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Since the early 1990s, telemedicine, or the use of information technology to support the delivery of health care from a distance, has increasingly gained the support of clinicians, administrators and policymakers across industrialised countries. However, the "theory of use" behind telemedicine-its rationale and the manner in which clinicians are expected to use it in their daily activities--has been only marginally investigated. In this paper we present the results of a qualitative study which examines the theory of use behind teleconsultation from the viewpoint of physicians (n = 37) in six specialities, practising in Quebec (Canada) hospitals. We employ Giddens' Structuration Theory (1984) to analyse the views, communications needs and referral strategies of physicians. Two questions are explored: (1) To what extent can teleconsultation be integrated into the routines of diverse medical specialities'? and (2) Why and how might clinicians use this technology? Our research indicates that specialities relying on either thorough physical examinations or specialised investigative techniques are unlikely to restructure their work routines to accommodate teleconsultation, which they view as limited. Specialities that primarily exploit images or numerical data tend to perceive teleconsultation as more useful. The perceived enabling properties of teleconsultation increase as a function of the distance the patient would have to travel to be seen directly by a consultant. The constraining properties are linked to the type of information transmitted, since physicians believe that only objective data can be safely consulted from a distance, whereas relying on the remote physician's interpretation of subjective information is deemed inappropriate. We thus conclude that the development of teleconsultation should be consolidated around applications whose theory of use is compatible with existing clinical routines, or offers opportunities to restructure clinical work according to the needs of providers and remote communities.

Abstract Wolverine distribution contracted along the southern periphery of its range in North America during the 19th and 20th centuries due primarily to human influences. This history, along with low densities, sensitivity to climate change, and concerns about connectivity among fragmented habitats spurred the recent US federal listing of threatened status and special concern status in Canada. To help inform large scale landscape connectivity, we collected 882 genetic samples genotyped at 19 microsatellite loci. We employed multiple statistical models to assess the landscape factors (terrain complexity, human disturbance, forest configuration, and climate) associated with wolverine genetic connectivity across 2.2 million km2 of southwestern Canada and the northwestern contiguous United States. Genetic similarity (positive spatial autocorrelation) of wolverines was detected up to 555 km and a high-to-low gradient of genetic diversity occurred from north-to-south. Landscape genetics analyses confirmed that wolverine genetic connectivity has been negatively influenced by human disturbance at broad scales and positively influenced by forest cover and snow persistence at fine- and broad–scales, respectively. This information applied across large landscapes can be used to guide management actions with the goal of maintaining or restoring population connectivity.

Abstract This study aimed to investigate whether the plant DNA damage levels and DNA damage response (DDR) are regulated during Agrobacterium infection and potentially manipulated by Agrobacterium to facilitate T-DNA integration. We investigated the plant genomic response to Agrobacterium infection by measuring gamma H2AX levels, which reflect the levels of double-strand DNA breaks (DSBs), and by characterizing transcription of three major DNA repair marker genes NAC82, KU70, and AGO2. These experiments revealed that, globally, Agrobacterium infection did not result in a major increase in DSB content in the host genome. The transcription of the DNA damage repair genes, on the other hand, was elevated upon the wild-type Agrobacterium infection. This transcriptional outcome was largely negated by a mutation in the bacterial virB5 gene which encodes the virulence (Vir) protein B5, a minor component of Agrobacterium pilus necessary for the translocation of Vir effector proteins into the host cell, suggesting that the transcriptional activation of the cellular DNA damage repair machinery requires the transport into the host cell of the Agrobacterium effectors, i.e., the VirD2, VirD5, VirE2, VirE3, and VirF proteins. Most likely, a combination of several of these Vir effectors is required to activate the host DNA repair as their individual loss- or gain-of-function mutants did not significantly affect this process.

Abstract Seminal plasma (SP) is the main vector of C. trachomatis (CT) during heterosexual transmission from male to female. It has immunomodulatory properties and impacts the susceptibility to HIV-1 infection, but its role has not been explored during CT infection. In the female reproductive tract (FRT), CT infection induces cytokine production and neutrophil recruitment. The role of neutrophils during CT infection is partially described, they could be at the origin of the pathology observed during CT infection. During this study, we developed an experimental in vitro model to characterize the impact of CT infection and SP on endocervical epithelial cell immune response in the FRT. We also studied the impact of the epithelial cell response on neutrophil phenotype and functions. We showed that the production by epithelial cells of pro-inflammatory cytokines increased during CT infection. Moreover, the pool of SP as well as individuals SP inhibited CT infection in a dose-dependent manner. The pool of SP inhibited cytokine production in a dose-dependent manner. The pool of SP altered gene expression profiles of infected cells. The culture supernatants of cells infected or not with CT, in presence or not of the pool of SP, had an impact on neutrophil phenotype and functions: they affected markers of neutrophil maturation, activation and adhesion capacity, as well as the survival, ROS production and phagocytosis ability. This study proposes a novel approach to study the impact of the environment on the phenotype and functions of neutrophils in the FRT. It highlights the impact of the factors of the FRT environment, in particular SP and CT infection, on the mucosal inflammation and the need to take into account the SP component while studying sexually transmitted infections during heterosexual transmission from male to female.

Abstract It has been suggested that having a reputation for being prosocial is a critical part of social status across all human societies. It has also been argued that prosocial behavior confers benefits, whether physiological, such as stress reduction, or social, such as building allies or becoming more popular. Here, we investigate the relationship between helping reputation (being named as someone others would go to for help), and hair-derived chronic stress (hair cortisol concentration). In a sample of 77 women and 62 men, we found that perceived helping reputation was not related to chronic stress. Overall, the results of our study suggest that, in an egalitarian society with fluid camp membership and widely practiced generosity such as the Hadza, helping reputation does not necessarily boost stress-related health benefits through prestige-signaling mechanisms observed in hierarchical, large-scale societies.

Abstract In order to survive and replicate, Salmonella has evolved mechanisms to gain access to intestinal epithelial cells of the crypt. However, the impact of Salmonella Typhimurium on stem cells and progenitors, which are responsible for the ability of the intestinal epithelium to renew and protect itself, remains unclear. Given that intestinal organoids growth is sustained by stem cells and progenitors activity, we have used this model to document the effects of Salmonella Typhimurium infection on epithelial proliferation and differentiation, and compared it to an in vivo model of Salmonella infection in mice. Among gut segments, the caecum was preferentially targeted by Salmonella. Analysis of infected crypts and organoids demonstrated increased length and size, respectively. mRNA transcription profiles of infected crypts and organoids pointed to upregulated EGFR-dependent signals, associated with a decrease in secretory cell lineage differentiation. To conclude, we show that organoids are suited to mimic the impact of Salmonella on stem cells and progenitors cells, carrying a great potential to drastically reduce the use of animals for scientific studies on that topic. In both models, the EGFR pathway, crucial to stem cells and progenitors proliferation and differentiation, is dysregulated by Salmonella, suggesting that repeated infections might have consequences on crypt integrity and further oncogenesis.

Abstract The rapid development of large language models (LLMs) motivates us to explore how such state-of-the-art natural language processing systems can inform aphasia research. What kind of language indices can we derive from a pre-trained LLM? How do they differ from or relate to the existing language features in aphasia? To what extent can LLMs serve as an interpretable and effective diagnostic and measurement tool in a clinical context? To investigate these questions, we constructed predictive and correlational models, which utilize mean surprisals from LLMs as predictor variables. Using AphasiaBank archived data, we validated our models’ efficacy in aphasia diagnosis, measurement, and prediction. Our finding is that LLMs-surprisals can effectively detect the presence of aphasia and different natures of the disorder, LLMs in conjunction with the existing language indices improve models’ efficacy in subtyping aphasia, and LLMs-surprisals can capture common agrammatic deficits at both word and sentence level. Overall, LLMs have potential to advance automatic and precise aphasia prediction. A natural language processing pipeline can be greatly benefitted from integrating LLMs, enabling us to refine models of existing language disorders, such as aphasia.

