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Abstract Anthropogenic perturbations profoundly affect aquatic ecosystem microbiomes and associated ecological functions. Comparatively, the effects of geological stresses on microbiome composition and stability remain poorly explored. Here, we monitored the archaeal, bacterial and microeukaryotes community structure over an 8-years period in Lake Dziani Dzaha (Comoros archipelago), that experienced a major earthquake swarm mid-survey, providing a rare opportunity to investigate the aftermaths of seismo-volcanic events on microbiome. Our results revealed the sensitivity of the aquatic microbial community towards seismicity and associated environmental changes, that triggered a major shift in microbiome composition and abundance with persisting consequences on structure and richness of the microbial ecosystem. Our findings suggest that seismological perturbations could be major drivers of the microbial community structure in aquatic environments through cascading effects on environmental conditions. Over geological time scales, such events may have been significant yet underestimated forces driving diversification and evolution of microbial communities.

Ageism might reduce the effectiveness and quality of care in older adults essential with the aging population. Although interventions to counter ageism were carried out among students, no clear integration of their results described the mechanisms underlying their impact. This study aimed to provide a comprehensive understanding of which interventions amongst undergraduate health and social services students are effective, under which circumstances, how, and with what outcomes. A realist review was carried out using 44 keywords in 6 databases. The configurations for contexts, mechanisms, and outcomes were identified for three types of interventions, considering their impact on stereotypes, prejudices, and discrimination toward older adults. In the 63 studies selected, intergenerational contact interventions exhibited the greatest proportion (14/15; 93.3%) of evidence supporting improvement in outcomes of ageism, followed by combined (67/84; 79.8%) and educational (51/67; 76.1%) interventions. Stereotypes and prejudices were challenged by the transmission of realistic and balanced information, as well as through meaningful and high-quality intergenerational contact. Meeting or hearing about a broad variety of older adults in specific conditions also helped to decrease ageism. Results highlighted the importance of seeing diversity and uniqueness in older adults, and their competencies rather than their limitations. Mechanisms were occasionally hampered by obstacles, such as induced anxiety and confirmation of negative aspects of aging. Countering ageism in health and social services students is essential to ensuring high-quality care. In knowing that educators, professionals, and institutions have a direct influence on students, their awareness of ageism should be enhanced by interventions targeting them.

Abstract Background This study constitutes a secondary analysis of a prospective cohort aiming to evaluate the potential correlation between nutritional risk and status at admission with the occurrence of post-discharge complications and hospital readmissions in children receiving care at high resource Centres. Methods Data was collected from 5 Canadian tertiary pediatric Centers between 2012 and 2016. Nutritional risk and status were evaluated at hospital admission with validated tools (STRONGkids and Subjective Global Nutrition Assessment [SGNA]) and anthropometric measurements. Thirty days after discharge, occurrence of post-discharge complications and hospital readmission were documented. Results A total of 360 participants were included in the study (median age, 6.1 years; median length of stay, 5 days). Following discharge, 24.1% experienced complications and 19.5% were readmitted to the hospital. The odds of experiencing complications were nearly tripled for participants with a high nutritional risk compared to a low risk (OR = 2.85; 95% CI [1.08–7.54]; P = 0.035) and those whose caregivers reported having a poor compared to a good appetite (OR = 2.96; 95% CI [1.59–5.50]; P

Abstract Corneal HSV-1 infections are a leading cause of infectious blindness globally by triggering tissue damage due to the intense inflammation. HSV-1 infections are treated mainly with antiviral drugs that clear the infections but are inefficient as prophylactics. The body produces innate cationic host defence peptides (cHDP), such as the cathelicidin LL37. Various epithelia, including the corneal epithelium, express LL37. cHDPs can cause disintegration of pathogen membranes, stimulate chemokine production, and attract immune cells. Here, we selected GF17, a peptide containing the LL37 fragment with bioactivity but with minimal cytotoxicity, and added two cell-penetrating amino acids to enhance its activity. The resulting GF19 was relatively cell-friendly, inducing only partial activation of antigen presenting immune cells in vitro. We showed that HSV-1 spreads by tunneling nanotubes in cultured human corneal epithelial cells. GF19 given before infection was able to block infection, most likely by blocking viral entry. When cells were sequentially exposed to viruses and GF19, the infection was attenuated but not arrested, supporting the contention that the GF19 mode of action was to block viral entry. Encapsulation into silica nanoparticles allowed a more sustained release of GF19, enhancing its activity. GF19 is most likely suitable as a prevention rather than a virucidal treatment.

Despite the high measurement fidelity that can now be reached, the dispersive qubit readout of circuit quantum electrodynamics is plagued by a loss of its quantum nondemolition character and a decrease in fidelity with increased measurement strength. In this work, we elucidate the nature of this dynamical process, which we refer to as transmon ionization. We develop a comprehensive framework which provides a physical picture of the origin of transmon ionization. This framework consists of three complementary levels of descriptions: a fully quantized transmon-resonator model, a semiclassical model where the resonator is treated as a classical drive on the transmon, and a fully classical model. Crucially, all three approaches preserve the full cosine potential of the transmon and lead to similar predictions. This framework identifies the multiphoton resonances responsible for transmon ionization. It also allows one to efficiently compute numerical estimates of the photon number threshold for ionization, which are in remarkable agreement with recent experimental results. The tools developed within this work are both conceptually and computationally simple, and we expect them to become an integral part of the theoretical underpinning of all circuit QED experiments.

