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Abstract Background Urinary tract infections are common affections, especially for women. Difficult access to a general practitioner to obtain a prescription has led France to offer dispensing under protocol by community pharmacists. The primary objective of this study is to evaluate the effectiveness of a pharmacist care protocol provided to manage women with urinary tract infection symptoms. This objective will be assessed using the Acute Cystitis Symptom Score. Methods PharmaCyst’ is an open-label, multicenter, controlled, cluster-randomized study conducted in the Loire region, France. Women aged between 18 and 65 years presenting to a pharmacy complaining of at least one symptom of an uncomplicated urinary tract infection present over the last 3 days (including burning pain during micturition, dysuria, pollakiuria, urgent urination) will be considered for inclusion. All patients will be contacted on day 3, 10, and month 3. A total of 480 patients need to be recruited for the 24 clusters participating in the research. The quantitative data will be described using means and standard deviations and compared using Student’s t-test. The qualitative data will be described using numbers and percentages and compared using chi2 test (or Fisher’s exact test if necessary). The primary and secondary outcomes analyses will consider the intention-to-treat population. Discussion PharmaCyst’ is the first clinical trial conducted in France only by community pharmacists. Its results could lead to an extension of the protocol. Trial registration The protocol has been approved by the French ethics committee on 2022/12/02 and is registered under the number 49RC22_0240 on ClinicalTrials.gov.

Abstract Background To describe French general practioners’ (GPs) adaptation strategies to ensure follow-up care of nursing home patients during the first wave of COVID-19 (May 2020) and to identify factors associated with each strategy. Methods A national cross-sectional study was conducted with online questionnaires in May 2020 among GPs practicing in France (metropolitan and overseas) and usually providing nursing home visits before pandemic. The outcome was defined as the GPs’ adaptation strategies for managing nursing home patients and was categorized into four groups: Maintenance of Nursing Home Visits NHV (reference), Stopping NHV, Numeric adaptation (teleconsultations only), Mixed adaptation (NHV and teleconsultations). The probability of adaptation strategies was analyzed by multilevel logistic models in which the GPs represented level 1 and the counties level 2. We applied three random-intercept multilevel logistic models with the county of GP’s practice as random effect. Results This analysis included 2,146 responses by GPs coming from 98 French counties. Overall, 40.4% of GPs maintained NHV, while other strategies were: Stopping visits (24.1%), Numeric adaptation (15.4%), Mixed adaptation (20.1%). Several individual (age, training GP, perceived status of being at high risk of severe COVID, compliance with temporary delegation of the patient’s management) and territorial factors (excess mortality rate due to COVID-19, GPs’ density, proportion of over-75s, presence of reinforcement measures for nursing home patients) were identified as associated with each strategy. Conclusions This study highlights a rapid adaptation of general practice to keep supporting nursing home patients. Heterogeneity of adaptation strategies could reflect both the lack of national guidelines and the heterogeneity among GPs’ usual practices. Policymakers should take actions at a territorial level (subnational) to strengthen support to nursing home patients considering adaptations to the local context of the pandemic outbreak and perspective of local actors.

Abstract Background A train-the-trainer approach can effectively support the integration of new practice standards for health and social services professionals. This study describes the effects of an enhanced train-the-trainer program to support registered nurses and social workers working in primary care clinics in their understanding of the fundamental principles of primary care. Methods We implemented an enhanced train-the-trainer program for registered nurses and social workers in six primary care clinics. We conducted a pre-post study using quantitative and qualitative data to assess trainers’ and trainees’ intention, commitment, and confidence in applying acquired knowledge. Results We trained 11 trainers and 33 trainees. All the trainers and trainees were satisfied with the program. Trainers were less confident in their abilities as trainers following the training, especially regarding tailored coaching (p = 0.03). Trainees’ commitment to becoming familiar with the functioning of their clinic (p = 0.05) and becoming part of the team increased significantly (p = 0.01); however, their intention to use their knowledge decreased (p = 0.02). Trainers and trainees identified organizational and professional barriers that may explain the observed decrease. Conclusion An enhanced train-the-trainer program positively impacted registered nurses’ and social workers’ assimilation of the fundamental principles of primary care. Further research is needed to understand the long-term effects of train-the-trainer programs on primary care trainees and how these effects translate into patient care.

