ABSTRACT
Neurons are frequently classified into distinct types on the basis of structural, physiological, or genetic attributes. To better constrain the definition of neuronal cell types, we characterized the transcriptomes and intrinsic physiological properties of over 4,200 mouse visual cortical GABAergic interneurons and reconstructed the local morphologies of 517 of those neurons. We find that most transcriptomic types (t-types) occupy specific laminar positions within visual cortex, and, for most types, the cells mapping to a t-type exhibit consistent electrophysiological and morphological properties. These properties display both discrete and continuous variation among t-types. Through multimodal integrated analysis, we define 28 met-types that have congruent morphological, electrophysiological, and transcriptomic properties and robust mutual predictability. We identify layer-specific axon innervation pattern as a defining feature distinguishing different met-types. These met-types represent a unified definition of cortical GABAergic interneuron types, providing a systematic framework to capture existing knowledge and bridge future analyses across different modalities.
Subject(s)
Cerebral Cortex/cytology , Electrophysiological Phenomena , GABAergic Neurons/cytology , GABAergic Neurons/metabolism , Transcriptome/genetics , Animals , Female , Gene Expression Profiling , Hippocampus/physiology , Ion Channels/metabolism , Male , Mice, Inbred C57BL , Nerve Tissue Proteins/metabolismABSTRACT
Dendritic and axonal morphology reflects the input and output of neurons and is a defining feature of neuronal types1,2, yet our knowledge of its diversity remains limited. Here, to systematically examine complete single-neuron morphologies on a brain-wide scale, we established a pipeline encompassing sparse labelling, whole-brain imaging, reconstruction, registration and analysis. We fully reconstructed 1,741 neurons from cortex, claustrum, thalamus, striatum and other brain regions in mice. We identified 11 major projection neuron types with distinct morphological features and corresponding transcriptomic identities. Extensive projectional diversity was found within each of these major types, on the basis of which some types were clustered into more refined subtypes. This diversity follows a set of generalizable principles that govern long-range axonal projections at different levels, including molecular correspondence, divergent or convergent projection, axon termination pattern, regional specificity, topography, and individual cell variability. Although clear concordance with transcriptomic profiles is evident at the level of major projection type, fine-grained morphological diversity often does not readily correlate with transcriptomic subtypes derived from unsupervised clustering, highlighting the need for single-cell cross-modality studies. Overall, our study demonstrates the crucial need for quantitative description of complete single-cell anatomy in cell-type classification, as single-cell morphological diversity reveals a plethora of ways in which different cell types and their individual members may contribute to the configuration and function of their respective circuits.
Subject(s)
Brain/cytology , Cell Shape , Neurons/classification , Neurons/metabolism , Single-Cell Analysis , Atlases as Topic , Biomarkers/metabolism , Brain/anatomy & histology , Brain/embryology , Brain/metabolism , Gene Expression Regulation, Developmental , Humans , Neocortex/anatomy & histology , Neocortex/cytology , Neocortex/embryology , Neocortex/metabolism , Neurogenesis , Neuroglia/cytology , Neurons/cytology , RNA-Seq , Reproducibility of ResultsABSTRACT
BACKGROUND: Bleeding complications are not uncommon after breast reduction surgery, and recently, tranexamic acid (TXA) as an antifibrinolytic agent has been used in various surgical specialties as a way to minimizes such adverse outcomes. We elected to evaluate the effectiveness of intravenous (IV) intraoperative TXA in reduction mammoplasty patients. METHODS: This is a retrospective chart review of clinical charts of all patients who received reduction mammoplasty by a single surgeon at Emory University Hospital or its affiliated Aesthetic Center from January 1, 2020, to March 1, 2022. Seventy-four consecutive breast reduction patients received 1-g IV TXA intraoperatively compared with 117 consecutive controls. The outcome of interest included 30-day postoperative bleeding complications. RESULTS: There was no significant difference in age ( P = 0.92), body mass index ( P = 0.98), percentage of smokers ( P = 0.56), operating time ( P = 0.87), estimated blood loss ( P = 0.90), or weight removed ( P = 0.98) between patients in each arm. There were 19 bleeding events (16.2%) in the non-TXA arm compared with 1 bleeding event (1.4%) in the TXA arm ( P = 0.0143). Of the 19, 6 (5.1%) were major events, and 13 were minor events (11.1%); the only bleeding event in the TXA arm was minor. Number needed to treat all bleeding events with use of TXA was 7, and the number needed to treat minor hematomas was 11. There was no significant difference in the rate of seroma, wound healing complications, infection, or nipple necrosis between the 2 arms ( P > 0.05). CONCLUSIONS: The use of IV TXA is a safe and effective way to reduce hematoma rates in patients receiving reduction mammoplasty.
