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The Kölliker-Fuse nucleus (KF), which is part of the parabrachial complex, participates in the generation of eupnoea under resting conditions and the control of active abdominal expiration when increased ventilation is required. Moreover, dysfunctions in KF neuronal activity are believed to play a role in the emergence of respiratory abnormalities seen in Rett syndrome (RTT), a progressive neurodevelopmental disorder associated with an irregular breathing pattern and frequent apnoeas. Relatively little is known, however, about the intrinsic dynamics of neurons within the KF and how their synaptic connections affect breathing pattern control and contribute to breathing irregularities. In this study, we use a reduced computational model to consider several dynamical regimes of KF activity paired with different input sources to determine which combinations are compatible with known experimental observations. We further build on these findings to identify possible interactions between the KF and other components of the respiratory neural circuitry. Specifically, we present two models that both simulate eupnoeic as well as RTT-like breathing phenotypes. Using nullcline analysis, we identify the types of inhibitory inputs to the KF leading to RTT-like respiratory patterns and suggest possible KF local circuit organizations. When the identified properties are present, the two models also exhibit quantal acceleration of late-expiratory activity, a hallmark of active expiration featuring forced exhalation, with increasing inhibition to KF, as reported experimentally. Hence, these models instantiate plausible hypotheses about possible KF dynamics and forms of local network interactions, thus providing a general framework as well as specific predictions for future experimental testing. KEY POINTS: The Kölliker-Fuse nucleus (KF), a part of the parabrachial complex, is involved in regulating normal breathing and controlling active abdominal expiration during increased ventilation. Dysfunction in KF neuronal activity is thought to contribute to respiratory abnormalities seen in Rett syndrome (RTT). This study utilizes computational modelling to explore different dynamical regimes of KF activity and their compatibility with experimental observations. By analysing different model configurations, the study identifies inhibitory inputs to the KF that lead to RTT-like respiratory patterns and proposes potential KF local circuit organizations. Two models are presented that simulate both normal breathing and RTT-like breathing patterns. These models provide testable hypotheses and specific predictions for future experimental investigations, offering a general framework for understanding KF dynamics and potential network interactions.
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Núcleo de Kölliker-Fuse , Síndrome de Rett , Humanos , Núcleo de Kölliker-Fuse/fisiologia , Respiração , Neurônios , Simulação por ComputadorRESUMO
BACKGROUND: Body contouring surgery after massive weight loss has emerged a safe and reliable option to improve self-esteem, social life, work ability, physical activity, and sexual activity, and it is considered as an essential step in the multidisciplinary approach to morbid obesity. In this study, we aim to provide a comprehensive overview of the current state of literature on body contouring after massive weight loss, identifying research trends and areas for future investigation. METHODS: The Web of Science Core Collection was used to identify the 50 most cited publications on post-massive weight loss surgery. Data collected from each article included: title, journal, publication year, total citations, average citations per year, authors, study type, study topic, country, and institution of origin. RESULTS: The top 50 most-cited articles include 44 original articles and 6 review articles. The most cited article, published by Lockwood in 1991, received a total of 224 citations. The research areas included surgical outcomes and complications (n=19, 38%), psychological aspects such as body image, quality of life and desire for body contouring procedures (n=18, 36%), surgical techniques (n=11, 22%), an anatomical study (n=1, 2%), and a classification system (n=1; 2%). Plastic and Reconstructive Surgery journal published most (44%) of the papers identified. The University of Pittsburgh was the single institution that contributed the most (n=11; 22%). CONCLUSION: This bibliometric analysis provides insights and research trends for clinicians interested in body contouring after massive weight loss, facilitating the understanding and evolution of post-bariatric surgery and elucidating the rationale behind current practice. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. 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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Bibliometria , Contorno Corporal , Redução de Peso , Humanos , Contorno Corporal/métodos , Obesidade Mórbida/cirurgia , Feminino , Masculino , Cirurgia Bariátrica/métodos , Qualidade de VidaRESUMO
BACKGROUND: Adult-Acquired Buried Penis is a disorder associated with systemic obesity that confers increased risks of malignancy, sexual dysfunction, urinary abnormalities, and psychological distress. Surgical correction improves patient-reported functional and psychological outcomes and often requires collaboration between plastic and urologic surgeons. To improve postoperative cosmetic outcomes and decrease wound complications following adult-acquired buried penis repair, we performed an anatomic and histologic study of the superficial fascial layers providing support to the external male genitalia and describe our approach for fascial reconstruction. METHODS: We characterized the superficial fascial anatomy in three patients undergoing adult-acquired buried penis repair, including two patients with Wisconsin Type II disease and one patient with Wisconsin Type IV disease. Gross specimens were sent from two patients histologic analysis using H&E and elastin-specific stains to characterize the identity of the superficial fibrofatty tissue. RESULTS: In all three patients, the fundiform ligament overlying the suspensory ligament was identified, isolated, and transected for removal with the suprapubic specimen. We found that reapproximation of this ligament following transection at the time of escutcheonectomy provided significant lift to the penis and genitals via improved support of dartos fascia. Histologic analysis of the superficial fibrofatty tissue located beneath the dermis revealed histologic similarities with the superficial fascial system described previously in abdominal and breast tissue. CONCLUSIONS: Reapproximation of the fundiform ligament and superficial fascial tissue following suprapubic/lower abdominal fat pad removal during adult-acquired buried penis may improve postoperative cosmesis by reducing strain on the dermal closure. LEVEL OF EVIDENCE V: 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 http://www.springer.com/00266 .
