Organisation, regulations, preparation and logistics of parenteral nutrition in hospitals and homes; the role of the nutrition support team – Guidelines on Parenteral Nutrition, Chapter 8

PN (parenteral nutrition) should be standardised to ensure quality and to reduce complications, and it should be carried out in consultation with a specialised nutrition support team whenever possible. Interdisciplinary nutrition support teams should be established in all hospitals because effectiveness and efficiency in the implementation of PN are increased. The tasks of the team include improvements of quality of care as well as enhancing the benefit to cost ratio. Therapeutic decisions must be taken by attending physicians, who should collaborate with the nutrition support team. “All-in-One” bags are generally preferred for PN in hospitals and may be industrially manufactured, industrially manufactured with the necessity to add micronutrients, or be prepared “on-demand” within or outside the hospital according to a standardised or individual composition and under consideration of sterile and aseptic conditions. A standardised procedure should be established for introduction and advancement of enteral or oral nutrition. Home PN may be indicated if the expected duration of when PN exceeds 4 weeks. Home PN is a well established method for providing long-term PN, which should be indicated by the attending physician and be reviewed by the nutrition support team. The care of home PN patients should be standardised whenever possible. The indication for home PN should be regularly reviewed during the course of PN

Designing Chatbots for Crises: A Case Study Contrasting Potential and Reality

Chatbots are becoming ubiquitous technologies, and their popularity and adoption are rapidly spreading. The potential of chatbots in engaging people with digital services is fully recognised. However, the reputation of this technology with regards to usefulness and real impact remains rather questionable. Studies that evaluate how people perceive and utilise chatbots are generally lacking. During the last Kenyan elections, we deployed a chatbot on Facebook Messenger to help people submit reports of violence and misconduct experienced in the polling stations. Even though the chatbot was visited by more than 3,000 times, there was a clear mismatch between the users’ perception of the technology and its design. In this paper, we analyse the user interactions and content generated through this application and discuss the challenges and directions for designing more effective chatbots

BCR and its mutants, the reciprocal t(9;22)-associated ABL/BCR fusion proteins, differentially regulate the cytoskeleton and cell motility

BACKGROUND: The reciprocal (9;22) translocation fuses the bcr (breakpoint cluster region) gene on chromosome 22 to the abl (Abelson-leukemia-virus) gene on chromosome 9. Depending on the breakpoint on chromosome 22 (the Philadelphia chromosome – Ph+) the derivative 9+ encodes either the p40((ABL/BCR) )fusion transcript, detectable in about 65% patients suffering from chronic myeloid leukemia, or the p96((ABL/BCR) )fusion transcript, detectable in 100% of Ph+ acute lymphatic leukemia patients. The ABL/BCRs are N-terminally truncated BCR mutants. The fact that BCR contains Rho-GEF and Rac-GAP functions strongly suggest an important role in cytoskeleton modeling by regulating the activity of Rho-like GTPases, such as Rho, Rac and cdc42. We, therefore, compared the function of the ABL/BCR proteins with that of wild-type BCR. METHODS: We investigated the effects of BCR and ABL/BCRs i.) on the activation status of Rho, Rac and cdc42 in GTPase-activation assays; ii.) on the actin cytoskeleton by direct immunofluorescence; and iii) on cell motility by studying migration into a three-dimensional stroma spheroid model, adhesion on an endothelial cell layer under shear stress in a flow chamber model, and chemotaxis and endothelial transmigration in a transwell model with an SDF-1α gradient. RESULTS: Here we show that both ABL/BCRs lost fundamental functional features of BCR regarding the regulation of small Rho-like GTPases with negative consequences on cell motility, in particular on the capacity to adhere to endothelial cells. CONCLUSION: Our data presented here describe for the first time an analysis of the biological function of the reciprocal t(9;22) ABL/BCR fusion proteins in comparison to their physiological counterpart BCR

