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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.)

Introduction: Social trust is an important driver of health seeking behaviours and plays a particularly important role for diseases that have a high degree of stigma associated with them, such as tuberculosis (TB). Individuals experiencing poverty also face additional social and financial barriers in accessing care for TB. We examined an active case finding (ACF) initiative embedded in a program targeting those living in poverty ( Transform) implemented by International Care Ministries (ICM), a Philippine-based non-governmental organization (NGO), and analyzed how different forms of social trust may affect the initial uptake of ACF., Methods: Program monitoring data and a cross-sectional survey conducted at the beginning of Transform included six dimensions of social trust: satisfaction with family life, satisfaction with friendships, and level of trust in relatives, neighbours, pastor or religious leader, and local government officials. Amongst individuals suspected of having TB who received referrals post-screening, multilevel modelling examined the effects of social trust on rural health unit (RHU) attendance., Results: Among the subset of 3350 individuals who received TB screening in 51 communities, 889 (26.5%) were symptom positive and required referral to the RHU, but only 24.1% of those who received referrals successfully attended the RHU. Multilevel regression analysis showed that for each unit increase on the Likert scale in baseline level of family satisfaction and level of trust in relatives, the odds of attending an RHU was 1.03 times (95% CI: 0.99, 1.07) and 1.06 times greater (95% CI: 1.00, 1.11), respectively, independent of other factors., Conclusion: These results suggest that social trust in family members could play a valuable role in addressing stigma and rejection, both cited as barriers to higher screening rates. It is recommended that ACF programs that target TB, or other diseases that are stigmatized, prioritize trust-building as an important component of their intervention., Competing Interests: Authors (LLL, NH, KL & JDF) receive renumeration from ICM. The authors have been provided academic freedom by ICM to publish both negative and positive results. We declare no other competing interests according to ICMJE., (© 2020 The Author(s).)

