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Background Patients with cirrhosis suffer from many complications, including malnutrition, which must be managed promptly and effectively by the healthcare team. Educating patients about their medical condition, the risk of malnutrition and other complications of cirrhosis, could contribute to optimal nutritional status, quality of life and general health. Objective This review provides an overview of the literature on a variety of nutritional education strategies used with patients suffering from cirrhosis. This review also identifies barriers and facilitators which impact the adherence in using these strategies. Patient involvement A patient-partner contributed to this review by providing insights on different issues and concerns that patients with cirrhosis might ask themselves regarding nutritional education strategies. The patient-partner was also involved in the overall revision of the review. Methods Articles published between the years 2000–2023 focusing on nutritional education strategies in patients living with cirrhosis were identified using Google Scholar and PubMed and were screened for inclusion in the study. All selected studies were intervention studies. A quality assessment of the included studies was conducted using the Mixed Methods Appraisal Tool (MMAT). Results Only a few nutritional education strategies in patients with cirrhosis were documented in the literature. The strategies ranged from using traditional printed materials to advanced technologies. These strategies may prove beneficial in complementing routine interventions provided by health professionals, such as registered dietitians, in their clinical practice. Discussion This narrative review clearly highlights the need for further research to elaborate and evaluate nutritional education strategies for people living with cirrhosis. Practical value Elaborating and evaluating educational strategies in nutrition for patients living with cirrhosis will be an adjuvant to health professionals and dietitians in their clinical practice by providing them, and the patients, with targeted education resources.

Hepatic encephalopathy (HE) is a decline in brain function arising due to liver insufficiency. The liver's diminished capacity to clear ammonia, and the subsequent accumulation of it, is highly implicated in pathogenesis of HE. Ammonia is endogenously generated from the catabolism of amino acids derived from dietary protein intake. Therefore, a conflict arises in cirrhosis where dietary protein intake may increase ammonia and precipitate HE, and at the same time, cirrhotic patients require high daily protein intake due to altered nutrient metabolism. A nutritional solution is needed to deliver sufficient doses of protein to patients without increasing the risk of HE. In order to address this issue, this review will discuss the catabolism of individual amino acids with a special focus on ammonia-generating steps and highlight a subset of amino acids that have the potential to generate multiple equivalents of ammonia. Following, studies investigating the effects of individual amino acids in cirrhosis on blood ammonia levels as well as development of HE will be reviewed.

Background The 3D printing technology allows to produce custom shapes and add functionalities to foot orthoses which offers better options for the treatment of flatfeet. This study aimed to assess the effect of 3D printed foot orthoses stiffness and/or a newly design posting on muscle activity, plantar pressures, and center of pressure displacement in individuals with flatfeet. Methods Nineteen individuals with flatfeet took part in this study. Two pairs of foot orthoses with different stiffness were designed for each participant and 3D printed. In addition, the flexible foot orthoses could feature an innovative rearfoot posting. Muscle activity, plantar pressures, and center of pressure displacement were recorded during walking. Findings Walking with foot orthoses did not alter muscle activity time histories. Regarding plantar pressures, the most notable changes were observed in the midfoot area, where peak pressures, mean pressures and contact area increased significantly during walking with foot orthoses. The latter was reinforced by increasing the stiffness. Concerning the center of pressure displacement, foot orthoses shifted the center of pressure forward and medially at early stance. At the end of the stance phase, a transition of the center of pressure in posterior direction was observed during the posting condition. No effect of stiffness was observed on center of pressure displacement. Interpretation The foot orthoses stiffness and the addition of posting influenced plantar pressures during walking. The foot orthoses stiffness mainly altered the plantar pressures under the midfoot area. However, posting mainly acted on peak and mean pressures under the rearfoot area.

Background: Gene expression profiling (GEP), next-generation sequencing (NGS) and copy number variation (CNV) analysis have led to an increasingly detailed characterization of the genomic profiles of DLBCL. The aim of this study was to perform a fully integrated analysis of mutational, genomic, and expression profiles to refine DLBCL subtypes. A comparison of our model with two recently published integrative DLBCL classifiers was carried out, in order to best reflect the current state of genomic subtypes. Methods: 223 patients with de novo DLBCL from the prospective, multicenter and randomized LNH-03B LYSA clinical trials were included. GEP data was obtained using Affymetrix GeneChip arrays, mutational profiles were established by Lymphopanel NGS targeting 34 key genes, CNV analysis was obtained by array CGH, and FISH and IHC were performed. Unsupervised independent component analysis (ICA) was applied to GEP data and integrated analysis of multi-level molecular data associated with each component (gene signature) was performed. Findings: ICA identified 38 components reflecting transcriptomic variability across our DLBCL cohort. Many of the components were closely related to well-known DLBCL features such as cell-of-origin, stromal and MYC signatures. A component linked to gain of 19q13 locus, among other genomic alterations, was significantly correlated with poor OS and PFS. Through this integrated analysis, a high degree of heterogeneity was highlighted among previously described DLBCL subtypes. Interpretation: The results of this integrated analysis enable a global and multi-level view of DLBCL, as well as improve our understanding of DLBCL subgroups. Keywords: Diffuse large B-cell lymphoma, Independent component analysis, Transcriptomic variability, Gene signatures, prognosis

Muscle mass loss or sarcopenia is a principle component of malnutrition which prevails in 65–90% of patients with end-stage liver disease [1]. Intuitively, the roots of malnutrition play a precipitating role in muscle catabolism. Undernutrition frequently occurs in cirrhosis since an inadequate diet is compounded by a hypermetabolic energy demand. However, multiple other factors contribute to the pathogenesis of malnutrition including malabsorption of nutrients, metabolic alterations, increased intestinal protein losses, reduced protein synthesis, increased protein catabolism and disturbance of substrate utilization [2,3].

Innovative technology-based solutions have the potential to improve access to clinically proven interventions for cannabis use disorder (CUD) in individuals with first episode psychosis (FEP). High patient engagement with app-based interventions is critical for achieving optimal outcomes. 104 individuals 18 to 35 years old with FEP and CUD from three Canadian provinces completed an electronic survey to evaluate preferences for online psychological intervention intensity, participation autonomy, feedback related to cannabis use, and technology platforms and app functionalities. The development of the questionnaire was informed by a qualitative study that included patients and clinicians. We used Best-Worst Scaling (BWS) and item ranking methodologies to measure preferences. Conditional logistic regression models for BWS data revealed high preferences for moderate intervention intensity (e.g., modules with a length of 15 min) and treatment autonomy that included preferences for using technology-based interventions and receiving feedback related to cannabis use once a week. Luce regression models for rank items revealed high preferences for smartphone-based apps, video intervention components, and having access to synchronous communications with clinicians and gamification elements. Results informed the development of iCanChange (iCC), a smartphone-based intervention for the treatment of CUD in individuals with FEP that is undergoing clinical testing.

Patients with hypermobile Ehlers-Danlos syndrome commonly present with painful shoulder disorders mostly represented by a multidirectional instability and with often painless episode of atraumatic shoulder dislocation and/or subluxation. Because of the generalized soft tissue fragility, most of the surgical treatments of shoulder instability, as the Bankart repair or the Latarjet procedure becomes not effective, exposing a risk of failure. Then, capsular plication has to be considered in order to reduce the articular joint volume and to diminish the mobility of the joint. Two main benefits of this surgical procedure are that it doesn’t modify the anatomy or damage the labrum or cartilage that is healthy. The purpose of this Technical Note is to present the arthroscopic capsular plication for the treatment of patient with hypermobile Ehlers-Danlos syndrome, which is associated with a multidirectional shoulder instability., Technique Video Video 1 After a first arthroscopic exploration of the glenohumeral joint, the first plication is initiated at the inferior capsule using the passing suture technique. Plications are performed with a nonabsorbable suture threads and with the arm maintained in 30° of abduction and forward flexion with a neutral rotation. The anterior capsular tissue is then assessed with the realization of two anterior plication at 3 o’clock and 5 o’clock position. Passing the arthroscope through the anterior portal, two other posterior capsular plications are then performed passing the suture thread through the posterior portal. Intraoperative drive-through test is eventually used, and additional capsular plication can be added if needed.

