Intersubject Variability in Cerebrovascular Hemodynamics and Systemic Physiology during a Verbal Fluency Task under Colored Light Exposure: Clustering of Subjects by Unsupervised Machine Learning.

There is large intersubject variability in cerebrovascular hemodynamic and systemic physiological responses induced by a verbal fluency task (VFT) under colored light exposure (CLE). We hypothesized that machine learning would enable us to classify the response patterns and provide new insights into the common response patterns between subjects. In total, 32 healthy subjects (15 men and 17 women, age: 25.5 ± 4.3 years) were exposed to two different light colors (red vs. blue) in a randomized cross-over study design for 9 min while performing a VFT. We used the systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS) approach to measure cerebrovascular hemodynamics and oxygenation at the prefrontal cortex (PFC) and visual cortex (VC) concurrently with systemic physiological parameters. We found that subjects were suitably classified by unsupervised machine learning into different groups according to the changes in the following parameters: end-tidal carbon dioxide, arterial oxygen saturation, skin conductance, oxygenated hemoglobin in the VC, and deoxygenated hemoglobin in the PFC. With hard clustering methods, three and five different groups of subjects were found for the blue and red light exposure, respectively. Our results highlight the fact that humans show specific reactivity types to the CLE-VFT experimental paradigm.

Elevated FGF23 and disordered renal mineral handling with reduced bone mineralization in chronically erythropoietin over-expressing transgenic mice.

Fibroblast Growth Factor 23 (FGF23) is a phosphaturic factor causing increased renal phosphate excretion as well as suppression of 1,25 (OH)2-vitamin D3. Highly elevated FGF23 can promote development of rickets and osteomalacia. We and others previously reported that acute application of erythropoietin (EPO) stimulates FGF23 production. Considering that EPO is clinically used as chronic treatment against anemia, we used here the Tg6 mouse model that constitutively overexpresses human EPO in an oxygen-independent manner, to examine the consequences of long-term EPO therapy on mineral and bone metabolism. Six to eight weeks old female Tg6 mice showed elevated intact and C-terminal fragment of FGF23 but normal plasma levels of PTH, calcitriol, calcium and phosphate. Renal function showed moderate alterations with higher urea and creatinine clearance and mild albuminuria. Renal phosphate excretion was normal whereas mild hypercalciuria was found. Renal expression of the key proteins TRPV5 and calbindin D28k involved in active calcium reabsorption was reduced in Tg6 mice. Plasma levels of the bone turnover marker osteocalcin were comparable between groups. However, urinary excretion of deoxypyridinoline (DPD) was lower in Tg6 mice. MicroCT analysis showed reduced total, cortical, and trabecular bone mineral density in femora from Tg6 mice. Our data reveal that chronic elevation of EPO is associated with high FGF23 levels and disturbed mineral homeostasis resulting in reduced bone mineral density. These observations imply the need to study the impact of therapeutically applied EPO on bone mineralization in patients, especially those suffering from chronic kidney disease.