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BACKGROUND: Hyperpigmented scars, particularly in exposed body areas, can be difficult to conceal and may evoke psychological distress. While the precise causes of scar dyschromia are not fully understood, alterations in melanogenic activity appear to hold more significance than changes in melanocyte quantity. Current treatments encompass laser interventions. However, it is essential to consider their costs and potential complications in relation to their limited proven effectiveness. Fat grafting has gained interest as a scar modulation technique due to its regenerative properties, and its efficacy in reducing scar hyperpigmentation is currently under investigation. METHODS: A systematic review and meta-analysis was reported according to PRISMA guidelines. PubMed, Embase, and Cochrane Library databases were accessed. PROSPERO registration number is CRD42023457778. The primary outcome was a change in scar pigmentation after fat grafting. Pigmentation changes after fat grafting were calculated using the standardized mean difference (SMD) between baseline and postoperative scores according to POSAS and VSS scales. Bias assessment was conducted according to the National Institute for Health and Clinical Excellence quality assessment tool. RESULTS: A total of 8 articles meeting inclusion and exclusion criteria were identified, involving 323 patients with hyperpigmented scars treated with fat grafting. A significant difference in scar pigmentation was noted after treatment with fat grafting according to observers' ratings, with a SMD of - 1.09 [95% CI: - 1.32; - 0.85], p<0.01. The SMD for patient-reported scar pigmentation after treatment with fat grafting was - 0.99 [96% CI: - 1.31; - 0.66], p<0.01. Four studies provided objective measurements of melanin changes after fat grafting and revealed inconsistent findings compared to subjective observations. CONCLUSIONS: Fat grafting shows promise in ameliorating hyperpigmented scars based on subjective assessments, but further corroborating evidence from objective measures is required. 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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Tecido Adiposo , Cicatriz , Hiperpigmentação , Humanos , Cicatriz/etiologia , Hiperpigmentação/etiologia , Tecido Adiposo/transplante , Feminino , Masculino , Resultado do Tratamento , Estética , Medição de Risco , Transplante Autólogo , AdultoRESUMO
Liposuction is a surgical procedure used to remove localized excess adipose tissue. According to The Aesthetic Society's latest annual report, liposuction is the most commonly performed cosmetic procedure. Despite its popularity, the existing literature lacks a unified understanding of the risks associated with liposuction. The aim of this study was to measure complications of liposuction. A systematic review and meta-analysis was reported according to PRISMA guidelines and registered on the PROSPERO database (CRD42023471626). The primary outcome was overall complication rate. The absolute risk for individual complications was also assessed. From 2957 articles, 39 studies were selected for analysis. In total, 29,368 patients were included, with a mean age of 40.62 years and mean BMI of 26.36â kg/m2. Overall, the rate of any complication was 2.62 (95% CI, 1.78-3.84). The most common complication was contour deformity, with a prevalence of 2.35% (95% CI, 1.05%-5.16%). The prevalence of hyperpigmentation was 1.49% (95% CI, 1.12%-1.99%), seroma 0.65% (95% CI, 0.33%-1.24%), hematoma 0.27% (95% CI, 0.12%-0.60%), superficial burn 0.25% (95% CI, 0.17%-0.36%), allergic reaction 0.16% (95% CI, 0.050%-0.52%), skin necrosis 0.046% (95% CI, 0.013%-0.16%), generalized edema 0.041% (95% CI, 0.0051%-0.32%), infection 0.020% (95% CI, 0.010%-0.050%), venous thromboembolism 0.017% (95% CI, 0.0060%-0.053%), and local anesthesia toxicity 0.016% (95% CI, 0.0040%-0.064%). Liposuction is a safe procedure with low complications, of which contour deformity is the most common. Raising awareness of specific risks can enhance surgical outcomes and improve patient-physician understanding.
