[Estilo de vida, hábitos de higiene oral y autopercepción del estado anímico en estudiantes de Odontología de la Comunidad de Madrid durante la pandemia de la COVID-19: ¿pudo la pandemia tener algún efecto favorable?] / Lifestyle, oral hygiene habits and self-perception of mood in Dental students of the Community of Madrid during the COVID-19 pandemic: could the pandemic have any favorable effect?

OBJECTIVE: The COVID-19 pandemic and its control measures seem to have altered the vital dynamics of the population. It was justifiable, therefore, to try to specify the impact on lifestyle, oral hygiene and mood, in specific groups, such as dental university students in Madrid, who were accessible to us. METHODS: An anonymous and voluntary cross-sectional observational study was carried out in the first fortnight of December 2021, through an ad hoc online questionnaire, in dentistry students from the Autonomous Community of Madrid. Descriptive analysis of the variables was performed and the associations and significance were assessed using Chi-square and T-student. RESULTS: There were received seventy-two surveys. 82% were women and 18% men, with 23±3 years of mean age. 94% had good oral hygiene habits that improved with the pandemic. Their usual diet was varied and complete. Women consumed less meat (p=0.014) and more fruit (p=0.066), habits that they maintained, and men have improved with an increase in fruits (p<0.002), vegetables and legumes (p<0.003) in the pandemic. Tobacco (23,4%) and alcohol (54%) consumption decreased in confinement and increase in post-confinement. 36% increased their physical activity, initially low, especially in post-confinement. CONCLUSIONS: The students in the sample have good oral hygiene and eating habits, which they keep and even improve with the pandemic, including an increase in physical exercise in a significant fraction of the sample. The confinement affect the mood and social relationships, even altering the sleep of women, with an increase in night awakenings, especially in post-confinement.

OBJECTIVE: La pandemia de la COVID-19 y sus medidas de control parecen haber alterado la dinámica vital de la población. Fue justificable, por tanto, tratar de precisar el impacto sobre el estilo de vida, la higiene bucodental y el estado anímico, en grupos específicos, como estudiantes universitarios de Odontología de Madrid, que nos eran accesibles. METHODS: Se realizó un estudio observacional transversal anónimo y voluntario en la primera quincena de diciembre de 2021, mediante cuestionario online ad hoc, en estudiantes de Odontología de universidades de la Comunidad Autónoma de Madrid (CAM). Se realizó análisis descriptivo de las variables y se valoraron las asociaciones y significación con Chi-cuadrado y T-student. RESULTS: Se recibieron setenta y dos encuestas. El 82% eran mujeres y el 18% varones, con 23±3 años de media. El 94% tenía buenos hábitos de higiene oral, que mejoraron con la pandemia. Su dieta habitual era variada y completa. Las mujeres consumían menos carne (p=0,014) y más fruta (p=0,066), hábitos que mantenían, y mejoraron los varones con incremento en frutas (p<0,002), verduras y legumbres (p<0,003) en la pandemia. El consumo de tabaco (23,4%) y alcohol (54%) disminuyó en confinamiento y subió en postconfinamiento. Un 36% aumentó, especialmente en postconfinamiento, su actividad física, antes baja. CONCLUSIONS: Los estudiantes de la muestra tienen buenos hábitos de higiene oral y alimentación que mantienen e incluso mejoran con la pandemia, incluido un incremento del ejercicio físico en una fracción importante de la muestra. El confinamiento afecta al estado anímico y las relaciones sociales, llegando a alterar el sueño de las mujeres, con aumento de despertares nocturnos, sobre todo, en postconfinamiento.

