β1-integrins signaling and mammary tumor progression in transgenic mouse models: implications for human breast cancer

Consistent with their essential role in cell adhesion to the extracellular matrix, integrins and their associated signaling pathways have been shown to be involved in cell proliferation, migration, invasion and survival, processes required in both tumorigenesis and metastasis. β1-integrins represent the predominantly expressed integrins in mammary epithelial cells and have been proven crucial for mammary gland development and differentiation. Here we provide an overview of the studies that have used transgenic mouse models of mammary tumorigenesis to establish β1-integrin as a critical mediator of breast cancer progression and thereby as a potential therapeutic target for the development of new anticancer strategies

Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data

Background: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. Methods: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0–1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0–2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4–6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. Findings: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10–2·03]; p=0·011), with low heterogeneity across studies (I2=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05–1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06–2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4–6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52–1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03–4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [<1%], adjusted OR 5·58 [1·22–25·50]; p=0·024). Interpretation: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. Funding: None

Protocol for a partially nested randomised controlled trial to evaluate the effectiveness of the scleroderma patient-centered intervention network COVID-19 home-isolation activities together (SPIN-CHAT) program to reduce anxiety among at-risk scleroderma patients

Objective: Contagious disease outbreaks and related restrictions can lead to negative psychological outcomes, particularly in vulnerable populations at risk due to pre-existing medical conditions. No randomised controlled trials (RCTs) have tested interventions to reduce mental health consequences of contagious disease outbreaks. The primary objective of the Scleroderma Patient-centered Intervention Network COVID-19 Home-isolation Activities Together (SPIN-CHAT) Trial is to evaluate the effect of a videoconference-based program on symptoms of anxiety. Secondary objectives include evaluating effects on symptoms of depression, stress, loneliness, boredom, physical activity, and social interaction.Methods: The SPIN-CHAT Trial is a pragmatic RCT that will be conducted using the SPIN-COVID-19 Cohort, a sub-cohort of the SPIN Cohort. Eligible participants will be SPIN-COVID-19 Cohort participants without a positive COVID-19 test, with at least mild anxiety (PROMIS Anxiety 4a v1.0 T-score >= 55), not working from home, and not receiving current counselling or psychotherapy. We will randomly assign 162 participants to intervention groups of 7 to 10 participants each or waitlist control. We will use a partially nested RCT design to reflect dependence between individuals in training groups but not in the waitlist control. The SPIN-CHAT Program includes activity engagement, education on strategies to support mental health, and mutual participant support. Intervention participants will receive the 4-week (3 sessions per week) SPIN-CHAT Program via video-conference. The primary outcome is PROMIS Anxiety 4a score immediately post-intervention.Ethics and dissemination: The SPIN-CHAT Trial will test whether a brief videoconference-based intervention will improve mental health outcomes among at-risk individuals during contagious disease outbreak

Extra-intestinal manifestations of inflammatory bowel disease (IBD)

Les manifestations extra-intestinales des maladies inflammatoires chroniques de l'intestin (MICI) sont fréquentes, elles précèdent, accompagnent ou sont indépendantes de la maladie intestinale sous-jacente. Elles peuvent être plus préoccupantes que l'atteinte intestinale. Les plus fréquentes sont les manifestations articulaires, oculaires et cutanées. Elles partagent un mécanisme commun avec les localisations intestinales. Elles posent peu de problèmes diagnostiques lorsqu'elles sont contemporaines de la poussée. Isolées, les rattacher à l'affection intestinale sous-jacente peut ne pas être facile et nécessiter une approche pluridisciplinaire. Sur le plan thérapeutique, dans un certain nombre de cas, elles amèneront à reconsidérer la thérapeutique initiale à visée intestinale initialement proposée, alors que dans d'autres situations, elles nécessiteront une prise en charge pluridisciplinaire. Ceci implique donc un abord multidisciplinaire des MICI avec manifestations extra-intestinales, mais aussi une information indispensable des patients, de façon à attirer leur attention sur tout signe clinique inhabituel non lié à l'atteinte digestive, mais aussi pour s'assurer de la bonne compliance des thérapeutiques proposées pour traiter ces manifestations extradigestives. Dans le futur, les progrès des traitements immuno-modulateurs devraient également modifier les conditions du diagnostic et du traitement de ces manifestations

Banc d'essai de L'ampliphotographie 105 mm à cadence rapide

Les auteurs rapportent les résultats obtenus avec une nouvelle caméra d'ampliphotographie 105 mm à cadence rapide (caméra GV 105 de la Compagnie générale de Radiologie). Grâce à une cadence atteignant 8 images/seconde, cette caméra apparaît particulièrement intéressante pour l'étude des sphincters et des phénomènes fugaces. Cependant, la qualité des images, comparable à celle des clichés strandards la rapidité des examens. la lecture aisée des clichés, la diminution importante des doses délivrées et l'économie de surface sensible rendent souhaitable l'emploi de cette technique en radiologie générale. Malheureusement il n'existe pas à l'heure actuelle de formule simple et rapide pour présenter les clichés obtenus. Des progrès devront également être réalisés pour faciliter le chargement de la caméra. La résolution rapide de ces inconvénients permettrait à cette technique d'avoir le développement qu'elle mérite