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Abstract Cell division is completed by the abscission of the intercellular bridge connecting the daughter cells. Abscission requires the polymerization of an ESCRT-III cone close to the midbody to both recruit the microtubule severing enzyme spastin and scission the plasma membrane. Here, we found that the microtubule and the membrane cuts are two separate events that are regulated differently. Using HeLa cells, we uncovered that the F-actin disassembling protein Cofilin-1 controls the disappearance of a transient pool of branched F-actin which is precisely assembled at the tip of the ESCRT-III cone shortly before the microtubule cut. Functionally, Cofilin-1 and Arp2/3-mediated branched F-actin favor abscission by promoting local severing of the microtubules but do not participate later in the membrane scission event. Mechanistically, we propose that branched F-actin functions as a physical barrier that limits ESCRT-III cone elongation and thereby favors stable spastin recruitment. Our work thus reveals that F-actin controls the timely and local disassembly of microtubules required for cytokinetic abscission.

Summary: Background: Although immunomodulators have established benefit against the new coronavirus disease (COVID-19) in general, it is uncertain whether such agents improve outcomes without increasing the risk of secondary infections in the specific subgroup of previously immunocompromised patients. We assessed the effect of immunomodulators on outcomes of immunocompromised patients hospitalized for COVID-19. Methods: The protocol was prospectively registered with PROSPERO (CRD42022335397). MEDLINE, Cochrane Central Register of Controlled Trials and references of relevant articles were searched up to 01-06-2022. Authors of potentially eligible randomized controlled trials were contacted to provide data on immunocompromised patients randomized to immunomodulators vs control (i.e., placebo or standard-of-care). Findings: Eleven randomized controlled trials involving 397 immunocompromised patients hospitalized for COVID-19 were included. Ten trials had low risk of bias. There was no difference between immunocompromised patients randomized to immunomodulators vs control regarding mortality [30/182 (16.5%) vs 41/215 (19.1%); RR 0.93, 95% CI 0.61–1.41; p = 0.74], secondary infections (RR 1.00, 95% CI 0.64–1.58; p = 0.99) and change in World Health Organization ordinal scale from baseline to day 15 (weighed mean difference 0.27, 95% CI -0.09–0.63; p = 0.15). In subgroup analyses including only patients with hematologic malignancy, only trials with low risk of bias, only trials administering IL-6 inhibitors, or only trials administering immunosuppressants, there was no difference between comparators regarding mortality. Interpretation: Immunomodulators, compared to control, were not associated with harmful or beneficial outcomes, including mortality, secondary infections, and change in ordinal scale, when administered to immunocompromised patients hospitalized for COVID-19. Funding: Hellenic Foundation for Research and Innovation.

Abstract Background To explore ways to reduce the overuse of antibiotics for acute respiratory infections (ARIs), we conducted a pilot clustered randomized controlled trial (RCT) to evaluate DECISION+, a training program in shared decision making (SDM) for family physicians (FPs). This pilot project demonstrated the feasibility of conducting a large clustered RCT and showed that DECISION+ reduced the proportion of patients who decided to use antibiotics immediately after consulting their physician. Consequently, the objective of this study is to evaluate, in patients consulting for ARIs, if exposure of physicians to a modified version of DECISION+, DECISION+2, would reduce the proportion of patients who decide to use antibiotics immediately after consulting their physician. Methods/design The study is a multi-center, two-arm, parallel clustered RCT. The 12 family practice teaching units (FPTUs) in the network of the Department of Family Medicine and Emergency Medicine of Université Laval will be randomized to a DECISION+2 intervention group (experimental group) or to a no-intervention control group. These FPTUs will recruit patients consulting family physicians and residents in family medicine enrolled in the study. There will be two data collection periods: pre-intervention (baseline) including 175 patients with ARIs in each study arm, and post-intervention including 175 patients with ARIs in each study arm (total n = 700). The primary outcome will be the proportion of patients reporting a decision to use antibiotics immediately after consulting their physician. Secondary outcome measures include: 1) physicians and patients' decisional conflict; 2) the agreement between the parties' decisional conflict scores; and 3) perception of patients and physicians that SDM occurred. Also in patients, at 2 weeks follow-up, adherence to the decision, consultation for the same reason, decisional regret, and quality of life will be assessed. Finally, in both patients and physicians, intention to engage in SDM in future clinical encounters will be assessed. Intention-to-treat analyses will be applied and account for the nested design of the trial will be taken into consideration. Discussion DECISION+2 has the potential to reduce antibiotics use for ARIs by priming physicians and patients to share decisional process and empowering patients to make informed, value-based decisions. Trial Registration ClinicalTrials.gov: NCT01116076