Stigma experienced by men diagnosed with COVID-19 / Estigma experimentado por hombres diagnosticados con COVID-19 / Estigma vivenciado por homens diagnosticados com COVID-19

ABSTRACT Objective: to analyze the stigma characteristics perceived in the experience of men who had COVID-19. Method: this qualitative study involved men living in Brazil, diagnosed with COVID-19, who answered semi-structured questions in an online form. Data were subjected to thematic and lexical analysis, interpreted in the light of the stigma theory. Results: 92 men, adults, cisgender, heterosexual, of mixed race/color, belonging to middle class, living in the urban area, with higher education participated. The stigma characteristics evidenced were the occurrence of leave, perception of impolite treatment, use of labels and discrimination by co-workers, family members, neighbors and even healthcare professionals, with consequences for the psycho-emotional dimension. Final considerations: discrimination and exclusion derived from stigma surprised men marked by class and gender privileges, little used to being downgraded in interactions when compared to other groups.

RESUMEN Objetivo: analizar las características del estigma percibido en la experiencia de hombres que experimentaron COVID-19. Método: estudio cualitativo con hombres residentes en Brasil diagnosticados de COVID-19, quienes respondieron preguntas semiestructuradas en forma online. Los datos fueron sometidos a un análisis temático y léxico, interpretados a la luz de la teoría del estigma. Resultados: participaron 92 hombres, adultos, cisgénero, heterosexuales, de raza/color morena, pertenecientes a la clase media, residentes en el área urbana, con educación superior. Las características del estigma evidenciadas fueron la ocurrencia de bajas, percepción de trato descortés, aplicación de etiquetas y discriminación derivada de compañeros de trabajo, familiares, vecinos e incluso profesionales de la salud, con consecuencias para la dimensión psicoemocional. Consideraciones finales: la discriminación y la exclusión derivada del estigma sorprendió a los hombres marcados por privilegios de clase y género, poco acostumbrados a ser degradados en las interacciones, en comparación con otros grupos.

RESUMO Objetivo: analisar as características do estigma percebidas na experiência de homens que vivenciaram a COVID-19. Método: estudo qualitativo, que envolveu homens residentes no Brasil diagnosticados com COVID-19, os quais responderam a questões semiestruturadas em formulário online. Os dados foram submetidos à análise temática e lexical, interpretados à luz da teoria do estigma. Resultados: participaram 92 homens, adultos, cisgêneros, heterossexuais, de raça/cor parda, pertencentes à classe média, residentes na área urbana, com nível superior. As características do estigma evidenciadas foram aocorrência de afastamento, percepção do tratamento descortês, aplicação de rótulos e discriminação advindas de colegas de trabalho, familiares, vizinhos e até mesmo profissionais de saúde, com consequências para a dimensão psicoemocional. Considerações finais: discriminação e exclusão derivada do estigma surpreenderam homens marcados por privilégios de classe e gênero, pouco habituados a serem rebaixados nas interações, quando comparado a outros grupos.

Stigma experienced by men diagnosed with COVID-19.

OBJECTIVE: to analyze the stigma characteristics perceived in the experience of men who had COVID-19. METHOD: this qualitative study involved men living in Brazil, diagnosed with COVID-19, who answered semi-structured questions in an online form. Data were subjected to thematic and lexical analysis, interpreted in the light of the stigma theory. RESULTS: 92 men, adults, cisgender, heterosexual, of mixed race/color, belonging to middle class, living in the urban area, with higher education participated. The stigma characteristics evidenced were the occurrence of leave, perception of impolite treatment, use of labels and discrimination by co-workers, family members, neighbors and even healthcare professionals, with consequences for the psycho-emotional dimension. FINAL CONSIDERATIONS: discrimination and exclusion derived from stigma surprised men marked by class and gender privileges, little used to being downgraded in interactions when compared to other groups.

Regulation of hepatic coenzyme Q biosynthesis by dietary omega-3 polyunsaturated fatty acids.

