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Introduction The aim of this study was to evaluate the bacterial contamination in endodontic consumables (gutta-percha points, rubber dams, paper mixing pads, caulking agents, and endodontic instrument sponges [EISs]) before and after clinical use and storage. Methods Materials were randomly sampled in triplicates at 3 time points (t 0 , at package opening; t 1 , at 7 days; and t 2 , at 14 days) during their clinical usage. The gutta-percha points and caulking agent (25 mg) were added to 1 mL phosphate-buffered saline (PBS). The rubber dam, paper mixing pad, and EIS were added to 25 mL PBS. After vortexing, centrifuging, and removing the supernatant, the pellet was resuspended in 1 mL PBS, plated on fastidious anaerobic agar, and incubated aerobically and anaerobically. The grown colonies were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The total bacterial load was calculated in the remaining volume (800 μL) from each sample by quantitative polymerase chain reaction after DNA extraction. Results All tested materials showed a varied number of contaminated samples at the 3 time points (except EIS at t 0 ) using MALDI-TOF MS. The most isolated genera were Propionibacterium (42%) and Staphylococcus (32%). By using non–culture-based approaches, all tested materials at the 3 time points (except gutta-percha at t 0 and the caulking agent at t 0, t 1, and t 2 ) carried bacterial DNA. Conclusions The majority of the tested materials harbored bacteria in their samples before and after clinical storage. Nosocomial infection derived from commonly used consumables could have an impact on the outcome of endodontic treatment. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Evidence associates Bulimia Nervosa (BN) with altered functioning of the hypothalamic-pituitary-adrenal (HPA) axis, but the clinical implications of such alterations need to be better understood. We contrasted cortisol responses to the dexamethasone suppression test (DST) in bulimic and non-eating disordered women and examined relationships among DST cortisol responses, eating symptoms and co-morbid disturbances. Method: Sixty women with Bulimia Spectrum (BS) Disorders (either BN or normal weight Eating Disorder NOS with regular binge eating or purging) and 54 non-eating disordered women of similar age and body mass index participated in a 0.5mg DST, and completed interviews and questionnaires assessing eating symptoms and co-morbid psychopathology. Results: Compared with the normal-eater group, the BS women demonstrated significantly less DST suppression. Among BS women, DST non-suppression was associated with more severe depression, anxiety and eating preoccupations. Conclusions: Our findings show BS women to show less DST suppression compared to normal eater women, and results link extent of non-suppression, in BS individuals, to severity of depression, anxiety and eating preoccupations. [Copyright &y& Elsevier]

Abstract: This study evaluated the hypothesis that traumatic stress can increase risk of bulimia nervosa (BN) in individuals who are genetically disposed towards lower modulation of physiological stress reactions. We explored the extent to which childhood abuse (physical or sexual), variants of a main glucocorticoid receptor (GR) polymorphism (Bcl1), or their interaction, differentiated women with and without BN. Women seeking treatment for BN (N =129) and non-eating-disordered comparison women (N =98) provided blood samples for assays of the Bcl1 polymorphism, and completed structured interviews assessing eating symptoms, psychiatric symptoms and childhood abuse. Compared to normal-eaters, bulimic women were significantly more likely to carry the low-function Bcl1 C allele (CC or CG genotypes), to report a history of childhood abuse and, more importantly, to be positive for both factors. We interpret our findings as indicating that traumatic stress, when impacting individuals disposed to lower GR modulation, can be etiological for BN. [Copyright &y& Elsevier]

Abstract: Alterations in serotonin function have been implicated in both anorexia and bulimia nervosa, and previous studies suggest associations between serotonin function and variations in pathological personality traits. Women meeting DSM-IV criteria for anorexia nervosa (AN, 16 with the restricting subtype and 14 with the binge–purge subtype) and 49 healthy control women (CW) provided blood samples for analyses of platelet [3H]paroxetine binding. Participants also filled out questionnaires tapping eating disorder symptoms, depression, and personality pathology. Compared with CW, women with restricting and binge–purge AN had significantly lower levels of paroxetine binding (respectively: 1012+487 vs. 560+253 vs. 618+217 fmol/mg protein). Simple correlation analyses showed that, within AN but not within controls, paroxetine binding was inversely related to dieting preoccupations, affective instability, anxiousness, compulsivity, restricted expression and social avoidance but independent of age, body mass index, depression, and other eating symptoms. Findings suggest that reduced peripheral serotonin transporter density in AN relates to increased dieting preoccupations, affective instability and anxiousness–fearfulness. [Copyright &y& Elsevier]

