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BACKGROUND AND OBJECTIVES: In Japan, apheresis donation of plasma is allowed to a maximum of 24 times a year, and plateletpheresis are counted as two plasmapheresis donations. Diversion of the initial blood flow is conducted for all donations, and additionally, blood remaining in apheresis machine circuit is lost. Here, we aimed to investigate on the health impact of frequent apheresis donations, as measured by the serum ferritin (sFer). MATERIALS AND METHODS: A total of 538 male apheresis donors and 538 age-matched whole blood (WB) donors, who gave informed consent to join the study, were enrolled. sFer were compared, according to age. Another group of 19 apheresis donors were followed during four consecutive donations. RESULTS: About half (48%) of repeat male apheresis donors had iron deficiency (sFer < 26 ng/mL), compared with lower rates (13.9%) among male WB donors. It was evident in all age groups, except for teenagers, possibly because of the lower number of donations. Follow-up of the 19 donors for 4 months revealed a progressive decrease in sFer. CONCLUSION: Blood remaining in the apheresis machine circuit and diversion of the initial blood flow have been implicated in iron deficiency for many years. Taking the present results, the manufacturer of apheresis equipment was requested to improve it to allow rinseback of the remaining blood, which was achieved only for plateletpheresis. Until further improvement, plasmapheresis frequency was reduced to 12 times a year. Additional measures, such as oral supplementation of iron, need to be considered.
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CONTEXT: Quantum computing is an exciting area, which has grown at an astonishing rate in the last decade. It is especially promising for the computational and theoretical chemistry area. One algorithm has received a lot of attention lately, the variational quantum eigensolver (VQE). It is used to solve electronic structure problems and it is suitable to the noisy intermediate-scale quantum (NISQ) hardware. VQE calculations require ansatze and one of the most known is the unitary coupled cluster (UCC). It uses the chosen basis set to generate a quantum computing circuit which will be iteratively minimized. The present work investigates the circuit depth and the number of gates as a function of basis sets and molecular size. It has been shown that for the current quantum devices, only the smallest molecules and basis sets are tractable. The H 2 molecule with the cc-pVTZ and aug-cc-pVTZ basis sets have circuit depths in the order of 10 6 to 10 7 gates and the C 2 H 6 molecule with 3-21G basis set has a circuit depth of 2.2 × 10 8 gates. At the same time the analysis demonstrates that the H 2 molecule with STO-3G basis set, requires at least 500 shots to reduce the error and that, although error mitigation schemes can diminish the error, they were not able to completely negate it. METHODS: The quantum computing and electronic structure calculations were performed using the Qiskit package from IBM and the PySCF package, respectively. The ansatze were generated using the UCCSD method as implemented in Qiskit, using the basis sets STO-3G, 3-21G, 6-311G(d,p), def2-TZVP, cc-pVDZ, aug-cc-pVDZ, cc-pVTZ, and aug-cc-pVTZ. The operators and the Hamiltonian were mapped using the Jordan-Wigner scheme. The classical optimizer chosen was the simultaneous perturbation stochastic approximation (SPSA). The quantum computers used were the Nairobi and Osaka, with 7 and 127 qubits respectively.
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Parkinson's disease (PD) is characterized by the degeneration of dopaminergic neurons in the striatum, predominantly associated with motor symptoms. However, non-motor deficits, particularly sensory symptoms, often precede motor manifestations, offering a potential early diagnostic window. The impact of non-motor deficits on sensation behavior and the underlying mechanisms remains poorly understood. In this study, we examined changes in tactile sensation within a Parkinsonian state by employing a mouse model of PD induced by 6-hydroxydopamine (6-OHDA) to deplete striatal dopamine (DA). Leveraging the conserved mouse whisker system as a model for tactile-sensory stimulation, we conducted psychophysical experiments to assess sensory-driven behavioral performance during a tactile detection task in both the healthy and Parkinson-like states. Our findings reveal that DA depletion induces pronounced alterations in tactile sensation behavior, extending beyond expected motor impairments. We observed diverse behavioral deficits, spanning detection performance, task engagement, and reward accumulation, among lesioned individuals. While subjects with extreme DA depletion consistently showed severe sensory behavioral deficits, others with substantial DA depletion displayed minimal changes in sensory behavior performance. Moreover, some exhibited moderate degradation of behavioral performance, likely stemming from sensory signaling loss rather than motor impairment. The implementation of a sensory detection task is a promising approach to quantify the extent of impairments associated with DA depletion in the animal model. This facilitates the exploration of early non-motor deficits in PD, emphasizing the importance of incorporating sensory assessments in understanding the diverse spectrum of PD symptoms.
