The Role of the IL-12 Cytokine Family in Directing T-Cell Responses in Oral Candidosis

Candida albicans is an opportunistic fungal pathogen that normally exists as a harmless commensal in humans. In instances where host debilitation occurs, Candida can cause a range of clinical infections, and whilst these are primarily superficial, effecting mucosal membranes, systemic infections can develop in severely immunocompromised individuals. The mechanism of host immunity during commensal carriage of C. albicans has been intensively studied. In this paper, we present the most recent information concerning host recognition of C. albicans leading to cytokine production and the subsequent T-cell responses generated in response to C. albicans. Particular focus is given to the role of the IL-12 cytokine family including IL-12, IL-23, IL-27, and IL-35, in host immunity to Candida. CD4+ T-cells are considered crucial in the regulation of immunity and inflammation. In this regard, the role of Th1/2, helper cells, together with the recently identified Th17 and Treg cells in candidosis will be discussed. Understanding the detailed mechanisms that underlie host immunity to Candida not only will be of benefit in terms of the infections caused by this organism but could also be exploited in the development of therapeutic interventions for other diseases

Role of Bacterial Lipopolysaccharide in Enhancing Host Immune Response to Candida albicans

Human infections involving yeast of the genus Candida often occur in the presence of bacteria, and, as such, it is important to understand how these bacteria influence innate host immunity towards Candida. Dectin-1 is a cell receptor of macrophages for Candida albicans recognition. The aim of this study was to examine dectin-1 expression by monocytes after stimulation with bacterial lipopolysaccharide (LPS), followed by heat-killed C. albicans (HKC). Freshly isolated human peripheral blood monocytes (PBMCs) and human monocytes cell line (THP-1) cells expressed low levels of dectin-1. Stimulation with LPS and GM-CSF/IL-4 was found to increase dectin-1 expression in both CD14(+) human PBMC and THP-1 cells. Enhanced dectin-1 expression resulted in increased phagocytosis of Candida. When THP-1 cells were challenged only with HKC, detectable levels of IL-23 were not evident. However, challenge by LPS followed by varying concentrations of HKC resulted in increased IL-23 expression by THP-1 cells in HKC dose-dependent manner. Increased expression of IL-17 by PBMC also occurred after stimulation with Candida and LPS. In conclusion, bacterial LPS induces an enhanced immune response to Candida by immune cells, and this occurs through increasing dectin-1 expression

Mental Health First Aid USA: The Implementation of a Mental Health First Aid Training Program in a Rural Healthcare Setting

Nearly one-quarter of adults in the United States suffer from a documented mental disorder. Consequently, anyone could encounter a person with symptoms of mental illness at some point as they carry out their daily life activities. Although laypersons may accurately identify physical illnesses, they may lack necessary skills to identify symptoms of mental disorders, or know how to adequately respond to persons in a mental health crisis. Mental Health First Aid USA is an evidence-based certification program designed to teach lay citizens to recognize certain symptoms of common mental illnesses, offer and provide first aid assistance, and guide a person toward appropriate services and other support. The program targets a broad audience, from teachers, police officers, clergy members, and healthcare professionals to the average citizen volunteer. This practice note describes a pilot implementation of Mental Health First Aid USA by a social worker at a rural hospital in Central California. The process and results of program implementation are discussed as well as implications for social work practice in rural healthcare settings

The differential risk of oral contraceptives: the impact of full exposure history*

Previous discussions have indicated that the small increases of risk of venous thromboembolism (VTE) associated with newer combined oral contraceptives (third generation, containing desogestrel and gestodene) may be attributed to bias due to cohort effects. In a case-control analysis, this may produce an overestimate of risk of newer preparations. In 10 centres in Germany and the UK, the Transnational Study analysed data from 502 women aged 16-44 years with VTE, and from 1864 controls matched for 5-year age group and region. Information on lifetime exposure history from all subjects was added to the dataset used in previous analyses and entered into a Cox regression model with time-dependent covariates. Based on 17 622 continuous exposure episodes comprising 47 914 person-years of observation, the adjusted hazard ratio (equivalent to odds ratio, OR) of VTE for the comparison of current users of third-generation versus current users of second-generation (primarily levonorgestrel compounds) combined oral contraceptives was 0.8 (0.5 to 1.3). The OR obtained in standard case-control analysis had been 1.5 (1.1 to 2.1). Adjustment for past exposures includes more information and appears more valid than the standard cross-sectional analysis. Using this approach, the Transnational Study data show no evidence for an increased risk of VTE with third- compared with second-generation combined oral contraceptive