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Lipectomia , Complicações Pós-Operatórias , Humanos , Lipectomia/efeitos adversos , Lipectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Medição de RiscoRESUMO
Robust and predictive pre-clinical models of recalcitrant diabetic wounds are critical for advancing research efforts toward improving healing. Murine models have logistic and genetic benefits versus larger animals; however, native murine healing inadequately represents clinically recalcitrant wounds in humans. Furthermore, current humanization techniques employing devices, deleterious mutations or chemical agents each carry model-specific limitations. To better replicate human wounds in a mouse, we developed a novel wound-edge inversion (WEI) technique that mimics the architecture of epibole and mitigates contracture, epithelialization, and consequently wound closure. In this study, we evaluated the reliability and durability of the WEI model in wild-type and obese diabetic mice and compared to healing after (i) punch biopsy, (ii) mechanical/silicone stenting or (iii) exogenous oxidative stressors. In wild-type mice, WEI demonstrated favourable closure characteristics compared to both control and stented wounds, however, wounds progressed to closure by 4 weeks. In contrast, diabetic WEI wounds persisted for 6-10 weeks with reduced contracture and epithelialization. In both diabetic and wild-type mice, WEI sites demonstrated persistence of inflammatory populations, absence of epithelialization, and histologic presence of alpha-SMA positive granulation tissue when compared to controls. We conclude that the WEI technique is particularly valuable for modelling recalcitrant diabetic wounds with sustained inflammation and dysfunctional healing.
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Diabetes Mellitus Experimental , Cicatrização , Camundongos , Humanos , Animais , Diabetes Mellitus Experimental/patologia , Reprodutibilidade dos Testes , Pele/patologia , ReepitelizaçãoRESUMO
BACKGROUND: Neurodevelopmental disorders increase brain tumor risk, suggesting that normal brain development may have protective properties. Mutations in epigenetic regulators are common in pediatric brain tumors, highlighting a potentially central role for disrupted epigenetic regulation of normal brain development in tumorigenesis. For example, lysine 27 to methionine mutation (H3K27M) in the H3F3A gene occurs frequently in Diffuse Intrinsic Pontine Gliomas (DIPGs), the most aggressive pediatric glioma. As H3K27M mutation is necessary but insufficient to cause DIPGs, it is accompanied by additional mutations in tumors. However, how H3K27M alone increases vulnerability to DIPG tumorigenesis remains unclear. RESULTS: Here, we used human embryonic stem cell models with this mutation, in the absence of other DIPG contributory mutations, to investigate how H3K27M alters cellular proliferation and differentiation. We found that H3K27M increased stem cell proliferation and stem cell properties. It interfered with differentiation, promoting anomalous mesodermal and ectodermal gene expression during both multi-lineage and germ layer-specific cell specification, and blocking normal differentiation into neuroectoderm. H3K27M mutant clones exhibited transcriptomic diversity relative to the more homogeneous wildtype population, suggesting reduced fidelity of gene regulation, with aberrant expression of genes involved in stem cell regulation, differentiation, and tumorigenesis. These phenomena were associated with global loss of H3K27me3 and concordant loss of DNA methylation at specific genes in H3K27M-expressing cells. CONCLUSIONS: Together, these data suggest that H3K27M mutation disrupts normal differentiation, maintaining a partially differentiated state with elevated clonogenicity during early development. This disrupted response to early developmental cues could promote tissue properties that enable acquisition of additional mutations that cooperate with H3K27M mutation in genesis of DMG/DIPG. Therefore, this work demonstrates for the first time that H3K27M mutation confers vulnerability to gliomagenesis through persistent clonogenicity and aberrant differentiation and defines associated alterations of histone and DNA methylation.
