Cell identity and nucleo-mitochondrial genetic context modulate OXPHOS performance and determine somatic heteroplasmy dynamics

Heteroplasmy, multiple variants of mitochondrial DNA (mtDNA) in the same cytoplasm, may be naturally generated by mutations but is counteracted by a genetic mtDNA bottleneck during oocyte development. Engineered heteroplasmic mice with nonpathological mtDNA variants reveal a nonrandom tissue-specific mtDNA segregation pattern, with few tissues that do not show segregation. The driving force for this dynamic complex pattern has remained unexplained for decades, challenging our understanding of this fundamental biological problem and hindering clinical planning for inherited diseases. Here, we demonstrate that the nonrandom mtDNA segregation is an intracellular process based on organelle selection. This cell type-specific decision arises jointly from the impact of mtDNA haplotypes on the oxidative phosphorylation (OXPHOS) system and the cell metabolic requirements and is strongly sensitive to the nuclear context and to environmental cues

EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI) : Study protocol for a multicentre, observational trial

More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369

Effect of oleic acid on gap junction cornrnunication in rat astrocytes during developrnent

El papel del ácido oleico en la permeabilidad de las uniones intercelulares fue estudiado en astrocitos de rata en cultivo primario. La incubación con ácido oleico causó una inhibición de forma dosis-dependiente, alcanzando un máximo del 79 .5% a 50 IlM. La inhibición de la permeabilidad de las uniones comunicantes por el ácido oleico fue reversible y fue prevenida por la albúmina. La potencia de compuestos relacionados con el ácido oleico en inhibir la permeabilidad de las uniones comunicantes fue: ácido araquidónico> ácido oleico> alcohol oleico> ácido palmitoleico>ácido esteárico> octanol> ácido caprílico> ácido palmitico> metil-oleil éster. El ácido oleico y el ácido araquidónico, pero no el oleil-metil éster, aumentaron la captación de glucosa por los astrocitos. Nuestros resultados sugieren que la inhibición de la permeabilidad de las uniones comunicantes está asociada con el incremento de la captación de glucosa. Por tanto, nuestros resultados sugieren que en el período perinatal, el ácido oleico puede ser un mediador fisiológico para la diferenciación de los astrocitos por su capacidad de modular la permeabilidad a través de las uniones comunicantes.The role of oleic acid in the modulation of gap junction permeability was studied in cultured rat astrocytes by the scrape-Ioading/Lucifer yellow transfer technique. lncubation with oleic acid caused a dose-dependent inhibition of gap junction permeability by 79.5% at 50 IlM and no further inhibition was observed by increasing the oleic acid concentration up to 100 1lM. The oleic acid-mediated inhibition of gap junction permeability was reversible and was prevented by bovine serum albumin (BSA). The potency of oleic acid-related compounds in inhibiting gap junction permeability was arachidonic acid > oleic acid > oleyl alcohol > palmitoleic acid > stearic acid > octanol > caprylic acid > palmitic acid > methyl-oleyl estero Oleic acid and arachidonic acid, but not methyl-oleyl ester, increased glucose uptake by astrocytes. Our results support the hypothesis that the inhibition of gap junction permeability is associated with the increase in glucose uptake. We suggest that iduring the perinatal period, oleic acid may be a physiological mediator in astrocyte differentiation by regulating intercellular communication

Effects of hydroxytyrosol on cardiovascular biomarkers in experimental diabetes mellitus

The aim of this study was to assess the influence of hydroxytyrosol (HT) on cardiovascular biomarkers and morphometric parameters of the arterial wall in streptozotocin-diabetic rats. Seven groups of rats (N=10 per group) were studied for 2 months: nondiabetic rats (NDR), diabetic rats treated with saline (DR) and DR treated with HT (0.5, 1, 2.5, 5 and 10 mg kg day p.o.). DR had higher platelet aggregation values, higher thromboxane B, plasma lipid peroxidation, 3-nitrotyrosine, oxidized LDL (oxLDL), myeloperoxidase, vascular cell adhesion molecule 1 (VCAM-1) and interleukin-1β (IL-1β) concentrations, and lower aortic 6-keto-prostaglandin F and nitric oxide production than NDR. Aortic wall area and smooth muscle cell count were also higher in DR than in NDR. HT significantly reduced both oxidative and nitrosative stress, oxLDL concentration, VCAM-1 and inflammatory mediators, platelet aggregation and thromboxane B production. Morphometric values in the aortic wall were reduced to values near those in NDR. In conclusion, HT influenced the major biochemical processes leading to diabetic vasculopathy, and reduced cell proliferation in the vascular wall in this experimental model.This work was supported in part by Grant P09-AGR-5098 (Proyecto de Investigación de Excelencia, Consejería de Innovación, Ciencia y Empresa) from the Junta de Andalucía, Spain.Peer Reviewe

