Multidimensional Impulsivity and Suicidal Behaviour: A Partial Test of the Integrated Motivational-Volitional (IMV) Model of Suicide.

OBJECTIVE: Suicide remains a public health problem within the United Kingdom (UK) and globally. Impulsivity is a key risk factor within the Integrated Motivational-Volitional Model (IMV) of Suicide warranting further study. The current study applied a multi-dimensional impulsivity framework (UPPS-P) to differentiate suicidality subgroups within an IMV framework (i.e., no suicidal behavior, suicidal ideation only, and suicide attempt). Impulsivity subscales were evaluated as moderators of the suicidal ideation-future suicide attempt link. METHOD: Adults living in the UK (N = 1027) completed an online survey addressing demographics, impulsivity, psychological distress, and lifetime suicidal behavior. We used analysis of variance (ANOVA) and linear regression with simple slopes analyses to investigate study objectives. RESULTS: Data analyses revealed that: (1) four impulsivity subtypes (negative urgency, positive urgency, lack of premeditation, sensation-seeking) differentially distinguished suicidal behavior groups; (b) negative urgency, positive urgency, and lack of premeditation were meaningfully associated with suicide outcomes, and (c) negative urgency served as a moderator of the suicidal ideation-future attempt link. CONCLUSIONS: Urgency, regardless of positive or negative valence, is important for understanding differences in lifetime suicidal behavior. Sensation-seeking may play a protective role for direct suicidal behavior. Negative urgency may be the most prominent aspect of impulsivity when considered as an IMV moderator. Findings are contextualized with respect to impulsivity and IMV frameworks. Clinical implications involve accounting for negative urgency in suicide risk assessment and intervention.

Urgency matters when differentiating persons with lifetime suicidal behavior.Negative urgency may be the most robust impulsivity IMV moderator.Suicide theory and prevention should account for the role of negative urgency.

Impacts of Metabolism and Organic Acids on Cell Wall Composition and Pseudomonas aeruginosa Susceptibility to Membrane Active Antimicrobials.

Reliable antimicrobial susceptibility testing is essential in informing both clinical antibiotic therapy decisions and the development of new antibiotics. Mammalian cell culture media have been proposed as an alternative to bacteriological media, potentially representing some critical aspects of the infection environment more accurately. Here, we use a combination of NMR metabolomics and electron microscopy to investigate the response of Escherichia coli and Pseudomonas aeruginosa to growth in differing rich media to determine whether and how this determines metabolic strategies, the composition of the cell wall, and consequently susceptibility to membrane active antimicrobials including colistin and tobramycin. The NMR metabolomic approach is first validated by characterizing the expected E. coli acid stress response to fermentation and the accompanying changes in the cell wall composition, when cultured in glucose rich mammalian cell culture media. Glucose is not a major carbon source for P. aeruginosa but is associated with a response to osmotic stress and a modest increase in colistin tolerance. Growth of P. aeruginosa in a range of bacteriological media is supported by consumption of formate, an important electron donor in anaerobic respiration. In mammalian cell culture media, however, the overall metabolic strategy of P. aeruginosa is instead dependent on consumption of glutamine and lactate. Formate doping of mammalian cell culture media does not alter the overall metabolic strategy but is associated with polyamine catabolism, remodelling of both inner and outer membranes, and a modest sensitization of P. aeruginosa PAO1 to colistin. Further, in a panel of P. aeruginosa isolates an increase between 2- and 3-fold in sensitivity to tobramycin is achieved through doping with other organic acids, notably propionate which also similarly enhances the activity of colistin. Organic acids are therefore capable of nonspecifically influencing the potency of membrane active antimicrobials.

Antimicrobial Constituents from Machaerium Pers.: Inhibitory Activities and Synergism of Machaeriols and Machaeridiols against Methicillin-Resistant Staphylococcus aureus, Vancomycin-Resistant Enterococcus faecium, and Permeabilized Gram-Negative Pathogens.

