An objective metric of individual health and aging for population surveys.

BACKGROUND: We have previously developed and validated a biomarker-based metric of overall health status using Mahalanobis distance (DM) to measure how far from the norm of a reference population (RP) an individual's biomarker profile is. DM is not particularly sensitive to the choice of biomarkers; however, this makes comparison across studies difficult. Here we aimed to identify and validate a standard, optimized version of DM that would be highly stable across populations, while using fewer and more commonly measured biomarkers. METHODS: Using three datasets (the Baltimore Longitudinal Study of Aging, Invecchiare in Chianti and the National Health and Nutrition Examination Survey), we selected the most stable sets of biomarkers in all three populations, notably when interchanging RPs across populations. We performed regression models, using a fourth dataset (the Women's Health and Aging Study), to compare the new DM sets to other well-known metrics [allostatic load (AL) and self-assessed health (SAH)] in their association with diverse health outcomes: mortality, frailty, cardiovascular disease (CVD), diabetes, and comorbidity number. RESULTS: A nine- (DM9) and a seventeen-biomarker set (DM17) were identified as highly stable regardless of the chosen RP (e.g.: mean correlation among versions generated by interchanging RPs across dataset of r = 0.94 for both DM9 and DM17). In general, DM17 and DM9 were both competitive compared with AL and SAH in predicting aging correlates, with some exceptions for DM9. For example, DM9, DM17, AL, and SAH all predicted mortality to a similar extent (ranges of hazard ratios of 1.15-1.30, 1.21-1.36, 1.17-1.38, and 1.17-1.49, respectively). On the other hand, DM9 predicted CVD less well than DM17 (ranges of odds ratios of 0.97-1.08, 1.07-1.85, respectively). CONCLUSIONS: The metrics we propose here are easy to measure with data that are already available in a wide array of panel, cohort, and clinical studies. The standardized versions here lose a small amount of predictive power compared to more complete versions, but are nonetheless competitive with existing metrics of overall health. DM17 performs slightly better than DM9 and should be preferred in most cases, but DM9 may still be used when a more limited number of biomarkers is available.

Mortality in homeless people enrolled in the French housing first randomized controlled trial: a secondary outcome analysis of predictors and causes of death.

BACKGROUND: Homeless people face large excess mortality in comparison with the general population, but little is known about the effect of housing interventions like Housing First (HF) on their mortality. AIMS OF THE STUDY: 1) to explore 2-years mortality among homeless people with severe mental illness (SMI) included in French HF randomized controlled trial (RCT). 2) To examine causes of death among homeless participants. METHODS: For 703 participants of HF RCT: 353 in experimental group (HF) and 350 in control group (Treatment As Usual - TAU), any proof of life or death and causes of death were collected with a thorough retrospective investigation among relatives, institutions and administrative databases. Data collection took place from March to June 2017. RESULTS: 4.8% (n = 34) of the study participants died over the study period. Mean age of death was 40.9 (+/- 11.4) years. The overall 2-years mortality rate was 0.065 in the HF group (n = 23) versus 0.034 in the TAU group (n = 11). Mortality was associated with medications for opioid use disorder in multivariate Cox analysis (HR: 2.37, 95%CI 1.15-5.04, p = 0.025). Those in HF group seem to be more at risk of death compared to TAU group, mainly during the first 6 months of being housed, although the difference did not reach significance (HR: 0.49, 95%CI 0.24-1.01, p = 0.054). Violent deaths occurred in 52.2% of HF group's deaths versus 18.2% of TAU group's deaths, this excess being explained by 34.8% (n = 8) deaths by overdoses in HF group versus none in TAU group. LIMITATIONS: 1) 8.7% (n = 2) people in HF group died before HF intervention but were analyzed in intention-to-treat. 2) No proof of life or death has been found for only 0.6% in HF group (n = 2) but for 9.5% people in TAU group (n = 33) that could be anonymous deaths. 3) Undetermined causes represented 8.7% of deaths in HF group versus 36.4% in TAU group. 4) The small number of events (deaths) in the study population is a limitation for statistical analysis. CONCLUSIONS: Due to important limitations, we cannot conclude on HF effect on mortality, but our results nevertheless confirm that the vulnerability of long-term homeless people with SMI persists after accessing independent housing. Earlier intervention in the pathways of homelessness should be considered, alongside active specific support for addictions. TRIAL REGISTRATION: Ethics Committee Sud Mediterrannée V n° 11.050: trial number 2011-A00668-33: 28/07/2011. Clinicaltrials ID NCT01570712 : 4/4/2012.