Objective: The American Heart Association’s Life’s Essential 8 (LE8) metric includes self-reported physical activity as one of the metrics for assessing cardiovascular health. Self-reported physical activity is prone to misclassification, whereas accelerometer measures are less biased. We examined associations of LE8 and incident cardiovascular disease (CVD) using self-reported and accelerometer-measured physical activity. Methods: Participants in the Women’s Health Initiative (WHI) Objective Physical Activity and Cardiovascular Health Study (n = 4,243; mean age = 79 ± 7 years) with no CVD history completed the WHI physical activity questionnaire and the Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire prior to wearing a hip-worn accelerometer for up to seven days in 2012–2014. LE8 components (physical activity, diet, sleep, body mass index, smoking, blood pressure, non-HDL cholesterol, and glucose) were scored according to guidelines. Scores were created using five physical activity measures: WHI questionnaire (LE8WHI), CHAMPS (LE8CHAMPS), accelerometer-measured physical activity (LE8A), and sample quantiles of accelerometer-measured physical activity (LE8AQ) and daily steps (LE8STEPS). Hazard ratios (HR) for physician-adjudicated CVD were estimated using Cox regression. Results: 707 incident CVD events occurred over an average 7.5 years. Multivariable HRs (95 % CI) comparing women in the highest vs. lowest quartiles of LE8 scores were: LE8WHI = 0.53 (0.43–0.67), LE8CHAMPS = 0.47 (0.38–0.60), LE8A = 0.44 (0.36–0.56), LE8AQ = 0.44 (0.35–0.55), and LE8STEPS = 0.45 (0.35–0.57). Conclusions: The LE8-incident CVD association varies by physical activity measurement, however all methods showed reduced risk. Device-measures of physical activity may be more accurate in the LE8, but when impractical to implement, also support use of self-reported measures.

Case description: We report here the case of a 64-year-old male presenting pathological fractures of T6 and T7 due to pseudomyxoma peritonei extension to the pleural cavity and thoracic spine. He presented interscapular pain with mild spinal cord compression symptoms. He was treated by achieving T5-T8 laminectomy, T2-T10 pedicle fixation, and T6-T7 vertebrectomy. The postoperative course was uneventful apart from a pulmonary embolism with favorable evolution under anticoagulants. Conclusion: Pseudomyxoma peritonei is a rare condition, with no previously described location in the spine. Here is described the case of a PMP extension to the thorax then the spine, treated with two-level vertebrectomy, laminectomy, and posterior fusion.

Key clinical Message Right sided posterior diaphragmatic hernias are a rare diagnosis, especially in adult populations. This patient presented with right thoracic pain for 20 years before investigation. Imaging has provided an accurate diagnosis in this case. Repair can be done safely laparoscopically.

Objective To test the effect of a complex, interdisciplinary, lifestyle and psychosocial intervention on metabolic and mental health outcomes in women with gestational diabetes mellitus during pregnancy and in the post partum.Design Single centred, single blinded, randomised, controlled trial (the MySweetheart trial).Setting Lausanne University Hospital, Switzerland, from 2 September 2016 to 25 October 2021.Participants 211 women aged at least 18 years with a diagnosis of gestational diabetes mellitus at 24-32 gestational weeks were randomly assigned (1:1) to the intervention (n=105) or to usual care (n=106).Interventions In addition to a comparator based on active guidelines for prepartum and postpartum usual care, the intervention consisted of four individual lifestyle visits during pregnancy and four interdisciplinary visits in the postpartum group, a peer support group workshop in pregnancy and post partum, and a bimonthly lifestyle coach support through telemedicine. The intervention focused on tailored behavioural and psychosocial strategies to improve diet, physical activity, mental health, social support, and adherence to gestational weight gain during pregnancy and weight retention recommendations.Main outcome measures Primary outcomes were between-group differences in the decrease in maternal weight and depression symptom scores between baseline and one year post partum. Secondary outcomes included changes in total and central body fat, anxiety, wellbeing, glycaemic parameters (homeostatic model assessment for insulin resistance (known as HOMA-IR) and Matsuda indices), aerobic fitness (maximal oxygen uptake), gestational weight gain, and weight retention. Assessors were blinded to primary and secondary outcomes.Results 84 (80%) of 105 women in the intervention and 95 (90%) of 106 in the usual care completed the study. There was not enough evidence of a difference in the decrease in weight (mean difference –0.38 kg (95% confidence interval –2.08 to 1.30)) or depression scores (–0.67 (–1.84 to 0.49)). The intervention led to an increase in fat-free mass (0.02 kg (0.01 to 0.03)). The intervention also decreased gestational weight gain since the first gestational diabetes mellitus visit (–1.20 kg (–2.14 to –0.26)) and weekly weight gain throughout the entire pregnancy (–0.14 kg (–0.25 to –0.03)), and led to a higher proportion of women without weight retention at one year post partum (34.1% (28/82) v 20.8% (20/96), P=0.034).Conclusions Compared with active usual care based on guidelines, there was not enough evidence to conclude that the intervention led to decrease in weight or depression symptoms. However, the intervention decreased gestational weight gain and increased the proportion of women without weight retention.Trial registration Clinicaltrials.gov NCT02890693.

Introduction The World Health Organization (WHO) estimates that ∼ 32 million children worldwide are affected by hearing loss (HL). Cochlear implant is the first-line treatment for severe to profound sensorineural HL. It is considered one of the most successful prostheses developed to date.

Abstract At the end of 2020, an outbreak of HPAI H5N8 was registered in captive African houbara bustards (Chlamydotis undulata) in the United Arab Emirates. In order to better understand the pathobiology of this viral infection in bustards, a comprehensive pathological characterization was performed. A total of six birds were selected for necropsy, histopathology, immunohistochemistry, RNAscope in situ hybridization and RT-qPCR and nanopore sequencing on formalin-fixed and paraffin-embedded (FFPE) tissue blocks. Gross lesions included mottled and/or hemorrhagic pancreas, spleen and liver and fibrinous deposits on air sacs and intestine. Necrotizing pancreatitis, splenitis and concurrent vasculitis, hepatitis and fibrino-heterophilic peritonitis were identified, microscopically. Viral antigens (nucleoprotein) and RNAs (matrix gene) were both detected within necro-inflammatory foci, parenchymal cells, stromal cells and endothelial cells of affected organs, including the myenteric plexus. Molecular analysis of FFPE blocks successfully detected HPAI H5N8, further confirming its involvement in the lesions observed. In conclusion, HPAI H5N8 in African houbara bustards results in hyperacute/acute forms exhibiting marked pantropism, endotheliotropism and neurotropism. In addition, our findings support the use of FFPE tissues for molecular studies of poorly characterized pathogens in exotic and endangered species, when availability of samples is limited.

