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To identify determinants that form nonapeptide hormone binding domains of the white sucker Catostomus commersoni [[Arg.sup.8]]vasotocin receptor, chimeric constructs encoding parts of the vasotocin receptor and parts of the isotocin receptor have been analyzed by [(3,[5.sup.-3]H)[Tyr.sup.2], [Arg.sup.8]]vasotocin binding to membranes of human embryonic kidney cells previously transfected with the different cDNA constructs and by functional expression studies in Xenopus laevis oocytes injected with mutant cRNAs. The results indicate that the N terminus and a region spanning the second extracellular loop and its flanking transmembrane segments, which contains a number of amino acid residues that are conserved throughout the nonapeptide receptor family, contribute to the affinity of the receptor for its ligand. Nonapeptide selectivity, however, is mainly defined by transmembrane region VI and the third extracellular loop. These results are complemented by a molecular model of the vasotocin receptor obtained by aligning its sequence with those of other G-protein coupled receptors as well as that of bacteriorhodopsin. The model indicates that amino acid residues of transmembrane regions II-VII that are located close to the extracellular surface also contribute to the binding of vasotocin.

Introduction: This study aimed to provide insight into the merits of DementiaNet, a network-based primary care innovation for community-dwelling dementia patients. Methods: Longitudinal mixed methods multiple case study including 13 networks of primary care professionals as cases. Data collection comprised continuously-kept logs; yearly network maturity score (range 0–24), yearly quality of care assessment (quality indicators, 0–100), and in-depth interviews. Results: Networks consisted of median nine professionals (range 5–22) covering medical, care and welfare disciplines. Their follow-up was 1–2 years. Average yearly increase was 2.03 (95%-CI:1.20–2.96) on network maturity and 8.45 (95%-CI:2.80–14.69) on quality indicator score. High primary care practice involvement and strong leadership proved essential in the transition towards more mature networks with better quality of care. Discussion: Progress towards more mature networks favored quality of care improvements. DementiaNet appeared to be effective to realize transition towards network-based care, enhance multidisciplinary collaboration, and improve quality of dementia care. [ABSTRACT FROM AUTHOR]

Since 2017, two immune checkpoint inhibitors (ICIs) have become the standard of care for the treatment of metastatic urothelial carcinoma in Europe: pembrolizumab as second-line therapy and avelumab as maintenance therapy. Our aim was to describe the use of ICIs as first and later lines of treatment in patients with metastatic bladder cancer (mBC) in the Netherlands. We identified all patients diagnosed with primary mBC between 2018 and 2021 in the Netherlands from the Netherlands Cancer Registry (NCR). NCR data were supplemented with data from the Dutch nationwide Prospective Bladder Cancer Infrastructure (ProBCI) collected from medical files, with follow-up until death or end of data collection on January 1, 2023. A total of 1525 patients were diagnosed with primary mBC between 2018 and 2021 in the Netherlands. Of these, 34.7% received at least one line of systemic treatment with chemotherapy or ICI. After first-line platinum-based chemotherapy, 34.1% received second-line ICI and 3.9% received maintenance ICI. Among patients who completed or discontinued first-line cisplatin- or carboplatin-based chemotherapy after approval of maintenance ICI in the Netherlands, 40.7% and 19.7% received second-line ICI, and 9.3% and 14.1% received maintenance ICI, respectively. ICI use for mBC treatment has not increased considerably since their introduction in 2017. Future research should assess whether the introduction of maintenance avelumab (available since April 2021 in the Netherlands) has led to increases in the proportion of patients with mBC patients receiving systemic treatment and the proportion receiving ICI., Patient Summary: We assessed the rate of immunotherapy use for patients with metastatic bladder cancer in the Netherlands. Since its introduction, immunotherapy has been used in a minority of patients, mostly as second-line treatment after platinum-based chemotherapy., (© 2023 The Author(s).)