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Monoclonal antibodies (MAbs) targeting the Spike glycoprotein of SARS-CoV-2 is a key strategy to prevent severe COVID-19. Here, the efficacy of two monoclonal antibody bitherapies against SARS-CoV-2 was assessed on 92 patients at high risk of severe COVID-19 between March and October 2021 (Bichat-Claude Bernard Hospital, Paris, France). Nine patients died despite appropriate management. From 14 days following treatment initiation, we observed a slower viral load decay for patients treated with the bitherapy Bamlanivimab/Etsevimab compared to the Casirivimab/Imdevimab association therapy ( P  = 0.045). The emergence of several mutations on the Spike protein known to diminish antiviral efficacy was observed from 1 to 3 weeks after infusion. The Q493R mutation was frequently selected, located in a region of joint structural overlap by Bamlanivimab/Etsevimab antibodies. Despite that this study was done on former SARS-CoV-2 variants (Alpha and Delta), the results provide new insights into resistance mechanisms in SARS-CoV-2 antibodies neutralization escape and should be considered for current and novel variants. IMPORTANCE Monoclonal antibody bitherapies (MAbs) are commonly prescribed to treat severe SARS-CoV-2-positive patients, and the rapid growth of resistance mutation emergence is alarming globally. To explore this issue, we conducted both clinical and genomic analyses of SARS-CoV-2 in a series of patients treated in 2021. We first noticed that the two dual therapies prescribed during the study had different kinetics of viral load decay. Rapidly after initiation of the treatments, resistance mutations emerged in the interface between the MAbs and the target Spike glycoprotein, demonstrating the importance to continuously screen the viral genome during treatment course. Taken together, the results highlight that viral mutations may emerge under selective pressure, conferring a putative competitive advantage, and could rapidly spread, as observed for the Omicron variant.

Background: The reduction of maternal mortality in developing countries such as the Democratic Republic of Congo (DRC) still raises many questions. Indeed, this large country in the heart of Africa ranks 4th among the eight countries that alone account for more than 50% of maternal deaths in the world, behind India, Nigeria and Pakistan. However, there is no up-to-date data on maternal mortality in eastern DRC. This study measures the mortality rate rate in health facilities in eastern DRC and identifies the associated risk factors., Methods: This analytical epidemiological study was based on retrospective data materna deaths recorded in 59 health facilities, in three health zones in the southern part of Maniema province in east DRC. The study was conducted from July 1, 2015 to June 30, 2020. Descriptive, bi and multivariate analyses were used., Results: The maternal mortality rate was estimated at 620 deaths per 100,000 live births, of which 46% of maternal deaths were related to a parturients' delayed decision in seeking healthcare in time (first delay). Maternal deaths were significantly associated with extreme ages (≤ 19 years and ≥ 40 years: p =  < 0.001), patient parity (in primigravidas and in large multiparas: p = 0.001), complications such as hemorrhagic, (p =  < 0.001), uterine ruptures:(p =  < 0.001), infections, (p =  < 0.001), and dystocia (p =  < 0.001)., Conclusion: Despite the efforts made by the DRC and its partners in the fight against maternal mortality, women continue to lose their lives when they decide to give birth. The results imply that it is imperative to strengthen both women and health professionals' knowledge about pregnancy and maternal health and their power to reduce instances of first delay by supporting women in formulating their birth plans., (© 2022. The Author(s).)

The multitude of national strategies used against the COVID-19 pandemic makes it necessary to review and synthesize them in order to identify potential gaps and shortcomings, and to help prioritize future control efforts. This systematic mapping review is aimed at identifying the coronavirus pandemic management strategies adopted by France, Tunisia, and Germany during the early stage of the COVID-19 outbreak. A set of government websites in addition to the PubMed and Google Scholar databases were searched to identify scientific articles and institutional documents related to the national strategies of the three countries up until July 2020. The references included were mapped and narratively synthesized based on the pillars of the Monitoring and Evaluation Framework of the Strategic Preparedness and Response Plan defined by the World Health Organization. Of the 2765 records screened, 65 documents were included in the study. The analysis of these documents showed that Germany was the first country to implement mass screening of cases and that France was the first country to implement measures to impose general containment at the national level. It also showed that Tunisia was the only country to have imposed the confinement of passengers on repatriation flights in dedicated containment centers and at the expense of the state.

