A novel ΔNp63-dependent immune mechanism improves prognosis of HPV-related head and neck cancer.

peer reviewed[en] BACKGROUND: Deconvoluting the heterogenous prognosis of Human Papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OSCC) is crucial for enhancing patient care, given its rapidly increasing incidence in western countries and the adverse side effects of OSCC treatments. METHODS: Transcriptomic data from HPV-positive OSCC samples were analyzed using unsupervised hierarchical clustering, and clinical relevance was evaluated using Kaplan-Meier analysis. HPV-positive OSCC cell line models were used in functional analyses and phenotypic assays to assess cell migration and invasion, response to cisplatin, and phagocytosis by macrophages in vitro. RESULTS: We found, by transcriptomic analysis of HPV-positive OSCC samples, a ΔNp63 dependent molecular signature that is associated with patient prognosis. ΔNp63 was found to act as a tumor suppressor in HPV-positive OSCC at multiple levels. It inhibits cell migration and invasion, and favors response to chemotherapy. RNA-Seq analysis uncovered an unexpected regulation of genes, such as DKK3, which are involved in immune response-signalling pathways. In agreement with these observations, we found that ΔNp63 expression levels correlate with an enhanced anti-tumor immune environment in OSCC, and ΔNp63 promotes cancer cell phagocytosis by macrophages through a DKK3/NF-κB-dependent pathway. CONCLUSION: Our findings are the first comprehensive identification of molecular mechanisms involved in the heterogeneous prognosis of HPV-positive OSCC, paving the way for much-needed biomarkers and targeted treatment

Etude comparative entre la maladie de Jessner et Kanof et le Lupus tumidus

La maladie de Jessner et Kanof est une dermatose bénigne rare dont le statut nosologique est discuté. Son appartenance au spectre du lupus reste controversée du fait de ses similitudes avec le lupus tumidus. Ces deux affections se présentent sous forme de lésions érythémato-papuleuses à disposition parfois annulaire, localisées au visage et au tronc, évoluant de façon chronique par poussées et, histologiquement, par un infiltrat lymphocytaire périvasculaire et périannexiel. Nous rapportons une étude rétrospective comparative de 16 patients atteints de maladie de Jessner et Kanof et de 10 patients atteints de lupus tumidus. Les principales différences observées entre les deux affections ont été, d'une part sur le plan clinique, un caractère oedémateux et une atteinte du visage plus fréquents dans le lupus tumidus, d'autre part sur le plan histologique, des altérations épidermiques et des modifications de la jonction dermo-épidermique retrouvées dans le lupus tumidus et absentes dans la maladie de Jessner et Kanof, enfin une fréquente positivité de l'immunofluorescence directe dans le lupus tumidus alors qu'elle est toujours négative dans la maladie de Jessner et Kanof.NANTES-BU Médecine pharmacie (441092101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Pandemic COVID-19: the residents' resilience

Healthcare workers are often exposed to secondary traumatic stress. The SARS-CoV-2 outbreak caused intense psychological pressure in various healthcare professionals, with increased risk of post-traumatic stress disorder. Objective of our study was to evaluate the incidence of post-traumatic stress disorder in italian residents in Intensive Care and Emergency Departments facing COVID-19 emergency

Oxidation-Sensitive Supramolecular Polymer Nanocylinders

International audienceThis study reports the synthesis and solution self-assembly of a bis(urea) derivative decorated with a poly(ethylene oxide) chain and an electroactive tetrathiafulvalene (TTF) unit, into oxidationsensitive supramolecular nanocylinders. As evidenced by cryo-transmission electron microscopy and light scattering experiments, the preparation pathway has a strong influence on the morphology and characteristics of the self-assembled structures, proving their frozen (out-of-2 equilibrium) nature. The targeted supramolecular nanocylinders could be obtained both in aqueous medium and acetonitrile. In water, TTF can be chemically oxidized to TTF •+ by Fe(III), resulting in a very moderate disassembly of the supramolecular nanocylinders. On the contrary, TTF can be oxidized up to TTF 2+ with the same oxidant in acetonitrile, leading to an almost complete disassembly of the nanocylinders. Oxidation of TTF eventually leads to its degradation in both solvents, even in the absence of oxygen and light. This paper shows that oxidation-sensitive supramolecular nanocylinders can be prepared in acetonitrile by combining bis(urea) and TTF units to a polymer

Exercise-Induced Vasculitis: A Review with Illustrated Cases

International audienceAlthough exercise-induced vasculitis (EIV) is usually misdiagnosed, it is not uncommon. Occurring mostly after prolonged exercise, especially in hot weather, EIV is an isolated cutaneous vasculitis with stereotypical presentation. This article reviews the clinical characteristics, treatments, and outcomes of EIV based on the published literature. We report 99 patients who developed EIV after walking, dancing, swimming, or hiking especially during hot weather, including the records of 16 patients with EIV treated at our hospital from 2007 to 2015. Erythematous or purpuric plaques arise on the lower legs, without the involvement of compression socks or stockings. Symptoms include itch, pain, and a burning sensation. EIV is an isolated cutaneous vasculitis. Lesions resolve spontaneously after 10 days. When triggering conditions persist, relapses are frequent (77.5 %). Histopathology demonstrates leukocytoclastic vasculitis in 95 % of cases with C3 or immunoglobulin M deposits in 88 and 46 % of cases, respectively. Blood investigations are negative. EIV appears to be a consequence of venous stasis induced by an acute failure of the muscle pump of the calf and thermoregulation decompensation. Both appear after prolonged and unusual exercise in hot weather. Treatment is not codified; topical corticosteroids may reduce symptoms and wearing light clothes might limit lesion occurrence

