Identification of Urine Metabolic Markers of Stroke Risk Using Untargeted Nuclear Magnetic Resonance Analysis.

Stroke remains the second leading cause of mortality worldwide, and the third leading cause of death and morbidity combined, affecting more than 12 million people every year. Stroke pathophysiology results from complex interactions of several risk factors related to age, family history, gender, lifestyle, and the presence of cardiovascular and metabolic diseases. Despite all the evidence, it is not possible to fully prevent stroke onset. In recent years, there has been an exploration of innovative methodologies for metabolite analysis aimed at identifying novel stroke biomarkers. Utilizing Nuclear Magnetic Resonance (NMR) spectroscopy, we investigated small molecule variations in urine across different stages of stroke risk. The Framingham Stroke Risk Score was used in people over 63 years of age living in long-term care facilities (LTCFs) to calculate the probability of suffering a stroke: low stroke risk (LSR, control), moderate stroke risk (MSR), and high stroke risk (HSR). Univariate statistical analysis showed that urinary 4-hydroxyphenylacetate levels increased while glycolate levels decreased across the different stroke risk groups, from the LSR to the HSR groups. Trimethylamine N-oxide (TMAO) had average concentration values that were significantly higher in elderly people in the HSR group, while trigonelline levels were significantly lower in the MSR group. These metabolic markers can be used for early detection and to differentiate stages of stroke risk more efficiently.

Preovulatory follicular fluid secretome added to in vitro maturation medium influences the metabolism of equine cumulus-oocyte complexes.

BACKGROUND: In vitro embryo production is a highly demanded reproductive technology in horses, which requires the recovery (in vivo or post-mortem) and in vitro maturation (IVM) of oocytes. Oocytes subjected to IVM exhibit poor developmental competence compared to their in vivo counterparts, being this related to a suboptimal composition of commercial maturation media. The objective of this work was to study the effect of different concentrations of secretome obtained from equine preovulatory follicular fluid (FF) on cumulus-oocyte complexes (COCs) during IVM. COCs retrieved in vivo by ovum pick up (OPU) or post-mortem from a slaughterhouse (SLA) were subjected to IVM in the presence or absence of secretome (Control: 0 µg/ml, S20: 20 µg/ml or S40: 40 µg/ml). After IVM, the metabolome of the medium used for oocyte maturation prior (Pre-IVM) and after IVM (Post-IVM), COCs mRNA expression, and oocyte meiotic competence were analysed. RESULTS: IVM leads to lactic acid production and an acetic acid consumption in COCs obtained from OPU and SLA. However, glucose consumption after IVM was higher in COCs from OPU when S40 was added (Control Pre-IVM vs. S40 Post-IVM: 117.24 ± 7.72 vs. 82.69 ± 4.24; Mean µM ± SEM; p < 0.05), while this was not observed in COCs from SLA. Likewise, secretome enhanced uptake of threonine (Control Pre-IVM vs. S20 Post-IVM vs. S40 Post-IVM: 4.93 ± 0.33 vs. 3.04 ± 0.25 vs. 2.84 ± 0.27; Mean µM ± SEM; p < 0.05) in COCs recovered by OPU. Regarding the relative mRNA expression of candidate genes related to metabolism, Lactate dehydrogenase A (LDHA) expression was significantly downregulated when secretome was added during IVM at 20-40 µg/ml in OPU-derived COCs (Control vs. S20 vs. S40: 1.77 ± 0.14 vs. 1 ± 0.25 vs. 1.23 ± 0.14; fold change ± SEM; p < 0.05), but not in SLA COCs. CONCLUSIONS: The addition of secretome during in vitro maturation (IVM) affects the gene expression of LDHA, glucose metabolism, and amino acid turnover in equine cumulus-oocyte complexes (COCs), with diverging outcomes observed between COCs retrieved using ovum pick up (OPU) and slaughterhouse-derived COCs (SLA).

Characterization of preovulatory follicular fluid secretome and its effects on equine oocytes during in vitro maturation.