ABSTRACT Pseudomonas aeruginosa, a bacterium causing infections in immunocompromised individuals, regulates several of its virulence functions using three interlinked quorum sensing (QS) systems (las, rhl, and pqs). Despite its presumed importance in regulating virulence, dysfunction of the las system regulator LasR occurs frequently in strains isolated from various environments, including clinical infections. This newfound abundance of LasR-defective strains calls into question existing hypotheses regarding their selection. Indeed, current assumptions concerning factors driving the emergence of LasR-deficient isolates and the role of LasR in the QS hierarchy must be reconsidered. Here, we propose that LasR is not the primary master regulator of QS in all P. aeruginosa genetic backgrounds, even though it remains ecologically significant. We also revisit and complement current knowledge on the ecology of LasR-dependent QS in P. aeruginosa, discuss the hypotheses explaining the putative adaptive benefits of selecting against LasR function, and consider the implications of this renewed understanding.

Introduction Lung transplantation (LTx) aims at improving survival and quality of life for patients with end-stage lung diseases. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is used as intraoperative support for LTx, despite no precise guidelines for its initiation. We aim to evaluate two strategies of VA-ECMO initiation in the perioperative period in patients with obstructive or restrictive lung disease requiring bilateral LTx. In the control ‘on-demand’ arm, high haemodynamic and respiratory needs will dictate VA-ECMO initiation; in the experimental ‘systematic’ arm, VA-ECMO will be pre-emptively initiated. We hypothesise a ‘systematic’ strategy will increase the number of ventilatory-free days at day 28.Methods and analysis We designed a multicentre randomised controlled trial in parallel groups. Adult patients with obstructive or restrictive lung disease requiring bilateral LTx, without a formal indication for pre-emptive VA-ECMO before LTx, will be included. Patients with preoperative pulmonary hypertension with haemodynamic collapse, ECMO as a bridge to transplantation, severe hypoxaemia or hypercarbia will be secondarily excluded. In the systematic group, VA-ECMO will be systematically implanted before the first pulmonary artery cross-clamp. In the on-demand group, VA-ECMO will be implanted intraoperatively if haemodynamic or respiratory indices meet preplanned criteria. Non-inclusion, secondary exclusion and VA-ECMO initiation criteria were validated by a Delphi process among investigators. Postoperative weaning of ECMO and mechanical ventilation will be managed according to best practice guidelines. The number of ventilator-free days at 28 days (primary endpoint) will be compared between the two groups in the intention-to-treat population. Secondary endpoints encompass organ failure occurrence, day 28, day 90 and year 1 vital status, and adverse events.Ethics and dissemination The sponsor is the Assistance Publique–Hôpitaux de Paris. The ECMOToP protocol version 2.1 was approved by Comité de Protection des Personnes Ile de France VIII. Results will be published in international peer-reviewed medical journals.Trial registration number NCT05664204.

This study investigated how 46 pre-service teachers (PSTs) planned for differentiation of instruction in mathematics. Content analysis was utilized to explore the differentiation strategies included and student characteristics considered in PST plans and how PSTs used differentiation strategies and student characteristics to differentiate lesson content, process, product, and environment. In addition, a rubric was designed and utilized to analyze the level of detail PSTs provided in their plans. Results indicated that overall, PSTs were developing in their planning for differentiation of instruction, using general terms to describe the modifications they would make to meet student needs. Moreover, results revealed that PSTs included strategies to differentiate lesson content and environment most often in their plans and frequently considered student readiness levels when planning for differentiation. Findings also revealed that PSTs need support in learning how to plan for differentiation based on student cultural backgrounds. Implications for mathematics teacher preparation are discussed.

There is an increasing demand for real-world data pertaining to the usage of cancer treatments, especially in settings where no standard treatment is specifically recommended. This study presents the first real-world analysis of third-line treatment patterns in HER2-positive metastatic breast cancer (mBC) patients in Canada. The purpose was to assess evolution of clinical practice and identify unmet needs in post-second-line therapy. Retrospective data from medical records of 66 patients who received third-line treatment before 31st October 2018, and data from 56 patients who received third-line treatment after this date, extracted from the Personalize My Treatment (PMT) cancer patient registry, were analyzed. In the first cohort, the study revealed heterogeneity in the third-line setting, with trastuzumab, lapatinib, and T-DM1 being the main treatment options. Even though data were collected before the wide availability of tucatinib, neratinib and trastuzumab deruxtecan in Canada, the PMT cohort revealed the emergence of new therapeutic combinations and a shift from lapatinib usage to T-DM1 choice was observed. These findings underscore the evolving nature of third-line treatment strategies in Canada, a facet that is intrinsically tied to the availability of new drugs. The absence of a consensus on post-second-line treatment highlights the pressing need for more efficient therapeutic alternatives beyond the currently available options. This study not only offers valuable insights into the present landscape of third-line treatment in Canada but validates the significance and effectiveness of the PMT registry as a tool for generating pan-Canadian real-world evidence in oncology and its capacity to provide information on evolution of therapeutic practices.

