Maternal fructose intake aggravates the harmful effects of a Western diet in rat male descendants impacting their cholesterol metabolism.

Scope: fructose consumption from added sugars correlates with the epidemic rise in MetS and CVD. Maternal fructose intake has been described to program metabolic diseases in progeny. However, consumption of fructose-containing beverages is allowed during gestation. Cholesterol is also a well-known risk factor for CVD. Therefore, it is essential to study Western diets which combine fructose and cholesterol and how maternal fructose can influence the response of progeny to these diets. Methods and results: a high-cholesterol (2%) diet combined with liquid fructose (10%), as a model of an unhealthy Western diet, was administered to descendants from control and fructose-fed mothers. Gene (mRNA and protein) expression and plasma, fecal and tissue parameters of cholesterol metabolism were measured. Interestingly, progeny from fructose-fed dams consumed less liquid fructose and cholesterol-rich chow than males from control mothers. Moreover, descendants of fructose-fed mothers fed a Western diet showed an increased cholesterol elimination through bile and feces than males from control mothers. Despite these mitigating circumstances to develop a proatherogenic profile, the same degree of hypercholesterolemia and severity of steatosis were observed in all descendants fed a Western diet, independently of maternal intake. An increased intestinal absorption of cholesterol, synthesis, esterification, and assembly into lipoprotein found in males from fructose-fed dams consuming a Western diet could be the cause. Moreover, an augmented GLP2 signalling seen in these animals would explain this enhanced lipid absorption. Conclusions: maternal fructose intake, through a fetal programming, makes a Western diet considerably more harmful in their descendants than in the offspring from control mothers.

The genomic profiling of high-risk smoldering myeloma patients treated with an intensive strategy unveils potential markers of resistance and progression.

Smoldering multiple myeloma (SMM) precedes multiple myeloma (MM). The risk of progression of SMM patients is not uniform, thus different progression-risk models have been developed, although they are mainly based on clinical parameters. Recently, genomic predictors of progression have been defined for untreated SMM. However, the usefulness of such markers in the context of clinical trials evaluating upfront treatment in high-risk SMM (HR SMM) has not been explored yet, precluding the identification of baseline genomic alterations leading to drug resistance. For this reason, we carried out next-generation sequencing and fluorescent in-situ hybridization studies on 57 HR and ultra-high risk (UHR) SMM patients treated in the phase II GEM-CESAR clinical trial (NCT02415413). DIS3, FAM46C, and FGFR3 mutations, as well as t(4;14) and 1q alterations, were enriched in HR SMM. TRAF3 mutations were specifically associated with UHR SMM but identified cases with improved outcomes. Importantly, novel potential predictors of treatment resistance were identified: NRAS mutations and the co-occurrence of t(4;14) plus FGFR3 mutations were associated with an increased risk of biological progression. In conclusion, we have carried out for the first time a molecular characterization of HR SMM patients treated with an intensive regimen, identifying genomic predictors of poor outcomes in this setting.

Estrategias de analgesia, sedación, delirium y confort individualizado en el enfermo crítico: Una revisión narrativa / Individualised analgesia, sedation, delirium and comfort management strategies in the ICU: a narrative review

Este grupo es producto del acuerdo de colaboración firmado por la Sociedad de Medicina Intensiva de Madrid (SOMIAMA) y la Sociedad de Anestesiología, Reanimación y Terapéutica del Dolor de Madrid (SAR MADRID), por el que las organizaciones acordaron crear grupos de trabajo conjuntos para mejorar la atención al paciente crítico.El dolor, el malestar, la agitación y el delirio causan sufrimiento, retrasan el alta y pueden provocar complicaciones graves en los pacientes ingresados en las unidades de cuidados críticos médicos y quirúrgicos y en las unidades de cuidados postanestésicos. Los principales objetivos en este tipo de unidades incluyen: asegurar el confort de los pacientes que sufren o se recuperan de una enfermedad crítica. Evitar las complicaciones asociadas a las medidas, sobre todo farmacológicas, adoptadas para asegurar ese confort. (AU)

