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Muscle aging is associated with a consistent decrease in the ability of muscle tissue to regenerate following intrinsic muscle degradation, injury or overuse. Age‐related imbalance of protein synthesis and degradation, mainly regulated by AKT/mTOR pathway, leads to progressive loss of muscle mass. Maintenance of anabolic and regenerative capacities of skeletal muscles may be regarded as a therapeutic option for sarcopenia and other muscle wasting diseases. Our previous studies have demonstrated that BIO101, a pharmaceutical grade 20‐hydroxyecdysone, increases protein synthesis through the activation of MAS receptor involved in the protective arm of renin‐angiotensin‐aldosterone system. The purpose of the present study was to assess the anabolic and pro‐differentiating properties of BIO101 on C2C12 muscle cells in vitroand to investigate its effects on adult and old mice models in vivo. The effects of BIO101 on C2C12 differentiation were assessed using myogenic transcription factors and protein expression of major kinases of AKT/mTOR pathway by Western blot. The in vivoeffects of BIO101 have been investigated in BIO101 orally‐treated (50 mg/kg/day) adult mice (3 months) for 28 days. To demonstrate potential beneficial effect of BIO101 treatment in a sarcopenic mouse model, we use orally treated 22‐month‐old C57Bl6/J mice, for 14 weeks with vehicle or BIO101. Mice body and muscle weight were recorded. Physical performances were assessed using running capacity and muscle contractility tests. Anabolic properties of BIO101 were confirmed by the rapid activation of AKT/mTOR, leading to an increase of C2C12 myotubes diameters (+26%, P< 0.001). Pro‐differentiating effects of BIO101 on C2C12 myoblasts were revealed by increased expression of muscle‐specific differentiation transcription factors (MyoD, myogenin), resulting in increased fusion index and number of nuclei per myotube (+39% and +53%, respectively, at day 6). These effects of BIO101 were like those of angiotensin (1–7) and were abolished with the use of A779, a MAS receptor specific antagonist. Chronic BIO101 oral treatment induced AKT/mTOR activation and anabolic effects accompanied with improved physical performances in adult and old animals (maximal running distance and maximal running velocity). Our data suggest beneficial anabolic and pro‐differentiating effects of BIO101 rendering BIO101 a potent drug candidate for treating sarcopenia and possibly other muscle wasting disorders.

Virtual reality (VR) is gaining more and more interest in multidisciplinary early design activities, from eliciting stakeholder needs to designing a system architecture. The design of a system architecture can be simplified as the definition of three views: functional, behavioural, and structural. The geometric modelling capabilities needed for the embodiment design are still based on desktop-based parametric CAD models, which were eventually transformed into a polyhedral model that can be visualised in VR. When a multidisciplinary team gets together to generate candidate design architecture, they need to create conceptual 3D shapes and determine the layout of components. In this paper, we propose the Virtual Reality Shape Modelling (VRSM) environment for the immersive direct modelling of 3D shapes in VR. VRSM integrates the open-source FreeCAD shape modeller with the game engine Unity. FreeCAD enables the user to capture the history of feature-based operations and to create a parametric representation needed for detailed CAD activities, whereas Unity allows the interaction with polyhedral models in a 3D environment. The current version of VRSM offers modelling capabilities to create, delete, move and resize canonical shapes and apply Boolean operators on a polyhedral model in VR. At the same time, the parametric definition in FreeCAD evolves synchronously.

This study aimed to investigate renal replacement therapy (RRT) practices in a representative nationwide sample of French intensive care units (ICUs).

