Helse Nord-Trøndelag HF

Chronic hyperglycemia impairs mitochondrial function of beta cells. Changes in mitochondrial function preceding a negative glucose effect have not been fully characterized, nor interactions with ketones. To compare effects on beta cell mitochondrial function by short and longer exposures to elevated glucose and interactions with ketones oxygen consumption rate (OCR) was measured in intact clonal beta cells by an OROBOROS and in rat islets by a Seahorse instrument. Proteins (subunits) of mitochondrial complexes (C) were measured by immunoblotting. ATP and ROS were measured in islets. In INS-1 832/13 cells, overnight exposure to 27 vs. 11 mm glucose increased OCR and uncoupled mitochondrial respiration. These effects vanished when prolonging the exposure time of elevated glucose. C1 was decreased after two days of culture with high glucose. Interactions with racemic 5 and 20 mm beta-hydroxybutyrate (BHB) were not detected. In islets, culture overnight at 27 vs.11 mm glucose enhanced basal OCR. No decrease in glucose-induced OCR was seen after prolonging 27 mm glucose for two days. Interactions with 5 mm BHB were not detected. Prolonged exposure to 27 mm glucose enhanced basal ECAR (extracellular acidification rate) and an ECAR response to acute elevation of glucose. C1 and 3 and 4 were decreased after two days of 27 vs. 11 mm glucose. ATP levels were decreased at this time-point and extracellular ROS increased. High glucose time-dependently affects mitochondrial function in clonal beta cells and islets. C1 was uniformly decreased. Interactions with BHB were not detected.

Electronic Health Record (EHR) implementations significantly affect healthcare professionals' work routines. Previous Epic implementations in Scandinavian hospitals have led to negative outcomes, highlighting the need for a thorough evaluation of employee experiences.

To qualitatively explore hospital employees' experiences six months after Epic EHR implementation and assess implications for employee well-being and patient safety.

A qualitative study conducted at a Norwegian university hospital, six months post-implementation. Free-text responses from 950 employees (out of 2,115 survey respondents) were analyzed using reflexive thematic analysis within a phenomenological framework. Data were triangulated with focus group interviews and observational findings.

Employees reported deep concerns and high emotional intensity post-implementation. Analysis revealed 13 themes, with usability being most prominent (n = 682 quotes). Participants described the system as cumbersome, inefficient, and counterintuitive. Other major themes included work strain and own health (n = 385), administration of medicine and patient safety (n = 201), and politics and hospital management (n = 184). Many employees experienced shifts in professional identity, with some expressing job abandonment intentions.

Poorly executed EHR implementations hinder professional performance, compromise patient care, and amplify emotional distress. Addressing workflow barriers and setting realistic expectations is critical for improving adoption. Future implementations must integrate employee perspectives and evidence-based strategies to ensure EHR systems enhance rather than obstruct healthcare delivery.

Congenital factor X (FX) deficiency is a rare bleeding disorder. Heterozygous patients may experience bleedings like epistaxis or bleeding complications after dental extraction and surgery, whereas homozygous individuals often experience more severe bleedings.

To characterize a new FX variant found in two unrelated probands with mild to moderate bleeding tendencies.

Prothrombin time (PT) Quick, APTT, FX activity, FX antigen, thrombin generation and DNA sequencing were performed for probands and their families. F10 variants were explored in programs for in silico predictions and structural analyses, and in vitro expression was used for further characterization.

A novel missense variant (c.415T>C, p.F139L) was found in heterozygous form in proband 1 and in compound heterozygous form in proband 2, in combination with a previously known missense variant (c.424G>A, p.E142K). All individuals carrying the p.F139L variant had borderline/prolonged PT Quick (11.9-15.9 s) and APTT (36-43 s) and reduced thrombin generation. Both FX antigen (30-51 %) and activity (37-63 IU/dL) were reduced, indicating a type I deficiency. Structural analysis indicated that interactions between the EGF-2 and the protease domain of FX could be disrupted in the p.F139L variant, causing destabilization of the protein. The p.E142K variant was predicted to have less impact on FX structure. In vitro expression results further supported plasma findings.

We report a new FX variant, p.F139L, causing a type I FX deficiency associated with mild to moderate bleedings in heterozygous and compound heterozygous form. The variant causes structural changes which likely affect intracellular processing of FX.