Chronic Low Back Pain: A Narrative Review of Recent International Guidelines for Diagnosis and Conservative Treatment

Chronic low back pain (cLBP) is a public and occupational health problem that is a major professional, economic and social burden. We aimed to provide a critical overview of current international recommendations regarding the management of non-specific cLBP. We conducted a narrative review of international guidelines for the diagnosis and conservative treatment of people with non-specific cLBP. Our literature search yielded five reviews of guidelines published between 2018 and 2021. In these five reviews, we identified eight international guidelines that fulfilled our selection criteria. We added the 2021 French guidelines into our analysis. Regarding diagnosis, most international guidelines recommend searching for so-called yellow, blue and black flags, in order to stratify the risk of chronicity and/or persistent disability. The relevance of clinical examination and imaging are under debate. Regarding management, most international guidelines recommend non-pharmacological treatments, including exercise therapy, physical activity, physiotherapy and education; however, multidisciplinary rehabilitation, in selected cases, is the core treatment recommended for people with non-specific cLBP. Oral, topical or injected pharmacological treatments are under debate, and may be offered to selected and well-phenotyped patients. The diagnosis of people with cLBP may lack precision. All guidelines recommend multimodal management. In clinical practice, the management of individuals with non-specific cLBP should combine non-pharmacological and pharmacological treatments. Future research should focus on improving tailorization

Barriers and facilitators to bracing in adults with painful degenerative scoliosis: a single-centred mixed-method feasibility study

Abstract Background Conservative treatments including bracing and exercise therapy are prescribed on the first-line in adults with degenerative scoliosis. However, adherence to conservative treatments is low. We aimed to assess barriers and facilitators to bracing in adults with painful degenerative scoliosis. Methods We conducted a single-centred mixed-method pilot and feasibility study. All patients scheduled for a multidisciplinary custom-made bracing consultation, from July 2019 to January 2020, in a French tertiary care centre, were screened. Patients were eligible if they had painful adult degenerative scoliosis and a prescription for a rigid custom-made lumbar-sacral orthosis. The primary outcome was barriers and facilitators to bracing assessed by a qualitative approach using semi-structured interviews. Secondary outcomes were back pain, spine-specific activity limitations, symptoms of depression and satisfaction with bracing post-intervention assessed by a quantitative approach. Results Overall, 56 patients were screened and 14 (25%) were included. Mean age was 68.2 (12.3) years. Mean follow-up was 9.8 (2.0) months. Barriers to bracing were increased limitations in some activities, discomfort in hot weather and burden of aesthetic appearance. Facilitators to bracing were reduced pain, improved activities of daily living, suitable weight and improved spinal alignment. Participants self-implemented solutions to enhance adherence. The mean reduction from baseline in pain intensity was 1.7 (2.3) of 10 points, and 6 of 13 patients (46%) had pain intensity < 4 of 10 points. Conclusion Bracing is a feasible intervention for people with painful adult degenerative scoliosis. Patients self-implemented their own solutions to enhance adherence

Hepatocellular Carcinoma Emergence in Diabetic Mice with Non-Alcoholic Steatohepatitis Depends on Diet and Is Delayed in Liver Exhibiting an Active Immune Response

International audienceThe increase of the sedentary lifestyle and high-calorie diet have modified the etiological landscape of hepatocellular carcinoma (HCC), with a recrudescence of non-alcoholic fatty liver disease (NAFLD), especially in Western countries. The purpose of our study was to evaluate the impact of high-fat diet feeding on non-alcoholic steatohepatitis (NASH) establishment and HCC development. Streptozotocin-induced diabetic male mice were fed with high-fat-high-cholesterol diet (HFHCD) or high-fat-high-sugar diet (HFHSD) from 1 to 16 weeks. Even if liver tumors appear regardless of the high-fat diet, two distinct physiopathological patterns were evidenced, with much more severe NASH hallmarks (liver injury, inflammation and fibrosis) in diabetic mice fed with HFHCD. The mild hepatic injury, weak inflammation and fibrosis observed in HFHSD were interestingly associated with earlier emergence of more numerous liver tumors. When activated helper and cytotoxic T cells, detected by flow cytometry, infiltrated the liver of HFHCD-fed diabetic mice, a delay in the appearance of tumor nodules and a limitation of their numbers were observed, suggesting that the immune activities partly controlled tumor emergence. These data highlighted two different mouse models of HCC progression in diabetic mice depending on diet, which could be useful to evaluate new therapeutic approaches for HCC by targeting the immune response

Selective Heart Rate Reduction Improves Metabolic Syndrome–related Left Ventricular Diastolic Dysfunction

International audienceEnhanced heart rate observed in metabolic syndrome (MS) contributes to the deterioration of left ventricular (LV) function via impaired LV filling and relaxation, increased myocardial O2 consumption, and reduced coronary perfusion. However, whether heart rate reduction (HRR) opposes LV dysfunction observed in MS is unknown