Methods to Identify Cognitive Alterations from Animals to Humans: A Translational Approach.

The increasing prevalence of cognitive dysfunction and dementia in developed countries, associated with population aging, has generated great interest in characterizing and quantifying cognitive deficits in these patients. An essential tool for accurate diagnosis is cognitive assessment, a lengthy process that depends on the cognitive domains analyzed. Cognitive tests, functional capacity scales, and advanced neuroimaging studies explore the different mental functions in clinical practice. On the other hand, animal models of human diseases with cognitive impairment are essential for understanding disease pathophysiology. The study of cognitive function using animal models encompasses multiple dimensions, and deciding which ones to investigate is necessary to select the most appropriate and specific tests. Therefore, this review studies the main cognitive tests for assessing cognitive deficits in patients with neurodegenerative diseases. Cognitive tests, the most commonly used functional capacity scales, and those resulting from previous evidence are considered. In addition, the leading behavioral tests that assess cognitive functions in animal models of disorders with cognitive impairment are highlighted.

Performance evaluation and users' perception of courtyards role in indoor areas of mediterranean social housing.

Cities confront two critical challenges: general overheating and inefficient use of energy resources within their housing buildings, both adversely affecting urban citizens' daily lives. To mitigate these issues, passive techniques offer promising solutions on enhancing building comfort levels from a sustainable approach. Although this energy efficiency of air-conditioning systems in buildings in warm climates has been extensively analysed, the influence of the microclimate of transitional spaces attached to them on this performance has not yet been properly assessed. Investigating the potential benefits of the implementation of courtyards within Seville's social housing infrastructure for passive conditioning purposes is one way of reducing this research gap. Furthermore, the study also includes the subjective perception of users' thermal well-being around these spaces and their own social relationship related to their use. The work relies on detailed data analyses carried out using DesignBuilder software to quantify the benefit effectively accrued from courtyard utilization. Concurrently, user surveys conducted help determine perceived thermal comfort aiding better configuration management and passive design strategies of urban social housing. Findings from monitoring and simulation reveal that courtyards work faultlessly as a highly effective and efficient passive cooling system whilst promoting energy efficiency up to 20,5%. Surveys confirmed these findings with data revealing significant improvements in thermal comforts perception inside courtyards and within indoor spaces adjacent to the courtyards. This research provides novel insights into how architects and urban managers might integrate passive strategies into future designs for optimizing comfort levels in social housing using courtyards as one possible environmental measure for achieving sustainability targets.

Insights into the Use of Peripherally Acting µ-Opioid Receptor Antagonists (PAMORAs) in Oncologic Patients: from Scientific Evidence to Real Clinical Practice.

OPINION STATEMENT: Management of chronic pain is crucial to improve the quality of life of cancer and palliative care patients. Opioid-based treatments used to control pain can be prolonged over time. Unfortunately, constipation is one of the most disturbing adverse effects of long-term use of opioids. Opioid-induced constipation (OIC) occurs when opioids bind to the specific receptors present in the gastrointestinal (GI) tract, and can affect any patients receiving chronic opioid therapy, including cancer patients. The limited efficacy of laxatives to treat OIC symptoms prompted the search for new therapeutic strategies. Peripherally acting µ-opioid receptor antagonists (PAMORAs) have recently emerged as new effective drugs for OIC management due to their specific binding to enteric µ-receptors. Little information is available on the use of PAMORAs in real-life practice for OIC treatment in cancer patients. In this paper, a panel of experts specializing in cancer and palliative care pools their clinical experience with PAMORAs in cancer patients presenting OIC and highlights the importance of timing and choice of therapy in achieving prompt OIC management and benefitting patients.

Mediterranean diet and endothelial function in patients with coronary heart disease: An analysis of the CORDIOPREV randomized controlled trial.

