Search

Abstract Vitamin D deficiency is a common deficiency worldwide, particularly among women of reproductive age. During pregnancy, it increases the risk of immune-related diseases in offspring later in life. However, how the body remembers exposure to an adverse environment during development is poorly understood. Herein, we explore the effects of prenatal vitamin D deficiency on immune cell proportions in offspring using vitamin D deficient mice established by dietary manipulation. We found that prenatal vitamin D deficiency alters immune cell proportions in offspring by changing the transcriptional properties of genes downstream of vitamin D receptor signaling in hematopoietic stem and progenitor cells of both the fetus and adults. Moreover, further investigations of the associations between maternal vitamin D levels and cord blood immune cell profiles from 75 healthy pregnant women and their term offspring also confirm that maternal vitamin D levels in the second trimester significantly affect immune cell proportions in the offspring. These findings imply that the differentiation properties of hematopoiesis act as long-term memories of prenatal vitamin D deficiency exposure in later life.

Compared to conventional monoethanolamine (MEA), alternative solvents are expected to substantially contribute to reduce the energy demand of post-combustion CO2 capture from flue gases. This study presents a comprehensive techno-economic analysis of a 27 wt% 2-amino-2-methyl-1-propanol (AMP) + 13 wt% piperazine (PZ) aqueous solution for CO2 capture, compared to a 30 wt% MEA solution. The study addresses the retrofit of a carbon capture unit to a biomass-fired combined heat and power (CHP) plant, effectively making it a bioenergy with a carbon capture and storage (BECCS) system. The treated flue gas has a flow rate of 23 tons/hour (t/h) with 11.54 vol% CO2 and a 90% capture rate is aimed for. Aspen Plus V14 was employed for process simulations. Initially, binary interaction parameters for AMP/PZ, AMP/H2O, and PZ/H2O are regressed using vapor-liquid equilibrium (VLE) data, which were retrieved from literature along with reaction kinetics. Validation of parameters from available experimental literature yields an average absolute relative deviation (AARD) of only 5.9%. Afterwards, a process simulation model is developed and validated against experimental data from a reference pilot plant, using a similar AMP/PZ blend, resulting in 5% AARD. Next, a sensitivity analysis optimizes operating conditions, including solvent rate, absorber/stripper packing heights, and stripper pressure, based on regeneration energy impact. Optimized results, compared to MEA, reveal that AMP/PZ reduces the energy consumption from 3.61 to 2.86 GJ/tCO2. The retrofitting of the capture unit onto the selected CHP plant is examined through the development of a dedicated model. Two control strategies are compared to address energy unavailability for supplying the capture unit. The analysis spans 4 months, selected to account for seasonal variations. At nominal capacity, CO2 emissions, rendered negative by biomass combustion and CO2 capture, reach a maximum of −3.4 tCO2/h compared to 0.36 tCO2/h before retrofitting. Depending on the control strategy and CHP plant operating point, the Specific Primary Energy Consumption for CO2 Avoided (SPECCA) ranges from 4.91 MJ/kgCO2 to 1.76 MJ/kgCO2. Finally, an economic comparison based on systematic methodology reveals a 7.87% reduction in capture cost favoring the AMP/PZ blend. Together, these findings highlight AMP/PZ as a highly favorable alternative solvent.

