Metabolomic analysis of mouse prefrontal cortex reveals upregulated analytes during wakefulness compared to sleep

By identifying endogenous molecules in brain extracellular fluid metabolomics can provide insight into the regulatory mechanisms and functions of sleep. Here we studied how the cortical metabolome changes during sleep, sleep deprivation and spontaneous wakefulness. Mice were implanted with electrodes for chronic sleep/wake recording and with microdialysis probes targeting prefrontal and primary motor cortex. Metabolites were measured using ultra performance liquid chromatography-high resolution mass spectrometry. Sleep/wake changes in metabolites were evaluated using partial least squares discriminant analysis, linear mixed effects model analysis of variance, and machine-learning algorithms. More than 30 known metabolites were reliably detected in most samples. When used by a logistic regression classifier, the profile of these metabolites across sleep, spontaneous wake, and enforced wake was sufficient to assign mice to their correct experimental group (pair-wise) in 80–100% of cases. Eleven of these metabolites showed significantly higher levels in awake than in sleeping mice. Some changes extend previous findings (glutamate, homovanillic acid, lactate, pyruvate, tryptophan, uridine), while others are novel (D-gluconate, N-acetyl-beta-alanine, N-acetylglutamine, orotate, succinate/methylmalonate). The upregulation of the de novo pyrimidine pathway, gluconate shunt and aerobic glycolysis may reflect a wake-dependent need to promote the synthesis of many essential components, from nucleic acids to synaptic membranes

Changes of consultation-liaison psychiatry practice in Italian general hospitals: A comparative 20-year multicenter study

Introduction: Conducted under the auspices of the Italian Society of Consultation Liaison Psychiatry (SIPC) the aim of this study was to describe the characteristics of Consultation Liaison Psychiatry (CLP) activity in Italy (SIPC-2—2018) over the past 20 years by comparing with data from the first Italian nation-wide study (SIPC-1—1998). Methods: We collected data on CLP visits of 3,943 patients from 10 Italian hospitals over a period of 1 year. Data were compared with those from the SIPC-1 1998 study (4,183 participants). Patients were assessed with the same ad hoc 60-item Patient Registration Form recording information from five different areas: Sociodemographic, hospitalization-related, consultation-related, interventions and outcome. Results: Compared with participants from the previous study, SIPC-2-2018 participants were significantly older (d = 0.54) and hospitalized for a longer duration (d = 0.20). The current study detected an increase in the proportion of referrals from surgical wards and for individuals affected by onco-hematologic diseases. Depressive disorders still represented the most frequent psychiatric diagnosis, followed by adjustment and stress disorders and delirium/dementia. Also, CLP psychiatrists prescribed more often antidepressants (Φ = 0.13), antipsychotics (Φ = 0.09), mood stabilizers (Φ = 0.24), and less often benzodiazepines (Φ = 0.07). Conclusion: CLP workload has increased considerably in the past 20 years in Italy, with changes in patient demographic and clinical characteristics. A trend toward increase in medication-based patient management was observed. These findings suggest that the psychiatric needs of patients admitted to the general hospital are more frequently addressed by referring physicians, although Italian CLP services still deserve better organization and autonomy

Response to erenumab assessed by HIT-6 is modulated by genetic factors and arterial hypertension - an explorative cohort study.

BACKGROUND Response predictors to erenumab (ERE) in migraine patients would benefit their clinical management. We investigate associations between patients' clinic characteristics and polymorphisms at CALCRL and RAMP1 genes and response to ERE treatment measured as clinically meaningful improvement of the headache impact test 6 (HIT-6) score. METHODS Post-hoc analysis of a prospective, multicenter, investigator-initiated study involving 110 migraine patients starting ERE 70 mg/month. Demographics, medical history, and migraine-related burden measured by HIT-6 score were collected during 3 months before and after ERE start. Selected polymorphic variants of calcitonin receptor-like receptor and receptor activity-modifying protein-1 genes were determined using Real-time PCR. Logistic regression models identified independent predictors for response to ERE, defined as HIT-6 score improvement ≥8 points (HIT-6 responders [HIT-6RESP], vs. HIT-6 non-responders [HIT-6NRESP]). RESULTS At month 3, 58 (52.7%) patients were HIT-6RESP. Comorbid hypertension predicted a lower probability of being HIT-6RESP [OR (95%CI] 0.160 (0.047-0.548), p=0.003). Compared to major alleles, minor alleles CALCRL rs6710852G and RAMP rs6431564G conferred an increased probability of being HIT-6RESP [for each G allele: OR (95%CI): 2.82(1.03-7.73), p=0.043; OR 95%CI): 2.10(1.05-4.22), p=0.037]. RAMP1 rs13386048A and RAMP1 rs12465864G decreased this probability [for each rs13386048A, OR (95%CI): 0.53(0.28-0.98), p=0.042; for each rs12465864G, OR(95%CI): 0.32(0.13-0.75), p=0.009). A genetic risk score based on the presence and number of identified risk alleles resulted independently associated with HIT-6RESP (OR, 0.49; 95%CI, 0.33-0.72; p= 0.0003) surviving Bonferroni's correction. CONCLUSIONS Response to ERE was associated with comorbid hypertension and specific allelic variants at CALCRL and RAMP1 genes. Results require confirmation in future studies

