The influence of psilocybin on subconscious and conscious emotional learning.

Serotonergic psychedelics hold promise as a treatment modality for various psychiatric disorders and are currently applied in psychedelic-assisted psychotherapy. We investigated the learning effects of the serotonin receptor agonist psilocybin in a probabilistic cue-reward task with emotional cues in the form of neutral or fearful faces, presented either consciously or subconsciously. This study represents the first investigation into reinforcement learning with psilocybin. Across different dosages, psilocybin preserved learning effects and was statistically noninferior compared to placebo, while suggesting a higher exploratory behavior. Notably, the 20 mg group exhibited significantly better learning rates against the placebo group. Psilocybin induced inferior results with subconscious cues compared to placebo, and better results with conscious neutral cues in some conditions. These findings suggest that modulating serotonin signaling in the brain with psilocybin sufficiently preservers reinforcement learning.

TMS-EEG and resting-state EEG applied to altered states of consciousness: oscillations, complexity, and phenomenology.

Exploring the neurobiology of the profound changes in consciousness induced by classical psychedelic drugs may require novel neuroimaging methods. Serotonergic psychedelic drugs such as psilocybin produce states of increased sensory-emotional awareness and arousal, accompanied by increased spontaneous electroencephalographic (EEG) signal diversity. By directly stimulating cortical tissue, the altered dynamics and propagation of the evoked EEG activity can reveal drug-induced changes in the overall brain state. We combine Transcranial Magnetic Stimulation (TMS) and EEG to reveal that psilocybin produces a state of increased chaotic brain activity which is not a result of altered complexity in the underlying causal interactions between brain regions. We also map the regional effects of psilocybin on TMS-evoked activity and identify changes in frontal brain structures that may be associated with the phenomenology of psychedelic experiences.

Bilateral subdural hematoma caused by spontaneous intracranial hypotension originating from a discogenic microspur successfully treated with duraplasty: A case report.

Introduction: Discogenic microspurs are calcified outgrowths from the intervertebral disc which can perforate the dura, causing a leak of cerebrospinal fluid (CSF). Spontaneous leaks of the CSF present a recognized cause of spontaneous intracranial hypotension (SIH). Moreover, subdural hematomas (SDH) are a potentially severe complication of SIH. Research question: We present a case of a bilateral subdural hematoma without orthostatic headaches caused by a discogenic microspur protruding from the T1-2 intervertebral disc. The microspur is conjectured to be the culprit of the leak by ventrally perforating the dura and catalyzing the causal chain leading to the formation of the subdural hemorrhage. Material and methods: A 79-year woman noticed a progressive gait disturbance accompanied by a decline of short-term memory over several months without experiencing orthostatic headaches. Magnetic resonance imaging (MRI) showed extensive bilateral subdural fronto-parietal hematoma, signs of CSF hypotension (dilated venous compartments), and computed tomography (CT) myelography revealed a CSF leak originating at the T1-2 level. Results: The leakage site was treated with microsurgical duraplasty leading to a regression of the symptoms and complete resolution of the subdural hematomas within five postoperative months. Discussion and conclusion: Discogenic microspurs can perforate the dura causing a CSF leak, leading to spontaneous intracranial hypotension, finally resulting in a bilateral subdural hematoma. This constellation of symptoms does not necessarily induce orthostatic headaches and can be treated with microsurgical duraplasty.

Association between the Prime Diet Quality Score and depressive symptoms in a Mediterranean population with metabolic syndrome. Cross-sectional and 2-year follow-up assessment from PREDIMED-PLUS study.

The burden of depression is increasing worldwide, specifically in older adults. Unhealthy dietary patterns may partly explain this phenomenon. In the Spanish PREDIMED-Plus study, we explored (1) the cross-sectional association between the adherence to the Prime Diet Quality Score (PDQS), an a priori-defined high-quality food pattern, and the prevalence of depressive symptoms at baseline (cross-sectional analysis) and (2) the prospective association of baseline PDQS with changes in depressive symptomatology after 2 years of follow-up. After exclusions, we assessed 6612 participants in the cross-sectional analysis and 5523 participants in the prospective analysis. An energy-adjusted high-quality dietary score (PDQS) was assessed using a validated FFQ. The cross-sectional association between PDQS and the prevalence of depression or presence of depressive symptoms and the prospective changes in depressive symptoms were evaluated through multivariable regression models (logistic and linear models and mixed linear-effects models). PDQS was inversely associated with depressive status in the cross-sectional analysis. Participants in the highest quintile of PDQS (Q5) showed a significantly reduced odds of depression prevalence as compared to participants in the lowest quartile of PDQS (Q1) (OR (95 %) CI = 0·82 (0·68, 0·98))). The baseline prevalence of depression decreased across PDQS quintiles (Pfor trend = 0·015). A statistically significant association between PDQS and changes in depressive symptoms after 2-years follow-up was found (ß (95 %) CI = -0·67 z-score (-1·17, -0·18). A higher PDQS was cross-sectionally related to a lower depressive status. Nevertheless, the null finding in our prospective analysis raises the possibility of reverse causality. Further prospective investigation is required to ascertain the association between PDQS and changes in depressive symptoms along time.

