Modelling the impact of liver regeneration on hepatoblastoma patient-derived-xenograft tumor growth.

BACKGROUND: Twenty percent of children with hepatoblastoma (HB) have lung metastasis at diagnosis. Treatment protocols recommend surgical removal of chemotherapy-refractory lung nodules, however no chronological order is established. As hepatectomy is followed by release of growth factors, it has been proposed that partial hepatectomy (PH) could boost local or distant residual tumor growth. METHODS: To evaluate the impact of PH on distant tumor growth, PH was performed in mice subcutaneously implanted with a HB patient-derived xenograft (PDX). The influence of PH on tumor growth at primary site was assessed by performing PH concomitantly to HB PDXs orthotopic implantation. RESULTS: Subcutaneously implanted HB PDX failed to show any influence of hepatectomy on tumor growth. Instead, intrahepatic tumor growth of one of the 4 HB PDXs implanted orthotopically was clearly enhanced. Cells derived from the hepatectomy-sensitive HB PDX exposed to hepatic growth factor (HGF) showed increased proliferation rate compared to cells derived from a hepatectomy-insensitive model, suggesting that the HGF/MET pathway could be one of the effectors of the crosstalk between liver regeneration and HB growth. CONCLUSION: These results suggest that hepatectomy can contribute to HB growth in some patients, further studies will be necessary to identify biomarkers predictive of patient risk of PH-induced HB recurrence. IMPACT: Key message: Cytokines and growth factors secreted following partial hepatectomy can contribute to intrahepatic tumor growth in some hepatoblastoma models. What does it add to the existing literature: It is the first article about the impact of liver regeneration induced by partial hepatectomy on hepatoblastoma local or distant tumoral growth in nude mice. What is the impact: It is important to identify the secreted factors that enhance tumor growth and to define biomarkers predictive of patient risk of partial hepatectomy-induced hepatoblastoma recurrence.

Non-vascularized coracoid process autograft for glenoid reconstruction in revision shoulder arthroplasty.

PURPOSE: To report the radiological and clinical outcomes of non-vascularized coracoid process autografts used for glenoid reconstruction during revision shoulder arthroplasty. MATERIAL AND METHOD: This is a retrospective, monocentric study from January 2016 to October 2022 targeting patients treated with a coracoid bone graft for glenoid reconstruction during revision of shoulder arthroplasty. The primary outcome measures were coracoid graft union rate and graft-implant osseointegration. Secondary outcome measures included clinical and CT-scan identified radiological complications and functional outcomes as measured by the Visual Analog Scale (VAS), Range of Motion (ROM), Subjective Shoulder Value (SSV), Constant score (absolute and ponderate), and ASES score. RESULTS: Fifteen patients (9 males, 6 females; mean age 66.9 years, range 38-85) were included. At a mean follow-up of 20.9 months (range 12-56 months), 93.3% achieved complete graft integration. One case of partial lysis without baseplate loosening was noted. Regarding range of motion, the mean forward elevation was 130° (range 90°-170°), external rotation at the side 25° (range 10°-40°), external rotation in 90° of abduction 45° (range 10°-80°), and internal rotation 52° (range 10-80°). The mean VAS for pain was 1.1 (range 0-8), mean SSV 67.3% (range 40-90%), mean ASES score 85.5 (range 65-98.3), mean Absolute Constant score 58.6 (range 21-83), and mean Ponderate Constant score 77.5% (range 28.8-110.7%). No neurological injuries were reported. CONCLUSION: Utilizing a non-vascularized coracoid graft during shoulder arthroplasty revision is a safe, reproducible, and time-efficient technique that demonstrated satisfactory osseointegration, implant stability, good functional results, and a low complication rate.

Slc11a1 gene polymorphism influences dextran sulfate sodium (DSS)-induced colitis in a murine model of acute inflammation.

Ulcerative Colitis (UC) is an inflammatory disease characterized by colonic mucosal lesions associated with an increased risk of carcinogenesis. UC pathogenesis involves environmental and genetic factors. Genetic studies have indicated the association of gene variants coding for the divalent metal ion transporter SLC11A1 protein (formerly NRAMP1) with UC susceptibility in several animal species. Two mouse lines were genetically selected for high (AIRmax) or low (AIRmin) acute inflammatory responses (AIR). AIRmax is susceptible, and AIRmin is resistant to DSS-induced colitis and colon carcinogenesis. Furthermore, AIRmin mice present polymorphism of the Slc11a1 gene. Here we investigated the possible modulating effect of the Slc11a1 R and S variants in DSS-induced colitis by using AIRmin mice homozygous for Slc11a1 R (AIRminRR) or S (AIRminSS) alleles. We evaluated UC by the disease activity index (DAI), considering weight loss, diarrhea, blood in the anus or feces, cytokines, histopathology, and cell populations in the distal colon epithelium. AIRminSS mice have become susceptible to DSS effects, with higher DAI, IL6, G-CSF, and MCP-1 production and morphological and colon histopathological alterations than AIRminRR mice. The results point to a role of the Slc11a1 S allele in DSS colitis induction in the genetic background of AIRmin mice.

A spatially explicit trait-based approach uncovers changes in assembly processes under warming.

The re-assembly of plant communities during climate warming depends on several concurrent processes. Here, we present a novel framework that integrates spatially explicit sampling, plant trait information and a warming experiment to quantify shifts in these assembly processes. By accounting for spatial distance between individuals, our framework allows separation of potential signals of environmental filtering from those of different types of competition. When applied to an elevational transplant experiment in the French Alps, we found common signals of environmental filtering and competition in all communities. Signals of environmental filtering were generally stronger in alpine than in subalpine control communities, and warming reduced this filter. Competition signals depended on treatments and traits: Symmetrical competition was dominant in control and warmed alpine communities, while hierarchical competition was present in subalpine communities. Our study highlights how distance-dependent frameworks can contribute to a better understanding of transient re-assembly dynamics during environmental change.

Opposing Responses to Scarcity Emerge from Functionally Unique Sociality Drivers.

AbstractFrom biofilms to whale pods, organisms across taxa live in groups, thereby accruing numerous diverse benefits of sociality. All social organisms, however, pay the inherent cost of increased resource competition. One expects that when resources become scarce, this cost will increase, causing group sizes to decrease. Indeed, this occurs in some species, but there are also species for which group sizes remain stable or even increase under scarcity. What accounts for these opposing responses? We present a conceptual framework, literature review, and theoretical model demonstrating that differing responses to sudden resource shifts can be explained by which sociality benefit exerts the strongest selection pressure on a particular species. We categorize resource-related benefits of sociality into six functionally distinct classes and model their effect on the survival of individuals foraging in groups under different resource conditions. We find that whether, and to what degree, the optimal group size (or correlates thereof) increases, decreases, or remains constant when resource abundance declines depends strongly on the dominant sociality mechanism. Existing data, although limited, support our model predictions. Overall, we show that across a wide diversity of taxa, differences in how group size shifts in response to resource declines can be driven by differences in the primary benefits of sociality.

An EMR-based alert with brief provider-led ART adherence counseling in Haiti: effects on information, motivation, and behavioral skills (IMB) and patient-provider communication (PPC).

We examined the secondary effects of an antiretroviral therapy (ART) adherence intervention on information, motivation, and behavioral skills (IMB) and patient-provider communication (PPC). Data were from a sample of 116 patients enrolled in a quasi-experimental mixed-methods study at two large ART clinics in Haiti. We examined changes in IMB and PPC scores after the intervention and the association between baseline PPC and endline IMB.The intervention was associated with increased scores in information (ß = 0.89, 95% CI [0.07, 1.70]) and motivation (ß = 2.55, 95% CI [0.38, 4.72]) but a decreased score in behavioral skills (ß = -2.39, 95% CI [-4.29, -0.49]), after controlling for demographic and clinical variables. Baseline PPC was associated with higher endline IMB total scores (ß = 0.17, 95% CI [0.02, 0.31]), controlling for demographic variables, clinical variables, and baseline IMB score. At the subscale level, baseline PPC was associated with higher endline motivation score (ß = 0.09, 95% CI [0.01, 0.17]), marginally associated with higher endline information score (ß = 0.04, 95% CI [0.00, 0.08]), after controlling for demographic and clinical variables.The intervention was beneficial to patients' adherence related motivation. Favorable patient-provider communication is associated with more motivation to adhere to ART.