White-matter injury leads to severe functional loss in many neurological diseases. Myelin staining on histological samples is the most common technique to investigate white-matter fibers. However, tissue processing and sectioning may affect the reliability of 3D volumetric assessments. The purpose of this study was to propose an approach that enables myelin fibers to be mapped in the whole rodent brain with microscopic resolution and without the need for strenuous staining. With this aim, we coupled in-line (propagation-based) X-ray phase-contrast tomography (XPCT) to ethanol-induced brain sample dehydration. We here provide the proof-of-concept that this approach enhances myelinated axons in rodent and human brain tissue. In addition, we demonstrated that white-matter injuries could be detected and quantified with this approach, using three animal models: ischemic stroke, premature birth and multiple sclerosis. Furthermore, in analogy to diffusion tensor imaging (DTI), we retrieved fiber directions and DTI-like diffusion metrics from our XPCT data to quantitatively characterize white-matter microstructure. Finally, we showed that this non-destructive approach was compatible with subsequent complementary brain sample analysis by conventional histology. In-line XPCT might thus become a novel gold-standard for investigating white-matter injury in the intact brain. This is Part I of a series of two articles reporting the value of in-line XPCT for virtual histology of the brain; Part II shows how in-line XPCT enables the whole-brain 3D morphometric analysis of amyloid-β (Aβ) plaques.

We examine relationships between interviewers’ nonverbal behaviors and adequate responding in face-to-face survey interviews. We videotaped professional interviewers administering face-to-face survey interviews and coded them for three interviewer nonverbal behaviors: smiling, nodding, and direct gaze. These nonverbal interviewer behaviors were associated with significant increases in the frequency of respondents’ adequate responses. Moreover, the nonverbal behaviors were equally likely to present in standardized and unstandardized utterances. These results suggest that interviewers’ nonverbal behaviors positively correlate with adequate responding without deviating from standardized interview protocols. We discuss implications for survey theory and interviewer training.

•Heat exchangers were produced using the Vacuum Bag Resin Transfer Moulding method.•Silicon Carbide powder was added to the matrix to improve thermal conductivity.•Fire-retardant coating was applied to the samples to enhance thermal protection.•The addition of powders and coatings significantly improves thermal properties.

Low reactive oxygen species (ROS) levels are well‐established characteristics of mouse hematopoietic stem cells (HSCs). However, little is known about these levels in human HSCs. This study aimed at quantifying ROS levels in human CD34+CD38lowand CD34+CD38highhuman progenitors from bone marrow, cord blood and cells mobilized for autologous HSC transplantation. A specifically devised multiparameter flow cytometry method was used to quantify ROS levels (H2DCFDA staining) in sub‐populations of primary cells. Results were confirmed by assessing gene expression level of the ROS scavenger GPX3,a key determinant of HSC self‐renewal, in sorted CD34+CD38lowand CD34+CD38highcells. CD34+CD38lowcells from bone marrow and cord blood displayed significantly lower levels of ROS than CD34+CD38highcells and other leukocytes. Moreover, the correlation between ROS and GPX3expression was verified in sorted CD34+CD38lowand CD34+CD38highcells. These results confirm, in human, data previously reported in mice. Moreover, the flow cytometry assay we developed could allow for a more precise enumeration of repopulating primitive progenitors in the course of HSC transplantation.

Clonal hematopoiesis (CH) of indeterminate potential has been described in blood samples from large series of patients. Its prevalence and consequences are still not well understood because sequencing methods vary and because most studies were performed in cohorts comprising individuals with nonhematologic diseases. Here, we investigated the frequency of CH in 82 paired bone marrow and blood samples from carefully selected healthy adult volunteers. Forty-one genes known to be mutated in myeloid malignancies were sequenced with a 1% threshold of detection. In bone marrow samples, clones were found in almost 40% of healthy volunteers more than 50 years old. The most frequent mutations were found in DNMT3A and TET2, with 1 individual carrying 3 variants. Variant allele frequencies were highly concordant between blood and bone marrow samples. Blood parameters were normal except for those in 2 individuals: 1 had a mild macrocytosis and 1 had a mild thrombocytosis. Furthermore, no morphologic abnormalities or dysplasia were detected when bone marrow smears were carefully evaluated. Individuals with CH differed from others by age (62.8 vs 38.6 years; P < .0001) and platelet count (294 vs 241 ×109/L; P = .0208), the latter being no more significant when removing the 2 individuals who carried the JAK2 p.V617F mutation. These results confirm that CH is a very common condition in healthy adults over 50 years old. Consequently, the detection of driver myeloid mutations should be interpreted with caution in the absence of cytologic abnormalities in the blood and/or the bone marrow.