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BACKGROUND AND OBJECTIVES: A more restrictive blood donation criterion has been applied in Japan, with a maximum volume of whole blood (WB) donation of 400 mL, allowing twice a year for female donors and thrice a year for male donors. However, iron deficiency was as high as 20.5% among female donors prior to donation, increasing to 37.7% after blood donation. More than 20 years have passed since then, so we set out to investigate the present situation. MATERIALS AND METHODS: A total of 2659 (male/female: 1496/1163) donors of 400 mL WB who gave informed consent to join the study were enrolled. Serum ferritin (sFer) of first-time/reactivated (FT/RA) donors were compared with those of repeat donors, according to gender and age; those who returned for subsequent donations during the study period were also followed up. RESULTS: About one-third of FT/RA female donors had iron deficiency, possibly reflecting its high incidence among the general population. Interestingly, although sFer levels were low among pre-menopausal FT/RA female donors, these values were not much different in repeat donors, whereas significant differences were observed between FT/RA and repeat donors among post-menopausal females and in most age groups among males. As expected, donors with a normal initial sFer (≥26 ng/mL) recovered faster than those with a low initial sFer. CONCLUSION: Female donors, especially, have iron deficiency even before donation, and the rate increased compared to what was found previously. Measures to prevent iron deficiency of blood donors is required, and studies are going on in Japan.
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While the response of Arabidopsis thaliana to drought, herbivory or fungal infection has been well-examined, the consequences of exposure to a series of such (a)biotic stresses are not well studied. This work reports on the genetic mechanisms underlying the Arabidopsis response to single osmotic stress, and to combinatorial stress, either fungal infection using Botrytis cinerea or herbivory using Pieris rapae caterpillars followed by an osmotic stress treatment. Several small-effect genetic loci associated with rosette dry weight (DW), rosette water content (WC), and the projected rosette leaf area in response to combinatorial stress were mapped using univariate and multi-environment genome-wide association approaches. A single-nucleotide polymorphism (SNP) associated with DROUGHT-INDUCED 19 (DI19) was identified by both approaches, supporting its potential involvement in the response to combinatorial stress. Several SNPs were found to be in linkage disequilibrium with known stress-responsive genes such as PEROXIDASE 34 (PRX34), BASIC LEUCINE ZIPPER 25 (bZIP25), RESISTANCE METHYLATED GENE 1 (RMG1) and WHITE RUST RESISTANCE 4 (WRR4). An antagonistic effect between biotic and osmotic stress was found for prx34 and arf4 mutants, which suggests PRX34 and ARF4 play an important role in the response to the combinatorial stress.
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Proteínas de Arabidopsis , Arabidopsis , Micoses , Estudo de Associação Genômica Ampla , Arabidopsis/microbiologia , Pressão Osmótica , Estresse Fisiológico/genética , Fatores de Transcrição/genética , Proteínas de Arabidopsis/genéticaRESUMO
Improved strategies in aortic valve-preserving operations appreciate the dynamic, three-dimensional complexity of the aortic root and its valve. This depends not only on detailed four-dimensional imaging of the planar dimensions of the aortic root but also on quantitative assessment of the valvar leaflets and their competency. The zones of apposition and resulting hemodynamic ventriculoarterial junction formed in diastole determine valvar competency. Current understanding and assessment of this junction is limited, often relying on intraoperative direct surgical inspection. However, this direct inspection itself is limited by evaluation in a nonhemodynamic state with limited field of view. In this review, we discuss the anatomy of the aortic root, including its hemodynamic junction. We review current echocardiographic approaches toward interrogating the incompetent aortic valve for presurgical planning. Furthermore, we introduce and standardize a complementary approach to assessing this hemodynamic ventriculoarterial junction by three-dimensional echocardiography to further personalize presurgical planning for aortic valve surgery.
