Search

Context: Leading oncology societies recommend monitoring symptoms and support needs through patient-reported outcome measures (PROMs), but their use for assessing specialist palliative care (SPC) need has not yet been explored. Research on SPC integration has focused on staff-assessed screening tools, which are time-consuming., Objectives: This study aimed to assess the diagnostic validity of the Integrated Palliative Outcome Scale (IPOS) and NCCN Distress Thermometer (NCCN DT) in identifying need for SPC in patients with incurable cancer., Methods: In a cross-sectional study, patients with incurable cancer (prognosis <2 years) completed PROMs. In an independent process, the palliative care consultation service (PCCS) assessed the need for SPC in each patient through multiprofessional case review, and this was used as the reference standard. ROC analyses were employed to determine diagnostic validity., Results: Of the 208 participants, 71 (34.1 %) were classified as having SPC need by the PCCS. Aiming for a minimum sensitivity of 80%, a cut-off of ≥2 items with high/very high burden in the IPOS resulted in a 90.2% sensitivity (specificity = 50; AUC = 0.791; CI 95%= 0.724-0.858). A cut-off of ≥5 resulted in a sensitivity of 80 % for NCCN DT (specificity = 49.5 %; AUC = 0.687; CI 95% = 0.596-0.777)., Conclusion: PROMs are useful for identifying SPC need in cancer patients. Their implementation might facilitate timely integration of SPC. Future research should focus on an integrated assessment approach with PROMs that combines the requirements of the different specialties to save patient and staff resources., (Copyright © 2023 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

The primary cilium is a sensory organelle at the cell surface with integral functions in cell signaling. It contains a microtubular axoneme that is rooted in the basal body (BB) and serves as a scaffold for the movement of intraflagellar transport (IFT) particles by Kinesin-2 along the cilium. Ift88, a member of the anterograde moving IFT-B1 complex, as well as the Kinesin-2 subunit Kif3a are required for cilia formation. To facilitate signaling, the cilium restricts the access of molecules to its membrane ("ciliary gate"). This is thought to be mediated by cytoskeletal barriers ("subciliary domains") originating from the BB subdistal/distal appendages, the periciliary membrane compartment (PCMC) as well as the transition fibers and zone (TF/TZ). The PCMC is a poorly characterized membrane domain surrounding the ciliary base with exclusion of certain apical membrane proteins. Here we describe that Ift88, but not Kinesin-2, is required for the establishment of the PCMC in MDCK cells. Likewise, in C. elegans mutants of the Ift88 ortholog osm-5 fail to establish the PCMC, while Kinesin-2 deficient osm-3 mutants form PCMCs normally. Furthermore, disruption of IFT-B1 into two subcomplexes, while disrupting ciliogenesis, does not interfere with PCMC formation. Our findings suggest that cilia are not a prerequisite for the formation of the PCMC, and that separate machineries with partially overlapping functions are required for the establishment of each., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 or PKD2, the genes encoding polycystin 1 (PC1) and polycystin 2 (PC2), respectively. PC1 and PC2 localize to the primary cilium and form a protein complex, which is thought to regulate signaling events. PKD1 mutations are associated with a stronger phenotype than PKD2, suggesting the existence of PC1 specific functions in renal tubular cells. However, the evidence for diverging molecular functions is scant. The bending of cilia by fluid flow induces a reduction in cell size through a mechanism that involves the kinase LKB1 but not PC2. Here, using different in vitro approaches, we show that contrary to PC2, PC1 regulates cell size under flow and thus phenocopies the loss of cilia. PC1 is required to couple mechanical deflection of cilia to mTOR in tubular cells. This study pinpoints divergent functions of the polycystins in renal tubular cells that may be relevant to disease severity in ADPKD., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Inherited mutations in genes encoding for ciliary proteins lead to a broad spectrum of human diseases, such as polycystic kidney disease (PKD), situs inversus and retinitis pigmentosa. In the human kidney, autosomal dominant PKD (ADPKD) is caused by mutations in PKD1 (PC1), or PKD2 (TRPP2). Both are necessary for ciliary mechanotransduction, whereby bending of the cilium elicits a calcium response in the cell. We have previously shown that overexpression of mutated forms of the chemosensor kidney injury molecule 1 (Kim1) abolishes the flow response in ciliated MDCK cells. Here we identify Kim1 as an endogenous ciliary protein. Kim1 co-precipitates with TRPP2. Mutational analysis reveals that the interaction between Kim1 and TRPP2 requires the ciliary sorting motif in the N-terminus of TRPP2, and the presence of a highly conserved tyrosine in the intracellular tail of Kim1, which has previously been shown to play a role in ciliary flow sensing. These data support the notion that TRPP2 functionally interacts with ciliary chemosensors.