A mouse model displays host and bacterial strain differences in Aerococcus urinae urinary tract infection

In recent years, the clinical significance of Aerococcus urinae has been increasingly recognized. A. urinae has been implicated in cases of urinary tract infection (UTI; acute cystitis and pyelonephritis) in both male and female patients, ranging from children to older adults. Aerococcus urinae can also be invasive, causing urosepsis, endocarditis, and musculoskeletal infections. Mechanisms of pathogenesis in A. urinae infections are poorly understood, largely due to the lack of an animal model system. In response to this gap, we developed a model of A. urinae urinary tract infection in mice. We compared A. urinae UTI in female C3H/HeN and C57BL/6 mice and compared four clinical isolates of A. urinae isolated from patients with UTI, urgency urinary incontinence, and overactive bladder. Our data demonstrate that host genetic background modulates A. urinae UTI. Female C57BL/6 female mice rapidly cleared the infection. Female C3H/HeN mice, which have inherent vesicoureteral reflux that flushes urine from the bladder up into the kidneys, were susceptible to prolonged bacteriuria. This result is consistent with the fact that A. urinae infections most frequently occur in patients with underlying urinary tract abnormalities or disorders that make them susceptible to bacterial infection. Unlike uropathogens such as E. coli, which cause infection and inflammation both of the bladder and kidneys in C3H/HeN mice, A. urinae displayed tropism for the kidney, persisting in kidney tissue even after clearance of bacteria from the bladder. Aerococcus urinae strains from different genetic clades displayed varying propensities to cause persistent kidney infection. Aerococcus urinae infected kidneys displayed histological inflammation, neutrophil recruitment and increased pro-inflammatory cytokines. These results set the stage for future research that interrogates host-pathogen interactions between A. urinae and the urinary tract

Co-production of the quality of patient-centered outcomes research partnerships instrument for people with mental health conditions

Mounting scientific evidence over the past decades in the field of psychiatry has shown community engagement in research produces more relevant research, increased uptake of research findings, and better clinical outcomes. Despite the need for the integration of community engagement methodologies into the scientific method, doctoral and master\u27s level competencies in the field of psychiatry commonly do not include dedicated training or coursework on community engagement methodologies. Without appropriate training or research experience, attempts to facilitate community engagement are often ineffective and burdensome and leave stakeholders feeling disenfranchised. The goal of this study was to co-produce an instrument designed to improve the quality of community engagement research practices by measuring the degree to which researchers have partnered with psychiatric patient stakeholders. The development of the Quality of Patient-Centered Outcomes Research Partnerships Instrument included an iterative co-production process with psychiatric patient stakeholders and scientists, including item formulation, followed by two phases of cognitive interviews with psychiatric patient stakeholders to assess and refine instrument items. A pilot study was conducted to assess acceptability and feasibility. The pilot study of the Patient-Centered Outcomes Research Partnerships Instrument suggested feasibility and acceptability among psychiatric patient stakeholders. The Quality of Patient-Centered Outcomes Research Partnerships Instrument may be a valuable tool to enhance the quality of community engagement research practices within the field of psychiatry. Experience Framework This article is associated with the Innovation & Technology lens of The Beryl Institute Experience Framework (https://www.theberylinstitute.org/ExperienceFramework). Access other PXJ articles related to this lens. Access other resources related to this len

Nocardia kroppenstedtii sp. nov., a novel actinomycete isolated from a lung transplant patient with a pulmonary infection

An actinomycete, strain N1286T, isolated from a lung transplant patient with a pulmonary infection, was provisionally assigned to the genus Nocardia. The strain had chemotaxonomic and morphological properties typical of members of the genus Nocardia and formed a distinct phyletic line in the Nocardia 16S rRNA gene tree. It was most closely related to Nocardia farcinica DSM 43665T (99.8% gene similarity) but was distinguished from the latter by a low level of DNA:DNA relatedness. These strains were also distinguished by a broad range of phenotypic properties. On the basis of these data, it is proposed that isolate N1286T (=DSM 45810T = NCTC 13617T) should be classified as the type strain of a new Nocardia species for which the name Nocardia kroppenstedtii is proposed

Core Competencies to Promote Consistency and Standardization of Best Practices for Digital Peer Support: Focus Group Study

Background: As digital peer support is quickly expanding across the globe in the wake of the COVID-19 pandemic, standardization in the training and delivery of digital peer support can advance the professionalism of this field. While telehealth competencies exist for other fields of mental health practice, such as social work, psychiatry, and psychology, limited research has been done to develop and promote digital peer support competencies. Objective: The goal of this study is to introduce the coproduction of core competencies that can guide digital peer support. Methods: Peer support specialists were recruited through an international listserv and participated in a 1-hour virtual focus group. A total of four focus groups were conducted with 59 peer support specialists from 11 US states and three countries. Results: Analysis was conducted using the rigorous and accelerated data reduction (RADaR) technique, and 10 themes were identified: (1) protecting the rights of service users, (2) technical knowledge and skills in the practice of digital peer support, (3) available technologies, (4) equity of access, (5) digital communication skills, (6) performance-based training, (7) self-care, (8) monitoring digital peer support and addressing digital crisis, (9) peer support competencies, and (10) health literacy (emerging). The authors present recommendations based on these themes. Conclusions: The introduction of digital peer support core competencies is an initial first step to promote the standardization of best practices in digital peer support. The established competencies can potentially act as a guide for training and skill development to be integrated into US state peer support specialist competencies and to enhance competencies endorsed by the Substance Abuse and Mental Health Services Administration (SAMHSA).publishedVersio

