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 ubiquitin-ligases 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.The proteasome is involved in the regulation of all cellular pathways and consequently plays a central role in the control of cellular homeostasis. Together with its regulators, it is at the frontline, both as an actor and as a target, in human health and when homeostasis is disturbed in disease. In this review, we aim to provide an overview of the many levels at which the functions of the proteasome and its regulators can be regulated to cope with cellular needs or are altered in pathological conditions.Ubiquitin defines a family of approximately 20 peptidic posttranslational modifiers collectively called the Ubiquitin-like (UbLs). They are conjugated to thousands of proteins, modifying their function and fate in many ways. Dysregulation of these modifications has been implicated in a variety of pathologies, in particular cancer. Ubiquitin, SUMO (-1 to -3), and Nedd8 are the best-characterized UbLs. They have been involved in the regulation of the activity and/or the stability of diverse components of various oncogenic or tumor suppressor pathways. Moreover, the dysregulation of enzymes responsible for their conjugation/deconjugation has also been associated with tumorigenesis and cancer resistance to therapies.  https://www.selleckchem.com/products/rin1.html  The UbL system therefore constitutes an attractive target for developing novel anticancer therapeutic strategies. Here, we review the roles and dysregulations of Ubiquitin, SUMO, and Nedd8 pathways in tumorigenesis, as well as recent advances in the identification of small molecules targeting their conjugating machineries for potential application in the fight against cancer.Ubiquitin ligases (E3) play a crucial role in the regulation of different cellular processes such as proliferation and differentiation via recognition, interaction, and ubiquitination of key cellular proteins in a spatial and temporal regulated manner. The type of ubiquitin chain formed determines the fate of the substrates. The ubiquitinated substrates can be degraded by the proteasome, display altered subcellular localization, or can suffer modifications on their interaction with functional protein complexes. Deregulation of E3 activities is frequently found in various human pathologies, including cancer. The illegitimated or accelerated degradation of oncosuppressive proteins or, inversely, the abnormally high accumulation of oncoproteins, contributes to cell proliferation and transformation. Anomalies in protein abundance may be related to mutations that alter the direct or indirect recognition of proteins by the E3 enzymes or alterations in the level of expression or activity of ubiquitin ligases. Through a few examples, we illustrate here the complexity and diversity of the molecular mechanisms related to protein ubiquitination involved in cell cycle regulation. We will discuss the role of ubiquitin-dependent degradation mediated by the proteasome, the role of non-proteolytic ubiquitination during cell cycle progression, and the consequences of this deregulation on cellular transformation. Finally, we will highlight the novel opportunities that arise from these studies for therapeutic intervention.INTRODUCTION Despite improved understanding of the risks of influenza and better vaccines for older patients, influenza vaccination rates remain subpar, including in high-risk groups such as older adults, and demonstrate significant racial and ethnic disparities. METHODS This study considers demographic, clinical, and geographic correlates of influenza vaccination among Medicare Fee-for-Service (FFS) beneficiaries in 2015-2016 and maps the data on a geographic information system (GIS) at the zip code level. RESULTS Analyses confirm that only half of the senior beneficiaries evidenced a claim for receiving an inactivated influenza vaccine (IIV), with significant disparities observed among black, Hispanic, rural, and poorer beneficiaries. More extensive disparities were observed for the high-dose (HD) vaccine, with its added protection for older populations and confirmed economic benefit. Most white beneficiaries received HD; no non-white subgroup did so. Mapping of the data confirmed subpar vaccination in vulnerable populations with wide variations at the zip code level. CONCLUSION Urgent and targeted efforts are needed to equitably increase IIV rates, thus protecting the most vulnerable populations from the negative health impact of influenza as well as the tax-paying public from the Medicare costs from failing to do so.Emergence delirium (ED) is defined as psychomotor agitation and delirium that typically occurs within 45 min from emergence of anesthesia. Preoperative patient conditions such as anxiety and confusion are risk factors for the development of postoperative ED. Common signs of ED are general non-purposeful resistive movements such as kicking, pulling, flailing as well as lack of eye contact and general lack of awareness of surroundings. The use of volatile anesthetics (VA) is contributory, while the use of total intravenous anesthetic techniques (TIVA) may help to reduce the incidence of emergence delirium. Furthermore, various pharmacologic strategies and alternatively non-pharmacologic strategies have been demonstrated to further diminish its occurrence. The objective of this manuscript is to provide a comprehensive review of anesthetic considerations for pediatric ED and to provide an update on techniques that have been found to be effective in reducing the overall risk of developing postoperative ED in pediatric patients.