Introduction An in-depth understanding of educational needs from the perspective of learners in pulmonary rehabilitation is lacking. To improve learning in pulmonary rehabilitation, understanding of factors that induce or enhance intrinsic motivation in both patients and their significant others is needed. Therefore, this study aims to gain in-depth understanding of what motivates patients with COPD or asthma referred for pulmonary rehabilitation and their significant others to learn and what their preferences are for education. Methods For this qualitative study, a sample was taken from a previous quantitative study. Data was collected through one-time face-to-face semi-structured interviews. The interviews were transcribed and independently analysed by two researchers using thematic analyses. Results Twelve patients and four significant others (56% female; age: 63±11 years) were interviewed. Participants expressed a variety of information needs and learning preferences. Subthemes that emerged within the theme of motivation for learning were: 1) curiosity, such as knowledge gaps and hope for new information; and 2) values and goals, such as own health, caring for loved ones and spending time with family. Discussion To enhance intrinsic motivation for learning within pulmonary rehabilitation, autonomy of individuals should be supported by offering several learning topics and education adapted to preferences, while curiosity should be fostered by targeting information needs. Moreover, health education programmes should match with the personal values and goals of individuals, such as own health, caring for loved ones and spending time with family.

Summary: Background: Circadian rhythms regulate cellular physiology and could influence the efficacy of endocrine therapy (ET) in breast cancer (BC). We prospectively tested this hypothesis within the UNIRAD adjuvant phase III trial (NCT01805271). Methods: 1278 patients with high-risk hormonal receptor positive (HR+)/HER2 negative (HER2-) primary BC were randomly assigned to adjuvant ET with placebo or everolimus. Patients prospectively reported in a diary the daily timing of ET intake among four 6-h slots (06:00–11:59 (morning), 12:00–17:59 (afternoon), 18:00–23:59 (evening), or 24:00–05:59 (nighttime). The association between ET timing and disease-free survival (DFS) was a prespecified secondary endpoint of the trial and the results of this observational study are reported here. Findings: ET timing was recorded by 855 patients (67.2%). Patients declaring morning (n = 465, 54.4%) or afternoon (n = 45, 5.4%) ET intake were older than those declaring evening (n = 339, 39.6%) or nighttime (n = 5, 0.6%) intake. With a median follow-up of 46.7 months, 118 patients had a local (n = 30) or metastasis relapse (n = 84), and 41 patients died. ET intake timing was not associated with DFS in the whole population (HR = 0.77, 95% CI [0.53–1.12]). The association between ET intake timing and DFS according to the stratification factors revealed interactions with ET agent (tamoxifen versus Aromatase inhibitors (AI) with an increased DFS in the group of evening/nighttime versus morning/afternoon tamoxifen intake (HR = 0.43, 95% CI [0.22–0.85]), while no association was found for AI intake (HR = 1.07, 95% CI [0.68–1.69]). The interaction between ET intake timing and ET agent remained in multivariable analysis (HR = 0.38 [0.16–0.91]). Interpretation: Tamoxifen intake in the evening/nighttime could be recommended in patients with high-risk HR+/HER2- BC while awaiting for results from further ET timing studies. Funding: UNIRAD was Supported by a grant from the French Ministry of Health PHRC 2012 and received funding from La Ligue contre le Cancer, Cancer Research-UK, Myriad Genetics, and Novartis.

Background: Patterns of physical activity and sedentary behavior among postmenopausal women are not well characterized. Objectives: To describe the patterns of accelerometer-assessed physical activity and sedentary behavior among postmenopausal women. Design: Cross-sectional study. Methods: Women 63–97 years (n = 6126) wore an ActiGraph GT3X + accelerometer on their hip for 1 week. Latent class analysis was used to classify women by patterns of percent of wake time in physical activity and sedentary behavior over the week. Results: On average, participants spent two-thirds of their day in sedentary behavior (62.3%), 21.1% in light low, 11.0% in light high, and 5.6% in moderate-to-vigorous physical activity. Five classes emerged for each single-component model for sedentary behavior and light low, light high, and moderate-to-vigorous physical activity. Six classes emerged for the multi-component model that simultaneously considered the four behaviors together. Conclusion: Unique profiles were identified in both single- and multi-component models that can provide new insights into habitual patterns of physical activity and sedentary behavior among postmenopausal women. Implications: The multi-component approach can contribute to refining public health guidelines that integrate recommendations for both enhancing age-appropriate physical activity levels and reducing time spent in sedentary behavior.

Abstract An in situ microscope based on pulsed transmitted light illumination via optical fiber was combined to artificial-intelligence to enable for the first time an online cell classification according to well-known cellular morphological features. A 848 192-image database generated during a lab-scale production process of antibodies was processed using a convolutional neural network approach chosen for its accurate real-time object detection capabilities. In order to induce different cell death routes, hybridomas were grown in normal or suboptimal conditions in a stirred tank reactor, in the presence of substrate limitation, medium addition, pH regulation problem or oxygen depletion. Using such an optical system made it possible to monitor real-time the evolution of different classes of animal cells, among which viable, necrotic and apoptotic cells. A class of viable cells displaying bulges in feast or famine conditions was also revealed. Considered as a breakthrough in the catalogue of process analytical tools, in situ microscopy powered by artificial-intelligence is also of great interest for research.

Abstract Liposomal formulations are hypothesized to alleviate anthracycline cardiotoxicity, although this has only been documented clinically for doxorubicin. We developed an in vitro multiparametric model using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) to assess the relative toxicity of anthracyclines across formulations. Proof of concept was established by treating hiPSC-CM with equivalent concentrations of free and liposomal doxorubicin. The study was then repeated with free daunorubicin plus cytarabine and CPX-351, a dual-drug liposomal encapsulation of daunorubicin/cytarabine. hiPSC-CM were treated with free-drug or liposomal formulations for 24 h on Days 1, 3, and 5 at equivalent concentrations ranging from 0 to 1000 ng/mL and assessed on subsequent days. Free-drug treatment resulted in concentration-dependent cumulative cytotoxicity (microscopy), more profound decrease in ATP levels, and significant time- and concentration-dependent decreases in oxygen consumption versus liposomal formulations (p

Abstract Appropriate in vitro models to investigate the impact of novel nutritional strategies on the gut microbiota of infants living in rural Africa are scarce. Here, we aimed to develop such a continuous gut fermentation model based on the PolyFermS platform, which allows controlled and stable long-term cultivation of colon microbiota in conditions akin the host. Nine immobilized Kenyan infant fecal microbiota were used as inoculum for continuous PolyFermS colon models fed with medium mimicking the weaning infant diet. Fructo-oligosaccharides (FOS) supplementation (1, 4 and 8 g/L) and cultivation pH (5.8 and 6.3) were investigated stepwise. Conditions providing a close match between fecal and in vitro microbiota (pH 5.8 with 1 g/L FOS) were selected for investigating long-term stability of four Kenyan infant PolyFermS microbiota. The shared fraction of top bacterial genera between fecal and in vitro microbiota was high (74–89%) and stable during 107 days of continuous cultivation. Community diversity was maintained and two distinct fermentation metabolite profiles of infant fecal microbiota were observed. Three propiogenic and one butyrogenic metabolite profile of infant fecal microbiota established from day 8 onwards and stayed stable. We present here the first rationally designed continuous cultivation model of African infant gut microbiota. This model will be important to assess the effect of dietary or environmental factors on the gut microbiota of African infants with high enteropathogen exposure.