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Neoplasias do Tronco Encefálico , Epigênese Genética , Neoplasias do Tronco Encefálico/genética , Neoplasias do Tronco Encefálico/metabolismo , Neoplasias do Tronco Encefálico/patologia , Carcinogênese/genética , Proliferação de Células , Criança , Histonas , Humanos , Mutação , Células-Tronco/metabolismoRESUMO
Rhinoplasty is one of the most popular aesthetic surgeries worldwide and often includes grafting techniques to achieve optimal results. One of these grafting techniques is autologous fat transfer, which has been used to increase volume, camouflage irregularities, and/or improve the quality of the nasal skin-soft tissue envelope. Moreover, minimally invasive approaches for altering the nasal appearance have recently increased and become known as "liquid" or "nonsurgical rhinoplasty." These nonsurgical approaches include altering the nasal appearance with filler injection to induce volumetric changes in lieu of extensive surgery. The use of fat grafting as a filler is favorable to achieve well-balanced aesthetic results without compromising the nasal skin-soft tissue envelope. This capability is partly because of the regenerative potential of fat grafts, serving to improve the quality of surrounding soft tissues. In contrast, commercial injectable fillers are inert. This article highlights the role of fat grafting in surgical and nonsurgical rhinoplasty to provide surgeons with an overview of the potential of these vastly abundant, biocompatible, and cost-effective grafts.
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Rinoplastia , Humanos , Rinoplastia/métodos , Estética Dentária , Nariz/cirurgia , Transplante Autólogo , Tecido Adiposo/transplanteRESUMO
BACKGROUND: As the prevalence of obesity increases, the number of patients seeking body contouring procedures after bariatric surgery for massive weight loss is increasing. Although the positive impact of bariatric surgery on physical and emotional health is well-described, few studies have reported on the psychosocial well-being of patients undergoing body contouring procedures. Psychosocial well-being can impact patient satisfaction and maintenance of weight loss, and is an important area to study. OBJECTIVE: The aim of this study was to characterize social and psychiatric factors of patients undergoing body contouring surgery, and to evaluate their impact on maintenance of weight loss. METHODS: A retrospective review was performed of patients who presented to a single institution for body contouring procedures between 2002 and 2018. Demographic details, medical history, psychosocial support, and operative details were collected. Univariate analysis and multinomial logistic regressions were performed with R statistical software (version 1.3.1093). RESULTS: A total of 1187 patients underwent at least 1 body contouring procedure during the study time frame. Mean BMI at presentation was 31.21 ± 10.49 kg/m2. Patients diagnosed with obesity at age 18 or older had significantly greater odds of suffering from generalized anxiety disorder (odds ratio [OR] 1.08 [95% CI, 1.02-1.15], P = .008). Patients with spousal support had 1.93 times higher odds of having maintained postbariatric weight loss at their 6-month follow-up (OR 1.93 [95% CI, 1.84-2.01], P = .028). CONCLUSIONS: Social support and age of obesity diagnosis impact psychological well-being and maintenance of weight loss following body contouring procedures.
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Cirurgia Bariátrica , Contorno Corporal , Obesidade Mórbida , Procedimentos de Cirurgia Plástica , Humanos , Adolescente , Procedimentos de Cirurgia Plástica/efeitos adversos , Obesidade/cirurgia , Cirurgia Bariátrica/efeitos adversos , Cirurgia Bariátrica/métodos , Redução de Peso , Obesidade Mórbida/cirurgiaRESUMO
BACKGROUND: Autologous fat grafting, although broadly indicated, is limited by unsatisfactory retention and often requires multiple procedures to achieve durable outcomes. Graft survival is strongly influenced by the magnitude and duration of post-engraftment ischemia. Calcitriol is a pleiotropic, safe nutrient with cell-specific influence on viability and metabolic flux. OBJECTIVES: Evaluate the efficacy of activated vitamin D3 (calcitriol) in improving grafting outcomes and examine its mechanisms. METHODS: Lipoaspirate was collected for ex vivo culture (7 unique donors), in vitro bioenergetic analysis (6 unique donors), and in vivo transplantation (5 unique donors). Ex vivo samples were incubated for up to 2 weeks before extraction of the stromal vascular fraction (SVF) for viability or flow cytometry. SVF was collected for Seahorse (Agilent; Santa Clara, CA) analysis of metabolic activity. Human endothelial cell lines were utilized for analyses of endothelial function. In vivo, samples were implanted into athymic mice with calcitriol treatment either (1) once locally or (2) 3 times weekly via intraperitoneal injection. Grafts were assessed photographically, volumetrically, and histologically at 1, 4, and 12 weeks. Hematoxylin and eosin (H&E), Sirius red, perilipin, HIF1α, and CD31 tests were performed. RESULTS: Calcitriol-treated lipoaspirate demonstrated dose-dependent increases in SVF viability and metabolic reserve during hypoxic stress. Calcitriol treatment enhanced endothelial mobility ex vivo and endothelial function in vitro. In vivo, calcitriol enhanced adipocyte viability, reduced fibrosis, and improved vascularity. Continuous calcitriol was sufficient to improve graft retention at 12 weeks (P < .05). CONCLUSIONS: Calcitriol increased fat graft retention in a xenograft model. Calcitriol has potential to be a simple, economical means of increasing fat graft retention and long-term outcomes.