Considering shoulder arthroscopy, lateral decubitus and beach chair are the 2 main employed positionings of the patient. Each include advantages and disadvantages. In our center, we perform all shoulder arthroscopy with the patient in supine position. The aim of this work is to present a stepwise approach of the accomplishment of a rotator cuff repair in supine position. Some specific technical notes are given to provide as much information as possible to help orthopaedic surgeons wishing to perform shoulder cuff repair in this position., Technique Video Video 1 A step-by-step approach of the realization of an arthroscopic rotator cuff repair with a patient in supine position. A Spider 2 Limb Positioner (Smith & Nephew) is used to help the surgeon in positioning the arm of the patient in the desired position during the whole surgery. The whole shoulder must be free of access. The surgery starts with the introduction of the arthroscope in a lateral portal for a direct visualization of the tear. An anterior and lateral portal is used to manage the long head of the biceps, to assess the glenohumeral joint, to realize the repair, and to perform an acromioplasty if it is needed. A waiting anterior portal helps the surgeon to prevent the entangling of the threads. The arthroscope must be maintained 90° relative to the ground to obtain a classical view during the procedure. A good assessment of all compartments is allowed with the patient in supine position without any added difficulty in the surgeon's movement and visualization.

Background Individuals with cerebral palsy (CP) have a reduced ability to perform motor tasks such as walking. During daily walking, they are confronted with environmental constraints such as irregular surfaces (e.g., relief and uneven surfaces) which may require adaptations to maintain stability and avoid falls. Laboratory gait assessments are conventionally conducted under ideal conditions (e.g., regular and even surfaces) and may overlook subtle problems which may only present in challenging walking environments. Increased knowledge of adaptations to successfully navigate irregular surfaces may contribute to a better understanding of everyday walking barriers. Research question This scoping review aims to describe gait adaptations to irregular surfaces in individuals with CP and contrast adaptations with those of healthy individuals. Methods This review followed the 6-stage Joanna Briggs Institute methodology and respected the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews statement. The MEDLINE, EMBASE, CINAHL, SPORTDiscus, and Web of Science databases were searched on March 2021. Results The research strategy identified 1616 studies published between 2014-2020, of which 10 were included after abstract and full-text screening. This review reported on 152 individuals with CP (diplegia: n=117, hemiplegia: n=35) and 159 healthy individuals. The included studies focused on spatial-temporal, kinematic, kinetic, and muscle activity parameters over relief, inclined, and staircase surfaces. 7/10 studies were conducted in laboratories, often using surfaces that are not representative of the real-world. The results suggest that for individuals with CP, adaptations on irregular surfaces differ from flat surface walking and across CP subtype. Moreover, individuals with CP present with typical and pathology-specific adaptations to irregular surfaces compared to healthy individuals. Significance This review highlights the clinical and research interest of focusing future studies on more ecologically valid data collection approaches and provides important recommendations to overcome research gaps in the existing literature.

International audience

Background Foot orthotics (FOs) are frequently prescribed to provide comfortable walking for patients. Finite element (FE) simulation and 3D printing pave the way to analyse, optimize and fabricate functionally graded lattice FOs where the local stiffness can vary to meet the therapeutic needs of each individual patient. Explicit FE modelling of lattice FOs with converged 3D solid elements is computationally prohibitive. This paper presents a more computationally efficient FE model of cellular FOs. Method The presented FE model features shell elements whose mechanical properties were computed from the numerical homogenization technique. To verify the results, the predictions of the homogenized models were compared to the explicit model's predictions when the FO was under a static pressure distribution of a foot. To validate the results, the predictions were also compared with experimental measurements when the FO was under a vertical displacement at the medial longitudinal arch. Results The verification procedure showed that the homogenized model was 46 times faster than the explicit model, while their relative difference was less than 8% to predict the local minimum of out-of-plane displacement. The validation procedure showed that both models predicted the same contact force with a relative difference of less than 1%. The predicted force-displacement curves were also within a 90% confidence interval of the experimental measurements having a relative difference smaller than 10%. In this case, using the homogenized model reduced the computational time from 22 h to 22 min. Conclusion The presented homogenized model can be therefore employed to speed up the FE simulation to predict the deformations of the cellular FOs.

Background Inter-joint coordination and variability during gait provide insight into control and adaptability of the neuromuscular system. To date, coordination research has been restricted to laboratory settings, and it is unclear how these findings translate to real-world, outdoor walking environments. Research Question Compared to flat walking, to what extent do outdoor surfaces impact lower-limb inter-joint coordination and variability during gait, in healthy adults? Methods Data from inertial measurement units placed on the lower-back, thigh, and shank were extracted from thirty healthy young adults (15 females, 23.5 ± 4.2 years) during outdoor walking on flat (paved sidewalk); irregular (cobblestone, grass); sloped (slope-up, slope-down); and banked (banked-right, banked-left) surfaces. Sagittal joint angles for the right knee and hip were computed and partitioned by gait phase (stance and swing). Continuous Relative Phase analysis determined inter-joint coordination and variability for the knee-hip joint pair using Mean Absolute Relative Phase (MARP) and Deviation Phase (DP), respectively. One-way repeated measures ANOVAs tested surface effects. Post-hoc Bonferroni adjusted surface comparisons were assessed. Results Significant knee-hip surface effects were seen during all gait phases for MARP (p

This case illustrates the rare presentation of endogenous Klebsiella pneumoniae endophthalmitis with concomitant orbital cellulitis from an acute pyelonephritis. A 59-year-old Caucasian female with type 2 diabetes mellitus was transferred from a regional hospital with decreased visual acuity, periorbital edema, photophobia, proptosis and pain of the right eye, as well as suprapubic discomfort. Initial ocular examination and B-scan ultrasonography were consistent with endophthalmitis and orbital cellulitis which lead to a vitreous tap and intravitreal antibiotics injection and systemic antibiotherapy. Vitreous and blood cultures confirmed Klebsiella pneumoniae as the causative organism. An orbital MRI showed a panophthalmitis with optic neuritis and further imaging confirmed a concomitant pyelonephritis secondary to a septic nephrolithiasis. The patient was given treatment with high-does intravenous antibiotics, oral and topical corticotherapy, and an early core pars plana vitrectomy (PPV), performed 5 days after presentation with repeat injections of antibiotics and dexamethasone. Unfortunately, two weeks following PPV, despite an initial stable postoperative course, the patient deteriorated and presented with purulent discharge from one of the vitrectomy port incision site. An emergency evisceration was performed in order to control the infection, revealing a large subretinal abscess and necrosed sclerotic tissue around the prior vitrectomy incision sites. Conclusion: This is the first case report of Klebsiella pneumoniae endophthalmitis or panophthalmitis presenting with orbital cellulitis and optic neuritis from an urinary tract infection. Prognosis is poor despite treatment including early vitrectomy.

International audience; A standardised, single-centre cross-sectional imaging protocol was utilised to investigate cortical grey matter and cerebral white matter alterations in 36 poliomyelitis survivors in contrast to healthy individuals and patients with amyotrophic lateral sclerosis (ALS) as a ‘disease-control’ group. [1] T1-weighted imaging and 32-direction diffusion tensor imaging data were obtained on a 3 Tesla Philips Achieva MRI system, using an IR-SPGR sequence and SE-EPI sequence respectively. Raw region-of-interest data and percentage change with respect to reference estimated marginal mean values are presented for grey and white matter metrics in key anatomical regions. Poliomyelitis survivors exhibit no frank grey or white matter degeneration. To the contrary, increased partial volumes can be detected in the brainstem, cerebellum and occipital lobes compared to healthy individuals. Higher fractional anisotropy was also noted in the corticospinal tracts, cerebellum, bilateral mesial temporal lobes and inferior frontal brain regions in poliomyelitis survivors in contrast to controls. Anatomical patterns of superior integrity metrics in polio survivors were concordant with anatomical regions of focal degeneration in ALS. Our imaging data indicate cortical and white matter reorganisation in polio survivors, which may be interpreted as compensatory adaptation to severe lower motor neuron injury acquired in infancy.

