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Diversity in brain health is influenced by individual differences in demographics and cognition. However, most studies on brain health and diseases have typically controlled for these factors rather than explored their potential to predict brain signals. Here, we assessed the role of individual differences in demographics (age, sex, and education; n = 1298) and cognition (n = 725) as predictors of different metrics usually used in case-control studies. These included power spectrum and aperiodic (1/f slope, knee, offset) metrics, as well as complexity (fractal dimension estimation, permutation entropy, Wiener entropy, spectral structure variability) and connectivity (graph-theoretic mutual information, conditional mutual information, organizational information) from the source space resting-state EEG activity in a diverse sample from the global south and north populations. Brain-phenotype models were computed using EEG metrics reflecting local activity (power spectrum and aperiodic components) and brain dynamics and interactions (complexity and graph-theoretic measures). Electrophysiological brain dynamics were modulated by individual differences despite the varied methods of data acquisition and assessments across multiple centers, indicating that results were unlikely to be accounted for by methodological discrepancies. Variations in brain signals were mainly influenced by age and cognition, while education and sex exhibited less importance. Power spectrum activity and graph-theoretic measures were the most sensitive in capturing individual differences. Older age, poorer cognition, and being male were associated with reduced alpha power, whereas older age and less education were associated with reduced network integration and segregation. Findings suggest that basic individual differences impact core metrics of brain function that are used in standard case-control studies. Considering individual variability and diversity in global settings would contribute to a more tailored understanding of brain function., Competing Interests: Declaration of competing interest none., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

NADPH-cytochrome1 P450 reductase and DT-diaphorase catalyze and one- and two-electron reduction of adrenochrome to its o-semiquinone and o-hydroquinone, respectively. Under aerobic conditions both adrenochrome o-semiquinone and o-hydroquinone proved to be unstable, undergoing autoxidation with concomitant oxygen consumption and continuous NADPH and NADH oxidation. Molecular oxygen was found to play a predominant role in autoxidation of o-semiquinone during reduction of adrenochrome catalyzed by NADPH-cytochrome P450 reductase. In addition, molecular oxygen, in the presence of manganese, was found to be responsible for the majority of autoxidation of o-semiquinone. However, the role of superoxide radicals in the autoxidation of leucoadrenochrome during the reduction of adrenochrome by DT-diaphorase was found to be predominant. Catalase different significantly with respect to NADPH and NADH oxidation during reduction of adrenochrome catalyzed by NADPH-cytochrome P450 reductase and DT-diaphorase. Catalase increased NADPH oxidation slightly, while NADH oxidation was inhibited during reduction of adrenochrome by NADPH cytochrome P450 reductase and DT-diaphorase, respectively. The presence of manganese in the incubation mixture was found to increase the prooxidant role of catalase on autoxidation during one-electron reduction of aminochrome catalyzed by NADPH cytochrome P450 reductase. A marked difference in the inhibitory effect of superoxide dismutase on oxygen consumption during adrenochrome reduction catalyzed by NADPH-cytochrome P450 reductase and DT-diaphorase was also observed. A possible mechanism for reduction of adrenochrome by NADPH-cytochrome P450 reductase and DT-diaphorase and a role for superoxide dismutase and catalase are proposed.

NADPH-cytochrome P-450 reductase catalyzes one-electron reduction of aminochrome to the corresponding ortho-semiquinone, which was found to be unstable as indicated by the occurrence of NADPH oxidation and oxygen consumption. The addition of superoxide dismutase and catalase, alone or together, to the incubation mixture, during reduction of aminochrome catalyzed by NADPH-cytochrome P-450 reductase, did not prevent the autoxidation of ortho-semiquinone, but instead they increased NADPH oxidation. These results contrast with the almost complete inhibition of autoxidation (NADH oxidation) of ortho-hydroquinone during reduction of aminochrome catalyzed by DT-diaphorase in the presence of both superoxide dismutase and catalase. However, the effect of superoxide dismutase and catalase on oxygen consumption was found to differ from the effect on NADH or NADPH oxidation, since these enzymes, alone or together, inhibited the oxygen consumption during the reduction of aminochrome catalyzed by both NADPH-cytochrome P-450 reductase and DT-diaphorase. These results support the proposed role of NADPH-cytochrome P-450 reductase in neurodegeneration as a consequence of activation of aminochrome to reactive oxygen species. In addition, they also support the protective and antioxidant role of DT-diaphorase, together with superoxide dismutase and catalase, by competing with NADPH-cytochrome P-450 reductase to reduce aminochrome to ortho-hydroquinone and prevent the formation of reactive oxygen species. A possible mechanism is proposed.

The effect of varying arterial perfusion pressure (Pa) on flow behavior of human normal (HbAA) and sickle (HbSS) erythrocytes was evaluated in isolated rat mesoappendix vasculature. Red cell velocity (Vrbc) and wall shear rate in single arterioles (i.d. 20.4 +/- 4.5 Microns means and SD) were determined and total peripheral vascular resistance (PRU) calculated. The vasculature initially perfused with Ringer's solution was then perfused with red cells suspended (HCT 2%) in the same medium. At Pa of 100 mm Hg, oxy HbSS cells resulted in higher (50%) PRU and lower Vrbc (7.1 +/- 2.2 mm/sec) and wall shear rates (1800 +/- 490 sec-1) than those recorded with HbAA cells which show a more rapid microvascular passage, i.e., Vrbc (14.4 +/- 2.8 mm/sec) and wall shear rates (3810 +/- 360 sec-1). At the same Pa, partial deoxygenation (PO2 40 mm Hg) of HbSS cells caused marked (300%) increase in PRU, and decrease in Vrbc (3.2 +/- 0.9 mm/sec), and wall shear rates (820 +/- 440 sec-1). During stepwise decrement of Pa (100-30 mm Hg), PRU for oxy HbSS cells remains elevated but the overall trend is similar to that for HbAA cells and Ringer's perfusion. At Pa of 30 mm Hg, oxy HbSS cells caused some microvascular obstruction. In contrast, with decrement in Pa below 80 mm Hg partially deoxy HbSS cells resulted in progressive increase in PRU and drastic decrease in Vrbc, coupled with progressive capillary obstruction and stasis. An increased propensity of these cells to cause irreversible vasoocclusion is demonstrated when low-pressure conditions prevail.