The effect of early life events on glucose levels in first-episode psychosis

First episode of psychosis (FEP) patients display a wide variety of metabolic disturbances at onset, which might underlie these patients' increased morbidity and early mortality. Glycemic abnormalities have been previously related to pharmacological agents; however, recent research highlights the impact of early life events. Birth weight (BW), an indirect marker of the fetal environment, has been related to glucose abnormalities in the general population over time. We aim to evaluate if BW correlates with glucose values in a sample of FEP patients treated with different antipsychotics. Two hundred and thirty-six patients were included and evaluated for clinical and metabolic variables at baseline and at 2, 6, 12, and 24 months of follow-up. Pearson correlations and linear mixed model analysis were conducted to analyze the data. Antipsychotic treatment was grouped due to its metabolic risk profile. In our sample of FEP patients, BW was negatively correlated with glucose values at 24 months of follow-up [r=-0.167, p=0.037]. BW showed a trend towards significance in the association with glucose values over the 24-month period (F=3.22; p=0.073) despite other confounders such as age, time, sex, body mass index, antipsychotic type, and chlorpromazine dosage. This finding suggests that BW is involved in the evolution of glucose values over time in a cohort of patients with an FEP, independently of the type of pharmacological agent used in treatment. Our results highlight the importance of early life events in the later metabolic outcome of patients

The effect of early life events on glucose levels in first-episode psychosis

First episode of psychosis (FEP) patients display a wide variety of metabolic disturbances at onset, which might underlie these patients’ increased morbidity and early mortality. Glycemic abnormalities have been previously related to pharmacological agents; however, recent research highlights the impact of early life events. Birth weight (BW), an indirect marker of the fetal environment, has been related to glucose abnormalities in the general population over time. We aim to evaluate if BW correlates with glucose values in a sample of FEP patients treated with different antipsychotics. Two hundred and thirty-six patients were included and evaluated for clinical and metabolic variables at baseline and at 2, 6, 12, and 24 months of follow-up. Pearson correlations and linear mixed model analysis were conducted to analyze the data. Antipsychotic treatment was grouped due to its metabolic risk profile. In our sample of FEP patients, BW was negatively correlated with glucose values at 24 months of follow-up [r=-0.167, p=0.037]. BW showed a trend towards significance in the association with glucose values over the 24-month period (F=3.22; p=0.073) despite other confounders such as age, time, sex, body mass index, antipsychotic type, and chlorpromazine dosage. This finding suggests that BW is involved in the evolution of glucose values over time in a cohort of patients with an FEP, independently of the type of pharmacological agent used in treatment. Our results highlight the importance of early life events in the later metabolic outcome of patients

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Study of PDZ–Peptide and PDZ–Lipid Interactions by Surface Plasmon Resonance/BIAcore

International audienc

Phospholipase D and phosphatidic acid in the biogenesis and cargo loading of extracellular vesicles

Extracellular vesicles released by viable cells (exosomes and microvesicles) have emerged as important organelles supporting cell-cell communication. Because of their potential therapeutic significance, important efforts are being made toward characterizing the contents of these vesicles and the mechanisms that govern their biogenesis. It has been recently demonstrated that the lipid modifying enzyme, phospholipase D (PLD)2, is involved in exosome production and acts downstream of the small GTPase, ARF6. This review aims to recapitulate our current knowledge of the role of PLD2 and its product, phosphatidic acid, in the biogenesis of exosomes and to propose hypotheses for further investigation of a possible central role of these molecules in the biology of these organelles

Short-term effect of high temperatures, hours of sunlight, and chemical pollution on daily emergency hospital admissions due to endocrine and metabolic causes in the Madrid region, Spain (2013-2018)

