Polysaccharides Cell Wall Architecture of Mucorales

Invasive fungal infections are some of the most life-threatening infectious diseases in the hospital setting. In industrialized countries, the most common fungal species isolated from immunocompromised patients are Candida and Aspergillus spp. However, the number of infections due to Mucorales spp. is constantly increasing and little is known about the virulence factors of these fungi. The fungal cell wall is an important structure protecting fungi from the environment. A better knowledge of its composition should improve our understanding of host-pathogen interactions. Cell wall molecules are involved in tissue adherence, immune escape strategies, and stimulation of host defenses including phagocytosis and mediators of humoral immunity. The fungal cell wall is also a target of choice for the development of diagnostic or therapeutic tools. The present review discusses our current knowledge on the cell wall structure of Mucorales in terms of the polysaccharides and glyco-enzymes involved in its biosynthesis and degradation, with an emphasis on the missing gaps in our knowledge

Megathrust friction determined from mechanical analysis of the forearc in the Maule earthquake area

The seismogenic potential of a given fault depends essentially on its frictional properties and on the mechanical properties of the medium. Determining the spatio-temporal variations of frictional properties is therefore a key issue in seismotectonics. This study aims to characterize the friction on the South America megathrust in the 2010 Mw 8.8 Maule earthquake area from mechanical analysis of the forearc structure and morphology. Based on the critical taper theory, we first show that the rupture area of the Maule earthquake, also shown to be locked in the interseismic period, coincides with the stable part of the wedge. In the surrounding area, the wedge is critical, a finding consistent with various evidence for active deformation there. This is in particular true for the Arauco Peninsula area which seems to have arrested the Maule earthquakeʼs rupture to the South. This observation lends support to the view that the seismic rupture is inhibited when propagating beneath a critical area. The geometry of the critical portion of the wedge suggests a standard internal friction (μ_(int)=0.7±0.13) and a hydrostatic pore pressure within the wedge. The effective friction beneath the critical outer wedge is estimated to be µ^(eff)_b = 0.7 ± 0.13. This could be related to intrinsically low friction minerals (clay) or high pore pressure along the megathrust. We next use the limit analysis approach to constrain the variation of the effective friction along the megathrust based on the location and geometry of internal faulting within the forearc. A low effective friction is found within the rupture area (µ^(eff)_b ≤ 0.14) to explain the reactivation of thrust fault such as the Santa Maria, updip of the coseismic rupture, or the activation of normal splay faults downdip of the rupture area. The low effective friction found there could reflect strong dynamic weakening

AGATHE: A tool for personalized rehabilitation of cognitive functions

Stroke, traumatic brain injury, multiple sclerosis, Parkinson's disease, Alzheimer's... Every year in France, tens of thousands of people fall victim to one of those neurological pathologies. Acquired brain injury leads to cognitive impairment and heavy loss of autonomy. Rehabilitation interventions are needed to enable people to recover capacity and return to Activities of Daily Living (ADL), such as grocery shopping. Unfortunately, the resources made available in cognitive rehabilitation are insufficient for the growing needs of victims of brain damage. The assets of virtual reality to address this big problem of public health are today scientifically recognized [Rizzo and Kim 2005; Klinger, et al. 2010]. In this context, we designed the AGATHE tool (Adaptable, configurable and upgradable tool for the generation of personalized therapeutic applications in cognitive rehabilitation) (AGATHE project, ANR-09-TECS-002).French National Research Agency (ANR) Laval Agglomération et Conseil Général de la Mayenn

Ecosystem mapping in the Central Arctic Ocean (CAO) during the SAS-Oden expedition

As a result of global warming, the marine ecosystem around the North Pole, the Central Arctic Ocean (CAO), is in fast transition from a permanently to a seasonally ice-covered ocean. The sea-ice loss is expected to enable summer access to the CAO for non-icebreaking ships, including fishery vessels, in the near future1. However, the lack of knowledge on the CAO ecosystem impedes any assessment of the sustainability of potential future fisheries in the CAO. Taking a precautionary approach, the EU and nine countries in October 2018 signed the Agreement to Prevent Unregulated High Seas Fisheries in the Central Arctic Ocean. This agreement entered into force in June 2021 and a.o. requires the establishment of a joint scientific program to improve the understanding of the CAO ecosystem, including mapping and monitoring. To reduce the existing lack of knowledge, 12 scientists from the EFICA Consortium participated, together with 26 other on-board scientists, in sampling and data collection of ecosystem data during the Swedish SAS-Oden expedition in summer 2021. This report describes the field work performed by the EFICA scientists using water-column acoustics, deep-sea optical observations, and fish, zooplankton, sediment otolith and eDNA sampling for targeting fish, zooplankton and mammals. Further ecosystem data (physical, chemical and biological) were collected by the EFICA scientists in collaboration with other scientists on-board. Together with this report, a metadata database containing lists of all collected samples and data that are relevant for future fish-stock modelling and assessment studies was delivered to the European Commission

AGATHE: A tool for personalized rehabilitation of cognitive functions

Stroke, traumatic brain injury, multiple sclerosis, Parkinson's disease, Alzheimer's... Every year in France, tens of thousands of people fall victim to one of those neurological pathologies. Acquired brain injury leads to cognitive impairment and heavy loss of autonomy. Rehabilitation interventions are needed to enable people to recover capacity and return to Activities of Daily Living (ADL), such as grocery shopping. Unfortunately, the resources made available in cognitive rehabilitation are insufficient for the growing needs of victims of brain damage. The assets of virtual reality to address this big problem of public health are today scientifically recognized [Rizzo and Kim 2005; Klinger, et al. 2010]. In this context, we designed the AGATHE tool (Adaptable, configurable and upgradable tool for the generation of personalized therapeutic applications in cognitive rehabilitation) (AGATHE project, ANR-09-TECS-002).French National Research Agency (ANR) Laval Agglomération et Conseil Général de la Mayenn

The legacies of coercion and the challenges of contingency: Mozambican unions in difficult times

Although insecure work may be found everywhere, the general lack of secure work in emerging economies is a particularly striking feature of the contemporary condition, undermining the continued viability of the labour movement in such countries. Yet, this topic is rarely tackled directly in African studies or business history journals. The two key questions addressed in this paper are, first, to what extent does the labour movement’s past define their present and future, and second, what are the challenges and opportunities affecting their ability to mobilise workers, influence government and effectively tackle employment security? This article details how in Mozambique, unions’ ability to mobilise has been affected by: the post-colonial, post-conflict and post-socialist historical context; the resulting legacies of regional and racial discrimination; international imperatives for liberalisation and privatisation; challenging relationships with the country’s African neighbours; and high levels of informal sector work. In order to remain viable, key imperatives include: effectively influencing national government, engaging internationally and working with organisations representing informal sector workers

Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921). Findings: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. Interpretation: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB

Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124–159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. INTERPRETATION: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir