Concepts and Approaches in the Management of Transgender and Gender-Diverse Patients.

The terms transgender and gender diverse (TGD) describe persons whose gender is different from the sex assigned to them at birth. While TGD persons have experienced a rise in cultural and social visibility in recent decades, they continue to experience significant health inequities, including adverse health outcomes and multiple barriers to accessing medical care. Transgender and gender-diverse persons are at a higher risk for pain conditions than their cisgender counterparts, but research on chronic pain management for TGD persons is lacking. Clinicians from all disciplines must be informed of best practices for managing chronic pain in the TGD population. This includes all aspects of care including history, physical examination, diagnosis, treatment, and perioperative management. Many TGD persons report delaying or avoiding care because of negative interactions with medical practitioners who do not have sufficient training in navigating the specific health care needs of TGD patients. Furthermore, TGD persons who do seek care are often forced to educate their practitioners on their specific health care needs. This paper provides an overview of existing knowledge and recommendations for physicians to provide culturally and medically appropriate care for TGD persons.

Emerging point-of-care autologous cellular therapy using adipose-derived stromal vascular fraction for neurodegenerative diseases.

Neurodegenerative disorders are characterized by the gradual decline and irreversible loss of cognitive functions and CNS structures. As therapeutic recourse stagnates, neurodegenerative diseases will cost over a trillion dollars by 2050. A dearth of preventive and regenerative measures to hinder regression and enhance recovery has forced patients to settle for traditional therapeutics designed to manage symptoms, leaving little hope for a cure. In the last decade, pre-clinical animal models and clinical investigations in humans have demonstrated the safety and promise of an emerging cellular product from subcutaneous fat. The adipose-derived stromal vascular fraction (SVF) is an early intervention and late-stage novel 'at point' of care cellular treatment, demonstrating improvements in clinical applications for Multiple Sclerosis, Alzheimer's disease, and Parkinson's disease. SVF is a heterogeneous fraction of cells forming a robust cellular ecosystem and serving as a novel and valuable source of point-of-care autologous cell therapy, providing an easy-to-access population that we hypothesize can mediate repair through 'bi-directional' communication in response to pathological cues. We provide the first comprehensive review of all pre-clinical and clinical findings available to date and highlight major challenges and future directions. There is a greater medical and economic urgency to innovate and develop novel cellular therapy solutions that enable the repair and regeneration of neuronal tissue that has undergone irreversible and permanent damage.

Melatonin Treatment Triggers Metabolic and Intracellular pH Imbalance in Glioblastoma.

Metabolic rewiring in glioblastoma (GBM) is linked to intra- and extracellular pH regulation. In this study, we sought to characterize the role of melatonin on intracellular pH modulation and metabolic consequences to identify the mechanisms of action underlying melatonin oncostatic effects on GBM tumor initiating cells. GBM tumor initiating cells were treated at different times with melatonin (1.5 and 3.0 mM). We analyzed melatonin's functional effects on GBM proliferation, cell cycle, viability, stemness, and chemo-radiosensitivity. We then assessed the effects of melatonin on GBM metabolism by analyzing the mitochondrial and glycolytic parameters. We also measured the intracellular and extracellular pH. Finally, we tested the effects of melatonin on a mouse subcutaneous xenograft model. We found that melatonin downregulated LDHA and MCT4, decreasing lactate production and inducing a decrease in intracellular pH that was associated with an increase in ROS and ATP depletion. These changes blocked cell cycle progression and induced cellular death and we observed similar results in vivo. Melatonin's cytotoxic effects on GBM were due, at least in part, to intracellular pH modulation, which has emerged as a newly identified mechanism, providing new insights into the oncostatic effect of melatonin on GBM.

Microglia senescence occurs in both substantia nigra and ventral tegmental area.