Dietary fats are important for human health, yet it is not fully understood how different fats affect various health problems. Although polyunsaturated fatty acids (PUFAs) are generally considered as highly oxidizable, those of the n-3 series can ameliorate the risk of many age-related disorders. Coenzyme Q (CoQ) is both an essential component of the mitochondrial electron transport chain and the only lipid-soluble antioxidant that animal cells can synthesize. Previous work has documented the protective antioxidant properties of CoQ against the autoxidation products of PUFAs. Here, we have explored in vitro and in vivo models to better understand the regulation of CoQ biosynthesis by dietary fats. In mouse liver, PUFAs increased CoQ content, and PUFAs of the n-3 series increased preferentially CoQ10. This response was recapitulated in hepatic cells cultured in the presence of lipid emulsions, where we additionally demonstrated a role for n-3 PUFAs as regulators of CoQ biosynthesis via the upregulation of several COQ proteins and farnesyl pyrophosphate levels. In both models, n-3 PUFAs altered the mitochondrial network without changing the overall mitochondrial mass. Furthermore, in cellular systems, n-3 PUFAs favored the synthesis of CoQ10 over CoQ9, thus altering the ratio between CoQ isoforms through a mechanism that involved downregulation of farnesyl diphosphate synthase activity. This effect was recapitulated by both siRNA silencing and by pharmacological inhibition of farnesyl diphosphate synthase with zoledronic acid. We highlight here the ability of n-3 PUFAs to regulate CoQ biosynthesis, CoQ content, and the ratio between its isoforms, which might be relevant to better understand the health benefits associated with this type of fat. Additionally, we identify for the first time zoledronic acid as a drug that inhibits CoQ biosynthesis, which must be also considered with respect to its biological effects on patients.

Molecular tools for the characterization of seizure susceptibility in genetic rodent models of epilepsy.

Epilepsy is a chronic neurological disorder characterized by abnormal neuronal activity that arises from imbalances between excitatory and inhibitory synapses, which are highly correlated to functional and structural changes in specific brain regions. The difference between the normal and the epileptic brain may harbor genetic alterations, gene expression changes, and/or protein alterations in the epileptogenic nucleus. It is becoming increasingly clear that such differences contribute to the development of distinct epilepsy phenotypes. The current major challenges in epilepsy research include understanding the disease progression and clarifying epilepsy classifications by searching for novel molecular biomarkers. Thus, the application of molecular techniques to carry out comprehensive studies at deoxyribonucleic acid, messenger ribonucleic acid, and protein levels is of utmost importance to elucidate molecular dysregulations in the epileptic brain. The present review focused on the great diversity of technical approaches available and new research methodology, which are already being used to study molecular alterations underlying epilepsy. We have grouped the different techniques according to each step in the flow of information from DNA to RNA to proteins, and illustrated with specific examples in animal models of epilepsy, some of which are our own. Separately and collectively, the genomic and proteomic techniques, each with its own strengths and limitations, provide valuable information on molecular mechanisms underlying seizure susceptibility and regulation of neuronal excitability. Determining the molecular differences between genetic rodent models of epilepsy and their wild-type counterparts might be a key in determining mechanisms of seizure susceptibility and epileptogenesis as well as the discovery and development of novel antiepileptic agents. This article is part of the Special Issue "NEWroscience 2018".

GH directly inhibits steatosis and liver injury in a sex-dependent and IGF1-independent manner.

A reduction in hepatocyte growth hormone (GH)-signaling promotes non-alcoholic fatty liver disease (NAFLD). However, debate remains as to the relative contribution of the direct effects of GH on hepatocyte function vs indirect effects, via alterations in insulin-like growth factor 1 (IGF1). To isolate the role of hepatocyte GH receptor (GHR) signaling, independent of changes in IGF1, mice with adult-onset, hepatocyte-specific GHR knockdown (aHepGHRkd) were treated with a vector expressing rat IGF1 targeted specifically to hepatocytes. Compared to GHR-intact mice, aHepGHRkd reduced circulating IGF1 and elevated GH. In male aHepGHRkd, the shift in IGF1/GH did not alter plasma glucose or non-esterified fatty acids (NEFA), but was associated with increased insulin, enhanced systemic lipid oxidation and reduced white adipose tissue (WAT) mass. Livers of male aHepGHRkd exhibited steatosis associated with increased de novo lipogenesis, hepatocyte ballooning and inflammation. In female aHepGHRkd, hepatic GHR protein levels were not detectable, but moderate levels of IGF1 were maintained, with minimal alterations in systemic metabolism and no evidence of steatosis. Reconstitution of hepatocyte IGF1 in male aHepGHRkd lowered GH and normalized insulin, whole body lipid utilization and WAT mass. However, IGF1 reconstitution did not reduce steatosis or eliminate liver injury. RNAseq analysis showed IGF1 reconstitution did not impact aHepGHRkd-induced changes in liver gene expression, despite changes in systemic metabolism. These results demonstrate the impact of aHepGHRkd is sexually dimorphic and the steatosis and liver injury observed in male aHepGHRkd mice is autonomous of IGF1, suggesting GH acts directly on the adult hepatocyte to control NAFLD progression.

