Characterization of Two-Pore Channel 2 by Nuclear Membrane Electrophysiology

Lysosomal calcium (Ca2+) release mediated by NAADP triggers signalling cascades that regulate many cellular processes. The identification of two-pore channel 2 (TPC2) as the NAADP receptor advances our understanding of lysosomal Ca2+ signalling, yet the lysosome is not amenable to traditional patch-clamp electrophysiology. Previous attempts to record TPC2 single-channel activity put TPC2 outside its native environment, which not reflect TPC2’s true physiological properties. To test the feasibility of using nuclear membrane electrophysiology for TPC2 channel characterization, we constructed a stable human TPC2-expressing DT40TKO cell line that lacks endogenous InsP3R and RyR (DT40TKO-hTPC2). Immunostaining revealed hTPC2 expression on the ER and nuclear envelope. Intracellular dialysis of NAADP into Fura-2-loaded DT40TKO-hTPC2 cells elicited cytosolic Ca2+ transients, suggesting that hTPC2 was functionally active. Using nuclear membrane electrophysiology, we detected a ~220 pS single-channel current activated by NAADP with K+ as the permeant ion. The detected single-channel recordings displayed a linear current-voltage relationship, were sensitive to Ned-19 inhibition, were biphasically regulated by NAADP concentration, and regulated by PKA phosphorylation. In summary, we developed a cell model for the characterization of the TPC2 channel and the nuclear membrane patch-clamp technique provided an alternative approach to rigorously investigate the electrophysiological properties of TPC2 with minimal manipulation.published_or_final_versio

Colorectal cancer screening behaviour and associated factors among Chinese aged 50 and above in Hong Kong - A population-based survey

Purpose: This study reports the uptake rate of colorectal cancer screening among Chinese people aged 50 or above and the identified factors associated with the likelihood of undergoing such screening. Methods: A cross-sectional population-based telephone survey was conducted in Hong Kong during the period 2 to 28 May 2007. The survey covered demographics, perceived health status and susceptibility to cancer, utilisation of complementary medicine, family history of cancer and cancer screening behaviour. Results: The survey was completed by 2004 Hong Kong Chinese residents aged 50 or older (response rate = 66.6%). The uptake rate of a fecal occult blood test and a colonoscopy was 12% and 19% respectively. Factors associated with colorectal cancer screening behaviour included: male participants, ex-smokers, with cancer or other serious disease, a family history of cancer, perceived health status fair or poor, regular visits to a doctor to look after health, and utilisation of complementary medicine. Conclusions: The uptake rate of this study population was low though an increasing trend did appear. Heath education and promotion programmes may focus on these identified factors to facilitate colorectal cancer screening in a Chinese population. © 2011 Elsevier Ltd.link_to_subscribed_fulltex

Colorectal cancer testing and associated factors among older Chinese adults

Letter to the Editorlink_to_subscribed_fulltex

Mucosite bucal rádio e quimioinduzida Radiation therapy and chemotherapy-induced oral mucositis

O aumento da intensidade da quimioterapia e radioterapia no tratamento do câncer tem elevado a incidência de efeitos colaterais, em especial da mucosite bucal. OBJETIVO E MÉTODO: Através de revisão bibliográfica realizou-se atualizar informações quanto à definição, características clínicas, incidência, etiologia, patofisiologia, morbidade associada, prevenção e tratamento dessa manifestação clínica. RESULTADOS: Estudos atuais definem a mucosite bucal como uma inflamação e ulceração dolorosa bastante freqüente na mucosa bucal apresentando formação de pseudomembrana. Sua incidência e severidade são influenciadas por variáveis associadas ao paciente e ao tratamento a que ele é submetido. A mucosite é conseqüência de dois mecanismos maiores: toxicidade direta da terapêutica utilizada sobre a mucosa e mielossupressão gerada pelo tratamento. Sua patofisiologia é composta por quatro fases interdependentes: fase inflamatória/vascular, fase epitelial, fase ulcerativa/bacteriológica e fase de reparação. É considerada fonte potencial de infecções com risco de morte, sendo a principal causa de interrupção de tratamentos antineoplásicos. Algumas intervenções mostraram-se potencialmente efetivas para sua prevenção e tratamento. Entretanto, faz-se necessária a realização de novos estudos clínicos mais bem conduzidos para obtenção de melhor evidência científica acerca do agente terapêutico de escolha para o controle da mucosite bucal, permitindo a realização da quimioterapia e radioterapia do câncer em parâmetros ideais.<br>Tincreasing the intensity of radiation therapy and chemotherapy in the management of cancer has increased the incidence of adverse effects, especially oral mucositis. AIM AND METHODS: a bibliographical review was conducted on the definition of oral mucositis, its clinical findings, the incidence, its etiology, the pathofisiology, associated morbidity, prevention and treatment. RESULTS: current studies define oral mucositis as a very frequent and painful inflammation with ulcers on the oral mucosa that are covered by a pseudo membrane. The incidence and severity of lesions are influenced by patient and treatment variables. Oral mucositis is a result of two major mechanisms: direct toxicity on the mucosa and myelosuppression due to the treatment. Its pathofisiology is composed of four interdependent phases: an initial inflammatory/vascular phase&#894; an epithelial phase&#894; an ulcerative/bacteriological phase&#894; and a healing phase. It is considered a potential source of life-threatening infection and often is a dose-limiting factor in anticancer therapy. Some interventions have been shown to be potentially effective to prevent and treat oral mucositis. Further intensive research through well-structured clinical trials to obtain the best scientific evidence over the standard therapy of oral mucositis is necessary to attain ideal parameters for radiotherapy and chemotherapy

Breadth and Depth Specialized Vocabulary Learning in Theology among Native and Non-Native English Speakers

A study examined native and nonnative English-speaker (NES and NNES) students\u27 knowledge and learning of specialized vocabulary over one academic term in a graduate school of theology. Findings revealed that both groups brought some breadth and depth of knowledge of specialized theological vocabulary to their studies, but the NNES group\u27s scores on both measures tended to be lower than those of NESs, there was an overall increase in scores at the end of the term, and the gap between the NNES and NES groups in breadth of vocabulary knowledge was essentially bridged but for depth of knowledge it actually widened