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Valva Aórtica , Ecocardiografia Tridimensional , Humanos , Ecocardiografia Tridimensional/métodos , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Hemodinâmica/fisiologia , Assistência Perioperatória/métodos , Aorta/diagnóstico por imagem , Aorta/cirurgiaRESUMO
The COVID-19 pandemic created challenges for U. S. nursing home administrators (NHA) and staff. This study explored organizational and psychological factors associated with NHA stress, dissatisfaction, and turnover intent (TI) during the third year of the pandemic. Results from a nationwide, cross-sectional survey of 1139 NHAs were merged with Centers for Medicare and Medicaid Services nursing home survey deficiency, staffing, complaint, and other operations data. A hierarchical, generalized estimating equations model with ordered logit link found that NHAs with higher COVID stress (AOR = 1.65, 95% CI = 1.22, 2.23), higher use of agency/contract staff (AOR = 1.50, 95% CI = 1.08.2.09) and higher role conflict were more likely to indicate TI. NHAs with higher job satisfaction in workload, work content, and rewards were less likely to hold TI. Industry leaders should create strategies to reduce NHA's job stress and role conflicts and provide opportunities for improving staff recruitment and retention, reducing reliance on agency staffing.
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COVID-19 , Satisfação no Emprego , Casas de Saúde , Reorganização de Recursos Humanos , Humanos , COVID-19/epidemiologia , COVID-19/psicologia , Casas de Saúde/organização & administração , Estudos Transversais , Estados Unidos , Masculino , Feminino , SARS-CoV-2 , Estresse Ocupacional/epidemiologia , Adulto , Pessoa de Meia-Idade , Pandemias , Carga de Trabalho/psicologia , Intenção , Inquéritos e QuestionáriosRESUMO
IMPORTANCE: The integration of metabolomics-based approaches into the discovery pipeline has enabled improved mining and prioritization of prolific secondary metabolite producers such as endophytic fungi. However, relying on automated untargeted analysis tools might lead to misestimation of the chemical complexity harbored in these organisms. Our study emphasizes the importance of isolation and structure elucidation of the respective metabolites in addition to deep metabolome analysis for the correct interpretation of untargeted metabolomics approaches such as molecular networking. Additionally, it encourages the further exploration of endophytic fungi from traditional medicinal plants for the discovery of natural products.
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Plantas Medicinais , Policetídeos , Endófitos , Lactonas/metabolismo , Policetídeos/metabolismo , Metabolômica , Fungos/metabolismoRESUMO
Benzofuran and naphthofuran derivatives are synthesized from readily available phenols and naphthols. Regioselective ring openings of 2H-azirine followed by in situ aromatization using a catalytic amount of Brønsted acid have established the novelty of the methodology. The involvement of a series of 2H-azirines with a variety of phenols, 1-naphthols, and 2-naphthols showed the generality of the protocol. In-depth density functional theory calculations revealed the reaction mechanism with the energies of the intermediates and transition states of a model reaction. An alternate pathway of the mechanism has also been proposed with computer modeling.
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Copper(II) complexes have become a potential alternative to the use of platinum drugs in cancer therapy due to their multi-target mode of action. In this context, we report the syntheses of new mononuclear and dinuclear coordination compounds of this element, 1 and 2, derived from the ligand 5-methylsalicylaldehyde 2-furoyl hydrazone (H2L). All three compounds were structurally and spectroscopically characterized, both in the solid state and in solution. In 1, Cu is coordinated by three donor-atoms from the hydrazonic ligand and one chloride ion. H2L is deprotonated at the phenol oxygen. The dinuclear complex 2 is, on the other hand, a dimeric form of 1 in which the chloride ions of a pair of mononuclear units are lost and phenoxo bridges take their places, double-connecting the metal centres and resulting in a single species with the ligand fully deprotonated. The compounds were fairly stable in aqueous medium at room temperature. An experimental-theoretical combined approach demonstrated that all of them are able to bind human serum albumin (HSA), although at different sites and with diverse stoichiometries and affinities (as concluded by the calculated binding energies). In view of this, and due to the well-known antiproliferative activity of hydrazone-containing copper complexes, we consider the compounds presented in here promising, and believe that they deserve more profound studies regarding the assessment of their potential against tumour cell lines.
