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Objective: Household food access remains a concern among primarily agricultural households in lower- and middle-income countries. We examined the associations among domains representing livelihood assets (human capital, social capital, natural capital, physical capital and financial capital) and household food access.Design: Cross-sectional survey (two questionnaires) on livelihood assets.Setting: Metropolitan Pillaro, Ecuador; Cochabamba, Bolivia; and Huancayo, Peru.Subjects: Households (n = 570) involved in small-scale agricultural production in 2008.Results: Food access, defined as the number of months of adequate food provisioning in the previous year, was relatively good; 41 % of the respondents indicated to have had no difficulty in obtaining food for their household in the past year. Using bivariate analysis, key livelihood assets indicators associated with better household food access were identified as: age of household survey respondent (P = 0.05), participation in agricultural associations (P = 0.09), church membership (P = 0.08), area of irrigated land (P = 0.08), housing material (P = 0.06), space within the household residence (P = 0.02) and satisfaction with health status (P = 0.02). In path models both direct and indirect effects were observed, underscoring the complexity of the relationships between livelihood assets and household food access. Paths significantly associated with better household food access included: better housing conditions (P = 0.01), more space within the household residence (P = 0.001) and greater satisfaction with health status (P = 0.001).Conclusions: Multiple factors were associated with household food access in these peri-urban agricultural households. Food security intervention programmes focusing on food access need to deal with both agricultural factors and determinants of health to bolster household food security in challenging lower- and middle-income country contexts. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether there are associations between exposure to pesticides and 4 chronic non-cancer health effects: dermatologic, neurologic, reproductive, and genotoxic effects.Data Sources: We searched PreMedline, MEDLINE, and LILACS using the key word pesticide combined with the term for the specific health effect being searched. Reviewers scanned the references of all articles for additional relevant studies.Study Selection: Studies since 1992 were assessed using structured inclusion and quality-of-methods criteria. Studies scoring <4 on a 7-point global methodologic quality scale were excluded. In total, 124 studies were included. These studies had a mean quality score of 4.88 out of 7.Synthesis: Strong evidence of association with pesticide exposure was found for all neurologic outcomes, genotoxicity, and 4 of 6 reproductive effects: birth defects, fetal death, altered growth, and other outcomes. Exposure to pesticides generally doubled the level of genetic damage as measured by chromosome aberrations in lymphocytes. Only a few high-quality studies focused on the dermatologic effects of pesticides. In some of these studies, rates of dermatitis were higher among those who had had high exposure to pesticides on the job.Conclusion: Evidence from research on humans consistently points to positive associations between pesticide exposure and 3 of the 4 non-cancer health outcomes studied. Physicians have a dual role in educating individual patients about the risks of exposure and in reducing exposure in the community by advocating for restrictions on use of pesticides. [ABSTRACT FROM AUTHOR]

Objective: To review literature documenting associations between pesticide use and cancer.Data Sources: We searched MEDLINE, PreMedline, CancerLit, and LILACS to find studies published between 1992 and 2003 on non-Hodgkin lymphoma, leukemia, and 8 solid-tumour cancers: brain, breast, kidney, lung, ovarian, pancreatic, prostate, and stomach cancer.Study Selection: Each title and abstract was assessed for relevance; disagreements among reviewers were resolved by consensus. Studies were assessed by a team of 2 trained reviewers and rated based on methodologic quality according to a 5-page assessment tool and a global assessment scale. Studies rated below a global score of 4 out of 7 were excluded.Synthesis: Most studies on non-Hodgkin lymphoma and leukemia showed positive associations with pesticide exposure. Some showed dose-response relationships, and a few were able to identify specific pesticides. Children's and pregnant women's exposure to pesticides was positively associated with the cancers studied in some studies, as was parents' exposure to pesticides at work. Many studies showed positive associations between pesticide exposure and solid tumours. The most consistent associations were found for brain and prostate cancer. An association was also found between kidney cancer in children and their parents' exposure to pesticides at work. These associations were most consistent for high and prolonged exposures. Specific weaknesses and inherent limitations in epidemiologic studies were noted, particularly around ascertaining whether and how much exposure had taken place.Conclusion: Our findings support attempts to reduce exposure to pesticides. Reductions are likely best achieved through decreasing pesticide use for cosmetic (non-commercial) purposes (where children might be exposed) and on the job. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Working under frequent deadlines was previously found to be associated with upper limb work-related musculoskeletal disorders (WMSDs) in newspaper workers. Further investigation was required so that concrete recommendations for change could be offered to the workplace parties (labour and management of a large metropolitan newspaper). STUDY DESIGN: The assessment was based on three methods. A questionnaire was used to clarify time-related aspects of work on deadlines for a larger group of workers. Experience sampling was used to document temporal variation in various aspects of physical and psychological demands over work shifts and deadline cycles. Focus groups were also conducted. RESULTS: Differences were found between the 'High' and 'Low' deadline groups: Those working with frequent deadlines more frequently were required: to work together with others, to perform tasks on a specific schedule and specific order, to work at a fast paced, to perceive their work as hectic and 'hard'. Experience sampling showed differential trends in workload across daily, weekly, and no deadline days. The lack of breaks for extended periods of time leading up to a deadline was noticeable. The focus groups were useful in highlighting issues not addressed by the other two methods and to understand the feasibility of various possible interventions. CONCLUSIONS: The integration of results from all methods lead to recommendations for issues upon which to focus prevention related activities where deadlines are present: delays in work flow from others, interruptions from technology related problems, excessive work, insufficient staff/insufficient time, extra/unexpected work, compromising of work quality for speed, and lack of time for breaks. [ABSTRACT FROM AUTHOR]