BACKGROUND: Endothelial dysfunction is a crucial step in atherosclerosis development, and its severity is determinant for the risk of cardiovascular recurrence. Diet may be an effective strategy to protect the endothelium, although there is no consensus about the best dietary model. The CORonary Diet Intervention with Olive oil and cardiovascular PREVention (CORDIOPREV) study is an ongoing prospective, randomized, single-blind, controlled trial in 1,002 coronary heart disease (CHD) patients, whose primary objective is to compare the effect of 2 healthy dietary patterns (low-fat versus Mediterranean diet) on the incidence of cardiovascular events. Here, we report the results of one secondary outcome of the CORDIOPREV study: to evaluate the effect of these diets on endothelial function, assessed by flow-mediated dilation (FMD) of the brachial artery. METHODS AND FINDINGS: From the total participants taking part in the CORDIOPREV study, 805 completed endothelial function study at baseline and were randomized to follow a Mediterranean diet (35% fat, 22% monounsaturated fatty acids [MUFAs], and <50% carbohydrates) or a low-fat diet (28% fat, 12% MUFAs, and >55% carbohydrates), with endothelial function measurement repeated after 1 year. As secondary objectives and to explore different underlying mechanisms in the modulation of endothelial function, we quantified endothelial microparticles (EMPs) and endothelial progenitor cells (EPCs) and evaluated, in 24 preselected patients, in vitro cellular processes related to endothelial damage (reactive oxygen species, apoptosis, and senescence) and endothelial repair (cell proliferation and angiogenesis), as well as other modulators (micro-RNAs [miRNAs] and proteins). Patients who followed the Mediterranean diet had higher FMD (3.83%; 95% confidence interval [CI]: 2.91-4.23) compared with those in the low-fat diet (1.16%; 95% CI: 0.80 to 1.98) with a difference between diets of 2.63% (95% CI: 1.89-3.40, p = 0.011), even in those patients with severe endothelial dysfunction. We observed higher EPC levels (group difference: 1.64%; 95% CI: 0.79-2.13, p = 0.028) and lower EMPs (group difference: -755 EMPs/µl; 95% CI: -1,010 to -567, p = 0.015) after the Mediterranean diet compared with the low-fat diet in all patients. We also observed lower intracellular reactive oxygen species (ROS) production (group difference: 11.1; 95% CI: 2.5 to 19.6, p = 0.010), cellular apoptosis (group difference: -20.2; 95% CI: -26.7 to -5.11, p = 0.013) and senescence (18.0; 95% CI: 3.57 to 25.1, p = 0.031), and higher cellular proliferation (group difference: 11.3; 95% CI: 4.51 to 13.5, p = 0.011) and angiogenesis (total master segments length, group difference: 549; 95% CI: 110 to 670, p = 0.022) after the Mediterranean diet than the low-fat diet. Each dietary intervention was associated with distinct changes in the epigenetic and proteomic factors that modulate biological process associated with endothelial dysfunction. The evaluation of endothelial function is a substudy of the CORDIOPREV study. As in any substudy, these results should be treated with caution, such as the potential for false positives because of the exploratory nature of the analyses. CONCLUSIONS: Our results suggest that the Mediterranean diet better modulates endothelial function compared with a low-fat diet and is associated with a better balance of vascular homeostasis in CHD patients, even in those with severe endothelial dysfunction. CLINICAL TRIAL REGISTRATION: URL, http://www.cordioprev.es/index.php/en. clinicaltrials.gov number NCT00924937.

Hypothermia Plus Melatonin in Asphyctic Newborns: A Randomized-Controlled Pilot Study.

OBJECTIVES: To investigate the effect of adding melatonin to hypothermia treatment on neurodevelopmental outcomes in asphyctic newborns. DESIGN: Pilot multicenter, randomized, controlled, double-blind clinical trial. Statistical comparison of results obtained in two intervention arms: hypothermia plus placebo and hypothermia plus melatonin. SETTING: Level 3 neonatal ICU. PATIENTS: Twenty-five newborns were recruited. INTERVENTIONS: The hypothermia plus melatonin patients received a daily dose of IV melatonin, 5 mg per kg body weight, for 3 days. General laboratory variables were measured both at neonatal ICU admission and after intervention. All infants were studied with amplitude-integrated electroencephalography and brain MRI within the first week of life. The neurodevelopmental Bayley III test, the Gross Motor Function Classification System, and the Tardieu scale were applied at the ages of 6 and 18 months. MEASUREMENTS AND MAIN RESULTS: Clinical characteristics, laboratory evaluations, MRI findings, and amplitude-integrated electroencephalography background did not differ between the treatment groups. The newborns in the hypothermia plus melatonin group achieved a significantly higher composite score for the cognitive section of the Bayley III test at 18 months old, with respect to the hypothermia plus placebo group (p = 0.05). There were no differences between the groups according to the Gross Motor Function Classification System and Tardieu motor assessment scales. CONCLUSIONS: The early addition of IV melatonin to asphyctic neonates is feasible and may improve long-term neurodevelopment. To our knowledge, this is the first clinical trial to analyze the administration of IV melatonin as an adjuvant therapy to therapeutic hypothermia.