Introduction: Moderate corneal alkali burns such as those sustained from accidental exposure to household chemicals are treated with topical corticosteroids. Side effects include increased intraocular pressure and slowing of wound healing. Here, we compare the effects of a cannabinoid receptor 2 (CB2r) agonist, TA-A001, that is involved in wound healing with that of the corticosteroid, prednisolone.Methods: TA-A001 was encapsulated with a polymeric micelle comprising polyvinylpyrrolidone: polylactide block copolymers referred to as SmartCelle™ to allow delivery of the very hydrophobic drug. Mouse corneas were given moderate alkali burns. Different doses of TA-A001 of 0.125%, 0.25% and 0.5% were used to treat the burns in comparison to the corticosteroid, prednisolone.Results: TA-A001 at 0.25% and 0.5% allowed for faster wound closure. However, the higher 0.5% dose also induced unwanted neovascularization. By comparison, burned corneas treated with prednisolone showed slower healing as well as disorganization of the cornea. Although 0.25% TA-A001 appeared to produce the most-optimal responses, this dose resulted in marked expression of the macrophage chemoattractant protein, MCP-1. However, there was also an increase in CD163 positive stained M2 anti-inflammatory macrophages in the TA-A001 corneas. TA-A001 treated corneas showed the presence of sensory nerve fibers throughout the corneal epithelium including the superficial cell layers as did Substance P staining.Discussion: We found that TA-A001 at the 0.25% doses was able to modulate inflammation resulting from a moderate alkali burn to the cornea. With more extensive testing, TA-A001 might prove to be a potential alternative to corticosteroids for treating alkali burns or other causes of corneal inflammation.

Perinatal depression is a major public health problem that is under-treated in low- and middle-income countries, with negative community attitudes often cited as a major barrier to help-seeking and treatment. In this paper, we investigate help-seeking for perinatal depression, some of whom may have experienced psychosis in the context of perinatal depression, and its cultural shaping in Nigeria. Our approach was informed by cultural constructivist and critical anthropological perspectives to situate perinatal depression in ecosocial context with systematic attention to the social-structural determinants. Help-seeking was controlled by caregivers, but patients and caregivers differed in their definitions of illness onset: caregivers focused on violation of norms for maternal behavior, whereas patients focused on somatic and psychological distress. Help-seeking entailed use of two different reasoning approaches. The default approach was ad-hoc and contingency-based, depending on: 1) the kinds of help immediately available and the fit with experiential knowledge; 2) the meanings of the patient's problem as negotiated in social interactions; 3) concerns about stigma that led to secrecy in seeking help; and 4) the perceived degree of immediate risk to safety. The second approach involved more explicit deliberation and took over in situations of uncertainty including: 1) worsening or unremitting illness despite treatment; 2) harm from treatment; and 3) perceived inadequacy of a treatment to bring about healing. Avoiding mental illness stigmatization was seen as dependent on limiting public awareness of the individual's affliction. The meanings of illness were locally informed and negotiated in ongoing social interactions and practices of social recognition and status negotiation that legitimated illness and influenced help-seeking. Clarifying the social context of mental health problems and identifying cultural and structural risk and protective factors can inform the design of health care systems to improve access to care and the development of culturally appropriate and effective intervention programmes.

The use of antibiotics to promote growth and prevent diarrhea in livestock production has raised concerns about the emergence of antibiotic-resistant bacteria. Probiotics, live microorganisms that confer health benefits, have been proposed as alternatives to antibiotics. In this study, we produced and characterized a downgraded maple syrup-based feed supplement containing Bacillus velezensis FZB42 as a potential synbiotic for animal nutrition. An optimized fermentation medium was developed through a central composite design to produce B. velezensis FZB42 at both the laboratory and pilot scale, reaching a concentration of 6.15 ± 0.46 × 109 CFU/mL. Subsequently, B. velezensis FZB42 was incorporated into a protective whey permeate matrix and spray-dried, resulting in a 31.4% yield with a moisture content of 4.38%. The survival of B. velezensis FZB42 in a simulated gastrointestinal tract was evaluated using the TIM-1 system, revealing a survival rate of 16.05% after passage through the gastric, duodenal, jejunal, and ileal compartments. These findings highlight the possibility of B. velezensis FZB42 being an economically viable and possibly functional synbiotic supplement and effective alternative to antibiotic growth promoters in livestock production.

