Microglia mediate chronic neuroinflammation following central nervous system (CNS) disease or injury, and in doing so, damage the local brain environment by impairing recovery and contributing to disease processes. Microglia are critically dependent on signaling through the colony-stimulating factor 1 receptor (CSF1R) and can be eliminated via administration of CSF1R inhibitors. Resolving chronic neuroinflammation represents a universal goal for CNS disorders, but long-term microglial elimination may not be amenable to clinical use. Notably, withdrawal of CSF1R inhibitors stimulates new microglia to fully repopulate the CNS, affording an opportunity to renew this cellular compartment. To that end, we have explored the effects of acute microglial elimination, followed by microglial repopulation, in a mouse model of extensive neuronal loss. Neuronal loss leads to a prolonged neuroinflammatory response, characterized by the presence of swollen microglia expressing CD68 and CD45, as well as elevated levels of cytokines, chemokines, complement, and other inflammatory signals. These collective responses are largely resolved by microglial repopulation. Furthermore, microglial repopulation promotes functional recovery in mice, with elevated plus maze performance matching that of uninjured mice, despite the loss of 80% of hippocampal neurons. Analyses of synaptic surrogates revealed increases in PSD95 and synaptophysin puncta with microglial repopulation, suggesting that these cells sculpt and regulate the synaptic landscape. Thus, our results show that short-term microglial elimination followed by repopulation may represent a clinically feasible and novel approach to resolve neuroinflammatory events and promote brain recovery.
IntroductionOnabotulinumtoxinA (OBTA) is approved for treating chronic headaches and migraines in adults, but there is limited scientific literature on the outcomes in pediatric patients. The aim of this study was to determine if subjects treated with OBTA reported a statistically significant improvement in the primary features (frequency, intensity, duration and disability scoring) associated with migraines compared with placebo at follow-up visits.MethodsAfter obtaining approval by the appropriate local (HS# 2016–3108) and federal institutions, the principal investigator enrolled candidates aged 8 to 17 years old diagnosed with chronic migraines (at least 6 months), and 15 or more headache days in a 4-week baseline period. This randomized control trial consisted of two phases: double-blind and open-label for the first two and last two sets of treatments, respectively. Subjects were randomly assigned to receive a treatment protocol—155 units at 31 injection sites—in 3-month intervals and follow-up visits every 6 weeks. Non-parametric testing (Wilcoxon signed-rank test) was performed using widely available open-source statistical software (‘R’).ResultsFrom February 2017 to November 2018, 17 subjects presented for a screening visit; 15 met eligibility criteria. Subjects that received OBTA reported a statistically significant decrease from the following baseline values compared with placebo 6-week post-treatment compared with placebo: frequency (20 (7 to 17) vs 28 (23 to 28); p=0.038), intensity (5 (3 to 7) vs 7 (5 to 9); p=0.047), and PedMIDAS (Pediatric Migraine Disability Score) (3 (2 to 4) vs 4 (4 to 4); p=0.047). There was no statistically significant difference in the duration (10 (2 to 24) vs 24 (4 to 24); p=0.148) of migraines between the two groups.DiscussionOnabotulinumtoxinA showed a statistically significant decrease in frequency and intensity of migraines compared with placebo. No adverse effects or serious adverse events related to the use of OBTA were reported. In the future, we aim to evaluate the specific nature of migraines, for example, quality/location of pain presented during an initial consult to predict the likelihood of OBTA being a truly effective modality of pain management for pediatric migraineurs.Trial registration numberNCT03055767.
The COVID-19 pandemic caused many shifts in the national economy, job market, and healthcare sector, especially elective procedures such as in cosmetic plastic surgery. While there has been research in the changes in cosmetic plastic surgery since the start of the COVID-19 pandemic, there have been no study to date determining the changes in distinct sectors, such as nonsurgical plastic surgery procedures and the popular trends that may be more sensitive to changes to general public interest. The Google Trends tool was used to determine these changes in interest. Nonsurgical procedures were retrieved from the American Society of Plastic Surgery (ASPS) website, grouped into categories, such as neurotoxin, chemical peel, filler, hair removal, dermaplaning, skin laser treatment, skin tightening, and thread lift, and used as Google Trends search terms. Search term weekly data were collected from March 2018 to March 2020 and March 2020 to March 2022, divided by the start of the COVID-19 lockdown, and compared. After the start of the COVID-19 pandemic, the majority of nonsurgical procedures showed an increase in interest, with the most significant changes including neurotoxin procedures especially lip Botox, filler in the chin, cheek, jawline, tear trough, lip, and nose, skin-improving treatments, non-invasive forms of body contouring, and thread lift. Brands like Dysport, Radiesse, Restylane, Sculptra, Versa, Emsculpt, and Morpheus8 showed increased interest. Most nonsurgical procedures increased in interest after the COVID-19 lockdown, with facial and skin-improving procedures showing the most increase in interest.
Background Historically, men have been shamed if they cared seemingly too much about their appearance and especially, if they pursued aesthetic surgery. However, due to the changing landscape of the culture, this stigma has seemed to decrease. Men have diverse and quickly changing interests in particular procedures that have not been readily explored in the currently available reports. To examine this, we analyzed interest in specific plastic surgery procedures in men over the last two decades using the Google Trends tool. Methods The most common cosmetic procedures were chosen from the American Society of Plastic Surgeons website and served as the search terms for the Google Trends tool from 2004 to 2021. All 19 procedures were examined for overall trends and for changes in the last decade through comparing the data in bisected time periods. Results Interest in all plastic surgery procedures in men increased since 2004 except for breast reduction. Most notably, jawline filler, Botox, microneedling, lip filler, chemical peel, CoolSculpting, and butt lift had the largest trend increases. In the last decade, all procedures showed a significant increase in interest. Conclusions While surgical volume data are valuable, our study shows that Google Trends is a beneficial tool to predict quickly changing and specific trends, especially as the patient population of plastic surgery grows with increased diversity and generational changes. Our study shows that there is an increase in male-centered plastic surgery procedures, especially nonsurgical facial procedures. Male interest in plastic surgery will continue to increase with time. Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
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