Plant population density is an important variable in agronomy and forestry and offers an experimental way to better understand plant-plant competition. We made a meta-analysis of responses of even-aged mono-specific stands to population density by quantifying for 3 stand and 33 individual plant variables in 334 experiments how much both plant biomass and phenotypic traits change with a doubling in density. Increasing density increases standing crop per area, but decreases the mean size of its individuals, mostly through reduced tillering and branching. Among the phenotypic traits, stem diameter is negatively affected, but plant height remains remarkably similar, partly due to an increased stem length-to-mass ratio and partly by increased allocation to stems. The reduction in biomass is caused by a lower photosynthetic rate, mainly due to shading of part of the foliage. Total seed mass per plant is also strongly reduced, marginally by lower mass per seed, but mainly because of lower seed numbers. Plants generally have fewer shoot-born roots, but their overall rooting depth seems hardly affected. The phenotypic plasticity responses to high densities correlate strongly with those to low light, and less with those to low nutrients, suggesting that at high density, shading affects plants more than nutrient depletion., (© 2020 The Authors. Plant, Cell & Environment published by John Wiley & Sons Ltd.)

A soil coring protocol was developed to cooptimize the estimation of root length distribution (RLD) by depth and detection of functionally important variation in root system architecture (RSA) of maize and bean. The functional-structural model OpenSimRoot was used to perform in silico soil coring at six locations on three different maize and bean RSA phenotypes. Results were compared to two seasons of field soil coring and one trench. Two one-sided T -test (TOST) analysis of in silico data suggests a between-row location 5 cm from plant base (location 3), best estimates whole-plot RLD/D of deep, intermediate, and shallow RSA phenotypes, for both maize and bean. Quadratic discriminant analysis indicates location 3 has ~70% categorization accuracy for bean, while an in-row location next to the plant base (location 6) has ~85% categorization accuracy in maize. Analysis of field data suggests the more representative sampling locations vary by year and species. In silico and field studies suggest location 3 is most robust, although variation is significant among seasons, among replications within a field season, and among field soil coring, trench, and simulations. We propose that the characterization of the RLD profile as a dynamic rhizo canopy effectively describes how the RLD profile arises from interactions among an individual plant, its neighbors, and the pedosphere., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2020 James D. Burridge et al.)

COVID-19 pneumonia can be severe, with an unpredictable evolution and high mortality prevalence in older patients. The diagnosis is usually performed by RT-PCR or CT chest scan. Lung ultrasonography (LUS) has been proposed as an alternative method to monitor patients with COVID-19 pneumonia. To assess the diagnostic performance of LUS, we performed LUS using a portable device and adapting a protocol already used in Acute Respiratory Syndrome. We used the score obtained with the index we created to assess for LUS diagnostic performance as compared to lung CT chest scan and to predict for oxygen requirements. Daily bedside LUS was easy to perform and microbiologically safe. LUS was 89% sensitive and 100% specific in predicting CT chest scan abnormalities, and 95% sensitive and 67% specific in detecting oxygen requirements. This is the first report on the diagnostic performance of LUS as compared to CT chest scan for the diagnosis of COVID-19 pneumonia and assessments of oxygen requirements by LUS. LUS could help in the orientation of dyspneic patients to intensive care. It could also be proposed when there is limited access to CT scan in the context of a pandemic crisis, or to implement clinical lung examinations for outpatient follow-up.

Root phenotypes regulate soil resource acquisition; however, their genetic control and phenotypic plasticity are poorly understood. We hypothesized that the responses of root architectural phenes to water deficit (stress plasticity) and different environments (environmental plasticity) are under genetic control and that these loci are distinct. Root architectural phenes were phenotyped in the field using a large maize association panel with and without water deficit stress for three seasons in Arizona and without water deficit stress for four seasons in South Africa. All root phenes were plastic and varied in their plastic response. We identified candidate genes associated with stress and environmental plasticity and candidate genes associated with phenes in well-watered conditions in South Africa and in well-watered and water-stress conditions in Arizona. Few candidate genes for plasticity overlapped with those for phenes expressed under each condition. Our results suggest that phenotypic plasticity is highly quantitative, and plasticity loci are distinct from loci that control phene expression in stress and non-stress, which poses a challenge for breeding programs. To make these loci more accessible to the wider research community, we developed a public online resource that will allow for further experimental validation towards understanding the genetic control underlying phenotypic plasticity., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