ABSTRACT Successful colonization of a multitude of ecological niches by the bacterium Pseudomonas aeruginosa relies on its ability to respond to concentrations of self-produced signal molecules. This intercellular communication system known as quorum sensing (QS) tightly regulates the expression of virulence determinants and a diversity of survival functions, including those required for social behaviors. In planktonic cultures of P. aeruginosa, the transcriptional regulator LasR is generally considered on top of the QS circuitry hierarchy; its activation relies on binding to 3-oxo-C12-homoserine lactone (3-oxo-C12-HSL), a product of LasI synthase. Transcription of lasI is activated by LasR, resulting in a positive feedback loop. Few studies have looked at the function of QS during surface growth even though P. aeruginosa typically lives in biofilm-like communities under natural conditions. Here, we show that surface-grown P. aeruginosa, including prototypical strain PA14, produces 3-oxo-C12-HSL in the absence of LasR. This phenotype is commonly observed upon surface association in naturally occurring environmental and clinical LasR-defective isolates, suggesting a conserved alternative function for the signal. Notably, in surface-grown cultures, 3-oxo-C12-HSL reaches higher levels than planktonic cells, and there is a delayed timing of its production. Accordingly, 3-oxo-C12-HSL upregulates the autologous expression of pyocyanin and LasR-controlled virulence determinants in neighboring cells even in the absence of the cognate regulator LasR. This highlights a possible role for 3-oxo-C12-HSL in shaping community responses and provides a possible evolutive benefit for mixed populations to carry LasR-defective cells, a common feature of natural populations of P. aeruginosa. IMPORTANCE The bacterium Pseudomonas aeruginosa colonizes and thrives in many environments, in which it is typically found in surface-associated polymicrobial communities known as biofilms. Adaptation to this social behavior is aided by quorum sensing (QS), an intercellular communication system pivotal in the expression of social traits. Regardless of its importance in QS regulation, the loss of function of the master regulator LasR is now considered a conserved adaptation of P. aeruginosa, irrespective of the origin of the strains. By investigating the QS circuitry in surface-grown cells, we found an accumulation of QS signal 3-oxo-C12-HSL in the absence of its cognate receptor and activator, LasR. The current understanding of the QS circuit, mostly based on planktonic growing cells, is challenged by investigating the QS circuitry of surface-grown cells. This provides a new perspective on the beneficial aspects that underline the frequency of LasR-deficient isolates.

Biosurfactants are microbial products that have applications as cleaning agents, emulsifiers, and dispersants. Detection and quantification of biosurfactants can be done by various methods, including colorimetric tests, high performance liquid chromatography (HPLC) coupled to several types of detectors, and tests that take advantage of biosurfactants reducing surface tension of aqueous liquids, allowing for spreading and droplet formation of oils. We present a new and simple method for quantifying biosurfactants by their ability, on paper, to reduce surface tension of aqueous solutions, causing droplet dispersion on an oiled surface in correlation with biosurfactant content. We validated this method with rhamnolipids, surfactin, sophorolipids, and ananatoside B; all are anionic microbial surfactants. Linear ranges for quantification in aqueous solutions for all tested biosurfactants were between 10 and 500 µM. Our method showed time-dependent biosurfactant accumulation in cultures of Pseudomonas aeruginosa strains PA14 and PAO1, and Burkholderia thailandensis E264. Mutants in genes responsible for surfactant production showed negligible activity on oiled paper. In summary, our simple assay provides the opportunity to quantify biosurfactant contents of aqueous solutions, for a diversity of surfactants, by means readily available in any laboratory.

Since May 2018, an unexpected long and intense seismic crisis started offshore Mayotte (Indian Ocean, France). This ongoing seismic sequence is associated with the birth of a newly discovered submarine volcano 50 km east of Petite Terre. Here, we investigate the indirect impact of this crisis on the stability of an atypical ecosystem located in Mayotte, the Dziani Dzaha Lake. This lacustrine system presented physical, chemical and biogeochemical characteristics that were distinct from those classically observed in modern lakes or seawater, e.g. high salinity (up to 70 psu), lack of nitrate, sulfate content below 3 mM, and permanent water column anoxia below ca. 1.5 m depth (2012–2017 period). Based on three surveys conducted in 2020 and 2021, we documented an episode of water column oxygenation, a significant pH decrease and an impressive change in the carbon isotope signatures. These preliminary data suggest that the functioning of biogeochemical cycles in the Dziani Dzaha Lake is impacted by increased CO2 inputs and the changes in the lake mixing dynamics, which is an indirect consequence of the ongoing seismo-volcanic crisis.

Abstract Background and Aim Patients with inflammatory bowel disease (IBD) are at increased risk for life‐threatening complications of Epstein–Barr virus (EBV), including lymphoproliferative diseases. These complications are likely related to inherent immune dysfunction and immunomodulating therapies often used. We aimed to determine the seroprevalence of EBV at diagnosis in our population, its impact on disease at onset, and the risk of active EBV infection. Methods We included patients newly diagnosed with IBD for whom an EBV serology was performed over a 2‐year period. Demographic information and data on disease characteristics were collected retrospectively. Stored serum from the time of diagnosis was retrieved when available for the patients with positive EBV serology, and quantitative polymerase chain reaction testing was performed to assess the pre‐treatment viral load of EBV. Results One hundred twenty patients were included in the study. Fifty‐three patients (44.2%) had positive EBV serology at diagnosis. Stratified by age group, the prevalence of seropositive patients was for 0 to

ABSTRACT The ability to generate a subpopulation of small colony variants (SCVs) is a conserved feature of Pseudomonas aeruginosa and could represent a key adaptive strategy to colonize and persist in multiple niches. However, very little is known about the role of the SCV phenotype, the conditions that promote its emergence, and its possible involvement in an adaptive strategy. In the present work, we investigated the in vitro selective conditions promoting the emergence of SCVs from the prototypical strain PA14, which readily forms SCVs in nonagitated standing cultures. We found that O2 limitation, which causes a redox imbalance, is the main factor selecting for the SCV phenotype, which promotes survival of the population via formation of a biofilm at the air-liquid interface to access the electron acceptor. When this selective pressure is relieved by aeration or supplementation of an alternative electron acceptor, SCVs are barely detectable. We also observed that SCV emergence contributes to redox rebalancing, suggesting that it is involved in an adaptive strategy. We conclude that selection for the SCV phenotype is an adaptive solution adopted by P. aeruginosa to access poorly available O2. IMPORTANCE The bacterium Pseudomonas aeruginosa is an opportunistic pathogen that thrives in many environments. It poses a significant health concern, notably because it is a causative agent of nosocomial infections and the most prevalent pathogen found in the lungs of people with cystic fibrosis. In infected hosts, its persistence is often related to the emergence of an alternative phenotype known as small colony variant (SCV). Identification of conditions selecting for the SCV phenotype contributes to knowledge regarding adaptive mechanisms exploited by P. aeruginosa to survive in multiple niches and persist during infections. Hindering this adaptation strategy could help control persistent P. aeruginosa infections.