This article summarizes recent advances in our knowledge of plankton biogeography obtained by genomic approaches and the impacts of global warming on it. Large-scale comparison of the genomic content of samples of different plankton size fractions revealed a partitioning of the oceans into genomic provinces and the impact of major oceanic currents on them. By defining ecological niches, these provinces are extrapolated to all oceans, with the exception of the Arctic Ocean. By the end of the 21st century, a major restructuring of these provinces is projected in response to a high emission greenhouse gas scenario over 50% of the surface of the studied oceans. Such a restructuring could lead to a decrease in export production by 4%. Finally, obtaining assembled sequences of a large number of plankton genomes defining this biogeography has allowed to better characterize the genomic content of the provinces and to identify the species structuring them. These genomes similarly enabled a better description of potential future changes of plankton communities under climate change.

Abstract Background Recent evidences show that education and rehabilitation while waiting for knee replacement have positive effects on the patients' health status. Identification of factors associated with worse pain, function and health-related quality of life (HRQoL) while waiting for surgery could help develop pre-surgery rehabilitation interventions that target specifically these factors and prioritize patients that may benefit the most from them. The objectives of this study were to measure pain, stiffness, function and HRQoL in patients at enrolment on waiting lists for knee replacement and to identify demographic, clinical, socioeconomic and psychosocial characteristics associated with these outcomes. Methods This study is part of a broader study measuring the effects of pre-surgery wait in patients scheduled for knee replacement. From 02/2006 to 09/2007, 197 patients newly scheduled for total knee replacement were recruited from the waiting lists of three university hospitals in Quebec City, Canada. Pain, stiffness and function were measured with the Western Ontario and McMaster Osteoarthritis Index (WOMAC) and HRQoL was measured with the SF-36 Health Survey. Stepwise multiple regression analysis was used to assess the strength of the associations between the independent variables and the WOMAC and SF-36 scores. Results The scores of all eight HRQoL physical and mental domains of the SF-36 were significantly lower than aged matched Canadian normative data (p < 0.05). Contralateral knee pain, higher psychological distress, higher body mass index (BMI) and the use of a walking aid were significantly associated with worse function (p < 0.05) and contributed to 22% of the variance of the WOMAC function score (multiple r = 0.47). A higher BMI, the use of a walking aid, contralateral knee pain and advanced age were significantly associated with worse physical function (p < 0.05) and contributed to 17% of the variance of the SF-36 HRQoL physical functioning score (multiple r = 0.41). Conclusion Patients waiting for knee replacement have poor function and HRQoL. Characteristics that were found to be associated with these outcomes could help develop pre-surgery rehabilitation program and prioritize patients that may benefit the most from them. Such programs could include interventions to reduce psychological distress, therapeutic exercises targeting both knees and weight loss management.

Abstract Background There is considerable interest today in shared decision-making (SDM), defined as a decision-making process jointly shared by patients and their health care provider. However, the data show that SDM has not been broadly adopted yet. Consequently, the main goal of this proposal is to bring together the resources and the expertise needed to develop an interdisciplinary and international research team on the implementation of SDM in clinical practice using a theory-based dyadic perspective. Methods Participants include researchers from Canada, US, UK, and Netherlands, representing medicine, nursing, psychology, community health and epidemiology. In order to develop a collaborative research network that takes advantage of the expertise of the team members, the following research activities are planned: 1) establish networking and on-going communication through internet-based forum, conference calls, and a bi-weekly e-bulletin; 2) hold a two-day workshop with two key experts (one in theoretical underpinnings of behavioral change, and a second in dyadic data analysis), and invite all investigators to present their views on the challenges related to the implementation of SDM in clinical practices; 3) conduct a secondary analyses of existing dyadic datasets to ensure that discussion among team members is grounded in empirical data; 4) build capacity with involvement of graduate students in the workshop and online forum; and 5) elaborate a position paper and an international multi-site study protocol. Discussion This study protocol aims to inform researchers, educators, and clinicians interested in improving their understanding of effective strategies to implement shared decision-making in clinical practice using a theory-based dyadic perspective.

