In this largest clinical trial of β-blockers for prevention of cardiotoxicity under contemporary ANT dosage, the authors noted a 13.5% to 14.5% incidence of cardiotoxicity. In this scenario, carvedilol had no impact on the incidence of early onset of LVEF reduction. However, the use of carvedilol resulted in a significant reduction in troponin levels and diastolic dysfunction. (Carvedilol Effect in Preventing Chemotherapy-Induced Cardiotoxicity [CECCY]; NCT01724450).

No abstract

Biallelic pathogenic variants in TBCK cause encephaloneuropathy, infantile hypotonia with psychomotor retardation, and characteristic facies 3 (IHPRF3). The molecular mechanisms underlying its neuronal phenotype are largely unexplored. In this study, we reported two sisters, who harbored biallelic variants in TBCK and met diagnostic criteria for IHPRF3. We provided evidence that TBCK may play an important role in the early secretory pathway in neuroprogenitor cells (iNPC) differentiated from induced pluripotent stem cells (iPSC). Lack of functional TBCK protein in iNPC is associated with impaired endoplasmic reticulum-to-Golgi vesicle transport and autophagosome biogenesis, as well as altered cell cycle progression and severe impairment in the capacity of migration. Alteration in these processes, which are crucial for neurogenesis, neuronal migration, and cytoarchitecture organization, may represent an important causative mechanism of both neurodevelopmental and neurodegenerative phenotypes observed in IHPRF3. Whether reduced mechanistic target of rapamycin (mTOR) signaling is secondary to impaired TBCK function over other secretory transport regulators still needs further investigation.

Linear discriminant analysis, a multivariate statistical procedure, applied to serum calcium, phosphate, alkaline phosphatase, bicarbonate, chloride, creatinine and tubular reabsorption of phosphate, proved to be effective in distinguishing patients with Primary Hyperparathyroidism from other hypercalcaemic patients in eithy-four retrospective cases. The application of the model to thirty-four prospective cases enabled us to separate correctly, hyperparathyroid patients from non-parathyroid hypercalcaemic patients.