In this paper, the dissolution of the silos between geography and business faculty to form a teaching partnership with a common set of questions and goals and how that partnership changed their academic perspectives will be explored. Faculty deepened the challenges for students, re-thought pedagogical models, and re-thought grading and evaluation. Business provides a wide range of messy or "wicked" problems where many decisions are unclear or uncertain for the actors. Quantitative methods and GIS help in their own way and often leave different aspects of uncertainty on the table for students. Integrating geography and business in teaching and student research, and exploring some of the early "academic territoriality" that gave way to build experiences for students is discussed. This evolution of teaching methods within the partnership moved to a more problem-based approach that evolved to affect courses outside the partnership. These changes eventually led the faculty to develop Course-embedded Undergraduate Research Experiences (CUREs) to pose messy, unstructured projects to students. Many of these projects resulted in external student conference presentations. Another outcome was a re-framing of grading and development of assessment that focuses on students engaging in the work. Finally, we identify the artificiality of our disciplinary divisions.

Mining in Canada stands as one of the most energy-intensive sectors, playing a pivotal role as a significant provider of copper, nickel, and cobalt to the international market. Anticipated growth in the global population, coupled with the transition of several low-income economies to middle-income status, is poised to escalate the demand for essential raw materials. This surge in demand is expected to drive an increase in energy consumption across various stages of the Canadian mining industry, encompassing exploration, extraction, processing, and refining. Due to their geographical constraints, most Canadian mining operations rely heavily on fossil fuels such as diesel and heavy fuel. Considering the global shift towards decarbonization and the pursuit of net-zero emission targets, exploring avenues for adopting electrification solutions and integrating renewable energy technologies, particularly in sizable surface mines, is imperative. Within this context, our study delves into the challenges and prospects associated with infusing renewable energy technologies and embracing electrification alternatives within Canadian mining practices. This exploration encompasses a comprehensive review of pertinent literature comprising academic research, technical analyses, and data disseminated by international entities and experts. The findings underscore a prevalent trend wherein Canadian mining enterprises are prominently investing in robust electric truck fleets, particularly for heavy-duty operations. Additionally, incorporating renewable energy solutions is notably prevalent in remote sites with extended operational lifespans. However, an in-depth examination reveals that the most formidable hurdles encompass successfully integrating renewable energy sources and battery electric vehicles. Financial constraints, logistical intricacies, and the imperative to enhance research and development competencies emerge as pivotal challenges that demand strategic addressing.

Plain Language Summary While the deleterious effects of FGM/C on physical health are well documented, we have little knowledge on the psychological experience of this harmful practice. This study aimed to understand the psychological experience of FGM/C in Izzi communities in Southeast Nigeria where FGM/C was widely practiced. In-depth interviews were completed with 38 women from the same ethnic group to explore the collective psychological experience of FGM/C before, during and after the procedure. Our results found that during adolescence, Izzi girls who had not yet undergone FGM/C reported being subjected to intense stigma, humiliation and rejection by their cut peers. This ongoing psychological suffering led many young women to accept or request to be cut, in order to end their psychological torture. Virtually all women reported experiencing severe distress before, during and after the procedure. Some expressed relief from knowing their psychological torture would end and that they would gain social acceptance and a rise in status from being cut. Newly cut young women also expressed that they looked forward to harassing and stigmatizing uncut ones, therein engaging in a complex behaviour that underscores their severe trauma as well as their newly acquired enhanced social status. Our results suggest that prevention strategies need to involve the whole community to develop preventive pathways in a participatory way that empowers girls and women while preventing the deleterious psychological effects of FGM/C and corresponding stigmatizing behaviour towards the uncut. Results suggest the need to provide psychological support for girls and women of practicing Izzi communities of Southeast Nigeria.

Interspecies interactions can drive the emergence of unexpected microbial phenotypes that are not observed when studying monocultures. The cystic fibrosis (CF) lung consists of a complex environment where microbes, living as polymicrobial biofilm-like communities, are associated with negative clinical outcomes for persons with CF (pwCF). However, the current lack of in vitro models integrating the microbial diversity observed in the CF airway hampers our understanding of why polymicrobial communities are recalcitrant to therapy in this disease. Here, integrating computational approaches informed by clinical data, we built a mixed community of clinical relevance to the CF lung composed of Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus sanguinis, and Prevotella melaninogenica. We developed and validated this model biofilm community with multiple isolates of these four genera. When challenged with tobramycin, a front-line antimicrobial used to treat pwCF, the microorganisms in the polymicrobial community show altered sensitivity to this antibiotic compared to monospecies biofilms. We observed that wild-type P. aeruginosa is sensitized to tobramycin in a mixed community versus monoculture, and this observation holds across a range of community relative abundances. We also report that LasR loss-of-function, a variant frequently detected in the CF airway, drives tolerance of P. aeruginosa to tobramycin specifically in the mixed community. Our data suggest that the molecular basis of this community-specific recalcitrance to tobramycin for the P. aeruginosa lasR mutant is increased production of phenazines. Our work supports the importance of studying a clinically relevant model of polymicrobial biofilms to understand community-specific traits relevant to infections.