Active surveillance of symptoms and disability due to musculoskeletal disorders (MSD) in working populations can map individual transitions in symptom intensity or disability level. Using repeat surveys, this study examined if aetiological risk factors for new symptoms or disability, measured by interference with activities, were similar to prognostic risk factors for subsequent outcomes of symptoms and disability. This paper reports on 379 Toronto newspaper workers who completed questionnaires in 1996 and 1997. Questions on pain/discomfort during the last year, episode frequency and duration formed the basis for constructing three mutually exclusive symptom levels: noncases (Level 1); mild cases (Level 2); and more severe or frequent pain cases (Level 3). A similar construction of overall interference levels was based on the frequency with which musculoskeletal pain/discomfort interfered with daily, recreational, social and family activities, or ability to do one's job during the previous 12 months. The last was also examined as work interference alone. Levels of symptoms were cross-tabulated by overall and work interference at the two time points and Markov models of transitions between states were formulated. Results indicate that period prevalence of symptoms and overall interference increased between phases, though only significantly for symptoms (Levels 2 and 3, 65.7-70.7%, p = 0.04), while work interference was unchanged (17.9-17.0%). Equivalent proportions of workers improved as worsened in symptoms (21.1 and 22.4%, respectively), overall interference (16.7 and 17.8%), and work interference (7.4 and 6.6%). The only significant predictor for those without work interference at time one was job tenure, which was protective against work interference (Odds Ratio (OR) 1.06, 95% Confidence Interval (CI) 1.01-1.12). Among those who had more severe/frequent symptoms at time one, lack of improvement over time was predicted by longer job tenure (OR = 0.92 per year, CI: 0.87-0.97), greater psychological demands of work (OR = 0.65 per point, CI: 0.51-0.84) and marginally by greater upper extremity disability score. At time one, women with work interference were more likely to have persistent interference at time two (OR = 7.22, CI: 1.57-33.20). Suggestive findings included opposite effects of social support at work: reduced risk of development of new symptoms but increased risk of persistence at the highest symptom level. [ABSTRACT FROM AUTHOR]

Background: Most clinicians would probably agree that what patients think will happen can influence what does happen over the clinical course. Yet despite useful narrative reviews on expectancy of therapeutic gain and the mechanisms by which expectancy can affect health outcomes, we were unable to locate a systematic review of the predictive relation between patients' recovery expectations and their health outcomes.Methods: We searched MEDLINE for English-language articles published from 1966 to June 1998 with a title or abstract containing at least 1 of the medical subject headings (MeSH) "self-assessment," "self-concept" or "attitude to health," or the MeSH subheading "psychology," and at least 1 word from each of 3 sets: "patient" and similar words; a form of "expectation," "belief" or "prediction"; and a form of "recover," "outcome," "survival" or "improve." Relevant articles contained original research data, measured patients' recovery expectations, independently measured a subsequent health outcome and analyzed the relation between expectations and outcomes. We assessed internal validity using quality criteria for prognostic studies based on 6 categories (case definition; patient selection; extent of follow-up; objective outcome criteria; measurement and reporting of recovery expectations; and analysis).Results: A total of 1243 titles or abstracts were identified through the computer search, and 93 full-text articles were retrieved. Forty-one of these articles met the relevance criteria, along with 4 additional articles identified through other means. Agreement beyond chance on quality assessments of 18 randomly selected articles was high (kappa = 0.87, p = 0.001). Sixteen of the 45 articles provided moderate-quality evidence and included a range of clinical conditions and study designs; 15 of the 16 showed that positive expectations were associated with better health outcomes. The strength of the relation depended on the clinical conditions and the measured used.Interpretation: Consistency across the studies reviewed and the evidence they provided support the need for clinicians to clarify patients' expectations and to assist them in having appropriate expectations of recovery. The understanding of the nature, extent and clinical implications of the relation between expectations and outcomes could be enhanced by more conceptually driven and methodologically sound research, including evaluations of intervention effectiveness. [ABSTRACT FROM AUTHOR]

This paper explores the associations, for working women and men, of high strain jobs with self-rated health in the 1994/95 Canadian National Population Health Survey (NPHS). NPHS data were obtained on men (n = 4230) and women (n = 4043), aged 18-64 who answered an abbreviated version of the job content questionnaire (JCQ). Using the upper and lower tertiles of psychological demands and decision latitude as cut points we classified workers into high strain and other jobs. Self-rated health was the outcome. We used polytomous logistic regression analyses and controlled for potential personal and home confounders; two risk parameters were estimated: for the odds of reporting poor/fair and good health both vs. very good/excellent health. High strain work was reported by 11% of of women and 9% of men. After adjusting for potential confounders, high job strain was consistently associated with worse self-rated health in both models for each gender. [ABSTRACT FROM AUTHOR]

Modified-work programs are designed to facilitate the return to work for employees with a work-related injury. Although extensive published literature exists that describes and evaluates 'ideal' programs, to date there is a paucity of data describing practice. To address this pertinent issue, we administered a survey to a large sample of 1833 workers with soft-tissue injuries in Ontario, Canada, and asked them detailed questions about modified work and employer contact. Our results reveal that most workers (66%) were contacted by someone from their workplace to check on how they were doing. However, only a minority (36%) were offered arrangements by their employer to help them return to work after developing a work-related soft-tissue injury. Most arrangements that were offered to injured workers consisted of such temporary modifications as reduced hours (24%), flexible work hours (25%), or a lighter job (57%) rather than more permanent changes to the way that work is conducted, such as changes to the work layout or equipment (8%). Merely being contacted by the workplace to check on how the worker was doing was not associated with reduced compensation benefit duration. Workplace offers of arrangements to help the worker return to work were associated with reduced compensation benefit duration but were not statistically associated with workers' pain grade. [ABSTRACT FROM AUTHOR]