Mountain ecosystems, contributing substantially to the global carbon (C) and nitrogen (N) biogeochemical cycles, are heavily impacted by global changes. Although soil respiration and microbial activities have been extensively studied at different elevation, little is known on the relationships between environmental drivers, microbial functions, and greenhouse gas fluxes (GHGs; carbon dioxide [CO2], methane [CH4] and nitrous oxide [N2O]) in soils of different elevation. Here, we measured how in situ GHG fluxes were linked to soil properties, soil organic matter (SOM) quantity and composition (the proportion of humic-like vs. protein-like OM), microbial biomass, enzyme activities and functional gene abundances in natural soils spanning an elevational gradient of ∼2400 m in Switzerland. Soil CO2 fluxes did not significantly vary from low (lowland zone) to higher (montane and subalpine zones) elevation forests, but decreased significantly (P

Theoretical physicists describe nature by i) building a theory model and ii) determining the model parameters. The latter step involves the dual aspect of both fitting to the existing experimental data and satisfying abstract criteria like beauty, naturalness, etc. We use the Yukawa quark sector as a toy example to demonstrate how both of those tasks can be accomplished with machine learning techniques. We propose loss functions whose minimization results in true models that are also beautiful as measured by three different criteria — uniformity, sparsity, or symmetry.

Abstract Staphylococcus aureus is a predominant cause of chronic lung infections. While the airway environment is rich in highly sialylated mucins, the interaction of S. aureus with sialic acid is poorly characterized. Using S. aureus USA300 as well as clinical isolates, we demonstrate that quorum-sensing dysfunction, a hallmark of S. aureus adaptation, correlates with a greater ability to consume free sialic acid, providing a growth advantage in an air-liquid interface model and in vivo. Furthermore, RNA-seq experiment reveals that free sialic acid triggers transcriptional reprogramming promoting S. aureus chronic lifestyle. To support the clinical relevance of our results, we show the co-occurrence of S. aureus, sialidase-producing microbiota and free sialic acid in the airway of patients with cystic fibrosis. Our findings suggest a dual role for sialic acid in S. aureus airway infection, triggering virulence reprogramming and driving S. aureus adaptive strategies through the selection of quorum-sensing dysfunctional strains.

Summary: We investigate the bacterial and fungal composition and functionality of the Ju|’hoansi intestinal microbiome (IM). The Juǀʼhoansi are a hunter-gatherer community residing in northeastern Namibia. They formerly subsisted by hunting and gathering but have been increasingly exposed to industrial dietary sources, medicines, and lifestyle features. They present an opportunity to study the evolution of the human IM in situ, from a predominantly hunter-gatherer to an increasingly Western urban-forager-farmer lifestyle. Their bacterial IM resembles that of typical hunter-gatherers, being enriched for genera such as Prevotella, Blautia, Faecalibacterium, Succinivibrio, and Treponema. Fungal IM inhabitants include animal pathogens and plant saprotrophs such as Fusarium, Issatchenkia, and Panellus. Our results suggest that diet and culture exert a greater influence on Ju|’hoansi IM composition than age, self-identified biological sex, and medical history. The Ju|’hoansi exhibit a unique core IM composition that diverges from the core IMs of other populations.

The Wadden Sea is a coastal system along the fringe of the land–sea borders of Denmark, Germany and the Netherlands. The Wadden Sea is extremely productive and influenced by strong variations in physical and biological forcing factors that act on timescales of hours to seasons. Productive coastal seas are known to dominate the ocean's methane emission to the atmosphere, but knowledge of controls and temporal variations in methane dynamics in these vastly dynamic systems is scarce. Here we address this knowledge gap by measuring methane inventories and methanotrophic activity at a temporal resolution of 1 h over a period of 2 d, repeatedly during four successive seasons in the central Dutch Wadden Sea. We found that methane dynamics varied between colder and warmer seasons, with generally higher water column methane concentrations and methanotrophic activity in the warmer seasons. The efflux of methane to the atmosphere was, on the other hand, lower in the warmer seasons because of lower wind speeds. On a diel scale, tides controlled methanotrophic activity, which increased ∼40 % at low tide compared to high tide. We estimate that methane oxidizing bacteria reduce the methane budget of the Dutch Wadden Sea by only 2 %, while ∼1/3 escapes to the atmosphere and ∼2/3 are flushed out into the open North Sea at ebb tide. Our findings indicate that tides play a key role in controlling methane dynamics and methanotrophic activity and highlight the importance of high-resolution and repeated sampling strategies to resolve methane dynamics in fast-changing coastal systems.