Abstract Background and Aim Data on factors influencing time to remission in pediatric Crohn's disease (CD) are very limited in the literature. The aim of this retrospective cohort study was to describe the trends of time to clinical remission over the past decade and to identify factors associated with time to clinical remission in children with luminal CD. Methods Patients under 18 years old diagnosed between 2009 and 2019 were included. All data were collected from the patients' medical records. Survival analyses and linear regression models were used to assess the impact of clinical, laboratory, endoscopic, histological, and therapeutic factors on time to clinical remission. Results A total of 654 patients were included in the study. There was no change in the time to clinical remission over the decade. Female sex in adolescents (adjusted bêta regression coefficient [aβ] = 31.8 days, P = 0.02), upper digestive tract involvement (aβ = 46.4 days, P = 0.04) perianal disease (aβ = 32.2 days, P = 0.04), presence of active inflammation on biopsies at diagnosis (aβ = 46.7 days, P = 0.01) and oral 5‐aminosalicylates (5‐ASA) exposure (aβ = 56.6 days, P = 0.002) were associated with longer time to clinical remission. Antibiotic exposure (aβ = −29.3 days, P = 0.04), increased eosinophils (aβ = −29.6 days, P = 0.008) and combination of exclusive enteral nutrition with tumor‐necrosis‐factor‐alpha (TNF‐alpha) inhibitors as induction therapy (aβ = −36.8 days, P = 0.04) were associated with shorter time to clinical remission. Conclusion In children with newly diagnosed Crohn's disease, time to clinical remission did not shorten during the decade. It was associated with baseline clinical and histological data and treatment strategies. Combination of enteral nutrition and TNF‐alpha inhibitors was associated with faster clinical remission.

Scientists played an important role in the management of the Covid-19 pandemic, a situation that can be considered a sociotechnical controversy. In this context, we are interested by the roles future scientists attribute to themselves, by the group of social actors they associate with when they exercise these roles, and by the ways they conciliate their multiple identities. Twelve future scientists took part in an individual semi-structured interview. They attribute to themselves five main roles in the context of the pandemic: be respectful of sanitary measures (as a citizen; lead by example (as a future scientist); contribute to the management of the pandemic through one’s student job (as an essential worker) or through one’s previous training (as a healthcare professional); take care of one’s loved ones (as a citizen); inquire (or stay informed) and inform others (as a citizen or a future scientist). Some participants present a merged identity, others a compartmentalized identity; still others a dominant identity.

Abstract Camera traps have become an extensively utilized tool in ecological research, but the manual processing of images created by a network of camera traps rapidly becomes an overwhelming task, even for small camera trap studies. We used transfer learning to create convolutional neural network (CNN) models for identification and classification. By utilizing a small dataset with an average of 275 labeled images per species class, the model was able to distinguish between species and remove false triggers. We trained the model to detect 17 object classes with individual species identification, reaching an accuracy up to 92% and an average F1 score of 85%. Previous studies have suggested the need for thousands of images of each object class to reach results comparable to those achieved by human observers; however, we show that such accuracy can be achieved with fewer images. With transfer learning and an ongoing camera trap study, a deep learning model can be successfully created by a small camera trap study. A generalizable model produced from an unbalanced class set can be utilized to extract trap events that can later be confirmed by human processors.

Severe HSV-1 infection can cause blindness due to tissue damage from severe inflammation. Due to the high risk of graft failure in HSV-1-infected individuals, cornea transplantation to restore vision is often contraindicated. We tested the capacity for cell-free biosynthetic implants made from recombinant human collagen type III and 2-methacryloyloxyethyl phosphorylcholine (RHCIII-MPC) to suppress inflammation and promote tissue regeneration in the damaged corneas. To block viral reactivation, we incorporated silica dioxide nanoparticles releasing KR12, the small bioactive core fragment of LL37, an innate cationic host defense peptide produced by corneal cells. KR12 is more reactive and smaller than LL37, so more KR12 molecules can be incorporated into nanoparticles for delivery. Unlike LL37, which was cytotoxic, KR12 was cell-friendly and showed little cytotoxicity at doses that blocked HSV-1 activity in vitro, instead enabling rapid wound closure in cultures of human epithelial cells. Composite implants released KR12 for up to 3 weeks in vitro. The implant was also tested in vivo on HSV-1-infected rabbit corneas where it was grafted by anterior lamellar keratoplasty. Adding KR12 to RHCIII-MPC did not reduce HSV-1 viral loads or the inflammation resulting in neovascularization. Nevertheless, the composite implants reduced viral spread sufficiently to allow stable corneal epithelium, stroma, and nerve regeneration over a 6-month observation period.

