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Introduction: Several factors, including changed dynamics of erythrocyte formation and degradation, can influence the degree of hemoglobin A1c (HbA1c) formation thereby affecting its use in monitoring diabetes. This study determines the influence of whole blood donation on HbA1c in both non-diabetic blood donors and blood donors with type 2 diabetes. Methods: In this observational study, 23 non-diabetic blood donors and 21 blood donors with type 2 diabetes donated 475 mL whole blood and were followed prospectively for nine weeks. Each week blood samples were collected and analyzed for changes in HbA1c using three secondary reference measurement procedures. Results: Twelve non-diabetic blood donors (52.2%) and 10 (58.8%) blood donors with type 2 diabetes had a significant reduction in HbA1c following blood donation (reduction >-4.28%, P < 0.05). All non-diabetic blood donors with a normal ferritin concentration predonation had a significant reduction in HbA1c. In the non-diabetic group the maximum reduction was -11.9%, in the type 2 diabetes group -12.0%. When eligible to donate again, 52.2% of the non-diabetic blood donors and 41.2% of the blood donors with type 2 diabetes had HbA1c concentrations significantly lower compared to their predonation concentration (reduction >-4.28%, P < 0.05). Conclusion: Patients with type 2 diabetes contributing to whole blood donation programs can be at risk of falsely lowered HbA1c. This could lead to a wrong interpretation of their glycemic control by their general practitioner or internist. [ABSTRACT FROM AUTHOR]

Delayed graft function (DGF) after kidney transplantation heralds a worse prognosis. In patients with hyperoxaluria, the incidence of DGF is high. Oxalic acid is a waste product that accumulates when kidney function decreases. We hypothesize that residual diuresis and accumulated waste products influence the DGF incidence. Patients transplanted between 2018-2022 participated in the prospective cohort study. Pre-transplant concentrations of oxalic acid and its precursors were determined. Data on residual diuresis and other recipient, donor or transplant related variables were collected. 496 patients were included, 154 were not on dialysis. Oxalic acid, and glyoxylic acid, were above upper normal concentrations in 98.8%, and 100% of patients. Residual diuresis was ≤150 mL/min in 24% of patients. DGF occurred in 157 patients. Multivariable binary logistic regression analysis demonstrated a significant influence of dialysis type, recipient BMI, donor type, age, and serum creatinine on the DGF risk. Residual diuresis and glycolic acid concentration were inversely proportionally related to this risk, glyoxylic acid directly proportionally. Results in the dialysis population showed the same results, but glyoxylic acid lacked significance. In conclusion, low residual diuresis is associated with increased DGF incidence. Possibly accumulated waste products also play a role. Pre-emptive transplantation may decrease the incidence of DGF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Post Hospers, Visser, Verhoeven, Laging, Baart, Mertens zur Borg, Hesselink, de Mik-van Egmond, Betjes, van Agteren, Severs, van de Wetering, Zietse, Vos, Kema, Kho, Reinders and Roodnat.)

Glycaemic control of diabetic patients, assessed by HbA1c measurements over time, reduces the risk of developing long-term complications. But how reliable is the HbA1c value? Are there circumstances in which a measured value should be questioned? This laboratory quiz describes the diagnostic value, interpretation and pitfalls of the HbA1c-assay.

Protein aggregation is a hallmark of many neuronal disorders, including the polyglutamine disorder spinocerebellar ataxia 3 and peripheral neuropathies associated with the K141E and K141N mutations in the small heat shock protein HSPB8. In cells, HSPB8 cooperates with BAG3 to stimulate autophagy in an eIF2α-dependent manner and facilitates the clearance of aggregate-prone proteins (Carra, S., Seguin, S. J., Lambert, H., and Landry, J. (2008) J. Biol. Chem. 283, 1437-1444; Carra, S., Brunsting, J. F., Lambert, H., Landry, J., and Kampinga, H. H. (2009) J. Biol. Chem. 284, 5523-5532). Here, we first identified Drosophila melanogaster HSP67Bc (Dm-HSP67Bc) as the closest functional ortholog of human HSPB8 and demonstrated that, like human HSPB8, Dm-HSP67Bc induces autophagy via the eIF2α pathway. In vitro, both Dm-HSP67Bc and human HSPB8 protected against mutated ataxin-3-mediated toxicity and decreased the aggregation of a mutated form of HSPB1 (P182L-HSPB1) associated with peripheral neuropathy. Up-regulation of both Dm-HSP67Bc and human HSPB8 protected and down-regulation of endogenous Dm-HSP67Bc significantly worsened SCA3-mediated eye degeneration in flies. The K141E and K141N mutated forms of human HSPB8 that are associated with peripheral neuropathy were significantly less efficient than wild-type HSPB8 in decreasing the aggregation of both mutated ataxin 3 and P182L-HSPB1. Our current data further support the link between the HSPB8-BAG3 complex, autophagy, and folding diseases and demonstrate that impairment or loss of function of HSPB8 might accelerate the progression and/or severity of folding diseases.

Background: The HSPB family is one of the more diverse families within the group of HSP families. Some members have chaperone-like activities and/or play a role in cytoskeletal stabilization. Some members also show a dynamic, stress-induced translocation to SC35 splicing speckles. If and how these features are interrelated and if they are shared by all members are yet unknown., Methods: Tissue expression data and interaction and co-regulated gene expression data of the human HSPB members was analyzed using bioinformatics. Using a gene expression library, sub-cellular distribution of the diverse members was analyzed by confocal microscopy. Chaperone activity was measured using a cellular luciferase refolding assay., Results: Online databases did not accurately predict the sub-cellular distribution of all the HSPB members. A novel and non-predicted finding was that HSPB7 constitutively localized to SC35 splicing speckles, driven by its N-terminus. Unlike HSPB1 and HSPB5, that chaperoned heat unfolded substrates and kept them folding competent, HSPB7 did not support refolding., Conclusion: Our data suggest a non-chaperone-like role of HSPB7 at SC35 speckles., General Significance: The functional divergence between HSPB members seems larger than previously expected and also includes non-canonical members lacking classical chaperone-like functions.

Drosophila S2 cells are easy to manipulate and culture and are a versatile model system for high-throughput screens such as genome-wide siRNA screens to find genes involved in stress or therapy resistance or for screening through large compound libraries to identify cytotoxins. Clonogenic assays are considered the gold-standard to investigate the cytotoxicity of specific treatments or to compare the sensitivity of various cell types for a specific treatment. However, this assay cannot be used for Drosophila S2 cells as they are virtually unable to grow in distinct colonies. We designed a novel fluorescence-based flow cytometry assay to study long-term proliferation of S2 cells under various conditions and in the presence of specific gene products or after downregulation of specific gene products. Here we validate this assay and we used this novel method to investigate the role of checkpoint genes grapes/Dchk1 and DmChk2 in cell survival responses. Our data demonstrate that Grapes/Dchk1 but not DmChk2 is required to survive hydroxyurea. Our assay will be of use to investigate the long-term effects of various treatments in S2 cells and to evaluate the role of specific proteins therein., ((c) 2008 International Society for Advancement of Cytometry)