Abstract Inborn errors of immunity (IEI) are a heterogeneous entity with an increasing number of late diagnoses. Besides infections, inflammatory manifestations are a growing part of the clinical landscape of IEI. These complications are of unknown causes and often lead to the prescription of immunosuppressive agents that worsen the underlying immune defect. We here report the case of an adult patient diagnosed with chronic Human Adenovirus C-1 arthritis in the setting of primary agammaglobulinemia. Metagenomic next-generation sequencing led to the correct diagnosis and high-dose intravenous immunoglobulins resulted in complete recovery. This observation gives new insights into adenoviral immunity and underlines the importance of metagenomics in the diagnosis of inflammatory manifestations in immunocompromised patients.

Genomic inference reveals potential climate change-driven range expansion of the phytoplankton species Pelagomonas calceolata.

BackgroundIn the context of concerns regarding the cardiorespiratory fitness (CRF) of youth populations, the aims of this study were: (1) to update reference values for the VO2max for school-aged Canadians and (2) to document secular trends in CRF after a 35-year interval.MethodsBetween September 2014 and April 2017, the CRF of 3725 students (53.2% boys; 6.0 to 17.9 yrs) was determined using the 20-m shuttle run test. The sample was collected in 36 different schools from six cities of Québec (Canada).ResultsMedian values of VO2max decreased with age in both sexes (p ≤ 0.05). By the age of 10, more than 20% of boys showed VO2max values below the recommended value (42 ml·kg−1·min−1). At the age of 17, that proportion reached 56.8%. A similar proportion of 12 yrs girls (20%) were under the recommended minimal value (37 ml·kg−1·min−1) and that value reached 69.9% at the age of 17. Compared to 1982, the VO2max at age 17 has declined by 18% for boys and 12% for girls. The situation is worse in terms of functional capacity (number of stages completed) with an overall decrease of more than 30%.ConclusionThis study demonstrates that, compared to data obtained using the same methodology 35 years ago, the CRF and functional capacity of children and adolescents has declined to levels that should raise concerns from a public health perspective. Thus, the development of strategies to promote a physically active lifestyle in youth is more relevant than ever.

Actin is among the most abundant proteins in eukaryotic cells and assembles into dynamic filamentous networks regulated by many actin binding proteins. The actin cytoskeleton must be finely tuned, both in space and time, to fulfill key cellular functions such as cell division, cell shape changes, phagocytosis and cell migration. While actin oxidation by reactive oxygen species (ROS) at non-physiological levels are known for long to impact on actin polymerization and on the cellular actin cytoskeleton, growing evidence shows that direct and reversible oxidation/reduction of specific actin amino acids plays an important and physiological role in regulating the actin cytoskeleton. In this review, we describe which actin amino acid residues can be selectively oxidized and reduced in many different ways (e.g. disulfide bond formation, glutathionylation, carbonylation, nitration, nitrosylation and other oxidations), the cellular enzymes at the origin of these post-translational modifications, and the impact of actin redox modifications both in vitro and in vivo. We show that the regulated balance of oxidation and reduction of key actin amino acid residues contributes to the control of actin filament polymerization and disassembly at the subcellular scale and highlight how improper redox modifications of actin can lead to pathological conditions.

The TULIP project (https://anr.fr/Projet-ANR-18-CE31-0023) aims to produce radioactive ion beams of short-lived neutron-deficient isotopes using fusion-evaporation nuclear reactions in an Isotope Separator On Line (ISOL) system. A Ni target was chosen to produce Rb and Sn isotopes, and was bombarded, respectively, by Ne and Cr primary beams at energies close to the Coulomb barrier. Owing to the Target Ion Source System (TISS) configuration, the operational TISS temperature had to be close to 1300°C. Several tests were performed to determine a configuration able to cope with the constraints related to the TISS, target and beam. This article presents a brief description of the TULIP principles and objectives, and the development of the Ni target.

BackgroundMyelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) are associated with cutaneous manifestations. Next-generation sequencing (NGS) is a tool capable of identifying clonal myeloid cells in the skin infiltrate and thus better characterize the link between hematological diseases and skin lesions.ObjectiveTo assess whether skin lesions of MDS/CMML are clonally related to blood or bone marrow cells using NGS.MethodsComparisons of blood or bone marrow and skin samples NGS findings from patients presenting with MDS/CMML and skin lesions in three French hospitals.ResultsAmong the 14 patients recruited, 12 patients (86%) had mutations in the skin lesions biopsied, 12 patients (86%) had a globally similar mutational profile between blood/bone marrow and skin, and 10 patients (71%) had mutations with a high variant allele frequency (>10%) found in the myeloid skin infiltrate. Mutations in TET2 and DNMT3A, both in four patients, were the most frequent. Two patients harbored a UBA1 mutation on hematopoietic samples.LimitationsLimited number of patients and retrospective collection of the data. Blood and skin sampling were not performed at the exact same time point for two patients.ConclusionSkin lesions in the setting of MDS/CMML are characterized by a clonal myeloid infiltrate in most cases.

A hyperspectral image provides fine details about the scene under analysis, due to its multiple bands. However, the resulting high dimensionality in the feature space may render a classification task unreliable, mainly due to overfitting and the Hughes phenomenon. In order to attenuate such problems, one can resort to dimensionality reduction (DR). Thus, this paper proposes a new DR algorithm, which performs an unsupervised band selection technique following a clustering approach. More specifically, the data set was split into a predefined number of clusters, after which the bands were iteratively selected based on the parameters of a separating hyperplane, which provided the best separation in the feature space, in a one-versus-all scenario. Then, a fine-tuning of the initially selected bands took place based on the separability of clusters. A comparison with five other state-of-the-art frameworks shows that the proposed method achieved the best classification results in 60% of the experiments.

High electronic excitations in radiation of metallic targets with swift heavy ion beams at the coulomb barrier play a dominant role in the damaging processes of some metals. The inelastic thermal spike model was developed to describe tracks in materials and is applied in this paper to some systems beams/targets employed recently in some nuclear physics experiments. Taking into account the experimental conditions and the approved electron-phonon coupling factors, the results of the calculation enable to interpret the observation of the fast deformation of some targets.

Hyperspectral images provide rich spectral details of the observed scene by exploiting contiguous bands. But, the processing of such images becomes heavy, due to the high dimensionality. Thus, band selection is a practice that has been adopted before any further processing takes place. Therefore, in this paper, a new unsupervised method for band selection based on clustering and neural network is proposed. A comparison with six other band selection frameworks shows the strength of the proposed method.

Infection of mice with Citrobacter rodentium serves as a model to study human intestinal infections. C. rodentium infection leads to increased production of inflammatory cytokines, immune cell infiltration and damage to the gut barrier. We used this model of colitis to evaluate the therapeutic properties of OM-X®, an extract prepared by fermentation of vegetables, seaweeds, fruits and mushrooms. Administration of OM-X® to C. rodentium-infected mice reduced damage to the intestinal epithelium, lowered inflammation scores, increased IL-10 expression and maintained FoxP3 gene expression. OM-X® also partially prevented bacterial translocation, increased expression of tight junction genes and increased proliferation of epithelial cells. PCR analysis of stool samples showed that OM-X® significantly reduced the populations of bacteria harboring buk gene (mostly Clostridium species). It is suggested that alterations of microbiota composition, following OM-X® consumption, contribute to protection against infection and epithelial damage, and lead to an increased expression of anti-inflammatory cytokines.

Objective: To evaluate the effectiveness of footwear, foot orthoses and training-related strategies to prevent lower extremity bone stress injury (BSI). Design: Systematic review and meta-analysis. Data sources: Four bibliographic databases (from inception until November 2021): Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and CINAHL. Eligibility criteria: Randomised controlled trials (RCTs) that assessed the risk of developing a BSI when using particular footwear, foot orthoses or training-related strategies such as muscle strengthening, stretching, and mechanical loading exercises. Results: Eleven studies were included in this systematic review. When wearing foot orthoses, the risk ratio of developing a BSI on any lower extremity bone is 0.47 (95% CI 0.26 to 0.87; p = 0.02). When doing pre-exercise dynamic stretching, the risk ratio of suffering a tibial BSI is 1.06 (95% CI 0.67 to 1.68; p = 0.79). No meta-analyses could be performed for footwear or training-related strategies. The quality of evidence for all these results is low considering the high risk of bias in each study, the low number of studies and the low number of cases in each study. Conclusion: This systematic review reveals the lack of high-quality studies in BSI prevention. Based on studies at high risk of bias, foot orthoses could potentially help prevent BSIs in the military setting. It is still unknown whether footwear and training-related strategies have any benefits. It is crucial to further investigate potential BSI prevention strategies in women and athletes. Research is also needed to assess the influence of running shoes and loading management on BSI incidence. [ABSTRACT FROM AUTHOR]