Clonal hematopoiesis (CH) of indeterminate potential has been described in blood samples from large series of patients. Its prevalence and consequences are still not well understood because sequencing methods vary and because most studies were performed in cohorts comprising individuals with nonhematologic diseases. Here, we investigated the frequency of CH in 82 paired bone marrow and blood samples from carefully selected healthy adult volunteers. Forty-one genes known to be mutated in myeloid malignancies were sequenced with a 1% threshold of detection. In bone marrow samples, clones were found in almost 40% of healthy volunteers more than 50 years old. The most frequent mutations were found in DNMT3Aand TET2, with 1 individual carrying 3 variants. Variant allele frequencies were highly concordant between blood and bone marrow samples. Blood parameters were normal except for those in 2 individuals: 1 had a mild macrocytosis and 1 had a mild thrombocytosis. Furthermore, no morphologic abnormalities or dysplasia were detected when bone marrow smears were carefully evaluated. Individuals with CH differed from others by age (62.8 vs 38.6 years; P< .0001) and platelet count (294 vs 241 ×109/L; P= .0208), the latter being no more significant when removing the 2 individuals who carried the JAK2p.V617F mutation. These results confirm that CH is a very common condition in healthy adults over 50 years old. Consequently, the detection of driver myeloid mutations should be interpreted with caution in the absence of cytologic abnormalities in the blood and/or the bone marrow.

•Many proton pump inhibitors prescriptions are in discordance with the guidelines.•Hospitalisation can be an opportunity for global medication reassessment.•Awareness sessions can improve proton pump inhibitors prescriptions.•Collaboration between physicians and pharmacists optimizes the care of patients.

The bone marrow (BM) niche impacts the progression of acute myeloid leukemia (AML) by favoring the chemoresistance of AML cells. Intimate interactions between leukemic cells and BM mesenchymal stromal cells (BM-MSCs) play key roles in this process. Direct intercellular communications between hematopoietic cells and BM-MSCs involve connexins, components of gap junctions. We postulated that blocking gap junction assembly could modify cell–cell interactions in the leukemic niche and consequently the chemoresistance. The comparison of BM-MSCs from AML patients and healthy donors revealed a specific profile of connexins in BM-MSCs of the leukemic niche and the effects of carbenoxolone (CBX), a gap junction disruptor, were evaluated on AML cells. CBX presents an antileukemic effect without affecting normal BM-CD34+progenitor cells. The proapoptotic effect of CBX on AML cells is in line with the extinction of energy metabolism. CBX acts synergistically with cytarabine (Ara-C) in vitro and in vivo. Coculture experiments of AML cells with BM-MSCs revealed that CBX neutralizes the protective effect of the niche against the Ara-C-induced apoptosis of leukemic cells. Altogether, these results suggest that CBX could be of therapeutic interest to reduce the chemoresistance favored by the leukemic niche, by targeting gap junctions, without affecting normal hematopoiesis.