Objectives: In the context of persistent child malnutrition in the Philippines, the objective of this study was to examine how different dimensions of trust affected programme retention and physiological outcomes when a faith-based organisation (FBO) addressed moderate and severe acute malnutrition among children from households experiencing extreme poverty., Setting: We retrospectively analysed survey data collected by International Care Ministries (ICM) in 2012-2013 across 150 communities in eight provinces (Negros Oriental, Negros Occidental, Bohol, Palawan, Sarangani, South Cotabato, Sultan Kudarat and Zamboanga del Norte) of the Philippines., Study Participants: Caregivers of 1192 children experiencing moderate acute malnutrition and severe acute malnutrition between the ages of 6 and 60 months., Intervention: A 16-week child malnutrition treatment programme called Malnourished Child Outreach offered by ICM in partnership with local religious leaders and institutions., Primary and Secondary Outcome Measures: Programme dropout and weight-for-height z-score (WHZ) at the end of the programme for enrolled children were the two outcomes of interest. A logistic mixed-effects model was built to assess factors associated with programme dropout and a linear mixed-effects model for factors associated with WHZ at the end of the programme., Results: Trust in religious leaders or institutions (-0.87 (95% CI: -1.43,-0.26)) was negatively associated with programme dropout, suggesting that with increasing levels of trust, decreasing proportions of children dropped out of treatment. Retention in the programme led to improved WHZ among participating children (-0.38 (95% CI: -1.43, 0.26)). Various measures of social capital, including trust in religious and public institutions, were not associated with WHZ at the end of the programme., Conclusions: Leveraging pre-existing trust in religious leaders and institutions among households experiencing extreme poverty is one way that ICM, and potentially other FBOs, can promote retention in child nutrition interventions among vulnerable populations., Competing Interests: Competing interests: Dr LLL reports that LLL and HLQ were paid salaries by ICM as research staff which informs our view on the value of partnerships with religious leaders and institutions in delivering health programmes in income poor settings. They were both given full freedom to publish positive and/or negative results., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The human fungal pathogen Aspergillus fumigatus causes life-threatening invasive aspergillosis in immunocompromised individuals. Adaptation to the host environment is integral to survival of A. fumigatus and requires the coordination of short- and long-distance vesicular transport to move essential components throughout the fungus. We previously reported the importance of MyoE, the only class V myosin, for hyphal growth and virulence of A. fumigatus. Class V myosins are actin-based, cargo-carrying motor proteins that contain unique binding sites for specific cargo. Specific cargo carried by myosin V has not been identified in any fungus, and previous studies have only identified single components that interact with class V myosins. Here we utilized a mass spectrometry-based whole proteomic approach to identify MyoE interacting proteins in A. fumigatus for the first time. Several proteins previously shown to interact with myosin V through physical and genetic approaches were confirmed, validating our proteomic analysis. Importantly, we identified novel MyoE-interacting proteins, including members of the cytoskeleton network, cell wall synthesis, calcium signaling and a group of coat protein complex II (COPII) proteins involved in the endoplasmic reticulum (ER) to Golgi transport. Furthermore, we analyzed the localization patterns of the COPII proteins, UsoA (Uso1), SrgE (Sec31), and SrgF (Sec23), which suggested a potential role for MyoE in ER to Golgi trafficking., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The 12-kDa FK506-binding protein (FKBP12) is the target of the commonly used immunosuppressive drug FK506. The FKBP12-FK506 complex binds to calcineurin and inhibits its activity, leading to immunosuppression and preventing organ transplant rejection. Our recent characterization of crystal structures of FKBP12 proteins in pathogenic fungi revealed the involvement of the 80's loop residue (Pro90) in the active site pocket in self-substrate interaction providing novel evidence on FKBP12 dimerization in vivo. The 40's loop residues have also been shown to be involved in reversible dimerization of FKBP12 in the mammalian and yeast systems. To understand how FKBP12 dimerization affects FK506 binding and influences calcineurin function, we generated Aspergillus fumigatus FKBP12 mutations in the 40's and 50's loop (F37 M/L; W60V). Interestingly, the mutants exhibited variable FK506 susceptibility in vivo indicating differing dimer strengths. In comparison to the 80's loop P90G and V91C mutants, the F37 M/L and W60V mutants exhibited greater FK506 resistance, with the F37M mutation showing complete loss in calcineurin binding in vivo. Molecular dynamics and pulling simulations for each dimeric FKBP12 protein revealed a two-fold increase in dimer strength and significantly higher number of contacts for the F37M, F37L, and W60V mutations, further confirming their varying degree of impact on FK506 binding and calcineurin inhibition in vivo., Competing Interests: Declaration of competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Chamas for Change (Chamas) is a group-based health education and microfinance program for pregnant and postpartum women that aims to address inequities contributing to high rates of maternal and infant mortality in rural western Kenya. In this prospective matched cohort study, we evaluated the association between Chamas participation and facility-based delivery. We additionally explored the effect of participation on promoting other positive maternal, newborn and child health (MNCH) behaviors., Methods: We prospectively compared outcomes between a cohort of Chamas participants and controls matched for age, parity, and prenatal care location. Between October-December 2012, government-sponsored community health volunteers (CHV) recruited pregnant women attending their first antenatal care (ANC) visits at rural health facilities in Busia County to participate in Chamas. Women enrolled in Chamas agreed to attend group-based health education and microfinance sessions for one year; controls received the standard of care. We used descriptive analyses, multivariable logistic regression models, and random effect models to compare outcomes across cohorts 12 months following enrollment, with α set to 0.05., Results: Compared to controls (n = 115), a significantly higher proportion of Chamas participants (n = 211) delivered in a health facility (84.4% vs. 50.4%, p < 0.001), attended at least four ANC visits (64.0% vs. 37.4%, p < 0·001), exclusively breastfed to six months (82.0% vs. 47.0%, p < 0·001), and received a CHV home visit within 48 h postpartum (75.8% vs. 38.3%, p < 0·001). In multivariable models, Chamas participants were over five times as likely as controls to deliver in a health facility (OR 5.49, 95% CI 3.12-9.64, p < 0.001). Though not significant, Chamas participants experienced a lower proportion of stillbirths (0.9% vs. 5.2%), miscarriages (5.2% vs. 7.8%), infant deaths (2.8% vs. 3.4%), and maternal deaths (0.9% vs. 1.7%) compared to controls., Conclusions: Chamas participation was associated with increased odds of facility-based delivery compared to the standard of care in rural western Kenya. Larger proportions of program participants also practiced other positive MNCH behaviors. Our findings demonstrate Chamas' potential to achieve population-level MNCH benefits; however, a larger study is needed to validate this observed effect., Trial Registration: ClinicalTrials.gov, NCT03188250 (retrospectively registered 31 May 2017).