Association of breast and gut microbiota dysbiosis and the risk of breast cancer: a case-control clinical study.

BACKGROUND: Breast cancer ranks first in women, and is the second cause of death in this gender. In addition to genetics, the environment contributes to the development of the disease, although the factors involved are not well known. Among the latter is the influence of microorganisms and, therefore, attention is recently being paid to the mammary microbiota. We hypothesize that the risk of breast cancer could be associated with the composition and functionality of the mammary/gut microbiota, and that exposure to environmental contaminants (endocrine disruptors, EDCs) might contribute to alter these microbiota. METHODS: We describe a case-control clinical study that will be performed in women between 25 and 70 years of age. Cases will be women diagnosed and surgically intervened of breast cancer (stages I and II). Women with antecedents of cancer or advanced tumor stage (metastasis), or who have received antibiotic treatment within a period of 3 months prior to recruitment, or any neoadjuvant therapy, will be excluded. Controls will be women surgically intervened of breast augmentation or reduction. Women with oncological, gynecological or endocrine history, and those who have received antibiotic treatment within a period of 3 months prior to recruitment will also be excluded. Blood, urine, breast tissue and stool samples will be collected. Data regarding anthropometric, sociodemographic, reproductive history, tumor features and dietary habits will be gathered. Metabolomic studies will be carried out in stool and breast tissue samples. Metagenomic studies will also be performed in stool and breast tissue samples to ascertain the viral, fungal, bacterial and archaea populations of the microbiota. Quantitation of estrogens, estrogen metabolites and EDCs in samples of serum, urine and breast tissue will also be performed. DISCUSSION: This is the first time that the contribution of bacteria, archaea, viruses and fungi together with their alteration by environmental contaminants to the risk of breast cancer will be evaluated in the same study. Results obtained could contribute to elucidate risk factors, improve the prognosis, as well as to propose novel intervention studies in this disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT03885648 , 03/25/2019. Retrospectively registered.

Frying oils with high natural or added antioxidants content, which protect against postprandial oxidative stress, also protect against DNA oxidation damage.

PURPOSE: Using sunflower oil as frying oil increases postprandial oxidative stress, which is considered the main endogenous source of DNA oxidative damage. We aimed to test whether the protective effect of virgin olive oil and oil models with added antioxidants against postprandial oxidative stress may also protect against DNA oxidative damage. METHODS: Twenty obese people received four breakfasts following a randomized crossover design consisting of different oils [virgin olive oil (VOO), sunflower oil (SFO), and a mixed seed oil (SFO/canola oil) with added dimethylpolysiloxane (SOX) or natural antioxidants from olives (SOP)], which were subjected to 20 heating cycles. RESULTS: We observed the postprandial increase in the mRNA levels of p53, OGG1, POLB, and GADD45b after the intake of the breakfast prepared with SFO and SOX, and an increase in the expression of MDM2, APEX1, and XPC after the intake of the breakfast prepared with SFO, whereas no significant changes at the postprandial state were observed after the intake of the other breakfasts (all p values <0.05). We observed lower 8-OHdG postprandial levels after the intake of the breakfast prepared with VOO and SOP than after the intake of the breakfast prepared with SFO and SOX (all p values <0.05). CONCLUSIONS: Our results support the beneficial effect on DNA oxidation damage of virgin olive oil and the oil models with added antioxidants, as compared to the detrimental use of sunflower oil, which induces p53-dependent DNA repair pathway activation.

The insulin resistance phenotype (muscle or liver) interacts with the type of diet to determine changes in disposition index after 2 years of intervention: the CORDIOPREV-DIAB randomised clinical trial.