Biologic and genetic characteristics of Toxoplasma gondii isolates in free-range chickens from Costa Rica, Central America

The prevalence of Toxoplasma gondii in free-ranging chickens is a good indicator of the prevalence of T. gondii oocysts in the soil because chickens feed from the ground. The prevalence of T. gondii in 144 free-range chickens (Gallus domesticus) from Costa Rica was determined. Antibodies to T. gondii were assayed by the modified agglutination test (MAT), and found in 60 (40.1%) of 144 chickens with titers of 1:5 in 16, 1:10 in 5, 1:20 in 2, 1:40 in 3, 1:80 in 5, and 1:160 or higher in 29. Tissues of all chickens were bioassayed for T. gondii in mice or cats. Hearts and brains of 52 chickens with titers of 1:5 or higher and 16 chickens with doubtful titers were pooled and bioassayed in mice. Tissues from 76 chickens with MAT titers of 1:10 or less were pooled and fed to three T. gondii-free cats. Fecal floats of cats were bioassayed orally in mice but were negative for T. gondii oocysts. T. gondii was isolated by bioassay in mice from 32 chickens with MAT titers of 1:10 or higher. All infected mice from 4 of the 32 isolates died of toxoplasmosis. Genotyping of these 32 isolates using polymorphisms at the loci SAG1, SAG2, SAG3, BTUB and GRA6 revealed five genotypes. Five isolates had type I alleles and one isolate had type III alleles at all loci. The rest 26 isolates contained the combination of type I and II or I and III alleles and were divided into three genotypes. None was found to have genotype II alleles at all five loci. This is the first report of genetic characterization of T. gondii isolates from Costa Rica, Central America.La prevalencia de Toxoplasma gondii en pollos criados en libertad es un buen indicador de la prevalencia de ooquistes de T. gondii en el suelo porque los pollos se alimentan del suelo. Se determinó la prevalencia de T. gondii en 144 pollos criados en libertad (Gallus domesticus) de Costa Rica. Los anticuerpos contra T. gondii se analizaron mediante la prueba de aglutinación modificada (MAT), y se encontraron en 60 (40,1%) de 144 pollos, con títulos de 1:5 en 16, 1:10 en 5, 1:20 en 2, 1:40 en 3, 1:80 en 5 y 1:160 o más en 29. Los tejidos de todos los pollos fueron bioensayos para T. gondii en ratones o gatos. Los corazones y cerebros de 52 pollos con títulos de 1:5 o superiores y 16 pollos con títulos dudosos dudosos fueron agrupados y sometidos a bioensayos en ratones. Los tejidos de 76 pollos con títulos de TMA de 1:10 o menos se agruparon y se alimentaron a tres gatos libres de T. gondii. Los flotadores fecales de los gatos se sometieron a bioensayos orales en ratones, pero fueron negativos para ooquistes de T. gondii. Se aisló T. gondii por bioensayo en ratones de 32 pollos con títulos de TMA de 1:10 o más. Todos los ratones infectados de 4 de los 32 aislados murieron de toxoplasmosis. La genotipificación de estos 32 aislados mediante polimorfismos en los loci SAG1, SAG2, SAG3, BTUB y GRA6 reveló cinco genotipos. Cinco aislados tenían alelos de tipo I y un aislado tenía alelos de tipo III en todos los loci. El resto de los 26 aislados contenían la combinación de alelos de tipo I y II o I y III y se dividieron en tres genotipos. Ninguno tenía alelos del genotipo II en los cinco loci. en los cinco loci. Este es el primer informe de caracterización genética de los aislados de T. gondii de Costa Rica, América Central.Universidad Nacional, Costa RicaEscuela de Medicina Veterinari

Qualidade do leite de vacas criadas no sistema silvipastoril no Vale do Cauca, Colômbia

O sistema silvipastoril caracteriza-se por aumentar a produção de leite, com maior número de vacas por hectare devido ao maior aporte de proteína na dieta. Neste sistema as vacas são alimentadas, além do pasto, de pequenas árvores e arbustos. O objetivo do presente estudo foi determinar os principais indicadores de qualidade do leite e agentes causais de mastite em vacas criadas em sistema silvipastoril. Foram avaliadas a composição (teor de gordura, proteína total, lactose, extrato seco, extrato seco desengordurado e nitrogênio uréico), contagem de células somáticas (CCS), contagem bacteriana total (CBT), ocorrência de mastite clínica e subclínica, isolamento microbiológico, perfil de sensibilidade bacteriana "in vitro" e detecção de resíduos antimicrobianos no leite produzido por 100 vacas, bem como do tanque de expansão e latões em propriedades do Vale do Cauca, Colômbia. Os teores médios dos principais constituintes do leite foram 3,24% de gordura, 3,27% de proteína total, 4,40% de lactose, 10,62% de extrato seco, 8,57% de extrato seco desengordurado e 15,82mg/dL de nitrogênio uréico, enquanto do tanque de expansão e latões foi 3,51% de gordura, 3,20% de proteína total, 4,34% de lactose, 11,72% de extrato seco, 8,47% de extrato seco desengordurado e 14,57mg/dL de nitrogênio uréico. A celularidade média dos quartos mamários e do tanque de expansão foi 141.252,75 CS/mL e 363.078,05 CS/mL respectivamente. A CBT média dos quartos mamários e do tanque de expansão foi 4.466,84 UFC/mL e 24.547,01 UFC/mL. Os principais micro-organismos isolados dos quartos mamários foram Corynebacterium bovis, Staphylococcus aureus, Staphylococcus hyicus, Staphylococcus spp., Streptococcus dysgalatiae, enquanto do tanque de expansão foram identificados Streptococcus spp., Enterobacter cloacae, Hafnia alveii, Streptococcus hemolítico e Streptococcus spp., com maior frequência. A presença de resíduos de antimicrobianos em leite de vacas e do tanque ou latão foi detectada em 30% e 86% das amostras, respectivamente. O sistema silvipastoril mostrou ser uma boa alternativa para produção de leite em vacas. No entanto, são necessários cuidados no tratamento mamário para evitar resíduos no leite e a análise de todos os parâmetros de qualidade para garantir um produto diferenciado

Reciclaje de baterías de plomo ácido en Costa Rica: un estudio de caso

This work describes the production of secondary lead in a smelter located in Costa Rica. The only input of the plant is scrap automotive batteries. We describe the environmental management strategies used for waste minimization, including the waste characterization and minimization of gaseous emissions. The waste characterization included the sulphidic slag containing varying quantities of lead (total lead content and TCLP), along with the gaseous analysis (SO2, TSP and P-Pb). Through process improvement, we reduced both the quantity of slag produced and the lead loss to the slag, as well as the concentrations of gas pollutants in the gaseous emissions.Este trabajo describe la producción de plomo secundario en una fundición ubicada en Costa Rica. El único insumo de la planta son las baterías de automóviles de desecho. Nosotros describir las estrategias de gestión ambiental utilizadas para la minimización de residuos, incluyendo la caracterización de residuos y minimización de emisiones gaseosas. los la caracterización de residuos incluyó la escoria sulfídica que contiene cantidades variables de plomo (contenido total de plomo y TCLP), junto con el análisis gaseoso (SO2, TSP y P-Pb). A través de la mejora del proceso, redujimos tanto la cantidad de escoria producido y la pérdida de plomo a la escoria, así como las concentraciones de gas contaminantes en las emisiones gaseosasUniversidad Nacional, Costa RicaEscuela de Químic

Evaluación de necesidades paliativas en el paciente con enfermedad renal crónica en hemodiálisis