This group is a product of the collaboration agreement signed by Sociedad de Medicina Intensiva de Madrid (SOMIAMA) and Sociedad de Anestesiología, Reanimación y Terapéutica del Dolor de Madrid (SAR MADRID), under which the organisations agreed to create joint working groups to improve critical patient care.Pain, discomfort, agitation, and delirium cause suffering, delay discharge, and can lead to serious complications in patients admitted to medical and surgical critical care units and post-anaesthesia care units. The main objectives in this type of unit include: Ensuring the comfort of patients suffering or recovering from a critical illness. Avoiding complications associated with the measures, particularly pharmacological, taken to ensure that comfort. (AU)

Individualised analgesia, sedation, delirium and comfort management strategies in the ICU: a narrative review.

This group is a product of the collaboration agreement signed by SOMIAMA (Sociedad de Medicina Intensiva de Madrid) and SAR MADRID (Sociedad de Anestesiología, Reanimación y Terapéutica del Dolor de Madrid) under which the organisations agreed to create joint working groups to improve critical patient care. Pain, discomfort, agitation, and delirium cause suffering, delay discharge, and can lead to serious complications in patients admitted to medical and surgical critical care units and post-anaesthesia care units. The main objectives in this type of unit include: Ensuring the comfort of patients suffering or recovering from a critical illness.Avoiding complications associated with the measures, particularly pharmacological, taken to ensure that comfort.

Endogenous PTEN-Induced Kinase 1 Regulates Dendritic Architecture and Spinogenesis.

Mutations in PTEN-induced kinase 1 (PINK1) contribute to autosomal recessive Parkinson's disease with cognitive and neuropsychiatric comorbidities. Disturbances in dendritic and spine architecture are hallmarks of neurodegenerative and neuropsychiatric conditions, but little is known of the impact of PINK1 on these structures. We used Pink1 -/- mice to study the role of endogenous PINK1 in regulating dendritic architecture, spine density, and spine maturation. Pink1 -/- cortical neurons of unknown sex showed decreased dendritic arborization, affecting both apical and basal arbors. Dendritic simplification in Pink1 -/- neurons was primarily driven by diminished branching with smaller effects on branch lengths. Pink1 -/- neurons showed reduced spine density with a shift in morphology to favor filopodia at the expense of mushroom spines. Electrophysiology revealed significant reductions in miniature EPSC (mEPSC) frequency in Pink1 -/- neurons, consistent with the observation of decreased spine numbers. Transfecting with human PINK1 rescued changes in dendritic architecture, in thin, stubby, and mushroom spine densities, and in mEPSC frequency. Diminished spine density was also observed in Golgi-Cox stained adult male Pink1 -/- brains. Western blot study of Pink1 -/- brains of either sex revealed reduced phosphorylation of NSFL1 cofactor p47, an indirect target of PINK1. Transfection of Pink1 -/- neurons with a phosphomimetic p47 plasmid rescued dendritic branching and thin/stubby spine density with a partial rescue of mushroom spines, implicating a role for PINK1-regulated p47 phosphorylation in dendrite and spine development. These findings suggest that PINK1-dependent synaptodendritic alterations may contribute to the risk of cognitive and/or neuropsychiatric pathologies observed in PINK1-mutated families.SIGNIFICANCE STATEMENT Loss of PINK1 function has been implicated in both familial and sporadic neurodegenerative diseases. Yet surprisingly little is known of the impact of PINK1 loss on the fine structure of neurons. Neurons receive excitatory synaptic signals along a complex network of projections that form the dendritic tree, largely at tiny protrusions called dendritic spines. We studied cortical neurons and brain tissues from mice lacking PINK1. We discovered that PINK1 deficiency causes striking simplification of dendritic architecture associated with reduced synaptic input and decreased spine density and maturation. These changes are reversed by reintroducing human PINK1 or one of its downstream mediators into PINK1-deficient mouse neurons, indicating a conserved function, whose loss may contribute to neurodegenerative processes.

Relationship between tricuspid annular plane systolic excursion, fluid responsiveness and volume status in hospitalised dogs with circulatory abnormalities.

