Protection against Clostridioides difficile disease by a naturally avirulent strain.

Clostridioides difficile is a leading cause of healthcare infections. Gut dysbiosis promotes C. difficile infection (CDI) and CDIs promote gut dysbiosis, leading to frequent CDI recurrence.

A ubiquitous mobile genetic element changes the antagonistic weaponry of a human gut symbiont.

DNA transfer is ubiquitous in the human gut microbiota, especially among species of the order Bacteroidales. In silico analyses have revealed hundreds of mobile genetic elements shared between these species, yet little is known about the phenotypes they encode, their effects on fitness, or pleiotropic consequences for the recipient's genome. In this work, we show that acquisition of a ubiquitous integrative conjugative element (ICE) encoding a type VI secretion system (T6SS) shuts down the native T6SS of .

Comprehensive analyses of a large human gut Bacteroidales culture collection reveal species- and strain-level diversity and evolution.

Species of the Bacteroidales order are among the most abundant and stable bacterial members of the human gut microbiome, with diverse impacts on human health. We cultured and sequenced the genomes of 408 Bacteroidales isolates from healthy human donors representing nine genera and 35 species and performed comparative genomic, gene-specific, metabolomic, and horizontal gene transfer analyses. Families, genera, and species could be grouped based on many distinctive features.

Protection against disease by a naturally avirulent strain.

strains belonging to the epidemic BI/NAP1/027 (RT027) group have been associated with increased transmissibility and disease severity. In addition to the major toxin A and toxin B virulence factors, RT027 strains also encode the CDT binary toxin. Our lab previously identified a toxigenic RT027 isolate, ST1-75, that is avirulent in mice despite densely colonizing the colon.

Comprehensive analyses of a large human gut Bacteroidales culture collection reveal species and strain level diversity and evolution.

Species of the Bacteroidales order are among the most abundant and stable bacterial members of the human gut microbiome with diverse impacts on human health. While Bacteroidales strains and species are genomically and functionally diverse, order-wide comparative analyses are lacking. We cultured and sequenced the genomes of 408 Bacteroidales isolates from healthy human donors representing nine genera and 35 species and performed comparative genomic, gene-specific, mobile gene, and metabolomic analyses.

Dietary- and host-derived metabolites are used by diverse gut bacteria for anaerobic respiration.

Respiratory reductases enable microorganisms to use molecules present in anaerobic ecosystems as energy-generating respiratory electron acceptors. Here we identify three taxonomically distinct families of human gut bacteria (Burkholderiaceae, Eggerthellaceae and Erysipelotrichaceae) that encode large arsenals of tens to hundreds of respiratory-like reductases per genome. Screening species from each family (Sutterella wadsworthensis, Eggerthella lenta and Holdemania filiformis), we discover 22 metabolites used as respiratory electron acceptors in a species-specific manner.

The lived experience of patients with breast cancer on adjuvant endocrine therapy: side effects and coping strategies during the first year of medication initiation.

Purpose: Adjuvant endocrine therapy (AET) is pivotal for hormone receptor-positive breast cancer patients, significantly enhancing survival rates. Yet, adherence to AET remains challenging due to side effects. This study delves into the lived experience of breast cancer survivors concerning AET-induced side effects and examines differences in symptom profiles between Tamoxifen and aromatase inhibitors (AIs).

Virulence and genomic diversity among clinical isolates of ST1 (BI/NAP1/027) Clostridioides difficile.

Clostridioides difficile produces toxins that damage the colonic epithelium, causing colitis. Variation in disease severity is poorly understood and has been attributed to host factors and virulence differences between C. difficile strains.

Tracking of activated cTfh cells following sequential influenza vaccinations reveals transcriptional profile of clonotypes driving a vaccine-induced immune response.

Introduction: A vaccine against influenza is available seasonally but is not 100% effective. A predictor of successful seroconversion in adults is an increase in activated circulating T follicular helper (cTfh) cells after vaccination. However, the impact of repeated annual vaccinations on long-term protection and seasonal vaccine efficacy remains unclear.