Kava is a plant root extract that is widely consumed by Pacific Islanders. Kava contains a class of lactone compounds called kavalactones. The sedative and anxiolytic effects of kava are likely attributed to the efficacies of kavalactones on the nervous system. Although some studies have implicated the potencies of certain kavalactone species on γ-aminobutyric acid transmission, evidence supporting the action of kavalactones on the eukaryotic neuromuscular junction (NMJ) and acetylcholine (ACh) transmission is scant. Here, we used behavioral assays to demonstrate the effects of kavalactones at the Caenorhabditis elegans NMJ. Our results suggest that kavalactones disrupt the inhibitory-excitatory balance at the NMJ. Such perturbation of NMJ activity is likely due to excess or prolonged ACh transmission. In addition, we found that kavain, a major constituent of kava, induced worm paralysis but not convulsions. Hence, the modulatory action of kavain could be distinct from the other kavalactone species., Competing Interests: DECLARATION OF CONFLICTING INTERESTS: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Soils vary widely in mineral nutrient availability and physical characteristics, but the influence of this variability on plant responses to elevated CO2 remains poorly understood. As a first approximation of the effect of global soil variability on plant growth response to CO2, we evaluated the effect of CO2 on tall fescue (Festuca arundinacea) grown in soils representing 10 of the 12 global soil orders plus a high-fertility control. Plants were grown in small pots in continuously stirred reactor tanks in a greenhouse. Elevated CO2 (800 ppm) increased plant biomass in the high-fertility control and in two of the more fertile soils. Elevated CO2 had variable effects on foliar mineral concentration-nitrogen was not altered by elevated CO2, and phosphorus and potassium were only affected by CO2 in a small number of soils. While leaf photosynthesis was stimulated by elevated CO2 in six soils, canopy photosynthesis was not stimulated. Four principle components were identified; the first was associated with foliar minerals and soil clay, and the second with soil acidity and foliar manganese concentration. The third principle component was associated with gas exchange, and the fourth with plant biomass and soil minerals. Soils in which tall fescue did not respond to elevated CO2 account for 83% of global land area. These results show that variation in soil physical and chemical properties have important implications for plant responses to global change, and highlight the need to consider soil variability in models of vegetation response to global change.

Suboptimal nitrogen (N) availability is a primary constraint for crop production in developing nations, while in rich nations, intensive N fertilization carries substantial environmental and economic costs. Therefore, understanding root phenes that enhance N acquisition is of considerable importance. Structural-functional modeling predicts that root cortical aerenchyma (RCA) could improve N acquisition in maize (Zea mays). We evaluated the utility of RCA for N acquisition by physiological comparison of maize recombinant inbred lines contrasting in RCA grown under suboptimal and adequate N availability in greenhouse mesocosms and in the field in the United States and South Africa. N stress increased RCA formation by 200% in mesocosms and by 90% to 100% in the field. RCA formation substantially reduced root respiration and root N content. Under low-N conditions, RCA formation increased rooting depth by 15% to 31%, increased leaf N content by 28% to 81%, increased leaf chlorophyll content by 22%, increased leaf CO2 assimilation by 22%, increased vegetative biomass by 31% to 66%, and increased grain yield by 58%. Our results are consistent with the hypothesis that RCA improves plant growth under N-limiting conditions by decreasing root metabolic costs, thereby enhancing soil exploration and N acquisition in deep soil strata. Although potential fitness tradeoffs of RCA formation are poorly understood, increased RCA formation appears be a promising breeding target for enhancing crop N acquisition., (© 2014 American Society of Plant Biologists. All Rights Reserved.)

