Management of pseudoaneurysms of the internal carotid artery in postirradiated nasopharyngeal carcinoma patients

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Large Intragenic Deletion in DSTYK Underlies Autosomal-Recessive Complicated Spastic Paraparesis, SPG23

SPG23 is an autosomal-recessive neurodegenerative subtype of lower limb spastic paraparesis with additional diffuse skin and hair dyspigmentation at birth followed by further patchy pigment loss during childhood. Previously, genome-wide linkage in an Arab-Israeli pedigree mapped the gene to an approximately 25 cM locus on chromosome 1q24–q32. By using whole-exome sequencing in a further Palestinian-Jordanian SPG23 pedigree, we identified a complex homozygous 4-kb deletion/20-bp insertion in DSTYK (dual serine-threonine and tyrosine protein kinase) in all four affected family members. DSTYK is located within the established linkage region and we also found the same mutation in the previously reported pedigree and another Israeli pedigree (total of ten affected individuals from three different families). The mutation removes the last two exons and part of the 3′ UTR of DSTYK. Skin biopsies revealed reduced DSTYK protein levels along with focal loss of melanocytes. Ultrastructurally, swollen mitochondria and cytoplasmic vacuoles were also noted in remaining melanocytes and some keratinocytes and fibroblasts. Cultured keratinocytes and fibroblasts from an affected individual, as well as knockdown of Dstyk in mouse melanocytes, keratinocytes, and fibroblasts, were associated with increased cell death after ultraviolet irradiation. Keratinocytes from an affected individual showed loss of kinase activity upon stimulation with fibroblast growth factor. Previously, dominant mutations in DSTYK were implicated in congenital urological developmental disorders, but our study identifies different phenotypic consequences for a recurrent autosomal-recessive deletion mutation in revealing the genetic basis of SPG23.The Centre for Dermatology and Genetic Medicine is supported by a Wellcome Trust Strategic Award (reference 098439/Z/12/Z). The work was supported by the MRC (MR/M018512/1) and the UK National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre (BRC) award to Guy’s and St. Thomas’ NHS Foundation Trust, in partnership with the King’s College London and King’s College Hospital NHS Foundation Trust. This study was also supported by UK Medical Research Council Project Grant (MR/M00046X/1) and Action Research grant SP3706 as well as medical student grants from the Jean Shanks Foundation and the British Association of Dermatologists

Management of nasopharyngeal carcinoma

Nasopharyngeal carcinoma is a distinctly radiosensitive and chemosensitive tumor. Best quality radiotherapy is demanded to build up the complex concave high-dose zone for this critical location. Intensity-modulated radiotherapy (IMRT) is advocated; image guidance to ensure setup precision and adaptive re-planning if major deviations from intended dose distribution occur during the treatment course are useful improvements if resources allow. Stringent dose constraint to organs at risk should be attempted to minimize late toxicities. Addition of cisplatin-based concurrent-adjuvant chemotherapy is recommended for patients with stages III–IVB and high-risk stage IIB diseases. Contemporary series using IMRT together with extensive use of chemotherapy reported very encouraging long-term results with locoregional control in excess of 85 % at 5 years; the key remaining problems are advanced T4 disease and distant failure. Further improvement of efficacy by more potent systemic therapy and changing chemotherapy sequence to induction-concurrent is being explored. The plasma level of Epstein–Barr Viral Deoxyribonucleic Acid is a well-established tool for non-keratinizing carcinoma for prognostication and monitoring disease progress. Integrated fluorodeoxyglucose positron emission tomography and computed tomography is useful for excluding distant metastases and posttreatment persistent/recurrent disease. Early detection of failure is critical; and aggressive treatment should be attempted as long survival could be achieved for patients with limited failure. Different salvage methods and reported results are summarized

Effects of an individualized exercise program plus behavioral change enhancement strategies for managing fatigue in older people who are frail : protocol for a cluster randomized controlled trial

202312 bckwAccepted ManuscriptRGCPublishedGreen (AAM

Effects of an individualised exercise programme plus behavioural change enhancement (BCE) strategies for managing fatigue in frail older adults : a cluster randomised controlled trial

202307 bckwVersion of RecordRGCOthersThe Hong Kong Polytechnic UniversityPublishe

Decentralized COVID-19 testing by means of nanoparticle-based one-step loop-mediated isothermal amplification assay

202210 bckwOther VersionRGCOthersFood and Health Bureau; The Hong Kong Polytechnic Universit