Mediterranean and low-fat diets are effective in the primary prevention of cardiovascular disease. We did a long-term randomised trial to compare the effects of these two diets in secondary ...prevention of cardiovascular disease.
The CORDIOPREV study was a single-centre, randomised clinical trial done at the Reina Sofia University Hospital in Córdoba, Spain. Patients with established coronary heart disease (aged 20–75 years) were randomly assigned in a 1:1 ratio by the Andalusian School of Public Health to receive a Mediterranean diet or a low-fat diet intervention, with a follow-up of 7 years. Clinical investigators (physicians, investigators, and clinical endpoint committee members) were masked to treatment assignment; participants were not. A team of dietitians did the dietary interventions. The primary outcome (assessed by intention to treat) was a composite of major cardiovascular events, including myocardial infarction, revascularisation, ischaemic stroke, peripheral artery disease, and cardiovascular death. This study is registered with ClinicalTrials.gov, NCT00924937.
From Oct 1, 2009, to Feb 28, 2012, a total of 1002 patients were enrolled, 500 (49·9%) in the low-fat diet group and 502 (50·1%) in the Mediterranean diet group. The mean age was 59·5 years (SD 8·7) and 827 (82·5%) of 1002 patients were men. The primary endpoint occurred in 198 participants: 87 in the Mediterranean diet group and 111 in the low-fat group (crude rate per 1000 person-years: 28·1 95% CI 27·9–28·3 in the Mediterranean diet group vs 37·7 37·5–37·9 in the low-fat group, log-rank p=0·039). Multivariable-adjusted hazard ratios (HRs) of the different models ranged from 0·719 (95% CI 0·541–0·957) to 0·753 (0·568–0·998) in favour of the Mediterranean diet. These effects were more evident in men, with primary endpoints occurring in 67 (16·2%) of 414 men in the Mediterranean diet group versus 94 (22·8%) of 413 men in the low-fat diet group (multiadjusted HR 0·669 95% CI 0·489–0·915, log-rank p=0·013), than in 175 women for whom no difference was found between groups.
In secondary prevention, the Mediterranean diet was superior to the low-fat diet in preventing major cardiovascular events. Our results are relevant to clinical practice, supporting the use of the Mediterranean diet in secondary prevention.
Fundacion Patrimonio Comunal Olivarero; Fundacion Centro para la Excelencia en Investigacion sobre Aceite de Oliva y Salud; local, regional, and national Spanish Governments; European Union.
Glutamic acid decarboxylase 65 antibodies (anti-GAD65) have been found in patients with late-onset chronic temporal lobe epilepsy (TLE). No prior neuroimaging studies have addressed how they affect ...hippocampal volume and shape and how they relate to cognitive abnormalities. We aimed to investigate both brain structure and function in patients with isolated TLE and high anti-GAD65 levels (RIA ≥ 2000 U/ml) compared to 8 non-immune mesial TLE (niTLE) and 8 healthy controls (HC). Hippocampal subfield volume properties were correlated with the duration of the disease and cognitive test scores. The affected hippocampus of GAD-TLE patients showed no volume changes to matched HC whereas niTLE volumes were significantly smaller. Epilepsy duration in GAD-TLE patients correlated negatively with volumes in the presubiculum, subiculum, CA1, CA2-3, CA4, molecular layer and granule cell-molecular layer of the dentate nucleus. We found differences by advanced vertex-wise shape analysis in the anterior hippocampus of the left GAD-TLE compared to HC whereas left niTLE showed bilateral posterior hippocampus deformation. Verbal deficits were similar in GAD-TLE and niTLE but did not correlate to volume changes. These data might suggest a distinct expression of hippocampal structural and functional abnormalities based on the immune response.
A method for the rational design of molecularly imprinted polymers with catalytic activity (MICs) that mimic hemeproteins is described. Density Functional Theory calculations applied to the ...pre-polymerization adduct and to a possible reaction intermediate allow to choose the best functional monomer that builds up the active sites. This functional monomer should stabilize both relevant stages, the first one in an adequate porogenic solvent and the second one in the aqueous reaction medium. In this work, a MIC was synthesized to catalyze the oxidation of 2,4,6-trichlorophenol (TCP), the substrate and template molecule. A hemin molecule was used as the catalytic centre and four functional monomers and six solvents were tested. According to the theoretical predictions, methacrylamide and 4-vinylpyridine MIPs successfully mimic the recently discovered ability of Chloroperoxidase (CPO) to catalyze the oxidative dechlorination of TCP in batch analysis. They exhibit good catalytic properties and substrate selectivity.