Comparative Effects of Intra-Articular versus Intravenous Mesenchymal Stromal Cells Therapy in a Rat Model of Osteoarthritis by Destabilization of Medial Meniscus.

Transplanted mesenchymal stromal cells (MSCs) exhibit a robust anti-inflammatory and homing capacity in response to high inflammatory signals, as observed in studies focused on rheumatic diseases that target articular cartilage (AC) health. However, AC degradation in osteoarthritis (OA) does not necessarily coincide with a highly inflammatory joint profile. Often, by the time patients seek medical attention, they already have damaged AC. In this study, we examined the therapeutic potential of a single bone marrow MSC transplant (2 × 106 cells/kgbw) through two different routes: intra-articular (MSCs-IAt) and intravenous (MSCs-IVt) in a preclinical model of low-grade inflammatory OA with an established AC degeneration. OA was induced through the destabilization of the medial meniscus (DMM) in female Wistar Kyoto rats. The animals received MSCs 9 weeks after surgery and were euthanized 4 and 12 weeks post-transplant. In vivo and ex vivo tracking of MSCs were analyzed via bioluminescence and imaging flow cytometry, respectively. Cytokine/chemokine modulation in serum and synovial fluid was measured using a multiplex panel. AC degeneration was quantified through histology, and hindlimb muscle balance was assessed with precision weighing. To our knowledge, we are the first group to show the in vivo (8 h) and ex vivo (12 h) homing of cells to the DMM-OA joint following MSCs-IVt. In the case of MSCs-IAt, the detection of cellular bioluminescence at the knee joint persisted for up to 1 week. Intriguingly, intra-articular saline injection (placebo-IAt) resulted in a worse prognosis of OA when compared to a non-invasive control (placebo-IVt) without joint injection. The systemic cytokines/chemokines profile exhibited a time-dependent variation between transplant routes, displaying a transient anti-inflammatory systemic response for both MSCs-IVt and MSCs-IAt. A single injection of MSCs, whether administered via the intra-articular or intravenous route, performed 9 weeks after DMM surgery, did not effectively inhibit AC degeneration when compared to a non-invasive control.

[Transitional care from hospital to home: how to target the right population?] / Soins de transition entre l'hôpital et le domicile: pour quels patient-es ?

When patients are discharged from the hospital and return home, they are at risk of adverse events if the continuity of care is broken. So far, the evidence for transitional care models to reduce readmission rates has focused mainly on patients with a single condition. Based on this observation, we identified the population that may benefit the most from the development of a new transitional care model, as part of the INSTEAD project, by consensus between patients and professionals in hospitals and the community. To ensure continuity of care, it is necessary to consider the patients' perception, their understanding of the care plan and changes impacting the home care plan. Interprofessional collaboration is essential to achieve this.

Lorsqu'un-e patient-e retourne à domicile suite à une hospitalisation il-elle est souvent confronté-e à des événements indésirables si la continuité de ses soins n'est pas assurée. Jusqu'à ce jour, les modèles de soins de transition qui ont montré une diminution du taux de réadmission concernaient des patient-es ne souffrant que d'une seule pathologie. Partant de ce constat, nous avons identifié la population qui pourrait le plus bénéficier de soins de transition, dans le cadre du projet INSTEAD, par un consensus incluant d'une part des patient-es et, d'autre part, des professionnel-les hospitaliers et communautaires. Pour assurer la continuité des soins, il s'avère nécessaire de prendre en compte la perception de la personne, sa compréhension ainsi que les changements influençant son plan de soins à domicile. Pour ce faire, une collaboration interprofessionnelle est indispensable.

Examining Different Regimes of Ionization-Induced Damage in GaN Through Atomistic Simulations.