In vitro maturation (IVM) of oocytes is clinically used in horses to produce blastocysts but current conditions used for horses are suboptimal. We analyzed the composition of equine preovulatory follicular fluid (FF) secretome and tested its effects on meiotic competence and gene expression in oocytes subjected to IVM. Preovulatory FF was obtained, concentrated using ultrafiltration with cut-off of 10 kDa, and stored at -80 °C. The metabolic and proteomic composition was analyzed, and its ultrastructural composition was assessed by cryo-transmission microscopy. Oocytes obtained post-mortem or by ovum pick up (OPU) were subjected to IVM in the absence (control) or presence of 20 or 40 µg/ml (S20 or S40) of secretome. Oocytes were then analyzed for chromatin configuration or snap frozen for gene expression analysis. Proteomic analysis detected 255 proteins in the Equus caballus database, mostly related to the complement cascade and cholesterol metabolism. Metabolomic analysis yielded 14 metabolites and cryo-transmission electron microscopy analysis revealed the presence of extracellular vesicles (EVs). No significant differences were detected in maturation rates among treatments. However, the expression of GDF9 and BMP15 significantly increased in OPU-derived oocytes compared to post-mortem oocytes (fold increase ± SEM: 9.4 ± 0.1 vs. 1 ± 0.5 for BMP15 and 9.9 ± 0.3 vs. 1 ± 0.5 for GDF9, respectively; p < 0.05). Secretome addition increased the expression of TNFAIP6 in S40 regardless of the oocyte source. Further research is necessary to fully understand whether secretome addition influences the developmental competence of equine oocytes.

Metabolomics as a powerful tool for diagnostic, pronostic and drug intervention analysis in COVID-19.

COVID-19 currently represents one of the major health challenges worldwide. Albeit its infectious character, with onset affectation mainly at the respiratory track, it is clear that the pathophysiology of COVID-19 has a systemic character, ultimately affecting many organs. This feature enables the possibility of investigating SARS-CoV-2 infection using multi-omic techniques, including metabolomic studies by chromatography coupled to mass spectrometry or by nuclear magnetic resonance (NMR) spectroscopy. Here we review the extensive literature on metabolomics in COVID-19, that unraveled many aspects of the disease including: a characteristic metabotipic signature associated to COVID-19, discrimination of patients according to severity, effect of drugs and vaccination treatments and the characterization of the natural history of the metabolic evolution associated to the disease, from the infection onset to full recovery or long-term and long sequelae of COVID.

Results of the Spanish National Polytrauma Registry. Where are we and where are we heading?

INTRODUCTION: In 2017, the Spanish National Polytrauma Registry (SNPR) was initiated in Spain with the goal to improve the quality of severe trauma management and evaluate the use of resources and treatment strategies. The objective of this study is to present the data obtained with the SNPR since its inception. METHODS: We conducted an observational study with prospective data collection from the SNPR. The trauma patients included were over 14 years of age, with ISS ≥ 15 or penetrating mechanism of injury, from a total of 17 tertiary hospitals in Spain. RESULTS: From 1/1/17 to 1/1/22, 2069 trauma patients were registered. The majority were men (76.4%), with a mean age of 45 years, mean ISS 22.8, and mortality 10.2%. The most common mechanism of injury was blunt trauma (80%), the most frequent being motorcycle accident (23%). Penetrating trauma was presented in 12% of patients, stab wounds being the most common (84%). On hospital arrival, 16% of patients were hemodynamically unstable. The massive transfusion protocol was activated in 14% of patients, and 53% underwent surgery. Median hospital stay was 11 days, while 73.4% of patients required intensive care unit (ICU) admission, with a median ICU stay of 5 days. CONCLUSIONS: Trauma patients registered in the SNPR are predominantly middle-aged males who experience blunt trauma with a high incidence of thoracic injuries. Early addressed detection and treatment of these kind of injuries would probably improve the quality of trauma care in our environment.

An NMR-Based Model to Investigate the Metabolic Phenoreversion of COVID-19 Patients throughout a Longitudinal Study.

