Proteostasis Dysregulation in Pancreatic Cancer

The most common form of pancreatic cancer, pancreatic ductal adenocarcinoma (PDAC), has a dismal 5-year survival rate of less than 5%. Radical surgical resection, in combination with adjuvant chemotherapy, provides the best option for long-term patient survival. However, only approximately 20% of patients are resectable at the time of diagnosis, due to locally advanced or metastatic disease. There is an urgent need for the identification of new, specific, and more sensitive biomarkers for diagnosis, prognosis, and prediction to improve the treatment options for pancreatic cancer patients. Dysregulation of proteostasis is linked to many pathophysiological conditions, including various types of cancer. In this review, we report on findings relating to the main cellular protein degradation systems, the ubiquitin-proteasome system (UPS) and autophagy, in pancreatic cancer. The expression of several components of the proteolytic network, including E3 ubiquitinligases and deubiquitinating enzymes, are dysregulated in PDAC, which accounts for approximately 90% of all pancreatic malignancies. In the future, a deeper understanding of the emerging role of proteostasis in pancreatic cancer has the potential to provide clinically relevant biomarkers and new strategies for combinatorial therapeutic options to better help treat the patients.Peer reviewe

Factors related to delayed intensive care unit admission from emergency department:a retrospective cohort study

Abstract Background: The delays in transferring patients from emergency department (ED) to intensive care unit (ICU) are known to be linked with several adverse events, including prolonged ICU stay and increased hospital mortality. The factors associated with delayed ICU admission include shortage of ICU beds, organizational factors, ED overcrowding, and patient‐related factors, including sepsis as admission diagnosis. The aim of this study was to examine ED‐related factors associated with prolonged ED stay. Methods: The study population consisted of adult patients admitted (n = 479) from ED to ICU between 31 May 2016 and 19 March 2017 in Oulu University Hospital. A patient’s ED length of stay (LOS) exceeding 180 minutes was considered delayed. Results: Most of the patients (380, 79.3%) were admitted to the ICU within 3 hours of hospital admission. In a logistic regression analysis, odds ratios (ORs) for ED LOS > 180 minutes were as follows: for Glasgow Coma Scale score > 9, 2.73 (1.39–5.32); for thrombocytes < 100 × 109/mmol, 6.69 (2.32–19.26); for absence of pre‐arrival notification, 5.27 (3.04–9.14); and for radiological examination, 3.95 (1.72‐9.10). Trauma and intoxicated patients had shorter ED LOS while patients with medical conditions had more often prolonged admissions. Conclusion: The delays in ICU admissions were linked to therapeutic and diagnostic procedures and absence of pre‐arrival notification. Patients were admitted to the ICU on the basis of diagnosis instead of clinical risk. However, the delays were not associated with worsening outcome, which indicates that sufficient care can be provided at the ED while the ICU admission is pending

Theory meets Practice – H. Paul Grice’s Maxims of Quality and Manner and the Trobriand Islanders’ language use

As I have already pointed out elsewhere (Senft 2008; 2010; 2014), the Gricean conversational maxims of Quality – “Try to make your contribution one that is true” – and Manner “Be perspicuous”, specifically “Avoid obscurity of expression” and “Avoid ambiguity” (Grice 1967; 1975; 1978) – are not observed by the Trobriand Islanders of Papua New Guinea, neither in forms of their ritualized communication nor in forms and ways of everyday conversation and other ordinary verbal interactions. The speakers of the Austronesian language Kilivila metalinguistically differentiate eight specific non-diatopical registers which I have called “situational-intentional” varieties. One of these varieties is called “biga sopa”. This label can be glossed as “joking or lying speech, indirect speech, speech which is not vouched for”. The biga sopa constitutes the default register of Trobriand discourse and conversation. This contribution to the workshop on philosophy and pragmatics presents the Trobriand Islanders’ indigenous typology of non-diatopical registers, especially elaborating on the concept of sopa, describing its features, discussing its functions and illustrating its use within Trobriand society. It will be shown that the Gricean maxims of quality and manner are irrelevant for and thus not observed by the speakers of Kilivila. On the basis of the presented findings the Gricean maxims and especially Grice’s claim that his theory of conversational implicature is “universal in application” is critically discussed from a general anthropological-linguistic point of view