A Curcumin-BODIPY Dyad and Its Silica Hybrid as NIR Bioimaging Probes

In this paper we describe the synthesis of a novel bichromophoric system in which an efficient photoinduced intercomponent energy transfer process is active. The dyad consists of one subunit of curcumin and one of BODIPY and is able to emit in the far-red region, offering a large Stokes shift, capable of limiting light scattering processes for applications in microscopy. The system has been encapsulated in MCM-41 nanoparticles with dimensions between 50 and 80 nm. Both the molecular dyad and individual subunits were tested with different cell lines to study their effective applicability in bioimaging. MCM-41 nanoparticles showed no reduction in cell viability, indicating their biocompatibility and bio-inertness and making them capable of delivering organic molecules even in aqueous-based formulations, avoiding the toxicity of organic solvents. Encapsulation in the porous silica structure directed the location of the bichromophoric system within cytoplasm, while the dyad alone stains the nucleus of the hFOB cell line

Metabolomic analysis of mouse prefrontal cortex reveals upregulated analytes during wakefulness compared to sleep

By identifying endogenous molecules in brain extracellular fluid metabolomics can provide insight into the regulatory mechanisms and functions of sleep. Here we studied how the cortical metabolome changes during sleep, sleep deprivation and spontaneous wakefulness. Mice were implanted with electrodes for chronic sleep/wake recording and with microdialysis probes targeting prefrontal and primary motor cortex. Metabolites were measured using ultra performance liquid chromatography-high resolution mass spectrometry. Sleep/wake changes in metabolites were evaluated using partial least squares discriminant analysis, linear mixed effects model analysis of variance, and machine-learning algorithms. More than 30 known metabolites were reliably detected in most samples. When used by a logistic regression classifier, the profile of these metabolites across sleep, spontaneous wake, and enforced wake was sufficient to assign mice to their correct experimental group (pair-wise) in 80–100% of cases. Eleven of these metabolites showed significantly higher levels in awake than in sleeping mice. Some changes extend previous findings (glutamate, homovanillic acid, lactate, pyruvate, tryptophan, uridine), while others are novel (D-gluconate, N-acetyl-beta-alanine, N-acetylglutamine, orotate, succinate/methylmalonate). The upregulation of the de novo pyrimidine pathway, gluconate shunt and aerobic glycolysis may reflect a wake-dependent need to promote the synthesis of many essential components, from nucleic acids to synaptic membranes

From Academia to Industry: Criteria for Upscaling Ionic Liquid-Based Thermo-Electrochemical Cells for Large-Scale Applications

Thermo-electrochemical cells (or thermocells) represent a promising technology to convert waste heat energy into electrical energy, generating power with minimal material consumption and a limited carbon footprint. Recently, the adoption of ionic liquids has pushed both the operational temperature range and the power output of thermocells. This research discusses the design challenges and the key performance limitations that need to be addressed to deploy the thermocells in real-world applications. For this purpose, a unique up-scaled design of a thermocell is proposed, in which the materials are selected according to the techno-economic standpoint. Specifically, the electrolyte is composed of EMI-TFSI ionic liquid supplemented by [Co(ppy)]3+/2+ redox couples characterized by a positive Seebeck coefficient (1.5 mV/K), while the electrodes consist of carbon-based materials characterized by a high surface area. Such electrodes, adopted to increase the rate of the electrode reactions, lead to a thermoelectric performance one order of magnitude greater than the Pt electrode-based counterpart. However, the practical applications of thermocells are still limited by the low power density and low voltage that can be generated

Biomarkers of Low-Level Environmental Exposure to Benzene and Oxidative DNA Damage in Primary School Children in Sardinia, Italy

Background: The main anthropic sources of exposure to airborne benzene include vehicular traffic, cigarette smoke, and industrial emissions. Methods: To detect early genotoxic effects of environmental exposure to benzene, we monitored environmental, personal, and indoor airborne benzene in children living in an urban area and an area near a petrochemical plant. We also used urinary benzene and S-phenylmercapturic acid (S-PMA) as biomarkers of benzene exposure and urinary 8-hydroxydeoxyguanosine (8-OHdG) as a biomarker of early genotoxic effects. Results: Although always below the European Union limit of 5 μg/m3, airborne benzene levels were more elevated in the indoor, outdoor, and personal samples from the industrial surroundings compared to the urban area (p = 0.026, p = 0.005, and p = 0.001, respectively). Children living in the surroundings of the petrochemical plant had urinary benzene values significantly higher than those from the urban area in both the morning and evening samples (p = 0.01 and p = 0.02, respectively). Results of multiple regression modelling showed that age was a significant predictor of 8-OHdG excretion, independent of the sampling hour. Moreover, at the low exposure level experienced by the children participating in this study, neither personal or indoor airborne benzene level, nor personal monitoring data, affected 8-OHdG excretion. Conclusions: Our results suggest the importance of biological monitoring of low-level environmental exposure and its relation to risk of genotoxic effects among children