Molecular epidemiology of Streptococcus agalactiae in non-pregnant populations: a systematic review.

Streptococcus agalactiae (group B Streptococcus, GBS) has recently emerged as an important pathogen among adults. However, it is overlooked in this population, with all global efforts being directed towards its containment among pregnant women and neonates. This systematic review assessed the molecular epidemiology and compared how the lineages circulating among non-pregnant populations relate to those of pregnant and neonatal populations worldwide. A systematic search was performed across nine databases from 1 January 2000 up to and including 20 September 2021, with no language restrictions. The Joanna Briggs Institute (JBI) Prevalence Critical Appraisal Tool (PCAT) was used to assess the quality of included studies. The global population structure of GBS from the non-pregnant population was analysed using in silico typing and phylogenetic reconstruction tools. Twenty-four articles out of 13 509 retrieved across 9 databases were eligible. Most studies were conducted in the World Health Organization European region (12/24, 50 %), followed by the Western Pacific region (6/24, 25 %) and the Americas region (6/24, 25 %). Serotype V (23%, 2310/10240) and clonal complex (CC) 1 (29 %, 2157/7470) were the most frequent serotype and CC, respectively. The pilus island PI1 : PI2A combination (29 %, 3931/13751) was the most prevalent surface protein gene, while the tetracycline resistance tetM (55 %, 5892/10624) was the leading antibiotic resistance gene. This study highlights that, given the common serotype distribution identified among non-pregnant populations (V, III, Ia, Ib, II and IV), vaccines including these six serotypes will provide broad coverage. The study indicates advanced molecular epidemiology studies, especially in resource-constrained settings for evidence-based decisions. Finally, the study shows that considering all at-risk populations in an inclusive approach is essential to ensure the sustainable containment of GBS.

Palidis: fast discovery of novel insertion sequences.

The diversity of microbial insertion sequences, crucial mobile genetic elements in generating diversity in microbial genomes, needs to be better represented in current microbial databases. Identification of these sequences in microbiome communities presents some significant problems that have led to their underrepresentation. Here, we present a bioinformatics pipeline called Palidis that recognizes insertion sequences in metagenomic sequence data rapidly by identifying inverted terminal repeat regions from mixed microbial community genomes. Applying Palidis to 264 human metagenomes identifies 879 unique insertion sequences, with 519 being novel and not previously characterized. Querying this catalogue against a large database of isolate genomes reveals evidence of horizontal gene transfer events across bacterial classes. We will continue to apply this tool more widely, building the Insertion Sequence Catalogue, a valuable resource for researchers wishing to query their microbial genomes for insertion sequences.

Predicting the Development of Adult Nature Connection Through Nature Activities: Developing the Evaluating Nature Activities for Connection Tool.

Nature Connection (NC) is considered an important driver of conservation behavior. Consequently, conservation organizations run many activities aiming to increase NC among participants. However, little is known about which activities are most effective at doing this and why. This study developed the Evaluating Nature Activities for Connection Tool (ENACT), to evaluate the effectiveness of activities for increasing participants' NC and nature-related intentions. ENACT comprises 11 activity aspects identified through two research phases. In Phase 1, a literature search, focus group and interviews identified desired, short-term behavioral outcomes of nature activities, and variables that might promote these. In Phase 2, 241 adults completed a pilot survey immediately post-nature activity, with 1-month follow-up (N = 145), to evaluate the impact of participation on NC, nature-related behavioral intentions and behaviors. ENACT correlated with NC measures and offered incremental validity in predicting nature-related behavioral intentions and self-reported behaviors after 1 month.

Probing the Mobilome: Discoveries in the Dynamic Microbiome.

There has been an explosion of metagenomic data representing human, animal, and environmental microbiomes. This provides an unprecedented opportunity for comparative and longitudinal studies of many functional aspects of the microbiome that go beyond taxonomic classification, such as profiling genetic determinants of antimicrobial resistance, interactions with the host, potentially clinically relevant functions, and the role of mobile genetic elements (MGEs). One of the most important but least studied of these aspects are the MGEs, collectively referred to as the 'mobilome'. Here we elaborate on the benefits and limitations of using different metagenomic protocols, discuss the relative merits of various sequencing technologies, and highlight relevant bioinformatics tools and pipelines to predict the presence of MGEs and their microbial hosts.

Abundance and diversity of resistomes differ between healthy human oral cavities and gut.

The global threat of antimicrobial resistance has driven the use of high-throughput sequencing techniques to monitor the profile of resistance genes, known as the resistome, in microbial populations. The human oral cavity contains a poorly explored reservoir of these genes. Here we analyse and compare the resistome profiles of 788 oral cavities worldwide with paired stool metagenomes. We find country and body site-specific differences in the prevalence of antimicrobial resistance genes, classes and mechanisms in oral and stool samples. Within individuals, the highest abundances of antimicrobial resistance genes are found in the oral cavity, but the oral cavity contains a lower diversity of resistance genes compared to the gut. Additionally, co-occurrence analysis shows contrasting ARG-species associations between saliva and stool samples. Maintenance and persistence of antimicrobial resistance is likely to vary across different body sites. Thus, we highlight the importance of characterising the resistome across body sites to uncover the antimicrobial resistance potential in the human body.

