Using model systems to unravel host-Pseudomonas aeruginosa interactions.

Using model systems in infection biology has led to the discoveries of many pathogen-encoded virulence factors and critical host immune factors to fight pathogenic infections. Studies of the remarkable Pseudomonas aeruginosa bacterium that infects and causes disease in hosts as divergent as humans and plants afford unique opportunities to shed new light on virulence strategies and host defence mechanisms. One of the rationales for using model systems as a discovery tool to characterise bacterial factors driving human infection outcomes is that many P. aeruginosa virulence factors are required for pathogenesis in diverse different hosts. On the other side, many host signalling components, such as the evolutionarily conserved mitogen-activated protein kinases, are involved in immune signalling in a diverse range of hosts. Some model organisms that have less complex immune systems also allow dissection of the direct impacts of innate immunity on host defence without the interference of adaptive immunity. In this review, we start with discussing the occurrence of P. aeruginosa in the environment and the ability of this bacterium to cause disease in various hosts as a natural opportunistic pathogen. We then summarise the use of some model systems to study host defence and P. aeruginosa virulence.

Climate Change Adaptation Activities and Needs in US State and Territorial Health Agencies.

OBJECTIVE: To characterize US State and Territorial Health Agencies' (S/THA) climate change adaptation activities and priorities to facilitate appropriate investments, skills development, and support that will strengthen health sector capacity in response to a changing climate. DESIGN: In 2021, we conducted an online survey of S/THA staff requesting information on current activities related to climate change and health, the state of climate and health programming, and anticipated needs and priorities for assistance. We analyzed survey results using descriptive statistics. SETTING: US State and Territorial Health Agencies. PARTICIPANTS: We received responses from 41 of 59 S/THAs (69.5%). MAIN OUTCOME MEASURES: Implementation of S/THA climate and health programs (CHPs); engagement in climate and health activities; maintenance of hazard early warning systems and action plans; employment of climate and health communications strategies; capability to assess risks and adaptation needs related to various climate-sensitive conditions; priorities and plans for climate change adaptation in relation to climate-sensitive health risks; climate change adaptation-related partnerships and collaborations; requests of the Association of State and Territorial Health Officials (ASTHO) for advancing climate change adaptation activities; and the impacts of the COVID-19 pandemic on climate change work. RESULTS: Nineteen S/THAs reported having CHPs, the majority of which are federally funded. On average, S/THAs without CHPs reported engagement in fewer climate and health activities and more early warning activities. The S/THAs reported the highest levels of concerns regarding non-vector-borne infectious disease (66%), vector-borne infectious diseases (61%), and extreme heat (61%) hazards. CONCLUSIONS: As S/THAs with CHPs report substantially greater climate and health capacity than those without, additional federal and state investments (eg, Building Resilience Against Climate Effects [BRACE]) are urgently needed to catalyze climate and health capacity.

Barriers and facilitators to state public health agency climate and health action: a qualitative assessment.

BACKGROUND: As the health implications of climate change become more apparent, agencies and institutions across the United States are developing recommendations for state and territorial health agencies (S/THAs) to implement evidence-informed climate and health adaptation strategies. The CDC established the Building Resilience Against Climate Effects (BRACE) framework in 2010 to encourage local and state public health engagement in climate change adaptation. However, even after a decade of the BRACE initiative, the elements that affect the adoption and implementation of climate and health programming by S/THAs are not well understood. METHODS: Using an implementation science framework, this study sought to further understand and define the barriers and facilitators that determine the breadth and success of climate change and health activities undertaken by state health agencies (SHAs). We conducted focus groups with representatives from SHAs with and without climate and health programs, and analyzed data using the framework method for qualitative research. RESULTS: This study identified funding, state and agency-level prioritization, staff capability and capacity, and political will and polarization as factors that influence the readiness for implementation and implementation climate for climate and health activities. CONCLUSIONS: As the impacts of climate change intensify, S/THAs will need to expand resources and capacity, and seek advocacy and assistance from external organizations in order to support the level of engagement required to strengthen climate resilience. Findings from this study have implications for public health policy and highlight potential pathways to expand support for climate and health activities in S/THAs in the U.S.

Caregiver Prediction of Driving Fitness in Older Adults with Dementia.

Objectives: To determine whether caregiver opinion of fitness to drive and the level of assistance needed for functional activities are useful in determining the need for a Comprehensive Driving Evaluation.Methods: This study examined a sample (N = 179) of drivers with dementia. Caregivers completed a questionnaire that included caregiver opinion of driving fitness and the Functional Assessment Questionnaire (FAQ). A univariate simple logistic regression model was used to examine the relationship of road test failure with caregiver opinion of driving fitness and FAQ scores. From the significant predictive variables from the univariate test, multiple logictic regression models were used to examine possible combination of variables as predictors of road test failure.Results: The combination of caregiver opinion of driving fitness and the FAQ sub-item for memory were found to have modest ability in predicting failure on a standardized on-road driving assessment (AUC 0.727).Conclusions: Caregiver opinion of driving fitness and most individual higher order activities of daily living were found to be independent predictors of failure on a standardized road test.Clinical Implications: Caregiver opinion of driving fitness and ratings of functional activities may be useful for families and clinicians in considering whether an adult with dementia should be more carefully assessed for fitness to drive.