Leptomeningeal carcinomatosis (LC) is an unmet medical need associated with death in 4-6 weeks without treatment, delayed by 4 months in some patients with favorable prognosis and aggressive multimodal therapy. Unfortunately, most clinical trials excluded patients with LC, and the best management remains unknown. Here we present the first report of a LC secondary to HR positive breast cancer with a complete response to CDK4/6 inhibitors abemaciclib, letrozole and hippocampal-avoidance whole-brain radiotherapy.

Background: Endometriosis is a gynaecological disease characterized by the presence of ectopic endometrial tissue that affects women during their reproductive years, having a strong impact on their lives, fertility and healthcare costs. The aetiology remains largely unknown, but current evidence suggests that it is multi-causal and oestrogen-dependent. Many epidemiologic studies have explored associations between organochlorine chemicals (OCCs) and endometriosis, but the findings are inconsistent. Objectives: A systematic review (SR) and meta-analysis were conducted to gather and synthesize all the available evidence from human epidemiological studies about the associations between OCCs and endometriosis. Data sources: The searches were conducted in PubMed and Web of Science in June 2016 with a final follow-up in August 2018. Study eligibility criteria: Only human epidemiological studies were considered, independent of participant age, body mass index or life-stage. Studies reporting individual measures of exposure to OCCs were included, considering but not limited to polychlorinated dibenzodioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), or organochlorine pesticides (OCPs). The primary health outcome was presence of endometriosis, including all sub-types. Eligibility criteria excluded articles not written in English, conference papers, reviews and studies with overlapping information. Study appraisal and synthesis methods: A SR protocol pre-registered at PROSPERO was applied in duplicate to gather and extract all eligible original papers from PUBMED and Web of Science databases. Odds ratios were pooled using the inverse variance method for random effects meta-analysis for each group of OCCs. Risk of bias was assessed using the National Toxicology Program/Office of Health Assessment and Translation (NTP/OHAT) Risk of Bias Rating Tool for Human and Animal Studies adapted to the review question. The confidence in the body of evidence and related level of evidence was measured by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) based NTP/OHAT framework. The results were structured and presented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Of the 51 studies retained for the full-text screening, 17 provided effect sizes and metrics sufficient for pooling estimates through meta-analysis. The overall odds ratios and 95% confidence intervals were 1.65 (1.14; 2.39) for dioxins (n = 10), 1.70 (1.20; 2.39) for PCBs (n = 9), and 1.23 (1.13; 1.36) for OCPs (n = 5). Despite being statistically significant, these estimates should be considered with caution given the notable heterogeneity and small estimated effect size. Misclassification of exposure, due to varying laboratory detection rate capabilities, and disease status, due to varying definitions of endometriosis, were identified as major sources of uncertainty. Limitations, conclusions, and implications of key findings: The level of evidence was considered to be “moderate” with “serious” risk of bias according the NTP/OHAT criteria, supporting the need for further well-designed epidemiological research to fill lingering data gaps. Given the complexity of endometriosis and lack of known biomarkers suitable for population-based research, carefully designed observational studies play an important role in better understanding the aetiology of endometriosis, as will evolving mixture modeling approaches capable of handling various environmental chemical exposures. Attention to critical windows of exposure will shed further light on the possible developmental origin of endometriosis. Considering the high economic and societal cost associated with endometriosis, further research on this field is urged. Systematic review registration number: CRD42018080956 Keywords: Endometriosis, Endocrine-disrupting chemicals, Dioxins, Polychlorinated biphenyls, Biomarkers, Meta-analysis

[Introduction] Healthcare-associated infections (HAI) are among the most common adverse events of medical care. Surveillance of HAI is a key component of successful infection prevention programmes. Conventional surveillance – manual chart review – is resource intensive and limited by concerns regarding interrater reliability. This has led to the development and use of automated surveillance (AS). Many AS systems are the product of in-house development efforts and heterogeneous in their design and methods. With this roadmap, the PRAISE network aims to provide guidance on how to move AS from the research setting to large-scale implementation, and how to ensure the delivery of surveillance data that are uniform and useful for improvement of quality of care., [Methods] The PRAISE network brings together 30 experts from ten European countries. This roadmap is based on the outcome of two workshops, teleconference meetings and review by an independent panel of international experts., [Results] This roadmap focuses on the surveillance of HAI within networks of healthcare facilities for the purpose of comparison, prevention and quality improvement initiatives. The roadmap does the following: discusses the selection of surveillance targets, different organizational and methodologic approaches and their advantages, disadvantages and risks; defines key performance requirements of AS systems and suggestions for their design; provides guidance on successful implementation and maintenance; and discusses areas of future research and training requirements for the infection prevention and related disciplines. The roadmap is supported by accompanying documents regarding the governance and information technology aspects of implementing AS., [Conclusions] Large-scale implementation of AS requires guidance and coordination within and across surveillance networks. Transitions to large-scale AS entail redevelopment of surveillance methods and their interpretation, intensive dialogue with stakeholders and the investment of considerable resources. This roadmap can be used to guide future steps towards implementation, including designing solutions for AS and practical guidance checklists., This network has been supported under the 7th transnational call within the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR), Network Call on Surveillance (2018) and was thereby funded by ZonMw (grant 549007001). This project also received support from the COMBACTE MAGNET EPI-Net project funded by the Innovative Medicines Initiative Joint Undertaking under grant agreement 115523 | 115620 | 115737 | 777362, resources of which are composed of financial contribution from the European Union Seventh Framework Programme (FP7/2007-2013) and EFPIA companies in kind contribution. J.K.V. was supported by grants from Region Stockholm and Vinnova. H.H. reports grants from Pfizer and Astellas as well as personal fees from Pfizer outside the submitted work.

Objective The main objectives were to 1) search and map current disability awareness and training activities in Quebec, Canada, 2) collectively reflect on these practices, and 3) develop a five-year strategic plan. Methods We used an integrated knowledge translation approach whereby researchers and community partners were involved in all stages. This project consisted of two sequential phases: 1) an environmental scan (web review and interview) of current practices, and 2) a reflection process with an external expert-facilitator in social transformation. Outcome results and process data are reported. Results We identified 129 activities (71 training, 58 awareness) from 39 organizations (from 123 organizations initially invited). A wide range of characteristics were collected for each activity which allowed for the identification of gaps. The working group met seven times in one year to discuss results from phase 1 and co-create a five-year strategic plan. Main priorities are 1) the development of a methodology for measuring collective impact and 2) content synchronization of activities. Conclusion Involvement of partners and researchers enabled a concerted and efficient approach to the development of a five-year strategic plan. Practice implications A transition committee led by partners will ensure implementation and sustainability of the plan across the province.

International audience; Background: Foot orthoses are commonly used to correct for foot alterations and especially address excessive foot pronation in individuals with flatfeet. In recent years, 3D printing has taken a key place in orthotic manufacturing processes as it offers more options and can be patient specific. Hence, the purpose of this study was to evaluate whether stiffness of 3D printed foot orthoses and a newly designed rearfoot posting have an effect on lower limb kinematics and kinetics in individuals with flatfeet.Methods: Nineteen patients with flexible flatfeet were provided two pairs of customized 3D printed ¾ length orthotics. Foot orthoses were of different stiffness and could feature a rearfoot posting, consisting of 2-mm carbon fiber plate. Lower limb kinematics and kinetics were computed using a multi-segment foot model. One-way ANOVAs using statistical non-parametric mapping, refined by effect sizes, were performed to determine the magnitude of the effect between conditions.Findings: Foot orthoses stiffness had little effect on midfoot and forefoot biomechanics. Reductions in midfoot eversion and forefoot abduction were observed during short periods of stance with rigid foot orthoses. Adding the posting had notable effects on rearfoot kinematics and on the ankle and knee kinetics in the frontal plane; it significantly reduced the eversion angle and inversion moment at the ankle, and increased the knee abduction moment.Interpretation: Using an anti-pronator component is more effective than increasing foot orthoses stiffness to observe a beneficial impact of foot orthoses on the control of excessive foot pronation in individuals with flatfeet.