* BACKGROUND: Decision rules (eg, Canadian computed tomography head rule [CCHR] for adults and Pediatric Emergency Care Applied Research Network [PECARN] rule for children/adolescents) are used in emergency settings (emergency room [ER] rules) to assess traumatic brain injuries (TBIs). The rules have a high-sensitivity and nearperfect negative predictive value that help to rule out more severe TBI. * CLINICAL QUESTION: Which criteria should be added to the Sport Concussion Assessment Tool 5 (SCAT5) to reach the sensitivity of the ER rules and improve the utility of the SCAT5 for screening for higher-severity head and brain injuries? * KEY RESULTS: We performed a comparative analysis of the SCAT5 with the CCHR and PECARN rules. We compared the presence (yes or no) and comparative "face value" sensitivity (lower, identical, or higher) of the SCAT5 criteria to the ER rules criteria. Loss of consciousness, vomiting, severe/ increasing headache, and seizure are SCAT "red flags" with similar or higher sensitivity compared to ER rules criteria. Five criteria had lower sensitivity or were absent from the SCAT. Emergency room rules include any abnormality on the Glasgow Coma Scale (GCS<15), but only a "deterioration of the state of consciousness" is considered a "red flag" in the SCAT5. Persistent retrograde amnesia for more than 30 minutes, age >65, severity of the mechanism of injury, and signs of skull fractures are not mentioned in the SCAT5. * CLINICAL APPLICATION: We identified 5 criteria that could inform the evolution the SCAT5 to improve its ability to rule out more severe TBI in a sideline assessment context. [ABSTRACT FROM AUTHOR]

Maritime space is often considered to be no longer a challenge for the major companies involved in liner shipping. Shipping lines have achieved a degree of maturity that results in a standardisation of services. They deploy vessels of similar size, serve global markets through their hub and spoke networks, take part in alliances and serve a limited number of major ports of call. From this point of view globalisation produces homogeneity.The aim of this paper is to differentiate the carriers between them by analysing the individual shipping networks of the 26 largest container shipping lines in 2002. Far from being uniform, their networks differ substantially one from another. The system of alliances hide the fragility of the Asiatic shipping lines which are highly dependent on their respective domestic market. They are faced by three European lines who act outside every alliance: Maersk, MSC and CMA-CGM. Besides the common factors related to their recent very strong growth, they are characterised by innovative maritime networks which are truly trans-national as they neither completely depend on the east-west circumterrestrial route, nor on the captive domestic markets.

Ports that are able to offer scale economies on land by using combined transport gain a competitive advantage in their port range. The recent rapid expansion of combined waterway-road services at French ports, Le Havre and Marseille, led us to carry out a theoretical and empirical analysis of the causes and conditions that underline this development. In order to more clearly understand the dynamics of the French situation, attention has been broadened to include other competing European ports, Antwerp and Rotterdam. The four-stage theoretical model highlights the interdependence between the setting up of combined waterway-road services, the competition between ports and the competition between shipping lines.

To describe ocular anomalies (OAs) in children and fetuses in a French general population, to estimate their prevalence, and to investigate a possible association between prenatal medication exposure and the occurrence of OA in utero or in early childhood. We conducted a case-control study using the EFEMERIS cohort, a database containing pregnancies registered in Haute-Garonne and their outcomes. We collected OA descriptions of fetuses at the time of pregnancy termination or of children at birth and the results of eye examinations of children at 9 months and 2 years of age. The prevalence of overall OAs was 2.13%, of which 0.04% were congenital ocular malformations (COMs). A total of 2,968 cases and 136,619 controls were selected for analysis. There was a significant difference between the two groups with regard to prenatal exposure to medications for the digestive tract and metabolism, the cardiovascular system, and the respiratory system. Multivariable analysis revealed an increased risk of OA in children of mothers exposed to magnesium during and 1 month before pregnancy (OR = 1.24; 95% CI, 1.11-1.38). This first pharmaco-epidemiological study on OA in France suggests that OA may be associated with exposure to commonly used medications. Given the rarity of COM, larger, international studies are warranted. [ABSTRACT FROM AUTHOR]