[MELALIB 15: A retrospective observational study of 383 cases of melanoma diagnosed by dermatologists in private practice]. / MELALIB15 : étude observationnelle rétrospective de 383 mélanomes dépistés par des dermatologues libéraux.

BACKGROUND: Early detection of melanoma constitutes a major challenge and is a common reason for dermatological consultations. There is no recent data on melanomas diagnosed in the private medical sector in France, nor on the circumstances of diagnosis. PATIENTS AND METHODS: This was a retrospective observational study on records collating data on all new consecutive cases of melanoma diagnosed between January 2015 and June 2018, in the private sector only, by volunteer dermatologists belonging to the association for continuing medical education, "Dermatologie Paris XV". A data collection sheet was prepared on which to record information about the dermatologist, the patient, the main complaint, the characteristics of the melanoma, and the initial treatment given, using the computerized list provided by our dermatopathology offices. RESULTS: The study involved 383 cases of melanoma, 37% in situ and 63% invasive, which consisted chiefly of superficial spreading melanoma. The median age of the cohort was 61 years and patients were predominantly female (58%). Follow-up of high-risk patients and complete routine examination (in those consulting for another reason) resulted in direct detection by a dermatologist of 202 of the 383 melanomas (52.7%); these melanomas had a lower median Breslow index than the rest of the cohort and were thin in the main. When patients consulted for a suspect lesion (139 cases), the lesion had been identified mostly by either the patient or by a relative (61% of cases). The decision to consult was made chiefly by the patients themselves, and the Breslow index was thicker. An initial consultation for nevus screening resulted in diagnosis of 42 melanomas, i.e. only 11% of the cohort. Dermoscopy was performed by 92% of the dermatologists participating in the study. Melanoma excision was performed in the office by the practitioner in 75% of cases, and management was validated at multidisciplinary meetings in 65% of cases. CONCLUSION: In terms of French primary care, dermatologists in private practice play a key role in ensuring early detection and initial management of melanoma.

Management of X-linked adrenoleukodystrophy in Morocco: actual situation.

OBJECTIVES: X-linked adrenoleukodystrophy is a neurodegenerative disorder caused by mutations in the ABCD1 gene. Adrenomyeloneuropathy and childhood cerebral Adrenoleukodystrophy are the most common phenotypes. This paper focuses on a descriptive study of the first program of diagnosis, treatment, and follow-up of this disease in Morocco. RESULTS: We developed three protocols of X-linked Adrenoleukodystrophy management: general protocol, asymptomatic protocol, and heterozygous protocol. Over a period of 5 years, we recruited eight families with 16 patients. Clinically, the presentation is primary adrenal insufficiency and behavioral changes. All patients had elevated levels of very long fatty acids. This is the first study of X-linked adrenoleukodystrophy in Morocco. It shows the importance of this metabolic disease and broadens perspectives in terms of its diagnosis and its treatment.

The local environment orchestrates mucosal decidual macrophage differentiation and substantially inhibits HIV-1 replication.

Macrophages from the decidua basalis (dM), the main uterine mucosa during pregnancy, are weakly permissive to HIV-1 infection. Here, we investigated the mechanisms underlying this natural control. We show, by using freshly purified decidual macrophages and ex vivo human decidual explants, that the local decidual environment influences dM differentiation and naturally protects these cells from HIV-1 infection. Interferon (IFN)-γ, present in the decidual tissue, contributes to maintenance of the dM phenotype and restricts HIV-1 infection by mechanisms involving the cyclin-dependent kinase inhibitor p21Cip1/Waf1. We also found that activation of Toll-like receptors 7 and 8 expressed by dM reinforces the low permissivity of dM to HIV-1 by restricting viral replication and inducing secretion of cytokines in the decidual environment, including IFN-γ, that shape dM plasticity. A major challenge for HIV-1 eradication is to control infection of tissue-resident macrophages in the female reproductive tract. Our findings provide clues to the development of novel strategies to prevent HIV-1 macrophage infection.

Role of human immunodeficiency virus type 1 envelope structure in the induction of broadly neutralizing antibodies.