• Pseudomonas aeruginosa produces 2-alkyl-4-quinolones (AQs) quorum sensing signal molecules. • AQs are detectable in the saliva of people with CF with chronic P. aeruginosa. • Salivary AQs correlate with sputum AQs and quantitative Pseudomonas aeruginosa load. • Salivary AQs have potential as non-invasive biomarkers of P. aeruginosa. Pseudomonas aeruginosa produces specific signalling molecules, 2-alkyl-4-quinolones (AQs) that are detectable in the sputum of adults with cystic fibrosis (CF) and who have pulmonary infection with this opportunistic pathogen. This study aimed to determine whether AQs could be detected in saliva of patients with CF and known infection with Pseudomonas aeruginosa. Saliva and sputum samples were obtained from 89 adults with CF and analyzed using liquid chromatography-tandem mass spectrometry. AQs were detected in 39/89 (43.8%) saliva samples and 70/77(90.9%) sputum samples. Salivary AQs had a sensitivity of 50% (95%CI; 37.8; 62.2), specificity of 100% (95%CI; 47.8; 100), when compared to a molecular microbiological measure of P. aeruginosa in sputum as measured using polymerase chain reaction. Specific AQs produced by P. aeruginosa can be detected in the saliva and warrant investigation as potential non-invasive biomarkers of pulmonary P. aeruginosa. [ABSTRACT FROM AUTHOR]

Rifaximin-α is efficacious for the prevention of recurrent hepatic encephalopathy (HE), but its mechanism of action remains unclear. We postulated that rifaximin-α reduces gut microbiota-derived endotoxemia and systemic inflammation, a known driver of HE. In a placebo-controlled, double-blind, mechanistic study, 38 patients with cirrhosis and HE were randomised 1:1 to receive either rifaximin-α (550 mg BID) or placebo for 90 days. Primary outcome: 50% reduction in neutrophil oxidative burst (OB) at 30 days. Secondary outcomes: changes in psychometric hepatic encephalopathy score (PHES) and neurocognitive functioning, shotgun metagenomic sequencing of saliva and faeces, plasma and faecal metabolic profiling, whole blood bacterial DNA quantification, neutrophil toll-like receptor (TLR)-2/4/9 expression and plasma/faecal cytokine analysis. Patients were well-matched: median MELD (11 rifaximin-α vs. 10 placebo). Rifaximin-α did not lead to a 50% reduction in spontaneous neutrophil OB at 30 days compared to baseline (p = 0.48). However, HE grade normalised (p = 0.014) and PHES improved (p = 0.009) after 30 days on rifaximin-α. Rifaximin-α reduced circulating neutrophil TLR-4 expression on day 30 (p = 0.021) and plasma tumour necrosis factor-α (TNF-α) (p < 0.001). Rifaximin-α suppressed oralisation of the gut, reducing levels of mucin-degrading sialidase-rich species, Streptococcus spp , Veillonella atypica and parvula, Akkermansia and Hungatella. Rifaximin-α promoted a TNF-α- and interleukin-17E-enriched intestinal microenvironment, augmenting antibacterial responses to invading pathobionts and promoting gut barrier repair. Those on rifaximin-α were less likely to develop infection (odds ratio 0.21; 95% CI 0.05-0.96). Rifaximin-α led to resolution of overt and covert HE, reduced the likelihood of infection, reduced oralisation of the gut and attenuated systemic inflammation. Rifaximin-α plays a role in gut barrier repair, which could be the mechanism by which it ameliorates bacterial translocation and systemic endotoxemia in cirrhosis. ClinicalTrials.gov NCT02019784. In this clinical trial, we examined the underlying mechanism of action of an antibiotic called rifaximin-α which has been shown to be an effective treatment for a complication of chronic liver disease which effects the brain (termed encephalopathy). We show that rifaximin-α suppresses gut bacteria that translocate from the mouth to the intestine and cause the intestinal wall to become leaky by breaking down the protective mucus barrier. This suppression resolves encephalopathy and reduces inflammation in the blood, preventing the development of infection. [Display omitted] • Rifaximin reduced gut-derived systemic inflammation by suppressing oralisation of the gut microbiome. • Rifaximin suppressed mucin-degrading species rich in sialidase, e.g. Streptococcus and Veillonella spp. • Rifaximin promotes an intestinal environment augmenting responses to pathobionts and promoting gut barrier repair. • Patients treated with rifaximin were less likely to develop infections. [ABSTRACT FROM AUTHOR]