Metabolomic analysis of plasma from breast tumour patients. A pilot study.

BACKGROUND: Patients at risk of breast cancer are submitted to mammography, resulting in a classification of the lesions following the Breast Imaging Reporting and Data System (BI-RADS®). Due to BI-RADS 3 classification problems and the great uncertainty of the possible evolution of this kind of tumours, the integration of mammographic imaging with other techniques and markers of pathology, as metabolic information, may be advisable. DESIGN AND METHODS: Our study aims to evaluate the possibility to quantify by gas chromatography-mass spectrometry (GC-MS) specific metabolites in the plasma of patients with mammograms classified from BI-RADS 3 to BI-RADS 5, to find similarities or differences in their metabolome. Samples from BI-RADS 3 to 5 patients were compared with samples from a healthy control group. This pilot project aimed at establishing the sensitivity of the metabolomic classification of blood samples of patients undergoing breast radiological analysis and to support a better classification of mammographic cases. RESULTS: Metabolomic analysis revealed a panel of metabolites more abundant in healthy controls, as 3-aminoisobutyric acid, cholesterol, cysteine, stearic, linoleic and palmitic fatty acids. The comparison between samples from BI-RADS 3 and BI-RADS 5 patients, revealed the importance of 4-hydroxyproline, found in higher amount in BI-RADS 3 subjects. CONCLUSION: Although the low sample number did not allow the attainment of high validated statistical models, some interesting data were obtained, revealing the potential of metabolomics for an improvement in the classification of different mammographic lesions.

Dietary Quality Changes According to the Preceding Maximum Weight: A Longitudinal Analysis in the PREDIMED-Plus Randomized Trial.

One-year dietary quality change according to the preceding maximum weight in a lifestyle intervention program (PREDIMED-Plus trial, 55-75-year-old overweight or obese adults; n = 5695) was assessed. A validated food frequency questionnaire was used to assess dietary intake. A total of 3 groups were made according to the difference between baseline measured weight and lifetime maximum reported weight: (a) participants entering the study at their maximum weight, (b) moderate weight loss maintainers (WLM), and (c) large WLM. Data were analyzed by General Linear Model. All participants improved average lifestyle. Participants entering the study at their maximum weight were the most susceptible to improve significantly their dietary quality, assessed by adherence to Mediterranean diet, DII and both healthful and unhealthful provegetarian patterns. People at maximum weight are the most benefitted in the short term by a weight management program. Long term weight loss efforts may also reduce the effect of a weight management program.

Primary HCMV infection in pregnancy from classic data towards metabolomics: An exploratory analysis.

BACKGROUND: Human cytomegalovirus (HCMV) is one of the most frequent risk of viral infections during pregnancy. The aim of this study was to evaluate the metabolic profile in amniotic fluid (AF) samples obtained from HCMV-infected, and uninfected fetuses in order to elucidate changes in metabolic pathways during congenital HCMV infection and to recognize new potential diagnostic and/or prognostic biomarkers. METHODS: A retrospective cohort study was conducted on 63 pregnant women: 20 contracted primary HCMV infection during pregnancy and, subsequently, transmitted the virus to the fetus (transmitters); 20 contracted the infection without transmitting the virus to the fetus (non-transmitters); 23 who underwent amniocentesis for cytogenetic-based diagnosis were considered controls. Metabolomics analysis was performed by using the hyphenated technique Gas chromatography-mass spectrometry (GC-MS) followed by a multivariate statistical approach. Four PLS-DA models were generated: controls vs. transmitters; controls vs. non-transmitters; transmitters vs. non-transmitters; and asymptomatic infected vs. symptomatic infected newborns. Subsequently, these models were exploited for network mapping. RESULTS: Compared with controls, HCMV transmitters showed significantly increased levels in glutamine, glycine, serine, pyruvic acid, threonine, threonic acid, and cystine; conversely, unknown U1715 and U1804, glutamic acid, U1437, fructose, sugar-like A203003 and A203005, and tyrosine levels were found decreased. In non-transmitters, glutamine, serine, glycine, threonic acid, threonine, 1-monostearin, urea, and cystine were found increased, while sorbitol, unknown U1804, sugar-like A203003, U1751, xylitol, leucine and fructose were decreased. The comparison between transmitters and non-transmitters did not produce a statistically significant model. Unlike controls' profile, a common feature of HCMV infected subjects (transmitters and non-transmitters) was the activation of glutamine-glutamate and pyrimidine metabolic pathways. In addition, a clusterization for asymptomatic vs. symptomatic outcome was also observed due to alteration of fatty acids biosynthesis. CONCLUSIONS: Metabolomics approach could highlight the significant modification of maternal and placental status during HCMV infection for both transmitter and non-transmitter subjects. A further separation was observed for asymptomatic vs. symptomatic HCMV congenital infections model. Therefore, metabolomics may be a promising tool to improve the accuracy of an early diagnosis, and the management of HCMV pregnancy-related infections.

