The “Eyeballing” technique : an emerging and alerting trend of alcohol misuse

Alternative methods of alcohol consumption have recently emerged among adolescents and young adults, including the alcohol “eyeballing”, which consist in the direct pouring of alcoholic substances on the ocular surface epithelium. In a context of drug and behavioural addictions change, “eyeballing” can be seen as one of the latest and potentially highly risky new trends. We aimed to analyze the existing medical literature as well as online material on this emerging trend of alcohol misusePeer reviewedFinal Published versio

Capgras-like syndrome in a patient with an acute urinary tract infection.

Delusional misidentification syndromes are a group of delusional phenomena in which patients misidentify familiar persons, objects, or themselves, believing that they have been replaced or transformed. In 25%-40% of cases, misidentification syndromes have been reported in association with organic illness. We report an acute episode of Capgras-like delusion lasting 8 days, focused on the idea that people were robots with human bodies, in association with an acute urinary infection. To our knowledge, this is the first case report associating urinary tract infection with Capgras-like syndrome. Awareness of the prevalence of delusional misidentification syndromes associated with acute medical illness should promote diligence on the part of clinicians in recognizing this disorder

Reprint of: Internalising symptoms mediate the longitudinal association between childhood inflammation and psychotic-like experiences in adulthood

Psychotic-like experiences (PLEs) are part of a continuum of psychosis. Previous longitudinal studies highlighted a relationship between peripheral inflammation during childhood and onset of PLEs in adulthood. In this study, we tested if this association is mediated by internalising and externalising symptoms experienced during childhood and adolescence. To test this hypothesis, we used data from the Avon Longitudinal Study of Parents and Children (ALSPAC). We investigated a subsample of 4525 individuals from this cohort with data on interleukin 6 (IL-6) and C-reactive protein (CRP) in childhood (age 9 years). We measured PLEs at age 18 years, and we used latent growth curve modelling to estimate longitudinal trajectories of internalising and externalising symptoms from ages 9 to 16 years. The individual predicted values of the intercept (set at baseline, 9 years) and the slope (rate of annual change) were then used in the mediation analysis. There was evidence for full mediation by the intercept of internalising symptoms. Our findings suggest that inflammation during childhood may be relevant for the future onset of PLEs via its association with a high level of internalising symptoms. These findings, although obtained from a non-clinical population, provide an additional step in advancing knowledge on the relationship between inflammation and symptoms of the psychosis continuum

Engineering Technology Reports, Volume 1: Laboratory Directed Research and Development FY00

In FY-2000, Engineering at Lawrence Livermore National Laboratory faced significant pressures to meet critical project milestones, and immediate demands to facilitate the reassignment of employees as the National Ignition Facility (the 600-TW laser facility being designed and built at Livermore, and one of the largest R&D construction projects in the world) was in the process of re-baselining its plan while executing full-speed its technology development efforts. This drive for change occurred as an unprecedented level of management and program changes were occurring within LLNL. I am pleased to report that we met many key milestones and achieved numerous technological breakthroughs. This report summarizes our efforts to perform feasibility and reduce-to-practice studies, demonstrations, and/or techniques--as structured through our technology centers. Whether using computational engineering to predict how giant structures like suspension bridges will respond to massive earthquakes or devising a suitcase-sized microtool to detect chemical and biological agents used by terrorists, we have made solid technical progress. Five Centers focus and guide longer-term investments within Engineering, as well as impact all of LLNL. Each Center is responsible for the vitality and growth of the core technologies it represents. My goal is that each Center will be recognized on an international scale for solving compelling national problems requiring breakthrough innovation. The Centers and their leaders are as follows: Center for Complex Distributed Systems--David B. McCallen; Center for Computational Engineering--Kyran D. Mish; Center for Microtechnology--Raymond P. Mariella, Jr.; Center for Nondestructive Characterization--Harry E. Martz, Jr.; and Center for Precision Engineering--Keith Carlisle

Metabolic abnormalities and low dietary Omega 3 are associated with symptom severity and worse functioning prior to the onset of psychosis: Findings from the North American Prodrome Longitudinal Studies Consortium

Objective: Patients with schizophrenia have a high prevalence of metabolic disorders and cardiovascular mortality. It is possible that a vulnerability to metabolic abnormalities is associated with risk for psychosis, symptoms and functionality. In this study, we evaluate demographic information, cardiometabolic indices, symptoms and functioning in an antipsychotic free cohort at Clinical High Risk (CHR) for psychosis from the NAPLS Omega 3 fatty acid clinical trial. Method: Subjects received physical exams and metabolic monitoring prior to randomization into the Omega 3 versus Placebo trial. Anthropometrical measures, vital signs, glucose, and lipids were assessed along with symptoms, functioning, dietary Omega 3 fatty acids, erythrocyte polyunsaturated fatty acid content and a measure of lipid peroxidation (TBARS, Thiobarbituric acid-reactive substances). Results: The sample included 113 CHR subjects (42.1% female; 17.5% Latino) ages 12–29. The mean BMI was 24.3 with a trend toward higher BMI and a higher incidence of metabolic syndrome in Latino subjects; 36% of the sample was obese/overweight; 37.6% met criteria for prehypertension/hypertension; 4.2% met criteria for prediabetes/diabetes; 9.6% showed evidence of insulin resistance and 44.7% had dyslipidemia. The TBARS was elevated at 9.8 μM ± 6.1 (normal 1.86–3.94 μM). Metabolic parameters and a diet low in Omega 3 rich foods were significantly associated with prodromal symptoms and poor functioning. Conclusions: CHR subjects show a high percentage of metabolic abnormalities prior to exposure to antipsychotic medication. These findings reinforce that early detection of metabolic disturbances and food insecurity is crucial since these factors are modifiable with the potential for significant gains in terms of quality of life, physical and mental health