Clinical characteristics and outcomes among hospitalized adults with severe COVID-19 admitted to a tertiary medical center and receiving antiviral, antimalarials, glucocorticoids, or immunomodulation with tocilizumab or cyclosporine: A retrospective observational study (COQUIMA cohort).

BACKGROUND: The COVID-19 outbreak challenges the Spanish health system since March 2020. Some available therapies (antimalarials, antivirals, biological agents) were grounded on clinical case observations or basic science data. The aim of this study is to describe the characteristics and impact of different therapies on clinical outcomes in a cohort of severe COVID-19 patients. METHODS: In this retrospective, single-center, observational study, we collected sequential data on adult patients admitted to Hospital Universitario Quironsalud Madrid. Eligible patients should have a microbiological (positive test on RT-PCR assay from a nasal swab) or an epidemiological diagnosis of severe COVID-19. Demographic, baseline comorbidities, laboratory data, clinical outcomes, and treatments were compared between survivors and non-survivors. We carried out univariate and multivariate logistic regression models to assess potential risk factors for in-hospital mortality. FINDINGS: From March 10th to April 15th, 2020, 607 patients were included. Median age was 69 years [interquartile range, {IQR} 22; 65% male). The most common comorbidities were hypertension (276 [46·94%]), diabetes (95 [16·16%]), chronic cardiac (133 [22·62%]) and respiratory (114 [19·39%]) diseases. 141 patients (23·2%) died. In the multivariate model the risk of death increased with older age (odds ratio, for every year of age, 1·15, [95% CI 1·11 - 1·2]), tocilizumab therapy (2·4, [1·13 - 5·11]), C-reactive protein at admission (1·07, per 10 mg/L, [1·04 - 1·10]), d-dimer > 2·5 µg/mL (1·99, [1·03 - 3·86]), diabetes mellitus (2·61, [1·19 - 5·73]), and the PaO2/FiO2 at admission (0·99, per every 1 mmHg, [0·98 - 0·99]). Among the prescribed therapies (tocilizumab, glucocorticoids, lopinavir/ritonavir, hydroxychloroquine, cyclosporine), only cyclosporine was associated with a significant decrease in mortality (0·24, [0·12 - 0·46]; p<0·001). INTERPRETATION: In a real-clinical setting, inhibition of the calcineurin inflammatory pathway, NF-κΒ, could reduce the hyperinflammatory phase in COVID-19. Our findings might entail relevant implications for the therapy of this disease and could boost the design of new clinical trials among subjects affected by severe COVID-19. FUNDING: Hospital Universitario Quironsalud Madrid. Own fundings for COVID-19 research.

Correction: Analysis of gene variants in the GASH/Sal model of epilepsy.

[This corrects the article DOI: 10.1371/journal.pone.0229953.].

Analysis of gene variants in the GASH/Sal model of epilepsy.

