The generation of human induced pluripotent stem cells (hiPSC) from somatic cells has enabled the possibility to provide patient-specific hiPSC for cell-based therapy, drug discovery, and other translational applications. Two major obstacles in using hiPSC for clinical application reside in the risk of genomic modification when they are derived with viral transgenes and risk of teratoma formation if undifferentiated cells are engrafted. In this study, we report the generation of ''footprint-free'' hiPSC-derived astrocytes. These are efficiently generated, have anatomical and physiological characteristics of fully differentiated astrocytes, maintain homing characteristics typical of stem cells, and do not give rise to teratomas when engrafted in the brain. Astrocytes can be obtained in sufficient numbers, aliquoted, frozen, thawed, and used when needed. Our results show the feasibility of differentiating astrocytes from ''footprint-free'' iPSC. These are suitable for clinical cell-based therapies as they can be induced from patients' specific cells, do not require viral vectors, and are fully differentiated. ''Footprint-free'' hiPSC-derived astrocytes represent a new potential source for therapeutic use for cell-based therapy, including treatment of high-grade human gliomas, and drug discovery.
OBJECTIVE Women neurosurgeons (WNs) continue to remain a minority in the specialty despite significant initiatives to increase their representation. One domain less explored is the regional distribution of WNs, facilitated by the hiring practices of neurosurgical departments across the US. In this analysis, the authors coupled the stated practice location of WNs with regional geospatial data to identify hot spots and cold spots of prevalence and examined regional predictors of increases and decreases in WNs over time. METHODS The authors examined the National Provider Identifier (NPI) numbers of all neurosurgeons obtained via the National Plan and Provider Enumeration System (NPPES), identifying the percentage of WNs in each county for which data were appended with data from the US Census Bureau. Change in WN rates was identified by calculating a regression slope for all years included (2015–2022). Hot spots and cold spots of WNs were identified through Moran’s clustering analysis. Population and surgeon features were compared for hot spots and cold spots. RESULTS WNs constituted 10.73% of all currently active neurosurgical NPIs, which has increased from 2015 (8.81%). Three hot spots were found—including the Middle Atlantic and Pacific divisions—that contrasted with scattered cold spots throughout the East Central regions that included Memphis as a major city. Although relatively rapidly growing, hot spots had significant gender inequality, with a median WN percentage of 11.38% and a median of 0.61 WNs added to each respective county per year. CONCLUSIONS The authors analyzed the prevalence of WNs by using aggregated data from the NPPES and US Census Bureau. The authors also show regional hot spots of WNs and that the establishment of WNs in a region is a predictor of additional WNs entering the region. These data suggest that female neurosurgical mentorship and representation may be a major driver of acceptance and further gender diversity in a given region.
OBJECTIVE Deep brain stimulation (DBS) has been approved as a therapy for movement disorders and obsessive-compulsive disorder. Recently, DBS has been studied in patients with anorexia nervosa (AN), which is a debilitating and life-threatening psychiatric disorder. Several stimulation locations have been tested without a clear indication of the best region. In this systematic review and network meta-analysis, the authors used patient-level data to identify stimulation targets with the greatest evidence for efficacy in increasing body mass index (BMI). METHODS A systematic search was performed on or before August 4, 2022, using PubMed/MEDLINE, Ovid, and Scopus. Articles were included if patient-level data were presented, patients were diagnosed with AN and treated with DBS, and 6 months or more of postoperative follow-up data were reported. Quality and risk of bias were assessed with the NIH assessment tools. Patient data were collected and stratified by stimulation location. A network meta-analysis was performed. This review was written in accordance with PRISMA guidelines for systematic reviews. RESULTS Eleven studies consisting of 36 patients were included. The mean age and BMI at the time of surgery were 38.07 (SD 11.64) years and 12.58 (SD 1.4) kg/m2, respectively. After 6 months of DBS, a significant difference in percentage change in BMI was found between the nucleus accumbens and subcallosal cingulate cortex (SCC) (SMD 0.78; 95% CI 0.10, 1.45) and between the SCC and ventral anterior limb of the internal capsule (SMD −1.51; 95% CI −2.39, −0.62). Similarly, at 9–12 months, a significant difference in percentage change in BMI was found between the SCC and ventral anterior limb of the internal capsule (SMD −1.18; 95% CI −2.21, −0.15). With hierarchical ranking, this study identified SCC as the most supported stimulation location for BMI change at 6 and 9–12 months (P-scores 0.9449 and 0.9771, respectively). CONCLUSIONS Several DBS targets have been tested for AN, and this study identified the SCC as the most supported region for BMI change. However, further studies with blinded on/off periods are necessary to confirm this finding.
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