Background: Chronic inflammation and residual HIV transcription persist in people living with HIV (PLWH) receiving antiretroviral therapy (ART), thus increasing the risk of developing non-AIDS co-morbidities. The mechanistic target of rapamycin (mTOR) is a key regulator of cellular metabolism and HIV transcription, and therefore represents an interesting novel therapeutic target. Methods: The LILAC pilot clinical trial, performed on non-diabetic ART-treated PLWH with CD4+/CD8+ T-cell ratios

The day-to-day variations of sleep and physical activity are associated with various health outcomes in adults, and previous studies suggested a bidirectional association between these behaviors. The daily associations between sleep and physical activity have been examined in observational or interventional contexts. The primary goal of the current systematic review and meta-analysis was to summarize existing evidence about daily associations between sleep and physical activity outcomes at inter- and intra-individual level in adults. A systematic search of records in eight databases from inception to July 2019 identified 33 peer-reviewed empirical publications that examined daily sleep-physical activity association in adults. The qualitative and quantitative analyses of included studies did not support a bidirectional daily association between sleep outcomes and physical activity. Multilevel meta-analyses showed that three sleep parameters were associated with physical activity the following day: sleep quality, sleep efficiency, and wake after sleep onset. However, the associations were small, and varied in terms of direction and level of variability (e.g., inter- or intra-individual). Daytime physical activity was associated with lower total sleep time the following night at an inter-person level with a small effect size. From a clinical perspective, care providers should monitor the effects of better sleep promotion on physical activity behaviors in their patients. Future studies should examine sleep and physical activity during a longer period and perform additional sophisticated statistical analyses. SYSTEMATIC REVIEW REGISTRATION: https://osf.io/w6uy5/.

An athlete's connection to their team and team members is an important part of their sport experience. However, researchers currently know little about the nature of these social dynamics with respect to concussed athletes. Our study explored athletes' recovery and reintegration into the team environment following a sport-related concussion. We conducted semi-structured interviews with each member of three athlete-teammate-coach triads (N = 9). We analysed the data using thematic narrative analysis and present the results as three stories that focused on each athlete's experience. For Cassie, we found two major plot points in her story: the transition in her role (and shift in identity) from athlete to student assistant coach/team manager and, once recovered, back to an athlete on the team. For Jess, we found that the main plot in her story was “pressure”. Specifically, the interplay between internal (placed on herself) and external (perceived from teammates and coaches) pressures to return to sport. In the third and final story, the main plot point was the tensions that arose from Jaden's preferences for social support and the type of support that his teammates and coaches believed he needed during his recovery. Our results highlight the interplay between athlete's personal and social identities, feelings of pressure to return and readiness, and the challenges of providing the right amount and type of social support. This research contributes to our limited understanding of the social dynamics involved in athletes' return to sport following a concussion.

Background The role of high-dose chemotherapy with autologous stem cell transplantation (ASCT) in the treatment of soft-tissue sarcoma (STS) remains an unsettled issue. Prospective clinical trials failed to prove a benefit of the procedure but were limited by small and heterogeneous patient cohorts. Thus, it is unknown if ASCT may be a valuable treatment option in specific patient subgroups. Methods The purpose of this study was to investigate the value of ASCT according to histological subtype in STS patients who were registered in the European Society for Blood and Marrow Transplantation database between 1996 and 2016. Results Median progression-free (PFS) and overall survival (OS) in the entire cohort of 338 patients were 8.3 and 19.8 months, respectively, and PFS and OS at 5 years were 13% and 25%, respectively. Analysis of outcomes in different subgroups showed that younger age, better remission status before transplantation and melphalan-based preparative regimen were predictive of benefit from ASCT, whereas histology and grading had no statistically significant impact. Conclusions Outcomes after ASCT compared favorably to those of recent trials on conventional chemotherapies and targeted therapies in STS, including histology-tailored approaches. ASCT, thus, should be reinvestigated in clinical trials focusing on defined patient subgroups.

Contagious caprine pleuropneumonia is an infectious and contagious disease affecting goats and wildlife ruminants, mostly in Africa and Asia. It is caused by a mycoplasma, Mycoplasma capricolum susbp. capripneumoniae, which is very fastidious. This may be the reason why there are few reports of its isolation and characterization. This study describes the development of a whole genome typing strategy based on sequencing reads assemblies on a reference genome (Abomsa, GenBank accession LM995445) and extraction of informative single nucleotide polymorphism. FASTA sequences inferred from the variant calling files were used to establish a comprehensive phylogenetic tree based on 2880 SNPs. This tree included a total of 34 strains originating from all the regions where CCPP has been detected, as well as strains isolated from wildlife. A recent isolate from West-Niger was positioned closely to another 1995 East-Niger isolate, an indication that CCPP may be extending westward in Africa. Six 2013 Tanzanian isolates had identical sequences in spite of diverse geographical origins. This could be explained by the clonal expansion of a virulent strain at that time in East Africa. Although all strains isolated from wildlife in the Middle East were in the same phylogenetic group, this may not sign an adaptation to new hosts. The most probable explanation for wildlife contamination remains the contact with goats. This strategy will easily accommodate new data in the near future and should become a gold-standard high-resolution typing procedure for the surveillance of contagious caprine pleuropneumonia., Bioinformatics; Genetics; Microbiology; Evolutionary biology; veterinary medicine; Contagious caprine pleuropneumonia; Mycoplasma capricolum subsp. capripneumoniae; whole genome phylogeny

Although (S)-ketamine was approved for use in treatment-resistant depression in 2019, new preclinical findings suggest that (R)-ketamine might produce better efficacy and tolerability relative to (S)-ketamine. Here we evaluated the effects of (R)-, (S)-, and (R,S)-ketamine on executive functions as measured in the attentional set shifting task (ASST) and on their discriminative stimulus effects in rats. Earlier data demonstrated that cognitive flexibility is compromised by (R,S)-ketamine, but the effects of enantiomers in rats are unknown. Separate cohorts of rats were tested in ASST and trained to discriminate either (R,S)-ketamine, (S)-ketamine, or (R)-ketamine (all at 10 mg/kg) from saline; in order to maintain the discrimination, a higher (R)-ketamine dose (17.5 mg/kg) was subsequently instituted. In ASST, all three forms increased the trials to criterion measure at reversal learning and extra-dimensional set-shifting phases. However, in contrast to (R)- and (S)-ketamine, (R,S)-ketamine prolonged the mean time to complete a single trial during early stages, suggesting increased reaction time, and/or unspecific side-effects related to motor or motivational impairments. In the drug discriminations, all rats acquired their respective discriminations between drug and saline. In (R,S)-ketamine-trained rats, (R)-ketamine and (S)-ketamine only partially substituted for the training dose of (R,S)-ketamine. Further, (R)-ketamine did not fully substitute in rats trained to (S)-ketamine. The data suggest more serious cognitive deficits produced by (R,S)-ketamine than its enantiomers. Furthermore, (R,S)-ketamine and its isomers share overlapping but not isomorphic discriminative stimulus effects predicting distinct subjective responses to (R)- vs. (S)-ketamine in humans.

Hepatic encephalopathy (HE) is a frequent and serious complication of both chronic liver disease and acute liver failure. HE manifests as a wide spectrum of neuropsychiatric abnormalities, from subclinical changes (mild cognitive impairment) to marked disorientation, confusion and coma. The clinical and economic burden of HE is considerable, and it contributes greatly to impaired quality of life, morbidity and mortality. This review will critically discuss the latest classification of HE, as well as the pathogenesis and pathophysiological pathways underlying the neurological decline in patients with end-stage liver disease. In addition, management strategies, diagnostic approaches, currently available therapeutic options and novel treatment strategies are discussed.