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal stem cell disorders with an inherent tendency for transformation in secondary acute myeloid leukemia. This study focused on the redox metabolism of bone marrow (BM) cells from 97 patients compared with 25 healthy controls. The level of reactive oxygen species (ROS) was quantified by flow cytometry in BM cell subsets as well as the expression level of 28 transcripts encoding for major enzymes involved in the antioxidant cellular response. Our results highlight increased ROS levels in BM nonlymphoid cells and especially in primitive CD34posCD38low progenitor cells. Moreover, we identified a specific antioxidant signature, dubbed “antioxidogram,” for the different MDS subgroups or secondary acute myeloblastic leukemia (sAML). Our results suggest that progression from MDS toward sAML could be characterized by 3 successive molecular steps: (1) overexpression of enzymes reducing proteic disulfide bonds (MDS with <5% BM blasts [GLRX family]); (2) increased expression of enzymes detoxifying H2O2 (MDS with 5% to 19% BM blasts [PRDX and GPX families]); and finally (3) decreased expression of these enzymes in sAML. The antioxidant score (AO-Score) defined by logistic regression from the expression levels of transcripts made it possible to stage disease progression and, interestingly, this AO-Score was independent of the revised International Scoring System. Altogether, this study demonstrates that MDS and sAML present an important disturbance of redox metabolism, especially in BM stem and progenitor cells and that the specific molecular antioxidant response parameters (antioxidogram, AO-Score) could be considered as useful biomarkers for disease diagnosis and follow-up.

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal stem cell disorders with an inherent tendency for transformation in secondary acute myeloid leukemia. This study focused on the redox metabolism of bone marrow (BM) cells from 97 patients compared with 25 healthy controls. The level of reactive oxygen species (ROS) was quantified by flow cytometry in BM cell subsets as well as the expression level of 28 transcripts encoding for major enzymes involved in the antioxidant cellular response. Our results highlight increased ROS levels in BM nonlymphoid cells and especially in primitive CD34posCD38lowprogenitor cells. Moreover, we identified a specific antioxidant signature, dubbed “antioxidogram,” for the different MDS subgroups or secondary acute myeloblastic leukemia (sAML). Our results suggest that progression from MDS toward sAML could be characterized by 3 successive molecular steps: (1) overexpression of enzymes reducing proteic disulfide bonds (MDS with <5% BM blasts [GLRX family]); (2) increased expression of enzymes detoxifying H2O2(MDS with 5% to 19% BM blasts [PRDX and GPX families]); and finally (3) decreased expression of these enzymes in sAML. The antioxidant score (AO-Score) defined by logistic regression from the expression levels of transcripts made it possible to stage disease progression and, interestingly, this AO-Score was independent of the revised International Scoring System. Altogether, this study demonstrates that MDS and sAML present an important disturbance of redox metabolism, especially in BM stem and progenitor cells and that the specific molecular antioxidant response parameters (antioxidogram, AO-Score) could be considered as useful biomarkers for disease diagnosis and follow-up.

•In 2022, the study enrolled 819 patients from Serbia and North Macedonia.•Subclinical bacteremia occurred in 8.06% of cases, primarily with Anaplasmaspp.•Uncharacterized Rickettsiaspp. and SFGR were dominant in North Macedonia and Serbia.•Phylogenetic analysis revealed high genetic diversity among the identified pathogens.

Peu valorisé et exposé à la précarité, le métier dit « de deuxième ligne » des caissier.es a vu ses conditions de travail se dégrader durant la crise du Covid-19. Prenant appui sur la littérature propre au sens du travail, à l’activité des caissier.es et aux effets du Covid sur les carrières, l’étude prévoyait que le sens donné au travail proviendrait essentiellement des interactions avec les client.es et de l’utilité sociale perçue. Il était aussi attendu que le sens se modifierait durant la crise du Covid-19, et que cette dernière aurait des effets sur les projections de carrière. La double analyse, automatisée via Iramuteq et manuelle, d’entretiens collectés chez des caissier.es à deux reprises durant les premier (n=10) et troisième confinements (n=7) confirme l’importance et l’ambivalence des interactions avec la clientèle dans le sens trouvé au travail de même que l’évolution du sens et des projections de carrière entre les deux confinements.

Germinal activity persists throughout life within the ventricular-subventricular zone (V-SVZ) of the postnatal forebrain, due to the presence of neural stem cells (NSCs). Accumulating evidence points at a recruitment for these cells following early brain injuries, and suggest their amenability to manipulations.