AIMS: To evaluate the echocardiographic variable tricuspid annular plane systolic excursion normalised to body weight (TAPSEnorm) as a predictor of fluid responsiveness in hospitalised dogs with haemodynamic and tissue perfusion alterations and to investigate the association of left ventricular internal diameter in diastole normalised to body weight (LVIDdN) and aortic velocity time integral (VTIAo) with TAPSEnorm. METHODS: A single-centre, prospective study was carried out in a cohort of spontaneously breathing dogs, hospitalised for any reason, with severe haemodynamic and tissue perfusion alterations. The echocardiographic variables TAPSEnorm, LVIDdN, and VTIAO were measured. A bolus of 30 mL/kg of lactated Ringer's solution was administered and then VTIAo was subsequently remeasured. Patients were classified as fluid responsive if VTIAo increased by ≥15% after fluid expansion, or non-responsive if VTIAo increased by <15% after fluid expansion. The area under the receiver operating characteristic (AUROC) curve was generated to evaluate the ability of TAPSE to predict fluid responsiveness. Simple regression models were used to assess the linear relationship between TAPSEnorm and LVIDdN or VTIAO. RESULTS: TAPSEnorm was lower in fluid responsive dogs (mean 0.57 (95% CI = 0.50-0.64) cm/kg) compared to non-responsive dogs (mean 0.76 (95% CI = 0.62-0.90) cm/kg). The AUROC for TAPSEnorm was 0.827 (95% CI = 0.65-1.00). The optimal cut-off point was 0.76 with sensitivity of 80 (95% CI = 28.4-99.5)% and specificity of 86.7 (95% CI = 69.3-99.2)%, positive predictive value of 50 (95% CI = 15.7-84.3)% and negative predictive value of 96.3 (95% CI = 81-99.9)%. A monotonic linear relationship was observed between TAPSEnorm and LVIDdN (p<0.001) and between TAPSEnorm and VTIAo (p=0.001). CONCLUSIONS AND CLINICAL RELEVANCE: TAPSEnorm could be useful in determining those dogs that are likely to respond to a fluid bolus from those that are likely to be non-responsive. Additionally, a positive linear association between the LVIDdN and the TAPSEnorm suggests that TAPSEnorm decreases at lower preload values. The present study results suggest that TAPSEnorm could be a valuable tool for evaluating blood volume status and fluid responsiveness in hospitalised dogs.Abbreviations: AUROC: Area under the receiver operating characteristic; CO: Cardiac output; ICC: Intraclass correlation coefficient; LVIDd: Left ventricular internal diameter in diastole; LVIDdN: Left ventricular internal diameter in diastole normalised to body weight; TAPSE: Tricuspid annular plane systolic excursion; TAPSEnorm: Tricuspid annular plane systolic excursion normalised to body weight; VTIAo: Aortic velocity time integral.

Understanding the contributions of VPS35 and the retromer in neurodegenerative disease.

Perturbations of the endolysosomal pathway have been suggested to play an important role in the pathogenesis of several neurodegenerative diseases, including Parkinson's disease (PD) and Alzheimer's disease (AD). Specifically, VPS35 and the retromer complex play an important role in the endolysosomal system and are implicated in the pathophysiology of these diseases. A single missense mutation in VPS35, Asp620Asn (D620N), is known to cause late-onset, autosomal dominant familial PD. In this review, we focus on the emerging role of the PD-linked D620N mutation in causing retromer dysfunction and dissect its implications in neurodegeneration. Additionally, we will discuss how VPS35 and the retromer are linked to AD, amyotrophic lateral sclerosis, and primary tauopathies. Interestingly, reduced levels of VPS35 and other retromer components have been observed in post-mortem brain tissue, suggesting a role for the retromer in the pathophysiology of these diseases. This review will provide a comprehensive dive into the mechanisms of VPS35 dysfunction in neurodegenerative diseases. Furthermore, we will highlight outstanding questions in the field and the retromer as a therapeutic target for neurodegenerative disease at large.

Complications during repeated tracheal intubation in the Intensive Care Unit. A prospective, observational study comparing the first intubation and the reintubation.