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Tecido Adiposo , Calcitriol , Camundongos , Animais , Humanos , Tecido Adiposo/transplante , Calcitriol/farmacologia , Colecalciferol/farmacologia , Xenoenxertos , Adipócitos/transplante , Modelos Animais de Doenças , Sobrevivência de EnxertoRESUMO
OBJECTIVE: This study aimed to prospectively assess outcomes for surgical autologous fat transfer (AFT) applied for traumatic and postsurgical craniofacial deformities. The minimally invasive nature of AFT has potential for reduced risk and superior outcomes compared with current reconstructive options. BACKGROUND: Craniofacial deformities have functional and psychosocial sequelae and can profoundly affect quality of life. Traditional reconstructive options are invasive, invasive, complex, and often lack precision in outcomes. Although AFT is safe, effective, and minimally invasive, only anecdotal evidence exists for reconstruction of craniofacial deformities. METHODS: In this Institutional Review Board-approved prospective cohort study, 20 subjects underwent AFT (average volume: 23.9â±â13.2âmL). Volume retention over time was determined using high-resolution computed tomography. Flow cytometry was used to assess cellular subpopulations and viability in the stromal vascular fraction. Quality of life assessments were performed. After the completion of 9-month follow-up, 5 subjects were enrolled for a second treatment. RESULTS: No serious adverse events occurred. Volume retention averaged 63â±â17% at 9 months. Three-month retention strongly predicted 9-month retention (r=0.996, P < 0.0001). There was no correlation between the total volume injected and retention. Patients undergoing a second procedure had similar volume retention as the first (P = 0.05). Age, sex, body mass index, and stromal vascular fraction cellular composition did not impact retention. Surprisingly, former smokers had greater volume retention at 9 months compared with nonsmokers (74.4% vs 56.2%, P = 0.009). Satisfaction with physical appearance (P = 0.002), social relationships (P = 0.02), and social functioning quality of life (P = 0.05) improved from baseline to 9 months. CONCLUSIONS: For craniofacial defects, AFT is less invasive and safer than traditional reconstructive options. It is effective, predictable, and reaches volume stability at 3 months. Patient-reported outcomes demonstrate a positive life-changing impact.
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Tecido Adiposo/transplante , Anormalidades Craniofaciais/cirurgia , Medidas de Resultados Relatados pelo Paciente , Procedimentos de Cirurgia Plástica/métodos , Qualidade de Vida , Adulto , Anormalidades Craniofaciais/diagnóstico , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tomografia Computadorizada por Raios X , Transplante Autólogo , Adulto JovemRESUMO
STUDY OBJECTIVE: Throughout the coronavirus disease 2019 pandemic, many emergency departments have been using passive protective enclosures ("intubation boxes") during intubation. The effectiveness of these enclosures remains uncertain. We sought to quantify their ability to contain aerosols using industry standard test protocols. METHODS: We tested a commercially available passive protective enclosure representing the most common design and compared this with a modified enclosure that incorporated a vacuum system for active air filtration during simulated intubations and negative-pressure isolation. We evaluated the enclosures by using the same 3 tests air filtration experts use to certify class I biosafety cabinets: visual smoke pattern analysis using neutrally buoyant smoke, aerosol leak testing using a test aerosol that mimics the size of virus-containing particulates, and air velocity measurements. RESULTS: Qualitative evaluation revealed smoke escaping from all passive enclosure openings. Aerosol leak testing demonstrated elevated particle concentrations outside the enclosure during simulated intubations. In contrast, vacuum-filter-equipped enclosures fully contained the visible smoke and test aerosol to standards consistent with class I biosafety cabinet certification. CONCLUSION: Passive enclosures for intubation failed to contain aerosols, but the addition of a vacuum and active air filtration reduced aerosol spread during simulated intubation and patient isolation.