Bacterias similares a Helicobacter pylori, en aguas de acueductos del estado Táchira y su probable asociación con patología gástrica / Similar bacteria to Helicobacter pylori, in water supplies of Táchira state and its possible association with gastric pathology

Introducción: Helicobacter pylori es uno de los agentes asociado al cáncer gástrico y posee una alta prevalencia en los países en vías de desarrollo. Sus rutas de transmisión no han sido totalmente establecidas; sin embargo, en algunos estudios se ha detectado su ADN en muestras de aguas residuales, subterráneas y superficiales. El objetivo de este trabajo fue detectar el ADN del género Helicobacter en muestras provenientes de acueductos rurales del municipio San Cristóbal y el Acueducto Regional del Táchira (ART). Materiales y métodos: Se recolectaron 500 ml de seis acueductos rurales y el ART. Se determinó la presencia de ADN del género Helicobacter a través de PCR y PCR semianidada con la posterior secuenciación de los productos de reacción. Resultados y discusión: El género Helicobacter no fue detectado mediante PCR, pero se observó la banda esperada en tres muestras mediante una PCR semianidada. La secuenciación de dos amplicones mostraron una similitud del 99% con Ralstonia pickettii, indicando que Helicobacter no fue detectada en los acueductos muestreados. Conclusiones: La secuenciación de los amplicones para el género Helicobacter, mostraron que se trata de R. pickettii un patógeno oportunista, con características similares a H. pylori.

Background: Helicobacter pylori is one of the agents associated with gastric cancer and has high prevalence in developing countries. Its routes of transmission have not been fully established, however, some studies have detected H. pylori DNA in wastewater, groundwater and surface water. The aim of our study was detect H. pylori DNA in water samples from rural water supplies of San Cristóbal and the Tachira’s Regional Water Supply (TRWS). Materials and methods: Water (500 ml) of six rural water supplies and the TRWS were collected. T DNA of Helicobacter genus was detected by Polimerase Chain Reaction (PCR) and seminested PCR and the PCR amplicons were sequenced. Results: Helicobacter genus PCR results were negative but the seminested PCR were positive in three samples. However the two amplicons sequenced showed a 99% similitud with Ralstonia pickettii. Conclusions: Helicobacter amplicon sequenced, showed a high similarity with R. pickettii, an oportunist pathogen, with similar characteristics to H. pylori.

Urinary metabolomics (GC-MS) reveals that low and high birth weight infants share elevated inositol concentrations at birth.

OBJECTIVE: Metabolomics is a new "omics" platform aimed at high-throughput identification, quantification and characterization of small-molecule metabolites. The metabolomics approach has been successfully applied to the classification different physiological states and identification of perturbed biochemical pathways. The purpose of the current investigation is the application of metabolomics to explore biological mechanisms which may lead to the onset of metabolic syndrome in adulthood. METHODS: We evaluated differences in metabolites in the urine collected within 12 h from 23 infants with IUGR (IntraUterine Growth Restriction), or LGA (Large for Gestational Age), compared to control infants (10 patients defined AGA: Appropriate for Gestational Age). Urinary metabolites were quantified by GC-MS and used to highlight similarities between the two metabolic diseases and identify metabolic markers for their predisposition. Quantified metabolites were analyzed using a multivariate statistics coupled with receiver operator characteristic curve (ROC) analysis of identified biomarkers. RESULTS: Urinary myo-inositol was the most important discriminant between LGA + IUGR and control infants, and displayed an area under the ROC curve = 1. CONCLUSION: We postulate that the increase in plasma and consequently urinary inositol may constitute a marker of altered glucose metabolism during fetal development in both IUGR and LGA newborns.

The urinary metabolomics profile of an Italian autistic children population and their unaffected siblings.

OBJECTIVE: A supervised multivariate model to classify the metabolome alterations between autistic spectrum disorders (ASD) patients and controls, siblings of autistic patients, has been realized and used to realize a network model of the ASD patients' metabolome. METHODS: In our experiment we propose a quantification of urinary metabolites with the Mass Spectroscopy technique couple to Gas Chromatography. A multivariate model has been used to extrapolate the variables of importance for a network model of interaction between metabolites. In this way we are able to propose a network-based approach to ASD description. RESULTS: Children with autistic disease composing our studied population showed elevated concentration of several organic acids and sugars. Interactions among diet, intestinal flora and genes may explain such findings. Among them, the 3-(3-hydroxyphenyl)-3-hydroxypropanoic acid has been previously described as altered in autistic subjects. Other metabolites increased are 3,4-dihydroxybutyric acid, glycolic acid and glycine, cis-aconitic acid; phenylalanine, tyrosine, p-hydroxyphenylacetic acid, and homovanillic acid are all involved in the tyrosine pathway leading to neurotransmitter cathecolamine. CONCLUSION: GC-MS-based metabolomic analysis of the urinary metabolome suggests to have the required sensitivity and specificity to gain insight into ASD phenotypes and aid a personalized network-based medicine approach.