Genetic and biochemical analyses of chromosome and plasmid gene homologues encoding ICL and ArCP domains in Vibrioanguillarum strain 775

Anguibactin, the siderophore produced by Vibrio anguillarum 775 is synthesized from 2,3-dihydroxybenzoic acid (DHBA), cysteine and hydroxyhistamine via a nonribosomal peptide synthetase (NRPS) mechanism. Most of the genes encoding anguibactin biosynthetic proteins are harbored by the pJM1 plasmid. In this work we report the identification of a homologue of the plasmid-encoded angB on the chromosome of strain 775. The product of both genes harbor an isochorismate lyase (ICL) domain that converts isochorismic acid to 2,3-dihydro-2,3-dihydroxybenzoic acid, one of the steps of DHBA synthesis. We show in this work that both ICL domains are functional in the production of DHBA in V. anguillarum as well as in E. coli. Substitution by alanine of the aspartic acid residue in the active site of both ICL domains completely abolishes their isochorismate lyase activity in vivo. The two proteins also carry an aryl carrier protein (ArCP) domain. In contrast with the ICL domains only the plasmid encoded ArCP can participate in anguibactin production as determined by complementation analyses and site-directed mutagenesis in the active site of the plasmid encoded protein, S248A. The site-directed mutants, D37A in the ICL domain and S248A in the ArCP domain of the plasmid encoded AngB were also tested in vitro and clearly show the importance of each residue for the domain function and that each domain operates independently.

The association between emotions and eating behaviour in an obese population with binge eating disorder

There is utility in understanding the antecedents of binge eating (BE), with a view to explaining poorer weight loss treatment responses in this subgroup. A systematic review was completed according to PRISMA guidelines with the aim of exploring Q3 associations between emotions and eating behaviour in a population affected by obesity and binge eating disorder (BED). A comprehensive literature search of four electronic databases (2004–2014) yielded 15 studies for inclusion. Included studies performed poorly on data quality analysis with respect to controlling for confounding variables, and sample size. Included papers largely focused on negative emotions as antecedents of BE; depression was consistently associated with a BEDobese classification and BE. Negative mood, sadness, tension and instability of emotions were found to be antecedents of BE in an adult BED-obese sample. However, findings were mixed regarding the role of stress, anger and positive emotions within the BED-obese population. Recommendations are presented for the identification of BED, and ecologically valid experimental designs that further understanding of the complex and varied emotions that associate with BE. The implications of these and other limitations for both researchers and practitioners are discussed. The paper concludes with recommendations for future research alongside suggestions for practitioners.University of Wolverhampto

Effectiveness and cost-effectiveness of transmural collaborative care with consultation letter (TCCCL) and duloxetine for major depressive disorder (MDD) and (sub)chronic pain in collaboration with primary care: design of a randomized placebo-controlled multi-Centre trial: TCC:PAINDIP

__Abstract__ Background: The comorbidity of pain and depression is associated with high disease burden for patients in terms of disability, wellbeing, and use of medical care. Patients with major and minor depression often present themselves with pain to a general practitioner and recognition of depression in such cases is low, but evolving. Also, physical symptoms, including pain, in major depressive disorder, predict a poorer response to treatment. A multi-faceted, patient-tailored treatment programme, like collaborative care, is promising. However, treatment of chronic pain conditions in depressive patients has, so far, received limited attention in research. Cost effectiveness of an integrated approach of pain in depressed patients has not been studied. This article describes the aims and design of a study to evaluate effects and costs of collaborative care with the antidepressant duloxetine for patients with pain symptoms and a depressive disorder, compared to collaborative care with placebo and compared to duloxetine alone

Five interpersonal factors are predictive of the response to treatment of major depression with antidepressants in primary care