Overlooked and underestimated? Problematic alcohol use in clients recovering from drug dependence.

AIMS: Despite recognition of the harms related to alcohol misuse and its potential to interfere substantially with sustained recovery from drug dependency, research evaluating drug treatment outcomes has not addressed the issue comprehensively. It has been overlooked possibly because treatment research has been framed according to the primary drug of choice, rather than investigating the interactions between different combinations of drugs and/or alcohol use. This paper reports on a systematic review investigating whether concurrent alcohol use could impede recovery from illicit drug use in two potential ways: first, alcohol could become a substitute addiction and/or secondly, alcohol misuse post-treatment may place an individual at risk for relapse to their primary drug problem. METHOD: A systematic search of four relevant databases was undertaken to identify peer-reviewed, quantitative drug treatment outcome studies that reported alcohol use pre-, post-treatment and follow-up. RESULTS: The search revealed 567 papers, of which 13 were assessed as fulfilling the key inclusion criteria.The review indicated inconsistent and therefore inconclusive support for the substitution hypothesis. However, the data revealed consistent support for the hypothesis that alcohol use increases relapse to drug use. CONCLUSIONS: (i) The potential negative impact of alcohol misuse on drug treatment outcomes remains under-researched and overlooked; (ii) alcohol consumption post-drug treatment may increase the likelihood that an individual will relapse to their primary drug; (ii) existing evidence regarding the substitution hypothesis is inconclusive, although there was an indication that a subgroup of participants will be vulnerable to alcohol becoming the primary addiction instead of drugs. We argue that future drug treatment outcome studies need to include detailed analysis of the influence of alcohol use pre- and post-drug treatment.

Evaluating candidate reactions to selection practices using organisational justice theory.

OBJECTIVES: This study aimed to examine candidate reactions to selection practices in postgraduate medical training using organisational justice theory. METHODS: We carried out three independent cross-sectional studies using samples from three consecutive annual recruitment rounds. Data were gathered from candidates applying for entry into UK general practice (GP) training during 2007, 2008 and 2009. Participants completed an evaluation questionnaire immediately after the short-listing stage and after the selection centre (interview) stage. Participants were doctors applying for GP training in the UK. Main outcome measures were participants' evaluations of the selection methods and perceptions of the overall fairness of each selection stage (short-listing and selection centre). RESULTS: A total of 23,855 evaluation questionnaires were completed (6893 in 2007, 10,497 in 2008 and 6465 in 2009). Absolute levels of perceptions of fairness of all the selection methods at both the short-listing and selection centre stages were consistently high over the 3years. Similarly, all selection methods were considered to be job-related by candidates. However, in general, candidates considered the selection centre stage to be significantly fairer than the short-listing stage. Of all the selection methods, the simulated patient consultation completed at the selection centre stage was rated as the most job-relevant. CONCLUSIONS: This is the first study to use a model of organisational justice theory to evaluate candidate reactions during selection into postgraduate specialty training. The high-fidelity selection methods are consistently viewed as more job-relevant and fairer by candidates. This has important implications for the design of recruitment systems for all specialties and, potentially, for medical school admissions. Using this approach, recruiters can systematically compare perceptions of the fairness and job relevance of various selection methods.

New machine-marked tests for selection into core medical training: evidence from two validation studies.

This study examined whether two machine-marked tests (MMTs; a clinical problem-solving test and situational judgement test), previously validated for selection into U.K. general practice (GP) training, could provide a valid methodology for shortlisting into core medical training (CMT). A longitudinal design was used to examine the MMTs' psychometric properties in CMT samples, and correlations between MMT scores and CMT interview outcomes. Independent samples from two years were used: in 2008, a retrospective analysis was conducted (n=1711), while in 2009, CMT applicants completed the MMTs for evaluation purposes (n=2265). Both MMTs showed good reliability in CMT samples, similar to GP samples. Both MMTs were good predictors of CMT interview performance (r = 0.56, p < 0.001 in 2008; r = 0.61, p < 0.001 in 2009) and offered incremental validity over the current shortlisting process. The GP MMTs offer an appropriate measurement methodology for selection into CMT, representing a significant innovation for selection methodology.

Evaluation of three short-listing methodologies for selection into postgraduate training in general practice.

OBJECTIVE: This study aimed to evaluate the effectiveness and efficiency of three short-listing methodologies for use in selecting trainees into postgraduate training in general practice in the UK. METHODS: This was an exploratory study designed to compare three short-listing methodologies. Two methodologies - a clinical problem-solving test (CPST) and structured application form questions (AFQs) - were already in use for selection purposes. The third, a new situational judgement test (SJT), was evaluated alongside the live selection process. An evaluation was conducted on a sample of 463 applicants for training posts in UK general practice. Applicants completed all three assessments and attended a selection centre that used work-related simulations at final stage selection. Applicant scores on each short-listing methodology were compared with scores at the selection centre. RESULTS: Results indicate the structured AFQs, CPST and SJT were all valid short-listing methodologies. The SJT was the most effective independent predictor. Both the structured AFQs and the SJT add incremental validity over the use of the CPST alone. Results show that optimum validity and efficiency is achieved using a combination of the CPST and SJT. CONCLUSIONS: A combination of the CPST and SJT represents the most effective and efficient battery of instruments as, unlike AFQs, these tests are machine-marked. Importantly, this is the first study to evaluate a machine-marked SJT to assess non-clinical domains for postgraduate selection. Future research should explore links with work-based assessment once trainees are in post to address long-term predictive validity.