AIMS/HYPOTHESIS: The aim of the study was to determine whether basal insulin resistance (IR) phenotype (muscle and/or liver) determines the effect of long-term consumption of a Mediterranean diet or a low-fat diet on tissue-specific IR and beta cell function. METHODS: The study was performed in 642 patients included in The effect of an olive oil rich Mediterranean diet on type 2 diabetes mellitus risk and incidence study (CORDIOPREV-DIAB). A total of 327 patients were randomised to a Mediterranean diet (35% fat; 22% from monounsaturated fatty acids) and 315 to a low-fat diet (<28% fat). At baseline, the patients were classified into four phenotypes according to the type of IR: (1) no IR; (2) muscle IR; (3) liver IR; (4) muscle + liver IR. The hepatic insulin resistance index (HIRI), muscular insulin sensitivity index (MISI) and disposition index were analysed at baseline and after 2 years of follow-up. RESULTS: At baseline, 322 patients presented no IR, 106 presented muscle IR, 109 presented liver IR, and 105 presented muscle + liver IR. With both dietary interventions, HIRI decreased in all patients (p < 0.001) and MISI increased in muscle IR and muscle + liver IR patients (p < 0.01). Long-term intake of the Mediterranean diet increased the disposition index and insulinogenic index in the muscle IR patients (p = 0.042 and p = 0.044, respectively) and the disposition index in the muscle + liver IR patients (p = 0.048), whereas the low-fat diet increased the disposition index in the liver IR patients (p = 0.017). CONCLUSIONS/INTERPRETATION: Although both diets improve insulin sensitivity, there are differences based on basal IR phenotypes. Moreover, according to insulinogenic and disposition index data, a low-fat diet might be more beneficial to patients with liver IR, whereas patients with muscle IR and muscle + liver IR might benefit more from a Mediterranean diet. Trial registration ClinicalTrials.gov NCT00924937 FUNDING: The study was supported by the Ministerio de Economia y Competitividad (AGL2012/39615) and by the Ministerio de Ciencia e Innovacion (PIE14/00005 and PI13/00023).

CORonary Diet Intervention with Olive oil and cardiovascular PREVention study (the CORDIOPREV study): Rationale, methods, and baseline characteristics: A clinical trial comparing the efficacy of a Mediterranean diet rich in olive oil versus a low-fat diet on cardiovascular disease in coronary patients.

Coronary heart disease (CHD) represents a major global health burden. However, despite the well-known influence that dietary habits exert over the progression of this disease, there are no well-established and scientifically sound dietary approaches to prevent the onset of clinical outcomes in secondary prevention. The objective of the CORonary Diet Intervention with Olive oil and cardiovascular PREVention study (CORDIOPREV study, clinical trials number NCT00924937) is to compare the ability of a Mediterranean diet rich in virgin olive oil versus a low-fat diet to influence the composite incidence of cardiovascular events after 7 years in subjects with documented CHD at baseline. For this purpose, we enrolled 1,002 coronary patients from Spain. Baseline assessment (2009-2012) included detailed interviews and measurements to assess dietary, social, and biological variables. Results of baseline characteristics: The CORDIOPREV study in Spain describes a population with a high body mass index (37.2% overweight and 56.3% obesity) and with a median of low-density lipoprotein cholesterol of 88.5 mg/dL (70.6% of the patients having <100 mg/dL and 20.3% patients <70 mg/dL). A total of 9.6% of the participants were active smokers, and 64.4% were former smokers. Metabolic syndrome was present in 58% of this population. To sum up, we describe here the rationale, methods, and baseline characteristics of the CORDIOPREV study, which will test for the first time the efficacy of a Mediterranean diet rich in extra virgin olive oil as compared with a low-fat diet on the incidence of CHD recurrence in a long-term follow-up study.

Virgin olive oil rich in phenolic compounds modulates the expression of atherosclerosis-related genes in vascular endothelium.