Subject(s)
Antifibrinolytic Agents , Mammaplasty , Tranexamic Acid , Female , Humans , Tranexamic Acid/therapeutic use , Retrospective Studies , Blood Loss, Surgical/prevention & control , Antifibrinolytic Agents/therapeutic use , Hematoma/prevention & control , Hematoma/chemically inducedABSTRACT
BACKGROUND: Minority patients and those from low socioeconomic backgrounds are faced with barriers to care regarding breast reconstruction. With this study, we seek to elucidate variances in demographics to determine predictors of complications in implant-based breast reconstruction. METHODS: Patients who underwent breast reconstruction with either direct to implant or immediate expander reconstruction by 1 surgeon were identified using the preoperative Breast-Q.Current income statistics available from the US Census Bureau by self-reported zip code were used to determine the median household income (MHI) to stratify differing socioeconomic backgrounds. Demographics were compared with body mass index, comorbidities, overall rate of postoperative complications, rate of implant infection, and type of reconstruction. RESULTS: Two hundred ninety-five patients met inclusion criteria. Overall rate of complications and rate of breast implant infection was higher for MHI of less than $50,000 compared with greater than $50,000 (P = 0.043 overall complications 40.20% vs 28.8%) (P = 0.04 implant infection 14.4% vs 7.1%). African American patients had higher body mass index (P = <0.001), rates of HTN (P = <0.001), and diabetes (P = 0.001), and were more likely to have a lower income (P = <0.001). There was, however, no difference in overall complications (P = 0.26), implant infection rate (P = 0.994), or capsular contracture (0.367) based on race. There was no difference in rate of comorbidities between low and high socioeconomic areas. CONCLUSION: This cohort demonstrates a higher rate of overall complications and infection in patients with a lower MHI and no difference based on race despite having higher risk factors for complications.Socioeconomic status is a multifaceted barrier to care that must be addressed in the perioperative period to decrease breast implant associated complications.
Subject(s)
Breast Implantation , Breast Implants , Breast Neoplasms , Mammaplasty , Breast Implantation/adverse effects , Breast Implants/adverse effects , Breast Neoplasms/complications , Female , Humans , Mammaplasty/adverse effects , Mastectomy/adverse effects , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retrospective Studies , Social Class , Tissue Expansion Devices/adverse effects , Treatment OutcomeABSTRACT
BACKGROUND: TikTok is one of the most popular and fastest-growing social media apps in the world. Previous studies have analyzed the quality of patient education information on older video platforms, but the quality of plastic and cosmetic surgery videos on TikTok has not yet been determined. OBJECTIVES: The aim of this study was to analyze the source and quality of certain cosmetic procedure videos on TikTok. METHODS: The TikTok mobile application was queried for content related to 2 popular face procedures (rhinoplasty and blepharoplasty) and 2 body procedures (breast augmentation and abdominoplasty). Two independent reviewers analyzed video content according to the DISCERN scale, a validated, objective instrument that assesses the quality of information on a scale of 1 to 5. Quality scores were compared between videos produced by medical and nonmedical creators and between different content categories. RESULTS: The included videos attracted 4.8 billion views and 76.2 million likes. Videos were created by medical doctors (56%) and laypersons (44%). The overall average DISCERN score out of 5 corresponded to very poor video quality for rhinoplasty (1.55), blepharoplasty (1.44), breast augmentation (1.25), and abdominoplasty (1.29). DISCERN scores were significantly higher among videos produced by doctors than by laypersons for all surgeries. Comedy videos consistently had the lowest average DISCERN scores, whereas educational videos had the highest. CONCLUSIONS: It is increasingly important that medical professionals understand the possibility of patient misinformation in the age of social media. We encourage medical providers to be involved in creating quality information on TikTok and educate patients about misinformation to best support health literacy.
Subject(s)
COVID-19 , Social Media , Surgery, Plastic , Communication , Humans , Information Dissemination , Video RecordingABSTRACT
A patient's preoperative satisfaction with their breasts and baseline psychosocial, sexual, and physical well-being are important considerations when planning breast reconstruction. We sought to elucidate variances in preoperative responses among patients undergoing postmastectomy breast reconstruction. Methods: Preoperative BREAST-Q responses and demographic data, including race, generation, median household incomeinstitutional review board and body mass index (BMI) were collected from breast cancer patients scheduled for mastectomy. Associations between demographic group and survey response were analyzed by chi-square or independent t-tests. Results: In total, 646 of 826 patients identified had complete data and were included in the final analysis. Patients in BMI group 1 (16-24.9) were more likely to report feeling "very satisfied" with how they looked unclothed compared with patients in other BMI groups (P = 0.031). Conversely, patients in groups 3 and 4 (35+), reported lower satisfaction (P = 0.037) and felt less attractive without clothes (P = 0.034). Asian women were less likely to feel attractive (P = 0.007), and Black patients were less likely to feel of equal worth to other women (P < 0.001). Finally, patients were less likely to report confidence in social settings if they were Black (P < 0.001), Asian (P < 0.001), from the millennial generation (P = 0.017), or living in zip codes with median household income less than $55,000 (P = 0.042). Conclusions: Breast cancer patients' feelings toward their natural breasts vary widely between demographic groups. Understanding baseline psychosocial factors in this population is key to informing preoperative discussions and interpreting postoperative satisfaction.
