Imaging of subclinical atherosclerosis improves cardiovascular risk prediction on top of traditional risk factors. However, cardiovascular imaging is not universally available. This work aims to ...identify circulating proteins that could predict subclinical atherosclerosis.
Hypothesis-free proteomics was used to analyze plasma from 444 subjects from PESA cohort study (222 with extensive atherosclerosis on imaging, and 222 matched controls) at two timepoints (three years apart) for discovery, and from 350 subjects from AWHS cohort study (175 subjects with extensive atherosclerosis on imaging and 175 matched controls) for external validation. A selected three-protein panel was further validated by immunoturbidimetry in the AWHS population and in 2999 subjects from ILERVAS cohort study.
PIGR, IGHA2, APOA, HPT and HEP2 were associated with subclinical atherosclerosis independently from traditional risk factors at both timepoints in the discovery and validation cohorts. Multivariate analysis rendered a potential three-protein biomarker panel, including IGHA2, APOA and HPT. Immunoturbidimetry confirmed the independent associations of these three proteins with subclinical atherosclerosis in AWHS and ILERVAS. A machine-learning model with these three proteins was able to predict subclinical atherosclerosis in ILERVAS (AUC 95%CI:0.73 0.70–0.74, p < 1 × 10−99), and also in the subpopulation of individuals with low cardiovascular risk according to FHS 10-year score (0.71 0.69–0.73, p < 1 × 10−69).
Plasma levels of IGHA2, APOA and HPT are associated with subclinical atherosclerosis independently of traditional risk factors and offers potential to predict this disease. The panel could improve primary prevention strategies in areas where imaging is not available.
This study was supported by competitive grants from the Spanish Ministry of Science, Innovation and Universities (BIO2015-67580-P, PGC2018-097019-B-I00, PID2019-106814RB-I00 and SAF2016-80843-R), through the Carlos III Institute of Health-Fondo de Investigacion Sanitaria grant PRB3 (IPT17/0019 - ISCIII-SGEFI / ERDF, ProteoRed), CIBERCV and CIBERDEM, the Fundacio MaratoTV3 (grant 122/C/2015) and “la Caixa” Banking Foundation (project HR17-00247). The PESA study is co-funded equally by the Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain, and Banco Santander, Madrid, Spain. The ILERVAS study was funded by the Diputacio de Lleida. The study also receives funding from the Instituto de Salud Carlos III (PI15/02019; PI18/00610; RD16/0009) and the FEDER funds. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia, Innovacion y Universidades (MCNU) and the Pro CNIC Foundation.
The elderly population living in nursing homes is particularly vulnerable to COVID-19 although individual susceptibility to SARS-CoV-2 infection may be related to the host microbiota. The objective ...of this work was to investigate the effect of Ligilactobacillus salivarius MP101 on the functional (Barthel index), cognitive (GDS/FAST), and nutritional (MNA) status as well as on the nasal and fecal inflammatory profiles of elderly residents living in a nursing home that is highly affected by COVID-19. A total of 25 residents participated in the trial, which involved the daily ingestion of a dairy product (L. salivarius MP101: 9.3 log10 CFU per unit) for 4 months. Nasal and fecal samples were analyzed for 37 immune factors at recruitment and at the end of the study. After the trial, no change in the GDS/FAST scores were found but, in contrast, the values for the Barthel index and the MNA score improved significantly. The concentrations of some immune factors changed significantly after the trial, including a decrease in the concentrations of BAFF/TNFSF13B, APRIL/TNFSF13, IL8, IL31, osteopontin, sTNF-R1, and sTNF-R2, and an increase in chitinase 3-like 1, IL19, IL35, and pentraxin 3 was also observed. In conclusion, L. salivarius MP101 seems to be a promising strain for improving or maintaining health in this highly vulnerable population.
Medical differential diagnosis (ddx) is based on the estimation of multiple distinct parameters in order to determine the most probable diagnosis. Building an intelligent medical differential ...diagnosis system implies using a number of knowledge-based technologies which avoid ambiguity, such as ontologies representing specific structured information, but also strategies such as computation of probabilities of various factors and logical inference, whose combination outperforms similar approaches. This paper presents ODDIN, an ontology-driven medical diagnosis system which applies the aforementioned strategies. The architecture and proof-of-concept implementation is described, and results of the evaluation are discussed.