BACKGROUND AND GOAL OF THE STUDY: The goal of the study was to compare the incidence of complications, technical difficulty of intubation and physiologic pre-intubation status between the first intubation and reintubation performed on the same patient in an ICU. MATERIALS AND METHODS: The study was approved by the ethics committee of Galicia (Santiago-Lugo, code No. 2015-012). Due to the observational, noninterventional, and noninvasive design of this study, the need for written consent was waived by the ethics committee of Galicia. Patients requiring tracheal intubation and reintubation in the ICU were included in this prospective observational study. Main endpoint was to compare the incidence of complications, physiologic pre-intubation status, and the rate of technical difficulty of intubation between the first intubation and reintubation performed on the same patient in an ICU. RESULTS AND DISCUSSION: 504 patients were intubated in our ICU during the study period, and 82 (16%) required reintubation. There was no difference between the first intubation and reintubation regarding number of total complication (35% vs 33%; P = ,86), hypotension (24% vs 24%; P = 1), hypoxia (26% vs 26%; P = 1), esophageal intubation (1% vs 1%; P = 1), and bronchoaspiration (2% vs 1%; P = ,86). Physiologic pre-intubation status and technical difficulty of intubation did not differ between the first intubation and reintubation. CONCLUSIONS: In our ICU patients requiring tracheal reintubation, incidence of complications, physiologic pre-intubation status, and technical difficulty of intubation did not differ between the first intubation and reintubation.

Efecto de la intervención de estimulación cognitiva individual de larga duración para personas con trastorno neurocognitivo leve / Effect of long-term individual cognitive stimulation intervention for people with mild neurocognitive disorder

Introducción: La estimulación cognitiva puede ser beneficiosa para ralentizar la progresión del trastorno neurocognitivo (TNC) leve, pero los resultados de las investigaciones existentes son inconsistentes. Además, no existen intervenciones a largo plazo ni intervenciones individuales (uno a uno) aplicadas por profesionales. Objetivo: El objetivo de este estudio fue evaluar la eficacia de una intervención de estimulación cognitiva individual de larga duración para personas con TNC leve. Pacientes y métodos: Se llevó a cabo un diseño pretest-postest con un grupo control no equivalente. Un total de 82 participantes con TNC leve fueron asignados a un grupo de intervención de estimulación cognitiva o a un grupo control. La intervención consistió en 88 sesiones de formato individual de aproximadamente 45 minutos, dos veces por semana. Evaluadores independientes evaluaron la cognición, la sintomatología depresiva y el nivel de autonomía en las actividades de la vida diaria en la preintervención (línea base), la intraintervención (seis meses) y la postintervención (12 meses). Resultados: En la intra- y la postintervención, se encontró una mejora significativa en la cognición y la sintomatología depresiva en el grupo de intervención en comparación con el grupo control. Los participantes más jóvenes y los que tenían una mejor función y estado cognitivo en la preintervención obtuvieron mejores resultados. La adhesión a la intervención fue alta. Conclusiones: Los resultados sugieren la eficacia de una intervención cognitiva individual de larga duración para personas con TNC leve, que podría retrasar la progresión hacia un TNC mayor.(AU)

Introduction: Cognitive stimulation may be beneficial in slowing the progression of mild neurocognitive disorder (NCD), but the results of existing research are inconsistent. Furthermore, there are no long-term interventions nor individual (one-on-one) interventions applied by professionals. Objetive: The aim of this study was to assess the efficacy of a long-term individual cognitive stimulation intervention on people with mild NCD. Patients and methods: A pre-post test design with a non-equivalent control group was conducted. A total of 82 participants with mild NCD were assigned to a cognitive stimulation intervention group or to a control group. The intervention consisted of 88 individual format sessions of approximately 45 minutes, twice per week. Independent evaluators assessed cognition, depressive symptomatology and autonomy level in activities of daily living at pre-intervention, intra-intervention (6 months) and post-intervention (12 months). Results: At intra- and post-intervention, significant improvement on cognition and depressive symptomatology in the intervention group compared to the control group were found. Younger participants and those with better cognitive function and status in pre-intervention achieved better results. Adherence to the intervention was high. Conclusions: Results suggest the efficacy of long-term individual cognitive intervention in people with mild NCD, which could delay the progression towards a major NCD.(AU)

Twitter data analysis to assess the interest of citizens on the impact of marine plastic pollution.