Epilepsy is a complex neurological disorder characterized by sudden and recurrent seizures, which are caused by various factors, including genetic abnormalities. Several animal models of epilepsy mimic the different symptoms of this disorder. In particular, the genetic audiogenic seizure hamster from Salamanca (GASH/Sal) animals exhibit sound-induced seizures similar to the generalized tonic seizures observed in epileptic patients. However, the genetic alterations underlying the audiogenic seizure susceptibility of the GASH/Sal model remain unknown. In addition, gene variations in the GASH/Sal might have a close resemblance with those described in humans with epilepsy, which is a prerequisite for any new preclinical studies that target genetic abnormalities. Here, we performed whole exome sequencing (WES) in GASH/Sal animals and their corresponding controls to identify and characterize the mutational landscape of the GASH/Sal strain. After filtering the results, moderate- and high-impact variants were validated by Sanger sequencing, assessing the possible impact of the mutations by "in silico" reconstruction of the encoded proteins and analyzing their corresponding biological pathways. Lastly, we quantified gene expression levels by RT-qPCR. In the GASH/Sal model, WES showed the presence of 342 variations, in which 21 were classified as high-impact mutations. After a full bioinformatics analysis to highlight the high quality and reliable variants, the presence of 3 high-impact and 15 moderate-impact variants were identified. Gene expression analysis of the high-impact variants of Asb14 (ankyrin repeat and SOCS Box Containing 14), Msh3 (MutS Homolog 3) and Arhgef38 (Rho Guanine Nucleotide Exchange Factor 38) genes showed a higher expression in the GASH/Sal than in control hamsters. In silico analysis of the functional consequences indicated that those mutations in the three encoded proteins would have severe functional alterations. By functional analysis of the variants, we detected 44 significantly enriched pathways, including the glutamatergic synapse pathway. The data show three high-impact mutations with a major impact on the function of the proteins encoded by these genes, although no mutation in these three genes has been associated with some type of epilepsy until now. Furthermore, GASH/Sal animals also showed gene variants associated with different types of epilepsy that has been extensively documented, as well as mutations in other genes that encode proteins with functions related to neuronal excitability, which could be implied in the phenotype of the GASH/Sal. Our findings provide valuable genetic and biological pathway data associated to the genetic burden of the audiogenic seizure susceptibility and reinforce the need to validate the role of each key mutation in the phenotype of the GASH/Sal model.

The Impact of Aging, Calorie Restriction and Dietary Fat on Autophagy Markers and Mitochondrial Ultrastructure and Dynamics in Mouse Skeletal Muscle.

Loss of skeletal muscle mass and function is a hallmark of aging. This phenomenon has been related to a dysregulation of mitochondrial function and proteostasis. Calorie restriction (CR) has been demonstrated to delay aging and preserve function until late in life, particularly in muscle. Recently, we reported the type of dietary fat plays an important role in determining life span extension with 40% CR in male mice. In these conditions, lard fed mice showed an increased longevity compared to mice fed soybean or fish oils. In this article, we analyze the effect of 40% CR on muscle mitochondrial mass, autophagy, and mitochondrial dynamics markers in mice fed these diets. In CR fed animals, lard preserved muscle fibers structure, mitochondrial ultrastructure, and fission/fusion dynamics and autophagy, not only compared to control animals, but also compared with CR mice fed soybean and fish oils as dietary fat. We focus our discussion on dietary fatty acid saturation degree as an essential predictor of life span extension in CR mice.

A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice.

Calorie restriction, without malnutrition, has been shown to increase lifespan and is associated with a shift away from glycolysis toward beta-oxidation. The objective of this study was to mimic this metabolic shift using low-carbohydrate diets and to determine the influence of these diets on longevity and healthspan in mice. C57BL/6 mice were assigned to a ketogenic, low-carbohydrate, or control diet at 12 months of age and were either allowed to live their natural lifespan or tested for physiological function after 1 or 14 months of dietary intervention. The ketogenic diet (KD) significantly increased median lifespan and survival compared to controls. In aged mice, only those consuming a KD displayed preservation of physiological function. The KD increased protein acetylation levels and regulated mTORC1 signaling in a tissue-dependent manner. This study demonstrates that a KD extends longevity and healthspan in mice.