The widespread adoption of gGaN in radiation-hard semiconductor devices relies on a comprehensive understanding of its response to strongly ionizing radiation. Despite being widely acclaimed for its high radiation resistance, the exact effects induced by ionization are still hard to predict due to the complex phase-transition diagrams and defect creation-annihilation dynamics associated with group-III nitrides. Here, the Two-Temperature Model, Molecular Dynamics simulations and Transmission Electron Microscopy, are employed to study the interaction of Swift Heavy Ions with GaN at the atomic level. The simulations reveal a high propensity of GaN to recrystallize the region melted by the impinging ion leading to high thresholds for permanent track formation. Although the effect exists in all studied electronic energy loss regimes, its efficiency is reduced with increasing electronic energy loss, in particular when there is dissociation of the material and subsequent formation of N2 bubbles. The recrystallization is also hampered near the surface where voids and pits are prominent. The exceptional agreement between the simulated and experimental results establishes the applicability of the model to examine the entire electronic energy loss spectrum. Furthermore, the model supports an empirical relation between the interaction cross sections (namely for melting and amorphization) and the electronic energy loss.

Using Low-Resolution Non-Invasive Infrared Sensors to Classify Activities and Falls in Older Adults.

The population is aging worldwide, creating new challenges to the quality of life of older adults and their families. Falls are an increasing, but not inevitable, threat to older adults. Information technologies provide several solutions to address falls, but smart homes and the most available solutions require expensive and invasive infrastructures. In this study, we propose a novel approach to classify and detect falls of older adults in their homes through low-resolution infrared sensors that are affordable, non-intrusive, do not disturb privacy, and are more acceptable to older adults. Using data collected between 2019 and 2020 with the eHomeseniors platform, we determine activity scores of older adults moving across two rooms in a house and represent an older adult fall through skeletonization. We find that our twofold approach effectively detects activity patterns and precisely identifies falls. Our study provides insights to physicians about the daily activities of their older adults and could potentially help them make decisions in case of abnormal behavior.

Unknown/enigmatic functions of extracellular ASC.

Apoptosis-associated speck-like protein containing a caspase recruit domain (ASC), encoded by PYCARD gene, is a 22 kDa small molecule, which aggregates into ASC specks during inflammasome activation. ASC protein is an adaptor protein present in several inflammasome complexes that performs several intra- and extracellular functions, in monomeric form or as ASC specks, during physiological and pathological processes related to inflammation and adaptive immunity. Extracellular ASC specks (eASC specks) released during cell death by pyroptosis can contribute as a danger signal to the propagation of inflammation via phagocytosis and activation of surrounding cells. ASC specks are found in the circulation of patients with chronic inflammatory diseases and have been considered as relevant blood biomarkers of inflammation. eASC amplifies the inflammatory signal, may induce the production of autoantibodies, transports molecules that bind to this complex, contributing to the generation of antibodies, and can induce the maturation of cytokines promoting the modelling of the adaptive immunity. Although several advances have been registered in the last 21 years, there are numerous unknown or enigmatic gaps in the understanding of the role of eASC specks in the organism. Here, we provide an overview about the ASC protein focusing on the probable roles of eASC specks in several diseases, up to the most recent studies concerning COVID-19.

Factors associated with hospital readmissions among patients with COVID-19: A single-center experience.