Musculoskeletal disorders (MSD) of the upper limb are of growing concern, although there is no consensus on how to define a 'case' of MSD. Varying the case definition has been shown to alter the description of the prevalence of the disorder. The purpose of this study was to compare the symptom description as well as the burden (disability costs, time off work) of MSD across four different published case definitions. A survey was conducted at a large urban newspaper, and 1003 (84% response rate) people responded. The questionnaire included measures of pain (intensity, frequency, duration), disability, work disability, and absence. Case definitions permitted creation of four overlapping samples, which were compared descriptively on the various measures of burden of MSD. The case definitions led to diferent descriptions of burden associated with MSD. Contrasting between the two extremes (Hunting and NIOSH), differences were found in prevalence (55% vs. 20%), overall disability (14.6 vs. 23.2/100, 100 = more disability) and difficulty at work (8 vs. 15.5/100), and proportion reporting pain interfering with work (27.3 vs. 16.2%). The various case definitions drew samples that were described by different experiences in terms of burden. Studies using different case definitions therefore lack comparability. The definition to use may depend on the study goals (primary or secondary prevention for example). However, consensus on a common definition would allow comparability across studies. [ABSTRACT FROM AUTHOR]

Reports on consultations held with four communities in Ontario as part of the development of health-based indicators of air quality. Relationships between air pollution and adverse health impacts; Improvements in self-reported ability of participants to assess and use air quality indicators; Suggestions for resolving tensions inherent in the development of environmental health indicators.

Details a study which explored the links between ecosystems and human health. Environmental burden of illness; Conditions for human well-being; Directions for action.

Traditional foods (TFs) hold increasing global relevance due to their potential to address health and dietary challenges. This study explores TF consumption and patterns in a middle-income country's general population. Using 2017 Ecuadorian highlands survey data, we identified four consumption clusters with distinct TF preferences. Chi-square tests identified variations in independent variables across clusters. Poisson regression models highlighted city, age, education, and food habits as independent predictors of TF-based clusters. Our findings broaden TF importance to nutrition beyond specific populations. Understanding consumption patterns and socioeconomic links supports nuanced public health strategies to tackle contemporary health, social equity, and sustainability issues.

Introduction: Natural products discovered from bacteria provide critically needed therapeutic leads for drug discovery, and myxobacteria are an established source for metabolites with unique chemical scaffolds and biological activities. Myxobacterial genomes accommodate an exceptional number and variety of biosynthetic gene clusters (BGCs) which encode for features involved in specialized metabolism., Methods: In this study, we describe the collection, sequencing, and genome mining of 20 myxobacteria isolated from rhizospheric soil samples collected in North America., Results: Nine isolates were determined to be novel species of myxobacteria including representatives from the genera Archangium, Myxococcus, Nannocystis, Polyangium, Pyxidicoccus, Sorangium , and Stigmatella . Growth profiles, biochemical assays, and descriptions were provided for all proposed novel species. We assess the BGC content of all isolates and observe differences between Myxococcia and Polyangiia clusters., Discussion: Continued discovery and sequencing of novel myxobacteria from the environment provide BGCs for the genome mining pipeline. Utilizing complete or near-complete genome sequences, we compare the chromosomal organization of BGCs of related myxobacteria from various genera and suggest that the spatial proximity of hybrid, modular clusters contributes to the metabolic adaptability of myxobacteria., Competing Interests: SD was employed by Molecular Research LP (MR DNA). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer DW is currently organizing a Research Topic with the author DS., (Copyright © 2023 Ahearne, Phillips, Knehans, Hoing, Dowd and Stevens.)

The frequency and intensity of wildfires have been increasing over the last 50 years and negatively impacted the wine industry. Previous methods of smoke mitigation during grape processing have shown little impact in reducing smoke taint in wines. Therefore, a novel method of using edible spray coatings for vineyard application was developed to help prevent volatile smoke phenol uptake in wine grapes. Four cellulose nanofiber-based coating suspensions incorporated with chitosan and/or β-cyclodextrin were evaluated. Films derived from the coating suspensions were exposed to volatile phenols found in wildfire smoke (guaiacol, 4-methyl guaiacol, m-cresol, o-cresol, p-cresol, syringol, and 4-methyl syringol) and evaluated with ultraviolet-visible spectroscopy where the results indicated that the coatings could uptake smoke phenols in varying degrees. The coatings were also applied in a vineyard at three different application times during grape growth: pea-sized, pre-bunch closure, and both at pea-sized and pre-bunch closure. The results showed that the application time did not have a significant (p < 0.05) effect on berry size, weight, °Brix, pH, or titratable acidity. The type of coating, time of application and washing were found to impact the number of volatile phenols in the grapes after a smoke event. Results from this study indicated that edible coatings could help mitigate smoke uptake in wine grapes without sacrificing the growth and key composition parameters of wine grapes. PRACTICAL APPLICATION: This research provides a novel spray coating that can be applied to wine grapes in the vineyard to potentially mitigate volatile smoke compounds in wine grapes without impacting fruit growth and key compositional parameters of wine grapes, thus maintaining high quality of wines for consumers. Results from this study can also be potentially applied to other agricultural commodities to solve the issues caused by the wildfire smoke., (© 2022 Institute of Food Technologists.)