Microresonator-based soliton frequency combs, microcombs, have recently emerged to offer low-noise, photonic-chip sources for applications, spanning from timekeeping to optical-frequency synthesis and ranging. Broad optical bandwidth, brightness, coherence, and frequency stability have made frequency combs important to directly probe atoms and molecules, especially in trace gas detection, multiphoton light-atom interactions, and spectroscopy in the extreme ultraviolet. Here, we explore direct microcomb atomic spectroscopy, using a cascaded, two-photon 1529-nm atomic transition in a rubidium micromachined cell. Fine and simultaneous repetition rate and carrier-envelope offset frequency control of the soliton enables direct sub-Doppler and hyperfine spectroscopy. Moreover, the entire set of microcomb modes are stabilized to this atomic transition, yielding absolute optical-frequency fluctuations at the kilohertz level over a few seconds and <1-MHz day-to-day accuracy. Our work demonstrates direct atomic spectroscopy with Kerr microcombs and provides an atomic-stabilized microcomb laser source, operating across the telecom band for sensing, dimensional metrology, and communication., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

As a collective organized to address the education implications of calls for public health engagement on the ecological determinants of health, we, the Ecological Determinants Group on Education (cpha.ca/EDGE), urge the health community to properly understand and address the importance of the ecological determinants of the public's health, consistent with long-standing calls from many quarters-including Indigenous communities-and as part of an eco-social approach to public health education, research and practice. Educational approaches will determine how well we will be equipped to understand and respond to the rapid changes occurring for the living systems on which all life-including human life-depends. We revisit findings from the Canadian Public Health Association's discussion paper on 'Global Change and Public Health: Addressing the Ecological Determinants of Health', and argue that an intentionally eco-social approach to education is needed to better support the health sector's role in protecting and promoting health, preventing disease and injury, and reducing health inequities. We call for a proactive approach, ensuring that the ecological determinants of health become integral to public health education, practice, policy, and research, as a key part of wider societal shifts required to foster a healthy, just, and ecologically sustainable future.

Chemical exchanges between plants and microbes within rhizobiomes are critical to the development of community structure. Volatile root exudates such as the phytohormone methyljasmonate (MeJA) contribute to various plant stress responses and have been implicated to play a role in the maintenance of microbial communities. Myxobacteria are competent predators of plant pathogens and are generally considered beneficial to rhizobiomes. While plant recruitment of myxobacteria to stave off pathogens has been suggested, no involved chemical signaling processes are known. Herein we expose predatory myxobacteria to MeJA and employ untargeted mass spectrometry, motility assays, and RNA sequencing to monitor changes in features associated with predation such as specialized metabolism, swarm expansion, and production of lytic enzymes. From a panel of four myxobacteria, we observe the most robust metabolic response from plant-associated Archangium sp. strain Cb G35 with 10 μM MeJA impacting the production of at least 300 metabolites and inducing a ≥ fourfold change in transcription for 56 genes. We also observe that MeJA induces A. sp. motility supporting plant recruitment of a subset of the investigated micropredators. Provided the varying responses to MeJA exposure, our observations indicate that MeJA contributes to the recruitment of select predatory myxobacteria suggesting further efforts are required to explore the microbial impact of plant exudates associated with biotic stress., (Copyright © 2020 Adaikpoh, Akbar, Albataineh, Misra, Sharp and Stevens.)

In the context of climate change, a nutritional transition, and increased pressures to migrate internally and internationally, this study examined the relationship between seasonal food insecurity and demographic, socioeconomic, and agricultural production factors among small-scale subsistence farmers in rural northern Honduras. Anchored by a partnership with the Fundación para la Investigación Participativa con Agricultores de Honduras (FIPAH) and the Yorito Municipal Health Centre, a cross-sectional household survey was administered in Yorito, Honduras, in July 2014. The study population included 1263 individuals from 248 households across 22 rural communities. A multivariate mixed effects negative binomial regression model was built to investigate the relationship between the self-reported number of months without food availability and access from subsistence agriculture in the previous year (August 2013-July 2014) and demographic, socioeconomic, and agricultural production variables. This study found a lengthier 'lean season' among surveyed household than previously documented in Honduras. Overall, 62.2% (95% confidence interval (CI): [59.52, 64.87]) of individuals experienced at least four months of insufficient food in the previous year. Individuals from poorer and larger households were more likely to experience insufficient food compared to individuals from wealthier and smaller households. Additionally, individuals from households that produced both maize and beans were less likely to have insufficient food compared to individuals from households that did not grow these staple crops (prevalence ratio (PR) = 0.83; 95% CI: [0.69, 0.99]). Receiving remittances from a migrant family member did not significantly reduce the prevalence of having insufficient food. As unpredictable crop yields linked to climate change and extreme weather events are projected to negatively influence the food security and nutrition outcomes of rural populations, it is important to understand how demographic, socioeconomic, and agricultural production factors may modify the ability of individuals and households engaged in small-scale subsistence agriculture to respond to adverse shocks., Competing Interests: The authors declare that they have no conflict of interest.