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Complexos de Coordenação , Albumina Sérica Humana , Humanos , Modelos Moleculares , Cobre/química , Ligantes , Cloretos , Furanos , Hidrazonas/farmacologia , Complexos de Coordenação/farmacologia , Complexos de Coordenação/químicaRESUMO
Immune checkpoint blockade is effective for some patients with cancer, but most are refractory to current immunotherapies and new approaches are needed to overcome resistance1,2. The protein tyrosine phosphatases PTPN2 and PTPN1 are central regulators of inflammation, and their genetic deletion in either tumour cells or immune cells promotes anti-tumour immunity3-6. However, phosphatases are challenging drug targets; in particular, the active site has been considered undruggable. Here we present the discovery and characterization of ABBV-CLS-484 (AC484), a first-in-class, orally bioavailable, potent PTPN2 and PTPN1 active-site inhibitor. AC484 treatment in vitro amplifies the response to interferon and promotes the activation and function of several immune cell subsets. In mouse models of cancer resistant to PD-1 blockade, AC484 monotherapy generates potent anti-tumour immunity. We show that AC484 inflames the tumour microenvironment and promotes natural killer cell and CD8+ T cell function by enhancing JAK-STAT signalling and reducing T cell dysfunction. Inhibitors of PTPN2 and PTPN1 offer a promising new strategy for cancer immunotherapy and are currently being evaluated in patients with advanced solid tumours (ClinicalTrials.gov identifier NCT04777994 ). More broadly, our study shows that small-molecule inhibitors of key intracellular immune regulators can achieve efficacy comparable to or exceeding that of antibody-based immune checkpoint blockade in preclinical models. Finally, to our knowledge, AC484 represents the first active-site phosphatase inhibitor to enter clinical evaluation for cancer immunotherapy and may pave the way for additional therapeutics that target this important class of enzymes.
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Imunoterapia , Neoplasias , Proteína Tirosina Fosfatase não Receptora Tipo 1 , Proteína Tirosina Fosfatase não Receptora Tipo 2 , Animais , Humanos , Camundongos , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos , Inibidores de Checkpoint Imunológico , Imunoterapia/métodos , Interferons/imunologia , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Neoplasias/tratamento farmacológico , Neoplasias/enzimologia , Neoplasias/imunologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Proteína Tirosina Fosfatase não Receptora Tipo 2/antagonistas & inibidores , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologiaRESUMO
Fungal laccases are promising for biotechnological applications, including bioremediation and dye biotransformation, due to their high redox potential and broad substrate specificity. However, current bioprospecting methods for identifying laccase-producing fungi can be challenging and time-consuming. For early detection, it was developed a three-step, multi-criteria weighting system that evaluates fungal strains based on: First, the biotransformation capacity of three dyes (i.e., Congo red, brilliant blue G-250, and malachite green), at three different pH values, and with a relative weighting supported for the redox potential of each colorant. The relative decolorization coefficient (RDC), used as th2e first classification criterion, expressed their potential performance. Second, under the same conditions, laccase activity was estimated by observing the different degrees of oxidation of a given substrate. The selection criterion was the relative oxidation coefficient (ROC). Finally, laccase activity was quantified in submerged fermentations using three inducers (i.e., loofah sponge, Tween 80, and veratyl alcohol). This multicriteria screening strategy evaluated sixteen isolated endophytic fungal strains from Otoba gracilipes. The system identified Beltraniopsis sp. ET-17 (at pH values of 5.00 and 5.50) as a promising strain for dye biotransformation, and Phlebia floridensis as the best laccase producer, achieving a high activity of 116 µmol min-1 L-1 with loofah sponge as an inducer. In-vitro testing confirmed the efficacy of P. floridensis, with 53.61 % decolorization of a dye mixture (brilliant blue-Congo red. ratio 1:1) after 15 days of incubation. Thus, with the proposed screening strategy it was possible to highlight two species of interest at an early bioprospecting stage on a Colombian native tree poorly explored.