Comparison of genotypes, antimicrobial resistance and virulence profiles of oral and non oral Enterococcus faecalis from Brazil, Japan and the United Kingdom

Objectives To determine whether phenotypic and genotypic differences amongst isolates ofEnterococcus faecalis relate to geographical and clinical origin. Methods E. faecalis from primary endodontic infections in Brazilian patients (n = 20), oral infections in UK patients (n = 10), and non-oral infections in Japanese patients (n = 9) were studied. In addition, 20 environmental vancomycin resistant Enterococcus faecalis (VRE) isolates from a UK hospital were analysed. For all isolates, polymerase chain reaction (PCR) was used to detect genes associated with antibiotic resistance and virulence, whilst randomly amplified polymorphic DNA-PCR (RAPD-PCR) was used to produce molecular profiles. Results Gelatinase gene (gelE) was prevalent amongst isolates (77–100%) and for oral isolates, genes of aggregation substances (agg), immune evasion protein (esp), cytolysin (cylB), tetracycline resistance (tetM; tetL) and erythromycin resistance (ermB) were detected to varying extent. Japanese non-oral isolates had a similar genetic profile to oral isolates, but with higher prevalence of ermB and cylB. All VRE isolates were positive for gelE, esp, agg, vanA, ermB and tetM, 95% were positive for cylB and 17% positive for tetL. All isolates were negative for ermA, asa373 vanB, vanC1 and vanC2/3. RAPD-PCR revealed clustering of VRE isolates. Conclusions RAPD-PCR analysis revealed extensive genetic variability among the tested isolates. Oral isolates carried antibiotic resistance genes for tetracycline and whilst they possessed genes that could contribute to pathogenicity, these were detected at lower incidence compared with non-oral and VRE isolates. RAPD-PCR proved to be a useful approach to elucidate relatedness of disparate isolates

Respiratory pathogen colonisation of dental plaque, the lower airways and endotracheal tube biofilms during mechanical ventilation

Purpose In mechanically ventilated patients, the endotracheal tube is an essential interface between the patient and ventilator, but inadvertently, it also facilitates the development of ventilator-associated pneumonia (VAP) by subverting pulmonary host defenses. A number of investigations suggest that bacteria colonizing the oral cavity may be important in the etiology of VAP. The present study evaluated microbial changes that occurred in dental plaque and lower airways of 107 critically ill mechanically ventilated patients. Materials and Methods Dental plaque and lower airways fluid was collected during the course of mechanical ventilation, with additional samples of dental plaque obtained during the entirety of patients' hospital stay. Results A “microbial shift” occurred in dental plaque, with colonization by potential VAP pathogens, namely, Staphylococcus aureus and Pseudomonas aeruginosa in 35 patients. Post-extubation analyses revealed that 70% and 55% of patients whose dental plaque included S aureus and P aeruginosa, respectively, reverted back to having a predominantly normal oral microbiota. Respiratory pathogens were also isolated from the lower airways and within the endotracheal tube biofilms. Conclusions To the best of our knowledge, this is the largest study to date exploring oral microbial changes during both mechanical ventilation and after recovery from critical illness. Based on these findings, it was apparent that during mechanical ventilation, dental plaque represents a source of potential VAP pathogens

Searching for faces differs from categorization: Evidence from scenes and eye movements

This study examined whether the detection of frontal, ¾ and profile face views differs from their categorization as faces. Experiment 1 compared three tasks that required observers to determine the presence or absence of a face but varied in the extent to which they had to search for faces in simple displays and small or large scenes to make this decision. Performance was equivalent for all face views in simple displays and small scenes, but was notably slower for profile views when this required the search for faces in extended scene displays. This search effect was confirmed in Experiment 2, which compared observers’ eye movements with their response times to faces in visual scenes. These results demonstrate that the categorization of faces at fixation is dissociable from the detection of faces in space. Consequently, we suggest that face detection should be studied with extended visual displays, such as natural scenes