Mitochondria play an essential role in regulating insulin secretion from beta cells by providing the ATP needed for the membrane depolarization that results in voltage-dependent Ca2+ influx and subsequent insulin granule exocytosis. Ca2+, in turn, is also rapidly taken up by the mitochondria and exerts important feedback regulation of metabolism. The aim of this study was to determine whether the distribution of mitochondria within beta cells is important for the secretory capacity of these cells. We find that cortically localized mitochondria are abundant in rodent beta cells, and that these mitochondria redistribute towards the cell interior following depolarization. The redistribution requires Ca2+-induced remodeling of the cortical F-actin network. Using light-regulated motor proteins, we increased the cortical density of mitochondria twofold and found that this blunted the voltage-dependent increase in cytosolic Ca2+ concentration and suppressed insulin secretion. The activity-dependent changes in mitochondria distribution are likely to be important for the generation of Ca2+ microdomains required for efficient insulin granule release.

Streptomyces species are experts in the production of bioactive secondary metabolites; however, their taxonomy has fallen victim of the tremendous interest

Objectives: To assess the reliability of the IPSG MRI scale for tibiotalar (TTJ) and subtalar joint (STJ) changes in young haemophilic patients, correlating MRI findings with functional scores and 3D‐rearfoot kinematics.Methods: A total of 37 haemophilic patients underwent bilateral MRI of the footankle, clinical evaluation and quantitative assessment of their 3D‐rearfoot kinematics during walking. TTJ and STJ soft tissues were assessed twice along with osteochondral changes by two radiologists using the IPSG MRI scale. Inter‐ and intra‐observer reproducibility of MRI scoring were tested by means of kappa statistics. Correlational analyses were performed between MRI findings and the Haemophilia Joint Health Score 2.1 (HJHS) and 3D‐rearfoot kinematic data.Results: The intra‐reader reliability of MRI scoring was good to excellent (Kappa: 0.62‐1), whereas the inter‐reader reliability was moderate to good (Kappa: 0.54‐0.79). Weak yet significant correlations were found between the frontal plane rearfoot range of motion (ROM) during loading response of gait and STJ score, as well as between frontal plane rearfoot ROM during the terminal stance phase and the rearfoot osteochondral lesions.Conclusion: The IPSG score appears applicable to not only the TTJ but also the STJ. Contrary to TTJ lesions, those of the STJ do not correlate with the HJHS but do with 3D‐rearfoot kinematic data.

Introduction: Treatment of haemophilia A (HA) requires infusions of factor VIII (FVIII) concentrates. The number of FVIII units infused to obtain a specific circulating FVIII level is calculated with the formula: [body weight (BW) (kg) × desired FVIII increase (%)]/2, with the assumption that each unit of FVIII infused per kg of BW increases the circulating FVIII level by 2%.Aim: The aim of this study was to evaluate the impact of several morphometric parameters (BW, body mass index (BMI)‐for‐age, height), age and type of FVIII concentrate on FVIII recovery in children with HA.Methods: A total of 66 children aged between 10 and 18 with severe HA selected from six pharmacokinetic (PK) clinical trials using two recombinant FVIII concentrates were included in the analysis. Regression tree (RT) was used to identify predictors of FVIII recovery.Results: The median age was 14.5 years with a median FVIII recovery of 2.09 for all children. The median FVIII recovery was not significantly different between age groups. Two groups were created by RT: children with a BMI‐for‐age percentile <P₉₅ (Median FVIII recovery: 1.94) and obese children with a BMI‐for‐age percentile ≥P₉₅ (Median FVIII recovery: 2.65). The FVIII recovery was significantly different between these two groups (P < 0.001).Conclusion: These results are consistent with previous studies conducted in adults with HA and confirm that the long‐held and current practice of applying an arbitrary and universal recovery of two to the calculations of FVIII dosage should be abolished in both children and adults.