Calcineurin (CN) is an attractive antifungal target as it is critical for growth, stress response, drug resistance, and virulence in fungal pathogens. The immunosuppressive drugs, tacrolimus (FK506) and cyclosporin A (CsA), are fungistatic and specifically inhibit CN through binding to their respective immunophilins, FK506-binding protein (FKBP12), and cyclophilin (CypA). We are focused on CN structure-based approaches for the development of non-immunosuppressive FK506 analogs as antifungal therapeutics. Here, we examined the effect of the novel CN inhibitor, CN585, on the growth of the human pathogen Aspergillus fumigatus , the most common cause of invasive aspergillosis. Unexpectedly, in contrast to FK506, CN585 exhibited off-target effect on A. fumigatus wild-type and the azole- and echinocandin-resistant strains. Unlike with FK506 and CsA, the A. fumigatus CN, FKBP12, CypA mutants (Δ cnaA , Δ fkbp12 , Δ cypA ) and various FK506-resistant mutants were all sensitive to CN585. Furthermore, in contrast to FK506 the cytosolic to nuclear translocation of the CN-dependent transcription factor (CrzA-GFP) was not inhibited by CN585. Molecular docking of CN585 onto human and A. fumigatus CN complexes revealed differential potential binding sites between human CN versus A. fumigatus CN. Our results indicate CN585 may be a non-specific inhibitor of CN with a yet undefined antifungal mechanism of activity.

Background: Chronic pulmonary aspergillosis (CPA) may be confused with, or a coinfection of, pulmonary tuberculosis (PTB), or may manifest itself after completion of antituberculous therapy (ATT)., Methods: Literature searches were conducted on PubMed. The selected studies stated the timing of CPA diagnosis with respect to PTB. The key assumptions for estimating the annual incidence, annual deaths, and 5-year-period prevalence related to CPA were: of the clinically diagnosed PTB patients , 19% of those HIV-negative had CPA and 7% of HIV-positive patients had CPA; the percentage of patients presenting in the first year after PTB diagnosis or developing CPA as ATT finished was 10%; the annual rate of development of CPA from 2-5 years after PTB diagnosis was 1.5%; and the mortality of CPA was 20% in year 1 and 7.5% thereafter to year 5., Findings: In India, the annual incidence of CPA arising in PTB patients in 2019 was estimated to be 363 601  cases (range 254 521 - 472 682) and 42 766 deaths (range 29  936-55 595) - 10.5% of total PTB deaths. The 5-year-period prevalence of CPA was estimated at   1 575 716 , with an additional 100 715 deaths' total range of deaths 100 436- 186 525) annually., Interpretation: The revised estimation indicates a substantial unmet need for better diagnosis of CPA as part of a complex PTB-related respiratory morbidity burden., (© 2022 The Author(s).)

Myxobacteria are excellent model organisms for investigation of predator-prey interactions and predatory shaping of microbial communities. This review covers interdisciplinary topics related to myxobacterial predation and provides current concepts and challenges for determining predatory performance. Discussed topics include the role of specialized metabolites during predation, genetic determinants for predatory performance, challenges associated with methodological differences, discrepancies between sequenced and environmental myxobacteria, and factors that influence predation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Phillips, Akbar and Stevens.)

Background: Infection is associated with impaired nutritional status, especially for infants younger than 5 years., Objectives: We assessed the impact of infection indicated by both acute phase proteins (APP), C-reactive protein (CRP), and α-1-acid-glycoprotein (AGP), and as reported by maternal recall on the nutritional status of infants., Materials and Methods: A total of 505 pregnant women were enrolled in a nested longitudinal cohort study of vitamin A (VA). Data from 385 children are reported here. The incidence and severity of respiratory infection and diarrhea (previous 14 days) were assessed by maternal recall; infant/child feeding practices were collected. Infant weight, recumbent length, and heel-prick capillary blood were taken at 9 months postpartum. Indicators of the VA status [retinol binding protein (RBP)], iron status (Hb, ferritin), and subclinical inflammation APP, CRP (>5 mg/L), and AGP (>1 g/L) were determined. Impacts of infection on the infant nutritional status were estimated using logistic regression models., Results: Infection prevalence, based on elevated CRP and AGP levels, was 36.7%. For diarrhea reported symptoms, 42.4% of infants at 9 months had no indication of infection as indicated by CRP and AGP; for acute respiratory reported symptoms, 42.6% had no indication of infection. There was a significant positive association with infection among VA-deficient (RBP < 0.83 μmol/L) infants based on maternal reported symptoms but not with iron deficiency (ferritin < 12 μg/L). The odds of having infection, based on increased CRP and AGP, in underweight infants was 3.7 times higher (OR: 3.7; 95% CI: 2.3, 4.5; P = 0.019). Infants with iron deficiency were less likely (OR: 0.40; 95% CI: 0.1, 0.7; P = 0.001) to have infection based on CRP and AGP, while infants with VA deficiency were five times more likely (OR: 5.06; 95% CI: 3.2, 7.1; P = 0.0001) to have infection., Conclusion: Acute phase proteins are more useful in defining infection in a population than reported symptoms of illness. Not controlling for inflammation in a population while assessing the nutritional status might result in inaccurate prevalence estimation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Grant, Wanjala, Low, Levin, Cole, Okuku, Ackatia-Armah and Girard.)