Intraperitoneal pressure in peritoneal dialysis. / La presión intraperitoneal en diálisis peritoneal.

The measure of intraperitoneal pressure in peritoneal dialysis is easy and provides clear therapeutic benefits. However it is measured only rarely in adult peritoneal dialysis units. This review aims to disseminate the usefulness of measuring intraperitoneal pressure. This measurement is performed in supine before initiating the drain of a manual exchange with "Y" system, by raising the drain bag and measuring from the mid-axillary line the height of the liquid column that rises from the patient. With typical values of 10-16 cmH2O, intraperitoneal pressure should never exceed 18 cmH2O. With basal values that depend on body mass index, it increases 1-3 cmH2O/L of intraperitoneal volume, and varies with posture and physical activity. Its increase causes discomfort, sleep and breathing disturbances, and has been linked to the occurrence of leaks, hernias, hydrothorax, gastro-esophageal reflux and enteric peritonitis. Less known and valued is its ability to decrease the effectiveness of dialysis significantly counteracting ultrafiltration and decreasing solute clearance to a smaller degree. Because of its easy measurement and potential utility, should be monitored in case of ultrafiltration failure to rule out its eventual contribution in some patients. Although not yet mentioned in the clinical practice guidelines for PD, its clear benefits justify its inclusion among the periodic measurements to consider for prescribing and monitoring peritoneal dialysis.

Kaempferol increases levels of coenzyme Q in kidney cells and serves as a biosynthetic ring precursor.

Coenzyme Q (Q) is a lipid-soluble antioxidant essential in cellular physiology. Patients with Q deficiencies, with few exceptions, seldom respond to treatment. Current therapies rely on dietary supplementation with Q10, but due to its highly lipophilic nature, Q10 is difficult to absorb by tissues and cells. Plant polyphenols, present in the human diet, are redox active and modulate numerous cellular pathways. In the present study, we tested whether treatment with polyphenols affected the content or biosynthesis of Q. Mouse kidney proximal tubule epithelial (Tkpts) cells and human embryonic kidney cells 293 (HEK 293) were treated with several types of polyphenols, and kaempferol produced the largest increase in Q levels. Experiments with stable isotope 13C-labeled kaempferol demonstrated a previously unrecognized role of kaempferol as an aromatic ring precursor in Q biosynthesis. Investigations of the structure-function relationship of related flavonols showed the importance of two hydroxyl groups, located at C3 of the C ring and C4' of the B ring, both present in kaempferol, as important determinants of kaempferol as a Q biosynthetic precursor. Concurrently, through a mechanism not related to the enhancement of Q biosynthesis, kaempferol also augmented mitochondrial localization of Sirt3. The role of kaempferol as a precursor that increases Q levels, combined with its ability to upregulate Sirt3, identify kaempferol as a potential candidate in the design of interventions aimed on increasing endogenous Q biosynthesis, particularly in kidney.

Clinical pretreatment risk factors and prediction of outcome using gallium 67 scintigraphy in patients with Hodgkin's lymphoma.