The PDZ Protein Canoe/AF-6 Links Ras-MAPK, Notch and Wingless/Wnt Signaling Pathways by Directly Interacting with Ras, Notch and Dishevelled

Over the past few years, it has become increasingly apparent that signal transduction pathways are not merely linear cascades; they are organized into complex signaling networks that require high levels of regulation to generate precise and unique cell responses. However, the underlying regulatory mechanisms by which signaling pathways cross-communicate remain poorly understood. Here we show that the Ras-binding protein Canoe (Cno)/AF-6, a PDZ protein normally associated with cellular junctions, is a key modulator of Wingless (Wg)/Wnt, Ras-Mitogen Activated Protein Kinase (MAPK) and Notch (N) signaling pathways cross-communication. Our data show a repressive effect of Cno/AF-6 on these three signaling pathways through physical interactions with Ras, N and the cytoplasmic protein Dishevelled (Dsh), a key Wg effector. We propose a model in which Cno, through those interactions, actively coordinates, at the membrane level, Ras-MAPK, N and Wg signaling pathways during progenitor specification

The Bcr Kinase Downregulates Ras Signaling by Phosphorylating AF-6 and Binding to Its PDZ Domain

The protein kinase Bcr is a negative regulator of cell proliferation and oncogenic transformation. We identified Bcr as a ligand for the PDZ domain of the cell junction and Ras-interacting protein AF-6. The Bcr kinase phosphorylates AF-6, which subsequently allows efficient binding of Bcr to AF-6, showing that the Bcr kinase is a regulator of the PDZ domain-ligand interaction. Bcr and AF-6 colocalize in epithelial cells at the plasma membrane. In addition, Bcr, AF-6, and Ras form a trimeric complex. Bcr increases the affinity of AF-6 to Ras, and a mutant of AF-6 that lacks a specific phosphorylation site for Bcr shows a reduced binding to Ras. Wild-type Bcr, but not Bcr mutants defective in binding to AF-6, interferes with the Ras-dependent stimulation of the Raf/MEK/ERK pathway. Since AF-6 binds to Bcr via its PDZ domain and to Ras via its Ras-binding domain, we propose that AF-6 functions as a scaffold-like protein that links Bcr and Ras to cellular junctions. We suggest that this trimeric complex is involved in downregulation of Ras-mediated signaling at sites of cell-cell contact to maintain cells in a nonproliferating state

CNK1 is a novel Akt interaction partner that promotes cell proliferation through the Akt-FoxO signalling axis.

The scaffold proteins connector enhancer of KSR (CNK) participate in Raf-, Rho- and NF-kappaB-dependent signalling and promote cell differentiation and invasion. In this study, we demonstrate that CNK1 downregulation inhibits, whereas CNK1 overexpression stimulates the proliferation of breast cancer cells and human embryonic kidney cells, respectively. This stimulatory effect depends on a functional phosphatidylinositol-3 kinase (PI3K) pathway because treatment of cells with the PI3K inhibitor, LY294002, abrogates CNK1-induced proliferation. CNK1 interacts with the PI3K effector Akt and knockdown of CNK1 decreases Akt activity in breast cancer cells. CNK1 controls Akt-dependent phosphorylation and transcriptional activity of FoxO, which is a negative regulator of proliferation. Consistent with this, CNK1-induced cell proliferation is blocked by FoxO overexpression. Moreover, CNK1 regulates anchorage-independent proliferation and focus formation of breast cancer cells. CNK1 is predominantly localized at the plasma membrane of breast cancer cells, whereas in non-transformed mammary epithelial cells, CNK1 is cytoplasmatic. Accordingly, CNK1 is found preferentially at the plasma membrane in carcinoma in situ and invasive breast cancer tumours compared with normal breast tissue sections. Analysis of multiple breast cancer samples reveals that CNK1-negative tumours show less Akt activity. Thus, CNK1 promotes oncogenic signalling through Akt in breast cancer cell lines and tumours