Virulence and genomic diversity among clinical isolates of ST1 (BI/NAP1/027) .

, a leading cause of nosocomial infection, produces toxins that damage the colonic epithelium and results in colitis that varies from mild to fulminant. Variation in disease severity is poorly understood and has been attributed to host factors (age, immune competence and intestinal microbiome composition) and/or virulence differences between strains, with some, such as the epidemic BI/NAP1/027 (MLST1) strain, being associated with greater virulence. We tested 23 MLST1(ST1) clinical isolates for virulence in antibiotic-treated C57BL/6 mice.

Evaluation of a nurse practitioner clinical practicum module using a capability education framework: A case study design.

Aims And Objectives: The aim of this research was to evaluate a nurse practitioner's clinical practicum module designed with a capability education framework. The objectives were to determine if the module prepared students adequately for their role and to determine if the Mini-CEX assessment tool was suitable for use with nurse practitioners.

Background: Capability is a necessary part of expertise, where a capable person takes responsibility to develop their own education, knowledge and skills.

Adaptation to HLA-associated immune pressure over the course of HIV infection and in circulating HIV-1 strains.

Adaptation to human leukocyte antigen (HLA)-associated immune pressure represents a major driver of human immunodeficiency virus (HIV) evolution at both the individual and population level. To date, there has been limited exploration of the impact of the initial cellular immune response in driving viral adaptation, the dynamics of these changes during infection and their effect on circulating transmitting viruses at the population level. Capturing detailed virological and immunological data from acute and early HIV infection is challenging as this commonly precedes the diagnosis of HIV infection, potentially by many years.

Leptin Promotes Greater Ki67 Expression in CD4 T Cells From Obese Compared to Lean Persons Living With HIV.

While antiretroviral therapy (ART) has proven effective in suppressing viremia and disease progression among people living with human immunodeficiency virus (HIV; PLWH), suboptimal CD4 T cell reconstitution remains a major obstacle in nearly 30% of ART-treated individuals. Epidemiological studies demonstrate that obesity, or a body mass index (BMI) ≥ 30 kg/m, is positively correlated with greater CD4 T cell recovery in PLWH on ART. Leptin is a known immunomodulator that is produced in proportion to fat mass and is increased in obese individuals, including PLWH.

The management of delirium in the older adult in advanced nursing practice.

Delirium is a term used to describe an array of symptoms that indicate a disruption in cerebral metabolism, a condition that is often under-recognised, leading to delayed interventions. The condition is a common cause of older adults presenting in hospital, with significant morbidity and mortality associated with increased length of stay. A case study is used to illustrate the use of a diagnostic algorithm for older adults presenting with delirium to an advanced nurse practitioner (ANP)-led service.

A Rapid Realist Review of Quality Care Process Metrics Implementation in Nursing and Midwifery Practice.

Quality measurement initiatives promote quality improvement in healthcare but can be challenging to implement effectively. This paper presents a Rapid Realist Review (RRR) of published literature on Quality Care-Process Metrics (QCP-M) implementation in nursing and midwifery practice. An RRR informed by RAMESES II standards was conducted as an efficient means to synthesize evidence using an expert panel.

Anticytomegalovirus CD4 T Cells Are Associated With Subclinical Atherosclerosis in Persons With HIV.

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Quality care process metrics (QCP-Ms) in nursing and midwifery care processes: a rapid realist review (RRR) protocol.

In 2018, the Office of the Nursing and Midwifery Services Director (ONMSD) completed phase one of work which culminated in the development and launch of seven research reports with defined suites of quality care process metrics (QCP-Ms) and respective indicators for the practice areas - acute care, midwifery, children's, public health nursing, older persons, mental health and intellectual disability nursing in Ireland. This paper presents a rapid realist review protocol that will systematically review the literature that examines QCP-Ms in practice; what worked, or did not work for whom, in what contexts, to what extent, how and why? The review will explore if there are benefits of using the QCP-Ms and what are the contexts in which these mechanisms are triggered. The essence of this rapid realist review is to ascertain how a change in context generates a particular mechanism that produces specific outcomes.

