Violent criminal behavior in the context of bipolar disorder: Systematic review and meta-analysis

BACKGROUND: Despite the potential importance of understanding violent criminal behavior (VCB) in individuals suffering from bipolar disorder (BD), previous findings are conflicting. The aims of the present study are to clarify the association of VCB and BD in comparison to general population and other psychiatric conditions. METHODS: A systematic review of literature from January 1st, 1980 through January 16th, 2017 from 3 electronic databases (MEDLINE/PubMed, EMBASE and PsycInfo), following the PRISMA and the MOOSE statements. Original peer-reviewed studies reporting data on VCB in BD were included. A random-effects meta-analysis was performed. Potential sources of heterogeneity were examined through subgroup and meta-regression analyses. The protocol was registered in PROSPERO, CRD42017054070. RESULTS: Twelve studies providing data from 58,475 BD participants. The prevalence of VCB in BD was 7.1% (95%CI = 3.0‒16.5%; k = 4). The association of BD and VCB compared to general population was not significant (OR = 2.784; 95% CI, 0.687‒11.287, P = .152). The association was significant only in cross-sectional studies, in studies in which VCB was assessed through self-reported measures, and in studies conducted in the USA. BD was more likely to be associated with VCB when BD patients were compared to controls with depressive disorders, whilst it was found to be less associated with VCB when BD was compared to psychotic disorders. LIMITATIONS: 1. the methodological heterogeneity across the included studies. 2. causal inferences were precluded by the inclusion of cross-sectional studies. CONCLUSIONS: These findings might provide a more balance portrait of the association between BD and VCB to clinicians, law enforcement and general public

The Host Microbiota Contributes to Early Protection Against Lung Colonization by Mycobacterium tuberculosis

Tuberculosis (TB), caused by the airborne bacterial pathogen Mycobacterium tuberculosis, remains a major source of morbidity and mortality worldwide. So far, the study of host-pathogen interactions in TB has mostly focused on the physiology and virulence of the pathogen, as well as, on the various innate and adaptive immune compartments of the host. Microbial organisms endogenous to our body, the so-called microbiota, interact not only with invading pathogens, but also with our immune system. Yet, the impact of the microbiota on host defense against M. tuberculosis remains poorly understood. In order to address this question, we adapted a robust and reproducible mouse model of microbial dysbiosis based on a combination of wide-spectrum antibiotics. We found that microbiota dysbiosis resulted in an increased early colonization of the lungs by M. tuberculosis during the first week of infection, correlating with an altered diversity of the gut microbiota during this time period. At the cellular level, no significant difference in the recruitment of conventional myeloid cells, including macrophages, dendritic cells and neutrophils, to the lungs could be detected during the first week of infection between microbiota-competent and -deficient mice. At the molecular level, microbiota depletion did not impact the global production of pro-inflammatory cytokines, such as interferon (IFN)γ, tumor necrosis factor (TNF)α and interleukin (IL)-1β in the lungs. Strikingly, a reduced number of mucosal-associated invariant T (MAIT) cells, a population of innate-like lymphocytes whose development is known to depend on the host microbiota, was observed in the lungs of the antibiotics-treated animals after 1week of infection. These cells produced less IL-17A in antibiotics-treated mice. Notably, dysbiosis correction through the inoculation of a complex microbiota in antibiotics-treated animals reversed these phenotypes and improved the ability of MAIT cells to proliferate. Altogether, our results demonstrate that the host microbiota contributes to early protection of lung colonization by M. tuberculosis, possibly through sustaining the function(s) of MAIT cells. Our study calls for a better understanding of the impact of the microbiota on host-pathogen interactions in TB. Ultimately, this study may help to develop novel therapeutic approaches based on the use of beneficial microbes, or components thereof, to boost anti-mycobacterial immunity

Type-3 Secretion System-induced pyroptosis protects Pseudomonas against cell-autonomous immunity