Identify factors associated with readmission after an index hospital admission for coronavirus disease 2019 (COVID-19) infection in a single center serving an underserved and predominantly minority population. This retrospective descriptive study included 275 patients who tested COVID-19 positive via reverse transcriptase-polymerase chain reaction assay at our institution and who survived the index hospitalization. The main outcomes were 1- and 6-month readmission rates after an index hospitalization for COVID-19. The mortality rate among the readmitted patients was also determined. Factors independently associated with readmission were investigated using multivariable logistic regression. A final sample of 275 patients was included. The mean age was 64.69 ± 14.64 (SD), 133 (48%) were female and 194 (70%) were African American. Their chronic medical conditions included hypertension 203 (74%) and diabetes mellitus 121 (44%). After the hospitalization, 1-month readmission rate was 7.6%, while 6-month readmission rate was 24%. Nine percent of patients who were readmitted subsequently died. Coronary artery disease (CAD) was significantly associated with 6-month readmission odds ratio (OR), 2.15 (95% confidence interval [CI]: 1.04-4.44; p = 0.039) after adjustment for age, gender, ethnicity, and comorbidities. Readmissions were due to cardiac, respiratory, and musculoskeletal symptoms. Hispanic ethnicity was associated with increased readmission OR, 3.16 (95% CI: 1.01-9.88; p = 0.048). No significant difference was found between inflammatory markers or clinical outcomes during the index hospitalization among patients who were readmitted compared to those who were not. A significant number of patients hospitalized for COVID-19 may be readmitted. The presence of CAD is independently associated with high rates of 6-month readmission.

Inference, Model Selection, and the Combinatorics of Growing Trees.

One can often make inferences about a growing network from its current state alone. For example, it is generally possible to determine how a network changed over time or pick among plausible mechanisms explaining its growth. In practice, however, the extent to which such problems can be solved is limited by existing techniques, which are often inexact, inefficient, or both. In this Letter, we derive exact and efficient inference methods for growing trees and demonstrate them in a series of applications: network interpolation, history reconstruction, model fitting, and model selection.

Short-Term Effects of the COVID-19 Pandemic on HIV Care Utilization, Service Delivery, and Continuity of HIV Antiretroviral Treatment (ART) in Haiti.

INTRODUCTION: Our study describes changes in HIV care service delivery and continuity of HIV antiretroviral therapy (ART) for people living with HIV (PLHIV) during the 8 weeks before and after diagnosis of the first coronavirus disease 2019 (COVID-19) cases in Haiti on March 19, 2020. METHODS: Using data from 96 out of 167 health facilities offering ART services, we compared four ART program indicators: (1) count of HIV visits; (2) proportion of ART dispenses in community-based settings (DAC); (3) proportion of multi-month dispensing of ART medications > 6 months (> 6 m MMD); and (4) proportion of timely ART refills. We used uncontrolled interrupted time series (ITS) models to estimate slope and level changes in each indicator with the arrival of COVID-19. RESULTS AND DISCUSSION: From week 1 to week 16, the average number of HIV visits fell from 121.5 to 92.5 visits, the proportion of DAC rose from 22.7% to 36.7%, the proportion of > 6 m MMD rose from 29.4% to 48.4%, and the proportion of timely ART refills fell from 51.9% to 43.8%. The ITS models estimated abrupt increases of 36% in > 6 m MMD (p < 0.001) and 37% in DAC (p < 0.001) at the time of COVID-19 arrival, and no change after arrival of COVID-19. The was an abrupt decline of 18% in timely ART refills with the arrival of COVID-19 and a decline of 1% per week thereafter, both non-statistically significant changes. CONCLUSIONS: The sudden changes in HIV service utilization represent dramatic adaptations needed to mitigate primary and secondary effects of the COVID-19 pandemic on PLHIV. This study underscores the urgency of optimizing ART delivery models in Haiti and beyond, in order to maintain progress toward HIV epidemic control.

Advanced practice physiotherapy for adults with spinal pain: a systematic review with meta-analysis.

OBJECTIVE: To appraise the available evidence on advanced practice physiotherapy (APP) models of care (MoC) in specialized secondary care such as orthopaedic, rheumatology or neurosurgery outpatients' clinics for adults with spinal pain. METHODS: Systematic review with meta-analysis. Electronic searches were conducted up to July 2020 in Medline, Embase, Cochrane CENTRAL and CINAHL. Studies on APP MoC in specialized secondary care for adults with spinal pain were included. RESULTS: Eighteen studies (n = 9405), including two randomized controlled trials and sixteen observational studies were included. One study was considered at high quality, fourteen studies were considered of moderate quality and three were considered of low quality. Pooled results for change in disability for patients with spinal pain reported no significant difference between APP and usual medical care (UMC). Mean wait time for initial consultation was lower with APP (1-9.4 weeks) than with UMC MoC (23-65 weeks). Following the implementation of APP MoC, wait time for a consultation with a medical specialist was reduced (6-16 weeks). Physiotherapists in APP MoC managed independently 89.2% of the patients referred (n = 8393). Stakeholders and patients reported high satisfaction with APP care. CONCLUSIONS: APP MoC and UMC likely result in comparable pain, disability and quality of life improvement for adults with spinal pain. However, APP MoC have the potential to improve health care access by reducing wait time for consultation in specialized care and maintaining a high level of satisfaction among stakeholders and patients.