Factors relating to the interpersonal relationship between the patient and their physician and social environment are important components, which contribute to their response to treatment for major depressive disorder. This study aimed to assess the influence of optimism, perfectionism, therapeutic alliance, empathy, social support, and adherence to medication regimen in the response to antidepressant treatments in the context of normal primary care clinical practice. Method: We conducted a prospective study in which 24 primary care physicians administered sertraline or escitalopram to 89 patients diagnosed with major depressive disorder. The response to treatment and remission of the episode was assessed at 4 and 12 weeks by Cox regression. The effect of adherence to the medication regimen was assessed by multiple regression statistical techniques. Results: Adherence to medication (HR = 0.262, 95% CI = 0.125-0.553, p < 0.001) and patient perfectionism (HR = 0.259, 95% CI = 0.017-0.624, p < 0.01) negatively predicted the initial response to treatment, whereas patient optimism (HR = 1.221, 95% CI = 1.080-1.380, p < 0.05) positively predicted it. Patient optimism (HR = 1.247, 95% CI = 1.1-1.4, p < 0.05), empathy perceived by the patient (HR = 1.01, 95% CI = 1001-1002, p < 0.05), and therapeutic alliance (HR = 1.02, 95% CI = 1001-1.04, p < 0.05) positively predicted episode remission, while patient perfectionism (HR = 0.219, 95% CI = 0.093-0.515, p < 0.001) and low adherence to the treatment regimen (HR = 0.293, 95% CI = 0.145-0.595, p < 0.001) negatively predicted it. Finally, social support (p < 0.01) and therapeutic alliance (p < 0.05) predicted adherence to the medication regimen. Conclusions: In addition to taking the antidepressant drug, other factors including the personal interactions between the patient with their primary care physician and with their social environment significantly influenced the patients' initial response and the final rate of episode remission

Deciphering the Multifactorial Nature of Acinetobacter baumannii Pathogenicity

Background: Acinetobacter baumannii is an emerging bacterial pathogen that causes a broad array of infections, particularly in hospitalized patients. Many studies have focused on the epidemiology and antibiotic resistance of A. baumannii, but little is currently known with respect to its virulence potential. Methodology/Principal Findings: The aim of this work was to analyze a number of virulence-related traits of four A. baumannii strains of different origin and clinical impact for which complete genome sequences were available, in order to tentatively identify novel determinants of A. baumannii pathogenicity. Clinical strains showed comparable virulence in the Galleria mellonella model of infection, irrespective of their status as outbreak or sporadic strains, whereas a non-human isolate was avirulent. A combined approach of genomic and phenotypic analyses led to the identification of several virulence factors, including exoproducts with hemolytic, phospholipase, protease and iron-chelating activities, as well as a number of multifactorial phenotypes, such as biofilm formation, surface motility and stress resistance, which were differentially expressed and could play a role in A. baumannii pathogenicity. Conclusion/Significance: This work provides evidence of the multifactorial nature of A. baumannii virulence. While A. baumannii clinical isolates could represent a selected population of strains adapted to infect the human host, subpopulations of highly genotypically and phenotypically diverse A. baumannii strains may exist outside the hospita

Topical antibiotics as a major contextual hazard toward bacteremia within selective digestive decontamination studies: a meta-analysis

BACKGROUND: Among methods for preventing pneumonia and possibly also bacteremia in intensive care unit (ICU) patients, Selective Digestive Decontamination (SDD) appears most effective within randomized concurrent controlled trials (RCCT’s) although more recent trials have been cluster randomized. However, of the SDD components, whether protocolized parenteral antibiotic prophylaxis (PPAP) is required, and whether the topical antibiotic actually presents a contextual hazard, remain unresolved. The objective here is to compare the bacteremia rates and patterns of isolates in SDD-RCCT’s versus the broader evidence base. METHODS: Bacteremia incidence proportion data were extracted from component (control and intervention) groups decanted from studies investigating antibiotic (SDD) or non-antibiotic methods of VAP prevention and summarized using random effects meta-analysis of study and group level data. A reference category of groups derived from purely observational studies without any prevention method under study provided a benchmark incidence. RESULTS: Within SDD RCCTs, the mean bacteremia incidence among concurrent component groups not exposed to PPAP (27 control; 17.1%; 13.1-22.1% and 12 intervention groups; 16.2%; 9.1-27.3%) is double that of the benchmark bacteremia incidence derived from 39 benchmark groups (8.3; 6.8-10.2%) and also 20 control groups from studies of non-antibiotic methods (7.1%; 4.8 – 10.5). There is a selective increase in coagulase negative staphylococci (CNS) but not in Pseudomonas aeruginosa among bacteremia isolates within control groups of SDD-RCCT’s versus benchmark groups with data available. CONCLUSIONS: The topical antibiotic component of SDD presents a major contextual hazard toward bacteremia against which the PPAP component partially mitigates. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-014-0714-x) contains supplementary material, which is available to authorized users