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Vermelho Congo , Lacase , Lacase/metabolismo , Biodegradação Ambiental , Endófitos/metabolismo , Corantes/metabolismo , Concentração de Íons de HidrogênioRESUMO
Cardiac computed tomography (CT) and magnetic resonance (CMR) supplement echocardiography in the evaluation of those with aortic root and ascending aortic dilation, determining timing for intervention, guiding pre-surgical planning and post-operative surveillance. The dynamic, three-dimensional complexity of the aortic root and how it relates to the base of the left ventricle must be understood in any surgical approach addressing the aneurysmal aortic root. With improved imaging technology and the importance for proper patient counseling, it is no longer acceptable to enter the operating theater without a detailed blue print of what the problem is, and how best to address it. In addition, reliance on surgical expertise alone for intraoperative evaluation and decision making could be suboptimal due to the unloaded condition of the aortic root and the variance of experience of the surgeons to successfully repair the aortic valve. This is exemplified by the selective surgeons and centers who have the ability to tackle these aortic valve and root pathologies, compared to mitral valve repair techniques that have been codified and are generalizable. This review discusses a multimodality imaging approach in the patient with aortic root aneurysm, focusing on the precision added with pre-surgical CT assessment to guide aortic-valve sparing operations. This precision is afforded with a detailed understanding of the anatomy of the aortic root and underlying support, and its accurate evaluation by standard two- and three-dimensional imaging. Furthermore, we describe the evolving ability to predict the location of ventricular components of the atrioventricular conduction axis with further clinical imaging to personalize surgical strategies.
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OBJECTIVES: A growing number of nurse practitioners (NPs) are employed in nursing homes (NHs) through various NP staffing mechanisms. The purpose of this study was to examine if having NH-employed NPs was associated with nursing staff turnover and resident care outcomes measured as hospital utilization, infection control citations, and substantiated complaints in NHs in 2021-2022. DESIGN: A cross-sectional, retrospective study. SETTING AND PARTICIPANTS: A total of 13,966 NHs from payroll-based journal (PBJ) and claim-based quality measures published by the Centers for Medicare and Medicaid Services in 2021-2022. METHODS: Facilities were identified as having NH-employed NPs if at least 1 employed NP with paid working hours ≥10 per week was reported through the PBJ. We examined if having NH-employed NPs was associated with nursing staff turnover rates, unplanned hospital utilization, infection control citations, and substantiated complaints using doubly robust estimation that combined inverse probability weight representing the NH's likelihood of employing NPs and outcome regression. RESULTS: Approximately, 2.8% of NHs had employed NPs. Facilities with NH-employed NPs tended to be larger, hospital affiliated, and not for profit with greater medical and nursing staff availability. In addition, a significantly higher proportion of facilities with NH-employed NPs were in metropolitan areas or states with full NP practice independence. We found that facilities with NH-employed NPs had significantly lower registered nurse (adjusted ß, -5.40; 95% CI, -9.50 to -1.30) and certified nursing assistant turnover rates (adjusted ß, -3.35; 95% CI, -6.29 to -0.40). Facilities with NH-employed NPs also had significantly fewer long-stay resident hospitalizations, infection control citations, and substantial complaints compared with those with no NH-employed NPs. CONCLUSIONS AND IMPLICATIONS: This study highlights the value of NH-employed NPs to improve registered nurse and certified nursing assistant staff retention and NH resident outcomes. NH stakeholders and policymakers may consider various strategies to incentivize NP employment in NHs such as removing regulatory barriers to NP practice.