ABSTRACT Interactions between different bacterial species shape bacterial communities and their environments. The opportunistic pathogens Pseudomonas aeruginosa and Burkholderia cenocepacia both can colonize the lungs of individuals affected by cystic fibrosis. Using the social surface behavior called swarming motility as a study model, we noticed intricate interactions between B. cenocepacia K56-2 and P. aeruginosa PA14. While strain K56-2 does not swarm under P. aeruginosa favorable swarming conditions, co-inoculation with a nonmotile PA14 flagellum-less ΔfliC mutant restored spreading for both strains. We show that P. aeruginosa provides the wetting agent rhamnolipids allowing K56-2 to perform swarming motility, while aflagellated PA14 appears to “hitchhike” along with K56-2 cells in the swarming colony. IMPORTANCE Pseudomonas aeruginosa and Burkholderia cenocepacia are important opportunistic pathogens often found together in the airways of persons with cystic fibrosis. Laboratory cocultures of both species often ends with one taking over the other. We used a surface motility assay to study the social interactions between populations of these bacterial species. Under our conditions, B. cenocepacia cannot swarm without supplementation of the wetting agent produced by P. aeruginosa. In a mixed colony of both species, an aflagellated mutant of P. aeruginosa provides the necessary wetting agent to B. cenocepacia, allowing both bacteria to swarm and colonize a surface. We highlight this peculiar interaction where both bacteria set aside their antagonistic tendencies to travel together.

Background: Anastomotic complications are common after lung transplantation (1.4–33% of cases) and still associated with a high morbi-mortality. Methods: The current study is a monocenter retrospective analysis of symptomatic anastomotic complications (SAC) occurring after lung transplantation between 2010 and 2016, using the macroscopic, diameter, and suture (M-D-S) classification from consensus of French experts in bronchoscopy. The objectives were to determine incidence from surgery, risk factors, and impact of survival of SAC. We defined SAC as M-D-S abnormalities (stenosis ⩾ 50% or dehiscence) requiring bronchoscopic or surgical interventions. Results: A total of 121 patients were included. SAC occurred in 26.5% of patients ( n = 32), divided in symptomatic stenosis for 23.7% ( n = 29), and symptomatic dehiscence in 2.5% ( n = 3). In multivariate analysis, donor bacterial lung infection [HR 2.08 (1.04–4.17), p = 0.04] and age above 50 years [HR 3.26 (1.04–10.26), p = 0.04] were associated with SAC occurrence. Cystic fibrosis etiology was associated with better survival on Kaplan–Meier curve ( p

The oil sands industry in Canada, produces heavy unconventional oils, diluted for transport and called diluted bitumen. However, despite advances in our knowledge of the ecotoxicological risk that these products represent, their effects on benthic organisms following a spill are still largely unknown. In order to fill these gaps, this study aims to determine the lethal and sublethal effects of two diluted bitumens (Bluesky and Cold Lake) and one conventional oil (Lloydminster) for two freshwater benthic invertebrates: Chironomus riparius and Hyalella azteca. The objective of this study is to assess the toxicity of dissolved hydrocarbons, resulting from the physical dispersion of oil, immediately after a spill on the benthic invertebrates. To this end, organisms were exposed for 7 days for chironomids and 14 days for amphipods to a fraction containing soluble hydrocarbons (WAF: water accommodated fraction; 10 g/L, 18 h of agitation, followed by 6 h of sedimentation) with natural or artificial sediment. After exposure, the effects of hydrocarbons were determined using size, mortality, and antioxidant capacities. Dissolved hydrocarbons induced mortality for both species, but these hydrocarbons disappeared very quickly from the water column, regardless of the oil type. The amphipods were sensitive to both types of oil while the chironomids were only sensitive to diluted bitumens. The presence of a natural sediment seems to provide a protective role against dissolved hydrocarbons. The antioxidant enzymes measured (CAT, SOD and GPx) do not appear to be relevant biomarkers for the exposure of these organisms to diluted bitumen.

Sterilization of biodegradable, collagen-based implants is challenging as irradiation sterilization methods can alter their mechanical properties. Electron beam (EB) irradiation is a terminal sterilization method that has been used for biologically-derived implants. Here, recombinant human collagen type III-phosphorylcholine (RHCIII-MPC) hydrogels were irradiated with EB doses of 17, 19, or 21 kGy and their subsequent biocompatibility and ability to promote regeneration in rabbit corneas was evaluated. Unirradiated hydrogels stored in 1% chloroform in phosphate-buffered saline (C-PBS) were the controls. There were no significant differences between irradiated and non-irradiated samples in optical or physical properties (tensile strength, modulus, elasticity), or the ability to support cell growth. However, irradiated implants were more sensitive to high levels of collagenase than unirradiated controls and the C-PBS implants had increased cell growth compared to EB and controls at 72 h. Corneal implants e-beamed at 17 kGy or e-beamed and subsequently frozen (EB-F) to increase shelf-life showed no adverse biological effects of the irradiation. EB, EB-F, and C-PBS implanted corneas all rapidly re-epithelialized but showed mild neovascularization that resolved over 6 months. The regenerated neo-corneas were transparent at 6 months post-operation. In vivo confocal microscopy confirmed normal morphology for the epithelium, stroma, sub-basal nerves and unoperated endothelium. Histology showed that all the regenerated corneas were morphologically similar to the normal. Immunohistochemistry indicated the presence of a differentiated corneal epithelium and functional tear film. In conclusion, the e-beamed corneal implants performed as well as non-irradiated control implants, resulting in fully regenerated neo-corneas with new nerves and without blood vessels or inflammation that may impede vision or corneal function. Therefore, a complete validation study to establish EB irradiation as an effective means for corneal implant sterilization prior to clinical application is necessary as a next step.