Display omitted
Joubert syndrome (JS) is a clinically and genetically heterogeneous genetic disorder. To date, 40 JS‐causing genes have been reported and CPLANE1 is one of the most frequently mutated, with biallelic ...pathogenic missense and truncating variants explaining up to 14% of JS cases. We present a case of JS diagnosed after the identification of a novel biallelic intragenic duplication of exons 20–46 of CPLANE1. The quadruplication was identified by short‐read sequencing and copy number variant analysis and confirmed in tandem by long PCR with the breakpoints defined by a nanopore‐based long‐read sequencing approach. Based on the genetic findings and the clinical presentation of the patient, a brain MRI was ordered, evidencing the molar tooth sign, which confirmed the diagnosis of JS in the patient. This is, to the best of our knowledge, the first report of an intragenic duplication in this gene as the potential molecular mechanism of JS.
Purpose
The main characteristics of mechanically ventilated ARDS patients affected with COVID-19, and the adherence to lung-protective ventilation strategies are not well known. We describe ...characteristics and outcomes of confirmed ARDS in COVID-19 patients managed with invasive mechanical ventilation (MV).
Methods
This is a multicenter, prospective, observational study in consecutive, mechanically ventilated patients with ARDS (as defined by the Berlin criteria) affected with with COVID-19 (confirmed SARS-CoV-2 infection in nasal or pharyngeal swab specimens), admitted to a network of 36 Spanish and Andorran intensive care units (ICUs) between March 12 and June 1, 2020. We examined the clinical features, ventilatory management, and clinical outcomes of COVID-19 ARDS patients, and compared some results with other relevant studies in non-COVID-19 ARDS patients.
Results
A total of 742 patients were analysed with complete 28-day outcome data: 128 (17.1%) with mild, 331 (44.6%) with moderate, and 283 (38.1%) with severe ARDS. At baseline, defined as the first day on invasive MV, median (IQR) values were: tidal volume 6.9 (6.3–7.8) ml/kg predicted body weight, positive end-expiratory pressure 12 (11–14) cmH
2
O. Values of respiratory system compliance 35 (27–45) ml/cmH
2
O, plateau pressure 25 (22–29) cmH
2
O, and driving pressure 12 (10–16) cmH
2
O were similar to values from non-COVID-19 ARDS patients observed in other studies. Recruitment maneuvers, prone position and neuromuscular blocking agents were used in 79%, 76% and 72% of patients, respectively. The risk of 28-day mortality was lower in mild ARDS hazard ratio (RR) 0.56 (95% CI 0.33–0.93),
p
= 0.026 and moderate ARDS hazard ratio (RR) 0.69 (95% CI 0.47–0.97),
p
= 0.035 when compared to severe ARDS. The 28-day mortality was similar to other observational studies in non-COVID-19 ARDS patients.
Conclusions
In this large series, COVID-19 ARDS patients have features similar to other causes of ARDS, compliance with lung-protective ventilation was high, and the risk of 28-day mortality increased with the degree of ARDS severity.
BackgroundMalnutrition is a recurring problem that has become more relevant in recent years. The aim of this study is to assess the risk of malnutrition and nutritional status on admission and its ...evolution until discharge in patients aged 65 and over admitted to medical and surgical hospitalization units in hospitals of the Spanish National Health System.MethodsProspective observational study to be carried out in the medical-surgical hospitalization units of 9 public hospitals between 01/09/2022 and 31/12/2024. Using consecutive sampling, a total of 4077 patients will be included (453 in each hospital). Variables included are related to the care process, functionality, cognition and comorbidity, risk profile, nutritional status and dysphagia; as well as frailty, dietary quality and contextual variables. The incidence of risk of malnutrition, undernutrition and dysphagia during the care process and at discharge will be calculated. The association with risk factors will be studied with logistic regression models and multivariate Cox regression models. In addition, an analysis of participants' satisfaction with food services will be carried out. The study was approved by the Ethics and Research Committee on 30/09/2020, approved for funding on 02/12/2021 and with registration number RBR-5jnbyhk in the Brazilian clinical trials database (ReBEC) for observational studies.DiscussionSome studies address nutritional status or dysphagia in older people in various care settings. However, there is a lack of large sample studies including both processes of the impact of hospitalization. The results of the project will provide information on the incidence and prevalence of both pathologies in the study subjects, their associated factors and their relationship with the average length of stay, mortality and early readmission. In addition, early detection of a problem such as malnutrition related to the disease and/or dysphagia during a hospital stay will favor the action of professionals to resolve both pathologies and improve the health status of patients.