XLI Reunión anual de la Sociedad Española de Epidemiología (SEE) y XVIII Congresso da Associação Portuguesa de Epidemiología (APE). Porto (Portugal), del 5 al 8 de septiembre de 2023.Background/Objectives: Studies which analyse the joint effect of acoustic or chemical air pollution variables and different meteorological variables on neuroendocrine disease are practically nonexistent. This study therefore sought to analyse the impact of air pollutants and environmental meteorological variables on daily unscheduled admissions due to endocrine and metabolic diseases in the Madrid Region from 01.01.2013 to 31.12.2018. Methods: We conducted a longitudinal, retrospective, ecological study of daily time series analysed by Poisson regression, with emergency neuroendocrine-disease admissions in the Madrid Region as the dependent variable. The independent variables were: mean daily concentrations of PM10, PM2.5, NO2 and O3; acoustic pollution; temperature; hours of sunlight; relative humidity; wind speed; and air pressure above sea level. Estimators of the statistically significant variables were used to calculate the relative risks (RRs). Results: A statistically significant association was found between the increase in temperatures in heat waves, RR: 1.123 95%CI (1.001-1.018), and the number of emergency admissions, making it the main risk factor. An association between a decrease in sunlight and an increase in hospital admissions, RR: 1.005 95%CI (1.002-1.008), was likewise observed. Similarly, ozone, in the form of mean daily concentrations in excess of 44 μg/m3, had an impact on admissions due to neuroendocrine disease, RR: 1.010 95%CI (1.007-1.035). The breakdown by sex showed that in the case of women, NO2 was also a risk factor, RR: 1.021 95%CI (1.007-1.035). Conclusions/Recommendations: The results obtained in this study serve to identify risk factors for this disease, such as extreme temperatures in heat waves, O3 or NO2. The robust association found between the decrease in sunlight and increase in hospital admissions due to neuroendocrine disease serves to spotlight an environmental factor which has received scant attention in public health until now.N

Fragment-based drug design targeting syntenin PDZ2 domain involved in exosomal release and tumour spread

International audienceSyntenin stimulates exosome production and its expression is upregulated in many cancers and implicated in the spread of metastatic tumor. These effects are supported by syntenin PDZ domains interacting with syndecans. We therefore aimed to develop, through a fragment-based drug design approach, novel inhibitors targeting syntenin-syndecan interactions. We describe here the optimization of a fragment, ‘hit’ C58, identified by in vitro screening of a PDZ-focused fragment library, which binds specifically to the syntenin-PDZ2 domain at the same binding site as the syndecan-2 peptide. X-ray crystallographic structures and computational docking were used to guide our optimization process and lead to compounds 45 and 57 (IC50 = 33 μM and 47 μM; respectively), two representatives of syntenin-syndecan interactions inhibitors, that selectively affect the syntenin-exosome release. These findings demonstrate that it is possible to identify small molecules inhibiting syntenin-syndecan interaction and exosome release that may be useful for cancer therapy

Syntenin mediates SRC function in exosomal cell-to-cell communication

The cytoplasmic tyrosine kinase SRC controls cell growth, proliferation, adhesion, and motility. The current view is that SRC acts primarily downstream of cell-surface receptors to control intracellular signaling cascades. Here we reveal that SRC functions in cell-to-cell communication by controlling the biogenesis and the activity of exosomes. Exosomes are viral-like particles from endosomal origin that can reprogram recipient cells. By gain- and loss-of-function studies, we establish that SRC stimulates the secretion of exosomes having promigratory activity on endothelial cells and that syntenin is mandatory for SRC exosomal function. Mechanistically, SRC impacts on syndecan endocytosis and on syntenin-syndecan endosomal budding, upstream of ARF6 small GTPase and its effector phospholipase D2, directly phosphorylating the conserved juxtamembrane DEGSY motif of the syndecan cytosolic domain and syntenin tyrosine 46. Our study uncovers a function of SRC in cell-cell communication, supported by syntenin exosomes, which is likely to contribute to tumor-host interactions.status: publishe

Syntenin mediates SRC function in exosomal cell-to-cell communication

The cytoplasmic tyrosine kinase SRC controls cell growth, proliferation, adhesion, and motility. The current view is that SRC acts primarily downstream of cell-surface receptors to control intracellular signaling cascades. Here we reveal that SRC functions in cell-to-cell communication by controlling the biogenesis and the activity of exosomes. Exosomes are viral-like particles from endosomal origin that can reprogram recipient cells. By gain- and loss-of-function studies, we establish that SRC stimulates the secretion of exosomes having promigratory activity on endothelial cells and that syntenin is mandatory for SRC exosomal function. Mechanistically, SRC impacts on syndecan endocytosis and on syntenin-syndecan endosomal budding, upstream of ARF6 small GTPase and its effector phospholipase D2, directly phosphorylating the conserved juxtamembrane DEGSY motif of the syndecan cytosolic domain and syntenin tyrosine 46. Our study uncovers a function of SRC in cell-cell communication, supported by syntenin exosomes, which is likely to contribute to tumor-host interactions.status: publishe

Syntenin mediates SRC function in exosomal cell-to-cell communication

International audienc