Inflammasome-induced pyroptosis comprises a key cell-autonomous immune process against intracellular bacteria, namely the generation of dying cell structures. These so-called pore-induced intracellular traps (PITs) entrap and weaken intracellular microbes. However, the immune importance of pyroptosis against extracellular pathogens remains unclear. Here, we report that Type-3 secretion system (T3SS)-expressing Pseudomonas aeruginosa ( P. aeruginosa ) escaped PIT immunity by inducing a NLRC4 inflammasome-dependent macrophage pyroptosis response in the extracellular environment. To the contrary, phagocytosis of Salmonella Typhimurium promoted NLRC4-dependent PIT formation and the subsequent bacterial caging. Remarkably, T3SS-deficient Pseudomonas were efficiently sequestered within PIT-dependent caging, which favored exposure to neutrophils. Conversely, both NLRC4 and caspase-11 deficient mice presented increased susceptibility to T3SS-deficient P. aeruginosa challenge, but not to T3SS-expressing P. aeruginosa. Overall, our results uncovered that P. aeruginosa uses its T3SS to overcome inflammasome-triggered pyroptosis, which is primarily effective against intracellular invaders. Importance Although innate immune components confer host protection against infections, the opportunistic bacterial pathogen Pseudomonas aeruginosa ( P. aeruginosa ) exploits the inflammatory reaction to thrive. Specifically the NLRC4 inflammasome, a crucial immune complex, triggers an Interleukin (IL)-1β and -18 deleterious host response to P. aeruginosa . Here, we provide evidence that, in addition to IL-1 cytokines, P. aeruginosa also exploits the NLRC4 inflammasome-induced pro-inflammatory cell death, namely pyroptosis, to avoid efficient uptake and killing by macrophages. Therefore, our study reveals that pyroptosis-driven immune effectiveness mainly depends on P. aeruginosa localization. This paves the way toward our comprehension of the mechanistic requirements for pyroptosis effectiveness upon microbial infections and may initiate targeted approaches in order to ameliorate the innate immune functions to infections. Graphical abstract Macrophages infected with T3SS-expressing P. aeruginosa die in a NLRC4-dependent manner, which allows bacterial escape from PIT-mediated cell-autonomous immunity and neutrophil efferocytosis. However, T3SS-deficient P. aeruginosa is detected by both NLRC4 and caspase-11 inflammasomes, which promotes bacterial trapping and subsequent efferocytosis of P. aeruginosa -containing-PITs by neutrophils

Implantació i Millora de l'European Project Semester (EPS) a l'EPSEVG

L'EPSEVG de la UPC va implantar l’European Project Semester (EPS) un programa formatiu innovador que respon a les demandes plantejades per la societat i l’Espai Europeu d’Ensenyament Superior (EEES) durant el curs 2007‐2008. L’EPS permet cobrir la demanda d’estudiants estrangers que volen venir a estudiar a l’escola, demanda, que, a nivell de grau en enginyeria no esta coberta en cap universitat catalana.L’EPS també és una oportunitat per augmentar el compromís de l’EPSEVG vers la sostenibilitat. El programa s’ha ambientalitzat d’acord amb les directrius del Pla UPC Sostenible 2015 essent la sostenibilitat un dels eixos transversals que li dona contingut i que identifica a tots els projectes desenvolupats. A més de la sostenibilitat, el programa inclou altres matèries transversals (com ara, la innovació, la gestió de projectes, l’accessibilitat...). L’EPS utilitza el model d’aprenentatge basat en projectes (Project Based Learning), i hi introdueix dos components nous: la docència en anglès i la interculturalitat dins de l’aula. Les noves tecnologies s’utilitzen tant per dinamitzar el treball dels grups com per facilitar el seu aprenentatge, doncs l’EPS inclou tallers i seminaris en la modalitat semipresencial.Peer Reviewe

An NAD+ Phosphorylase Toxin Triggers Mycobacterium tuberculosis Cell Death.