PURPOSE: Previous studies have shown the anti-inflammatory and antioxidant properties of phenolic compounds of virgin olive oil (VOO). However, the effect of bioavailable phenolic compounds on the vascular endothelium is unknown. We aimed to evaluate the effect of the consumption of virgin olive oil rich in phenolic compounds on the vascular endothelium. METHODS: We treated HUVEC with human serum obtained in fasting state and after the intake of a breakfast prepared with VOO with a high or low content of phenolic compounds. RESULTS: Treatment of HUVEC with serum obtained 2 h after the intake of the high-phenol VOO-based breakfast decreased p65 and MCP-1 gene expression (p < 0.001 and p = 0.002, respectively) and increased MT-CYB, SDHA and SOD1 gene expression (p = 0.004, p = 0.012 and p = 0.001, respectively), as compared with the treatment of HUVEC with the serum obtained 2 h after the intake of the low-phenol VOO-based breakfast. The treatment with serum obtained 4 h after the intake of the high-phenol VOO-based breakfast decreased MCP-1 and CAT gene expression (p < 0.001 and p = 0.003, respectively) and increased MT-CYB gene expression (p < 0.001), as compared to the treatment with serum obtained 4 h after the intake of the low-phenol VOO-based breakfast. CONCLUSION: Our results suggest that the consumption of virgin olive oil rich in phenolic compounds may reduce the risk of atherosclerosis development by decreasing inflammation and improving the antioxidant profile in the vascular endothelium.

Proteome from patients with metabolic syndrome is regulated by quantity and quality of dietary lipids.

BACKGROUND: Metabolic syndrome is a multi-component disorder associated to a high risk of cardiovascular disease. Its etiology is the result of a complex interaction between genetic and environmental factors, including dietary habits. We aimed to identify the target proteins modulated by the long-term consumption of four diets differing in the quality and quantity of lipids in the whole proteome of peripheral blood mononuclear cells (PBMC). RESULTS: A randomized, controlled trial conducted within the LIPGENE study assigned 24 MetS patients for 12 weeks each to 1 of 4 diets: a) high-saturated fatty acid (HSFA), b) high-monounsaturated fatty acid (HMUFA), c) low-fat, high-complex carbohydrate diets supplemented with placebo (LFHCC) and d) low-fat, high-complex carbohydrate diets supplemented with long chain (LC) n-3 polyunsaturated fatty acids (PUFA) (LFHCC n-3). We analyzed the changes induced in the proteome of both nuclear and cytoplasmic fractions of PBMC using 2-D proteomic analysis. Sixty-seven proteins were differentially expressed after the long-term consumption of the four diets. The HSFA diet induced the expression of proteins responding to oxidative stress, degradation of ubiquitinated proteins and DNA repair. However, HMUFA, LFHCC and LFHCC n-3 diets down-regulated pro-inflammatory and oxidative stress-related proteins and DNA repairing proteins. CONCLUSION: The long-term consumption of HSFA, compared to HMUFA, LFHCC and LFHCC n-3, seems to increase the cardiovascular disease (CVD) risk factors associated with metabolic syndrome, such as inflammation and oxidative stress, and seem lead to DNA damage as a consequence of high oxidative stress.

Angiotensin II prevents calcification in vascular smooth muscle cells by enhancing magnesium influx.

BACKGROUND: Vascular calcification (VC) is highly prevalent in patients with chronic kidney disease (CKD). Low magnesium levels are associated with VC, and recent in vitro studies confirm a protective role of magnesium, which is mediated by its entry into the VSMCs through the Transient Receptor Potential Melastatin 7 (TRPM7) channel. The role of Angiotensin II (Ang II) on VC is still unclear. As Ang II is able to stimulate TRPM7 activity, we hypothesize that it might prevent VC. Thus, the aim of this study was to dissect the direct effect of Ang II on VC. MATERIALS AND METHODS: We worked with a model of high phosphate (HP)-induced calcification in human aortic smooth muscle cells, which resembles the CKD-related VC. RESULTS: Addition of Ang II to cells growing in HP decreased calcification, which was associated with the upregulation of the osteogenic factors BMP2, Runx2/Cbfa1, Osterix and ALP. A reduction of magnesium entry into the HP-calcifying cells was found. The treatment with Ang II avoided this reduction, which was reversed by the cotreatment with the TRPM7-inhibitor 2-APB. The protective effect of Ang II was related to AT1R-induced ERK1/2 MAPKinase activation. HP-induced calcification was also associated with the upregulation of the canonical Wnt/beta-catenin pathway, while its downregulation was related to attenuation of calcification by Ang II. CONCLUSION: As hypothesized, Ang II prevented phosphate-induced calcification in VSMCs, which appears mediated by the increase of magnesium influx and by the activation of the ERK1/2 and the inhibition of the canonical Wnt/beta-catenin signalling pathways.

Evidence on the benefits of probiotics for preterm infants.