In situ QXAS study of sulfidation/oxidative regeneration reactions of zinc molybdate (ZnMoO4) and ZnO-MoO3 materials.

Recent technologies such as those using coal, natural gas or biomass as fuel are often facing the challenge of removing H2S impurities. Among the various existing routes for sulfur removal, the conversion of transition metal oxides into sulfides is often considered for deep gas purification. The ideal regenerative system, preventing waste generation, should combine a high affinity material towards H2S and an easy way for its regeneration into the initial oxide form. The present paper describes the reactivity of the ZnMoO4 mixed oxide material and ZnO-MoO3 oxides mixture as potential candidates for the regenerative H2S sorption process. The use of the QXAS technique allowed us to get time resolved information about both sulfidation and oxidative regeneration processes at Mo and Zn K-edges. Faced with the complexity of gas-solid reactions involving several phases, QXAS in combination with multivariate data analysis enabled us to follow the sulfidation and oxidative regeneration kinetics of both materials, with a description of the evolution of several intermediate phases. Both Mo and Zn K-edge spectroscopic data were analyzed and comparison of the evolution of ternary oxides containing the two elements proved to be an effective way for validating the results.

Problems maintaining collaborative approaches with excluded populations in a randomised control trial: lessons learned implementing Housing First in France.

BACKGROUND: In 2006, a local collective combating homelessness set up an 'experimental squat' in an abandoned building in Marseille, France's second largest city. They envisioned the squat as an alternative to conventional health and social services for individuals experiencing long-term homelessness and severe psychiatric disorders. Building on what they learned from the squat, some then joined a larger coalition that succeeded in convincing national government decision-makers to develop a scientific, intervention-based programme based on the Housing First model. This article analyses the political process through which social movement activism gave way to support for a state-funded programme for homeless people with mental disorders. METHODS: A qualitative study of this political process was conducted between 2006 and 2014, using a hybrid theoretical perspective that combines attention to both top-down and bottom-up actions with a modified Advocacy Coalition Framework. In addition to document analysis of published and grey literature linked to the policy process, researchers drew on participant observation and observant participation of the political process. Data analysis consisted primarily of a thematic analysis of field-notes and semi-structured interviews with 65 relevant actors. RESULTS: A coalition of local activists, state officials and national service providers transformed knowledge about a local innovation (an experimental therapeutic squat) into the rationale for a national, scientifically based project consisting of a randomised controlled trial of four state-supported Housing First sites, costing several million euros. The coalition's strategy was two-pronged, namely to defend a social cause (the right to housing) and to promote a scientifically validated means of realising positive outcomes (housing tenure) and cost-effectiveness (reduced hospitalisation costs). CONCLUSION: Activists' self-agency, especially that of making themselves audible to public authorities, was enhanced by the coalition's ability to seize 'windows of opportunities' to their advantage. However, in contrast to the United States and Canadian Housing First contexts, which are driven by implementation science and related approaches, it was grassroots activists who promoted a scientific-technical approach among government officials unfamiliar with evidence-based practices in France. The windows of opportunity nevertheless failed to attract participation of those most in need of housing, raising the question of whether and how marginalised and/or subordinate groups can be integrated into collaborative research when a social movement-driven innovation turns into a scientific approach. TRIAL REGISTRATION: The current clinical trial number is NCT01570712 . Registered July 17, 2011. First patient enrolled August 18, 2011.