This study was conducted to investigate the prognostic effect and implications of gallium 67 scintigraphy (gallium scan) at mid-treatment and at the end of first-line treatment in patients with early- and advanced-stage Hodgkin's lymphoma (HL). A total of 216 HL patients were included in the study. Gallium scan was performed at mid-treatment and at the end of first-line treatment. The overall survival (OS) and event-free survival (EFS) were calculated using the Kaplan-Meier method. The log-rank test was used to identify univariate predictors of EFS and OS. For early-stage disease, bulky mediastinal involvement (yes vs. no, 98 vs. 79%, respectively; P=0.01), erythrocyte sedimentation rate (good vs. adverse, 98 vs. 88%, respectively; P=0.03), presence of B symptoms (no vs. yes, 94 vs. 78%, respectively; P=0.006), post-chemotherapy disease status [complete response (CR) vs. unconfirmed CR (uCR) vs. partial response (PR) vs. progressive disease (PGR), 95 vs. 90 vs. 87 vs. 0%, respectively; P<0.01] and gallium scan at mid-treatment and at the end of treatment (negative vs. positive, 88 vs. 20%, P<0.001; and 85 vs. 10%, P<0.001, respectively) significantly affected the EFS. In addition, age (<50 vs. ≥50 years, 96 vs. 78%, respectively; P=0.01), presence of B symptoms (no vs. yes, 97 vs. 87%, respectively; P=0.03), post-chemotherapy disease status (CR vs. uCR vs. PR vs. PGR, 95 vs. 90 vs. 90 vs. 0%, respectively; P<0.01) and gallium scan results at mid-treatment and at the end of treatment (negative vs. positive, 87 vs. 60%, P<0.001; and 95 vs. 0%, P<0.001, respectively) significantly affected the OS. For advanced-stage disease, Hassenclever index (1-3 vs. 4-6, 80 vs. 57%, respectively; P=0.05) and gallium scan results at mid-treatment and at the end of treatment (negative vs. positive, 84 vs. 18%, P<0.001; and 84 vs. 0%, P<0.001, respectively) significantly affected the EFS, whereas age at diagnosis (<50 vs. ≥50 years, 92 vs. 78%, respectively; P=0.04), Hassenclever index (1-3 vs. 4-6, 86 vs. 61%, respectively; P=0.04) and gallium scan results at mid-treatment and at the end of treatment (negative vs. positive, 98 vs. 40%, P<0.001; and 97 vs. 23%, P<0.001, respectively) significantly affected the OS. On the multivariate analysis, gallium scan at the end of first-line treatment retained statistical significance in terms of EFS and OS. In conclusion, post-chemotherapy gallium scan is an important prognostic factor in patients with early- or advanced-stage HL and a predictor of adverse outcome.

Olive Oil and the Hallmarks of Aging.

Aging is a multifactorial and tissue-specific process involving diverse alterations regarded as the "hallmarks of aging", which include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion and altered intracellular communication. Virtually all these hallmarks are targeted by dietary olive oil, particularly by virgin olive oil, since many of its beneficial effects can be accounted not only for the monounsaturated nature of its predominant fatty acid (oleic acid), but also for the bioactivity of its minor compounds, which can act on cells though both direct and indirect mechanisms due to their ability to modulate gene expression. Among the minor constituents of virgin olive oil, secoiridoids stand out for their capacity to modulate many pathways that are relevant for the aging process. Attenuation of aging-related alterations by olive oil or its minor compounds has been observed in cellular, animal and human models. How olive oil targets the hallmarks of aging could explain the improvement of health, reduced risk of aging-associated diseases, and increased longevity which have been associated with consumption of a typical Mediterranean diet containing this edible oil as the predominant fat source.

The influence of dietary fat source on liver and skeletal muscle mitochondrial modifications and lifespan changes in calorie-restricted mice.

The Membrane Theory of Aging proposes that lifespan is inversely related to the level of unsaturation in membrane phospholipids. Calorie restriction (CR) without malnutrition extends lifespan in many model organisms, which may be related to alterations in membrane phospholipids fatty acids. During the last few years our research focused on studying how altering the predominant fat source affects the outcome of CR in mice. We have established four dietary groups: one control group fed 95 % of a pre-determined ad libitum intake (in order to prevent obesity), and three CR groups fed 40 % less than ad libitum intake. Lipid source for the control and one of the CR groups was soybean oil (high in n-6 PUFA) whereas the two remaining CR groups were fed diets containing fish oil (high in n-3 PUFA), or lard (high in saturated and monounsaturated fatty acids). Dietary intervention periods ranged from 1 to 18 months. We performed a longitudinal lifespan study and a cross-sectional study set up to evaluate several mitochondrial parameters which included fatty acid composition, H(+) leak, activities of electron transport chain enzymes, ROS generation, lipid peroxidation, mitochondrial ultrastructure, and mitochondrial apoptotic signaling in liver and skeletal muscle. These approaches applied to different cohorts of mice have independently indicated that lard as a fat source often maximizes the effects of 40 % CR on mice. These effects could be due to significant increases of monounsaturated fatty acids levels, in accordance with the Membrane Theory of Aging.