Validity and Reliability of the Traffic Sign Naming Test (TSNT) and Written Exam for Driving Decisions (WEDD) as Measures of Fitness to Drive Among Older Adults.

IMPORTANCE: Occupational therapists need valid and reliable tools to help determine fitness to drive of older drivers with medical conditions such as dementia. OBJECTIVE: To establish the validity and reliability of the Traffic Sign Naming Test (TSNT) and Written Exam for Driving Decisions (WEDD) as measures of fitness to drive of adults with and without dementia. DESIGN: Cross-sectional. SETTING: Washington University Medical School in St. Louis in collaboration with the Rehabilitation Institute of St. Louis. PARTICIPANTS: Older drivers diagnosed with dementia (n = 130) and without dementia (n = 34). Drivers with dementia required a physician referral indicating a medical need for a driving evaluation, a diagnosis of dementia, and an Alzheimer Detection 8 score of 2. Drivers without dementia were required to be age 55 yr or older and not meet criteria for dementia. OUTCOMES AND MEASURES: Participants completed a comprehensive driving evaluation (CDE) that included clinical measures of vision, motor, and cognition; TSNT; and WEDD. The outcome measure was performance on a standardized on-road assessment. RESULTS: The TSNT's interrater reliability was determined to be strong (κ = .80). The TSNT and WEDD demonstrated convergent validity with cognitive measures (p < .001) and discriminant validity with visual and motor measures in the CDE. The TSNT (area under the curve [AUC] = .74) and WEDD (AUC = .71) had fair ability to predict failure on a standardized on-road assessment. CONCLUSION AND RELEVANCE: TSNT and WEDD are recommended for use by occupational therapists in combination with other performance measures when determining fitness to drive or need for a CDE. WHAT THIS ARTICLE ADDS: The TSNT and WEDD can be included as screening tools (in addition to other performance measures) to assist clinicians in determining which clients need to be referred for a CDE. The TSNT and WEDD can also be included as part of a CDE to assist driving rehabilitation specialists in making final recommendations regarding fitness to drive. The scores generated from the TSNT and WEDD address driving knowledge in a way that may be more understandable to clients and more relatable to skills needed to actually drive.

Rhodoquinone biosynthesis in C. elegans requires precursors generated by the kynurenine pathway.

Parasitic helminths infect over a billion humans. To survive in the low oxygen environment of their hosts, these parasites use unusual anaerobic metabolism - this requires rhodoquinone (RQ), an electron carrier that is made by very few animal species. Crucially RQ is not made or used by any parasitic hosts and RQ synthesis is thus an ideal target for anthelmintics. However, little is known about how RQ is made and no drugs are known to block RQ synthesis. C. elegans makes RQ and can use RQ-dependent metabolic pathways - here, we use C. elegans genetics to show that tryptophan degradation via the kynurenine pathway is required to generate the key amine-containing precursors for RQ synthesis. We show that C. elegans requires RQ for survival in hypoxic conditions and, finally, we establish a high throughput assay for drugs that block RQ-dependent metabolism. This may drive the development of a new class of anthelmintic drugs. This study is a key first step in understanding how RQ is made in parasitic helminths.

A comparative study of allowable pesticide residue levels on produce in the United States.

BACKGROUND: The U.S. imports a substantial and increasing portion of its fruits and vegetables. The U.S. Food and Drug Administration currently inspects less than one percent of import shipments. While countries exporting to the U.S. are expected to comply with U.S. tolerances, including allowable pesticide residue levels, there is a low rate of import inspections and few other incentives for compliance. METHODS: This analysis estimates the quantity of excess pesticide residue that could enter the U.S. if exporters followed originating country requirements but not U.S. pesticide tolerances, for the top 20 imported produce items based on quantities imported and U.S. consumption levels. Pesticide health effects data are also shown. RESULTS: The model estimates that for the identified items, 120 439 kg of pesticides in excess of U.S. tolerances could potentially be imported to the U.S., in cases where U.S. regulations are more protective than those of originating countries. This figure is in addition to residues allowed on domestic produce. In the modeling, the top produce item, market, and pesticide of concern were oranges, Chile, and Zeta-Cypermethrin. Pesticides in this review are associated with health effects on 13 body systems, and some are associated with carcinogenic effects. CONCLUSIONS: There is a critical information gap regarding pesticide residues on produce imported to the U.S. Without a more thorough sampling program, it is not possible accurately to characterize risks introduced by produce importation. The scenario presented herein relies on assumptions, and should be considered illustrative. The analysis highlights the need for additional investigation and resources for monitoring, enforcement, and other interventions, to improve import food safety and reduce pesticide exposures in originating countries.