Objective How variations of treatment time affect the safety and efficacy of Gamma Knife (GK) radiosurgery is a matter of considerable debate. With the relative simplicity of treatment planning for trigeminal neuralgia (TN), this question has been addressed in a group of these patients. Using the concept of the biologically effective dose (BED), the effect of the two key variables, dose and treatment time, were considered. Methods A retrospective analysis was performed of 408 TN cases treated from 1997 to 2010. Treatment involved the use of a single 4 mm isocenter. If conditions allowed, the isocenter was placed at a median distance of 7.5 mm from the emergence of the trigeminal nerve from the brain stem. The effects were assessed in terms of the incidence of the complication, hypoesthesia, and in terms of efficacy using the incidence of pain free after 30 days and 1 and 2 years. These responses were evaluated with respect to both the physical dose and the BED, the latter using a bi-exponential repair model. Results RE-evaluation showed that the prescription doses, at the 100% isodose, varied from 75 to 97.9 Gy, delivered in 25–135 minutes. The relationship between the physical dose and the incidence of hypoesthesia was not significant; the overall incidence was ∼20%. However, a clear relationship was found between the BED and the incidence of hypoesthesia, with the incidence increasing from Conclusions These results strongly suggest that safety and efficacy might be better achieved by prescribing a specific BED instead of a physical dose. A dose and time to BED conversion table has been prepared to enable iso-BED prescriptions. This finding could dramatically change dose-planning strategies in the future. However, this concept requires validation for other indications for which more complex dose planning is required.

BACKGROUND: In RECOURSE (, trifluridine/tipiracil significantly improved overall survival and progression-free survival (PFS) versus placebo in patients with pretreated metastatic colorectal cancer (mCRC). PRECONNECT was designed to further characterise safety and clinical use of trifluridine/tipiracil. METHODS: In this ongoing, international, multicentre, open-label trial, patients with pretreated mCRC received oral trifluridine/tipiracil 35 mg/m2 twice daily on days 1-5 and 8-12 of each 28-day cycle. The primary endpoint was safety; secondary endpoints included PFS and quality of life (QoL). RESULTS: 793 patients (median age 62 years) from 13 countries received trifluridine/tipiracil for a median of 2.84 months (IQR 2.64). Adverse events (AEs) were experienced by 96.7%; the most common (≥20% of patients) were neutropaenia, asthenia/fatigue, nausea, anaemia and diarrhoea. Grade ≥3 AEs occurred in 73.9% of patients, with the most common being neutropaenia (39.1% of patients), anaemia (9.8%) and asthenia/fatigue (5.0%). Median PFS was 2.8 months (95% CI 2.7 to 2.9). Median time to Eastern Cooperative Oncology Group performance status deterioration (≥2) was 8.9 months (range 0.03-14.72). There was no clinically relevant change from baseline in QoL. CONCLUSIONS: PRECONNECT showed consistent results with the previously demonstrated safety and efficacy profile of trifluridine/tipiracil, with no new safety concerns identified. QoL was maintained during treatment. TRIAL REGISTRATION NUMBER: NCT03306394. ispartof: ESMO OPEN vol:5 issue:3 ispartof: location:England status: published

Late second language (L2) learners report difficulties in specific linguistic areas such as syntactic processing, presumably because brain plasticity declines with age (following the critical period hypothesis). While there is also evidence that L2 learners can achieve native-like online-processing with sufficient proficiency (following the convergence hypothesis), considering multiple mediating factors and their impact on language processing has proven challenging. We recorded EEG while native (n = 36) and L2-speakers of French (n = 40) read sentences that were either well-formed or contained a syntactic-category error. a lexical-semantic anomaly, or both. Consistent with the critical period hypothesis, group differences revealed that while native speakers elicited a biphasic N400-P600 in response to ungrammatical sentences, L2 learners as a group only elicited an N400. However, individual data modeling using a Random Forests approach revealed that language exposure and proficiency are the most reliable predictors in explaining ERP responses, with N400 and P600 effects becoming larger as exposure to French as well as proficiency increased, as predicted by the convergence hypothesis.

Background: Lead exposure predicts altered neurodevelopment and lower intelligence quotient (IQ) in children, but few studies have examined this association in children who have relatively low blood lead concentrations. Objectives: To test the associations between blood lead concentrations and cognitive function in Canadian preschoolers, with a possible moderation by sex. Methods: The data were gathered from 609 mother-child pairs from the Maternal–Infant Research on Environmental Chemicals (MIREC) Study. Lead was measured in umbilical and maternal blood, and in children's venous blood at age 3–4 years. Cognitive function was measured with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) at 3–4 years. We tested the relationship between WPPSI-III scores and blood lead concentrations with multiple linear regression, adding child sex as a moderator. Results: Median blood lead concentrations for the mother at 1st trimester and 3rd trimester of pregnancy, and for cord and child blood were 0.60 μg/dL, 0.58 μg/dL, 0.79 μg/dL and 0.67 μg/dL, respectively. We found no association between cord blood lead concentrations and WPPSI-III scores in multivariable analyses. However, cord blood lead concentrations showed a negative association with Performance IQ in boys but not in girls (B = 3.44; SE = 1.62; 95% CI: 0.82, 5.98). No associations were found between WPPSI-III scores and prenatal maternal blood or concurrent child blood lead concentrations. Conclusions: Prenatal blood lead concentrations below 5 μg/dL were still associated with a decline in cognitive function in this Canadian cohort, but only for boys. Keywords: Blood lead concentrations, Sex differences, Intelligence quotient, Canadian children

Background: Exposure to triclosan, an antimicrobial chemical, is ubiquitous among pregnant women and may reduce thyroid hormone levels that are important for fetal neurodevelopment. Few studies have examined the association between prenatal triclosan exposure and children's neurobehavior. Objective: We investigated the relationship of prenatal urinary triclosan concentrations with children's behavior and cognitive abilities at age three years in a prospective pregnancy and birth cohort in Canada. Methods: We measured triclosan in urine samples collected at ~12 weeks of gestation in 794 Canadian women enrolled in a prospective pregnancy and birth cohort study (MIREC) from 2008 to 2011. Around age 3 years, we assessed children's cognitive abilities using the Wechsler Primary and Preschool Scale of Intelligence-III (WPPSI-III), and two scales of the Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P). Parents reported children's problem and reciprocal social behaviors using the Behavior Assessment System for Children-2 (BASC-2) and Social Responsiveness Scale-2 (SRS-2), respectively. Results: After adjusting for confounders using multivariable linear regression, triclosan was not associated with most of the 30 examined neurobehavioral scales. Each 10-fold increase in triclosan was associated with better WPPSI-III picture completion scores (β: 0.2; 95% CI: 0,0.5) and BASC-2 externalizing (β: −0.5; 95% CI: −1.1, 0) and hyperactivity (β: −0.6; 95% CI: −1.2, −0.1) scores, suggesting less externalizing and hyperactive behaviors. Child sex did not modify these associations. Conclusions: In this cohort, urinary triclosan concentrations measured once in early pregnancy were not associated with most assessed aspects of neurobehavior and weakly associated with a few others, but not in the hypothesized direction. Keywords: Triclosan, Prenatal exposure, Child neurobehavior, Children's environmental health

Background & Aims In several types of cancers, tumor cells invade adjacent tissues by migrating along the resident nerves of the tumor microenvironment. This process, called perineural invasion, typically occurs along extrinsic nerves, with Schwann cells providing physical guidance for the tumor cells. However, in the colorectal cancer microenvironment, the most abundant nervous structures belong to the nonmyelinated intrinsic enteric nervous system (ENS). In this study, we investigated whether colon cancer cells interact with the ENS. Methods Tumor epithelial cells (TECs) from human primary colon adenocarcinomas and cell lines were cocultured with primary cultures of ENS and cultures of human ENS plexus explants. By combining confocal and atomic force microscopy, as well as video microscopy, we assessed tumor cell adhesion and migration on the ENS. We identified the adhesion proteins involved using a proteomics approach based on biotin/streptavidin interaction, and their implication was confirmed further using selective blocking antibodies. Results TEC adhered preferentially and with stronger adhesion forces to enteric nervous structures than to mesenchymal cells. TEC adhesion to ENS involved direct interactions with enteric neurons. Enteric neuron removal from ENS cultures led to a significant decrease in tumor cell adhesion. TECs migrated significantly longer and further when adherent on ENS compared with on mesenchymal cells, and their trajectory faithfully followed ENS structures. Blocking N-cadherin and L1CAM decreased TEC migration along ENS structures. Conclusions Our data show that the enteric neuronal network guides tumor cell migration, partly via L1CAM and N-cadherin. These results open a new avenue of research on the underlying mechanisms and consequences of perineural invasion in colorectal cancer., Graphical abstract