The clinical heterogeneity of coenzyme Q10 deficiency results from genotypic differences in the Coq9 gene.

Primary coenzyme Q10 (CoQ10) deficiency is due to mutations in genes involved in CoQ biosynthesis. The disease has been associated with five major phenotypes, but a genotype-phenotype correlation is unclear. Here, we compare two mouse models with a genetic modification in Coq9 gene (Coq9(Q95X) and Coq9(R239X)), and their responses to 2,4-dihydroxybenzoic acid (2,4-diHB). Coq9(R239X) mice manifest severe widespread CoQ deficiency associated with fatal encephalomyopathy and respond to 2,4-diHB increasing CoQ levels. In contrast, Coq9(Q95X) mice exhibit mild CoQ deficiency manifesting with reduction in CI+III activity and mitochondrial respiration in skeletal muscle, and late-onset mild mitochondrial myopathy, which does not respond to 2,4-diHB. We show that these differences are due to the levels of COQ biosynthetic proteins, suggesting that the presence of a truncated version of COQ9 protein in Coq9(R239X) mice destabilizes the CoQ multiprotein complex. Our study points out the importance of the multiprotein complex for CoQ biosynthesis in mammals, which may provide new insights to understand the genotype-phenotype heterogeneity associated with human CoQ deficiency and may have a potential impact on the treatment of this mitochondrial disorder.

Spatial and temporal dynamics of primary and secondary metabolism in Phaseolus vulgaris challenged by Pseudomonas syringae.

Many defense mechanisms contribute to the plant immune system against pathogens, involving the regulation of different processes of the primary and secondary metabolism. At the same time, pathogens have evolved mechanisms to hijack the plant defense in order to establish the infection and proliferate. Localization and timing of the host response are essential to understand defense mechanisms and resistance to pathogens (Rico et al. 2011). Imaging techniques, such as fluorescence imaging and thermography, are a very valuable tool providing spatial and temporal information about a series of plant processes. In this study, bean plants challenged with two pathovars of Pseudomonas syringae have been investigated. Pseudomonas syringae pv. phaseolicola 1448A and P. syringae pv. tomato DC3000 elicit a compatible and incompatible interaction in bean, respectively. Both types of host-pathogen interaction triggered different changes in the activity of photosynthesis and the secondary metabolism. We conclude that the combined analysis of leaf temperature, chlorophyll fluorescence and green fluorescence emitted by phenolics allows to discriminate compatible from incompatible P. syringae-Phaseolus vulgaris interactions in very early times of the infection, prior to the development of symptoms. These can constitute disease signatures that would allow an early identification of emerging plagues in crops.

Mitochondrial ultrastructure and markers of dynamics in hepatocytes from aged, calorie restricted mice fed with different dietary fats.

In this paper we analyzed changes in hepatocyte mitochondrial mass and ultrastructure as well as in mitochondrial markers of fission/fusion and biogenesis in mice subjected to 40% calorie restriction (CR) for 18 months versus ad libitum-fed controls. Animals subjected to CR were separated into three groups with different dietary fats: soybean oil (also in controls), fish oil and lard. Therefore, the effect of the dietary fat under CR was studied as well. Our results show that CR induced changes in hepatocyte and mitochondrial size, in the volume fraction occupied by mitochondria, and in the number of mitochondria per hepatocyte. Also, mean number of mitochondrial cristae and lengths were significantly higher in all CR groups compared with controls. Finally, CR had no remarkable effects on the expression levels of fission and fusion protein markers. However, considerable differences in many of these parameters were found when comparing the CR groups, supporting the idea that dietary fat plays a relevant role in the modulation of CR effects in aged mice.