Toxin-antitoxin (TA) systems regulate fundamental cellular processes in bacteria and represent potential therapeutic targets. We report a new RES-Xre TA system in multiple human pathogens, including Mycobacterium tuberculosis. The toxin, MbcT, is bactericidal unless neutralized by its antitoxin MbcA. To investigate the mechanism, we solved the 1.8 Å-resolution crystal structure of the MbcTA complex. We found that MbcT resembles secreted NAD+-dependent bacterial exotoxins, such as diphtheria toxin. Indeed, MbcT catalyzes NAD+ degradation in vitro and in vivo. Unexpectedly, the reaction is stimulated by inorganic phosphate, and our data reveal that MbcT is a NAD+ phosphorylase. In the absence of MbcA, MbcT triggers rapid M. tuberculosis cell death, which reduces mycobacterial survival in macrophages and prolongs the survival of infected mice. Our study expands the molecular activities employed by bacterial TA modules and uncovers a new class of enzymes that could be exploited to treat tuberculosis and other infectious diseases

Proceedings of the 13th annual conference of INEBRIA

CITATION: Watson, R., et al. 2016. Proceedings of the 13th annual conference of INEBRIA. Addiction Science & Clinical Practice, 11:13, doi:10.1186/s13722-016-0062-9.The original publication is available at https://ascpjournal.biomedcentral.comENGLISH SUMMARY : Meeting abstracts.https://ascpjournal.biomedcentral.com/articles/10.1186/s13722-016-0062-9Publisher's versio

Violent criminal behavior in the context of bipolar disorder: Systematic review and meta-analysis

International audienc

Jejunum inflammation in obese and diabetic mice impairs enteric glucose detection and modifies nitric oxide release in the hypothalamus.

Intestinal detection of nutrients is a crucial step to inform the whole body of the nutritional status. In this paradigm, peripheral information generated by nutrients is transferred to the brain, which in turn controls physiological functions, including glucose metabolism. Here, we investigated the effect of enteric glucose sensors stimulation on hypothalamic nitric oxide (NO) release in lean or in obese/diabetic (db/db) mice. By using specific NO amperometric probes implanted directly in the hypothalamus of mice, we demonstrated that NO release is stimulated in response to enteric glucose sensors activation in lean but not in db/db mice. Alteration of gut to hypothalamic NO signaling in db/db mice is associated with a drastic increase in inflammatory, oxidative/nitric oxide (iNOS, IL-1β), and endoplasmic reticulum stress (CHOP, ATF4) genes expression in the jejunum. Although we could not exclude the importance of the hypothalamic inflammatory state in obese and diabetic mice, our results provide compelling evidence that enteric glucose sensors could be considered as potential targets for metabolic diseases

Identification and characterization of lung commensal bacteria that modulate immune response in Tuberculosis

Meeting Abstract 66.2https://doi.org/10.4049/jimmunol.202.Supp.66.2International audienceTuberculosis (TB) is still one of the deadliest infectious diseases in humans. As TB disease is driven by exacerbation of the immune response, promising approaches include host-targeting therapies aiming at controlling the balance between pathogen eradication and limitation of the inflammation in order to prevent immunopathology. Such immune modulation has been observed through modification of the gut-microbiota compartment with oral administration of specific bacterial strains (i.e. probiotics) in other respiratory diseases. In TB, a dysbiosis of the microbiota is observed in patients, and microbiota perturbation in mice increases susceptibility to Mycobacterium tuberculosis (Mtb). Here, we assessed whether bacterial strains isolated from the recently described lung microbiota could have a local impact on Mtb infection by protecting against immune dysfunction for the host benefit. Through intranasal administration in mice, we identified different microbiota strains isolated from mouse lungs with a strong ability to modulate the lung T cell compartment. The same in vivo approach in Mtb-infected mice revealed one strain with a remarkable capacity to diminish Mtb infection-associated lung immunopathology, accompanied by a specific immune signature characterized by an increase level of regulatory T cells sharing surprisingly T-helper 17 cell markers. Collectively, this work may contribute to the design of host-directed therapies to reduce the destructive inflammatory response in TB, without further fomenting the occurrence of multiple-drug resistant Mtb strains. It will also shed light on poorly described populations in the lungs such as the RORgt+ Foxp3+ biTregs and their interactions with the microbiota