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Profissionais de Enfermagem , Recursos Humanos de Enfermagem , Idoso , Humanos , Estados Unidos , Estudos Retrospectivos , Estudos Transversais , Medicare , Casas de Saúde , EmpregoRESUMO
Pepper (Capsicum annuum) is an important vegetable crop that has been subjected to intensive breeding, resulting in limited genetic diversity, especially for sweet peppers. Previous studies have reported pepper draft genome assemblies using short read sequencing, but their capture of the extent of large structural variants (SVs), such as presence-absence variants (PAVs), inversions, and copy-number variants (CNVs) in the complex pepper genome falls short. In this study, we sequenced the genomes of representative sweet and hot pepper accessions by long-read and/or linked-read methods and advanced scaffolding technologies. First, we developed a high-quality reference genome for the sweet pepper cultivar 'Dempsey' and then used the reference genome to identify SVs in 11 other pepper accessions and constructed a graph-based pan-genome for pepper. We annotated an average of 42 972 gene families in each pepper accession, defining a set of 19 662 core and 23 115 non-core gene families. The new pepper pan-genome includes informative variants, 222 159 PAVs, 12 322 CNVs, and 16 032 inversions. Pan-genome analysis revealed PAVs associated with important agricultural traits, including potyvirus resistance, fruit color, pungency, and pepper fruit orientation. Comparatively, a large number of genes are affected by PAVs, which is positively correlated with the high frequency of transposable elements (TEs), indicating TEs play a key role in shaping the genomic landscape of peppers. The datasets presented herein provide a powerful new genomic resource for genetic analysis and genome-assisted breeding for pepper improvement.
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Global pork production has an annual growth of approximately 2.1%, and its economic and environmental impact are related with the treatment of waste in the production chain. There is little evidence of research advances to generate alternatives for using these wastes. The lack of research related to microalgae cultivation using digestate produced by porcine residues generates negative environmental impact, inadequate and inefficient technologies, low recovery and use of waste and loss of value and competitiveness in the market. The available literature focuses mainly on the treatment of anaerobic digestion liquid effluents for the removal of components, but not on the generation of value-added products. Therefore, there is a need to collect the available information, analyze it and propose other new methodologies. This article presents the information obtained from conducting a systematic review of the literature with a bibliometric and a comparative analysis; achieving an analysis of the temporal and geographical distribution, the main topics, the most influential players, the degree of maturity of the research and different strategies collected for microalgae-based swine manure digestate treatment. In this way, it was possible to capture an overview of the current state of the development of research focused on the use of digestate for the cultivation of microalgae, visualizing important aspects as the evolution of publications, identifying China and USA as the main players in research, biomass and wastewater as potential topics also Spirulina, Astaxanthin and beta-carotene as the main products based on microalgae. Thus, achieving an structure, organized and synthesized landscape of scientific and technological knowledge available for the proposal of investigations that allow the use of anaerobic digestion liquid effluents as cultivation medium for microalgae.
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Background: In 2014, the Plastic Surgery Residency Review Committee of the Accreditation Council for Graduate Medical Education (ACGME) increased minimum aesthetic surgery requirements. Consequently, the resident aesthetic clinic (RAC) has become an ever more important modality for training plastic surgery residents. Objectives: To analyze demographics and long-term surgical outcomes of aesthetic procedures performed at the Johns Hopkins and University of Maryland (JH/UM) RAC. A secondary objective was to evaluate the JH/UM RAC outcomes against those of peer RACs as well as board-certified plastic surgeons. Methods: We performed a retrospective chart review of all patients who underwent aesthetic procedures at the JH/UM RAC between 2011 and 2020. Clinical characteristics, minor complication rates, major complication rates, and revision rates from the JH/UM RAC were compared against 2 peer RACs. We compared the incidence of major complications between the JH/UM RAC and a cohort of patients from the CosmetAssure (Birmingham, AL) database. Pearson's chi-square test was used to compare complication rates between patient populations, with a significance set at 0.05. Results: Four hundred ninety-five procedures were performed on 285 patients. The major complications rate was 1.0% (n = 5). Peer RACs had total major complication rates of 0.2% and 1.7% (P = .07 and P = .47, respectively). CosmetAssure patients matched to JH/UM RAC patients were found to have comparable total major complications rates of 1.8% vs 0.6% (P = .06), respectively. At JH/UM, the minor complication rate was 13.9%, while the revision rate was 5.9%. Conclusions: The JH/UM RAC provides residents the education and training necessary to produce surgical outcomes comparable to peer RACs as well as board-certified plastic surgeons.