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What is the neuronal basis for whether an experience is recalled or forgotten? In contrast to recognition, recall is difficult to study in nonhuman primates and rarely is accessible at the single neuron level in humans. We recorded 128 medial temporal lobe (MTL) neurons in patients implanted with intracranial microelectrodes while they encoded and recalled word paired associates. Neurons in the amygdala, entorhinal cortex, and hippocampus showed altered activity during encoding (9%), recall (22%), and both task phases (23%). The responses of hippocampal neurons during encoding predicted whether or not subjects later remembered the pairs successfully. Entorhinal cortex neuronal activity during retrieval was correlated with recall success. These data provide support at the single neuron level for MTL contributions to encoding and retrieval, while also suggesting there may be differences in the level of contribution of MTL regions to these memory processes.

Keratoacanthomas (KAs) and cutaneous squamous cell carcinomas (cuSCCs) develop in 15-30% of patients with BRAFV600E metastatic melanoma treated with BRAF inhibitors (BRAFi). These lesions resemble mouse skin tumors induced by the two-stage DMBA/TPA skin carcinogenesis protocol; in this protocol BRAFi accelerates tumor induction. Since prior studies demonstrated cyclooxygenase 2 (COX-2) is necessary for DMBA/TPA tumor induction, we hypothesized that COX-2 inhibition might prevent BRAFi-accelerated skin tumors. Celecoxib, a COX-2 inhibitor, significantly delayed tumor acceleration by the BRAFi inhibitor PLX7420 and decreased tumor number by 90%. Tumor gene expression profiling demonstrated that celecoxib partially reversed the PLX4720-induced gene signature. In PDV cuSCC cells, vemurafenib (a clinically approved BRAFi) increased ERK phosphorylation and soft agar colony formation; both responses were greatly decreased by celecoxib. In clinical trials trametinib, a MEK inhibitor (MEKi) increases BRAFi therapy efficacy in BRAFV600E melanomas and reduces BRAFi-induced KA and cuSCC frequency. Trametinib also reduced vemurafenib-induced PDV soft agar colonies, but less efficiently than celecoxib. The trametinb/celecoxib combination was more effective than either inhibitor alone. In conclusion, celecoxib suppressed both BRAFi-accelerated skin tumors and soft-agar colonies, warranting its testing as a chemopreventive agent for non-melanoma skin lesions in patients treated with BRAFi alone or in combination with MEKi.

Influence of environmental temperature on the occurrence of non-necrotizing cellulitis of the leg SIR, Non-necrotizing cellulitis of the leg is a common cutaneous bacterial infection whose risk factors include venous insufficiency, lymphoedema and toe-web intertrigo. The role of environmental temperature remains controversial. 1 To study the relationship between environmental temperature and the frequency of non-necrotizing cellulitis of the leg, we reviewed all patients hospitalized with nonnecrotizing cellulitis of the leg in a university hospital in a temperate region of France during a 4-year period, and correlated findings with the local environmental temperature during the same period.Patients included in this study were consecutive patients referred for non-necrotizing cellulitis of the leg from January 1995 to December 1998 in the Departments of Dermatology, Internal Medicine and Infectious Diseases of the Rouen University Hospital. The diagnosis of cellulitis of the leg was retrospectively identified using the database of the Medical Information System. The mean and maximum temperatures of each the 8 days prior to the date of hospital admission were obtained from the local meteorological unit for each case. Correlations between the mean and maximum daily temperature of each day from day ) 8 to the admission day (lag 0-8 days) and the daily number of patients hospitalized for cellulitis of the leg were studied using a nonparametric Poisson regression model to adjust for time trends and days of the week (generalized additive model). 2 Eight hundred and ninety-eight patients with cellulitis of the leg [342 men (38%) and 556 women (62%)] were

The protein kinase BRAF regulates cell growth through the mitogen-activated protein kinase (MAPK) pathway. In about half of the melanomas, BRAF is mutated and acts as a driver oncogene that stimulates cell proliferation, survival, and tumor progression (Davies et al., 2002; Gray-Schopfer et al., 2007). The anti-BRAF drugs vemurafenib (PLX4032/RG7204) and dabrafenib (GSK2118436) achieve objective clinical responses in about 60% of melanoma patients whose tumors express mutant BRAF (Flaherty et al., 2010; Chapman et al., 2011; Sosman et al., 2012), validating these drugs as a