Beyond Binary: Influence of Sex and Gender on Outcome after Traumatic Brain Injury.

Traumatic brain injury (TBI) affects millions of individuals each year and is a leading cause of death and disability worldwide. TBI is heterogeneous and outcome is influenced by a combination of factors that include injury location, severity, genetics, and environmental factors. More recently, sex as a biological variable has been incorporated into TBI research, although there is conflicting literature regarding clinical outcomes in males versus females after TBI. We review the current clinical literature investigating sex differences after TBI. We focus our discussion on differences within contemporary gender categories to suggest that binary categories of male and female are not sufficient to guide clinical decisions for neurotrauma. Some studies have considered physiological variables that influence sex such as hormone cycles and stages in males and females pre- and post-TBI. These data suggest that there are phasic differences within male populations and within female populations that influence an individual's outcome after TBI. Finally, we discuss the impact of gender identity and expression on outcome after TBI and highlight the lack of neurotrauma research that includes non-binary individuals. Social constructs regarding gender impact an individual's vulnerability to violence and consequent TBI, including the successful reintegration to society after TBI. We call for incorporation of gender beyond the binary in TBI education, research, and clinical care. Precision medicine necessarily must progress beyond the binary to treat individuals after TBI.

Parkinson's Disease Skin Fibroblasts Display Signature Alterations in Growth, Redox Homeostasis, Mitochondrial Function, and Autophagy.

The discovery of biomarkers for Parkinson's disease (PD) is challenging due to the heterogeneous nature of this disorder, and a poor correlation between the underlying pathology and the clinically expressed phenotype. An ideal biomarker would inform on PD-relevant pathological changes via an easily assayed biological characteristic, which reliably tracks clinical symptoms. Human dermal (skin) fibroblasts are accessible peripheral cells that constitute a patient-specific system, which potentially recapitulates the PD chronological and epigenetic aging history. Here, we compared primary skin fibroblasts obtained from individuals diagnosed with late-onset sporadic PD, and healthy age-matched controls. These fibroblasts were studied from fundamental viewpoints of growth and morphology, as well as redox, mitochondrial, and autophagic function. It was observed that fibroblasts from PD subjects had higher growth rates, and appeared distinctly different in terms of morphology and spatial organization in culture, compared to control cells. It was also found that the PD fibroblasts exhibited significantly compromised mitochondrial structure and function when assessed via morphological and oxidative phosphorylation assays. Additionally, a striking increase in baseline macroautophagy levels was seen in cells from PD subjects. Exposure of the skin fibroblasts to physiologically relevant stress, specifically ultraviolet irradiation (UVA), further exaggerated the autophagic dysfunction in the PD cells. Moreover, the PD fibroblasts accumulated higher levels of reactive oxygen species (ROS) coupled with lower cell viability upon UVA treatment. In essence, these studies highlight primary skin fibroblasts as a patient-relevant model that captures fundamental PD molecular mechanisms, and supports their potential utility to develop diagnostic and prognostic biomarkers for the disease.