Increased Frequency of Memory CD4+ T-Cell Responses in Individuals With Previously Treated Extrapulmonary Tuberculosis.

Extrapulmonary TB (EPTB) occurs with increased frequency in persons with underlying immunodeficiency. Even after recovery from acute illness, differences in immune phenotype and activation persist. Studies defining characteristics of immune responses after recovery from extrapulmonary TB may provide insights into factors that increase TB risk.

Deep sequence analysis of HIV adaptation following vertical transmission reveals the impact of immune pressure on the evolution of HIV.

Human immunodeficiency virus (HIV) can adapt to an individual's T cell immune response via genomic mutations that affect antigen recognition and impact disease outcome. These viral adaptations are specific to the host's human leucocyte antigen (HLA) alleles, as these molecules determine which peptides are presented to T cells. As HLA molecules are highly polymorphic at the population level, horizontal transmission events are most commonly between HLA-mismatched donor/recipient pairs, representing new immune selection environments for the transmitted virus.

Modifying the Impact of Eveningness Chronotype ("Night-Owls") in Youth: A Randomized Controlled Trial.

Objective: To determine whether an intervention to reduce eveningness chronotype improves sleep, circadian, and health (emotional, cognitive, behavioral, social, physical) outcomes.

Method: Youth aged 10 to 18 years with an evening chronotype and who were "at risk" in 1 of 5 health domains were randomized to: (a) Transdiagnostic Sleep and Circadian Intervention for Youth (TranS-C; n = 89) or (b) Psychoeducation (PE; n = 87) at a university-based clinic. Treatments were 6 individual, weekly 50-minute sessions during the school year.

Enablers and challenges to advanced nursing and midwifery practice roles.

Aim: To describe the enablers and challenges to the development and implementation of advanced nursing and midwifery practice roles in Ireland.

Background: Leadership strategies need to be put in place to enhance the development and implementation of advanced nursing and midwifery practice roles.

Method: A descriptive qualitative approach using semi-structured interviews with key stakeholders (n = 15) was undertaken with nurses and midwives working in specialist and advanced practice roles and participants from other areas such as legislative, regulatory, policy, pharmacy, medicine and education.

"Heart disease never entered my head": Women's understanding of coronary heart disease risk factors.

Aims And Objectives: This study investigated experiences of women with a primary diagnosis of ACS (NSTEMI & Unstable Angina). The study explored how women interpreted their risk for coronary heart disease (CHD) and how this influenced their treatment-seeking decisions.

Background: Efforts to reduce the incidence of cardiovascular disease, the number one killer of women, require aggressive risk factor modification, risk assessment and evidence-based treatments.

Developing and sustaining specialist and advanced practice roles in nursing and midwifery: A discourse on enablers and barriers.

Aims And Objectives: To collate, synthesise and discuss published evidence and expert professional opinion on enablers and barriers to the development and sustainability of specialist and advanced practice roles in nursing and midwifery.

Background: Expanded practice is a response to population health needs, healthcare costs and practitioners' willingness to expand their scope of practice through enhanced responsibility, accountability and professional autonomy.

Design: This discursive paper is based on a rapid review of literature on enablers and barriers to the development and sustainability of specialist and advanced practice roles and is part of a wider policy analysis.

Brief Report: Circulating Markers of Immunologic Activity Reflect Adiposity in Persons With HIV on Antiretroviral Therapy.

Background: Obesity alters adipose tissue immunology, and these changes may be reflected in circulating soluble inflammatory biomarker and T-cell subset profiles measured in HIV research studies.

Methods: We recruited 70 adults with HIV (50% obese) on efavirenz, tenofovir, and emtricitabine, virologic suppression for >2 years, and no rheumatologic or other known inflammatory conditions. We measured fasting plasma levels of several markers of innate immunity and major CD4 and CD8 T-cell subsets.