Abstract Our planet teeters on the brink of massive ecosystem collapses, and arid regions experience manifold environmental and climatic challenges that increase the magnitude of selective pressures on already stressed ecosystems. Ultimately, this leads to their aridification and desertification, that is, to simplified and barren ecosystems (with proportionally less microbial load and diversity) with altered functions and food webs and modification of microbial community network. Thus, preserving and restoring soil health in such a fragile biome could help buffer climate change's effects. We argue that microorganisms and the protection of their functional properties and networks are key to fight desertification. Specifically, we claim that it is rational, possible and certainly practical to rely on native dryland edaphic microorganisms and microbial communities as well as dryland plants and their associated microbiota to conserve and restore soil health and mitigate soil depletion in newly aridified lands. Furthermore, this will meet the objective of protecting/stabilizing (and even enhancing) soil biodiversity globally. Without urgent conservation and restoration actions that take into account microbial diversity, we will ultimately, and simply, not have anything to protect anymore.

Microbes have a dominant role in nutrient cycling processes in the world’s deserts, where growth and activity are limited by the availability of water. In order to understand the dynamics of water availability in a desert system and how it may affect the soil microbiome, we analysed soil temperature and relative humidity fluctuations recorded between April 2018 and April 2020 across a precipitation gradient in the Namib Desert and compared them with recorded data from satellites and nearby weather stations. This allowed us to assess the possible impact of fog and rain events in terms of biologically-available water. Using published literature on the water activity limits for various physiological processes in microorganisms, we were able to infer the annual ‘metabolic windows’ for desert microbial communities across the longitudinal precipitation gradient. Specifically, soil surface microbial communities were estimated to have the capacity for active growth for an average of 184- 363 hours per year with the duration heavily dependent on intermittent rainfall events. During the relatively wet period of April 2018 - March 2019, the maximum growth window was found in the hyper-arid central region of the transect (approximately 100 km from the coast). During the dryer 2019- 2020 period, there was almost no predicted growth capacity in the hyper-arid region but substantial metabolic windows both near the coast and for the eastern inland areas, where water input comes in the form of fog and moist coastal air, and higher rainfall, respectively. As the first detailed study of the temperature and relative humidity characteristics of Namib Desert near-surface soils, this study provides valuable insights into the biogeography of microbial communities. In addition, the estimates for organismal functionality calculated in this study offer a baseline for future quantitation of the impacts of climate change on the functional capacity of desert soil microbiomes.

The development of advanced photocatalysts for air pollution removal is essential to improve indoor air quality. TiO2/mesoporous silica SBA-15 nanocomposites were synthesized using an organometallic decoration method, which leverages the high reactivity of Ti precursors to be hydrolyzed on the surface water groups of silica supports. Both lab-made Ti(III) amidinate and commercial Ti(IV) amino precursors were utilized to react with water-rich SBA-15, obtained through a hydration process. The hydrated SBA-15 and the TiO2/SBA-15 nanocomposites were characterized using TGA, FTIR, 1H and 29Si NMR, TEM, SEM, N2 physisorption, XRD, and WAXS. This one-step TiO2 decoration method achieved a loading of up to 51.5 wt.% of approximately 9 nm anatase particles on the SBA-15 surface. This structuring provided excellent accessibility of TiO2 particles for photocatalytic applications under pollutant gas and UV-A light exposure. The combination with the high specific surface area of SBA-15 resulted in the efficient degradation of 400 ppb of NO pollutant gas. Due to synergistic effects, the best nanocomposite in this study demonstrated a NO abatement performance of 4.0% per used mg of TiO2, which is 40% more efficient than the reference photocatalytic material TiO2 P-25.