Abstract: Rapid point-of-care pathogen detection remains a challenge in routine diagnostics. A Staphylococcus aureus–specific lateral flow immunochromatography (LFI) test has been developed using a specific monoclonal antibody to the S. aureus cell-wall peptidoglycan. The LFI test was shown to be specific for S. aureus with no signal development for other Staphylococcal species or common respiratory pathogens. Evaluation of S. aureus isolates spiked into induced sputum and bronchoalveolar lavage samples derived from severe asthmatic patients showed a detection limit of 106 CFU/mL for the LFI. The test was also shown to successfully detect S. aureus in 1 sample independently determined to be S. aureus positive by quantitative polymerase chain reaction. The ability of the LFI test to rapidly detect S. aureus in clinical respiratory samples suggests that it might be a useful platform for further development of point-of-care diagnostic applications. [Copyright &y& Elsevier]

Abstract: Across populations, findings suggest that rates of self-mutilation, suicidal acts, and other self-harming behaviors (SHBs) may be influenced by polymorphisms that code for activity of the serotonin transporter (e.g., 5HTTLPR) and the enzyme, monoamine oxidase A (e.g., MAOAuVNTR). SHBs being common in patients with Eating Disorders (EDs), we evaluated (in a large sample of eating-disordered women) relationships between triallelic 5HTTLPR and MAOAuVNTR variants, on the one hand, and SHBs, on the other. We had 399 eating-disordered women report on eating symptoms and lifetime history of SHBs, and provide blood samples for genotyping. Individuals carrying high-function MAOAuVNTR alleles reported a history of SHBs about twice as often as did carriers of low-function alleles. We obtained no comparable main effect of 5HTTLPR, or MAOAuVNTR×5HTTLPR interaction effect. Genetic variations did not predict severity of eating symptoms. As in other populations, our findings link the MAOAuVNTR high-function alleles with increased risk of self-directed harm in bulimic females. We discuss theoretical and clinical ramifications of our results. [ABSTRACT FROM AUTHOR]

Many plants exhibit circadian clock-driven leaf movements whereby the leaves are raised during the day to achieve a relatively high angle during the evening, before lowering late in the night. Such leaf movements were first recorded over 2000 years ago but there is still much debate as to their purpose. We investigated whether such leaf movements within Arabidopsis, a ruderal rosette plant, can aid in overtopping leaves of neighboring plants. Wild type and circadian clock mutant plants were grown in an alternating grid system so that their leaves would meet as the plants grew. Experiments were performed using day lengths that matched the endogenous rhythm of either wild type or mutant. Plants grown in a day length shorter than their endogenous rhythm were consistently overtopped by plants which were in synchrony with the day night cycle, demonstrating a clear overtopping advantage resulting from circadian leaf movement rhythms. Furthermore, we found that this leaf overtopping as a result of correctly synchronized circadian leaf movements is additive to leaf overtopping due to shade avoidance. Curiously, this did not apply to plants grown in a day length longer than their endogenous period. Plants grown in a day length longer than their endogenous period were able to adapt their leaf rhythms and suffered no overtopping disadvantage. Crucially, our results show that, in a context-dependent manner, circadian clock-driven leaf movements in resonance with the external light/dark cycle can facilitate overtopping of the leaves of neighboring plants. [ABSTRACT FROM AUTHOR]

Highlights: [•] Interpreting complex microbiota in infective contexts is a pressing challenge. [•] Potentially, associations can be interpreted spuriously as causal. [•] We argue for the need to include ecological theory in clinical interpretation. [•] Cystic fibrosis lung infections are used as an illustrative model system. [Copyright &y& Elsevier]