Calcineurin is an essential virulence factor that is conserved across human fungal pathogens, including Cryptococcus neoformans, Aspergillus fumigatus, and Candida albicans. Although an excellent target for antifungal drug development, the serine-threonine phosphatase activity of calcineurin is conserved in mammals, and inhibition of this activity results in immunosuppression. FK506 (tacrolimus) is a naturally produced macrocyclic compound that inhibits calcineurin by binding to the immunophilin FKBP12. Previously, our fungal calcineurin-FK506-FKBP12 structure-based approaches identified a nonconserved region of FKBP12 that can be exploited for fungus-specific targeting. These studies led to the design of an FK506 analog, APX879, modified at the C-22 position, which was less immunosuppressive yet maintained antifungal activity. We now report high-resolution protein crystal structures of fungal FKBP12 and a human truncated calcineurin-FKBP12 bound to a natural FK506 analog, FK520 (ascomycin). Based on information from these structures and the success of APX879, we synthesized and screened a novel panel of C-22-modified compounds derived from both FK506 and FK520. One compound, JH-FK-05, demonstrates broad-spectrum antifungal activity in vitro and is nonimmunosuppressive in vivo . In murine models of pulmonary and disseminated C. neoformans infection, JH-FK-05 treatment significantly reduced fungal burden and extended animal survival alone and in combination with fluconazole. Furthermore, molecular dynamic simulations performed with JH-FK-05 binding to fungal and human FKBP12 identified additional residues outside the C-22 and C-21 positions that could be modified to generate novel FK506 analogs with improved antifungal activity. IMPORTANCE Due to rising rates of antifungal drug resistance and a limited armamentarium of antifungal treatments, there is a paramount need for novel antifungal drugs to treat systemic fungal infections. Calcineurin has been established as an essential and conserved virulence factor in several fungi, making it an attractive antifungal target. However, due to the immunosuppressive action of calcineurin inhibitors, they have not been successfully utilized clinically for antifungal treatment in humans. Recent availability of crystal structures of fungal calcineurin-bound inhibitor complexes has enabled the structure-guided design of FK506 analogs and led to a breakthrough in the development of a compound with increased fungal specificity. The development of a calcineurin inhibitor with reduced immunosuppressive activity and maintained therapeutic antifungal activity would add a significant tool to the treatment options for these invasive fungal infections with exceedingly high rates of mortality.

Accelerating ecological and societal changes require re-imagining the role of primary care and public health to address eco-social concerns in rural and remote places. In this narrative review, we searched literatures on: community-oriented primary care, patient-oriented research engagement, public health and primary care synergies, and primary care addressing social determinants of health. Our analysis was guided by questions oriented to utility for addressing concerns of social-ecological systems in rural, remote contexts characterized by a high degree of reliance on resource extraction and development (e.g., forestry, mining, oil and gas, fisheries, agriculture, ranching and/or renewables). We describe a range of useful frameworks, processes and tools that are oriented toward bolstering the resilience and engagement of both primary care and public health, though few explicitly incorporated considerations of eco-social approaches to health or broader eco-social context(s). In synthesizing the existing evidence base for integration between primary care and public health, the results signal that for community-oriented primary care and related frameworks to be useful in rural and remote community settings, practitioners are required to grapple with complexity, durable relationships, sustainable resources, holistic approaches to clinician training, Indigenous perspectives, and governance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Buse, Allison, Cole, Fumerton, Parkes and Woollard.)

We propose and demonstrate a protocol for high-fidelity indirect readout of trapped ion hyperfine qubits, where the state of a ^{9}Be^{+} qubit ion is mapped to a ^{25}Mg^{+} readout ion using laser-driven Raman transitions. By partitioning the ^{9}Be^{+} ground-state hyperfine manifold into two subspaces representing the two qubit states and choosing appropriate laser parameters, the protocol can be made robust to spontaneous photon scattering errors on the Raman transitions, enabling repetition for increased readout fidelity. We demonstrate combined readout and back-action errors for the two subspaces of 1.2&#95;{-0.6}^{+1.1}×10^{-4} and 0&#95;{-0}^{+1.9}×10^{-5} with 68% confidence while avoiding decoherence of spectator qubits due to stray resonant light that is inherent to direct fluorescence detection.

Multiomic analysis of transcriptional and metabolic responses from the predatory myxobacteria Myxococcus xanthus and Cystobacter ferrugineus exposed to prey signalling molecules of the acylhomoserine lactone and quinolone quorum signalling classes provided insight into predatory specialization. Acylhomoserine lactone quorum signals elicited a general response from both myxobacteria. We suggest that this is likely due to the generalist predator lifestyles of myxobacteria and ubiquity of acylhomoserine lactone signals. We also provide data that indicates the core homoserine lactone moiety included in all acylhomoserine lactone scaffolds to be sufficient to induce this general response. Comparing both myxobacteria, unique transcriptional and metabolic responses were observed from Cystobacter ferrugineus exposed to the quinolone signal 2-heptylquinolin-4(1H)-one (HHQ) natively produced by Pseudomonas aeruginosa. We suggest that this unique response and ability to metabolize quinolone signals contribute to the superior predation of P. aeruginosa observed from C. ferrugineus. These results further demonstrate myxobacterial eavesdropping on prey signalling molecules and provide insight into how responses to exogenous signals might correlate with prey range of myxobacteria., (© 2021 The Authors. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd.)

We demonstrate a simplified method for dissipative generation of an entangled state of two trapped-ion qubits. Our implementation produces its target state faster and with higher fidelity than previous demonstrations of dissipative entanglement generation and eliminates the need for auxiliary ions. The entangled singlet state is generated in ∼7  ms with a fidelity of 0.949(4). The dominant source of infidelity is photon scattering. We discuss this error source and strategies for its mitigation.