Abstract Background The mechanisms shaping the rare microbial biosphere and its role in ecosystems remain unclear. We developed an approach to study ecological patterns in the rare biosphere and use it on a vast collection of marine microbiomes, sampled in coastal ecosystems at a regional scale. We study the assembly processes, and the ecological strategies constituting the rare protistan biosphere. Using the phylogeny and morpho-trophic traits of these protists, we also explore their functional potential. Results Taxonomic community composition remained stable along rank abundance curves. Conditionally rare taxa, driven by selection processes, and transiently rare taxa, with stochastic distributions, were evidenced along the rank abundance curves of all size-fractions. Specific taxa within the divisions Sagenista, Picozoa, Telonemia, and Choanoflagellida were rare across time and space. The distribution of traits along rank abundance curves outlined a high functional redundancy between rare and abundant protists. Nevertheless, trophic traits illustrated an interplay between the trophic groups of different size-fractions. Conclusions Our results suggest that rare and abundant protists are evolutionary closely related, most notably due to the high microdiversity found in the rare biosphere. We evidenced a succession of assembly processes and strategies of rarity along rank abundance curves that we hypothesize to be common to most microbiomes at the regional scale. Despite high functional redundancy in the rare protistan biosphere, permanently rare protists were evidenced, and they could play critical functions as bacterivores and decomposers from within the rare biosphere. Finally, changes in the composition of the rare protistan biosphere could be influenced by the trophic regime of aquatic ecosystems. Our work contributes to understanding the role of rare protists in microbiomes.

Abstract Introduction Pertussis, a highly infectious respiratory disease caused by Bordetella pertussis, affects people of all ages. Older adults are particularly susceptible to its severe outcomes and complications. Methods In this retrospective cohort study, the incidence rate of pertussis among individuals aged ≥ 50 years was assessed during 2009–2018 using Clinical Practice Research Datalink and Hospital Episode Statistics databases, United Kingdom. Health care resource utilisation (HCRU) and direct medical costs (DMCs) were compared between patients with a pertussis diagnosis and propensity score-matched controls (matched on demographic and clinical variables). Results Among 5,222,860 individuals, 1638 had a pertussis diagnosis (incidence rate: 5.8 per 100,000 person-years; 95% confidence interval 5.5–6.0). Baseline (– 18 to – 6 months) HCRU and DMC were similar among 1480 pertussis patients and 1480 matched controls. However, there were increases in HCRU in the pertussis vs. matched cohort around the pertussis diagnosis (from months – 6 to – 1 to 5–11). The most notable increases (pertussis vs. controls) were in the rates of general practitioner (GP)/nurse visits (4.7-fold), clinical assessments (4.1-fold), and accident and emergency visits (3.0-fold) during the month before diagnosis and GP/nurse visits during the 2 months after diagnosis (2.5-fold) (all p

Ancient genomic evidence for Rickettsia felis presence in human remains from 2000 years ago reframes previous hypotheses of R. felis as a novel or emergent pathogen in modern humans.

Abstract Background Musculoskeletal disorders (MSD) are multifactorial requiring multidisciplinary treatment including physiotherapy. General practitioners (GP) have a central role in managing MSDs and mostly solicit physiotherapists accounting for 76.1% of physiotherapy referrals in France. Patient, physician, and contextual factors, including healthcare accessibility, can influence physiotherapy referral rates. Objective To identify patient, physician, and contextual factors associated with physiotherapy referral in adult patients with MSDs in general practice. Methods This study is based on the 2011/2012 French cross-sectional ECOGEN study. Analyses included working-age patients consulting their GP for any MSD. Physiotherapy referral was assessed initially, then adjusted multilevel logistic model analysis of patient, physician, geographical area-related factors associated with these referrals was performed. Results Among the 2305 patients included, 456 (19.8%) were referred to a physiotherapist. Following multilevel multivariate analyses, physiotherapist referral was more frequent for female patients (OR 1.28; 95% CI [1.03, 1.59]) with spinal (OR 1.47; 95% CI [1.18, 1.83]) and upper limb disorders (OR 1.66; 95% CI [1.20, 2.29]), and less frequent for patients ≥ 50 years (OR 0.69; 95% CI [0.52, 0.91]), living in deprived geographical areas (OR 0.60; 95% CI [0.40, 0.90]). GPs referred to a physiotherapist less frequently if they were ≥ 50 years (OR 0.50; 95% CI [0.39, 0.63]), had a high number of annual consultations, or were practicing in semi-urban area in a multidisciplinary team. Conclusion This multilevel analysis identifies factors associated with physiotherapy referral for patients with MSDs, including living in deprived geographical areas. This constitutes an original contribution towards addressing healthcare disparities.