This article reviews the evidence for the use of different strains of probiotics in the prevention of prevalent pathologies in premature neonates. A systematic review was conducted of the use of probiotics in neonates with less than 37 weeks of gestational age, based on a search for systematic reviews and observational and experimental studies performed during the period from January 2014 to February 2021. For this purpose, the PubMed, MEDLINE and Cochrane Library databases were consulted. The aim of this article was to review the existing data on the relationship between the administration of probiotics (with different strains and doses) and the risk of necrotising enterocolitis, mortality, late sepsis and other disease parameters in premature infants. The literature search obtained 240 articles, of which we selected 16, representing a total sample of over 200,000 premature infants. Analysis of the data obtained reveals statistical evidence that the combined administration of probiotics (especially of Lactobacillus and Bifidobacterium strains) reduces the incidence of grade II or higher necrotising enterocolitis, all-cause mortality, late sepsis, length of hospital stay and time until complete enteral nutrition is achieved. However, no benefits were apparent with respect to alleviating bronchopulmonary dysplasia, retinopathy of prematurity or intraventricular haemorrhage. Further research is needed to determine the most appropriate strains, doses and treatment duration for preterm infants to achieve the health benefits identified.

[Medical nutrition therapy in amyotrophic lateral sclerosis - Do we act or react? A case report and multidisciplinary review]. / Tratamiento médico nutricional en la esclerosis lateral amiotrófica: ¿Actuamos o reaccionamos? Un caso clínico y revisión multidisciplinar.

Introduction: Background: amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a progressive course. The current prevalence is between 3 and 6 cases/100,000. Malnutrition is closely related to patient prognosis in ALS. The implications of this conditions have been that we should recommend patient care in a multidisciplinary unit. Case report: the case presented shows the evolution of a patient with ALS. The patient was referred to different clinical departments after neurological evaluation and her nutritional, functional and respiratory status were assessed. There was no nutritional deterioration at diagnosis; however, intake was below energy-protein requirements. The clinical evolution of the patient showed a decrease in muscle mass with preservation of weight and fat mass. "Aggressive" measures to control nutritional status such as gastrostomy were rejected in the initial stages of the disease, but had to be carried out after development of dysphagia and associated malnutrition. This situation of progressive morphofunctional deterioration and the development of disease-related complications made essential the participation of different health services and professionals in its control. Dicussion: the management of ALS in a multidisciplinary manner allows to improve the course of the disease and the quality of life of both the patients and their families. Patient follow-up is based on the adjustment and management of complications. The basis of the relationship with these patients includes maintaining an adequate communication with them and their families, and ensuring joint decision-making about their condition.

Introducción: Introducción: la esclerosis lateral amiotrófica (ELA) es una enfermedad neurodegenerativa cuya prevalencia en la actualidad está entre 3 y 6 casos/100.000. La desnutrición está íntimamente relacionada con el pronóstico en el paciente con ELA. Las implicaciones de esta enfermedad hacen que se deba recomendar al paciente la asistencia en una unidad multidisciplinar. Caso clínico: el caso presentado muestra la evolución de una paciente con esclerosis lateral amiotrófica desde el diagnóstico. Tras la valoración por parte de Neurología, se remitió a la paciente a los distintos servicios de seguimiento (Endocrinología, Rehabilitación, Neumología). No se observó deterioro nutricional al diagnóstico; no obstante, la ingesta se encontraba por debajo de los requerimientos. En la progresión de la enfermedad se observó un deterioro de la masa muscular con estabilidad ponderal y de la masa grasa, pero la paciente desarrolló disfagia, síntoma típico de la enfermedad. El planteamiento de medidas "agresivas" para controlar el estado nutricional, como la gastrostomía, fue rechazado al inicio, pero hubo que realizarlas tras la progresión de la disfagia y la desnutrición asociada. Esta situación de deterioro morfofuncional y el desarrollo de complicaciones plantearon la participación de distintos profesionales sanitarios en su control. Discusión: el manejo de la ELA de manera multidisciplinar permite mejorar la evolución de la enfermedad y la calidad de vida del paciente y sus familiares. El seguimiento se basa en el ajuste y el manejo de las complicaciones, en mantener una adecuada comunicación con el paciente y sus familiares, y en tomar de manera conjunta las decisiones sobre su patología.