Forced migration and extended time spent migrating may lead to prolonged marginalization and increased risk of HIV. We conducted a population-based cohort study to examine whether secondary migration status, where secondary migrants resided in a transition country prior to arrival in Ontario, Canada and primary migrants arrived directly from their country of birth, modified the relationship between refugee status and HIV. Unadjusted and adjusted prevalence ratios (APR) and 95% confidence intervals (CI) were estimated using log-binomial regression. In sensitivity analysis, refugees with secondary migration were matched to the other three groups on country of birth, age and year of arrival (+/- 5 years) and analyzed using conditional logistic regression. Unmatched and matched models were adjusted for age and education. HIV prevalence among secondary and primary refugees and non-refugees was 1.47% (24/1629), 0.82% (112/13,640), 0.06% (7/11,571) and 0.04% (49/114,935), respectively. Secondary migration was a significant effect modifier ( p -value = .02). Refugees with secondary migration were 68% more likely to have HIV than refugees with primary migration (PR = 1.68, 95% CI 1.06, 2.68; APR = 1.68, 95% 1.04, 2.71) with a stronger effect in the matched model. There was no difference among non-refugee immigrants. Secondary migration may amplify HIV risk among refugee but not non-refugee immigrant mothers.

Objective : To explore rural clinicians' understanding of farmers' mental health and well-being, current health services, and potential responses. Methods : Qualitative design, with semi-structured, taped interviews of five family physicians and four mental health nurses-counselors practicing in rural Grey-Bruce counties, Ontario. Transcripts analyzed with N-Vivo through iterative coding of emergent themes and mapping of relationships among themes. Results : Participating rural clinicians all expressed admiration for farmers. They shared insights around three main themes: 1) farming as a unique subculture; 2) farming involved both benefits and challenges for health; and 3) farmers rarely seek care. Clinicians need to take advantage of contact opportunities to ask about mental health. Several suggested ways to meet farmers where they are, e.g., through better funding for house-farm calls and community events. Conclusion : Clinician responses to farmers' mental health challenges include recognizing farmers' distinct context. Complementary health promotion in conjunction with farm organizations is needed to reach farmers.

Introduction: The intersecting vulnerabilities of migrant agricultural workers (MAWs) impact both their health and their access to health care in rural areas, yet rural clinicians' voices are rarely documented. The purpose of this study was to explore health professionals' perspectives on health care for MAWs in sending countries and rural Ontario, Canada., Methods: Qualitative research design occurred over three distinct projects, using a multi-methodological approach including semi-structured interviews in Mexico, Jamaica and rural Ontario (n=43), and session field notes and questionnaires administered to healthcare providers (n=65) during knowledge exchange sessions in rural Ontario. A systematic analysis of these data was done to identify common themes, using NVivo software initially and then Microsoft Excel for application of a framework approach., Results: Structural challenges posed by migrant workers' context included difficulties preventing and managing work-related conditions, employers or supervisors compromising confidentiality, and MAWs' fears of loss of employment and return to countries of origin prior to completing treatments. Structural challenges related to health services included lack of adequate translation/interpretation services and information about insurance coverage and MAWs' work and living situations; scheduling conflicts between clinic hours and MAWs' availability; and difficulties in arranging follow-up tests, treatments and examinations. Intercultural challenges included language/communication barriers; cultural barriers /perceptions; and limited professional knowledge of MAWs' migration and work contexts and MAWs' knowledge of the healthcare system. Transnational challenges arose around continuity of care, MAWs leaving Canada during/prior to receiving care, and dealing with health problems acquired in Canada. A range of responses were suggested, some in place and others requiring additional organization, testing and funding., Conclusion: Funding to strengthen responses to structural and intercultural challenges, including research assessing improved supports to rural health professionals serving MAWs, are needed in rural Canada and rural Mexico and Jamaica, in order to better address the structural and intersecting vulnerabilities and the care needs of this specific population.

Integrated nutrition and agricultural interventions have the potential to improve the efficiency and effectiveness of investments in food security and nutrition. This article aimed to estimate the costs of an integrated agriculture and health intervention (Mama SASHA) focused on the promotion of orange-fleshed sweet potato (OFSP) production and consumption in Western Kenya. Programme activities included nutrition education and distribution of vouchers for OFSP vines during antenatal care and postnatal care (PNC) visits. We used expenditures and activity-based costing to estimate the financial costs during programme implementation (2011-13). Cost data were collected from monthly expense reports and interviews with staff members from all implementing organizations. Financial costs totalled US$507 809 for the project period. Recruiting and retaining women over the duration of their pregnancy and postpartum period required significant resources. Mama SASHA reached 3281 pregnant women at a cost of US$155 per beneficiary. Including both pregnant women and infants who attended PNC services with their mothers, the cost was US$110 per beneficiary. Joint planning, co-ordination and training across sectors drove 27% of programme costs. This study found that the average cost per beneficiary to implement an integrated agriculture, health and nutrition programme was substantial. Planning and implementing less intensive integrated interventions may be possible, and economies of scale may reduce overall costs. Empirical estimates of costs by components are critical for future planning and scaling up of integrated programmes., (© The Author(s) 2019. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.)