© 2020 The Authors., [Objectives]: To expand on previous reports of synergy between polymyxin B (PMB) and minocycline (MIN) against Acinetobacter baumannii; and to gain insight into the qualitative and quantitative determinants of their synergy., [Methods]: A semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model was developed on the basis of data from in vitro time-kill experiments with determination of resistant bacterial count to describe the effects of PMB and MIN alone and in combination. The model was enriched by complementary experiments providing information on the characteristics of the resistant subpopulation., [Results]: The model successfully described the data and made possible quantification of the strength of interaction between the two drugs and formulation of hypotheses about the mechanisms of the observed interaction. The effect of the combination was driven by MIN, with PMB acting as an helper drug; simulations at clinically achievable concentrations showed that 1.5 mg/L MIN +0.2 mg/L PMB is expected to produce sustained killing over 30 hours, while 0.3 mg/L MIN +1 mg/L PMB is met by bacterial regrowth. Interaction equations showed that maximal synergy is reached for PMB concentrations ≥0.1 mg/L and MIN concentrations ≥1 mg/L., [Conclusions]: Semi-mechanistic PK/PD modelling was used to investigate the quantitative determinants of synergy between PMB and MIN on a PMB-resistant A. baumannii strain. The developed model, improving on usual study techniques, showed asymmetry in the drug interaction, as PMB acted mostly as a helper to MIN, and provided simulations as a tool for future studies., We thank L. Friberg (Uppsala University) for input related to model building and E. Marquizeau (Université de Poitiers) for technical support.

The linear reverse blotting assays are valid methods for accurate human papillomavirus (HPV) typing required to manage women at risk of developing cervical cancer. However, some samples showed a positive signal in HPV lines but failed to display a positive signal in subsequent typing lines (designated as HPV-X), which indicate that certain types were not available on the respective typing blots. The aim of this study is to elucidate the types or variants of HPV through the high-throughput sequencing (HTS) of 54 ASCUS cervical samples in which the viruses remained untypeable with INNO LiPA HPV® assays. Low-risk (LR)-HPV types (HPV6, 30, 42, 62, 67, 72, 74, 81, 83, 84, 87, 89, 90 and 114), high-risk (HR)-HPV35 and possibly (p)HR-HPV73 were detected among HPV-X. Individual multiple infections (two to seven types) were detected in 40.7% of samples. Twenty-two specimens contained variants characterised by 2–10 changes. HPV30 reached the maximal number of 17 variants with relative abundance inferior or equal to 2.7%. The presence of L1 quasispecies explains why linear reverse blotting assays fail when variants compete or do not match the specific probes. Further studies are needed to measure the LR-HPV quasispecies dynamics and its role during persistent infection., Highlights • Types which linear reverse blotting assays are unable to identify are mainly multiple LR-HPV. • Deep sequencing of L1 permits to identify minority variants in 41% of these samples. • Understanding of LR-HPV quasispecies dynamics during infection is awaited.

Background Communication partner training could be employed to train people working in the community to facilitate interaction with individuals who live with a variety of communication disorders. However, current evidence syntheses are limited to a single disorder (e.g., aphasia) and focus on a variety of familiar and unfamiliar communication partners. An understanding of the scope of literature across the evidence-base of acquired neurological populations may provide a better basis to develop interventions and future research tailored for community workers. Aims To explore the scope of literature on paid worker and unfamiliar partner communication training for acquired neurogenic communication disorders with a focus on describing: 1) the types of communication disorders addressed by interventions; 2) the types of learners who received the interventions; 3) the nature of the interventions; and 4) the reported effects on trainees and people with a communication disorder. Methods & procedures A scoping review was conducted. Studies were selected by a systematic keyword search, undertaken through four databases. Eligibility criteria included studies that: (i) reported an intervention directed at paid workers or unfamiliar partners where the primary goal was to improve communication with people with acquired neurogenic communication disorders, (ii) reported original results, (iii) contained quantitative or qualitative data on the effects of the intervention, (iv) were written in English or French and (v) were published in a peer-reviewed journal. The PRISMA-ScR was used to guide design and reporting of the scoping review. Results Seventy publications met the inclusion criteria. Interventions were mostly disorder-specific and addressed communication with people with dementia, aphasia or traumatic brain injury. 15/70 studies examined training programs that were not restructured to a specific population (e.g., aphasia). Learners were mostly working or studying in the healthcare field and only 2/70 studies included community workers without primarily health training. Sixty different interventions were reported and were mostly delivered by speech-language pathologists. Training varied in terms of duration (a few minutes to 46 h) and content, but many shared training methods (e.g., presentation of theory on communication disorders). Nearly all studies demonstrated positive results, 23/26 studies suggested that paid worker and unfamiliar partner communication training may increase the knowledge of trainees, 24/26 studies suggested that it could improve their confidence when interacting with people with a communication disorder and 44/46 studies suggested that it could improve the trainees’ communication abilities. Conclusion A small developing evidence-base exists for communication training programs for paid and unfamiliar communications partners that focuses beyond a single diagnosis or disorder. However, there is very limited knowledge on interventions for community workers from non-health professions. Future research should focus on the evaluation of existing programs tailored to, or explicitly designed for this context with the aim of identifying active ingredients that lead to improved and sustainable outcomes.

Objective Foot orthoses (FOs) are popular treatment to alleviate several abnormalities of lower extremity. FO designs might alter lower extremity biomechanics differently, but the association is not yet known. This review aimed to evaluate how different FO designs, namely FO with medial posting, lateral posting, arch support, or arch & heel support, change lower limb kinematics and kinetics during walking. Literature survey Electronic database search were conducted from inception to March 2019, and 25 papers passed the inclusion criteria. Two independent reviewers checked the quality using a modified Downs and Black checklist (73.7 ± 5.5%) and a biomechanical quality checklist (71.4 ± 17.1%). Effect sizes for differences between with- and without- FO walking were calculated, and meta-analysis was performed whenever at least two studies reported the same variable. Results Medial posting reduced peak ankle eversion moment. Lateral posting brought about higher peak ankle dorsiflexion and peak ankle eversion for kinematics, as well as higher peak ankle abduction moment, lower peak knee adduction moment, and higher peak mediolateral ground reaction force (GRF) for kinetics. FOs with either arch support or arch & heel support tended to decrease vertical ground reaction force, but it was not significant. Conclusion The findings of this review reveal that medial or lateral posting work efficiently to change foot and knee kinematics and kinetics. However, the impact force is just slightly decreased by arch-supported and heel supported FOs. Due to the small number of available studies, and heterogeneity in meta-analysis findings, further research with more standardized biomechanical approach are required.

Objectives Hepatokines are proteins secreted by the liver that impact the functions of the liver and various tissues through autocrine, paracrine, and endocrine signaling. Recently, Tsukushi (TSK) was identified as a new hepatokine that is induced by obesity and cold exposure. It was proposed that TSK controls sympathetic innervation and thermogenesis in brown adipose tissue (BAT) and that loss of TSK protects against diet-induced obesity and improves glucose homeostasis. Here we report the impact of deleting and/or overexpressing TSK on BAT thermogenic capacity, body weight regulation, and glucose homeostasis. Methods We measured the expression of thermogenic genes and markers of BAT innervation and activation in TSK-null and TSK-overexpressing mice. Body weight, body temperature, and parameters of glucose homeostasis were also assessed in the context of TSK loss and overexpression. Results The loss of TSK did not affect the thermogenic activation of BAT. We found that TSK-null mice were not protected against the development of obesity and did not show improvement in glucose tolerance. The overexpression of TSK also failed to modulate thermogenesis, body weight gain, and glucose homeostasis in mice. Conclusions TSK is not a significant regulator of BAT thermogenesis and is unlikely to represent an effective target to prevent obesity and improve glucose homeostasis., Highlights • Loss of TSK does not affect brown fat thermogenic capacity. • Loss of TSK does not protect mice against the development of obesity. • Loss of TSK does not improve glucose homeostasis. • Overexpression of TSK does not affect thermogenesis, body weight gain and glucose homeostasis.