Calcineurin is a critical enzyme in fungal pathogenesis and antifungal drug tolerance and, therefore, an attractive antifungal target. Current clinically accessible calcineurin inhibitors, such as FK506, are immunosuppressive to humans, so exploiting calcineurin inhibition as an antifungal strategy necessitates fungal specificity in order to avoid inhibiting the human pathway. Harnessing fungal calcineurin-inhibitor crystal structures, we recently developed a less immunosuppressive FK506 analog, APX879, with broad-spectrum antifungal activity and demonstrable efficacy in a murine model of invasive fungal infection. Our overarching goal is to better understand, at a molecular level, the interaction determinants of the human and fungal FK506-binding proteins (FKBP12) required for calcineurin inhibition in order to guide the design of fungus-selective, nonimmunosuppressive FK506 analogs. To this end, we characterized high-resolution structures of the Mucor circinelloides FKBP12 bound to FK506 and of the Aspergillus fumigatus, M. circinelloides , and human FKBP12 proteins bound to the FK506 analog APX879, which exhibits enhanced selectivity for fungal pathogens. Combining structural, genetic, and biophysical methodologies with molecular dynamics simulations, we identify critical variations in these structurally similar FKBP12-ligand complexes. The work presented here, aimed at the rational design of more effective calcineurin inhibitors, indeed suggests that modifications to the APX879 scaffold centered around the C 15 , C 16 , C 18 , C 36 , and C 37 positions provide the potential to significantly enhance fungal selectivity. IMPORTANCE Invasive fungal infections are a leading cause of death in the immunocompromised patient population. The rise in drug resistance to current antifungals highlights the urgent need to develop more efficacious and highly selective agents. Numerous investigations of major fungal pathogens have confirmed the critical role of the calcineurin pathway for fungal virulence, making it an attractive target for antifungal development. Although FK506 inhibits calcineurin, it is immunosuppressive in humans and cannot be used as an antifungal. By combining structural, genetic, biophysical, and in silico methodologies, we pinpoint regions of the FK506 scaffold and a less immunosuppressive analog, APX879, centered around the C 15 to C 18 and C 36 to C 37 positions that could be altered with selective extensions and/or deletions to enhance fungal selectivity. This work represents a significant advancement toward realizing calcineurin as a viable target for antifungal drug discovery.

Invasive aspergillosis (IA) due to Aspergillus fumigatus is a deadly infection for which new antifungal therapies are needed. Here, we demonstrate the efficacy of a Gwt1 inhibitor, APX2041, and its prodrug, APX2104, against A. fumigatus. The wild-type, azole-resistant, and echinocandin-resistant A. fumigatus strains were equally susceptible to APX2041 in vitro . APX2104 treatment in vivo significantly prolonged survival of neutropenic mice challenged with the wild-type and azole-resistant strains, revealing APX2104 as a potentially promising therapeutic against IA.

Predation contributes to the structure and diversity of microbial communities. Predatory myxobacteria are ubiquitous to a variety of microbial habitats and capably consume a broad diversity of microbial prey. Predator-prey experiments utilizing myxobacteria have provided details into predatory mechanisms and features that facilitate consumption of prey. However, prey resistance to myxobacterial predation remains underexplored, and prey resistances have been observed exclusively from predator-prey experiments that included the model myxobacterium Myxococcus xanthus. Utilizing a predator-prey pairing that instead included the myxobacterium, Cystobacter ferrugineus, with Pseudomonas putida as prey, we observed surviving phenotypes capable of eluding predation. Comparative transcriptomics between P. putida unexposed to C. ferrugineus and the survivor phenotype suggested that increased expression of efflux pumps, genes associated with mucoid conversion, and various membrane features contribute to predator avoidance. Unique features observed from the survivor phenotype when compared to the parent P. putida include small colony variation, efflux-mediated antibiotic resistance, phenazine-1-carboxylic acid production, and increased mucoid conversion. These results demonstrate the utility of myxobacterial predator-prey models and provide insight into prey resistances in response to predatory stress that might contribute to the phenotypic diversity and structure of bacterial communities., (© 2021. The Author(s).)

Characterization and suppression of noise are essential for the control of harmonic oscillators in the quantum regime. We measure the noise spectrum of a quantum harmonic oscillator from low frequency to near the oscillator resonance by sensing its response to amplitude modulated periodic drives with a qubit. Using the motion of a trapped ion, we experimentally demonstrate two different implementations with combined sensitivity to noise from 500 Hz to 600 kHz. We apply our method to measure the intrinsic noise spectrum of an ion trap potential in a previously unaccessed frequency range.

Discoveries of novel myxobacteria have started to unveil the potentially vast phylogenetic diversity within the family Myxococcaceae and have brought about an updated approach to myxobacterial classification. While traditional approaches focused on morphology, 16S gene sequences, and biochemistry, modern methods including comparative genomics have provided a more thorough assessment of myxobacterial taxonomy. Herein, we utilize long-read genome sequencing for two myxobacteria previously classified as Archangium primigenium and Chondrococcus macrosporus , as well as four environmental myxobacteria newly isolated for this study. Average nucleotide identity and digital DNA-DNA hybridization scores from comparative genomics suggest previously classified as A. primigenium to instead be a novel member of the genus Melittangium , C. macrosporus to be a potentially novel member of the genus Corallococcus with high similarity to Corallococcus exercitus , and the four isolated myxobacteria to include another novel Corallococcus species, a novel Pyxidicoccus species, a strain of Corallococcus exiguus , and a potentially novel Myxococcus species with high similarity to Myxococcus stipitatus . We assess the biosynthetic potential of each sequenced myxobacterium and suggest that genus-level conservation of biosynthetic pathways support our preliminary taxonomic assignment. Altogether, we suggest that long-read genome sequencing benefits the classification of myxobacteria and improves determination of biosynthetic potential for prioritization of natural product discovery.