Primary mitochondrial diseases result from mutations in nuclear DNA (nDNA) or mitochondrial DNA (mtDNA) genes, encoding proteins crucial for mitochondrial structure or function. Given that few ...disease-specific therapies are available for mitochondrial diseases, novel treatments to reverse mitochondrial dysfunction are necessary. In this work, we explored new therapeutic options in mitochondrial diseases using fibroblasts and induced neurons derived from patients with mutations in the
gene. This gene encodes the essential mitochondrial translation elongation factor G1 involved in mitochondrial protein synthesis. Due to the severe mitochondrial defect, mutant
fibroblasts cannot survive in galactose medium, making them an ideal screening model to test the effectiveness of pharmacological compounds. We found that the combination of polydatin and nicotinamide enabled the survival of mutant
fibroblasts in stress medium. We also demonstrated that polydatin and nicotinamide upregulated the mitochondrial Unfolded Protein Response (mtUPR), especially the SIRT3 pathway. Activation of mtUPR partially restored mitochondrial protein synthesis and expression, as well as improved cellular bioenergetics. Furthermore, we confirmed the positive effect of the treatment in
mutant induced neurons obtained by direct reprogramming from patient fibroblasts. Overall, we provide compelling evidence that mtUPR activation is a promising therapeutic strategy for
mutations.
La Banya spit, located at the south of the River Ebro Delta, is a sandy formation, developed by annexation of bars forming successive beach ridges, which are oriented and modeled by the eastern and ...southern waves. The initial ridges run parallel to the coastline, and above them small dunes developed, the crests of which are oriented by dominant winds, forming foredune ridges and barchans. This study attempted to test a number of techniques in order to understand the dune dynamic on this coastal spit between 2004 and 2012: LiDAR data were used to reconstruct changes to the surface and volume of the barchan dunes and foredunes; ground-penetrating radar was applied to obtain an image of their internal structure, which would help to understand their recent evolution. GPS data taken on the field, together with application of GIS techniques, made possible the combination of results and their comparison. The results showed a different trend between the barchan dunes and the foredunes. While the barchan dunes increased in area and volume between 2004 and 2012, the foredunes lost thickness. This was also reflected in the radargrams: the barchan dunes showed reflectors related to the growth of the foresets while those associated with foredunes presented truncations associated with storm events. However, the global balance of dune occupation for the period 2004–2012 was positive.
Infectious mastitis is a common condition among lactating women, with staphylococci and streptococci being the main aetiological agents. In this context, some lactobacilli strains isolated from ...breast milk appear to be particularly effective for treating mastitis and, therefore, constitute an attractive alternative to antibiotherapy. A 1H NMR-based metabolomic approach was applied to detect metabolomic differences after consuming a probiotic strain (Lactobacillus salivarius PS2) in women with mastitis. 24h urine of women with lactational mastitis was collected at baseline and after 21 days of probiotic (PB) administration. Multivariate analysis (OSC-PLS-DA and hierarchical clustering) showed metabolome differences after PB treatment. The discriminant metabolites detected at baseline were lactose, and ibuprofen and acetaminophen (two pharmacological drugs commonly used for mastitis pain), while, after PB intake, creatine and the gut microbial co-metabolites hippurate and TMAO were detected. In addition, a voluntary desertion of the pharmacological drugs ibuprofen and acetaminophen was observed after probiotic administration. The application of NMR-based metabolomics enabled the identification of the overall effects of probiotic consumption among women suffering from mastitis and highlighted the potential of this approach in evaluating the outcomes of probiotics consumption. To our knowledge, this is the first time that this approach has been applied in women with mastitis during lactation.
Currently, there continues to be a lack of evidence regarding outcomes associated with device-based therapy for ventricular arrhythmias in elderly patients, even more in primary-prevention ...indications. We aimed to describe the follow-up in terms of efficacy and safety of implantable cardioverter-defibrillator (ICD) therapy in a large cohort of elderly patients.
Retrospective multicentre study performed in 15 Spanish hospitals. Consecutive patients referred for ICD implantation before 2011 were included. One hundred and sixty-two of 1174 patients (13.8%) ≥75 years were considered as 'elderly'. When compared with those patients <75, this subgroup presented more co-morbid conditions, including hypertension, chronic obstructive pulmonary disease , and renal failure, and more previous hospitalizations due to heart failure (HF). During a mean follow-up of 104.4 ± 3.3 months, 162 patients (14%) died, 120 in the younger age (12.4%), and 42 (24.4%) in the elderly. Kaplan-Meier analysis showed an increased probability of death with increasing age (17, 24, 28, and 69% at 12, 24, 48, and 60 months of follow-up in the elderly group). There was neither difference regarding the rate of appropriate nor inappropriate ICD intervention.