[Mobile applications for smoking cessation in primary care]. / Applications mobiles et désaccoutumance au tabac avec l'aide du praticien.

Primary care physicians are in an excellent position to address smoking during routine consultations. To this end, physicians have assessment tools and brief interventions appropriate for the duration of consultations. However, these tools are difficult to use consistently in practice. Mobile applications (apps) aimed at stopping smoking could help solve this problem, provided they meet certain quality criteria. This article provides criteria for evaluating these apps to facilitate their identification and use by clinicians. Five French-speaking apps are described. If integrated into routine Primary Care, these apps could facilitate smoking cessation.

Le médecin de premier recours a une place privilégiée pour aborder le problème du tabagisme en consultation de routine. Il dispose, à cet effet, d'outils d'évaluations et d'interventions brèves compatibles avec le temps de consultation. Ces outils sont difficiles à implémenter systématiquement. Les applications mobiles (apps) visant à l'arrêt du tabac pourraient contribuer à résoudre ce problème pour autant qu'elles satisfassent à certains critères de qualité. Le présent article propose des critères d'évaluation de ces apps pour faciliter leur identification et leur utilisation par le clinicien. Cinq apps francophones sont décrites. Intégrées à la consultation de médecine générale, de telles apps, pourraient faciliter la désaccoutumance au tabac.

An EMR-Based Alert with Brief Provider-Led ART Adherence Counseling: Promising Results of the InfoPlus Adherence Pilot Study Among Haitian Adults with HIV Initiating ART.

To promote HIV antiretroviral therapy (ART) outcomes in Haiti, we developed a culturally relevant intervention (InfoPlus Adherence) that combines an electronic medical record alert identifying patients at elevated risk of treatment failure and provider-delivered brief problem-solving counseling. We conducted a quasi-experimental mixed-methods study among 146 patients at two large ART clinics in Haiti with 728 historical controls. We conducted quantitative assessments of patients at baseline and intervention completion (6 months) as well as focus groups with health workers and exit interviews with patients. The primary quantitative outcome measures were HIV viral suppression according to medical record and ART adherence in terms of ≥ 90% for "proportion of days covered" (PDC) according to pharmacy dispensing data. Results indicated that the proportion of intervention patients with suppressed VL during the study/historical periods was 80.0%/86.0% and 76.8%/87.4% for controls. In a difference-in-differences (DID) analytic model, the adjusted relative risk for viral suppression with the intervention was 1.15 (95% CI 0.92-1.45, p = 0.21), representing favorable but non-significant association between the intervention and the trajectory of VL outcomes. PDC ≥ 90% during the study/historical periods was 30.9%/11.0% among intervention participants and 16.9%/19.4% among controls. In the adjusted DID model, the relative risk for of PDC ≥ 90% with the intervention was 4.00 (95% CI 1.91-8.38, p < 0.001), representing a highly favorable association between the intervention and the trajectory of PDC outcomes. Qualitative data affirmed acceptability of the intervention, although providers reported some challenges consistently implementing it. Future research is needed to demonstrate efficacy and explore optimal implementation strategies.

Expanded access to viral load testing and use of second line regimens in Haiti: time trends from 2010-2017.