Identification and manipulation of the pleuromutilin gene cluster from Clitopilus passeckerianus for increased rapid antibiotic production

Semi-synthetic derivatives of the tricyclic diterpene antibiotic pleuromutilin from the basidiomycete Clitopilus passeckerianus are important in combatting bacterial infections in human and veterinary medicine. These compounds belong to the only new class of antibiotics for human applications, with novel mode of action and lack of cross-resistance, representing a class with great potential. Basidiomycete fungi, being dikaryotic, are not generally amenable to strain improvement. We report identification of the seven-gene pleuromutilin gene cluster and verify that using various targeted approaches aimed at increasing antibiotic production in C. passeckerianus, no improvement in yield was achieved. The seven-gene pleuromutilin cluster was reconstructed within Aspergillus oryzae giving production of pleuromutilin in an ascomycete, with a significant increase (2106%) in production. This is the first gene cluster from a basidiomycete to be successfully expressed in an ascomycete, and paves the way for the exploitation of a metabolically rich but traditionally overlooked group of fungi

An online intervention for improving stroke survivors' health-related quality of life : study protocol for a randomised controlled trial

Background: Recurrent stroke is a major contributor to stroke-related disability and costs. Improving health-risk behaviours and mental health has the potential to significantly improve recovery, enhance health-related quality of life (HRQoL), independent living, and lower the risk of recurrent stroke. The primary aim will be to test the effectiveness of an online intervention to improve HRQoL among stroke survivors at 6 months' follow-up. Programme effectiveness on four health behaviours, anxiety and depression, cost-effectiveness, and impact on other hospital admissions will also be assessed. Methods/design: An open-label randomised controlled trial is planned. A total of 530 adults will be recruited across one national and one regional stroke registry and block randomised to the intervention or minimal care control group. The intervention group will receive access to the online programme Prevent 2nd Stroke (P2S); the minimal care control group will receive an email with Internet addresses of generic health sites designed for the general population. The primary outcome, HRQoL, will be measured using the EuroQol-5D. A full analysis plan will compare between groups from baseline to follow-up. Discussion: A low-cost per user option to supplement current care, such as P2S, has the potential to increase HRQoL for stroke survivors, and reduce the risk of second stroke

Genotype-Guided Hydralazine Therapy

Background: Despite its approval in 1953, hydralazine hydrochloride continues to be used in the management of resistant hypertension, a condition frequently managed by nephrologists and other clinicians. Hydralazine hydrochloride undergoes metabolism by the N-acetyltransferase 2 (NAT2) enzyme. NAT2 is highly polymorphic as approximately 50% of the general population are slow acetylators. In this review, we first evaluate the link between NAT2 genotype and phenotype. We then assess the evidence available for genotype-guided therapy of hydralazine, specifically addressing associations of NAT2 acetylator status with hydralazine pharmacokinetics, antihypertensive efficacy, and toxicity. Summary: There is a critical need to use hydralazine in some patients with resistant hypertension. Available evidence supports a significant link between genotype and NAT2 enzyme activity as 29 studies were identified with an overall concordance between genotype and phenotype of 92%. The literature also supports an association between acetylator status and hydralazine concentration, as fourteen of fifteen identified studies revealed significant relationships with a consistent direction of effect. Although fewer studies are available to directly link acetylator status with hydralazine antihypertensive efficacy, the evidence from this smaller set of studies is significant in 7 of 9 studies identified. Finally, 5 studies were identified which support the association of acetylator status with hydralazine-induced lupus. Clinicians should maintain vigilance when prescribing maximum doses of hydralazine. Key Messages: NAT2 slow acetylator status predicts increased hydralazine levels, which may lead to increased efficacy and adverse effects. Caution should be exercised in slow acetylators with total daily hydralazine doses of 200 mg or more. Fast acetylators are at risk for inefficacy at lower doses of hydralazine. With appropriate guidance on the usage of NAT2 genotype, clinicians can adopt a personalized approach to hydralazine dosing and prescription, enabling more efficient and safe treatment of resistant hypertension

Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions.

We developed a systematic approach to map human genetic networks by combinatorial CRISPR-Cas9 perturbations coupled to robust analysis of growth kinetics. We targeted all pairs of 73 cancer genes with dual guide RNAs in three cell lines, comprising 141,912 tests of interaction. Numerous therapeutically relevant interactions were identified, and these patterns replicated with combinatorial drugs at 75% precision. From these results, we anticipate that cellular context will be critical to synthetic-lethal therapies

Introducing Interprofessional Education (IPE) Grand Rounds: Lessons from a New Student-led IPE Initiative

Learning Objectives • Describe 2-3 benefits for enhancing student exposure to real world collaborative practice teams • Develop an action plan for starting an IPE Interest Group at your institution • Describe 3 practical tips for implementing an IPE Grand Round