Abstract The formation of protein aggregates is a hallmark of many neurodegenerative diseases and systemic amyloidoses. These disorders are associated with the fibrillation of a variety of proteins/peptides, which ultimately leads to cell toxicity and tissue damage. Understanding how amyloid aggregation occurs and developing compounds that impair this process is a major challenge in the health science community. Here, we demonstrate that pathogenic proteins associated with Alzheimer’s disease, diabetes, AL/AA amyloidosis, and amyotrophic lateral sclerosis can aggregate within stress-inducible physiological amyloid-based structures, termed amyloid bodies (A-bodies). Using a limited collection of small molecule inhibitors, we found that diclofenac could repress amyloid aggregation of the β-amyloid (1–42) in a cellular setting, despite having no effect in the classic Thioflavin T (ThT) in vitro fibrillation assay. Mapping the mechanism of the diclofenac-mediated repression indicated that dysregulation of cyclooxygenases and the prostaglandin synthesis pathway was potentially responsible for this effect. Together, this work suggests that the A-body machinery may be linked to a subset of pathological amyloidosis, and highlights the utility of this model system in the identification of new small molecules that could treat these debilitating diseases.

IntroductionModifiable cardiovascular risk factors (CVRF) are highly prevalent in SubSaharan African communities. In these countries the burden of CVRF during early pregnancy has been poorly documented.AimThe objective of this study was to describe the frequency of CVRF in pregnant women before the 20th week of gestation in Benin.MethodsConsecutive pregnant women with a gestational age < 20th week were included in 30 maternity clinics in Benin. Univariate and multivariate analyses were used to determine characteristics associated with CVRF.Results1244 pregnant women were included (680 (54.7%) in urban areas and 584 (45.3%) in rural areas). The median age was 26 years. The frequencies of high blood pressure (HBP), obesity and diabetes were 18.9%, 15.0% and 3.1% respectively. Very few women (25.3%) were aware of the HBP disorder. HBP was associated with an age ≥ 35 years (OR = 1.7, 95%CI:1.1-2.7), a rural setting (OR = 2.6; 95%CI:1.9-3.5), an insufficient consumption of fruits and vegetables (OR = 3.2; 95%CI:2.0-5.3) and a history of at least 2 fetal losses (OR = 1.9; 95% CI [1.4-2.7]). The risk of being overweight was associated with an age >24 years old (OR = 1.6; 95%CI:1.1-2.2) conversely a rural setting was protective (OR = 0.7; 95%CI:0.5-0.9). Obesity was associated with an age > 35 years old (OR = 4.1; 95%CI:2.5-6.8) and a rural setting (OR = 0.3; 95%CI: 0.2-0.5).ConclusionThe frequency of CVRF in women before 20th week of gestation was high. Most of the women were unaware of the disorder. Thus the screening of CVRF among women of reproductive age might be relevant.

BackgroundDescribing correlates of physical activity (PA) and sedentary behavior (SB) among postmenopausal cancer survivors can help identify risk profiles and can be used to support development of targeted interventions to improve PA and reduce SB in this population.ObjectiveTo describe PA/SB and identify correlates of PA/SB among cancer and cancer-free post-menopausal women.MethodsWomen from the Women's Health Study (N = 16,629) and Women's Health Initiative/Objective Physical Activity and Cardiovascular Health Study (N = 6,079) were asked to wear an accelerometer on the hip for 7 days. Multiple mixed-effects linear regression models were used to identify sociodemographic-, health-, and chronic condition-related correlates (independent variables) associated with PA and SB (dependent variables) among women with (n = 2,554) and without (n = 20,154) a history of cancer. All correlates were mutually adjusted for each other.ResultsIn unadjusted analyses, women with a history of cancer took fewer mean daily steps (4,572 (standard deviation 2557) vs 5,029 (2679) steps/day) and had lower mean moderate-to-vigorous PA (74.9 (45.0) vs. 81.6 (46.7) minutes/day) than cancer-free women. In adjusted analyses, for cancer and cancer-free women, age, diabetes, overweight, and obesity were inversely associated with all metrics of PA (average vector magnitude, time in moderate-to-vigorous PA, step volume, time at ≥40 steps/minutes, and peak 30-minute step cadence). In unadjusted analyses, mean SB was similar for those with and without cancer (529.7 (98.1) vs. 521.7 (101.2) minutes/day). In adjusted analyses, for cancer and cancer-free women, age, diabetes, cardiovascular disease, current smoking, overweight, and obesity were positive correlates of SB, while Black or Hispanic race/ethnicity, weekly/daily alcohol intake, and excellent/very good/good self-rated health were inverse correlates of SB.ConclusionSeveral sociodemographic, health, and chronic conditions were correlates of PA/SB for postmenopausal women with and without cancer. Future studies should examine longitudinal relationships to gain insight into potential determinants of PA/SB.

Abstract Pancreatic ductal adenocarcinoma (PDAC) has a high fatality rate, mainly due to its asymptomatic nature until late-stage disease and therefore delayed diagnosis that leads to a lack of timely treatment intervention. Consequently, there is a significant need for better methods to screen populations that are at high risk of developing PDAC. Such advances would result in earlier diagnosis, more treatment options, and ultimately better outcomes for patients. Several recent studies have applied the concept of liquid biopsy, which is the sampling of a biofluid (such as blood plasma) for the presence of disease biomarkers, to develop screening approaches for PDAC; several of these studies have focused on analysis of extracellular vesicles (EVs) and their cargoes. While these studies have identified many potential biomarkers for PDAC that are present within EVs, their application to clinical practice is hindered by the lack of a robust, reproducible method for EV isolation and analysis that is amenable to a clinical setting. Our previous research has shown that the Vn96 synthetic peptide is indeed a robust and reproducible method for EV isolation that has the potential to be used in a clinical setting. We have therefore chosen to investigate the utility of the Vn96 synthetic peptide for this isolation of EVs from human plasma and the subsequent detection of small RNA biomarkers of PDAC by Next-generation sequencing (NGS) analysis. We find that analysis of small RNA from Vn96-isolated EVs permits the discrimination of PDAC patients from non-affected individuals. Moreover, analyses of all small RNA species, miRNAs, and lncRNA fragments are most effective at segregating PDAC patients from non-affected individuals. Several of the identified small RNA biomarkers have been previously associated with and/or characterized in PDAC, indicating the validity of our findings, whereas other identified small RNA biomarkers may have novel roles in PDAC or cancer in general. Overall, our results provide a basis for a clinically-amendable detection and/or screening strategy for PDAC using a liquid biopsy approach that relies on Vn96-mediated isolation of EVs from plasma.

Abstract This paper investigates thermal transport in a nanocomposite system consisting of a porous silicon matrix filled with ionic liquid. Firstly, the thermal conductivity and heat capacity of two imidazolium and one ammonium ionic liquids were evaluated using the photoacoustic approach in piezoelectric configuration and differential scanning calorimetry, respectively. Then, the thermal transport properties of the composite system "ionic liquid confined inside porous silicon matrix" were investigated with the photoacoustic approach in gas-microphone configuration. The results demonstrated a significant enhancement of the thermal conductivity of the composite system when compared to the individual components, i.e. (i) more than two times for pristine porous silicon and (ii) more than eight times for ionic liquids. These results provide new paths for innovative solutions in the field of thermal management, particularly in the development of highly efficient energy storage devices.

Abstract In a large retrospective study, we assessed the putative use of circulating microvesicles (MVs), as innovative biomarkers of radiation toxicity in a cohort of 208 patients with prostate adenocarcinoma overexposed to radiation. The level of platelet (P)-, monocyte (M)- and endothelial (E)-derived MVs were assessed by flow cytometry. Rectal bleeding toxicity scores were collected at the time of blood sampling and during the routine follow-up and were tested for association with MVs using a multivariate logistic regression. MVs dosimetric correlation was investigated using dose volume histograms information available for a subset of 36 patients. The number of PMVs was significantly increased in patients with highest toxicity grades compared to lower grades. Risk prediction analysis revealed that increased numbers of PMVs, and an increased amount of MMVs relative to EMVs, were associated with worst rectal bleeding grade compared to the time of blood sampling. Moreover, a significant correlation was found between PMV and MMV numbers, with the range of doses up to the median exposure (40 Gy) of bladder/rectum and anterior rectal wall, respectively. MVs could be considered as new biomarkers to improve the identification of patients with high toxicity grade and may be instrumental for the prognosis of radiation therapy complications.