BACKGROUND: Haiti initiated the scale-up of HIV viral load (VL) testing in 2015-2016, with plans to achieve 100% coverage for all patients on antiretroviral therapy (ART) for treatment of HIV/AIDS. In the absence of HIV drug susceptibility testing, VL testing is a key tool for monitoring response to ART and optimizing treatment results. This study describes trends in expanded use of VL testing, VL results, and use of second-line ART regimens, and explores the association between VL testing and second-line regimen switching in Haiti from 2010 to 2017. METHODS: We conducted a retrospective cohort study with 66,042 patients drawn from 88 of Haiti's 160 national ART clinics. Longitudinal data from the iSanté electronic data system was used to analyze the trends of interest. We described patients' VL testing status in five categories based on up to two most recent VL test results: no test; suppressed; unsuppressed followed by no test; re-suppressed; and confirmed failure. Among those with confirmed failure, we described ART adherence level. Finally, we used Cox proportional hazards regression to estimate the risk of second-line regimen switching by VL testing status, after adjusting for other individual characteristics. RESULTS: The number of patients who had tests done increased annually from 11 in 2010 to 18,828 in the first 9 months of 2017, while the number of second-line regimen switches rose from 21 to 279 during this same period. Compared with patients with no VL test, the hazard ratio (HR) for switching to a second-line regimen was 22.2 for patients with confirmed VL failure (95% confidence interval [CI] for HR: 18.8-26.3; p < 0.005) after adjustment for individual characteristics. Among patients with confirmed VL failure, 44.7% had strong adherence, and fewer than 20% of patients switched to a second-line regimen within 365 days of VL failure. CONCLUSIONS: Haiti has significantly expanded access to VL testing since 2016. In order to promote optimal patient health outcomes, it is essential for Haiti to continue broadening access to confirmatory VL testing, to expand evidence-based initiatives to promote strong ART adherence, and to embrace timely switching for patients with confirmed ART failure despite strong ART adherence.

NOTCH1 nuclear interactome reveals key regulators of its transcriptional activity and oncogenic function.

Activating mutations in NOTCH1, an essential regulator of T cell development, are frequently found in human T cell acute lymphoblastic leukemia (T-ALL). Despite important advances in our understanding of Notch signal transduction, the regulation of Notch functions in the nucleus remains unclear. Using immunoaffinity purification, we identified NOTCH1 nuclear partners in T-ALL cells and showed that, beyond the well-characterized core activation complex (ICN1-CSL-MAML1), NOTCH1 assembles a multifunctional complex containing the transcription coactivator AF4p12, the PBAF nucleosome remodeling complex, and the histone demethylases LSD1 and PHF8 acting through their demethylase activity to promote epigenetic modifications at Notch-target genes. Remarkably, LSD1 functions as a corepressor when associated with CSL-repressor complex and as a NOTCH1 coactivator upon Notch activation. Our work provides new insights into the molecular mechanisms that govern Notch transcriptional activity and represents glimpse into NOTCH1 interaction landscape, which will help in deciphering mechanisms of NOTCH1 functions and regulation.

[Legal aspects of teleconsultation]. / Aspects juridiques de la téléconsultation.

There is no specific legal framework in Switzerland for the practice of telemedicine. The doctor carrying out a teleconsultation must therefore respect the general principles of medical practice : provide care online with professional recommendations, provide his patient with clear, appropriate and complete information, and also respect medical confidentiality. The doctor, due in particular to the limitation of the senses and the absence of direct physical examination, must maintain a degree of caution in the practice of remote consultations. He also remains responsible for the medical data exchanged and it is up to him to use a telemedicine solution adapted to the data security and confidentiality standards.

Il n'existe pas en Suisse de cadre légal spécifique à l'exercice de la télémédecine. Le médecin réalisant une téléconsultation doit ainsi respecter les principes généraux de l'exercice médical : apporter des soins en adéquation avec les recommandations professionnelles, délivrer à son patient une information claire, adaptée et complète, mais aussi respecter le secret médical. Le médecin, du fait notamment de la limitation des sens et de l'absence d'examen physique direct, doit garder un degré de prudence dans la pratique de consultations à distance. Il reste également responsable des données médicales échangées et il lui appartient d'utiliser une solution de télémédecine adaptée aux normes de sécurité et de confidentialité des données en vigueur.