Few studies have mined social media platforms to assess environmental concerns. In this study, Twitter was scraped to obtain a ~140,000 tweet dataset related specifically to marine plastic pollution. The goal is to understand what kind of users profiles are tweeting and how and when they do it. In addition, topic modelling and graph theory techniques have allowed us to identify main concerns on this topic: i) impact on wildlife, ii) microplastics/water pollution, iii) estimates/reports, iv) legislation/protection, and v) recycling/cleaning initiatives. Results reveal a scarce influence of organizations involved in research and marine environmental awareness, so some guidelines are depicted that could help to adjust their communication plans. This is relevant to engage society through reliable information, change habits and reinforce sustainable behaviour. A visualization tool has been created to analyze the results over time.

Effect of long-term individual cognitive stimulation intervention for people with mild neurocognitive disorder. / Efecto de la intervención de estimulación cognitiva individual de larga duración para personas con trastorno neurocognitivo leve.

INTRODUCTION: Cognitive stimulation may be beneficial in slowing the progression of mild neurocognitive disorder (NCD), but the results of existing research are inconsistent. Furthermore, there are no long-term interventions nor individual (one-on-one) interventions applied by professionals. Objetive. The aim of this study was to assess the efficacy of a long-term individual cognitive stimulation intervention on people with mild NCD. PATIENTS AND METHODS: A pre-post test design with a non-equivalent control group was conducted. A total of 82 participants with mild NCD were assigned to a cognitive stimulation intervention group or to a control group. The intervention consisted of 88 individual format sessions of approximately 45 minutes, twice per week. Independent evaluators assessed cognition, depressive symptomatology and autonomy level in activities of daily living at pre-intervention, intra-intervention (6 months) and post-intervention (12 months). RESULTS: At intra- and post-intervention, significant improvement on cognition and depressive symptomatology in the intervention group compared to the control group were found. Younger participants and those with better cognitive function and status in pre-intervention achieved better results. Adherence to the intervention was high. CONCLUSIONS: Results suggest the efficacy of long-term individual cognitive intervention in people with mild NCD, which could delay the progression towards a major NCD.

TITLE: Efecto de la intervención de estimulación cognitiva individual de larga duración para personas con trastorno neurocognitivo leve.Introducción. La estimulación cognitiva puede ser beneficiosa para ralentizar la progresión del trastorno neurocognitivo (TNC) leve, pero los resultados de las investigaciones existentes son inconsistentes. Además, no existen intervenciones a largo plazo ni intervenciones individuales (uno a uno) aplicadas por profesionales. Objetivo. El objetivo de este estudio fue evaluar la eficacia de una intervención de estimulación cognitiva individual de larga duración para personas con TNC leve. Pacientes y métodos. Se llevó a cabo un diseño pretest-postest con un grupo control no equivalente. Un total de 82 participantes con TNC leve fueron asignados a un grupo de intervención de estimulación cognitiva o a un grupo control. La intervención consistió en 88 sesiones de formato individual de aproximadamente 45 minutos, dos veces por semana. Evaluadores independientes evaluaron la cognición, la sintomatología depresiva y el nivel de autonomía en las actividades de la vida diaria en la preintervención (línea base), la intraintervención (seis meses) y la postintervención (12 meses). Resultados. En la intra- y la postintervención, se encontró una mejora significativa en la cognición y la sintomatología depresiva en el grupo de intervención en comparación con el grupo control. Los participantes más jóvenes y los que tenían una mejor función y estado cognitivo en la preintervención obtuvieron mejores resultados. La adhesión a la intervención fue alta. Conclusiones. Los resultados sugieren la eficacia de una intervención cognitiva individual de larga duración para personas con TNC leve, que podría retrasar la progresión hacia un TNC mayor.

Clinicopathological factors associated with the presence of hypercapnia at admission in hospitalised cats with decompensated chronic kidney disease.