Study objective Multisource feedback is a process through which different members of the care team assess and provide feedback on residents' competencies, usually those that are less often addressed by traditional assessment methods (ie, communication, collaboration, and professionalism). Feasibility and reliability of multisource feedback have been addressed in previous research. The present study explores emergency residents' perceptions of multisource feedback provided by teaching physicians, nurses, and patients they have worked with during a rotation in an emergency department (ED). Methods A multisource feedback intervention was proposed to residents during 9 months in the ED of a tertiary care university hospital. Residents distributed feedback questionnaires to physicians, nurses, and patients that focused on competencies (collaboration, communication, and professionalism) from the CanMEDS framework. Responses were compiled and reported to participating residents. To assess residents' perceptions of multisource feedback, semistructured group and individual interviews were held 3 months after the intervention. Transcripts were analyzed qualitatively, following Miles and Huberman's method for intrasite case analysis. Results According to residents (n=10), each source (physicians, nurses, and patients) provided relevant comments that differed significantly in their content. Physicians focused primarily on medical expertise; nurses addressed competencies related to leadership, collaboration, and communication; and patients commented on the competencies of professionalism and communication. Residents concluded that obtaining feedback from nurses and patients was acceptable and useful. They reported modifying certain behaviors after receiving the multisource feedback. Conclusion Residents perceived the multisource feedback to be acceptable and useful for the assessment of medical competencies such as communication, collaboration, professionalism, and leadership.

Capnocytophaga sputigena is an unusual cause of community-acquired pneumonia. A 22-year-old woman presented an amoxicillin-resistant pneumonia. Sputum examination detected C. sputigena from 3 specimens with a significant bacterial load. The strain produced beta lactamase. Evolution was favorable after introduction of amoxicillin-clavulanate acid. Physicians might be aware of the presence of this unusual bacterium in cases of community-acquired pneumonia. Keywords: Community-acquired pneumonia, Capnocytophaga sputigena

International audience; Motile cilia and sperm flagella share an evolutionarily conserved axonemal structure. Their structural and/or functional defects are associated with primary ciliary dyskinesia (PCD), a genetic disease characterized by chronic respiratory-tract infections and in which most males are infertile due to asthenozoospermia. Among the well-characterized axonemal protein complexes, the outer dynein arms (ODAs), through ATPase activity of their heavy chains (HCs), play a major role for cilia and flagella beating. However, the contribution of the different HCs (γ-type: DNAH5 and DNAH8 and β-type: DNAH9, DNAH11, and DNAH17) in ODAs from both organelles is unknown. By analyzing five male individuals who consulted for isolated infertility and displayed a loss of ODAs in their sperm cells but not in their respiratory cells, we identified bi-allelic mutations in DNAH17. The isolated infertility phenotype prompted us to compare the protein composition of ODAs in the sperm and ciliary axonemes from control individuals. We show that DNAH17 and DNAH8, but not DNAH5, DNAH9, or DNAH11, colocalize with α-tubulin along the sperm axoneme, whereas the reverse picture is observed in respiratory cilia, thus explaining the phenotype restricted to sperm cells. We also demonstrate the loss of function associated with DNAH17 mutations in two unrelated individuals by performing immunoblot and immunofluorescence analyses on sperm cells; these analyses indicated the absence of DNAH17 and DNAH8, whereas DNAH2 and DNALI, two inner dynein arm components, were present. Overall, this study demonstrates that mutations in DNAH17 are responsible for isolated male infertility and provides information regarding ODA composition in human spermatozoa.

Background Venous congestion might lead to congestive encephalopathy after cardiac surgery. However, objective signs of congestion have yet to be associated with delirium. Portal vein flow pulsatility is a congestion marker that may identify a subgroup of patients at risk. Methods We performed a retrospective study and a prospective study in patients undergoing cardiac surgery. Adult patients who underwent portal vein Doppler imaging by the attending physician during usual care in the intensive care unit were included in the retrospective cohort. For the prospective cohort, patients had a cognitive and echocardiographic evaluation the day before surgery and daily for 3 days after surgery. Delirium was independently assessed by the nursing staff in the prospective cohort. Results A total of 237 patients in the retrospective cohort and 145 patients in the prospective cohort were included, for whom 1074 portal Doppler evaluations were performed. An association was found between delirium and portal vein pulsatility in the retrospective cohort (odds ratio [OR], 2.69; confidence interval [CI], 1.47-4.90; P = 0.001). In the prospective cohort, significant associations were found between the presence of portal vein pulsatility and the development of cognitive dysfunction and asterixis assessed by the investigators (OR, 2.10; CI, 1.25-3.53; P = 0.005 and OR, 2.23; CI, 1.13; 4.41; P = 0.02, and delirium detected by the nursing staff (hazard ratio, 2.63; CI, 1.13-6.11; P = 0.025). Higher N-terminal pro-beta natriuretic peptide measurements (OR, 4.03; CI, 1.78-9.15; P = 0.001) and cerebral desaturations (OR, 2.54; CI, 1.12-5.76; P = 0.03) were associated with cognitive dysfunction. Conclusion These data present an association among hepatic congestion, delirium, and encephalopathy in patients undergoing cardiac surgery. Further studies should explore whether those neurological complications may have a congestive origin in some patients., Contexte La congestion veineuse peut entraîner une encéphalopathie congestive après une chirurgie cardiaque. Toutefois, aucune association n’a été établie jusqu’à présent entre les signes objectifs de la congestion et le délire. La pulsatilité du flux de la veine porte est un marqueur de la congestion qui pourrait permettre de distinguer un sous-groupe de patients à risque. Méthodologie Nous avons effectué une étude rétrospective et une étude prospective portant sur des patients subissant une chirurgie cardiaque. Des patients adultes qui se sont prêtés à un examen de la veine porte par imagerie Doppler, réalisé par le médecin dans le cadre des soins standard dispensés à l’unité des soins intensifs, ont été inclus dans la cohorte rétrospective. Pour la cohorte prospective, les patients avaient fait l’objet d’une évaluation cognitive et échocardiographique la veille de l’intervention chirurgicale et quotidiennement pendant les 3 jours suivant la chirurgie. Dans la cohorte prospective, le délire était évalué de façon indépendante par le personnel infirmier. Résultats Au total, 237 patients ont été inclus dans la cohorte rétrospective et 145 patients dans la cohorte prospective, chez lesquels 1074 examens Doppler de la veine porte avaient été effectués. Une association a été observée entre le délire et la pulsatilité de la veine porte dans la cohorte rétrospective (rapport de cotes [RC] : 2,69; intervalle de confiance [IC] : de 1,47 à 4,90; p = 0,001). Dans la cohorte prospective, les chercheurs ont observé des associations significatives entre la présence d’une pulsatilité de la veine porte et l’apparition d’une dysfonction cognitive et d’un astérixis (RC : 2,10; IC : de 1,25 à 3,53; p = 0,005 et RC : 2,23; IC : de 1,13 à 4.41; p = 0,02) ainsi que le délire détecté par le personnel infirmier (RC : 2,63; IC : de 1,13 à 6,11; p = 0,025). Des valeurs élevées du fragment propeptide natriurétique de type B N-terminal (RC : 4,03; IC : de 1,78 à 9,15; p = 0,001) et la désaturation cérébrale (RC : 2,54; IC : de 1,12 à 5,76; p = 0,03) étaient associées à une dysfonction cognitive. Conclusions Ces données montrent l’association existant entre la congestion hépatique, le délire et l’encéphalopathie chez des patients subissant une chirurgie cardiaque. Des études additionnelles devraient être menées dans le but de voir si ces complications neurologiques pourraient avoir une origine congestive chez certains patients.