Very soon after the discovery of neutralizing antibodies (NAbs) toward human immunodeficiency virus type 1 (HIV-1) infection, it became apparent that characterization of these NAbs would be an important step in finding a cure for or a vaccine to eradicate HIV-1. Since the initial description of broadly cross-clade NAbs naturally produced in HIV-1 patients, numerous studies have described new viral targets for these antibodies. More recently, studies concerning new groups of patients able to control their viremia, such as long-term nonprogressors (LTNPs) or elite controllers, have described the generation of numerous envelope-targeted NAbs. Recent studies have marked a new stage in research on NAbs with the description of antibodies obtained from a worldwide screening of HIV-positive patients. These studies have permitted the discovery of NAb families with great potential for both neutralization and neutralization breadth, such as PG, PGT, CH, and highly active agonistic anti-CD4 binding site antibodies (HAADs), of which VRC01 and its variants are members. These antibodies are able to neutralize more than 80% of circulating strains without any autoreactivity and can be rapidly integrated into clinical trials in order to test their protective potential. In this review, we will focus on new insights into HIV-1 envelope structure and their implications for the generation of potent NAbs.

Promyelocytic leukemia-nuclear body formation is an early event leading to retinoic acid-induced differentiation of neuroblastoma cells.

Neuroblastoma is one of the most common cancers in children. Neuroblastoma differentiation is linked to the presence of the promyelocytic leukemia (PML) protein. Retinoic acid, a powerful differentiation-inducer in vitro, is a potent agent for the treatment of neuroblastoma. Using two different human neuroblastoma cell lines, SH-SY5Y and LA-N-5, we show here that PML protein leads to the formation of nuclear bodies (PML-NB) after only 1 h of retinoic acid treatment and that this formation is mediated by the extracellular signal-regulated kinase (ERK) pathway. Inhibition of protein kinase C also leads to formation of PML-NB via the ERK pathway. Both sumoylation and phosphorylation of PML in an ERK-dependent pathway are also required for formation of PML-NB. Finally, we show that PML-NB formation in neuroblastoma cells is associated with neurite outgrowth. These results support the proposal that the formation of PML-NB is correlated with the differentiation of neuroblastoma cells.

[Aseptic cerebral venous thrombosis and multiple cerebral tuberculomas associated with pulmonary miliary tuberculosis]. / Thrombose veineuse cérébrale aseptique et tuberculomes cérébraux compliquant une miliaire tuberculeuse pulmonaire.

INTRODUCTION: Severe pulmonary tuberculosis may be complicated by deep vein thrombosis due to a state of hypercoagulability. OBSERVATION: We report a case of pulmonary miliary tuberculosis associated with cerebral venous thrombosis and multiple intracranial tuberculomas. A 65-year-old woman developed a confusional syndrome one week after starting treatment for pulmonary military tuberculosis. Neuroimaging reveals a thrombus in the right lateral sinus and multiple silent intracranial tuberculoma. CONCLUSION: The patient was given anticoagulants and fully recovered.

[An unusual cause of hemoptysis: a leech]. / Une cause inhabituelle d'hémoptysie: la sangsue.

We report an exceptional case of hemoptysis observed in a 38-year-old woman with an uneventful past history. Bronchial fibroscopy demonstrated the presence of a leech attached to the laryngeal orifice. This condition is common in endemic areas but is underdiagnosed. The association of hemoptysis, voice alterations, and difficult respiration are suggestive signs. Extraction should be achieved rapidly to avoid death due to acute respiratory failure.

The challenge of understanding ammonium homeostasis and the role of the Rh glycoproteins.

Rh glycoproteins belong to the superfamily of ammonium transporters, but until recent functional studies their functional role was unknown. This review focuses on the functional results obtained in our laboratory after the heterologous expression of RhAG (the erythroid Rh glycoprotein) and RhCG (an epithelial Rh glycoprotein). RhAG and RhCG were expressed in two different expression systems (HeLa cells and Xenopus laevis oocytes) that differed in their endogenous membrane permeabilities for NH3 and NH4+. To check if RhAG and RhCG are ammonium transporters, we measured intracellular pH changes in cells exposed to an ammonium-containing solution, and analyzed the ammonium-induced NH3 and NH4+ transmembrane fluxes in control versus transfected cells. We observed that RhAG and RhCG expression induced an enhancement of the ammonium-induced initial alkalinization (related to NH3 influx into the cell) and secondary acidification (related to NH4+ influx into the cell). Moreover, sub-millimolar ammonium concentrations induced inward currents in voltage-clamped RhAG- and in RhCG-expressing oocytes. Taken together, these results show not only that RhAG and RhCG are ammonium transporters, but also that they are promoting the transmembrane transport of NH3 and of NH4+. Data from our laboratory and from other groups raise several questions that are discussed.