration were recognized with numerous protozoans morphologically resembling Balantidium coli trophozoites adhered to the necrotic surface of the cecum. Lawsonia intracellularis was identified intralesionally by Warthin-Starry stain and immunohistochemistry. Lawsonia intracellularis should be considered a differential etiologic diagnosis for diarrhea and enteropathy in swine in Uruguay.Facultad de Ciencias Veterinaria

NKG2D-CAR-transduced natural killer cells efficiently target multiple myeloma

CAR-T-cell therapy against MM currently shows promising results, but usually with serious toxicities. CAR-NK cells may exert less toxicity when redirected against resistant myeloma cells. CARs can be designed through the use of receptors, such as NKG2D, which recognizes a wide range of ligands to provide broad target specificity. Here, we test this approach by analyzing the antitumor activity of activated and expanded NK cells (NKAE) and CD45RA− T cells from MM patients that were engineered to express an NKG2D-based CAR. NKAE cells were cultured with irradiated Clone9.mbIL21 cells. Then, cells were transduced with an NKG2D-4-1BB-CD3z-CAR. CAR-NKAE cells exhibited no evidence of genetic abnormalities. Although memory T cells were more stably transduced, CAR-NKAE cells exhibited greater in vitro cytotoxicity against MM cells, while showing minimal activity against healthy cells. In vivo, CAR-NKAE cells mediated highly efficient abrogation of MM growth, and 25% of the treated mice remained disease free. Overall, these results demonstrate that it is feasible to modify autologous NKAE cells from MM patients to safely express a NKG2D-CAR. Additionally, autologous CAR-NKAE cells display enhanced antimyeloma activity demonstrating that they could be an effective strategy against MM supporting the development of NKG2D-CAR-NK-cell therapy for MM.This study was supported by a grant from the Spanish Society for Hematology and Hemotherapy to Alejandra Leivas, the CRIS Foundation to Beat Cancer and the Instituto de Salud Carlos III (PI18/01519)

Effects of Sex, Age and Height on Symphysis–Ischial Spine Distance Measured on a Pelvic CT

Objective: To examine the influence of age, sex and height on the symphysis–ischial spine distance (SID) measured on pelvic Computed tomography (CT)images in subjects of reproductive age, and to determine the interobserver reproducibility. This measurement (SID) is of great importance because the use of intrapartum ultrasound is based on the assumption of a specific value (30 mm) of such a measurement. Methods: This was a cross-sectional descriptive study in which SID was measured in subjects aged 20 to 44 years who had been scheduled for pelvic CT at our centre from January 2018 to May 2021 for different reasons. Radiographic measurements of the pelvis were obtained through the multiplanar reconstruction of the CT image. The images obtained from all of the participants were independently assessed by three senior radiologists, and the SID measurements made by each one were blinded from those of the remaining observers. Correlations between the SID and patient age, height and sex were analyzed by univariate and multivariate linear regression. Results: The mean SID for 87 of the enrolled participants (45 women, 42 men) was 28.2 ± 6.25 mm. Among the observers, the mean difference in this distance was 1 to 2 mm, and was scarcely related to measurement size, with agreement being greater than 70%. The mean SID was significantly related to sex and height (SID = −24.9 − 6.51 × sex (0 or 1) + 0.34 × height (cm); p = 0.01; sex equals 1 for a man and 0 for a woman), such that it was a mean of 2.5 mm greater in women than men (29.50 mm vs. 26.99 mm). Conclusion: Measurements of SID on CT images show good interobserver reproducibility, and are related to sex and height.Depto. de Salud Pública y Materno - InfantilFac. de MedicinaTRUEUnión EuropeaComunidad de MadridInstituto de Salud Carlos IIIHalekulani S.L.pu

Detección de yemas brotadas para la estimación temprana del rendimiento de una plantación de kiwi