International audience; PURPOSE: This work reports, in melanoma models, the theranostic potential of ICF15002 as a single fluorinated and iodinated melanin-targeting compound. METHODS: Studies were conducted in the murine syngeneic B16BL6 model and in the A375 and SK-MEL-3 human xenografts. ICF15002 was radiolabeled with fluorine-18 for positron emission tomography (PET) imaging and biodistribution, with iodine-125 for metabolism study, and iodine-131 for targeted radionuclide therapy (TRT). TRT efficacy was assessed by tumor volume measurement, with mechanistics and dosimetry parameters being determined in the B16BL6 model. Intracellular localization of ICF15002 was characterized by secondary ion mass spectrometry (SIMS). RESULTS: PET imaging with [ 18 F]ICF15002 evidenced tumoral uptake of 14.33 ± 2.11%ID/g and 4.87 ± 0.93%ID/g in pigmented B16BL6 and SK-MEL-3 models, respectively, at 1 hour post inoculation. No accumulation was observed in the unpigmented A375 melanoma. SIMS demonstrated colocalization of ICF15002 signal with melanin polymers in melanosomes of the B16BL6 tumors. TRT with two doses of 20 MBq [ 131 I]ICF15002 delivered an absorbed dose of 102.3 Gy to B16BL6 tumors, leading to a significant tumor growth inhibition [doubling time (DT) of 2.9 ± 0.5 days in treated vs 1.8 ± 0.3 in controls] and a prolonged median survival (27 days vs 21 in controls). P53S15 phosphorylation and P21 induction were associated with a G2/M blockage, suggesting mitotic catastrophe. In the human SK-MEL-3 model, three doses of 25 MBq led also to a DT increase (26.5 ± 7.8 days vs 11.0 ± 3.8 in controls) and improved median survival (111 days vs 74 in controls). CONCLUSION: Results demonstrate that ICF15002 fulfills suitable properties for bimodal imaging/TRT management of patients with pigmented melanoma.

Background/purpose The motivations of dental students for their studies have largely been investigated in numerous countries using psychometric questionnaires. This is not the case in France since validated tools are still lacking. The aim of the present work was dedicated to the psychometric validation of a motivation questionnaire adapted for predoctoral French dental students. Material and methods The design corresponded to a monocentric study realized at the dental school of Nantes University, France. A 14-item questionnaire was translated into French and adapted for dental studies. It was autoadministered by the students between March 2014 and May 2014. Exploratory and confirmatory factorial analyses were used to investigate the psychometric properties of the French version. Results The rate of reply was 88.7% with a sex allocation consisting of 44.4% men and 55.6% women. The internal reliability and the item-sampling adequacy of the questionnaire reached acceptance thresholds. Exploratory and confirmatory factorial analyses established a four-factor structure with good internal reliability. The factors consisted in “altruism,” “status and incomes,” “scientific curiosity,” and “educational advantages.” Factors correlated well with the overall questionnaire. The overall motivation score did not differ between male and female students, although “altruism” was best scored by female students while “status and incomes” obtained a higher score in the population of male students. Both male and female students displayed similar “scientific curiosity” and “educational advantages” scorings. Conclusion Our data establish that the French motivation questionnaire has good psychometric properties and that it is relevant for further studies.

Children who develop greater negatively-biased recall of pain (ie, recalled pain is higher than the initial pain report) following surgery are at risk for developing chronic pain; therefore, identifying risk factors for the development of biased pain memories is important. Higher anxiety has been implicated in the development of greater negatively-biased recall of pain; however, studies have not examined anxiety at multiple time points before and after a surgery and its relationship to children's postsurgical pain memories after 1 year. This prospective study examined a cohort of 237 children and adolescents undergoing major surgery. Anxiety sensitivity, pain catastrophizing, and pain anxiety were assessed at baseline, 48 to 72 hours after surgery, and at 6- and 12-month follow-ups. Pain intensity at rest, movement-evoked pain intensity, and pain unpleasantness were assessed daily in hospital. Memories for pain were elicited via telephone 1-year post surgery. Findings revealed that children who had higher levels of anxiety at baseline and 48 to 72 hours after surgery developed greater negatively-biased recall of pain intensity 12 months after surgery. Specifically, higher anxiety sensitivity at baseline and greater tendencies to catastrophize about pain at baseline and in the immediate acute recovery phase were most strongly linked to greater negatively-biased recall of pain. Greater negatively-biased recall of pain was related to higher pain intensity at 6 and 12 months post surgery. Findings support conceptual models of anxiety and pain memory biases and can inform intervention efforts to reduce anxiety in the pre- and post-op periods to minimize negative biases in pain memories.

Background Braking forces absorbed by the leading paretic limb are greater than expected with regard to gait speed and not correlated with propulsive forces generated by the non-paretic limb in individuals with severe hemiparesis. Altered foot placement due to poor sensorimotor capacities may explain excessive braking forces. Research question The main objective of this study was to determine whether paretic foot placement was related to paretic braking forces in post-stroke individuals with various self-selected walking speeds and motor deficits. Methods In this cross-sectional study, 34 chronic hemiparetic post-stroke individuals, divided into slow (

The Liver Imaging Reporting And Data System (LI-RADS) was created with the support of the American College of Radiology (ACR) to standardize the acquisition, interpretation, reporting, and data collection for imaging examinations in patients at risk for hepatocellular carcinoma (HCC). A comprehensive and rigorous system developed by radiologists, hepatologists, pathologists, and surgeons, LI-RADS addresses a wide range of imaging contexts. Currently, 4 algorithms are available publicly on the ACR website: ultrasound for HCC surveillance, computed tomography and magnetic resonance imaging for HCC diagnosis and tumor staging, contrast-enhanced ultrasound for HCC diagnosis, and computed tomography/magnetic resonance imaging for treatment response assessment. Each algorithm is supported by a decision tree, categorization table, lexicon, atlas, technical requirements, and reporting and management guidance. Category codes reflecting the relative probability of HCC and malignancy are assigned to imaging-detected liver observations, with emerging evidence suggesting that LI-RADS accurately stratifies HCC and malignancy probabilities. LI-RADS is an evolving system and has been updated and refined iteratively since 2011 based on scientific evidence, expert opinion, and user feedback, with input from the American Association for the Study of Liver Diseases and the Organ Procurement Transplantation Network/United Network for Organ Sharing. Concurrent with its most recent update, LI-RADS was integrated into the American Association for the Study of Liver Diseases HCC guidance released in 2018. We anticipate continued refinement of LI-RADS and progressive adoption by radiologists worldwide, with the eventual goal of culminating in a single unified system for international use.

Objectives To evaluate the diagnostic validity of the Kerlan-Jobe orthopedic clinic shoulder and elbow score (KJOC) and the Closed kinetic upper extremity stability test (CKCUEST) to assess functional impairments associated with shoulder injury in overhead female athletic populations. Design Cross-sectional design. Methods Thirty-four synchronized swimming and team handball female athletes completed the KJOC and the CKCUEST during their respective team selection trials. Unsupervised learning using k-means algorithm was used on collected data to perform group clustering and classify athletes as Injured or Not Injured. Odds ratios, likelihood ratios, sensitivity and specificity were computed based on the self-reported presence of shoulder injury at the time of testing or during the previous year. Results Seven of the 34 athletes were injured or had suffered a time-loss injury in the previous year, representing a 20.5% prevalence rate. Clustering method using KJOC data resulted in a sensitivity of 86%, a specificity of 100% and a 229.67 diagnostic odds ratio. Clustering method using CKCUEST data resulted in a sensitivity of 86%, a specificity of 37% and a 3.53 diagnostic odds ratio. Conclusions KJOC had good diagnostic validity to assess shoulder function and differentiate between injured and non-injured elite synchronized swimming and team handball female athletes. The CKCUEST seemed to be a poor screening test but may be an interesting test to evaluate functional upper extremity strength and plyometric capacity. Unsupervised learning methods allow to make decisions based on numerous variables which is an advantage when considering the usually substantial overlap in screening test scores between high- and low-risk athletes.

Although placebo analgesia is a well-recognized phenomenon with important clinical implications, the possibility that placebo effects occur during sleep has received little attention. This experimental study examined whether responsiveness to acute heat pain stimuli applied during sleep could be reduced following a placebo conditioning procedure administered before sleep. Healthy individuals (n = 9) underwent polysomnographic recordings for one habituation night followed by one placebo analgesia night and one control night in counterbalanced order. Conditioning induced robust analgesia expectations before the placebo night. In the morning after the placebo night, participants reported less nocturnal pain, anxiety, and associated sleep disturbance (all p's