Background and Aims: Early detection and advancement in cancer treatments have drastically improved survivorship. Hence, there is a shift towards long-term quality of life goals such as protecting the oncologic patient’s fertility potential. The study aims to determine the uptake and use of fertility preservation options in women presenting at a tertiary institution in Singapore. This is the first review to outline the uptake rates, methods and fertility outcomes among women undergoing fertility preservation in Singapore.Method: The study is a retrospective review of premenopausal female patients presenting to a single tertiary institution between 2010 and 2019 for fertility preservation. Our primary outcome measures are the uptake rate, type of fertility preservation undertaken and live birth rate. Our secondary outcome are reasons for decline of fertility preservation.Results: Forty-one patients were referred between 2010 and 2019. There were 2 referrals received in 2010 compared to 10 referrals in 2019. Twenty-nine patients underwent fertility preservation procedures, with 27 (93.1%) successful fertility preservation procedures performed. Most of the patients opted for embryo cryopreservation (44.4%) or oocyte cryopreservation (33.3%). Three patients (11.1%) underwent ovarian tissue cryopreservation. Two patients (7.4%) opted for a combination of oocyte and embryo cryopreservation and 1 patient (3.7%) had a combination of ovarian tissue and oocyte cryopreservation. There were 3 successful live births. One patient achieved a live birth from stored embryos achieved from in-vitro maturation subsequent fertilisation. The other two patients achieved live births from stored embryos and oocytes respectively. The most commonly cited reason for declining fertility preservation was financial limitations (41.7%).Conclusion: While the referral rates have been increasing over the years, the rates remain low. Further studies can be done to assess the barriers to fertility preservation referrals. Funding for fertility preservation procedures may increase uptake in this group of women.

Les femmes qui allaitent se retrouvent souvent seules face à leurs questionnements. Le soutien par les pairs est l’une des clés de la réussite de l’allaitement maternel. Des associations, comme Galactée, créée en 1982 de la rencontre de deux femmes qui désiraient partager leur expérience, proposent une écoute et des conseils de mères à mères.

Tomographic diffractive microscopy (TDM) has gained interest in recent years due to its ability to deliver high-resolution, three-dimensional images of unlabeled samples. It has been applied to transparent samples in transmission mode, as well as to surface studies in reflection mode. Mudry et al. [Opt. Lett.35, 1857 (2010)OPLEDP0146-959210.1364/OL.35.001857] introduced the concept of mirror-assisted TDM (MA-TDM), an elegant approach for achieving quasi-isotropic-resolution microscopic imaging, but which is still to be experimentally applied. In this work, we show that a simplified version of MA-TDM allows for transforming a reflective TDM setup into a more versatile instrument, also capable of observing transparent samples in transmission mode if using specific sample holders made out of a mirror and coated with a low-thickness transparent spacer.

Background: Vitamin D insufficiency is associated with brain changes, and cognitive and mobility declines in older adults. Objective: Our objective was to investigate in older adults whether vitamin D insufficiency<50nmol/L was associated with thinner cingulate cortex, a brain area related to cognitive functions influenced by vitamin D. Methods: Two hundred and fifteen Caucasian older community-dwellers (mean±SD, 72.1±5.5years; 40% female) received a blood test and brain MRI. The thickness of perigenual anterior cingulate cortex, midcingulate cortex and posterior cingulate cortex was measured using FreeSurfer from T1-weighted MR images. Age, gender, education, BMI, mean arterial pressure, comorbidities, use of vitamin D supplements or anti-vascular drugs, MMSE, GDS, IADL, serum calcium and vitamin B9 concentrations, creatinine clearance were used as covariables. Results: Participants with vitamin D insufficiency (n=80) had thinner total cingulate thickness than the others (24.6±1.9mm versus 25.3±1.4mm, P=0.001); a significant difference found for all 3 regions. Vitamin D insufficiency was cross-sectionally associated with a decreased total cingulate thickness (β=- 0.49, P=0.028). Serum 25OHD concentration correlated positively with the thickness of perigenual anterior (P=0.011), midcingulate (P=0.013) and posterior cingulate cortex (P=0.021). Conclusion: Vitamin D insufficiency was associated with thinner cingulate cortex in the studied sample of older adults. These findings provide insight into the pathophysiology of cognitive and mobility declines in older adults with vitamin D insufficiency.