Abstract In recent years there has been much research regarding the extent to which social status is related to long-term indices of health. The majority of studies looking at the interplay between social status and health have been conducted in industrialized societies. However, it has been argued that most of human evolution took place in small, mobile and egalitarian hunter-gatherer groups where individuals exhibited very little variation in terms of material wealth or possessions. In this study, we looked at the extent to which two domains of social status, hunting reputation (being perceived as a good hunter) and popularity (being perceived as a friend), are related to physiological stress levels among Hadza men, hunter-gatherers living in Northern Tanzania. The results of our study show that neither hunting reputation nor popularity is associated with stress levels. Overall, our data suggest that, in at least some traditional small-scale societies exhibiting an egalitarian social model, such as the Hadza, the variation in social status measures based on both popularity and hunting reputation does not translate into one of the commonly used indices of wellbeing.

Introduction Food cravings are common in pregnancy and along with emotional eating and eating in the absence of hunger, they are associated with excessive weight gain and adverse effects on metabolic health including gestational diabetes mellitus (GDM). Women with GDM also show poorer mental health, which further can contribute to dysregulated eating behaviour. Food cravings can lead to greater activity in brain centres known to be involved in food ‘wanting’ and reward valuation as well as emotional eating. They are also related to gestational weight gain. Thus, there is a great need to link implicit brain responses to food with explicit measures of food intake behaviour, especially in the perinatal period. The aim of this study is to investigate the spatiotemporal brain dynamics to visual presentations of food in women during pregnancy and in the post partum, and link these brain responses to the eating behaviour and metabolic health outcomes in women with and without GDM.Methods and analysis This prospective observational study will include 20 women with and 20 without GDM, that have valid data for the primary outcomes. Data will be assessed at 24–36 weeks gestational age and at 6 months post partum. The primary outcomes are brain responses to food pictures of varying carbohydrate and fat content during pregnancy and in the post partum using electroencephalography. Secondary outcomes including depressive symptoms, current mood and eating behaviours will be assessed with questionnaires, objective eating behaviours will be measured using Auracle and stress will be measured with heart rate and heart rate variability (Actiheart). Other secondary outcome measures include body composition and glycaemic control parameters.Ethics and dissemination The Human Research Ethics Committee of the Canton de Vaud approved the study protocol (2021-01976). Study results will be presented at public and scientific conferences and in peer-reviewed journals.

Abstract Objectives ‘Integrative and Conjugative Elements’ (ICEs) and ‘Integrative and Mobilizable Elements’ (IMEs) are two classes of mobile genetic elements that are complex to detect and delineate. Therefore, they are yet poorly annotated in bacterial genomes. FirmiData provides to the scientific community of microbiologists and bioinformaticians a reference resource of annotated ICEs and of IMEs from Firmicutes. It illustrates their prevalence and their diversity but also gives information on their organization. FirmiData was designed to assist the scientific community in identifying and annotating these elements by using the sequences of these ICEs and IMEs for the identification of related elements in other genomes of Firmicutes. Therefore, Firmidata meets the needs of the scientific community. Data description Firmidata provides a manually curated annotation of 98 ICEs and 148 IMEs identified in 40 chromosomes of Firmicutes. The delineation at the nucleotide level of almost all of these elements allows for the characterization of the genes they carry.

Abstract Access to a comprehensive molecular alteration screening is patchy in Europe and quality of the molecular analysis varies. SPECTAlung was created in 2015 as a pan-European screening platform for patients with thoracic malignancies. Here we report the results of almost 4 years of prospective molecular screening of patients with thoracic malignancies, in terms of quality of the program and molecular alterations identified. Patients with thoracic malignancies at any stage of disease were recruited in SPECTAlung, from June 2015 to May 2019, in 7 different countries. Molecular tumour boards were organised monthly to discuss patients’ molecular and clinical profile and possible biomarker-driven treatments, including clinical trial options. FFPE material was collected and analysed for 576 patients with diagnosis of pleural, lung, or thymic malignancies. Ultimately, 539 patients were eligible (93.6%) and 528 patients were assessable (91.7%). The turn-around time for report generation and molecular tumour board was 214 days (median). Targetable molecular alterations were observed in almost 20% of cases, but treatment adaptation was low (3% of patients). SPECTAlung showed the feasibility of a pan-European screening platform. One fifth of the patients had a targetable molecular alteration. Some operational issues were discovered and adapted to improve efficiency.

Abstract In the days to weeks following an earthquake, landslides can display specific post-seismic motions, including delayed initiations and post-seismic relaxations. These motions have an uncertain origin, sometimes attributed to specificities of the landslide basal interface or to fluid transports in the landslide basal shear zone. Here we address this question, by documenting the co- and post-seismic motions of slow-moving landslides accelerated by the Gorkha earthquake (Mw 7.8, 25/04/2015, Nepal). We detect 11 slow-moving landslides over an area of 750 km $$^2$$ 2 in the near field of the earthquake, and monitor their motions thanks to a time-series of Pléiades optical satellite images and SAR Sentinel-1 images. The post-seismic landslide motions are much larger than the co-seismic ones, reaching up to $$34 \,\pm\, 0.6$$ 34 ± 0.6 m accommodated over 2 months. A delayed initiation of several days (> 4 days) is also measured for at least two of the landslides. We analyze our findings in regards with all the previous observations on slow-moving landslides accelerated by earthquakes, and propose that the post-seismic motions are caused by diffusion of groundwater from co-seismic material contraction up to the landslide basal shear zone or from internal landslide reconfiguration. Our observations strongly suggest the main control of the hydrology in the landslide processes under seismic forcings.

Objectives Women of low socioeconomic status have been described as having suboptimal prenatal care, which in turn has been associated with poor pregnancy outcomes. Many types of conditional cash transfer (CCT) programmes have been developed, including programmes to improve prenatal care or smoking cessation during pregnancy, and their effects demonstrated. However, ethical critiques have included paternalism and lack of informed choice. Our objective was to determine if women and healthcare professionals (HPs) shared these concerns.Design Prospective qualitative research.Setting We included economically disadvantaged women, as defined by health insurance data, who participated in the French NAITRE randomised trial assessing a CCT programme during prenatal follow-up to improve pregnancy outcomes. The HP worked in some maternities participating in this trial.Participants 26 women, 14 who received CCT and 12 who did not, mostly unemployed (20/26), and - 7 HPs.Interventions We conducted a multicentre cross-sectional qualitative study among women and HPs who participated in the NAITRE Study to assess their views on CCT. The women were interviewed after childbirth.Results Women did not perceive CCT negatively. They did not mention feeling stigmatised. They described CCT as a significant source of aid for women with limited financial resources. HP described the CCT in less positive terms, for example, expressing concern about discussing cash transfer at their first medical consultation with women. Though they emphasised ethical concerns about the basis of the trial, they recognised the importance of evaluating CCT.Conclusions In France, a high-income country where prenatal follow-up is free, HPs were concerned that the CCT programme would change their relationship with patients and wondered if it was the best use of funding. However, women who received a cash incentive said they did not feel stigmatised and indicated that these payments helped them prepare for their baby’s birth.Trial registration number NCT02402855