The discovery and application of new types of helical peptidic foldamers have been an attractive endeavor to enable the development of new materials, catalysts and biological molecules. To maximize their application potential through structure-based design, it is imperative to control their helical handedness based on their molecular scaffold. Herein we first demonstrate the generalizability of the solid-state right-handed helical propensity of the 4 13 -helix of L-α/L-sulfono-γ-AA peptides that as short as 11-mer, using the high-resolution X-ray single crystallography. The atomic level folding conformation of the foldamers was also elucidated by 2D NMR and circular dichroism under various conditions. Subsequently, we show that the helical handedness of this class of foldamer is controlled by the chirality of their chiral side chains, as demonstrated by the left-handed 4 13 -helix comprising 1:1 D-α/D-sulfono-γ-AA peptide. In addition, a heterochiral coiled-coil-like structure was also revealed for the first time, unambiguously supporting the impact of chirality on their helical handedness. Our findings enable the structure-based design of unique folding biopolymers and materials with the exclusive handedness or the racemic form of the foldamers in the future., (© 2021. The Author(s).)

Scholarship on the health impacts of resource extraction displays prominent gaps and apparent corporate and neocolonial footprints that raise questions about how science is produced. We analyze production of knowledge, on the health impacts of mining, carried out in relation to the Canadian International Resources and Development Institute (CIRDI), a university-based organization with substantial extractive industry involvement and links to Canada's mining-dominated foreign policy. We use a "political ecology of knowledge" framework to situate CIRDI in the context of neoliberal capitalism, neocolonial sustainable development discourses, and mining industry corporate social responsibility techniques. We then document the interactions of specific health disciplinary conventions and knowledges within CIRDI-related research and advocacy efforts involving a major Canadian global health organization. This analysis illustrates both accommodation and resistance to large-scale political economic structures and the need to directly confront the global North governments and sectors pushing extractive-led neoliberal development globally. Resumen La investigación sobre los impactos en la salud de la extracción de recursos naturales delata brechas importantes y huellas corporativas y neocoloniales, que plantean dudas acerca de cómo se produce la ciencia. Analizamos la producción de conocimiento sobre los impactos en la salud de la minería en relación con el Instituto Canadiense de Desarrollo y Recursos Internacionales (CIRDI, siglas en inglés), una organización universitaria que cuenta con participación sustancial de la industria extractiva y tiene vínculos con la política exterior de Canadá, la cual es dominada por intereses mineros. Utilizamos un marco de "ecología política del conocimiento" para situar a CIRDI en el contexto del capitalismo neoliberal, los discursos neocoloniales de desarrollo sostenible y las técnicas de responsabilidad social corporativa de la industria minera. Luego, documentamos las interacciones entre los conocimientos y convenciones disciplinarias de salud dentro de los esfuerzos de investigación y promoción relacionados con CIRDI que involucran a una importante organización canadiense de salud global. Este análisis muestra tanto la complacencia como la resistencia a las estructuras políticas económicas a gran escala, y la necesidad de confrontar directamente a los gobiernos y sectores del Norte global que manejan el desarrollo neoliberal impulsado por la extracción a nivel mundial.

During laboratory cultivation of the myxobacterium Archangium violaceum strain Cb vi76, a reoccurring contaminant was isolated and sequenced. Comparative taxonomic analysis of the draft genome suggested the contaminant to be a novel species, currently designated Aneurinibacillus sp. strain BA2021, from the genus Aneurinibacillus , members of which are considered promising biocontrol agents., (Copyright © 2021 Adaikpoh et al.)

Background: Social prescribing (SP) assists patients to engage in social activities and connect to community supports as part of a holistic approach to primary care . Rx: Community was a SP project, which was implemented within 11 community health centres (CHCs) situated across Ontario, Canada., Aim: To explore how SP as a process facilitates positive outcomes for patients., Design & Setting: Qualitative methods were used. Eighteen focus groups were conducted at CHCs or by video-conferencing, and involved 88 patients. In addition, eight in-depth telephone interviews were undertaken., Method: Interviews and focus groups were transcribed verbatim, and analysed thematically using a theoretical framework based on self-determination theory (SDT)., Results: Participants who had received social prescriptions described SP as an empathetic process that respects their needs and interests. SP facilitated the patient's voice in their care, helped patients to develop skills in addressing needs important to them, and fostered trusting relationships with staff and other participants. Patients reported their social support networks were expanded, and they had improved mental health and ability in self-management of chronic conditions. Patients who became involved in SP as voluntary 'health champions' reported this was a positive experience and they gained a sense of purpose by giving back to their communities in ways that felt meaningful for them., Conclusion: SP produced positive outcomes for patients, and it fits well within the community health centre model of primary care. Future research should examine the impact on health outcomes and examine the return on investment of developing and implementing SP programmes., (Copyright © 2021, The Authors.)