In a real-world scenario, elderly patients comprise ∼15% of ICD implantations for primary prevention of sudden cardiac death (SCD). Although the rate of appropriate therapy is similar between groups, the benefit of ICD is attenuated for a major increase in mortality risk among those patients ≥75 years at the moment of device implantation.
Cardiovascular diseases stem from modifiable risk factors. Peer support is a proven strategy for many chronic illnesses. Randomized trials assessing the efficacy of this strategy for global ...cardiovascular risk factor modification are lacking.
This study assessed the hypothesis that a peer group strategy would help improve healthy behaviors in individuals with cardiovascular risk factors.
A total of 543 adults 25 to 50 years of age with at least 1 risk factor were recruited; risk factors included hypertension (20%), overweight (82%), smoking (31%), and physical inactivity (81%). Subjects were randomized 1:1 to a peer group-based intervention group (IG) or a self-management control group (CG) for 12 months. Peer-elected leaders moderated monthly meetings involving role-play, brainstorming, and activities to address emotions, diet, and exercise. The primary outcome was mean change in a composite score related to blood pressure, exercise, weight, alimentation, and tobacco (Fuster-BEWAT score, 0 to 15). Multilevel models with municipality as a cluster variable were applied to assess differences between groups.
Participants' mean age was 42 ± 6 years, 71% were female, and they had a mean baseline Fuster-BEWAT score of 8.42 ± 2.35. After 1 year, the mean scores were significantly higher in the IG (n = 277) than in the CG (n = 266) (IG mean score: 8.84; 95% confidence interval (CI): 8.37 to 9.32; CG mean score: 8.17; 95% CI: 7.55 to 8.79; p = 0.02). The increase in the overall score was significantly larger in the IG compared with the CG (difference: 0.75; 95% CI: 0.32 to 1.18; p = 0.02). The mean improvement in the individual components was uniformly greater in the IG, with a significant difference for the tobacco component.
The peer group intervention had beneficial effects on cardiovascular risk factors, with significant improvements in the overall score and specifically on tobacco cessation. A follow-up assessment will be performed 1 year after the final assessment reported here to determine long-term sustainability of the improvements associated with peer group intervention. (Peer-Group-Based Intervention Program Fifty-Fifty; NCT02367963).
Uncontrolled inflammation following COVID-19 infection is an important characteristic of the most seriously ill patients. The present study aims to describe the clusters of inflammation in COVID-19 ...and to analyze their prognostic role. This is a retrospective observational study including 15,691 patients with a high degree of inflammation. They were included in the Spanish SEMI-COVID-19 registry from March 1, 2020 to May 1, 2021. The primary outcome was in-hospital mortality. Hierarchical cluster analysis identified 7 clusters. C1 is characterized by lymphopenia, C2 by elevated ferritin, and C3 by elevated LDH. C4 is characterized by lymphopenia plus elevated CRP and LDH and frequently also ferritin. C5 is defined by elevated CRP, and C6 by elevated ferritin and D-dimer, and frequently also elevated CRP and LDH. Finally, C7 is characterized by an elevated D-dimer. The clusters with the highest in-hospital mortality were C4, C6, and C7 (17.4% vs. 18% vs. 15.6% vs. 36.8% vs. 17.5% vs. 39.3% vs. 26.4%). Inflammation clusters were found as independent factors for in-hospital mortality. In detail and, having cluster C1 as reference, the model revealed a worse prognosis for all other clusters: C2 (OR = 1.30,
p
= 0.001), C3 (OR = 1.14,
p
= 0.178), C4 (OR = 2.28,
p
< 0.001), C5 (OR = 1.07,
p
= 0.479), C6 (OR = 2.29,
p
< 0.001), and C7 (OR = 1.28,
p
= 0.001). We identified 7 groups based on the presence of lymphopenia, elevated CRP, LDH, ferritin, and D-dimer at the time of hospital admission for COVID-19. Clusters C4 (lymphopenia + LDH + CRP), C6 (ferritin + D-dimer), and C7 (D-dimer) had the worst prognosis in terms of in-hospital mortality.
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