The two-pore domain K ؉ channel, TRESK (TWIK-related spinal cord K ؉ channel) is reversibly activated by the calcium/ calmodulin-dependent protein phosphatase, calcineurin. In the present study, we report that 14-3-3 proteins directly bind to the intracellular loop of TRESK and control the kinetics of the calcium-dependent regulation of the channel. Coexpression of 14-3-3 with TRESK blocked, whereas the coexpression of a dominant negative form of 14-3-3 accelerated the return of the K ؉ current to the resting state after the activation mediated by calcineurin in Xenopus oocytes. The direct action of 14-3-3 was spatially restricted to TRESK, since 14-3-3 was also effective, when it was tethered to the channel by a flexible polyglutaminecontaining chain. The effect of both the coexpressed and chained 14-3-3 was alleviated by the microinjection of Ser(P)-Raf259 phosphopeptide that competes with TRESK for binding to 14-3-3. The ␥ and isoforms of 14-3-3 controlled TRESK regulation, whereas the ␤, , ⑀, , and isoforms failed to influence the mechanism significantly. Phosphorylation of serine 264 in mouse TRESK was required for the binding of 14-3-3. Because 14-3-3 proteins are ubiquitous, they are expected to control the duration of calcineurin-mediated TRESK activation in all the cell types that express the channel, depending on the phosphorylation state of serine 264. This kind of direct control of channel regulation by 14-3-3 is unique within the two-pore domain K ؉ channel family.Members of the 14-3-3 family are dimeric proteins, and each subunit possesses a single polypeptide binding groove (1). Proteins that bind these grooves typically encode either the RSXpSXP (mode I) or RX(Y/F)XpSXP (mode II) consensus motif (where X may be any amino acid, and pS denotes phosphoserine (2, 3). Several different interacting partners of 14-3-3 have been described, and 14-3-3 proved to be an important constituent of large protein complexes implicated in such diverse processes as the initiation of DNA replication, transcription, control of cell cycle, intracellular trafficking, and the modulation of ion channel function (4, 5).Two-pore domain potassium (2PK ϩ ) channels give rise to background (leak) K ϩ currents that are pivotal regulators of the excitability in neurons and other cell types (6). Members of this potassium channel family attracted particular attention as the stimulation of their currents essentially contributed to the therapeutically important action of volatile anesthetics (7-10). Among the 15 2PK ϩ channels, so far only TASK-1 and TASK-3 subunits have been shown to interact with 14-3-3␤ andthrough an unconventional (mode III) C-terminal motif. The binding of 14-3-3 overrides the endoplasmic reticulum retention signal and redirects these TASK channels to the cell surface (11-13).TRESK, 2 the 15th member of the 2PK ϩ channel family, was cloned from human spinal cord (14) and mouse cerebellum (15). Its mRNA is also expressed in the testis (15), spleen, thymus, placenta (16), and in the cerebrum (9). Recently, TRESK ...

Malignant fibrous histiocytoma (MFH) also known as undifferentiated high-grade pleomorphic sarcoma (UHPS) is a soft tissue sarcoma, composed of undifferentiated mesenchymal tumors possessed fibrohistiocytic morphology without definite true histiocytic differentiation. Head and neck localization is very rare, showing an incidence ranging from 4 % to 10 % in different series of investigations. The most frequent involved sites in UHPS are the neck and parotid, followed by the scalp, face, anterior skull base and orbit. Upper aerodigestive tract, lateral skull base and ear are rare locations. The incidence of the lymphatic metastases is also rare. The aim of this article is to report a case of UHPS in the maxillary sinus with palatal, orbital and ethmoidal involvement, with lymphatic metastasis and its surgical treatment. In addition, we review the literature of similar cases of the past 12 years.

Depth of invasion is an important predictor of survival. A study by the International Consortium (ICOR) for Outcome Research proposed incorporation of it (together with the greatest surface dimension, or the anatomical criteria, or both) into the T stage. This has been adopted in part by the 8th edition of the Union for International Cancer Control (UICC) TNM 8 classification of malignant tumours for oral squamous cell carcinoma (SCC). Our aim was to verify depth of invasion as an independent prognostic factor, and to validate the staging by comparing it with that specified in the 7th edition (TNM 7) and the T-staging model proposed by the International Consortium. We retrospectively studied 449 patients who had had operations for a previously untreated primary oral cancer between 2006 and 2014 at a single centre, and analysed the independent predictive value of depth of invasion for both disease-specific and overall survival. It was an independent predictor of disease-specific survival as were sex, perineural invasion, and N stage. It was also an independent predictor of overall survival together with sex and N status. Staging in TNM 8 gave a better balance of distribution than that in TNM 7, but did not discriminate between prognosis in patients with T3 and T4 disease. The proposed International Consortium rules for T-staging gave an improved balance in distribution and hazard discrimination. The incorporation of depth of invasion into the T-staging rules for oral SCC improved prognostic accuracy and is likely to influence the selection of patients for adjuvant treatment. Our findings suggest that the TNM 8 staging lacks hazard discrimination in patients with locally-advanced disease because its T4 staging is restricted to anatomical criteria.

Head and neck necrotising soft-tissue infection is exceptionally uncommon in the paediatric population. necrotising soft-tissue infection is severe and often life-threatening. Rapid spread of infection and systemic illness make necrotising soft-tissue infection a challenge for the medical and surgical teams. Early identification and surgical intervention are essential for a favourable patient outcome. This report details the case of periorbital necrotising soft-tissue infection in a 12-year-old male patient following an uncomplicated facial laceration. Prompt surgical debridement with planned return visits to theatre and guided empirical antibiotic therapy ensured that a satisfactory patient outcome was achieved. The failure of current necrotising soft-tissue infection diagnostic scoring tools to be positive in this case may suggest that these tools require refinement and validation.

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