Quantitative power Doppler ultrasonography is a sensitive measure of metacarpophalangeal joint synovial vascularity in rheumatoid arthritis and declines significantly following a 2-week course of oral low-dose corticosteroids.

OBJECTIVE: To investigate the stability over 2 weeks of ultrasonographic assessments of synovial thickness and vascularity in all 10 metacarpophalangeal joints of subjects with rheumatoid arthritis (RA) with a range of disease activities as measured by the validated Disease Activity Score-28 joint score (DAS28-ESR). And in subjects with severe disease activity, to compare the sensitivity of these measurements, acute-phase markers, and vascular endothelial growth factor to change in response to 2 weeks of oral prednisolone (7.5 mg daily). METHODS: A group of 38 subjects with RA were enrolled, 13 (mean DAS28 2.1), 14 (mean DAS28 5.2), and 11 (mean DAS28 5.7) meriting oral corticosteroid treatment. Synovial thickness and vascularity were assessed by ultrasonography at 3 timepoints. Images were ranked by semiquantitative scale. Vascularity was also measured by quantitative determination of the power Doppler area (PDA). RESULTS: In the whole RA cohort, baseline indices of synovial thickness and vascularity correlated with DAS28, as did PDA (r = 0.42, p < 0.05). In the RA groups on stable therapy, synovial thickness and vascularity showed little variation over 2 weeks. In the corticosteroid group, PDA had fold changes of -1.9-fold (p < 0.05) after 1 week and -2.2-fold (p < 0.05) after 2 weeks. These were the largest fold changes of all measured variables. CONCLUSION: Ultrasonographic measures can differentiate disease severity in RA correlating closely with DAS28. Quantitative power Doppler signal was significantly reduced within 1 week of oral prednisolone, a rapid kinetic suggesting that PDA may have value as a sensitive early marker of therapeutic response.

HIV testing among lesbian women: social contexts and subjective meanings.

This study provides descriptive statistics on prevalence of testing, testing sites, and reasons for testing among lesbian women in the United States. It also provides qualitative data about the social meanings and specific circumstances of their HIV testing experiences. Analysis draws on a sample of lesbian women living in a single large southeastern city. An especially diverse snowball and chain-referral sample of 162 lesbian women was given a questionnaire, and qualitative data were gathered from 24 women participating in three focus groups and from 67 women participating in depth-interviews. A large majority of women in the survey sample (80%) reported at least one test, and more than one in four women were tested five or more times. More than one in ten were tested during drug treatment or while incarcerated. The most common testing sites were clinics and hospitals, and the most common reason women gave was because they "thought they were at risk." Most tests were voluntary rather than mandatory occupational or institutional requirements. The subjective meanings associated with HIV testing, as well as the women's counseling needs before, during, and after testing are analyzed. The implications for a better understanding of lesbian women's sexual health are discussed.

Prevalence of subjective voice impairment in rheumatoid arthritis.

Rheumatoid arthritis (RA) might lead to voice impairment through several mechanisms but its prevalence has been little investigated. RA patients attending a rheumatology outpatient clinic had joint assessments and completed the Voice Handicap Index-10 (VHI-10). A comparator group consisted of patients attending the department with other diseases. Seventy-three patients with RA and 73 comparators were recruited. Four patients with RA (5%) and one comparator (1%) had significantly abnormal VHI-10 scores. RA patients with a Disease Activity Score 28 >3.2, indicating more active disease, had significantly higher VHI-10 scores. A low prevalence of self-reported voice handicap occurs in RA and associates with more active disease.

Nuances and shifts in lesbian women's constructions of STI and HIV vulnerability.

This study examines the subjective side of vulnerability as a social construct rooted in interpersonal relationships and community membership. Analysis is based on a survey of an especially diverse sample of 162 lesbian women, 67 of whom also participated in depth interviews. Another 24 of the original sample also participated in transcribed focus groups. One third were African American, Latina, and Asian, and two thirds were white. This sample reported an overall infection rate of 23%. Three subjective stances, or risk frames, are identified: essentially invulnerable, socially inoculated, and fundamentally vulnerable. Some women describe shifts in their interpretations of their own vulnerability, moving from one stance to another in response to obtaining information, becoming infected, having friends or acquaintances who become infected, and becoming involved with new partners. It is suggested that these shifts comprise a subjective "vulnerability career". The significance of lesbian women's constructions of vulnerability is examined, and the implications of this study for a better understanding of their risk for STIs are discussed.