Two new epimeric bibenzylated monoterpenes machaerifurogerol (1a) and 5-epi-machaerifurogerol (1b), and four known isoflavonoids (+)-vestitol (2), 7-O-methylvestitol (3), (+)-medicarpin (4), and 3,8-dihydroxy-9-methoxypterocarpan (5) were isolated from Machaerium Pers. This plant was previously assigned as Machaerium multiflorum Spruce, from which machaeriols A-D (6-9) and machaeridiols A-C (10-12) were reported, and all were then re-isolated, except the minor compound 9, for a comprehensive antimicrobial activity evaluation. Structures of the isolated compounds were determined by full NMR and mass spectroscopic data. Among the isolated compounds, the mixture 10 + 11 was the most active with an MIC value of 1.25 µg/mL against methicillin-resistant Staphylococcus aureus (MRSA) strains BAA 1696, -1708, -1717, -33591, and vancomycin-resistant Enterococcus faecium (VRE 700221) and E. faecalis (VRE 51299) and vancomycin-sensitive E. faecalis (VSE 29212). Compounds 6-8 and 10-12 were found to be more potent against MRSA 1708, and 6, 11, and 12 against VRE 700221, than the drug control ciprofloxacin and vancomycin. A combination study using an in vitro Checkerboard method was carried out for machaeriols (7 or 8) and machaeridiols (11 or 12), which exhibited a strong synergistic activity of 12 + 8 (MIC 0.156 and 0.625 µg/mL), with >32- and >8-fold reduction of MIC's, compared to 12, against MRSA 1708 and -1717, respectively. In the presence of sub-inhibitory concentrations on polymyxin B nonapeptide (PMBN), compounds 10 + 11, 11, 12, and 8 showed activity in the range of 0.5-8 µg/mL for two strains of Acinetobacter baumannii, 2-16 µg/mL against Pseudomonas aeruginosa PAO1, and 2 µg/mL against Escherichia coli NCTC 12923, but were inactive (MIC > 64 µg/mL) against the two isolates of Klebsiella pneumoniae.

Microglial nodules provide the environment for pathogenic T cells in human encephalitis.

Microglia nodule formation is a common feature in inflammatory brain diseases mediated by T lymphocytes such as viral and paraneoplastic encephalitis, multiple sclerosis, and Rasmussen encephalitis (RE). However, its role has not been fully understood yet. We hypothesized that, in RE, microglial nodules provide an environment for the initiation of the later dominating T-cell cytotoxicity. In RE stage 0, small primary microglia nodules could be identified in the absence of T cells. These primary nodules showed inflammasome activation and endosomal Toll-like receptor upregulation. In stage 1, T cells migrate into the parenchyma and intermingle with microglial cells, thereby forming secondary nodules in which neurons are destroyed. Whole-genome transcriptome analysis at this point showed upregulation of several inflammatory pathways including interferon signaling and major histocompatibility complex-I signaling. Inflammatory profiles, like the ones observed in RE, could be induced upon TLR3 stimulation in neonatal microglial cell cultures. Taken together, our results point towards activation of endosomal TLRs, resulting in increased interferon signaling, inflammasome activation, and chemokine upregulation as early steps in RE pathogenesis. This activity sets the scene for subsequent infiltration of T cells and destruction of neurons. Similar to RE, this microglial microenvironment might be a crucial step in other T-cell-mediated inflammatory brain diseases.

The heirs of Aradia, daughters of Diana: community in the second and third wave.

What happens when young third wave feminists learn from second wave feminists what living in community means? This article gives an account of engagement between generations of second and third wave feminists as the younger women began documenting the herstory of Aradia, a radical, separatist and mostly lesbian community and non-profit organization in conservative West Michigan in the 1970s and 1980s. The younger women learned the importance of non-hierarchical political organizing to counter differences of experience and power. They learned that divisions of work and play prevent the development of community and that "high play" is critically important for creative energy and insight. And they learned that mythmaking is more than fantasy; it creates reality. The older women learned that for the third wave identity and sexuality are more fluid. They learned that the younger feminists recognized and valued their contributions, and sought to carry feminist goals forward. Both generations were empowered by the encounter and learned the radical effects of women speaking across generations.