Suboptimal availability of water and nutrients is a primary limitation to plant growth in terrestrial ecosystems. The acquisition of soil resources by plant roots is therefore an important component of plant fitness and agricultural productivity. Plant root systems comprise a set of phenes, or traits, that interact. Phenes are the units of the plant phenotype, and phene states represent the variation in form and function a particular phene may take. Root phenes can be classified as affecting resource acquisition or utilization, influencing acquisition through exploration or exploitation, and in being metabolically influential or neutral. These classifications determine how one phene will interact with another phene, whether through foraging mechanisms or metabolic economics. Phenes that influence one another through foraging mechanisms are likely to operate within a phene module, a group of interacting phenes, that may be co-selected. Examples of root phene interactions discussed are: (1) root hair length × root hair density, (2) lateral branching × root cortical aerenchyma (RCA), (3) adventitious root number × adventitious root respiration and basal root growth angle (BRGA), (4) nodal root number × RCA, and (5) BRGA × root hair length and density. Progress in the study of phenes and phene interactions will be facilitated by employing simulation modeling and near-isophenic lines that allow the study of specific phenes and phene combinations within a common phenotypic background. Developing a robust understanding of the phenome at the organismal level will require new lines of inquiry into how phenotypic integration influences plant function in diverse environments. A better understanding of how root phenes interact to affect soil resource acquisition will be an important tool in the breeding of crops with superior stress tolerance and reduced dependence on intensive use of inputs.

Background and Aims: Root cortical aerenchyma (RCA) increases water and nutrient acquisition by reducing the metabolic costs of soil exploration. In this study the hypothesis was tested that living cortical area (LCA; transversal root cortical area minus aerenchyma area and intercellular air space) is a better predictor of root respiration, soil exploration and, therefore, drought tolerance than RCA formation or root diameter., Methods: RCA, LCA, root respiration, root length and biomass loss in response to drought were evaluated in maize (Zea mays) recombinant inbred lines grown with adequate and suboptimal irrigation in soil mesocosms., Key Results: Root respiration was highly correlated with LCA. LCA was a better predictor of root respiration than either RCA or root diameter. RCA reduced respiration of large-diameter roots. Since RCA and LCA varied in different parts of the root system, the effects of RCA and LCA on root length were complex. Greater crown-root LCA was associated with reduced crown-root length relative to total root length. Reduced LCA was associated with improved drought tolerance., Conclusions: The results are consistent with the hypothesis that LCA is a driver of root metabolic costs and may therefore have adaptive significance for water acquisition in drying soil.

Originally used in Asia for the treatment of pain, spasms, nausea and insomnia, marijuana is the most consumed psychotropic drug worldwide. The interest of medical cannabis has been reconsidered recently, leading to many scientific researches and commercialization of these drugs. Natural and synthetic cannabinoids display beneficial antiemetic, anti-inflammatory and analgesic effects in numerous diseases, however accompanied with undesirable effects due to the CB1 receptor. Present researches focus on the design of therapeutical molecules targeting the CB2 receptors, and thus avoiding central side effects and therefore psychotropic effects caused by the CB1 receptor., (© 2013 médecine/sciences – Inserm.)

After the age of 65 yrs the specific impact of unrecognised sleep-related breathing disorders (SRBD) on 24-h blood pressure (BP) levels remains under debate. We tested the cross-sectional relationship between the severity of obstructive sleep apnoea/hypopnoea (OSAH) and the increase of BP using ambulatory BP monitoring (ABPM) in the PROOF (PROgnostic indicator OF cardiovascular and cerebrovascular events study)-SYNAPSE (Autonomic Nervous System Activity, Aging and Sleep Apnea/Hypopnea study) cohort. 470 subjects (aged 68 yrs) neither treated for hypertension nor diagnosed for SRBD were included. All subjects underwent ABPM, and unattended at-home polygraphic studies. OSAH was defined by an apnoea/hypopnoea index (AHI) >15 · h(-1). The severity of the sleep apnoea was also quantified as the index of dips in oxyhaemoglobin saturation >3% (ODI). Results are expressed in per protocol analysis. Severe OSAH (AHI >30 · h(-1), 17% of subjects) was associated with a significant 5 mmHg increase in both diurnal and nocturnal systolic BP (SBP), and with a nocturnal 3 mmHg increase in diastolic BP (DBP). Systolic (mean SBP >135 mmHg) or diastolic (mean DBP >80 mmHg) hypertension were more frequently encountered in subjects suffering from moderate (AHI 15-30) or severe OSAH. After adjustment, the independent association between severe OSAH and 24-h systolic hypertension remained significant (OR 2.42, 95% CI 1.1-5.4). The relationship was further reinforced when SRBD severity was expressed using ODI >10 · h(-1). The impact of unrecognised SRBD on BP levels also exists at the age of 68 yrs. The hypoxaemic load appears to be the pathophysiological cornerstone for such a relationship.