A Clustering Study of Sociodemographic Data, Dietary Patterns, and Gut Microbiota in Healthy and Breast Cancer Women Participating in the MICROMA Study.

SCOPE: This work is part of the clinical study NCT03885648 registered in ClinicalTrials.gov, aimed at studying the relationship among breast cancer, microbiota, and exposure to environmental pollutants. As a first step, we characterized and evaluated risk factors of the participants. METHODS AND RESULTS: A case-control study was designed with breast cancer (cases, n = 122) and healthy women (controls, n = 56) recruited in two hospitals of Andalusia (Southern Spain). Participants answered questionnaires of Mediterranean diet adherence and food frequency. Data were collected from medical histories and microbiota was analyzed on stool samples. Most cases (78.2%) were diagnosed as stages I and II. Cases had higher age, body mass index (BMI), glucose, cholesterol, and potassium values than controls. Cases exhibited higher adherence to the Mediterranean diet and their food consumption was closer to that dietary pattern. A hierarchical cluster analysis revealed that the Bacillota/Bacteroidota ratio was the most relevant variable in women with breast cancer, which was higher in this group compared with controls. CONCLUSION: Although cases exhibited higher adherence to the Mediterranean diet compared with controls, they presented features and microbiota alterations typical of the metabolic syndrome, probably due to their higher BMI and reflecting changes in their lifestyle around the time of diagnosis.

Endothelial aging associated with oxidative stress can be modulated by a healthy mediterranean diet.

Aging is a condition which favors the development of atherosclerosis, which has been associated with a breakdown in repair processes that occurs in response to cell damage. The dysregulation of the biological systems associated with aging are produced partly through damage which accumulates over time. One major source of this injury is oxidative stress, which can impair biological structures and the mechanisms by which they are repaired. These mechanisms are based on the pathogenesis of endothelial dysfunction, which in turn is associated with cardiovascular disease, carcinogenesis and aging. The dependent dysfunction of aging has been correlated with a reduction in the number and/or functional activity of endothelial progenitor cells, which could hinder the repair and regeneration of the endothelium. In addition, aging, inflammation and oxidative stress are endogenous factors that cause telomere shortening, which is dependent on oxidative cell damage. Moreover, telomere length correlates with lifestyle and the consumption of a healthy diet. Thus, diseases associated with aging and age may be caused by the long-term effects of oxidative damage, which are modified by genetic and environmental factors. Considering that diet is a very important source of antioxidants, in this review we will analyze the relationship between oxidative stress, aging, and the mechanisms which may be involved in a higher survival rate and a lower incidence of the diseases associated with aging in populations which follow a healthy diet.

[Analysis of characteristics of elderly patients admitted to an intensive care unit during six waves of the SARS-CoV-2 pandemic: Implications for medical care]. / Análisis de las características de los pacientes mayores que ingresaron en una unidad de cuidados intensivos durante las 6 olas de la pandemia por SARS-CoV-2: implicaciones para la atención médica.

OBJECTIVE: To analyze the characteristics of seriously ill elderly patients during the six waves of the COVID-19 pandemic. METHOD: Retrospective, observational and analytical study of patients over 70 years of age admitted to the ICU (March-2020 to March-2022). Patients were categorized into three groups based on age: 70-74 years; 75-79 years; and >80 years. A descriptive and comparative analysis of the sample was initially performed; and a 28-, 60- and 90-day survival analysis using the Kaplan-Meier method. Multivariate survival analysis was performed by fitting a Cox model. RESULTS: Of 301 patients, the lowest number of admissions occurred during the first wave (20 (6%)), compared to the wave with the highest number of admissions: the sixth wave (76 (25%)). The survival curves at 28 days, 60 days and 90 days showed a higher probability of survival in the younger age groups (P<.01 and P=.01, respectively). Troponin at admission (per unit, ng/l) showed a significant association with 28- and 60-day mortality (HR: 1.00; 95% CI: 1.00-1.01; P<.05). Taking the 1st wave of the pandemic as a reference, admission in the 3rd wave behaved as a protective factor against mortality at 28 and 60 days of follow-up (HR: 0.18; 95% CI: 0.02-0.64; P<.05; HR: 0.13; 95% CI: 0.02-0.64; P<.05, respectively). CONCLUSIONS: The time of admission and biomarkers, such as troponin, constitute prognostic markers independent of age in the elderly population.

