👤 Ricard Ferrer

Individuals with schizophrenia spectrum disorders experience impairments across multiple domains, including cognition, quality of life, and social functioning. Structured exercise interventions may improve these outcomes. We hypothesised that aerobic and combined (aerobic plus resistance) exercise programs would enhance cognitive function, reduce symptom severity, and improve well-being. A PRISMA-guided search of PubMed, EMBASE, PsycINFO, Web of Science, SciELO, and ClinicalTrials.gov (2009-2024) identified 17 randomized controlled trials. Standardized mean differences (SMDs) were pooled using a random-effects model. Subgroup analyses examined age and gender. Risk of bias was assessed using RoB 2, publication bias with Egger's test, and certainty of evidence through GRADE. Structured exercise produced a moderate-to-large improvement in overall well-being (SMD = 0.68; 95% CI: 0.43-0.93; p < .001). Significant benefits were also observed in cognition (SMD = 0.59), symptom severity (SMD = 0.71), quality of life (SMD = 0.60), and social functioning (SMD = 0.55). Age and gender moderated treatment effects, with the strongest benefits in males and individuals aged 36-45. Sensitivity analyses confirmed the robustness of results. Mechanistic evidence suggests that improvements may be mediated through increased brain-derived neurotrophic factor (BDNF) and reduced inflammatory signaling. Structured exercise is an effective adjunctive intervention for schizophrenia spectrum disorders, improving psychiatric and functional outcomes beyond standard care. Findings support the integration of personalized, scalable exercise programs within routine psychiatric treatment. Show less

Alzheimer's disease (AD)'s multifactorial nature stresses the role of epigenetics in affecting different pathological pathways. We demonstrated that one-carbon metabolism epigenetically impacts AD-like phenotype. Here, we investigated the crosstalk between methylation and microRNAs in AD. We altered one-carbon metabolism to induce hypo- and hyper-methylation, in SK-N-BE neuroblastoma cells and TgCRND8 mice. miRNAs were profiled through a polymerase chain reaction array, then we focused on miR-29a expression and methylation of its genomic locus. Finally, we assessed miR-29a expression and methylation in the brain of AD subjects. MiR-29a was repressed in hypomethylating and expressed in hypermethylating conditions. The expression of miR-29a and of its target, BACE1, was inversely correlated. We demonstrated for the first time that miR-29a is modulated by one-carbon metabolism through DNA methylation, disclosing the molecular mechanisms regulating BACE1 expression in AD. These data confirm miR-29a's protective role in AD and support miR-29a as a potential biomarker for AD. Show less

Pathogenic variants in KANSL1 and 17q21.31 microdeletions are causative of Koolen-de Vries syndrome (KdVS), a neurodevelopmental syndrome with characteristic facial dysmorphia. Our previous work has shown that syndromic conditions caused by pathogenic variants in epigenetic regulatory genes have identifiable patterns of DNA methylation (DNAm) change: DNAm signatures or episignatures. Given the role of KANSL1 in histone acetylation, we tested whether variants underlying KdVS are associated with a DNAm signature. We profiled whole-blood DNAm for 13 individuals with KANSL1 variants, four individuals with 17q21.31 microdeletions, and 21 typically developing individuals, using Illumina's Infinium EPIC array. In this study, we identified a robust DNAm signature of 456 significant CpG sites in 8 individuals with KdVS, a pattern independently validated in an additional 7 individuals with KdVS. We also demonstrate the diagnostic utility of the signature and classify two KANSL1 VUS as well as four variants in individuals with atypical clinical presentation. Lastly, we investigated tissue-specific DNAm changes in fibroblast cells from individuals with KdVS. Collectively, our findings contribute to the understanding of the epigenetic landscape related to KdVS and aid in the diagnosis and classification of variants in this structurally complex genomic region. Show less

The search for new biomarkers that allow an early diagnosis in sepsis and predict its evolution has become a necessity in medicine. The objective of this study is to identify, through omics techniques, potential protein biomarkers that are expressed in patients with sepsis and their relationship with organ dysfunction and mortality. Prospective, observational and single-center study that included adult patients (≥ 18 years) who were admitted to a tertiary hospital and who met the criteria for sepsis. A mass spectrometry-based approach was used to analyze the plasma proteins in the enrolled subjects. Subsequently, using recursive feature elimination classification and cross-validation with a vector classifier, an association of these proteins with mortality and organ dysfunction was established. The protein-protein interaction network was analyzed with String software. 141 patients were enrolled in this study. Mass spectrometry identified 177 proteins. Of all of them, and by recursive feature elimination, nine proteins (GPX3, APOB, ORM1, SERPINF1, LYZ, C8A, CD14, APOC3 and C1QC) were associated with organ dysfunction (SOFA > 6) with an accuracy of 0.82 ± 0.06, precision of 0.85 ± 0.093, sensitivity 0.81 ± 0.10, specificity 0.84 ± 0.10 and AUC 0.82 ± 0.06. Twenty-two proteins (CLU, LUM, APOL1, SAA1, CLEBC3B, C8A, ITIH4, KNG1, AGT, C7, SAA2, APOH, HRG, AFM, APOE, APOC1, C1S, SERPINC1, IGFALS, KLKB1, CFB and BTD) were associated with mortality with an accuracy of 0.86 ± 0.05, a precision of 0.91 ± 0.05, a sensitivity of 0.91 ± 0.05, a specificity of 0.72 ± 0.17, and an area under the curve (AUC) of 0.81 ± 0.08 with a confidence interval of 95%. In sepsis there are proteomic patterns associated with organ dysfunction and mortality. Show less