Se presentan aquí resultados de detección de órganos vegetales en imágenes usando redes convolucionales, correspondientes a la primera etapa de un proyecto que propone desarrollar procedimientos para estimar en forma temprana el rendimiento de un lote de producción de kiwi. Para lograr la predicción del rendimiento, se consideran tres estadíos fenológicos del crecimiento del kiwi y para validar, se dispondrá de resultados finales de cosecha. Para cada etapa se consideran 1000 imágenes, capturadas en toda el área cubierta por el cultivo, que permiten entrenar y elegir un modelo para conteo automático de objetos. Además, el modelo se evalúa en 50 sitios elegidos al azar en la plantación, donde se compara el conteo manual con el conteo automático obtenido sobre imágenes de cada sitio. Los resultados en esta primera etapa, realizada sobre yemas brotadas en 47 sitios de la plantación, son promisorios en cuanto a la utilización de modelos de deep learning para detección de objetos y muestran la necesidad de profundizar en el ajuste de modelos y estrategias de conteo. Esto permite inferir que puede utilizarse el conteo automático como input en el modelo predictivo final. La metodología propuesta permitirá la predicción del rendimiento total de la plantación.Red de Universidades con Carreras en Informátic

Respiratory viruses detected in Mexican children younger than 5 years old with community-acquired pneumonia: a national multicenter study

Background: Acute respiratory infections are the leading cause of mortality in children worldwide, especially in developing countries. Pneumonia accounts for 16% of all deaths of children under 5 years of age and was the cause of death of 935 000 children in 2015. Despite its frequency and severity, information regarding its etiology is limited. The aim of this study was to identify respiratory viruses associated with community-acquired pneumonia (CAP) in children younger than 5 years old. Methods: One thousand four hundred and four children younger than 5 years of age with a clinical and/or radiological diagnosis of CAP in 11 hospitals in Mexico were included. Nasal washes were collected, placed in viral medium, and frozen at �70 C until processing. The first 832 samples were processed using the multiplex Bio-Plex/Luminex system and the remaining 572 samples using the Anyplex multiplex RT-PCR. Clinical data regarding diagnosis, clinical signs and symptoms, radiographic pattern, and risk factors were obtained and recorded. Results: Of the samples tested, 81.6% were positive for viruses. Respiratory syncytial virus (types A and B) was found in 23.7%, human enterovirus/rhinovirus in 16.6%, metapneumovirus in 5.7%, parainfluenza virus (types 1–4) in 5.5%, influenza virus (types A and B) in 3.6%, adenovirus in 2.2%, coronavirus (NL63, OC43, 229E, and HKU1) in 2.2%, and bocavirus in 0.4%. Co-infection with two or more viruses was present in 22.1%; 18.4% of the samples were negative. Using biomass for cooking, daycare attendance, absence of breastfeeding, and co-infections were found to be statistically significant risk factors for the presence of severe pneumonia. Conclusions: Respiratory syncytial virus (types A and B), human enterovirus/rhinovirus, and metapneumovirus were the respiratory viruses identified most frequently in children younger than 5 years old with CAP. Co-infection was present in an important proportion of the children

Everolimus plus minimized tacrolimus on kidney function in liver transplantation: REDUCE, a prospective, randomized controlled study

Background and aim: reduction in calcineurin inhibitor levels is considered crucial to decrease the incidence of kidney dysfunction in liver transplant (LT) recipients. The aim of this study was to evaluate the safety and impact of everolimus plus reduced tacrolimus (EVR + rTAC) vs. mycophenolate mofetil plus tacrolimus (MMF + TAC) on kidney function in LT recipients from Spain. Methods: the REDUCE study was a 52-week, multicenter, randomized, controlled, open-label, phase 3b study in de novo LT recipients. Eligible patients were randomized (1:1) 28 days post-transplantation to receive EVR + rTAC (TAC levels <_ 5 ng/mL) or to continue with MMF + TAC (TAC levels = 6-10 ng/mL). Mean estimated glomerular filtration rate (eGFR), clinical benefit in renal function, and safety were evaluated. Results: in the EVR + rTAC group (n = 105), eGFR increased from randomization to week 52 (82.2 [28.5] mL/min/1.73 m2 to 86.1 [27.9] mL/min/1.73 m2) whereas it decreased in the MMF + TAC (n = 106) group (88.4 [34.3] mL/min/1.73 m2 to 83.2 [25.2] mL/min/1.73 m2), with significant (p < 0.05) differences in eGFR throughout the study. However, both groups had a similar clinical benefit regarding renal function (improvement in 18.6 % vs. 19.1 %, and stabilization in 81.4 % vs. 80.9 % of patients in the EVR + rTAC vs. MMF + TAC groups, respectively). There were no significant differences in the incidence of acute rejection (5.7 % vs. 3.8 %), deaths (5.7 % vs. 2.8 %), and serious adverse events (51.9 % vs. 44.0 %) between the 2 groups. Conclusion: EVR + rTAC allows a safe reduction in tacrolimus exposure in de novo liver transplant recipients, with a significant improvement in eGFR but without significant differences in renal clinical benefit 1 year after liver transplantation