Comprehensive proteome profiling in Aedes albopictus to decipher Wolbachia-arbovirus interference phenomenon.

BACKGROUND: Aedes albopictus is a vector of arboviruses that cause severe diseases in humans such as Chikungunya, Dengue and Zika fevers. The vector competence of Ae. albopictus varies depending on the mosquito population involved and the virus transmitted. Wolbachia infection status in believed to be among key elements that determine viral transmission efficiency. Little is known about the cellular functions mobilized in Ae. albopictus during co-infection by Wolbachia and a given arbovirus. To decipher this tripartite interaction at the molecular level, we performed a proteome analysis in Ae. albopictus C6/36 cells mono-infected by Wolbachia wAlbB strain or Chikungunya virus (CHIKV), and bi-infected. RESULTS: We first confirmed significant inhibition of CHIKV by Wolbachia. Using two-dimensional gel electrophoresis followed by nano liquid chromatography coupled with tandem mass spectrometry, we identified 600 unique differentially expressed proteins mostly related to glycolysis, translation and protein metabolism. Wolbachia infection had greater impact on cellular functions than CHIKV infection, inducing either up or down-regulation of proteins associated with metabolic processes such as glycolysis and ATP metabolism, or structural glycoproteins and capsid proteins in the case of bi-infection with CHIKV. CHIKV infection inhibited expression of proteins linked with the processes of transcription, translation, lipid storage and miRNA pathways. CONCLUSIONS: The results of our proteome profiling have provided new insights into the molecular pathways involved in tripartite Ae. albopictus-Wolbachia-CHIKV interaction and may help defining targets for the better implementation of Wolbachia-based strategies for disease transmission control.

Reconstitution Properties of Sucrose and Maltodextrins.

Carbohydrates such as sucrose and maltodextrins are commonly used in dehydrated food beverages. However, these ingredients may have, in some cases, negative impacts on the reconstitution performance (e.g., lump formation), compromising key consumer's expectations. In this study, we propose to discuss the performance of carbohydrates with regard to major physical steps of reconstitution (wetting, capillarity, dispersion, and dissolution). We show how particle size and water temperature drive the kinetics of dissolution of crystalline sucrose and propose descriptive equations. For amorphous maltodextrin, we quantify variations in wetting, capillarity, and dissolution performance as a function of important solid properties (moisture content, molecular weight, and particle size) as well as the liquid temperature. By doing so, we highlight the important role of the glass-transition temperature in relation to the moisture content of the powder. The comprehensive understanding provided by this work may be used to optimize product formulation in term of reconstitution performance.

Comparative genomics, proteomics and transcriptomics give new insight into the exoproteome of the basidiomycete Hebeloma cylindrosporum and its involvement in ectomycorrhizal symbiosis.

Extracellular proteins play crucial roles in the interaction between mycorrhizal fungi and their environment. Computational prediction and experimental detection allowed identification of 869 proteins constituting the exoproteome of Hebeloma cylindrosporum. Small secreted proteins (SSPs) and carbohydrate-active enzymes (CAZymes) were the two major classes of extracellular proteins. Twenty-eight per cent of the SSPs were secreted by free-living mycelia and five of the 10 most abundant extracellular proteins were SSPs. By contrast, 63-75% of enzymes involved in nutrient acquisition were secreted. A total of 150 extracellular protein-coding genes were differentially expressed between mycorrhizas and free-living mycelia. SSPs were the most affected. External environmental conditions also affected expression of 199 exoproteome genes in mycorrhizas. SSPs displayed different patterns of regulation in response to presence of a host plant or other environmental signals. Several of the genes most overexpressed in the presence of organic matter encoded oxidoreductases. Hebeloma cylindrosporum has not fully lost its ancestral saprotrophic capacities but rather adapted them not to harm its hosts and to use soil organic nitrogen. The complex and divergent patterns of regulation of SSPs in response to a symbiotic partner and/or organic matter suggest various roles in the biology of mycorrhizal fungi.