Considered a key taxon in soil and marine microbial communities, myxobacteria exist as coordinated swarms that utilize a combination of lytic enzymes and specialized metabolites to facilitate predation of microbes. This capacity to produce specialized metabolites and the associated abundance of biosynthetic pathways contained within their genomes have motivated continued drug discovery efforts from myxobacteria. Of all myxobacterial biosynthetic gene clusters deposited in the antiSMASH database, only one putative acylhomoserine lactone (AHL) synthase, agpI, was observed, in genome data from Archangium gephyra. Without an AHL receptor also apparent in the genome of A. gephyra, we sought to determine if AgpI was an uncommon example of an orphaned AHL synthase. Herein we report the bioinformatic assessment of AgpI and discovery of a second AHL synthase from Vitiosangium sp. During axenic cultivation conditions, no detectible AHL metabolites were observed in A. gephyra extracts. However, heterologous expression of each synthase in Escherichia coli provided detectible quantities of 3 AHL signals including 2 known AHLs, C8-AHL and C9-AHL. These results suggest that A. gephyra AHL production is dormant during axenic cultivation. The functional, orphaned AHL synthase, AgpI, is unique to A. gephyra, and its utility to the predatory myxobacterium remains unknown.

Child growth standards are commonly used to derive age- and sex-standardized anthropometric indices but are often inappropriately applied to preterm-born children (<37 weeks of gestational age (GA)) in epidemiology studies. Using the 2004 Pelotas Birth Cohort, we examined the impact of correcting for GA in the application of child growth standards on the magnitude and direction of associations in 2 a priori-selected exposure-outcome scenarios: infant length-for-age z score (LAZ) and mid-childhood body mass index (scenario A), and infant LAZ and mid-childhood intelligence quotient (scenario B). GA was a confounder that had a strong (scenario A) or weak (scenario B) association with the outcome. Compared with uncorrected postnatal age, using GA-corrected postnatal age attenuated the magnitude of associations, particularly in early infancy, and changed inferences for associations at birth. Although differences in the magnitude of associations were small when GA was weakly associated with the outcome, model fit was meaningfully improved using corrected postnatal age. When estimating population-averaged associations with early childhood growth in studies where preterm- and term-born children are included, incorporating heterogeneity in GA at birth in the age scale used to standardize anthropometric indices postnatally provides a useful strategy to reduce standardization errors., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Competing Interests: Competing interests: None declared.

Objectives: Psychosocial adaptation to climate change-related events remains understudied. We sought to assess how the psychosocial consequences of a major event were addressed via public health responses (e.g., programs, policies, and practices) that aimed to enhance, protect, and promote mental health., Methods: We report on a study of health and social service responses to the long-term mental health impacts of the 2013 Southern Alberta flood, in High River, Alberta. Qualitative research methods included (i) telephone interviews (n = 14) with key informant health and social services leaders, (ii) four focus group sessions with front-line health and social services workers (n = 14), and (iii) semi-structured interviews with a sample of community members (n = 18) who experienced the flood. We conducted a descriptive thematic analysis, with a focus on participants' perceptions and experiences., Results: Findings of this study suggest (1) the long-term psychosocial impacts of extreme weather and climate change require sustained recovery interventions rooted in local knowledge and interdisciplinary action; (2) there are unintended consequences related to psychosocial interventions that can incite complex emotions and impact psychosocial recovery; and (3) perceptions of mental health care, among people exposed to climate-related trauma, can guide climate change and mental health response and recovery interventions., Conclusion: Based on this initial exploration, policy and practice opportunities for public health to enhance psychosocial adaptation to our changing climate are highlighted.

In evolutionary terms, the transformations which humans have engendered in social, ecological and built environments are increasingly out of step with their biological makeup. We briefly review the evidence on health-relevant practices and status of our Paleolithic ancestors and contrast these with current food, transportation, work and governance systems with their associated impacts on human health. As public health and planning practitioners engaged in the EcoHealth Ontario Collaborative, we argue for recognition of our hunter-gatherer nature to promote joint efforts in building sustainable and equitable community infrastructures, both built and green. Although such efforts are underway at multiple jurisdictional levels across Canada, the pace is frustratingly slow for the burden of endemic chronic diseases and global environmental change which humans face. Reminding reluctant stakeholders of the hunter-gatherers in us all could bring about deeper reflection on the urgent work in redirecting community planning.

Triazole antifungals are the primary therapeutic option against invasive aspergillosis. However, resistance to azoles has increased dramatically over the last decade. Azole resistance is known to primarily occur due to point mutations in the azole target protein Cyp51A, one of two paralogous 14-α sterol demethylases found in Aspergillus fumigatus Despite the importance of Cyp51A, little is known about the function of its paralog, Cyp51B, and the behavior of these proteins within the cell or their functional interrelationship. In this study, we addressed two important aspects of the Cyp51 proteins: (i) we characterized their localization patterns under normal growth versus stress conditions, and (ii) we determined how the proteins compensate for each other's absence and respond to azole treatment. Both the Cyp51A and Cyp51B proteins were found to localize in distinct endoplasmic reticulum (ER) domains, including the perinuclear ER and the peripheral ER. Occasionally, the Cyp51 proteins concentrated in the peripheral ER network of tubules along the hyphal septa and at the hyphal tips. Exposure to voriconazole, caspofungin, and Congo red led to significant increases in fluorescence intensity in these alternative localization sites, indicative of Cyp51 protein translocation in response to cell wall stress. Furthermore, deletion of either Cyp51 paralog increased susceptibility to voriconazole, though a greater effect was observed following deletion of cyp51A , indicating a compensatory response to stress conditions., (Copyright © 2020 American Society for Microbiology.)