Investigating the role of the endocannabinoid system and gut-microbiome in psychotic and severe mental illness: a focus on negative symptoms

Negative symptoms, such as anhedonia and amotivation, represent unmet therapeutic needs and key determinants of functional loss in severe mental illness. Albeit traditionally considered a unique feature of schizophrenia, anhedonia and amotivation manifest outside the psychotic spectrum, where they are equally debilitating and difficult to treat. A number of clinical trials using newly developed compounds or re-repurposing existing drugs have tried to treat negative symptoms without success. There is therefore urgent need of clarifying the mechanisms underlying negative symptoms, before engaging in further trials. The aim of my DPhil was to investigate the relevance for negative symptoms of two recently discovered biological systems, the gut-microbiome and the endocannabinoid systems. The rationale was based on emerging evidence showing an independent contribution of these two systems to the pathophysiology of severe mental illness and their proven interplay in other fields of medicine. I initially explored the independent contribution of the endocannabinoid system and the gut microbiome to schizophrenia and severe mental illness through two systematic reviews and meta-analyses. The first meta-analysis aimed at investigating disturbance of the endocannabinoid system in psychotic illness. Pooled results from 18 studies including 442 patients and 590 controls showed that anandamide, the main agonist of the endocannabinoid system, was increased in blood and cerebrospinal fluid of patients with psychotic illness, at any stage (including the prodrome) and independent of medication status. Across the included studies the increase in anandamide was inversely related to the severity of negative symptoms, suggesting endocannabinoids are protective towards illness mechanisms and severity of clinical features. The second meta-analysis aimed at investigating blood biomarkers of reduced microbial diversity (gut dysbiosis) in severe mental illnesses (schizophrenia, depression, and bipolar disorder) and chronic fatigue. Pooled results from 33 studies including 2,761 patients and 1,847 controls showed that blood biomarkers of gut dysbiosis were increased and positively associated with severity of negative symptoms in patients vs controls, independent of medication status and across diagnostic boundaries. I then brought the gut-microbiome and the endocannabinoid system together and explored the relevance of their interplay for negative symptoms in a general population cohort (TwinsUK). Data from 786 individuals showed that the endocannabinoid system mediated the association between gut dysbiosis and the severity of negative symptoms. In particular, gut dysbiosis was associated with increased faecal excretion of endocannabinoids (protective for mental health), which in turn was associated with more severe symptoms. These findings advocate for the existence of a gut microbiome- endocannabinoid axis, relevant for negative symptoms and a putative novel target for intervention. I therefore explored if existing molecules targeting the first node of this axis, the gut-microbiome, could palliate negative symptoms in severe mental illness using two systematic reviews and meta-analyses. The first meta-analysis investigated the efficacy of already known gut-microbiome-targeted therapeutics (antibiotics, antimicrobials, pre and probiotics) for the treatment of negative symptoms in psychotic illness. Pooled results from 28 eligible randomised controlled trials showed that none of the already known gut-microbiome based therapeutics were effective for treating negative symptoms of psychotic illness. Results were mainly led by antibiotics and antimicrobics (25 trials), with paucity of evidence on pre and probiotics. The second meta-analysis investigated the efficacy of metformin, which novel evidence showed to have a specific action on the gut-microbiome (i.e., increase in the relative abundance of butyrate-producing bacteria, beneficial for the host’s mental health). Analyses on the TwinsUK cohort showed that the relative abundance of these bacteria is associated with fecal levels of endocannabinoid metabolites. Pooled results from 5 eligible randomised controlled trials showed that metformin has pro-cognitive effects, with preliminary evidence showing efficacy on negative symptoms. Altogether these findings suggest that aspecific approaches targeting the gutmicrobiome are not effective for the treatment of negative symptoms, while more defined approaches targeting a specific biological axis might translate into clinically meaningful results. In conclusion, findings from my DPhil advocate for the existence of a gut microbiome-endocannabinoid axis, which might be relevant for negative symptoms across severe mental illness and beyond, such as in chronic fatigue and in general population. Future studies should validate findings in a well-powered clinical sample of patients with severe mental illness and test the efficacy of compounds targeting this axis.</p

Hydrogen Bridges and Electron-transfer In Biomolecules - Study of A Possible Mechanism On A Model Charge Recombination System

t is suggested that internal electron transfer in biomolecules such as multiheme proteins can take place along H-bridge/peptide-link chains by a proton-relay process followed by radicalic return to the initial condition. The plausibility of such a process is assessed by (a) reference to published suggestions and evidence; (b) estimates of vibrational characteristics and of the free energies of the various states of a model system consisting of three H-bridges and one peptide group. It appears that the proposed mechanism is highly efficient and very fast, at least if the H-bonds formed by a peptide group evolve in a concerted manner