Albumin determined by bromocresol green leads to erroneous results in routine evaluation of patients with chronic kidney disease

Objectives: Measurement of plasma albumin is pivotal for clinical decision-making in patients with chronic kidney disease (CKD). Routinely used methods as bromocresol green (BCG) and bromocresol purple (BCP) can suffer from aselectivity, but the impact of aselectivity on the accuracy of plasma albumin results of CKD-patients is still unknown. Therefore, we evaluated the performance of BCG-, BCP- and JCTLM-endorsed immunological methods in patients with various stages of CKD. Methods:We evaluated the performance of commonly used albumin methods in patients with CKD stages G1 through G5, the latter divided in two groups based on whether they received hemodialysis treatment. In total, 163 patient plasma samples were measured at 14 laboratories, on six different BCG and BCP-platforms, and four different immunological platforms. The results were compared with an ERM-DA-470k-corrected nephelometric assay. The implications on outcome is evaluated by the proportion of patient results &lt;38g/L for the diagnosis of protein energy wasting. Results:Albumin results determined with BCP- and immunological methods showed the best agreement with the target value (92.7 and 86.2%, respectively vs. 66.7% for BCG, namely due to overestimation). The relative agreement of each method with the target value was platform-dependent, with larger variability in agreement between platforms noted for BCG and immunological methods (3.2-4.6 and 2.6-5.3%) as opposed to BCP (0.7-1.5%). The stage of CKD had similar effects on the variability in agreement for the three method-groups (0.6-1.8% vs. 0.7-1.5% vs. 0.4-1.6%). The differences between methods cause discrepancies in clinical decision-making, as structurally fewer patients were diagnosed with protein energy wasting upon using BCG-based albumin results. Conclusions: Our study shows that BCP is fit for the intended use to measure plasma albumin levels in CKD patients from all stages, including patients on hemodialysis. In contrast, most BCG-based platforms falsely overestimate the plasma albumin concentration.</p

One territory, four questions, one atlas : Barcelona, 7-13 June 2022

"ETSAB, DUOT, LUB" -- Portada"Barcelona School of Architecture ETSAB, UPC Barcelona TECH, with AHO Arkitektur- og designhøgskolen i Oslo, Faculteit Architectuur KULeuven, Escola de Arquitetura, Arte e Design da Universidade do Minho" -- Coberta"ETSAB summer workshop" -- CobertaDescripció del recurs: 20 setembre 2023One territory, four questions, one atlas arises from the need to rethink the collaboration between the four academic institutions (KULeuven; UMinho; AHO; ETSAB-UPC) after four years of Summer Workshops (3 editions in Belgium; 1 in Portugal). The intention is to generate new synergies and a common theoretical-practical body that becomes the seed for future joint collaborations (Summerschools, BIP, other shared intensive programs). How do we map space and experiences? How do we map global (climate change, monetary flows) vs. local processes? How do we map concepts? (boundaries, regularity, porosity) How do we map tangibles and intangibles? How do we map sensations (noises, flavours, smells)? How do we map paths and movement? How do we represent dynamics in a static drawing? What is the (ir)relevance of geographical precision? The disciplines of architecture and urban design have representation as their main communication tool. However, in recent years, the possibilities of access to information (digital archives, open cartographic sources) and the emergence of geographic information systems have shaken the way of representing and explaining issues that were until recently linked to the physical condition of places. This booklet presents an academic experience, “One territory, four questions, one atlas”, an intensive summer research program between four institutions (KULeuven; UMinho; AHO; ETSAB-UPC), aimed to generate new synergies and a common theoretical-practical body to trigger a joint discussion on how to represent and visualise cities and life, spatial design and spatial reframing, ruptures and permanence, people and time by the act of mapping. Twelve participants (eight professors and five PhD students) worked together grouped in three teams during one week in which four questions were progressively launched to which the participants responded by drawing. The questions triggered assorted 8-hours speed maps, which in turn served as an entry for a common discussion and unlocked hidden hypothesis. The program explored the process based on an expanded dialogue to use domestic digital tools (hand drawings, pictures, video, google maps, cad and GIS cartographies, big data, open-source data, sound recordings) to produce incomplete understandings of the territory instead of achieving a finished product

Comprehensive dissection of prevalence rates, sex differences, and blood level-dependencies of clozapine-associated adverse drug reactions