Aims: Agate workers in Khambhat, India and their community members are exposed to high levels of silica dust and related diseases. Use of effective prevention practices remains low, prompting the need for effective interventions which increase the uptake of and investment in prevention practices. We sought: (a) to describe knowledge, self-efficacy, and practices among a population of workers, their family members, and neighbors involved in or located close to agate processing; and (b) to explore which factors are related to use of prevention practices and willingness to invest in new dust control technologies., Methods: A community survey was conducted to measure demographics, occupation and financial factors, knowledge, prevention practices, barriers, risk perceptions, and efficacy beliefs. Descriptive statistics were used and, among agate workers, hierarchical logistic regression explored predictors of prevention practice use and willingness to invest., Results: Among 1120 respondents, approximately 44%, 35%, and 8% of workers, family members, and neighbors used prevention practices, respectively. Knowledge and risk perceptions were generally high, where efficacy beliefs were low. Workers who had high levels of education, worked at home, and had high efficacy beliefs were more likely to report using prevention practices and being willing to invest. Barriers to prevention practice use included financial barriers, and beliefs that prevention is ineffective and health is not at risk., Conclusions: Interventions and future research should be designed to engage the community to improve preventive behavior, and implement affordable and effective dust control interventions in the agate industry., (© 2019 The Authors. Journal of Occupational Health published by John Wiley & Sons Australia, Ltd on behalf of The Japan Society for Occupational Health.)

We predict subharmonic entrainment of breather-soliton oscillations to a periodic perturbation at the round-trip time T&#95;{R} in Kerr-nonlinear optical resonators; an integer ratio T&#95;{b}/T&#95;{R}=N≫1 results for breathing period T&#95;{b}. Rigid entrainment is observed with intermediate finesse (F∼30-40) for N up to 20, and we propose a way to realize higher entrainment ratios at higher finesse. This nontrivial synchronization across the widely separated timescales of the photon lifetime and round-trip time points to a new direction for research in this field and may find application, for example, in the measurement of a pulse train repetition rate that is electronically inaccessible.

Strategic planning, in its various forms, is an evaluation practice that is ubiquitous in academic medicine. However, published reports of strategic planning at academic health centers usually ignore theory. In a 2017 strategic planning exercise at the Wilson Centre, a scholarly model evolved using a theoretical framework and a research approach rather than a conventional management model, which typically identifies outcomes and how to achieve them. After completing this exercise, the authors considered the larger questions of the assumptions underpinning different models of strategic planning and strategic planning's value to academic medicine. To elaborate on these questions, the authors examine relevant literature and set out the Wilson Centre's emergent scholarly model. They describe the main features of the scholarly model, including ways it differs from a management approach and from the typical approach to strategic planning in the authors' experience and in the field of health professions education research. The authors also share lessons learned as a means to encourage consideration by other academic organizations.

Calcineurin is important for fungal virulence and a potential antifungal target, but compounds targeting calcineurin, such as FK506, are immunosuppressive. Here we report the crystal structures of calcineurin catalytic (CnA) and regulatory (CnB) subunits complexed with FK506 and the FK506-binding protein (FKBP12) from human fungal pathogens (Aspergillus fumigatus, Candida albicans, Cryptococcus neoformans and Coccidioides immitis). Fungal calcineurin complexes are similar to the mammalian complex, but comparison of fungal and human FKBP12 (hFKBP12) reveals conformational differences in the 40s and 80s loops. NMR analysis, molecular dynamic simulations, and mutations of the A. fumigatus CnA/CnB-FK506-FKBP12-complex identify a Phe88 residue, not conserved in hFKBP12, as critical for binding and inhibition of fungal calcineurin. These differences enable us to develop a less immunosuppressive FK506 analog, APX879, with an acetohydrazine substitution of the C22-carbonyl of FK506. APX879 exhibits reduced immunosuppressive activity and retains broad-spectrum antifungal activity and efficacy in a murine model of invasive fungal infection.