Plasma apolipoprotein AIV (apo AIV) level has been shown to be a good marker of triglyceride changes after a high-fat diet. However, the distribution of apo AIV between apo B- and non-apo B-containing lipoproteins (Lp) during the postprandial state has not been described as well as the influence of obesity on this distribution. Our aim was to study the influence of parameters related to obesity and insulin resistance on the postprandial changes in apo AIV-containing Lp after a high-fat meal in obese women. Twenty-three overweight or obese women (body mass index [BMI] ranging from 29.1 and 64.0 kg.1 m(-2)), for whom blood samples were taken after fasting overnight, participated in the study. Thirteen of these obese women were given a fatty meal and, in this case, blood samples were taken at fast and 30 minutes, 1, 2, 4, and 6 hours after ingestion of the fat meal. Apo AIV-containing particle families, Lp B:AIVf (family [f] of particles containing at least apo B and apo AIV) and Lp AIV non-Bf (family [f] of particles containing apo AIV, but free of apo B) were quantified by sandwich enzyme-linked immunosorbent assay (ELISA). When fasting, Lp B:AIVf and Lp AIV non-Bf did not correlate with any of the parameters related to obesity and insulin resistance, if one excepts a positive correlation between HDL-cholesterol (HDL-C) and Lp AIV non-Bf. Postprandial lipemia was associated with a trend towards an increase in the plasma levels of apo AIV-containing Lp 6 hours after fat ingestion. The postprandial peak of Lp B:AIVf and Lp AIV non-Bf occurred 2 hours after the triglyceride peak. The distribution between apo B- and non-apo B-containing Lp did not change after ingestion of the fat meal, if one excepts a tendancy towards a lower ratio of bound and nonbound forms at 8 hours. Fasting plasma Lp B:AIVf concentration correlated with the area under the curve (AUC) of plasma triglycerides (beta = 0.11, P <.02). In a multivariate analysis, BMI (beta = 51.85, P <.001), fasting triglycerides (beta = 431.08, P <.01), and low-density lipoprotein-cholesterol (LDL-C) (beta = 2638.57, P <.005) were independent and positive determinants of the AUC of Lp AIV non-Bf, while waist circumference (beta = -23.94, P <.001), cholesterol (beta = -1655.02, P <.01), and systolic blood pressure (beta = -6.34, P <.05) were negative and independent determinants of this AUC. Fasting Lp B:AIVf may represent a good marker of the postprandial triglyceride increase in obese women. Changes in apo AIV concentrations in apo B- and non-apo B-containing Lp after a fat meal depend mainly on the degree of obesity rather than on insulin resistance. This effect is more obvious for Lp AIV non-Bf than for Lp B:AIVf. Show less

A reliable method for plasma would be useful to investigate the role of apolipoprotein (apo) AIV when associated with apo B-containing or triglyceride-rich lipoproteins. We used a sandwich ELISA to quantify lipoprotein B:AIV particles (Lp B:AIVf; lipoproteins containing at least apo B and apo AIV) in plasma. The method used microtiter plates coated with purified anti-apo B immunoglobulins that selectively retained apo B-containing particles. Lipoproteins containing both apo B and apo AIV were distinguished from those containing only apo B by use of a peroxidase-labeled anti-apo AIV antibody. These subspecies were revealed by ABTS reagent and further quantified by spectrophotometry. Results were expressed in mg/L apo AIV associated with apo B. This method was applied to samples with different cholesterol and triglyceride concentrations. The developed sandwich ELISA method identified and quantified Lp B:AIVf in plasma samples. Within- and between-run CVs were approximately 10%, and analytical recoveries were 95-107%. Results were not significantly influenced by addition of triglycerides or by storage at -20 degrees C (up to 9 months). Under these conditions, plasma Lp B:AIVf concentrations were statistically higher in hypercholesterolemic and mixed hyperlipidemic individuals (53 +/- 13 mg/L; P <0.001 and 70 +/- 18 mg/L; P <0.001, respectively) than in normolipidemic individuals (43 +/- 12 mg/L). Lp B:AIVf concentration appeared to be well correlated with total cholesterol, triglycerides, LDL-cholesterol, and apo B. These results were in contrast to total apo AIV, which was not different between dyslipidemic and normolipidemic individuals. The developed ELISA method for Lp B:AIVf in plasma combines specificity, reliability, and speed. The increase in Lp B:AIVf concentrations in various dyslipidemic states, together with a lack of change in total apo AIV concentrations, suggests a redistribution of apo AIV toward apo B-containing lipoproteins when these lipoproteins accumulate. Show less