Life-threatening parkinsonism-hyperpyrexia syndrome following bilateral deep brain stimulation of the subthalamic nucleus

Parkinsonism-hyperpyrexia syndrome (PHS), or neuroleptic malignant syndrome (NMS), is a neurophysiologic reaction to the acute withdrawal/decrease of central dopamine levels. It is a severe complication characterized by rigidity, change in consciousness level, fever, hypertension, and autonomic instability, that can be fatal. To the best of our knowledge, PHS following deep brain stimulation (DBS) of subthalamic nucleus (STN) surgery due to anti-Parkinson drug discontinuation has been previously reported only six times. Half of these cases resulted in fatalities. Herein, we report on an early diagnosed case of PHS following bilateral STN-DBS which was successfully treated with the administration of dopamine agonists, fluid replacement, and activation of DBS

A Synthetic Tympanic Membrane for Middle Ear Acoustic Sensor Tests of a Fully Implantable Cochlear Prosthesis

A physical model of human Tympanic Membrane (TM), based on PDMS, as an easily accessible test platform for acoustic transducers was designed and fabricated. • A primitive ear canal simulator (TM holder) design was done using COMSOL FEA. • Vibration behavior of TM was tested with a Scanning Laser Doppler Vibrometer (SLDV). • Effect of an attached mass on the membrane was performed utilizing 32 mg and 57 mg accelerometers. • The model reproduced the basic vibrational characteristics of a human TMThe authors acknowledge European Research Council (ERC) for the financial support through FLAMENCO Project (Project No: 682756)

Kanser hastalarında palyatif bakım ve fitoterapi

Cancer is defined as a complex disease that occurs with the uncontrolled proliferation of cells and develops under the influence of genetic and environmental conditions. Chemotherapy and radiotherapy are frequently used in cancer treatment. Side effects related to these treatments are observed in most of the patients. Palliative care, which is an important part of cancer management today, aims to alleviate the symptoms and side effects of these treatments and to increase the quality of life of the patient. A growing number of patients with cancer are inclined towards complementary and integrative medicine, including herbal medicine. The interest in this field is increasing because it has been shown by preclinical and clinical studies that some phytotherapeutic products can reduce the side effects of chemotherapy and radiotherapy. This review summarizes phytotherapeutic approaches supported by clinical studies for palliative care in cancer patients.Kanser, hücrelerin kontrolsüz çoğalması ile ortaya çıkan, genetik ve çevresel koşulların etkisi altında gelişen kompleks bir hastalık olarak tanımlanmaktadır. Kemoterapi ve radyoterapi kanser tedavisinde sıklıkla kullanılmakta ve hastaların çoğunda buna bağlı yan etkiler gözlenmektedir. Günümüzde kanser yönetiminin önemli bir parçası olan palyatif bakım da bu tedavilerde ortaya çıkan semptomların ve yan etkilerin hafifletilmesini sağlayıp hastanın yaşam kalitesini artırmayı hedeflemektedir. Giderek artan sayıdaki kanser hastası, bitkisel ilaçlar da dahil olmak üzere tamamlayıcı ve entegratif tıbba yönelmiş durumdadır. Bazı fitoterapötik ürünlerin kemoterapi ve radyoterapiye bağlı yan etkileri azaltabildiğinin preklinik ve klinik çalışmalarda gösterilmesi sebebiyle bu alana olan ilgi artmaktadır. Bu derleme kanser hastalarında uygulanabilecek palyatif bakımda, klinik çalışmalarla desteklenen fitoterapötik yaklaşımları özetlemektedir

Molecular mechanisms of imatinib resistance in gastrointestinal stromal tumor with focus on microRNAs

Gastrointestinal stromal tumor (GIST) is mainly initialized by mutations in receptor tyrosine kinase genes KIT or PDGFRA. The development of imatinib, a small molecule inhibitor that targets these tyrosine kinase receptors, remarkably improved patient outcome. However, imatinib resistance remains a major therapeutic challenge in GIST therapy, and its underlying mechanisms are still not completely understood. This thesis work aimed to explore the role of microRNAs (miRNAs) and DOG1 in imatinib resistance of GIST. In Paper I, we identified specific miRNA signatures associated with imatinib resistance, metastatic disease, KIT mutational status and survival in GIST patients treated with neoadjuvant imatinib. Importantly, we demonstrate that miR-125a-5p modulates imatinib response in the single KIT-mutated GIST882 cells through PTPN18 regulation. This study highlights the clinical impact of miRNAs in GIST patients treated with imatinib pre-operatively, and suggests the important role of miR-125a-5p and PTPN18 in imatinib resistance of GISTs. In Paper II, we tested our hypothesis that miR-125a-5p overexpression in imatinib-resistant GISTs suppresses PTPN18 expression that subsequently leads to defective FAK dephosphorylation. Indeed, we demonstrate that silencing of PTPN18 increased FAK phosphorylation in GIST cells, and the acquired imatinib-resistant GIST882R cells exhibited higher pFAK and lower PTPN18 expressions than the imatinib-sensitive parental cells. FAK and pFAK expressions are also associated with imatinib resistance in GIST specimens. This study highlights the potential role of PTPN18 and pFAK in imatinib resistance of GIST. In Paper III, we found that miR-320a and miR-320b are upregulated and their potential target MCL1 is downregulated in imatinib-treated GISTs. Imatinib treatment affects MCL1 and miR-320 levels in GIST882 cells, and the imatinib-resistant GIST882R cells showed higher levels of the anti-apoptotic MCL1L isoform and lower expression of miR-320a/b as compared to GIST882 cells. This study suggests that miR-320a/b and MCL1 play a role in imatinib-induced cell death and resistance in GIST. In Paper IV, we evaluated the functional role of DOG1 in imatinib-resistant GIST48 and –sensitive GIST882 cells using specific DOG1 activator and inhibitor. We showed that DOG1 is localized in different cellular compartments in imatinib-resistant and -sensitive GIST cells. Pharmacological modulation of DOG1 activity has subtle effect on cell viability and proliferation, but may shift early apoptotic cells to late apoptotic stages in GIST48 cells. Overall, this thesis work describes the role of miRNAs in cell viability and resistance to imatinib treatment in GIST