[Retrospective study of the effect of vaccination against SARS-CoV-2 in seriously ill patients admitted to an intensive care unit]. / Estudio retrospectivo del efecto de la vacunación frente al SARS-CoV-2 en enfermos graves que ingresan en una unidad de cuidados intensivos.

BACKGROUND AND OBJECTIVE: Our study aims to compare the clinical and epidemiological characteristics, length of stay in the ICU, and mortality rates of COVID-19 patients admitted to the ICU who are fully vaccinated, partially vaccinated, or unvaccinated. PATIENTS AND METHODS: Retrospective cohort study (March 2020-March 2022). Patients were classified into unvaccinated, fully vaccinated, and partially vaccinated groups. We initially performed a descriptive analysis of the sample, a multivariable survival analysis adjusting for a Cox regression model, and a 90-day survival analysis using the Kaplan-Meier method for the death time variable. RESULTS: A total of 894 patients were analyzed: 179 with full vaccination, 32 with incomplete vaccination, and 683 were unvaccinated. Vaccinated patients had a lower incidence (10% vs. 21% and 18%) of severe ARDS. The survival curve did not show any differences in the probability of surviving for 90 days among the studied groups (p = 0.898). In the Cox regression analysis, only the need for mechanical ventilation during admission and the value of LDH (per unit of measurement) in the first 24 hours of admission were significantly associated with mortality at 90 days (HR: 5.78; 95% CI: 1.36-24.48); p = 0.01 and HR: 1.01; 95% CI: 1.00-1.02; p = 0.03, respectively. CONCLUSIONS: Patients with severe SARS-CoV-2 disease who are vaccinated against COVID-19 have a lower incidence of severe ARDS and mechanical ventilation than unvaccinated patients.

Systematic evaluation of plasma signaling cascades by functional proteomics approaches: SARS-CoV-2 infection as model.

PURPOSE: Acute phase reactants (APRs) play a critical role in inflammation. The difference in their physiological functions or the different dynamic ranges of these proteins in plasma makes it difficult to detect them simultaneously and to use several of these proteins as a tool in clinical practice. EXPERIMENTAL DESIGN: A novel multiplex assay has been designed and optimized to carry out a high-throughput and simultaneous screening of APRs, allowing the detection of each of them at the same time and in their corresponding dynamic range. RESULTS: Using Sars-CoV-2 infection as a model, it has been possible to profile different patterns of acute phase proteins that vary significantly between healthy and infected patients. In addition, severity profiles (acute respiratory distress syndrome and sepsis) have been established. CONCLUSIONS AND CLINICAL RELEVANCE: Differential profiles in acute phase proteins can serve as a diagnostic and prognostic tool, among patient stratification. The design of this new platform for their simultaneous detection paves the way for them to be more extensive use in clinical practice.

ABCA1 gene variants regulate postprandial lipid metabolism in healthy men.

OBJECTIVE: Genetic variants of ABCA1, an ATP-binding cassette (ABC) transporter, have been linked to altered atherosclerosis progression and fasting lipid concentration, mainly high-density lipoproteins and apolipoprotein A1; however, results from different studies have been inconsistent. METHODS AND RESULTS: To further characterize the effects of ABCA1 variants in human postprandial lipid metabolism, we studied the influence of 3 single nucleotide polymorphisms (i27943 [rs2575875]; i48168 [rs4149272]; R219K [rs2230806]) in the postprandial lipemia of 88 normolipidemic young men who were given a fatty meal. For i27943 and i48168 single nucleotide polymorphisms, fasting and postprandial values of apolipoprotein A1 were higher and postprandial lipemia was much lower in homozygotes for the major alleles, total triglycerides in plasma, and large triglyceride-rich lipoprotein triglycerides. These persons also showed a higher apolipoprotein A1/apolipoprotein B ratio. Major allele homozygotes for i48168 and i27943 showed additionally higher high-density lipoproteins and lower postprandial apolipoprotein B. CONCLUSION: Our work shows that major allele homozygotes for ABCA1 single nucleotide polymorphisms i27943 and i48168 have a lower postprandial response as compared to minor allele carriers. This finding may further characterize the role of ABCA1 in lipid metabolism.