ABSTRACT
Rodent studies have demonstrated that synaptic dynamics from excitatory to inhibitory neuron types are often dependent on the target cell type. However, these target cell-specific properties have not been well investigated in human cortex, where there are major technical challenges in reliably obtaining healthy tissue, conducting multiple patch-clamp recordings on inhibitory cell types, and identifying those cell types. Here, we take advantage of newly developed methods for human neurosurgical tissue analysis with multiple patch-clamp recordings, post-hoc fluorescent in situ hybridization (FISH), machine learning-based cell type classification and prospective GABAergic AAV-based labeling to investigate synaptic properties between pyramidal neurons and PVALB- vs. SST-positive interneurons. We find that there are robust molecular differences in synapse-associated genes between these neuron types, and that individual presynaptic pyramidal neurons evoke postsynaptic responses with heterogeneous synaptic dynamics in different postsynaptic cell types. Using molecular identification with FISH and classifiers based on transcriptomically identified PVALB neurons analyzed by Patch-seq, we find that PVALB neurons typically show depressing synaptic characteristics, whereas other interneuron types including SST-positive neurons show facilitating characteristics. Together, these data support the existence of target cell-specific synaptic properties in human cortex that are similar to rodent, thereby indicating evolutionary conservation of local circuit connectivity motifs from excitatory to inhibitory neurons and their synaptic dynamics.
Subject(s)
Neocortex , Humans , Neocortex/physiology , Synaptic Transmission/physiology , In Situ Hybridization, Fluorescence , Prospective Studies , Neurons/physiology , Pyramidal Cells/physiology , Synapses/physiology , Interneurons/physiologyABSTRACT
COVID-19 significantly impacted the residency match process. Away rotations and in-person interviews were canceled in 2021, resulting in a geographic shift in integrated plastic surgery match results. Although several of these limitations were lifted during the 2022 cycle, the resulting geographic outcomes have yet to be described. This study aims to determine whether the changes seen during the previous cycle persisted despite loosened restrictions. Methods: Integrated plastic surgery match results and applicants' home institutions from the 2022 match cycle were determined using publicly available data. Geographic data from this cycle were then compared with pre-COVID-19 match cycles (2016-2020) and the COVID-19-affected 2021 match cycle. Results: Eighty percent (n = 68) of US integrated plastic surgery programs were included in this study. In 2022, 18.42% of applicants matched at their home institution compared with 25.12% in 2021. There was no significant difference in home, state, or regional match rates between 2022 and the five cycles preceding the pandemic (2016-2020). Combining these data to reflect the non-COVID-19-affected cycles (2016-2020 and 2022) and comparing to the COVID-19-affected cycle (2021), a significant difference in rates of home matches (P = 0.0395) was identified. Conclusions: A significant increase in home institution match rates was not noted during the 2022 cycle. This return to pre-COVID-19 rates is likely attributed to the loosening of restrictions and more opportunities for interaction between applicants and programs outside of their home institution.
ABSTRACT
We present a unique, extensive, and open synaptic physiology analysis platform and dataset. Through its application, we reveal principles that relate cell type to synaptic properties and intralaminar circuit organization in the mouse and human cortex. The dynamics of excitatory synapses align with the postsynaptic cell subclass, whereas inhibitory synapse dynamics partly align with presynaptic cell subclass but with considerable overlap. Synaptic properties are heterogeneous in most subclass-to-subclass connections. The two main axes of heterogeneity are strength and variability. Cell subclasses divide along the variability axis, whereas the strength axis accounts for substantial heterogeneity within the subclass. In the human cortex, excitatory-to-excitatory synaptic dynamics are distinct from those in the mouse cortex and vary with depth across layers 2 and 3.
Subject(s)
Neocortex/physiology , Neural Pathways , Neurons/physiology , Synapses/physiology , Synaptic Transmission , Adult , Animals , Datasets as Topic , Excitatory Postsynaptic Potentials , Female , Humans , Inhibitory Postsynaptic Potentials , Male , Mice , Mice, Transgenic , Models, Neurological , Neocortex/cytology , Temporal Lobe/cytology , Temporal Lobe/physiology , Visual Cortex/cytology , Visual Cortex/physiologyABSTRACT
Understanding the diversity of cell types in the brain has been an enduring challenge and requires detailed characterization of individual neurons in multiple dimensions. To systematically profile morpho-electric properties of mammalian neurons, we established a single-cell characterization pipeline using standardized patch-clamp recordings in brain slices and biocytin-based neuronal reconstructions. We built a publicly accessible online database, the Allen Cell Types Database, to display these datasets. Intrinsic physiological properties were measured from 1,938 neurons from the adult laboratory mouse visual cortex, morphological properties were measured from 461 reconstructed neurons, and 452 neurons had both measurements available. Quantitative features were used to classify neurons into distinct types using unsupervised methods. We established a taxonomy of morphologically and electrophysiologically defined cell types for this region of the cortex, with 17 electrophysiological types, 38 morphological types and 46 morpho-electric types. There was good correspondence with previously defined transcriptomic cell types and subclasses using the same transgenic mouse lines.