Factores de riesgo para trastornos de la alimentación en los alumnos de la Universidad de Manizales

ResumenObjetivo: Determinar la frecuencia de los factores de riesgo para trastornos de la alimentaci&oacute;n en estudiantes de la Universidad de Manizales. Materiales y m&eacute;todos: De 3,610 estudiantes regulares de la Universidad&nbsp; de Manizales se tom&oacute; una muestra de 165 estudiantes, quienes respondieron un cuestionario integrado compuesto por variables demogr&aacute;ficas, las escalas de Zung para ansiedad o depresi&oacute;n,el Eating Disorderrs Inventory (EDI2) y el Apgar familiar; adem&aacute;s se tomaron las medidas de peso, talla, &iacute;ndice de masa corporal y pliegue en el antebrazo. Resultado: Un12.7% de la poblaci&oacute;n present&oacute; factor de riesgo positivo para trastornos de la conducta alimentar&iacute;a, 17.3% de la poblaci&oacute;n femenina y el 3.8% de la poblaci&oacute;n masculina; las personas con mayor factor de riesgo fueron las mujeres en la facultad de Comunicaci&oacute;n Social y Periodismo (24.1%). Se determin&oacute; una&nbsp; relaci&oacute;n significativa entre la variable impulso por la delgadez con la ansiedad o depresi&oacute;n. El mayor &iacute;ndice de masa corporal y de porcentaje de grasa est&aacute; asociado con un aumentoen la variable impulso por la delgadez. Conclusiones:Se encontraron factores de riesgo asociados con trastornos de la alimentaci&oacute;n. La frecuencia del factor de riesgo seg&uacute;n EDI2 en este estudio fue m&aacute;s baja que la encontrada en estudios realizados en Medell&iacute;n y Bogot&aacute;.[Cano AA, Casta&ntilde;o JJ, Corredor DA, Garc&iacute;a AM, Gonz&aacute;lez M, Lloreda OL, et al. Factores de riesgo para trastornos de la alimentaci&oacute;n en los alumnos de la Universidad de Manizales. MedUNAB 2007; 10:187-194].Palabras claves: Trastornos de la conducta alimentaria, factores de riesgo; Anorexia nerviosa, Bulimia

Impact of mediterranean diet promotion on environmental sustainability: a longitudinal analysis

[EN]This article aims to estimate the differences in environmental impact (greenhouse gas [GHG] emissions, land use, energy used, acidification and potential eutrophication) after one year of promoting a Mediterranean diet (MD). Methods Baseline and 1-year follow-up data from 5800 participants in the PREDIMED-Plus study were used. Each participant's food intake was estimated using validated semi-quantitative food frequency questionnaires, and the adherence to MD using the Dietary Score. The influence of diet on environmental impact was assessed through the EAT-Lancet Commission tables. The influence of diet on environmental impact was assessed through the EAT-Lancet Commission tables. The association between MD adherence and its environmental impact was calculated using adjusted multivariate linear regression models.SIPublicación en abierto financiada por el Consorcio de Bibliotecas Universitarias de Castilla y León (BUCLE), con cargo al Programa Operativo 2014ES16RFOP009 FEDER 2014-2020 DE CASTILLA Y LEÓN, Actuación:20007-CL - Apoyo Consorcio BUCL