Abstract: We explored the influence of interactions between polymorphisms acting upon postsynaptic receptors (DRD2 TaqA1 rs1800497 and DRD4 7R) and dopamine regulators (COMT rs4680 and DAT1) on the expression of eating symptoms and personality traits in women with bulimia-spectrum eating disorders. We had 269 bulimic women provide blood for genetic assays, and measured eating-disorder symptoms and psychopathological traits using structured interviews and self-report questionnaires. We observed two epistatic interactions on symptom indices: interactions (in predicted directions) of DRD2 by DAT were seen on Body Mass Index (p =.023), and of DRD4 by COMT on self-harming behaviors (p =.014) —with genetic effects that would correspond to reduced dopamine transmission coinciding with more-pathological scores. Our findings suggest that genes acting in the dopamine system interact to influence both eating-related and personality psychopathology, with the result that lower levels of dopamine neuro-transmission correspond to increased psychopathology and body mass in women with bulimia-spectrum disorders. We discuss the implications of our observations. [Copyright &y& Elsevier]

Abstract: Objective: We explored interaction effects involving polymorphisms of targeted dopamine system genes and selected forms of childhood abuse (sexual, physical and emotional) acting upon severity of binge-eating and psychopathological symptoms in women with Bulimia-Spectrum Disorders (BSDs). Methods: Women diagnosed with a BSD (n = 216) were assessed for childhood traumata, eating-disorder (ED) symptoms, and selected psychopathological features (sensation seeking, impulsivity, compulsivity and affective instability), and then provided blood samples for genotyping of main polymorphisms of dopamine-2 receptor (DRD2), dopamine transporter (DAT1) and catechol o-methyltransferase (COMT) genes. Results: Sensation Seeking was elevated in carriers of the low-function allele of the DRD2 Taq1A polymorphism who also reported childhood sexual abuse, relative to that in individuals showing other combinations of alleles and abuse exposures. In addition, carriers of a low-function allele of COMT scored higher on compulsivity, lower on impulsivity, and marginally lower on frequency of binge-eating than did individuals in whom the allele was absent. Discussion: Our results suggest that genes acting within the dopamine system may contribute, either directly or indirectly (i.e., in interaction with traumatic childhood experiences), to variations in the presentation of comorbid traits and, possibly, of bulimic symptoms. [Copyright &y& Elsevier]

Abstract: We recently documented a gene-environment interaction suggesting that individuals with Bulimia Nervosa (BN) differed from normal eaters as to the combined presence of the low-function allele of the glucocorticoid receptor polymorphism, BcII, and childhood abuse. The present study examined the extent to which any such interaction effect may have been attributable to behavioral impulsivity, sensation seeking, affective instability or depression. We had 174 bulimic and 130 nonbulimic women provide blood for genetic assays, and measured psychopathological traits and childhood abuse using structured interviews and self-report questionnaires. As expected, we observed a significant BcII × abuse interaction indicating genetic and environmental susceptibilities to co-occur significantly more often in bulimic than in nonbulimic individuals. The BcII × abuse interaction was attenuated when levels of depression were accounted for, but was surprisingly unaffected by controls for motoric impulsivity, sensation seeking or affective instability. Our findings suggest that stress-induced alterations in glucocorticoid sensitivity contribute to BN and depressive disturbances—without being associated with the behavioral/affective dysregulation seen in many BN sufferers. We discuss theoretical and clinical implications of these observations. [Copyright &y& Elsevier]

As a new generation of culture-independent analytical strategies emerge, the amount of data on polymicrobial infections will increase dramatically. For these data to inform clinical thinking, and in turn to maximise benefits for patients, an appropriate framework for their interpretation is required. Here, we use cystic fibrosis (CF) lower airway infections as a model system to examine how conceptual and technological advances can address two clinical questions that are central to improved management of CF respiratory disease. Firstly, can markers of the microbial community be identified that predict a change in infection dynamics and clinical outcomes? Secondly, can these new strategies directly characterize the impact of antimicrobial therapies, allowing treatment efficacy to be both assessed and optimized? [ABSTRACT FROM AUTHOR]