AIMS: To evaluate associations between clinicopathological variables and hypercapnia measured in cats with decompensated chronic kidney disease (CKD) on admission to a veterinary hospital. METHODS: This is a retrospective, cross-sectional study of cats (n = 39) that presented to a tertiary veterinary hospital in Argentina between June 2015 and December 2017 with blood creatinine concentrations >140 µmol/L, and abdominal ultrasound results consistent with CKD. Data recorded included venous partial pressure of CO2 (PvCO2), blood pH, haematocrit and concentrations of glucose, potassium, sodium, corrected sodium (Na+c), and ionised calcium in blood. A logistic regression model was used to assess associations between the presence of hypercapnia (PvCO2 ≥ 44.7 mmHg) and the other clinicopathologic variables. The duration of hospitalisation was compared in cats with and without hypercapnia using the Wilcoxon Rank Sum test. RESULTS: The final study population comprised 39 cats. Eleven cats (28.2%) had hypercapnia. In the logistic regression model, two independent variables were associated with the presence of hypercapnia at admission in cats with CKD: the concentration of creatinine in blood (OR = 1.06 (95% CI = 1.016-1.108); p = 0.007) and Na+c (OR = 1.33 (95% CI = 1.08-1.63); p = 0.005). There were no statistically significant differences in the length of hospital stay between the two groups. CONCLUSIONS AND CLINICAL RELEVANCE: There appears to be an association between elevated concentrations of creatinine and Na+c in blood, and hypercapnia in cats with CKD, suggesting careful assessment of blood gas and electrolyte parameters during hospitalisation is required. Further prospective studies are needed to evaluate the mechanisms behind this association and the association of hypercapnia with disease outcome including mortality.

State-of-the-Art of Analytical Techniques to Determine Food Fraud in Olive Oils.

The benefits of the food industry compared to other sectors are much lower, which is why producers are tempted to commit fraud. Although it is a bad practice committed with a wide variety of foods, it is worth noting the case of olive oil because it is a product of great value and with a high percentage of fraud. It is for all these reasons that the authenticity of olive oil has become a major problem for producers, consumers, and legislators. To avoid such fraud, it is necessary to develop analytical techniques to detect them. In this review, we performed a complete analysis about the available instrumentation used in olive fraud which comprised spectroscopic and spectrometric methodology and analyte separation techniques such as liquid chromatography and gas chromatography. Additionally, other methodology including protein-based biomolecular techniques and analytical approaches like metabolomic, hhyperspectral imaging and chemometrics are discussed.

Chemical inhibition of FBXO7 reduces inflammation and confers neuroprotection by stabilizing the mitochondrial kinase PINK1.

Mitochondrial quality control is mediated by the PTEN-induced kinase 1 (PINK1), a cytoprotective protein that is dysregulated in inflammatory lung injury and neurodegenerative diseases. Here, we show that a ubiquitin E3 ligase receptor component, FBXO7, targets PINK1 for its cellular disposal. FBXO7, by mediating PINK1 ubiquitylation and degradation, was sufficient to induce mitochondrial injury and inflammation in experimental pneumonia. A computational simulation-based screen led to the identification of a small molecule, BC1464, which abrogated FBXO7 and PINK1 association, leading to increased cellular PINK1 concentrations and activities, and limiting mitochondrial damage. BC1464 exerted antiinflammatory activity in human tissue explants and murine lung inflammation models. Furthermore, BC1464 conferred neuroprotection in primary cortical neurons, human neuroblastoma cells, and patient-derived cells in several culture models of Parkinson's disease. The data highlight a unique opportunity to use small molecule antagonists that disrupt PINK1 interaction with the ubiquitin apparatus to enhance mitochondrial quality, limit inflammatory injury, and maintain neuronal viability.

Change Management in Healthcare Organizations: Soft Skills Training Strategies Through Blended Learning Environments.

Teaching soft skills for change management in healthcare organizations is becoming increasingly necessary, even more, when implementing health information systems (HIS). There is little evidence that these skills can be learned through online teaching environments. This paper describes the experience of having taught soft skills to health informatics master's degree students, through blended learning environments.

Polyploid Hepatocytes Facilitate Adaptation and Regeneration to Chronic Liver Injury.