Anaerobic Antibiotic Coverage in Aspiration Pneumonia and the Associated Benefits and Harms: A Retrospective Cohort Study.

BACKGROUND: Antibiotics with extended anaerobic coverage are used commonly to treat aspiration pneumonia, which is not recommended by current guidelines. RESEARCH QUESTION: In patients admitted to hospital for community-acquired aspiration pneumonia, does a difference exist between antibiotic therapy with limited anaerobic coverage (LAC) vs antibiotic therapy with extended anaerobic coverage (EAC) in terms of in-hospital mortality and risk of Clostridioides difficile colitis? STUDY DESIGN AND METHODS: We conducted a multicenter retrospective cohort study across 18 hospitals in Ontario, Canada, from January 1, 2015, to January 1, 2022. Patients were included if the physician diagnosed aspiration pneumonia and prescribed guideline-concordant first-line community-acquired pneumonia parenteral antibiotic therapy to the patient within 48 h of admission. Patients then were categorized into the LAC group if they received ceftriaxone, cefotaxime, or levofloxacin. Patients were categorized into the EAC group if they received amoxicillin-clavulanate, moxifloxacin, or any of ceftriaxone, cefotaxime, or levofloxacin in combination with clindamycin or metronidazole. The primary outcome was all-cause in-hospital mortality. Secondary outcomes included incident C difficile colitis occurring after admission. Overlap weighting of propensity scores was used to balance baseline prognostic factors. RESULTS: The LAC and EAC groups included 2,683 and 1,316 patients, respectively. In hospital, 814 patients (30.3%) and 422 patients (32.1%) in the LAC and EAC groups died, respectively. C difficile colitis occurred in five or fewer patients (≤ 0.2%) and 11 to 15 patients (0.8%-1.1%) in the LAC and EAC groups, respectively. After overlap weighting of propensity scores, the adjusted risk difference of EAC minus LAC was 1.6% (95% CI, -1.7% to 4.9%) for in-hospital mortality and 1.0% (95% CI, 0.3%-1.7%) for C difficile colitis. INTERPRETATION: We found that extended anaerobic coverage likely is unnecessary in aspiration pneumonia because it was associated with no additional mortality benefit, only an increased risk of C difficile colitis.

Secretomes: the fungal strike force.

Microorganisms, although being very diverse because they comprise prokaryotic organisms such as bacteria or eukaryotic organisms such as fungi, all share an essential exodigester function. The consequence is their essential need to have a secretome adapted to their environment. The selection pressure exerted by environmental constraints led to the emergence of species with varying complexity in terms of composition of their secretomes. This review on fungal secretomes highlights the extraordinary variability among these organisms, even within the same species, and hence the absolute necessity to fully characterize all their components in the aims of understanding the fundamental mechanisms responsible for secretome plasticity and developing applications notably toward a better control of diseases caused by these pathogens.

Extracellular Vesicles of the Plant Pathogen Botrytis cinerea.

Fungal secretomes are known to contain a multitude of components involved in nutrition, cell growth or biotic interactions. Recently, extra-cellular vesicles have been identified in a few fungal species. Here, we used a multidisciplinary approach to identify and characterize extracellular vesicles produced by the plant necrotroph Botrytis cinerea. Transmission electron microscopy of infectious hyphae and hyphae grown in vitro revealed extracellular vesicles of various sizes and densities. Electron tomography showed the co-existence of ovoid and tubular vesicles and pointed to their release via the fusion of multi-vesicular bodies with the cell plasma membrane. The isolation of these vesicles and exploration of their protein content using mass spectrometry led to the identification of soluble and membrane proteins involved in transport, metabolism, cell wall synthesis and remodeling, proteostasis, oxidoreduction and traffic. Confocal microscopy highlighted the capacity of fluorescently labeled vesicles to target cells of B. cinerea, cells of the fungus Fusarium graminearum, and onion epidermal cells but not yeast cells. In addition, a specific positive effect of these vesicles on the growth of B. cinerea was quantified. Altogether, this study broadens our view on the secretion capacity of B. cinerea and its cell-to-cell communication.