During cell division, chromosome segregation is orchestrated by a microtubule-based spindle. Interaction between spindle microtubules and kinetochores is central to the bi-orientation of chromosomes. Initially dynamic to allow spindle assembly and kinetochore attachments, which is essential for chromosome alignment, microtubules are eventually stabilized for efficient segregation of sister chromatids and homologous chromosomes during mitosis and meiosis I, respectively. Therefore, the precise control of microtubule dynamics is of utmost importance during mitosis and meiosis. Here, we study the assembly and role of a kinetochore module, comprised of the kinase BUB-1, the two redundant CENP-F orthologs HCP-1/2, and the CLASP family member CLS-2 (hereafter termed the BHC module), in the control of microtubule dynamics in Caenorhabditis elegans oocytes. Using a combination of in vivo structure-function analyses of BHC components and in vitro microtubule-based assays, we show that BHC components stabilize microtubules, which is essential for meiotic spindle formation and accurate chromosome segregation. Overall, our results show that BUB-1 and HCP-1/2 do not only act as targeting components for CLS-2 at kinetochores, but also synergistically control kinetochore-microtubule dynamics by promoting microtubule pause. Together, our results suggest that BUB-1 and HCP-1/2 actively participate in the control of kinetochore-microtubule dynamics in the context of an intact BHC module to promote spindle assembly and accurate chromosome segregation in meiosis.

BackgroundBenzodiazepines are commonly used to treat anxiety and/or insomnia but are associated with substantial safety risks. Changes to prescribing patterns in primary care may be facilitated through tailored quality improvement strategies. Academic detailing (AD) may be an effective method of promoting safe benzodiazepine prescribing. The objective of this study was to evaluate the effectiveness of AD on benzodiazepine prescribing among family physicians.Methods and findingsWe used an interrupted time series matched cohort design using population-based administrative claims databases. Participants were family physicians practicing in Ontario, Canada. The intervention was a voluntary AD service which involves brief service-oriented educational outreach visits by a trained pharmacist. The focus was on key messages for safer benzodiazepine prescribing in primary care with an emphasis on judicious prescribing to older adults aged 65 and older. Physicians in the intervention group were those who received at least one AD visit on benzodiazepine use between June 2019 and February 2020. Physicians in the control group were included if they did not receive an AD visit during the study period. Intervention physicians were matched to control physicians 1:4, on a variety of characteristics. Physicians were excluded if they had inactive billing or billing of less than 100 unique patient visits in the calendar year prior to the index date. The primary outcome was mean total benzodiazepine prescriptions at the level of the physician. Secondary outcomes were rate (per 100) of patients with long-term prescriptions, high-risk prescriptions, newly started prescriptions, and benzodiazepine-related patient harms. Data were analyzed using a repeated measures pre-post comparison with an intention-to-treat. Analyses were then stratified to focus on effects within higher-prescribing physicians. There were 1337 physicians were included in the study; 237 who received AD and 1064 who did not. There was no significant change in benzodiazepine prescribing when considering all physicians in the intervention and matched control groups. Although not significant, a greater reduction in total benzodiazepine prescriptions was observed amongst the highest-volume prescribing physicians who received the intervention (% change in slope = -0.53, 95%CI = -2.34 to 1.30, p > .05). The main limitation of our study was the voluntary nature of the AD intervention, which may have introduced a self-selection bias of physicians most open to changing their prescribing.ConclusionThis study suggests that future AD interventions should focus on physicians with the greatest room for improvement to their prescribing.

BackgroundImproved tools are required to detect bacterial infection in children with fever without source (FWS), especially when younger than 3 years old. The aim of the present study was to investigate the diagnostic accuracy of a host signature combining for the first time two viral-induced biomarkers, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and interferon γ-induced protein-10 (IP-10), with a bacterial-induced one, C-reactive protein (CRP), to reliably predict bacterial infection in children with fever without source (FWS) and to compare its performance to routine individual biomarkers (CRP, procalcitonin (PCT), white blood cell and absolute neutrophil counts, TRAIL, and IP-10) and to the Labscore.MethodsThis was a prospective diagnostic accuracy study conducted in a single tertiary center in children aged less than 3 years old presenting with FWS. Reference standard etiology (bacterial or viral) was assigned by a panel of three independent experts. Diagnostic accuracy (AUC, sensitivity, specificity) of host individual biomarkers and combinatorial scores was evaluated in comparison to reference standard outcomes (expert panel adjudication and microbiological diagnosis).Results241 patients were included. 68 of them (28%) were diagnosed with a bacterial infection and 5 (2%) with invasive bacterial infection (IBI). Labscore, ImmunoXpert, and CRP attained the highest AUC values for the detection of bacterial infection, respectively 0.854 (0.804-0.905), 0.827 (0.764-0.890), and 0.807 (0.744-0.869). Labscore and ImmunoXpert outperformed the other single biomarkers with higher sensitivity and/or specificity and showed comparable performance to one another although slightly reduced sensitivity in children < 90 days of age.ConclusionLabscore and ImmunoXpert demonstrate high diagnostic accuracy for safely discriminating bacterial infection in children with FWS aged under and over 90 days, supporting their adoption in the assessment of febrile patients.

BackgroundEndometriosis is a common gynecological condition with a wide range of symptoms, including infertility, dyspareunia, intestinal disorders, and pelvic pain. Laparoscopy and laparotomy are used widely for diagnosing and managing endometriosis. We will conduct a systematic review and meta-analysis with the aims of reporting complications rates following each type of surgeries for endometriosis and determinants of complications.MethodWe will search Medline (via PubMed), Embase, the Cochrane Library, Web of Science, and Google Scholar for both retrospective and prospective cohorts or trials of at least 30 participants reporting perioperative and postoperative complications for endometriosis surgeries. We will restrict the studies to those conducted after 2011, to be representative of current practices, and will exclude studies of surgeries for gynecological cancer, or other concomitant benign gynecologic surgeries such as myomectomy. Two reviewers will independently screen references and select eligible studies. A standardized form will be used to collect data related to the baseline characteristics, potential determinants of complications, types of interventions, and outcomes. Cumulative incidences of complications will be pooled using DerSimonian and Laird random-effects method. The relation between potential determinants and complications will be reported with risk ratios and their 95% of confidence intervals. Subgroup analysis of surgical approach, surgical procedure, superficial and deep infiltrating endometriosis, and the indication of surgery will be conducted. Sensitivity analyses restricted to studies with low risk of bias will be performed.DiscussionThis systematic review will provide information on the rates of complications for different surgical approaches and procedures for the treatment of endometriosis. It will contribute to inform patients when making decisions regarding their care. Identifying potential determinants of complications will also help to improve care by identifying women being at higher risk of complications.Trial registrationSystematic review registration: CRD42021293865.