The liver contains diploid and polyploid hepatocytes (tetraploid, octaploid, etc.), with polyploids comprising ≥90% of the hepatocyte population in adult mice. Polyploid hepatocytes form multipolar spindles in mitosis, which lead to chromosome gains/losses and random aneuploidy. The effect of aneuploidy on liver function is unclear, and the degree of liver aneuploidy is debated, with reports showing aneuploidy affects 5% to 60% of hepatocytes. To study relationships among liver polyploidy, aneuploidy, and adaptation, mice lacking E2f7 and E2f8 in the liver (LKO), which have a polyploidization defect, were used. Polyploids were reduced fourfold in LKO livers, and LKO hepatocytes remained predominantly diploid after extensive proliferation. Moreover, nearly all LKO hepatocytes were euploid compared with control hepatocytes, suggesting polyploid hepatocytes are required for production of aneuploid progeny. To determine whether reduced polyploidy impairs adaptation, LKO mice were bred onto a tyrosinemia background, a disease model whereby the liver can develop disease-resistant, regenerative nodules. Although tyrosinemic LKO mice were more susceptible to morbidities and death associated with tyrosinemia-induced liver failure, they developed regenerating nodules similar to control mice. Analyses revealed that nodules in the tyrosinemic livers were generated by aneuploidy and inactivating mutations. In summary, we identified new roles for polyploid hepatocytes and demonstrated that they are required for the formation of aneuploid progeny and can facilitate adaptation to chronic liver disease.

[Long-term individual cognitive stimulation program in patients with mild neurocognitive disorder: a pilot study]. / Programa de estimulacion cognitiva individual de larga duracion para personas con trastorno neurocognitivo leve: estudio piloto.

INTRODUCTION: There is evidence to suggest that cognitive stimulation produces cognitive benefits in people with mild neurocognitive disorder. However, the effect has been previously demonstrated to be minimal to moderate and the effect of long-term individual interventions, namely on specific cognitive domains, is unknown. AIM: To assess the efficacy, feasibility and acceptability of a long-term individual cognitive stimulation intervention for patients with mild neurocognitive disorder. PATIENTS AND METHODS: Patients (n = 30) with mild neurocognitive disorder were assigned to a cognitive stimulation intervention group (n = 15) or to a control group (n = 15). The intervention consisted of 88 individual sessions, approximately 45 minutes long, with two sessions per week. External evaluators assessed the level of alteration in cognitive performance, depressive symptoms and the level of independence in the performance of basic activities of daily living. RESULTS: After the intervention, a significant improvement was found in the intervention group compared to the control group in overall cognitive performance (d = 0.83), specifically in the language domain (d until 1.50). There were also lower depressive symptoms in the intervention group compared to the control group (d = 0.93). Only 6.7% of the participants dropped out the study, with participants attending a mean of 83 ± 12.1 sessions. CONCLUSIONS: The results support the efficacy, feasibility and acceptability of the intervention for mild neurocognitive disorder and justify a randomized controlled trial of the program with a larger sample.

TITLE: Programa de estimulacion cognitiva individual de larga duracion para personas con trastorno neurocognitivo leve: estudio piloto.Introduccion. Existen evidencias que sugieren que la estimulacion cognitiva produce beneficios cognitivos en personas con trastorno neurocognitivo leve. Sin embargo, el tamaño del efecto encontrado es de pequeño a moderado, y se desconoce el efecto de las intervenciones individuales de larga duracion y, mas concretamente, sobre dominios cognitivos especificos. Objetivo. Evaluar la eficacia, viabilidad y aceptabilidad de una intervencion de estimulacion cognitiva individual de larga duracion para personas con trastorno neurocognitivo leve. Pacientes y metodos. Un total de 30 personas con trastorno neurocognitivo leve fueron asignadas a un grupo de intervencion de estimulacion cognitiva (n = 15) o a un grupo control (n = 15). La intervencion consistio en 88 sesiones individuales de unos 45 minutos, con una periodicidad de dos veces por semana. Evaluadores independientes valoraron el nivel de rendimiento cognitivo, los sintomas depresivos y el nivel de autonomia en la realizacion de actividades basicas de la vida diaria. Resultados. Tras la intervencion, se encontro una mejoria significativa en el grupo de intervencion en comparacion con el grupo control en el rendimiento cognitivo global (d = 0,83), concretamente en el dominio del lenguaje (d hasta 1,50), y una menor sintomatologia depresiva en el grupo de intervencion en comparacion con el control (d = 0,93). Solo un 6,7% de los participantes abandono el estudio, asistiendo a un promedio de 83 ± 12,1 sesiones. Conclusiones. Los resultados apoyan la eficacia, viabilidad y aceptabilidad de la intervencion, y justifican la realizacion de un ensayo controlado aleatorizado aplicado a una muestra mayor.