The Snail family of transcription factors has previously been implicated in the differentiation of epithelial cells into mesenchymal cells (epithelial-mesenchymal transitions) during embryonic ...development. Epithelial-mesenchymal transitions are also determinants of the progression of carcinomas, occurring concomitantly with the cellular acquisition of migratory properties following downregulation of expression of the adhesion protein E-cadherin. Here we show that mouse Snail is a strong repressor of transcription of the E-cadherin gene. Epithelial cells that ectopically express Snail adopt a fibroblastoid phenotype and acquire tumorigenic and invasive properties. Endogenous Snail protein is present in invasive mouse and human carcinoma cell lines and tumours in which E-cadherin expression has been lost. Therefore, the same molecules are used to trigger epithelial-mesenchymal transitions during embryonic development and in tumour progression. Snail may thus be considered as a marker for malignancy, opening up new avenues for the design of specific anti-invasive drugs.
The need for novel biomarkers that could aid in non-small cell lung cancer (NSCLC) detection, together with the relevance of Matrix Metalloproteases (MMPs) -1, -2, -7, -9 and -10 in lung ...tumorigenesis, prompted us to assess the diagnostic usefulness of these MMPs and the Tissue Inhibitor of Metalloproteinase (TIMP) -1 in NSCLC patients.
Markers were evaluated in an initial study cohort (19 NSCLC cases and 19 healthy controls). Those that better performed were analyzed in a larger sample including patients with benign lung diseases. Serum MMPs and TIMP-1 were determined by multiplexed immunoassays. Logistic regression was employed for multivariate analysis of biomarker combinations.
MMPs and TIMP-1 were elevated in the serum of NSCLC patients compared to healthy controls. MMP-1, -7 and -9 performed at best and were further evaluated in the sample including benign pathologies, corroborating the superiority of MMP-9 in NSCLC discrimination, also at early-stage NSCLC. The optimal diagnostic value was obtained with the model including MMP-9, gender, age and smoking history, that demonstrated an AUC of 0.787, 85.54% sensitivity and 64.89% specificity.
Our results suggest that MMP-9 is a potential biomarker for NSCLC diagnosis and its combined measurement with other biomarkers could improve NSCLC detection.
A methodology based on density functional theory calculations for the design of molecularly imprinted polymers (MIPs) is described. The method allows the rational choice of the most suitable monomer ...and polymerization solvent among a set of chemicals traditionally used in MIP formulations for the molecular imprinting of a given template. It is based on the comparison of the stabilization energies of the prepolymerization adducts between the template and different functional monomers. The effect of the polymerization solvent is included using the polarizable continuum model. A voltammetric sensor for homovanillic acid was constructed using different MIPs as recognition element, confirming that the solvent (toluene) and functional monomer (methacrylic acid) selected according to the theoretical predictions lead to the most efficient molecular recognition sensing phase. With the voltammetric sensor prepared using the MIP designed according to the theoretical predictions, a linear response for concentrations of homovanillic acid between 5 x 10(-8) and 1 x 10(-5) M can be obtained. The limit of detection is 7 x 10(-9) M. The selectivity obtained for homovanillic acid over other structurally related compounds buttresses the validity of this strategy of design.
The transcription factor NRF2 is a master regulator of cellular antioxidant and detoxification responses, but it also regulates other processes such as autophagy and pluripotency. In human embryonic ...stem cells (hESCs), NRF2 antagonizes neuroectoderm differentiation, which only occurs after NRF2 is repressed via a Primary Cilia-Autophagy-NRF2 (PAN) axis. However, the functional connections between NRF2 and primary cilia, microtubule-based plasma membrane protrusions that function as cellular antennae, remain poorly understood. For instance, nothing is known about whether NRF2 affects cilia, or whether cilia regulation of NRF2 extends beyond hESCs. Here, we show that NRF2 and primary cilia reciprocally regulate each other. First, we demonstrate that fibroblasts lacking primary cilia have higher NRF2 activity, which is rescued by autophagy-activating mTOR inhibitors, indicating that the PAN axis also operates in differentiated cells. Furthermore, NRF2 controls cilia formation and function. NRF2-null cells grow fewer and shorter cilia and display impaired Hedgehog signaling, a cilia-dependent pathway. These defects are not due to increased oxidative stress or ciliophagy, but rather to NRF2 promoting expression of multiple ciliogenic and Hedgehog pathway genes. Among these, we focused on GLI2 and GLI3, the transcription factors controlling Hh pathway output. Both their mRNA and protein levels are reduced in NRF2-null cells, consistent with their gene promoters containing consensus ARE sequences predicted to bind NRF2. Moreover, GLI2 and GLI3 fail to accumulate at the ciliary tip of NRF2-null cells upon Hh pathway activation. Given the importance of NRF2 and ciliary signaling in human disease, our data may have important biomedical implications.
PDF