Clozapine is often underused due to concerns about adverse drug reactions (ADRs) but studies into their prevalences are inconclusive. We therefore comprehensively examined prevalences of clozapineassociated ADRs in individuals with schizophrenia and demographic and clinical factors associated with their occurrence. Data from a multi-center study (n=698 participants) were collected. The mean number of ADRs during clozapine treatment was 4.8, with 2.4% of participants reporting no ADRs. The most common ADRs were hypersalivation (74.6%), weight gain (69.3%), and increased sleep necessity (65.9%), all of which were more common in younger participants. Participants with lower BMI prior to treatment were more likely to experience significant weight gain (>10%). Constipation occurred more frequently with higher clozapine blood levels and doses. There were no differences in ADR prevalence rates between participants receiving clozapine monotherapy and polytherapy. These findings emphasize the high prevalence of clozapine-associated ADRs and highlight several demographic and clinical factors contributing to their occurrence. By understanding these factors, clinicians can better anticipate and manage clozapine-associated ADRs, leading to improved treatment outcomes and patient well-being

Cep55 stabilization is required for normal execution of cytokinesis

Cep55 is a mitotic phosphoprotein that plays an important role in cytokinesis, the final stage of cell division during which physical separation of the two daughter cells is accomplished. We recently demonstrated that the peptidyl-prolyl isomerase Pin1 regulates this cell cycle event by enhancing the Plk1-dependent phosphorylation of Cep55. We show here that Cep55 is stabilized post-translationally during mitosis and that siRNA-mediated knockdown of Pin1 prevents this stabilization. Consistent with this, Cep55 is unstable in Pin1 knockout mouse embryonic fibroblasts. Moreover, mutation of the Pin1 binding sites in Cep55 reduces its stability during mitosis. Mutation of the Plk1 phosphorylation site also lowers Cep55 stability, whereas overexpression of Plk1 increases Cep55 levels, in keeping with Pin1 regulating Plk1-mediated phosphorylation of Cep55. Importantly, expression of wild-type Cep55 at levels similar to that of the phosphorylation mutants only partially reverts the cytokinesis defect induced by depletion of Cep55, indicating that inadequate levels of Cep55 prevent proper execution of cytokinesis. Taken together, these data provide more insight into the regulation of the final stages of cell division. As cytokinesis defects can cause chromosomal instability, knowledge about the processes that regulate normal cytokinesis adds to our understanding of events that lead to tumorigenesis

Automated prediction of low ferritin concentrations using a machine learning algorithm

Objectives: Computational algorithms for the interpretation of laboratory test results can support physicians and specialists in laboratory medicine. The aim of this study was to develop, implement and evaluate a machine learning algorithm that automatically assesses the risk of low body iron storage, reflected by low ferritin plasma levels, in anemic primary care patients using a minimal set of basic laboratory tests, namely complete blood count and C-reactive protein (CRP). Methods: Laboratory measurements of anemic primary care patients were used to develop and validate a machine learning algorithm. The performance of the algorithm was compared to twelve specialists in laboratory medicine from three large teaching hospitals, who predicted if patients with anemia have low ferritin levels based on laboratory test reports (complete blood count and CRP). In a second round of assessments the algorithm outcome was provided to the specialists in laboratory medicine as a decision support tool. Results: Two separate algorithms to predict low ferritin concentrations were developed based on two different chemistry analyzers, with an area under the curve of the ROC of 0.92 (Siemens) and 0.90 (Roche). The specialists in laboratory medicine were less accurate in predicting low ferritin concentrations compared to the algorithms, even when knowing the output of the algorithms as support tool. Implementation of the algorithm in the laboratory system resulted in one new iron deficiency diagnosis on average per day. Conclusions: Low ferritin levels in anemic patients can be accurately predicted using a machine learning algorithm based on routine laboratory test results. Moreover, implementation of the algorithm in the laboratory system reduces the number of otherwise unrecognized iron deficiencies

FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity protein hSir2(SIRT1)

FOXO transcription factors have important roles in metabolism, cellular proliferation, stress tolerance, and aging. FOXOs are negatively regulated by protein kinase B/c-Akt-mediated phosphorylation. Here we show that FOXO factors are also subject to regulation by reversible acetylation. We provide evidence that the acetyltransferase CREB-binding protein (CBP) binds FOXO resulting in acetylation of FOXO. This acetylation inhibits FOXO transcriptional activity. Binding of CBP and acetylation are induced after treatment of cells with peroxide stress. Deacetylation of FOXOs involves binding of the NAD-dependent deacetylase hSir2SIRT1. Accordingly, hSir2SIRT1-mediated deacetylation precludes FOXO inhibition through acetylation and thereby prolongs FOXO-dependent transcription of stress-regulating genes. These data demonstrate that acetylation functions in a second pathway of negative control for FOXO factors and provides a novel mechanism whereby hSir2SIRT1 can promote cellular survival and increase lifespan