Plants are reported to over-proliferate roots in response to belowground competition, thereby reducing reproductive biomass. This has been cited as an instance of the 'tragedy of the commons'. Many of the studies that report this response suggest that plants can sense neighbours and discriminate between 'self' and 'non-self' roots. To test the alternate hypothesis that root responses to a neighbouring plant are mediated by resource depletion, common bean plants were supplied with the same phosphorus (P) fertiliser dose in varying rooting volumes, or with neighbouring plants separated by plastic film, nylon mesh, or no barrier to vary access to a neighbour. Phosphorus concentration, but not the presence of a neighbour or rooting volume, strongly influenced biomass allocation to roots. Root architecture was significantly altered by both neighbours and P availability. When exposed to the roots of a neighbour, plants altered the vertical and horizontal distribution of roots, placing fewer roots in soil domains occupied by roots of a neighbour. These results support the hypothesis that root responses to neighbouring plants are mediated by resource depletion by the neighbour rather than sensing of 'non-self' roots and show that the presence of a neighbour may affect root architecture without affecting biomass allocation to roots.

Background and Aims: Timing of reproduction is a key life-history trait that is regulated by resource availability. Delayed reproduction in soils with low phosphorus availability is common among annuals, in contrast to the accelerated reproduction typical of other low-nutrient environments. It is hypothesized that this anomalous response arises from the high marginal value of additional allocation to root growth caused by the low mobility of phosphorus in soils., Methods: To better understand the benefits and costs of such delayed reproduction, a two-resource dynamic allocation model of plant growth and reproduction is presented. The model incorporates growth, respiration, and carbon and phosphorus acquisition of both root and shoot tissue, and considers the reallocation of resources from senescent leaves. The model is parameterized with data from Arabidopsis and the optimal reproductive phenology is explored in a range of environments., Key Results: The model predicts delayed reproduction in low-phosphorus environments. Reproductive timing in low-phosphorus environments is quite sensitive to phosphorus mobility, but is less sensitive to the temporal distribution of mortality risks. In low-phosphorus environments, the relative metabolic cost of roots was greater, and reproductive allocation reduced, compared with high-phosphorus conditions. The model suggests that delayed reproduction in response to low phosphorus availability may be reduced in plants adapted to environments where phosphorus mobility is greater., Conclusions: Delayed reproduction in low-phosphorus soils can be a beneficial response allowing for increased acquisition and utilization of phosphorus. This finding has implications both for efforts to breed crops for low-phosphorus soils, and for efforts to understand how climate change may impact plant growth and productivity in low-phosphorus environments.

Plant phenology, the timing of plant growth and development, is changing in response to global climate change. Changing temperature, soil moisture, nitrogen availability, light, and elevated CO(2) are all likely to affect plant phenology. Alteration of plant phenology by global climate change may alter the ability of plants to acquire soil resources (water and nutrients) by altering the timing and duration of the deployment of roots and leaves, which drive resource acquisition. The potential importance of phenologically-driven changes in soil resource acquisition for plant fitness and productivity have received little attention. General hypotheses are proposed for how plant acquisition of soil resources may be affected by the alteration of phenology. It is expected that the acquisition of mobile resources will be approximately proportional to total transpiration. Alteration of phenology that increases total transpiration should increase, while changes in phenology that reduce transpiration should decrease the acquisition of mobile resources. The acquisition of immobile resources will be approximately proportional to root length duration, thus changes in phenology that increase growth duration should increase the acquisition of immobile resources and vice versa. For both groups of resources, longer growing seasons would tend to increase resource acquisition, and shorter growing seasons would tend to decrease resource acquisition. In the case of resources that exhibit seasonal variability in availability, the synchrony of resource availability and acquisition capacity is important, and subject to disturbance by the alteration of phenology.