Health Equity Implications of the COVID-19 Lockdown and Visitation Strategies in Long-Term Care Homes in Ontario: A Mixed Method Study.

The COVID-19 pandemic has negatively impacted the lives and well-being of long-term care home residents. This mixed-method study examined the health equity implications of the COVID-19 lockdown and visitation strategies in long-term care homes in Ontario. We recruited long-term care home residents, their family members and designated caregivers, as well as healthcare workers from 235 homes in Ontario, Canada. We used online surveys and virtual interviews to assess the priority, feasibility, and acceptability of visitation strategies, and to explore the lived experiences of participants under the lockdown and thereafter. A total of n = 201 participants completed a survey and a purposive sample of n = 15 long-term care home residents and their family members completed an interview. The initial lockdown deteriorated residents' physical, mental, and cognitive well-being, and disrupted family and community ties. Transitional visitation strategies, such as virtual visits, were criticised for lack of emotional value and limited feasibility. Designated caregiver programs emerged as a prioritised and highly acceptable strategy, one that residents and family members demanded continuous and unconditional access to. Our findings suggest a series of equity implications that highlight a person-centred approach to visitation strategies and promote emotional connection between residents and their loved ones.

Evidence for marine microfossils from amber.

Amber usually contains inclusions of terrestrial and rarely limnetic organisms that were embedded in the places were they lived in the amber forests. Therefore, it has been supposed that amber could not have preserved marine organisms. Here, we report the discovery amber-preserved marine microfossils. Diverse marine diatoms as well as radiolarians, sponge spicules, a foraminifer, and a spine of a larval echinoderm were found in Late Albian and Early Cenomanian amber samples of southwestern France. The highly fossiliferous resin samples solidified approximately 100 million years ago on the floor of coastal mixed forests dominated by conifers. The amber forests of southwestern France grew directly along the coast of the Atlantic Ocean and were influenced by the nearby sea: shells and remnants of marine organisms were probably introduced by wind, spray, or high tide from the beach or the sea onto the resin flows.

Effect of subcutaneous selenium injection and supplementary selenium source on blood selenium and glutathione peroxidase in feedlot heifers.

This study measured the effect on glutathione peroxidase (GSH-Px) and selenium (Se) in whole blood and plasma associated with subcutaneous Se injections in beef heifers fed organic or inorganic Se. Heifers (n = 120) were randomly divided into 2 groups, 1 of which received subcutaneous Se injections. Both groups were given the same total mixed ration with 3 mg of organic or inorganic Se daily. Until week 2, heifers that had received Se injections showed higher concentrations of plasma Se and GSH-Px and whole blood Se (P < 0.001) than those having had no injections. Concentrations of plasma Se and GSH-Px were higher in the group receiving organic Se than the group receiving inorganic Se. Whole blood GSH-Px concentrations increased significantly (P < 0.001) throughout a 12-week period but were not affected by Se source. Combination of Se injections and supplementation could help maintain normal Se and GSH-Px blood status in beef heifers during the first few weeks in the feedlot.

Common Infectious Diseases.

The initial assessment of immigrant and refugee patients, including which health concerns to address and which infectious diseases may benefit from early screening, may present challenges to clinicians. Evidence-based research suggests certain infectious diseases should be screened for and treated in refugees. Overseas refugee preemptive treatment programs have reduced the burden of some diseases but have not removed the value of in-country screening programs. This article provides discussion of a series of common tropical and infectious diseases providing refugee and geographic contexts and links to international resources that have been developed to improve the care of newly arriving immigrants and refugees.

Access to Refugee and Migrant Mental Health Care Services during the First Six Months of the COVID-19 Pandemic: A Canadian Refugee Clinician Survey.