Introduction Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) increases the risk of pulmonary embolism (PE). AECOPD and PE have similar symptoms which results in a high proportion of patients with AECOPD undergoing imaging to rule out PE. Finding predictors and explanatory factors of PE in AECOPD, such as purulence status, could help reduce the need for imaging. This systematic review with meta-analysis aims to evaluate if there is an association between purulence status in AECOPD and PE diagnosis.Methods and analysis MEDLINE, EMBASE and CENTRAL will be searched from database inception to April 2024. Randomised trials, cohort studies and cross-sectional studies on the prevalence of PE in patients with AECOPD will be included if the prevalence of PE based on the AECOPD purulence status is available. There will be no restriction on language. The primary outcome will be PE at the initial assessment and secondary outcomes will be all venous thromboembolism (deep venous thrombosis (DVT) and PE) and DVT, respectively, diagnosed at the initial assessment. Relative risks with their 95% CI will be calculated by using a Mantel-Haenszel random-effect model to compare the association between the risk of PE and the AECOPD purulence status (purulent vs non-purulent/unknown). Subgroup analyses will be performed based on the type of study, systematic search of PE versus no systematic search of PE and localisation of PE. Risk of bias will be evaluated by the ROBINS-E tool, publication bias will be evaluated with the funnel plot. The manuscript will be drafted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement.Ethics and dissemination This study does not require ethics approval. This work will be submitted for presentation at an international conference and for publication in a peer-reviewed journal.PROSPERO registration number CRD42023459429.

Introduction Pulmonary embolism (PE) is a challenge to diagnose and when missed, exposes patients to potentially fatal recurrent events. Beyond CT pulmonary angiography (CTPA) and planar ventilation/perfusion (V/Q) scan, single photon emission CT (SPECT) V/Q emerged a new diagnostic modality of scintigraphic acquisition that has been reported to improve diagnostic performances. To date, no management outcome study or randomised trial evaluated an algorithm based on SPECT V/Q for PE diagnosis. We present the design of a randomised multicentre, international management study comparing SPECT V/Q with validated strategies.Material and methods We will include a total of 3672 patients with suspected PE requiring chest imaging, randomised into three different groups, each using a different diagnostic strategy based on SPECT V/Q, CTPA and planar V/Q scan. Randomisation will be unbalanced (2:1:1), with twice as many patients in SPECT V/Q arm (n=1836) as in CTPA and planar V/Q arms (n=918 in each). Our primary objective will be to determine whether a diagnostic strategy based on SPECT V/Q is non-inferior to previously validated strategies in terms of diagnostic exclusion safety as assessed by the 3-month risk of thromboembolism in patients with a negative diagnostic workup. Secondary outcomes will be the proportion of patients diagnosed with PE in each arm, patients requiring additional tests, the incidence of major and clinically relevant non-major bleeding and the incidence and cause of death in each arm.Ethics and dissemination This trial is funded by a grant from Brest University Hospital and by INVENT. The study protocol was approved by Biomedical Research Ethics Committee. The investigator or delegate will obtain signed informed consent from all patients prior to inclusion in the trial. Our results will inform future clinical practice guidelines and solve the current discrepancy between nuclear medicine guidelines and clinical scientific society guidelines.Trial registration number NCT02983760

Not available.

Abstract Clinical immunity against Plasmodium falciparum infection develops in residents of malaria endemic regions, manifesting in reduced clinical symptoms during infection and in protection against severe disease but the mechanisms are not fully understood. Here, we compare the cellular and humoral immune response of clinically immune (0-1 episode over 18 months) and susceptible (at least 3 episodes) during a mild episode of Pf malaria infection in a malaria endemic region of Malawi, by analysing peripheral blood samples using high dimensional mass cytometry (CyTOF), spectral flow cytometry and single-cell transcriptomic analyses. In the clinically immune, we find increased proportions of circulating follicular helper T cells and classical monocytes, while the humoral immune response shows characteristic age-related differences in the protected. Presence of memory CD4+ T cell clones with a strong cytolytic ZEB2+ T helper 1 effector signature, sharing identical T cell receptor clonotypes and recognizing the Pf-derived circumsporozoite protein (CSP) antigen are found in the blood of the Pf-infected participants gaining protection. Moreover, in clinically protected participants, ZEB2+ memory CD4+ T cells express lower level of inhibitory and chemotactic receptors. We thus propose that clonally expanded ZEB2+ CSP-specific cytolytic memory CD4+ Th1 cells may contribute to clinical immunity against the sporozoite and liver-stage Pf malaria.