[spa] Introducción: Los cuidados paliativos aportan una atención necesaria que promueve una respuesta integral y coordinada del sistema sanitario respetando la autonomía y valores de los pacientes en situación de final de vida. Objetivos: Determinar la prevalencia de necesidad de cuidados paliativos en la unidad de hemodiálisis de nuestro centro mediante el instrumento validado NECPAL CCOMSS-ICO e identificar la situación de complejidad en pacientes con necesidades paliativas usando la herramienta de IDC-Pal. Material y Método: Estudio observacional transversal. Tres enfermeras con formación en cuidados paliativos y en el uso de los cuestionarios NECPAL CCOMS-ICO y el IDC-Pal evaluaron de forma independiente a todos los pacientes de la unidad de crónicos de hemodiálisis. Las evaluaciones fueron realizadas entre los días 6 y 10 de marzo. Las discrepancias se resolvieron consensuando el resultado final entre las tres profesionales. Resultados: Se analizaron a 50 pacientes, con una edad media de 68.24. El perfil de paciente más frecuente fue aquel con un tiempo de permanencia en hemodiálisis de 48,8 meses de media. La enfermedad renal primaria y comorbilidad más prevalente fueron la nefropatía diabética (26%) y la hipertensión arterial (56%) respectivamente. Se identificaron 20 pacientes con necesidad de atención paliativa (40%). Respecto a la evaluación del IDC-Pal, se obtuvieron 19 pacientes en situación de complejidad y 1 en situación de no complejidad. Conclusiones: Las necesidades paliativas complejas sugieren la necesidad de realizar evaluaciones perió- dicas en las unidades de hemodiálisis, así como un enfoque asistencial multidisciplinar para dar respuesta a las necesidades identificadas. PALABRAS CLAVE: hemodiálisis; cuidados paliativos; necesidad paliativa; integración

Neuroprotective Effect of Hydroxytyrosol in Experimental Diabetic Retinopathy: Relationship with Cardiovascular Biomarkers

The aim of the study was to test the neuroprotective effect of hydroxytyrosol (HT) on experimental diabetic retinopathy. Animals were divided in four groups: (1) control nondiabetic rats, (2) streptozotocin-diabetic rats (DR), (3) DR treated with 1 mg/kg/day p.o. HT, and (4) DR treated with 5 mg/kg/day p.o. HT. Treatment with HT was started 7 days before inducing diabetes and was maintained for 2 months. In the DR group, total area occupied by extracellular matrix was increased, area occupied by retinal cells was decreased; both returned to near-control values in DR rats treated with HT. The number of retinal ganglion cells in DR was significantly lower (44%) than in the control group, and this decrease was smaller after HT treatment (34% and 9.1%). Linear regression analysis showed that prostacyclin, platelet aggregation, peroxynitrites, and the dose of 5 mg/kg/day HT significantly influenced retinal ganglion cell count. In conclusion, HT exerted a neuroprotective effect on diabetic retinopathy, and this effect correlated significantly with changes in some cardiovascular biomarkers.This work was supported in part by Grant P09-AGR-5098 (Proyecto de Investigación de Excelencia, Consejería de Innovación, Ciencia y Empresa) from the Junta de Andalucía, Spain.Peer Reviewe

Neuroprotective Effect of Hydroxytyrosol in Experimental Diabetes Mellitus

The aim of the study was to analyze the possible neuroprotective effect of hydroxytyrosol (HT) in diabetic animals in a model of hypoxia-reoxygenation. Rats (10 animals/group) were distributed in five groups: nondiabetic rats, control diabetic rats (DR), and DR rats treated for 2 months with 1, 5, or 10 mg/kg/day po HT. At the end of follow-up, an experimental model of hypoxia-reoxygenation in brain slices was tested. The DR group showed increased cell death, oxidative and nitrosative stress, and an increase in brain inflammatory mediators. These alterations were significantly greater in DR than in normoglycemic animals. HT significantly reduced oxidative (38.5-52.4% lipid peroxidation) and nitrosative stress (48.0-51.0% nitric oxide and 43.9-75.2% peroxynitrite concentration) and brain inflammatory mediators (18.6-40.6% prostaglandin E and 17.0-65.0% interleukin 1β concentration). Cell death was reduced by 25.9, 37.5, and 41.0% after the administration of 1, 5, or 10 mg/kg/day. The administration of HT in rats with experimental diabetes thus had a neuroprotective effect