5-Fluorouracil signaling through a calcium-calmodulin-dependent pathway is required for p53 activation and apoptosis in colon carcinoma cells

5-Fluorouracil (5-FU) is an anti-metabolite that is in clinical use for treatment of several cancers. In cells, it is converted into three distinct fluoro-based nucleotide analogs, which interfere with DNA synthesis and repair, leading to genome impairment and, eventually, apoptotic cell death. Current knowledge states that in certain cell types, 5-FU-induced stress is signaling through a p53-dependent induction of tumor necrosis factor-receptor oligomerization required for death-inducing signaling complex formation and caspase-8 activation. Here we establish a role of calcium (Ca 2+) as a messenger for p53 activation in response to 5-FU. Using a combination of pharmacological and genetic approaches, we show that treatment of colon carcinoma cells stimulates entry of extracellular Ca 2+ through long lasting-type plasma membrane channels, which further directs posttranslational phosphorylation of at least three p53 serine residues (S15, S33 and S37) by means of calmodulin (CaM) activity. Obstructing this pathway by the Ca 2+ -chelator BAPTA (1,2-bis(o-aminophenoxy)ethane- N,N,N',N'-tetraacetic acid) or by inhibitors of CaM efficiently reduces 5-FU-induced caspase activities and subsequent cell death. Moreover, ectopic expression of p53 S15A in HCT116 p53 -/- cells confirmed the importance of a Ca 2+ -CaM-p53 axis in 5-FU-induced extrinsic apoptosis. The fact that a widely used therapeutic drug, such as 5-FU, is operating via this pathway could provide new therapeutic intervention points, or specify new combinatorial treatment regimes. © 2013 Macmillan Publishers Limited.Swedish Science Foundation; Swedish and Stockholm Cancer Societies; Swedish Childhood Cancer Foundation; EC-FP-6 (Chemores); EC-FP-7 (APO-SYS

A hemophagocytic lymphohistiocytosis case with newly defined UNC13D (C.175G>C; p.Ala59Pro) mutation and a rare complication

Hemophagocytic lymphohistiocytosis (HLH) represents a severe hyperinflammatory condition with cardinal symptoms of prolonged fever, cytopenias, hepatosplenomegaly, and hemophagocytosis by activated, morphologically benign macrophages with impaired function of natural killer cells and cytotoxic T lymphocytes. A 2-month-old girl, who was admitted with fever, was diagnosed with HLH and her genetic examination revealed a newly defined mutation in the UNC13D (c.175G>C; p.Ala59Pro) gene. She was treated with dexamethasone, etoposide, and intrathecal methotrexate. During the second week of treatment, after three doses of etoposide, it was noticed that there was a necrotic plaque lesion on the soft palate. Pathologic examination of debrided material in PAS and Grocott staining revealed lots of septated hyphae, which was consistent with aspergillosis infection. Etoposide was stopped and amphotericin B treatment was given for six weeks. HLH 2004 protocol was completed to eight weeks with cyclosporine A orally. There was no patient with invasive aspergillosis infection as severe as causing palate and nasal septum perforation during HLH therapy. In immuncompromised patients, fungal infections may cause nasal septum perforation and treatment could be achieved by antifungal therapy and debridement of necrotic tissue. © 2015 Turkish Society of Hematology. All rights reserved

Work-related injuries sustained by emergency medical technicians and paramedics in Turkey

BACKGROUND: Evaluated in the present study were locations, descriptions, and results of work-related injuries (WRIs) sustained by emergency medical technicians (EMTs) and paramedics in Turkey’s most crowded city, İstanbul. METHODS: After the present study had been accepted by the urban health authority, a questionnaire was emailed to the healthcare personnel of İstanbul’s 195 ambulance stations. RESULTS: Included in the present study were the responses of 901 members of staff (660 EMTs and 241 paramedics), with a mean age of 29.5±6.1 (min: 18; max: 61). The majority of participants (94.9%) had encountered verbal abuse from the public, and 39.8% had encountered physical violence from patients’ relatives. Levels of satisfaction with work in emergency medical services (EMS) was also evaluated, and 510 participants (57.6%) were unhappy. Regarding gender, female employees were more likely to be verbally attacked (p=0.01), while males were more likely to be physically attacked (p=0.001). It was reported that motor vehicle accidents (MVAs) were the most common cause of WRIs (81.4%), followed by needle-stick injuries (52.2%), ocular exposure to blood and other fluids (30.9%), and sharp injuries (22.5%). Only 10.5% (n=95) of WRIs were reported to authorities; 488 (54.2%) of participants just attended to the practice to prevent possible WRIs. CONCLUSION: For paramedics and EMTs, risk of WRI is obviously high. Strategies to decrease and prevent verbal and physical violence should be developed. © 2016 TJTES

The Impact of Dementia on Women Internationally: an Integrative Review

Women are disproportionately affected by dementia, both in terms of developing dementia and becoming caregivers. We conducted an integrative review of English language literature of the issues affecting women in relation to dementia from an international perspective. The majority of relevant studies were conducted in high income countries, and none were from low-income countries. The effects of caregiving on health, wellbeing and finances are greater for women; issues facing women, particularly in low and middle-income countries need to be better understood. Research should focus on building resilience to help people adjust and cope long term

The use of Silicon Wafer Barriers in the Electrochemical Reduction of Solid Silica to Form Silicon in Molten Salts

Nowadays, silicon is the most critical element in solar cells and/or solar chips. Silicon having 98 to 99% Si as being metallurgical grade, requires further refinement/purification processes such as zone refining [1,2] and/or Siemens process [3] to upgrade it for solar applications. A promising method, based on straightforward electrochemical reduction of oxides by FFC Cambridge Process [4], was adopted to form silicon from porous SiO2 pellets in molten CaCl2 and CaCl2-NaCl salt mixture [5]. It was reported that silicon powder contaminated by iron and nickel emanated from stainless steel cathode, consequently disqualified the product from solar applications. SiO2 pellets sintered at 1300oC for 4 hours, were placed in between pure silicon wafer plates to defeat the contamination problem. Encouraging results indicated a reliable alternative method of direct solar grade silicon production for expanding solar energy field