Abstract Females present a higher risk of adverse drug reactions. Sex‐related differences in drug concentrations may contribute to these observations but they remain understudied given the underrepresentation of females in clinical trials. The aim of this study was to investigate whether anthropometric and socioeconomic factors and comorbidities could explain sex‐related differences in concentrations and dosing for metoprolol and oxypurinol, the active metabolite of allopurinol. We conducted an analysis of two cross‐sectional studies. Participants were self‐described “White” adults taking metoprolol or allopurinol selected from the Montreal Heart Institute Hospital Cohort. A total of 1007 participants were included in the metoprolol subpopulation and 459 participants in the allopurinol subpopulation; 73% and 86% of the participants from the metoprolol and allopurinol subpopulations were males, respectively. Females presented higher age‐ and dose‐adjusted concentrations of both metoprolol and oxypurinol (both p

Abstract Background Prevalence, risk factors and medical management of persistent pain symptoms after critical care illness have not been thoroughly investigated. Methods We performed a prospective multicentric study in patients with an intensive care unit (ICU) length of stay ≥ 48 h. The primary outcome was the prevalence of significant persistent pain, defined as a numeric rating scale (NRS) ≥ 3, 3 months after admission. Secondary outcomes were the prevalence of symptoms compatible with neuropathic pain (ID-pain score > 3) and the risk factors of persistent pain. Results Eight hundred fourteen patients were included over a 10-month period in 26 centers. Patients had a mean age of 57 (± 17) years with a SAPS 2 score of 32 (± 16) (mean ± SD). The median ICU length of stay was 6 [4–12] days (median [interquartile]). At 3 months, the median intensity of pain symptoms was 2 [1–5] in the entire population, and 388 (47.7%) patients had significant pain. In this group, 34 (8.7%) patients had symptoms compatible with neuropathic pain. Female (Odds Ratio 1.5 95% CI [1.1–2.1]), prior use of anti-depressive agents (OR 2.2 95% CI [1.3–4]), prone positioning (OR 3 95% CI [1.4–6.4]) and the presence of pain symptoms on ICU discharge (NRS ≥ 3) (OR 2.4 95% CI [1.7–3.4]) were risk factors of persistent pain. Compared with sepsis, patients admitted for trauma (non neuro) (OR 3.5 95% CI [2.1–6]) were particularly at risk of persistent pain. Only 35 (11.3%) patients had specialist pain management by 3 months. Conclusions Persistent pain symptoms were frequent in critical illness survivors and specialized management remained infrequent. Innovative approaches must be developed in the ICU to minimize the consequences of pain. Trial registration. NCT04817696. Registered March 26, 2021.

As we celebrate the 20th anniversary of the digital journal e-Rea, this paper aims to look back to the issues of this journal from a statistical perspective. It analyses significant data and figures such as the quantity of published articles or book reviews, with a view to shedding light on editorial choices as seen over the years in the emergence of new sections. Visitor statistics highlight the internationalization of the journal and its increasing visibility in the field of English studies.

In the wake of the celebration of the 20th anniversary of the digital journal e-Rea, this paper aims to look back to issue number 17.2 entitled “Reported speech and the expression of subjectivity”, which was published in this journal in June 2020. Presenting the research topic and the different theoretical approaches selected for the volume, it links this publication to current research on reported speech, especially discourse analysis based on digital posts from social media.