Aponogeton madagascariensis, commonly known as the lace plant, produces leaves that form perforations by programmed cell death (PCD). Leaf development is divided into several stages beginning with “pre-perforation” furled leaves enriched with red pigmentation from anthocyanins. The leaf blade is characterized by a series of grids known as areoles bounded by veins. As leaves develop into the “window stage”, anthocyanins recede from the center of the areole towards the vasculature creating a gradient of pigmentation and cell death. Cells in the middle of the areole that lack anthocyanins undergo PCD (PCD cells), while cells that retain anthocyanins (non-PCD cells) maintain homeostasis and persist in the mature leaf. Autophagy has reported roles in survival or PCD promotion across different plant cell types. However, the direct involvement of autophagy in PCD and anthocyanin levels during lace plant leaf development has not been determined. Previous RNA sequencing analysis revealed the upregulation of autophagy-related gene Atg16 transcripts in pre-perforation and window stage leaves, but how Atg16 affects PCD in lace plant leaf development is unknown. In this study, we investigated the levels of Atg16 in lace plant PCD by treating whole plants with either an autophagy promoter rapamycin or inhibitors concanamycin A (ConA) or wortmannin. Following treatments, window and mature stage leaves were harvested and analyzed using microscopy, spectrophotometry, and western blotting. Western blotting showed significantly higher Atg16 levels in rapamycin-treated window leaves, coupled with lower anthocyanin levels. Wortmannin-treated leaves had significantly lower Atg16 protein and higher anthocyanin levels compared to the control. Mature leaves from rapamycin-treated plants generated significantly fewer perforations compared to control, while wortmannin had the opposite effect. However, ConA treatment did not significantly change Atg16 levels, nor the number of perforations compared to the control, but anthocyanin levels did increase significantly in window leaves. We propose autophagy plays a dual role in promoting cell survival in NPCD cells by maintaining optimal anthocyanin levels and mediating a timely cell death in PCD cells in developing lace plant leaves. How autophagy specifically affects anthocyanin levels remained unexplained.

Silver-Russell syndrome (SRS) is a rare imprinting disorder characterized by prenatal and postnatal growth retardation. The two principal causes of SRS are loss of methylation on chromosome 11p15 (11p15 LOM) and maternal uniparental disomy of chromosome 7 (UPD(7)mat). Knowledge of the neuropsychological profile of SRS remains sparse and incomplete even if several difficulties related to attention and learning have been reported both in the literature and by patients with SRS. These difficulties could be the result of troubles in different cognitive domains, but also of executive dysfunction. Nevertheless, executive functioning has never been investigated, even though executive functions play an essential role in psychological development, and are extensively involved in daily life. The present study explored the executive functioning of individuals with SRS due to UPD(7)mat or 11p15 LOM. A battery of executive tasks assessing cognitive flexibility, inhibitory control, and working memory, together with a task assessing sustained attention, was administered to 19 individuals with SRS (13-39 years) and 19 healthy controls. The Behavior Rating Inventory of Executive Function was also completed by the participants' families. The results showed that participants with SRS had similar performance (z-scores) to our controls, in a context of normal intellectual efficiency. Group comparisons with Bayesian statistics showed a single difference between the 11p15 LOM and control groups: the completion time for part A of the Trail Making Test appeared to be longer in the 11p15 LOM group than in the control group. However, at the clinical level, several participants with SRS had clinically significant scores on various measures of EFs. Thus, the cognitive phenotype of SRS did not appear to be characterized by executive dysfunction, but individuals with SRS could be at high risk of developing executive dysfunction or attention-deficit/hyperactivity disorder. These results provide new insights into the neuropsychological profile of individuals with SRS.

The built environment can influence physical activity behavior. Walk Score is a widely used measure of the neighborhood built environment to support walking. However, studies of the association between Walk Score and accelerometer-measured physical activity are equivocal and no studies have examined this relationship among older adults. We analyzed data from a large, diverse sample of women (n = 5650) with a mean age of 79.5 (SD = 6.7) at time of accelerometry wear in the Women’s Health Initiative Objective Physical Activity Cardiovascular Health Study in the United States to examine associations between neighborhood Street Smart Walk Score (SSWS) and accelerometer-measured physical activity. Participants wore triaxial accelerometers for seven days and SSWS was determined from home addresses. 67 % of the sample lived in “car-dependent” locations (SSWS 0–49 out of 100); only 3 % lived in “walker’s paradise” locations (SSWS 90–100). The multivariable model indicated an association between SSWS and accelerometer-measured physical activity (steps/day) in the total sample. The association varied by neighborhood socioeconomic status; in high socioeconomic status neighborhoods, higher SWSS was associated with greater steps per day, while no significant association between SWSS and physical activity was observed in low socioeconomic neighborhoods. This study should catalyze furtherresearch regarding the utility of SSWS in determining neighborhood walkability for older women across different neighborhood settings and suggests other built environment factors must be considered when determining walkability. Future studies should examine what factors influence walkability and develop age-relevant methods to assess and characterize neighborhood walkability.

Aim: To test the validity of Borg’s 6–20 rating of perceived exertion scale in assessing the exertion intensity over a multi-activity session in young and older adults.Materials and methods: This cross-sectional study included 56 healthy participants. All participants underwent a single session of activities including working on a computer, treadmill walking, biking, and treadmill running.Results: Results showed a non-significant correlation between the overall perceived exertion and energy expenditure in young people (Rho=−0.05, p=0.75) and in older adults (Rho=−0.05, p=0.78) for the whole session. However, results showed that older adults perceived significantly higher exertion compared to young people while working on a computer, walking and running, whereas they presented lower energy expenditure while resting and working on a computer.Conclusions: Combining the perceived exertion method with other commonly used methods to estimate exercise intensity would be recommended for older adults.

Abstract Objectives The introduction of a new technology has the potential to modify clinical practices, especially if easy to use, reliable and non-invasive. This observational before/after multicenter service evaluation compares fluid management practices during surgery (with fluids volumes as primary outcome), and clinical outcomes (secondary outcomes) before and after the introduction of the Pleth Variability Index (PVI), a non-invasive fluid responsiveness monitoring. Results In five centers, 23 anesthesiologists participated during a 2-years period. Eighty-eight procedures were included. Median fluid volumes infused during surgery were similar before and after PVI introduction (respectively, 1000 ml [interquartile range 25–75 [750–1700] and 1000 ml [750–2000]). The follow-up was complete for 60 from these and outcomes were similar. No detectable change in the fluid management was observed after the introduction of a new technology in low to moderate risk surgery. These results suggest that the introduction of a new technology should be associated with an implementation strategy if it is intended to be associated with changes in clinical practice.

Fly-in fly-out (FIFO) continues to be a fact of life for many men working in the mining industry. The goal of this article is to gain a better understanding of the impacts of FIFO on the overall health of men working in the mining sector and the relationship these men have to seeking help. A qualitative study of 22 men was conducted using a semi-structured interview guide modeled after Torkington et al. Results indicate that men present poor health as a result of workplace-specific performance requirements (long workdays, difficult environmental conditions), being physically far away from their family, and the fact that they do not often seek mental health help. Additional studies with a much larger sample of men are necessary.

Abstract Background Anemia is common in neurocritically ill patients. Considering the limited clinical evidence in this population, preclinical data may provide some understanding of the potential impact of anemia and of red blood cell transfusion in these patients. We aim to estimate the association between different transfusion strategies and neurobehavioral outcome in animal models. Methods We will conduct a systematic review of comparative studies of red blood cell transfusion strategies using animal models of traumatic brain injury, ischemic stroke or cerebral hemorrhage. We will search MEDLINE, EMBASE, and Web of Science databases for eligible studies from inception onwards. Two independent reviewers will perform study selection and data extraction. We will report our results in a descriptive synthesis focusing on characteristics of included studies, reported outcomes, risk of bias, and construct validity. Our primary outcome is the neurological function (neurobehavioral performance) and our secondary outcomes include mortality, infarct size, intracranial pressure, cerebral perfusion pressure, cerebral blood flow, and brain tissue oxygen tension. If appropriate, we will also perform a quantitative synthesis and pool results using random-effect models. Heterogeneity will be expressed with I 2 statistics. Subgroup analyses are planned according to animal model characteristics, co-interventions, and risks of bias. Discussion Our study is aligned with the efforts to better understand the level of evidence on the impact of red blood cell transfusion strategies from preclinical studies in animal models of acute brain injury and the potential translation of information from the preclinical to the clinical research field. Systematic review registration PROSPERO CRD42018086662 .