Biased use of VH5 IgE-positive B cells in the nasal mucosa in allergic rhinitis.

BACKGROUND: IgE antibody-producing B cells are enriched in the nasal mucosa in patients with allergic rhinitis because of local class switching to IgE. The expressed IgE VH genes also undergo somatic hypermutation in situ to generate clonal families. The antigenic driving force behind these events is unknown. OBJECTIVE: To examine the possible involvement of a superantigen in allergic rhinitis, we compared the variable (VH) gene use and patterns of somatic mutation in the expressed IgE heavy-chain genes in nasal biopsy specimens and blood from allergic patients and the IgA VH use in the same biopsy specimens and also those from nonallergic controls. METHODS: We extracted mRNA from the nasal biopsy specimens of 13 patients and 4 nonallergic control subjects and PBMCs from 7 allergic patients. IgE and IgA VH regions were RT-PCR amplified, and the DNA sequences were compared with those of control subjects. We constructed a molecular model of VH5 to locate amino acids of interest. RESULTS: We observed a significantly increased frequency of IgE and IgA VH5 transcripts in the nasal mucosa of the allergic patients compared with the normal PBMC repertoire. Within IgE and IgA VH5 sequences in the nasal mucosa, the distribution of replacement amino acids was skewed toward the immunoglobulin framework regions. Three of 4 nonintrinsic hotspots of mutation identified in the VH5 sequences were in framework region 1. The hotspots and a conserved VH5-specific framework residue form a tight cluster on the surface of VH5. CONCLUSION: Our results provide evidence for the activity of a superantigen in the nasal mucosa in patients with allergic rhinitis.

Improving the management and quality of life of patients with allergic rhinitis.

Allergic rhinitis affects up to a fifth of the population in the West, yet there is little specialist care to support and manage patients, and medical and nursing curicula fail to address the issue of allergies. This paper looks at the main causes of allergic rhinitis and its symptoms, and describes the available treatments to manage the conditon.

Allergen drives class switching to IgE in the nasal mucosa in allergic rhinitis.

IgE-expressing B cells are over 1000 times more frequent in the nasal B cell than the peripheral blood B cell population. We have investigated the provenance of these B cells in the nasal mucosa in allergic rhinitis. It is generally accepted that expression of activation-induced cytidine deaminase and class switch recombination (CSR) occur in lymphoid tissue, implying that IgE-committed B cells must migrate through the circulation to the nasal mucosa. Our detection of mRNA for activation-induced cytidine, multiple germline gene transcripts, and epsilon circle transcripts in the nasal mucosa of allergic, in contrast to nonallergic control subjects, however, indicates that local CSR occurs in allergic rhinitis. The germline gene transcripts and epsilon circle transcripts in grass pollen-allergic subjects are up-regulated during the season and also when biopsies from allergic subjects are incubated with the allergen ex vivo. These results demonstrate that allergen stimulates local CSR to IgE, revealing a potential target for topical therapies in allergic rhinitis.

Relation of CD4+CD25+ regulatory T-cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease.

BACKGROUND: Allergic diseases are frequent and rising in prevalence, and result from activation of T-helper (Th) 2 cells by allergens. CD4+CD25+ regulatory T cells suppress T-cell activation in vitro and prevent pathological findings in animal models of disease. We aimed to investigate whether the amount of inhibition of allergic responses by CD4+CD25+ T cells was related to atopy and allergic disease. METHODS: Blood CD4+CD25+ and CD4+CD25- T cells were isolated from three groups of donors: non-atopic individuals; those atopic with no present symptoms; and patients with hayfever studied during and out of the grass-pollen season. We investigated the ability of CD25+ T cells from these donors to suppress allergen-stimulated T-cell proliferation and cytokine production in vitro. FINDINGS: CD4+CD25+ T cells from non-atopic donors suppressed proliferation and interleukin 5 production by their own allergen-stimulated CD4+CD25- T cells. Inhibition of proliferation by CD4+CD25+ T cells from atopic donors was significantly reduced (p=0.0012), and was even more diminished by CD4+CD25+ T cells isolated from patients with hayfever during the pollen season (p=0.0003). In patients with hayfever, out-of-season suppression remained less than that seen by regulatory cells from non-atopic donors. INTERPRETATION: Allergic disease can result from an inappropriate balance between allergen activation of regulatory CD4+CD25+ T cells and effector Th2 cells. This imbalance could result from a deficiency in suppression by regulatory T cells or strong activation signals could overcome such regulation. Treatment to enhance regulatory T-cell responses, in concert with reduction of Th2 cell activation, might be useful in prevention and treatment of allergic disease.