Abstract Background Genetic diversity is a necessary condition for populations to evolve under natural adaptation, artificial selection, or both. However, genetic diversity is often threatened, in particular in domestic animal populations where artificial selection, genetic drift and inbreeding are strong. In this context, cryopreserved genetic resources are a promising option to reintroduce lost variants and to limit inbreeding. However, while the use of ancient genetic resources is more common in plant breeding, it is less documented in animals due to a longer generation interval, making it difficult to fill the gap in performance due to continuous selection. This study investigates one of the only concrete cases available in animals, for which cryopreserved semen from a bull born in 1977 in a lost lineage was introduced into the breeding scheme of a French local dairy cattle breed, the Abondance breed, more than 20 years later. Results We found that this re-introduced bull was genetically distinct with respect to the current population and thus allowed part of the genetic diversity lost over time to be restored. The expected negative gap in milk production due to continuous selection was absorbed in a few years by preferential mating with elite cows. Moreover, the re-use of this bull more than two decades later did not increase the level of inbreeding, and even tended to reduce it by avoiding mating with relatives. Finally, the reintroduction of a bull from a lost lineage in the breeding scheme allowed for improved performance for reproductive abilities, a trait that was less subject to selection in the past. Conclusions The use of cryopreserved material is an efficient way to manage the genetic diversity of an animal population, by mitigating the effects of both inbreeding and strong selection. However, attention should be paid to mating of animals to limit the disadvantages associated with incorporating original genetic material, notably a discrepancy in the breeding values for selected traits or an increase in inbreeding. Therefore, careful characterization of the genetic resources available in cryobanks could help to ensure the sustainable management of populations, in particular local or small populations. These results could also be transferred to the conservation of wild threatened populations.

Abstract Background Global warming raises serious concerns about the persistence of species and populations locally adapted to their environment, simply because of the shift it produces in their adaptive landscape. For instance, the phenological cycle of tree species may be strongly affected by higher winter temperatures and late frost in spring. Given the variety of ecosystem services they provide, the question of forest tree adaptation has received increasing attention in the scientific community and catalyzed research efforts in ecology, evolutionary biology and functional genomics to study their adaptive capacity to respond to such perturbations. Results In the present study, we used an elevation gradient in the Pyrenees Mountains to explore the gene expression network underlying dormancy regulation in natural populations of sessile oak stands sampled along an elevation cline and potentially adapted to different climatic conditions mainly driven by temperature. By performing analyses of gene expression in terminal buds we identified genes displaying significant dormancy, elevation or dormancy-by-elevation interaction effects. Our Results highlighted that low- and high-altitude populations have evolved different molecular strategies for minimizing late frost damage and maximizing the growth period, thereby increasing potentially their respective fitness in these contrasting environmental conditions. More particularly, population from high elevation overexpressed genes involved in the inhibition of cell elongation and delaying flowering time while genes involved in cell division and flowering, enabling buds to flush earlier were identified in population from low elevation. Conclusion Our study made it possible to identify key dormancy-by-elevation responsive genes revealing that the stands analyzed in this study have evolved distinct molecular strategies to adapt their bud phenology in response to temperature.

Abstract Small studies suggest that amiodarone is a weak inhibitor of cytochrome P450 (CYP) 2D6. Inhibition of CYP2D6 leads to increases in concentrations of drugs metabolized by the enzyme, such as metoprolol. Considering that both metoprolol and amiodarone have β‐adrenergic blocking properties and that the modest interaction between the two drugs would result in increased metoprolol concentrations, this could lead to a higher risk of bradycardia and atrioventricular block. The primary objective of this study was to evaluate whether metoprolol plasma concentrations collected at random timepoints from patients enrolled in the Montreal Heart Institute Hospital Cohort could be useful in identifying the modest pharmacokinetic interaction between amiodarone and metoprolol. We performed an analysis of a cross‐sectional study, conducted as part of the Montreal Heart Institute Hospital Cohort. All participants were self‐described “White” adults with metoprolol being a part of their daily pharmacotherapy regimen. Of the 999 patients being treated with metoprolol, 36 were also taking amiodarone. Amiodarone use was associated with higher metoprolol concentrations following adjustment for different covariates (p = .0132). Consistently, the association between amiodarone use and lower heart rate was apparent and significant after adjustment for all covariates under study (p = .0001). Our results highlight that single randomly collected blood samples can be leveraged to detect modest pharmacokinetic interactions.