Insuficiencia ovárica prematura / Premature ovarian insufficiency

RESUMEN La insuficiencia ovárica prematura es la pérdida de la función ovárica antes de los 40 años de edad. Se caracteriza por hipogonadismo hipergonadotrófico y amenorrea u oligomenorrea. Su etiología es multifactorial, pudiendo deberse a causas iatrogénicas, genéticas, metabólicas, autoinmunes y ambientales; siendo de origen idiopático en el 90 % de los casos. Su incidencia es de 1 cada 100 mujeres menores de 40 años y 1 cada 1000 mujeres menores de 30 años. En la actualidad no existe un único marcador que se pueda utilizar para calcular la reserva ovárica; sin embargo, en los últimos años la hormona antimülleriana ha demostrado presentar algunas ventajas respecto a los biomarcadores clásicamente utilizados. Además, diversos estudios indican que existe una correlación positiva entre los niveles de esta hormona y el recuento de folículos antrales, que es, por el momento, el método más confiable para evaluar reserva ovárica debido a las actuales dificultades técnicas para la determinación de hormona antimülleriana.

ABSTRACT Premature ovarian insufficiency, the loss of ovarian function before the age of 40 years, is characterized by hipergonadotrofic hipogonadism and amenorrhea or oligomenorrhea. The etiology is multifactorial, and can be due to genetic, metabolic, autoimmune, environmental or iatrogenic causes, being idiopathic 90% of cases. Currently there is not a single marker that can be used for estimate ovarian reserve in this patients; however, in recent years antimüllerian hormone has proved to have some advantages over other classical biomarkers. Moreover, several studies indicate a positive correlation between antimüllerian hormone concentration and antral follicle count, considered nowadays the most reliable method for ovarian reserve estimation.

The Polyploid State Restricts Hepatocyte Proliferation and Liver Regeneration in Mice.

The liver contains a mixture of hepatocytes with diploid or polyploid (tetraploid, octaploid, etc.) nuclear content. Polyploid hepatocytes are commonly found in adult mammals, representing ~90% of the entire hepatic pool in rodents. The cellular and molecular mechanisms that regulate polyploidization have been well characterized; however, it is unclear whether diploid and polyploid hepatocytes function similarly in multiple contexts. Answering this question has been challenging because proliferating hepatocytes can increase or decrease ploidy, and animal models with healthy diploid-only livers have not been available. Mice lacking E2f7 and E2f8 in the liver (liver-specific E2f7/E2f8 knockout; LKO) were recently reported to have a polyploidization defect, but were otherwise healthy. Herein, livers from LKO mice were rigorously characterized, demonstrating a 20-fold increase in diploid hepatocytes and maintenance of the diploid state even after extensive proliferation. Livers from LKO mice maintained normal function, but became highly tumorigenic when challenged with tumor-promoting stimuli, suggesting that tumors in LKO mice were driven, at least in part, by diploid hepatocytes capable of rapid proliferation. Indeed, hepatocytes from LKO mice proliferate faster and out-compete control hepatocytes, especially in competitive repopulation studies. In addition, diploid or polyploid hepatocytes from wild-type (WT) mice were examined to eliminate potentially confounding effects associated with E2f7/E2f8 deficiency. WT diploid cells also showed a proliferative advantage, entering and progressing through the cell cycle faster than polyploid cells, both in vitro and during liver regeneration (LR). Diploid and polyploid hepatocytes responded similarly to hepatic mitogens, indicating that proliferation kinetics are unrelated to differential response to growth stimuli. Conclusion: Diploid hepatocytes proliferate faster than polyploids, suggesting that the polyploid state functions as a growth suppressor to restrict proliferation by the majority of hepatocytes.