The COVID-19 pandemic has had a major impact on the mental health of refugees and migrants. This study aimed to assess refugee clinician perspectives on mental health care during the COVID-19 pandemic, specifically access to and delivery of community mental health care services. We utilized a mixed methods design. We surveyed members of a national network of Canadian clinicians caring for refugees and migrants. Seventy-seven clinicians with experience caring for refugee populations, representing an 84% response rate, participated in the online survey, 11 of whom also participated in semi-structured interviews. We report three major themes: exacerbation of mental health issues and inequities in social determinants of health, and decreased access to integrated primary care and community migrant services. Clinicians reported major challenges delivering care during the first 6 months of the pandemic related to access to care and providing virtual care. Clinicians described perspectives on improving the management of refugee mental health, including increasing access to community resources and virtual care. The majority of clinicians reported that technology-assisted psychotherapy appears feasible to arrange, acceptable and may increase health equity for their refugee patients. However, major limitations of virtual care included technological barriers, communication and global mental health issues, and privacy concerns. In summary, the COVID-19 pandemic has exacerbated social and health inequities within refugee and migrant populations in Canada and challenged the way mental health care is traditionally delivered. However, the pandemic has provided new avenues for the delivery of care virtually, albeit not without additional and unique barriers.

Resisting Aridification: Adaptation of Sap Conduction Performance in Moroccan Wild Olive Subspecies Distributed Over an Aridity Gradient.

In the current context of global change, the increasing frequency and the length of drought periods are testing the resistance capacities of plants of dry habitats. However, although the adaptation of plants to drought has been widely studied, the anatomical features of wood influencing the functional responses of plants to drought are still lacking at the intraspecific level, especially for species with a wide geographical distribution. As a result, we have studied the variation of wood anatomical traits related to sap conduction (i.e., vessel surface area, vessel density, and number of vessels joined by radial file) in two wild olive subspecies distributed in Morocco (i.e., Olea europaea subsp. europaea. var. sylvestris and Olea europaea subsp. maroccana), in relation to various drought conditions. This functional study, based on wood trait measurements of 351 samples from 130 trees and 13 populations, explores potential sap conduction in relation to environmental parameters and as a result, strategies to resist water stress. We found that (1) branch diameter (BD) captured 78% of total wood trait variation, (2) vessel size (SVS) expressed 32% of intraspecific variation according to cambium age, and (3) the positive relationship between SVS and BD could be explained by climate type, vegetation cover changes, and therefore available water resources. Taking into consideration the diameter of the branch as the main factor of anatomical variation, established reaction norms (linear models) at the intrapopulation scale of vessel lumen area according to aridity show for the first time how the functioning of the cambium modulates and controls sap conduction, according to aridity and thus available water resources. They pinpoint the risks incurred by the wild olive tree in the perspective of a dramatic increase in aridity, in particular, the inability of the cambium to produce large enough vessels to efficiently transport sap and irrigate the leaves. Finally, this study opens new and interesting avenues for studying at a Mediterranean scale, the resistance and the vulnerability of wild forms and cultivated varieties of olive to heterogeneous and changing environmental conditions.

Testate amoebae from a cretaceous forest floor microbiocoenosis of france.

Amber-preserved shells of testate amoebae often provide as many diagnostic features as the tests of modern taxa. Most of these well-preserved microfossils are morphologically assignable to modern species indicating either evolutionary stasis or convergent evolution. Here we describe two Lower Cretaceous testate amoebae that are clearly distinguishable from modern species. Centropyxis perforata n. sp. and Leptochlamys galippei n. sp. possessed perforate shells that were previously unknown in these genera. They are preserved in highly fossiliferous amber pieces from the Upper Albian (ca. 100 million years old) of Archingeay/Les Nouillers (Charente-Maritime, southwestern France). Syninclusions of soil and litter dwelling arthropods and microorganisms indicate a limnetic-terrestrial microhabitat at the floor of a coastal conifer forest.