Abstract Background Top-soil microbiomes make a vital contribution to the Earth’s ecology and harbor an extraordinarily high biodiversity. They are also key players in many ecosystem services, particularly in arid regions of the globe such as the African continent. While several recent studies have documented patterns in global soil microbial ecology, these are largely biased towards widely studied regions and rely on models to interpolate the microbial diversity of other regions where there is low data coverage. This is the case for sub-Saharan Africa, where the number of regional microbial studies is very low in comparison to other continents. Results The aim of this study was to conduct an extensive biogeographical survey of sub-Saharan Africa’s top-soil microbiomes, with a specific focus on investigating the environmental drivers of microbial ecology across the region. In this study, we sampled 810 sample sites across 9 sub-Saharan African countries and used taxonomic barcoding to profile the microbial ecology of these regions. Our results showed that the sub-Saharan nations included in the study harbor qualitatively distinguishable soil microbiomes. In addition, using soil chemistry and climatic data extracted from the same sites, we demonstrated that the top-soil microbiome is shaped by a broad range of environmental factors, most notably pH, precipitation, and temperature. Through the use of structural equation modeling, we also developed a model to predict how soil microbial biodiversity in sub-Saharan Africa might be affected by future climate change scenarios. This model predicted that the soil microbial biodiversity of countries such as Kenya will be negatively affected by increased temperatures and decreased precipitation, while the fungal biodiversity of Benin will benefit from the increase in annual precipitation. Conclusion This study represents the most extensive biogeographical survey of sub-Saharan top-soil microbiomes to date. Importantly, this study has allowed us to identify countries in sub-Saharan Africa that might be particularly vulnerable to losses in soil microbial ecology and productivity due to climate change. Considering the reliance of many economies in the region on rain-fed agriculture, this study provides crucial information to support conservation efforts in the countries that will be most heavily impacted by climate change. Video Abstract

BackgroundLow back pain (LBP) is a common musculoskeletal condition and, globally, a leading cause of years lived with disability. It leads to reduced social participation, impaired quality of life, and direct and indirect costs due to work incapacity. A coordinated approach focusing on psychosocial risk factors, active reeducation, and the early use of tools to maintain employment, may be effective for improving prognosis of patients with LBP. Primary care professionals and multidisciplinary teams, who see patients in the early stages of LBP may be in the best position to implement such a coordinated approach. We designed this study to assess a coordinated multi-faceted strategy in primary care for patients with subacute or recurrent acute LBP.MethodsThe CO.LOMB study was designed as a multicentric, cluster-randomized, controlled study. Patients aged 18–60 years, with subacute or recurrent acute LBP are eligible. Patients also need to be employed (but can be on sick leave) with access to occupational health services. The clusters of GPs will be randomized (1:1) to either the Coordinated-care group or the Usual-care group. Patients will be assigned the group allocated to their GP. The healthcare professionals (GPs and associated physiotherapists) allocated to the Coordinated-care group will perform a 2-session study training. The following interventions are planned in the Coordinated-care group: exploration and management of psychosocial factors, active reeducation with a physiotherapist, the implementing of tools to maintain employment, and a reinforced cooperation between primary healthcare professionals. The primary objective is to assess the benefit of coordinated primary care to reduce disability in LBP patients at 12 months after enrollment: measure using the validated French version of the Roland Morris Disability Questionnaire. Secondary objectives include the evaluation of pain, work status, and quality of life at various time points. The study plans to enroll 500 patients in 20 GP clusters. Patients will be followed up for 12months.DiscussionThis study will evaluate the benefit of a coordinated multi-faceted strategy in primary care for patients with LBP. Notably whether this approach will alleviate the associated disability, attenuate pain, and promote the maintenance or return to work.Clinical Trial RegistrationNCT04826757.