After SARS-CoV-2 infection, the molecular phenoreversion of the immunological response and its associated metabolic dysregulation are required for a full recovery of the patient. This process is patient-dependent due to the manifold possibilities induced by virus severity, its phylogenic evolution and the vaccination status of the population. We have here investigated the natural history of COVID-19 disease at the molecular level, characterizing the metabolic and immunological phenoreversion over time in large cohorts of hospitalized severe patients (n = 886) and non-hospitalized recovered patients that self-reported having passed the disease (n = 513). Non-hospitalized recovered patients do not show any metabolic fingerprint associated with the disease or immune alterations. Acute patients are characterized by the metabolic and lipidomic dysregulation that accompanies the exacerbated immunological response, resulting in a slow recovery time with a maximum probability of around 62 days. As a manifestation of the heterogeneity in the metabolic phenoreversion, age and severity become factors that modulate their normalization time which, in turn, correlates with changes in the atherogenesis-associated chemokine MCP-1. Our results are consistent with a model where the slow metabolic normalization in acute patients results in enhanced atherosclerotic risk, in line with the recent observation of an elevated number of cardiovascular episodes found in post-COVID-19 cohorts.

Corpus callosum size, hypnotic susceptibility and empathy in women with alleged mediumship: a controlled study.

AIM: Evidence indicates that highly hypnotizable subjects may have larger area of the rostrum of the corpus callosum (CC). Mediumship can be defined as the alleged ability to communicate regularly with deceased personalities, and self-hypnosis is postulated as an underlying mechanism for this ability. Therefore, we aimed to investigate the CC area, hypnotic susceptibility, self-reported dissociation, and empathy in alleged mediums in comparison with healthy, non-medium controls. METHODS: The study sample consisted of 16 Spiritist mediums (medium group (MG)) and 16 non-medium controls. Magnetic resonance imaging scans were performed to measure the CC areas (total and subdivisions). The Harvard Group Scale of Hypnotic Susceptibility was used to assess hypnotizability, and self-reported measures were used to investigate anomalous experiences, mental health using the Self-Reporting Questionnaire-SRQ, dissociative experiences using the Dissociative Experiences Scale, and empathy using the Interpersonal Reactivity Index. RESULTS: No between-group differences were found in the total or subdivided CC areas or in hypnotizability, with both groups showing intermediate levels. The rostrum of the CC area and hypnotizability were not correlated. The MG presented with significantly more anomalous experiences, but the two groups had similar scores for dissociation, empathy, and mental health. CONCLUSION: The normal CC areas found in the MG are in contrast with the abnormal results typically observed in subjects with psychotic and dissociative disorders. Although hypnotizability was not different between groups, further studies are needed to replicate these findings in other samples.

Pineal gland and schizophrenia: A systematic review and meta-analysis.

Melatonin (MLT), the main hormone of the pineal gland (PG), is assumed to support initiation and maintenance of sleep, and a stable sleep-wake cycle, exerting antioxidative and neuroprotective actions. Evidence demonstrates that sleep and circadian rhythm abnormalities are very common in schizophrenia patients. Some imaging studies suggest structural abnormalities of the PG in these patients as well. We aimed to critically appraise the literature on PG imaging and melatonin secretion in schizophrenia patients, in comparison to matched healthy controls, and to review placebo-controlled trials of add-on exogenous MLT treatment in schizophrenia patients. In this systematic review, twenty-nine studies were included. Meta-analytical evaluation of data was possible only for MLT secretion finding that midnight plasma levels were significantly reduced in individuals with schizophrenia as compared to healthy controls (Hedge`s g = 1.32, p < 0.01). Imaging studies demonstrated greater prevalence of enlarged calcifications (>1 cm) of the PG (2 out of 2 computed tomography studies) and smaller PG volume (2 out of 3 magnetic resonance studies) compared with healthy controls. Anatomic and functional abnormalities of the PG were not associated with duration of illness or with treatment factors, maybe suggesting them to be primary characteristics of the disease and genetically based. Add-on MLT treatment leads to a modest improvement of objective and subjective sleep quality, of metabolic adverse effects of antipsychotics, and of tardive dyskinesia symptoms in schizophrenia patients. It remains to be established whether MLT treatment in prodromal phases of the disease could prevent neurostructural abnormalities.