Previous research has documented substantial overqualification and an association with social disadvantage and fields of study. Overqualification persistence has been less studied. Persistence is more important than prevalence because skill and job matches are likely to involve lags. Our data set allows us to estimate the prevalence, the correlates, and the persistence of overqualification among Canadian postsecondary graduates using two different measures. We find: i) substantial overqualification and overqualification persistence; ii) the socially disadvantaged and those with less vocational diplomas were more likely to be overqualified but not more likely to move to a match; iii) mobility and academic performance seem to influence catch-up; iv) choice of overqualification measure has large effects on results.

Abstract As the residual vision following a traumatic optic nerve injury can spontaneously recover over time, we explored the spontaneous plasticity of cortical networks during the early post-optic nerve crush (ONC) phase. Using in vivo wide-field calcium imaging on awake Thy1-GCaMP6s mice, we characterized resting state and evoked cortical activity before, during, and 31 days after ONC. The recovery of monocular visual acuity and depth perception was evaluated in parallel. Cortical responses to an LED flash decreased in the contralateral hemisphere in the primary visual cortex and in the secondary visual areas following the ONC, but was partially rescued between 3 and 5 days post-ONC, remaining stable thereafter. The connectivity between visual and non-visual regions was disorganized after the crush, as shown by a decorrelation, but correlated activity was restored 31 days after the injury. The number of surviving retinal ganglion cells dramatically dropped and remained low. At the behavioral level, the ONC resulted in visual acuity loss on the injured side and an increase in visual acuity with the non-injured eye. In conclusion, our results show a reorganization of connectivity between visual and associative cortical areas after an ONC, which is indicative of spontaneous cortical plasticity.

An amendment to this paper has been published and can be accessed via the original article.

Résumé Contexte Les mutilations génitales féminines (MGF) peuvent nuire à la santé des filles/femmes. Plusieurs études ont identifié les déterminants socioculturels de cette tradition, or aucune n’a focalisé sur des personnes vivant dans un contexte où les MGF sont hautement pratiquées et qui refusent de faire exciser leurs filles. En Guinée, la prévalence des MGF est très élevée et la pression sociale pour faire exciser les filles est forte. Cette recherche a donc exploré les profils démographiques et socioculturels, et l’expérience de Guinéens qui ne pratiquent pas les MGF. Méthodes Nous avons utilisé une méthodologie « d’ethnographie focalisée », et mené des entretiens individuels semi-structurés avec 30 femmes et hommes de différentes générations (jeunes adultes, parents, grands-parents) vivant à Conakry, en Guinée. Résultats Nous avons constaté que les participants 1) ne divulguent pas tous leur statut de non-pratique, et 2) ont différentes expériences de pression sociale. Nous avons créé une typologie pour les décrire selon leurs différents profils et expériences, et les avons surnommés ainsi: 1) « activistes », 2) « discrets », 3) « courageux », 4) « stratèges ». Discussion Vouloir abandonner la pratique des MGF ne suffit pas. Les principales conditions permettant aux participants de mettre en oeuvre leur décision de ne pas faire exciser leurs filles sont: bénéficier de soutien social (capital social positif), ou être financièrement indépendant du réseau de solidarité traditionnel (capital économique suffisant). Nous recommandons donc de trouver des moyens pour accroître l’autonomisation des femmes/familles pour qu’elles puissent mettre en œuvre leur décision de ne pas faire exciser leurs filles, principalement en les soutenant pour accéder à 1) du soutien social, et 2) l’indépendance financière, y compris par la scolarisation et l’accès à des emplois mieux rémunérés. Conclusions Cette étude a été la première à explorer l’expérience de personnes qui ne pratiquent pas les MGF dans un contexte de forte prévalence des MGF et de pression sociale. Les résultats et recommandations de cette recherche peuvent éclairer les stratégies d’abandon des MGF et ainsi contribuer à améliorer ou à développer des stratégies d’intervention qui favorisent la santé et le bien-être des filles/femmes.

Bioreporter systems based on detectable enzyme activity, such as that of beta-galactosidase or luciferase, are key in novel bacterial promoter discovery and study. While these systems permit quantification of gene expression, their use is limited by the toxicity of the expressed reporter enzymes in a given host. Indeed, the most potent promoters may be overlooked if their activity causes a lethal overproduction of the reporter genes when screening for transcriptional activity of potential promoter sequences with the luxCDABE cassette. To overcome this limitation, a variation of the mini-CTX-lux plasmid has been designed which allows reduction of promoter activity via the addition of an adjacent fluoride riboswitch. The riboswitch adds a layer of regulation between the promoter and the reporter gene, allowing cloning of stronger promoters by weakening expression, while giving the potential to induce with fluoride to provide a good signal for weaker promoters, thus circumventing limitations associated with reporter toxicity. We noticed the riboswitch potential portability issues between species, suggesting caution when using riboswitches non-native to the species where it is being used. This study introduces a new molecular biology tool which will allow for the identification of previously unverifiable or uncharacterized potent promoters and also provides a cloning vector for translational fusion with luciferase in a plasmid compatible with many species such as from the genera Burkholderia and Pseudomonas.