Abstract Chronic disease of people living with human immunodeficiency virus (HIV) infection are now approaching those of the general population. Previous, in vitro studies shown that HIV causes arterial injuries resulting in inflammation and atherosclerosis but direct relationship between HIV infection clinical stages and lower extremity arterial disease (LEAD) remain controversial. No study assessed, with an accurate method, both the prevalence of LEAD and the influence of HIV severity on LEAD in HIV outpatients in Central Africa. A cross-sectional study was conducted among 300 HIV-infected outpatients, aged ≥ 40 years in Bujumbura, Burundi. All patients underwent ankle-brachial index (ABI) measurement and LEAD was diagnosed by ABI ≤ 0.9. The prevalence of LEAD was 17.3% (CI 95% 13.2–22.1). The mean age was 49.6 ± 7.1 years. On multivariable analysis, factors associated with LEAD were hypertension (OR = 2.42; 95% CI 1.10–5.80), and stage IV HIV clinical infection (OR = 4.92, 95% CI 1.19–20.36). This is the first study performed on a large HIV population in Central Africa, reporting high LEAD prevalence. It underlines the influence of HIV infection on peripheral atherosclerosis at latest clinical stages and the need for LEAD screening in HIV-infected patients.

Abstract Our aim was to develop practical models built with simple clinical and radiological features to help diagnosing Coronavirus disease 2019 [COVID-19] in a real-life emergency cohort. To do so, 513 consecutive adult patients suspected of having COVID-19 from 15 emergency departments from 2020-03-13 to 2020-04-14 were included as long as chest CT-scans and real-time polymerase chain reaction (RT-PCR) results were available (244 [47.6%] with a positive RT-PCR). Immediately after their acquisition, the chest CTs were prospectively interpreted by on-call teleradiologists (OCTRs) and systematically reviewed within one week by another senior teleradiologist. Each OCTR reading was concluded using a 5-point scale: normal, non-infectious, infectious non-COVID-19, indeterminate and highly suspicious of COVID-19. The senior reading reported the lesions’ semiology, distribution, extent and differential diagnoses. After pre-filtering clinical and radiological features through univariate Chi-2, Fisher or Student t-tests (as appropriate), multivariate stepwise logistic regression (Step-LR) and classification tree (CART) models to predict a positive RT-PCR were trained on 412 patients, validated on an independent cohort of 101 patients and compared with the OCTR performances (295 and 71 with available clinical data, respectively) through area under the receiver operating characteristics curves (AUC). Regarding models elaborated on radiological variables alone, best performances were reached with the CART model (i.e., AUC = 0.92 [versus 0.88 for OCTR], sensitivity = 0.77, specificity = 0.94) while step-LR provided the highest AUC with clinical-radiological variables (AUC = 0.93 [versus 0.86 for OCTR], sensitivity = 0.82, specificity = 0.91). Hence, these two simple models, depending on the availability of clinical data, provided high performances to diagnose positive RT-PCR and could be used by any radiologist to support, modulate and communicate their conclusion in case of COVID-19 suspicion. Practically, using clinical and radiological variables (GGO, fever, presence of fibrotic bands, presence of diffuse lesions, predominant peripheral distribution) can accurately predict RT-PCR status.

Summary: Background: Severe COVID-19 is associated with a high circulating level of calprotectin, the S100A8/S100A9 alarmin heterodimer. Baseline calprotectin amount measured in peripheral blood at diagnosis correlates with disease severity. The optimal use of this biomarker along COVID-19 course remains to be delineated. Methods: We focused on patients with a WHO-defined moderate COVID-19 requiring hospitalization in a medical ward. We collected plasma and serum from three independent cohorts (N = 626 patients) and measured calprotectin amount at admission. We performed longitudinal measures of calprotectin in 457 of these patients (1461 samples) and used a joint latent class mixture model in which classes were defined by age, body mass index and comorbidities to identify calprotectin trajectories predicting the risk of transfer into an intensive care unit or death. Findings: After adjustment for age, sex, body mass index and comorbidities, the predictive value of baseline calprotectin in patients with moderate COVID19 could be refined by serial monitoring of the biomarker. We discriminated three calprotectin trajectories associated with low, moderate, and high risk of poor outcome, and we designed an algorithm available as online software (https://calpla.gustaveroussy.fr:8443/) to monitor the probability of a poor outcome in individual patients with moderate COVID-19. Interpretation: These results emphasize the clinical interest of serial monitoring of calprotectin amount in the peripheral blood to anticipate the risk of poor outcomes in patients with moderate COVID-19 hospitalized in a standard care unit. Funding: The study received support (research grants) from ThermoFisher immunodiagnostics (France) and Gustave Roussy Foundation.

Abstract Listeria monocytogenes is a foodborne pathogen responsible for human listeriosis. The increasing incidence of listeriosis induced governments and food manufacturing enterprises to act to diminish the problem. Several methods for the detection of Listeria monocytogenes in food industries were developed. However, they are time-consuming and require the use of specialized equipment. To reduce the detection time of Listeria monocytogenes in food, in this work we developed a fluorescence sandwich immunoassay based on the use of an innovative chitosan-cellulose nanocrystal (CNC) membrane that improves the antigen capture during bacterial growth. The combined use of CNC film for the capture of p60 protein-specific antigen together with the use of fluorescence detection reduced the time of analysis from 24 to 12 h with a limit of detection (LOD) of the assay of 102 CFU/mL (2 Log). In addition, the use of monoclonal anti-PepD covalently immobilized to a CNC membrane assured a high specificity of the assay. Interestingly, the obtained results show no cross-reactivity with the five most diffused pathogen bacteria strains tested.

Abstract Background Fetal bladder rupture causing urinary ascites is uncommon. It is generally related to invasive fetal medicine procedures or obstructive disorders such as in posterior urethral valves in male fetuses. An exceptional case of spontaneous bladder rupture in a female fetus occurred in a pregnant woman treated with high doses of opiates in an intensive care unit. This unusual obstetric situation leads to discussion of the possible causes of fetal bladder rupture, its management, and the pediatric prognosis. Case presentation We report the case of a 30-year-old nulliparous black woman with a history of mesenteric cystic lymphangioma and multiple bowel resections leading to chronic malabsorption. During her pregnancy, our patient presented with an occlusive syndrome and major bilateral renal dilation. Urinary derivation resulted in iatrogenic bilateral ureteral perforation. Our patient thus presented with major uroperitoneum, bilateral pleural effusion and acute renal failure, treated by thoracic drainage and bilateral nephrostomy. Postoperative pain required treatment with level III analgesics. In this context, 5 days after morphine treatment introduction an enlarged fetal bladder was observed, followed 3 days later by voluminous fetal ascites. The diagnosis of spontaneous bladder rupture was suspected. After multidisciplinary discussion, expectant management was decided. At 31 weeks and 4 days gestation, our patient went into spontaneous labor with a subsequent vaginal delivery. The infant required resuscitation and paracentesis of ascites at birth. Her neonatal course was favorable with a simple urethral bladder drainage. Cystography at day 9 was normal. At 2 years of follow-up, the mother and the child have a normal course. Conclusions An iatrogenic origin of megacystis in a female fetus must be evoked in the event of maternal administration of high doses of opiates in the second part of her pregnancy. In our case, the megacystis was followed by spontaneous bladder rupture at 30 weeks of gestation, with a favorable maternal fetal issue.