ObjectiveThe primary objective is to compare miscarriage rates in frozen-thawed embryo transfer (FET) cycles, according to the endometrial preparation used either artificial through the administration of exogenous estrogen and progesterone or natural without any treatment, during a spontaneous ovulatory cycle. The secondary objective is to compare the live birth rates between the two endometrial preparations.Study designThis is a retrospective study done at KK Women’s and Children’s Hospital Singapore. We included women who underwent FET cycles either with hormone replacement treatment (HRT) or no treatment (natural) for the endometrial preparation, regardless of their cycle number, from 1 January 2011 till 31 December 2015.ResultsA total of 2,752 FET cycles were included in our analysis. The natural cycle followed by vaginal progesterone support was used in 1,221 cycles and the HRT cycle with estrogen and vaginal progesterone was used in 1,531 cycles. There is a significantly higher miscarriage rate in the HRT group (38.4%) compared with the natural group (22.3%). The live birth rate is significantly higher in the natural group (22.8%) compared with the HRT group (17.3%). The multivariate analysis further shows that the HRT therapy is independently associated with an increased risk of miscarriage (adjusted odds ratio 2.05; 95% confidence interval 1.45–2.90; p<0.001) and hence lower odds of live birth (adjusted odds ratio 0.69; 95% confidence interval 0.56–0.84; p<0.001) after adjusting for the patient’s age at which the embryo was cryopreserved, race, body mass index, main indications for in vitro fertilization, number of embryos transferred and type of embryo transferred.ConclusionWe have shown in this study that the miscarriage rate is higher in the HRT FET group and that this increased miscarriage rate translates into a lower live birth rate in the HRT group. Thus, we conclude that patients with regular menstrual cycles should be offered a natural FET cycle to achieve better outcomes in terms of live birth rate and reducing the miscarriage rate.

Une patiente a présenté un syndrome orellanien (dialysée depuis), suivi d’une myocardite un mois après. Le bilan étiologique exhaustif n’a pas identifié d’autre cause à cette myocardite, l’IRM cardiaque étant, par ailleurs, en faveur d’une origine toxique. Notre objectif a été d’évaluer la cardiotoxicité aiguë des intoxications par des champignons.

L’inadhésion thérapeutique représente aujourd’hui la première cause de handicap acquis chez l’adulte et la deuxième cause de mortalité dans le monde. Le risque de récidive après un premier AVCi est d’environ 10 % à 1 an et 20 à 30 % à 5 ans. Sa prévention repose sur la prise d’anticoagulants oraux ou d’antiagrégants plaquettaires, d’hypolipémiants et/ou d’antihypertenseurs.

The Workshop Program of the Association for the Advancement of Artificial Intelligence's International Conference on Web and Social Media (AAAI‐17) was held in Montréal, Québec, Canada, on Monday, May 15, 2017. There were eight workshops in the program: Digital Misinformation, Events Analytics Using Social Media Data, News and Public Opinion, Observational Studies through Social Media, Perceptual Biases and Social Media, Social Media and Demographic Research, Studying User Perceptions and Experiences with Algorithms, and The ICWSM Science Slam. Workshops were held on the first day of the conference. Workshop participants met and discussed issues with a selected focus — providing an informal setting for active exchange among researchers, developers, and users on topics of current interest. Organizers from two of the workshops chose to include papers in the AAAI Technical Reports series (Observational Studies through Social Media and News and Public Opinion). Their papers were included as a nonarchival part of the ICWSM proceedings. Organizers from four of the workshops (Digital Misinformation, News and Public Opinion, Perceptual Biases and Social Media, and Studying User Perceptions and Experiences with Algorithms) submitted reports, which are reproduced in this report. Brief summaries of the other four workshops have been reproduced from their website descriptions.