Low phosphorus availability (low P) often delays flowering and maturity in annual plants, while abiotic stress generally accelerates flowering and maturity. The utility of this response is unknown. We hypothesize that phenological delay in low P is beneficial by permitting more time for phosphorus acquisition and utilization. We grew seven genotypes of Arabidopsis thaliana with contrasting phenology in high and low P. Low P delayed bolting and maturity in all genotypes. Low P decreased root length, but not root-length duration (the integral of root length over time), because phenological delay allowed low-P plants to compensate for shorter root length. Root-length duration was correlated with phosphorus accumulation. Leaf phosphorus duration (the integral of leaf phosphorus over time) was correlated with reproductive biomass, indicating the utility of increased phosphorus utilization. Phenological delays accounted for up to 30% of biomass production when low-P plants were compared to models of plants with no delays. These results support the hypothesis that phenological delay in low P is adaptive and leads to increased phosphorus acquisition and utilization. Because low P conditions are prevalent, understanding the utility of this response could be useful in crop breeding and in predicting plant responses to global climate change.

Multidetector computed tomography (MDCT) acquisition during a single breath hold using thin collimation provides high resolution volumetric data set permitting multiplanar and three dimensional reconstruction of the proximal airways. In chronic obstructive pulmonary disease (COPD) patients, this technique provides an accurate assessment of bronchial wall thickening, tracheobronchial deformation, outpouchings reflecting dilatation of the submucous glands, tracheobronchomalacia, and expiratory air trapping. New software developed to segment adequately the lumen and walls of the airways on MDCT scans allows quantitative assessment of the airway dimensions which has shown to be reliable in clinical practice. This technique can become important in longitudinal studies of the pathogenesis of COPD, and in the assessment of therapeutic interventions.

Place-based resource management, such as watershed or ecosystem management, is being promoted to replace the media-focused approach for achieving water quality protection. We monitored the agricultural area of a 740-ha watershed to determine the nature and scale of farm material transfers, N and P balances, and farmer decisions that influenced them. Using field data and farmer interviews we found that 3 of 15 farms, emphasizing hog, dairy, or cash crops with poultry production, accounted for more than 80% of the inputs and outputs of N and P for the 362-ha agricultural area (332 ha of managed cropland and animal facilities). Feed for hogs (38% each of total N and P) and manure applied to fields as part of the cash crop and poultry operation (28 and 38% of total N and P, respectively) were the dominant inputs. No crops grown in the watershed were fed to animals in the watershed and more manure nutrients were applied from animals outside than from those in the watershed. A strategic decision by the hog farmer to begin marketing finished hogs changed the material transfers and nutrient balances more than tactical decisions by other farmers in allocating manure to cropland. Since the components of agricultural production were not all interconnected, the fundamental assumption of place-based management programs is not well-suited to this situation. Alternative approaches to managing the effect of agriculture on water quality should consider the organization of agricultural production and the role of strategic decisions in controlling farm nutrient balances.

Objective: To know the students' opinion concerning semiology teaching and teachers., Methods: Annual enquiry between 1990-91 and 2000-01, before and after a reform increasing to 400 the hours dedicated to medical clerkships in the second and third years of the courses., Results: Before the reform, at least 62% of the students were in favor of the general organization, while a growing percentage (reaching 79.6%; p < 0.0001) considered the number of hours dedicated to clinical clerkship as insufficient. Concerning the teachers, the assessment concerning the "assistant heads of departments" (AHD) showed great disparities. Out of 100 teachers-year, 4 obtained a score lesser than 10/20 and 59 greater than 15/20. After the reform, 19 AHD out of 33 obtained more than 15/20 and 5 less than 10/20. The reintroduction of lectures was not criticized. The professors who gave lectures were reproached by the students for delaying them or for not having given them at all. They were also reproached for their lack of relationship with the teaching objectives. The scores allocated to professors ranged from 4.5 to 15.9/20., Conclusion: Enhancing the value of teaching for an AHD's university career and reducing the administrative burden for all teachers would be useful to improve medical education, especially in semiology.