Abstract: Context: Efforts to classify eating-disordered individuals based on concurrent personality traits have consistently converged on a typology encompassing “over-regulated”, “dysregulated”, and “low psychopathology” subgroups. In various populations, evidence has associated personality variations of an “over-regulated/dysregulated” type with differences on serotonin-system indices, and specifically, with different loadings of serotonin transporter promoter regulatory region polymorphism (5HTTLPR) genotypes and alleles. We explored the extent to which an empirical, trait-defined typology of eating-disordered individuals coincided systematically with variations in 5HTTLPR, assayed using biallelic and triallelic models. Method: We tested 185 women with a DSM-IV eating disorder (108 with Bulimia Nervosa, 17 Anorexia Nervosa, and 60 an Eating Disorder Not Otherwise Specified) and 93 with no eating disorder on measures reflecting psychopathological traits and 5HTTLPR (biallelic and triallelic) genotypes and alleles. Results: The highest-function, triallelic (LA/LA) genotype occurred significantly more frequently among eating-disordered individuals than among controls. However, a more fine-grained analysis suggested that this association was attributable to the fact that, among eating-disordered participants, those displaying an “Inhibited/Compulsive” profile (derived using latent class analysis) were more likely than those of a “Dissocial/Impulsive” or a “Low Psychopathology” group to carry the triallelic 5HTTLPR gain-of-function LA allele and to be LA/LA homozygotes. Discussion: This study’s empirically derived classes coincide with interpretable differences on genetic indices—associating an “Inhibited/Compulsive” group with 5HTTLPR gain-of-function genotypes (and alleles) that have elsewhere been linked to trait compulsivity. The findings, furthermore, suggest that 5HTTLPR, by influencing personality-trait manifestations may, in turn, influence eating-disorder risk and symptom expression. [Copyright &y& Elsevier]

Abstract: The genus Pseudomonas contains species that can act as human pathogens and are important in many infections such as those occurring in the lungs of many cystic fibrosis (CF) patients. Current methodologies that rely on the cultivation of bacteria are too cumbersome and often lack sufficient discriminatory power to define the diversity of Pseudomonas spp. As a result, molecular-based approaches have many advantages when attempting to differentiate between species of this genus. This study assessed the ability of terminal restriction fragment length polymorphism (T-RFLP) profiling of the 16S–23S rRNA ITS1 gene region to differentiate species of the genus Pseudomonas. Before application to clinical samples, this approach was validated on a panel of 10 different Pseudomonas spp. T-RFLP profiling of the 16S–23S rRNA ITS1 gene region amplified from these strains differentiated all Pseudomonas spp. tested. The presence of Pseudomonas spp. in CF sputum was assessed through the detection of this ITS1 gene region as amplified from DNA extracted from 40 samples of CF sputum. The ITS1 gene region was detected in 75% of these samples, including 5 from which no Pseudomonas spp. had been identified using culture-based methods. In silico analysis showed that all sequences amplified had a high homology with the ITS1 region of Pseudomonas aeruginosa. T-RFLP gave data that were consistent with the band being generated from P. aeruginosa for each patient. No correlation between Pseudomonas diversity and severity of lung disease was observed in this group of CF patients. This study has however shown that molecular analysis of the ITS1 region is effective in resolving diversity within the genus Pseudomonas. The wider use of this application is discussed. [Copyright &y& Elsevier]

Abstract: Identification of bacteria in clinical samples is fundamental to combating infections. Modern molecular genetic approaches exploit nucleic acids signals from clinical samples. However, DNA-derived signals can originate from nonviable bacterial cells and, therefore, generate data that could be misinterpreted. Terminal restriction fragment length polymorphism profiling of cystic fibrosis sputum samples was combined with propidium monoazide (PMA) photo-induced cross-linking. PMA is highly membrane impermeant and is excluded from viable bacteria but readily penetrates dead cells. Exposure to a light source renders DNA in permeable cells incapable of contributing to polymerase chain reaction. PMA treatment was shown to effectively prevent dead bacteria, spiked into sputum samples, from contributing to profiles. Comparison of treated and untreated clinical samples indicated that dead bacterial cells significantly bias untreated profiles. These findings highlight the significant contribution that nonviable bacteria can make to DNA-based diagnostic analysis of clinical samples while providing a simple and effective means of avoiding such bias. [Copyright &y& Elsevier]