During aging humans lose midbrain dopamine neurons, but not all dopamine regions exhibit vulnerability to neurodegeneration. Microglia maintain tissue homeostasis and neuronal support, but microglia become senescent and likely lose some of their functional abilities. Since aging is the greatest risk factor for Parkinson's disease, we hypothesized that aging-related changes in microglia and neurons occur in the vulnerable substantia nigra pars compacta (SNc) but not the ventral tegmental area (VTA). We conducted stereological analyses to enumerate microglia and dopaminergic neurons in the SNc and VTA of 1-, 6-, 9-, 18-, and 24-month-old C57BL/J6 mice using sections double-stained with tyrosine hydroxylase (TH) and Iba1. Both brain regions show an increase in microglia with aging, whereas numbers of TH+ cells show no significant change after 9 months of age in SNc and 6 months in VTA. Morphometric analyses reveal reduced microglial complexity and projection area while cell body size increases with aging. Contact sites between microglia and dopaminergic neurons in both regions increase with aging, suggesting increased microglial support/surveillance of dopamine neurons. To assess neurotrophin expression in dopaminergic neurons, BDNF and TH mRNA were quantified. Results show that the ratio of BDNF to TH decreases in the SNc, but not the VTA. Gait analysis indicates subtle, aging-dependent changes in gait indices. In conclusion, increases in microglial cell number, ratio of microglia to dopamine neurons, and contact sites suggest that innate biological mechanisms compensate for the aging-dependent decline in microglia morphological complexity (senescence) to ensure continued neuronal support in the SNc and VTA.

A Novel Method to Eliminate Preservatives in Eye Drops.

PURPOSE: Multiuse eye drops must maintain sterility and typically accomplish this by added preservatives. However, preservatives often cause harmful side effects. A gauze barrier dressing ("BIOGUARD®") recently cleared by the FDA has an immobilized poly diallyldimethylammonium chloride (p-DADMAC) coating and is an effective antimicrobial with minimal compound release into solution. To implement use of this dressing as a replacement for preservatives in multidose eye drop bottles, its ability to maintain sterility without interacting with the active ingredient (AI) of the ophthalmic medication was tested. METHODS: To determine immobilized p-DADMAC's microbicidal efficacy, it was added to eye drop bottles, then contaminated with Staphylococcus aureus (SA113) bacteria. To assess interference with AI in eye drops, high performance liquid chromatography was used to determine whether the AIs timolol and dorzolamide were affected after exposure to p-DADMAC. To further investigate effects on AI, the microbicidal activity of Vigamox® (moxifoxacin) was assessed after p-DADMAC gauze exposure. RESULTS: S. aureus bacteria were eliminated by p-DADMAC-treated gauze for all samples. The concentrations of both timolol and dorzolamide increased after exposure to p-DADMAC-treated gauze, but spectrometric analysis showed that this did not occur when the p-DADMAC-coated material was presoaked in deionized water. The microbicidial activity of moxifloxacin was unaffected by exposure to p-DADMAC-treated gauze. CONCLUSIONS: Due to its lack of effect on eye drop AI and its microbicidal efficacy, p-DADMAC treatment would make an excellent candidate for replacing preservatives in eye drops.

Minimally Invasive Resection of Intra-axial Posterior Fossa Tumors Using Tubular Retractors.

OBJECTIVE: Posterior fossa tumor surgery is associated with a significant risk of complications, and the complications are typically more frequent compared with similar supratentorial surgeries. This study aimed to evaluate 1) the extent of resection and neurologic outcomes and 2) perioperative complications with use of minimally invasive approaches for intra-axial posterior fossa tumors from our case series. METHODS: All consecutive patients who underwent nonbiopsy surgery of a posterior fossa tumor using tubular retractors and exoscopic visualization from January 2016 to May 2018 were prospectively identified and included. RESULTS: During the reviewed period, 15 patients underwent resection of an intra-axial posterior fossa tumor. Eight (53%) patients were men, and the median age was 63.0 years (interquartile range: 45.0-67.5 years). The tumor was located in the cerebellar hemisphere in 11 (73%) cases, vermis in 3 (20%) cases, and middle cerebellar peduncle in 1 (7%) case. The median preoperative and postoperative lesion volumes were 21.6 cm3 (interquartile range: 10.1-33.0 cm3) and 0 cm3 (interquartile range: 0-1.2 cm3), respectively. The percent resection was 100% (92%-100%). Following surgery, 12 (80%) patients had improved and 3 (20%) patients had stable Karnofsky performance scale scores, whereas no patients had a decline in Karnofsky performance scale score postoperatively. No patients incurred other postoperative regional or medical complications. CONCLUSIONS: We demonstrated the possible efficacy of a minimally invasive approach with the use of tubular retractors and exoscopic visualization for resecting posterior fossa intra-axial tumors with relatively high efficacy and low morbidity.