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COVID-19/prevenção & controle , Controle de Infecções/instrumentação , Intubação Intratraqueal/instrumentação , Pneumonia Viral/prevenção & controle , Aerossóis , COVID-19/transmissão , Infecção Hospitalar/prevenção & controle , Desenho de Equipamento , Filtração/instrumentação , Humanos , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Manequins , Pandemias , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , SARS-CoV-2 , VácuoRESUMO
BACKGROUND: Aesthetic surgery is a critical component of academic plastic surgery. As institutions are placing increased focus on aesthetic surgery, there is an opportunity to identify factors that facilitate the creation and maintenance of successful aesthetic plastic surgery programs. OBJECTIVES: The aim of this study was to conduct a national survey to evaluate the current state of academic aesthetic surgery and to identify factors that contribute to success. METHODS: A REDCap 122-question survey was developed and validated by members of the Academic Aesthetic Surgery Roundtable (AASR). The national survey was distributed to department chairs and division chiefs with active ACGME-approved plastic surgery programs (n = 92). Responses underwent Pearson's chi-squared, Wilcoxon rank-sum, and postselection inference analyses. AASR members convened to interpret data and identify best practices. RESULTS: Responses were received from 64 of 92 queries (69.6%). The multivariate analysis concluded traits associated with successful academic aesthetic surgery practices included the presence of aesthetic surgery-focused, full-time faculty whose overall practice includes >50% aesthetic surgery (P = 0.040) and nonphysician aesthetic practitioners who provide injection services (P = 0.025). In the univariate analysis, factors associated with strong aesthetic surgery training programs included resident participation in faculty aesthetic clinics (P = 0.034), aesthetic research (P = 0.006), and discounted resident aesthetic clinics (P < 0.001). CONCLUSIONS: The growth of academic aesthetic surgery practices represents a significant opportunity for advancement of resident training, departmental financial success, and diversification of faculty practices. By identifying and sharing best practices and strategies, academic aesthetic surgery practices can be further enhanced.
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Internato e Residência , Procedimentos de Cirurgia Plástica , Cirurgia Plástica , Estética , Docentes , Humanos , Cirurgia Plástica/educação , Inquéritos e QuestionáriosRESUMO
Radiation therapy to anatomic regions, including the head and neck, chest wall, and extremities, can produce radiation-induced fibrosis (RIF). To elucidate the cellular and molecular mechanism(s) involved in RIF, female C57BL/6J mice were irradiated to the right flank to 35 Gy in single fraction using 6 Mv electrons. Radiation fibrosis was detected by day 14, was increased by day 28, and confirmed by Masson's trichrome histological staining for collagen. Biopsied tissue at day 14 showed an increase in expression of fibrosis-related genes including transforming growth factor-ß (TGF-ß) and collagens 1-6. A single adipose-derived stem cell (ASC) injection on day 28 at the irradiated site decreased by day 40: epithelial thickness, collagen deposition, and significantly improved limb excursion compared with irradiated controls. Noncontact transwell coculture of ASCs above a monolayer of irradiated human foreskin fibroblasts downregulated fibrosis-related genes TGF-ß, connective tissue growth factor, interleukin-1, NF-kB, tumor necrosis factor, and collagens 1-6. Hepatocyte growth factor (HGF) secreted by ASCs was identified as a novel mechanism by which ASCs exert antifibrotic effects by downregulating fibrotic gene expression in irradiated cells and recruiting bone marrow cells to the irradiated site. In conclusion, these data indicate a mechanistic role of HGF secreted by ASCs in reducing RIF. Stem Cells 2019;37:791-802.
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Células da Medula Óssea/metabolismo , Fator de Crescimento de Hepatócito/genética , Lesões Experimentais por Radiação/terapia , Transplante de Células-Tronco , Células-Tronco/metabolismo , Fator de Crescimento Transformador beta1/genética , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Animais , Células da Medula Óssea/citologia , Movimento Celular , Técnicas de Cocultura , Colágeno/genética , Colágeno/metabolismo , Fator de Crescimento do Tecido Conjuntivo/genética , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Feminino , Fibroblastos/metabolismo , Fibroblastos/patologia , Fibrose , Regulação da Expressão Gênica , Fator de Crescimento de Hepatócito/metabolismo , Interleucina-1/genética , Interleucina-1/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/genética , NF-kappa B/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Lesões Experimentais por Radiação/genética , Lesões Experimentais por Radiação/metabolismo , Lesões Experimentais por Radiação/patologia , Células-Tronco/citologia , Fator de Crescimento Transformador beta1/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
AIMS: The food supply is a potential source of antimicrobial resistance. Current surveillance programmes targeting food are limited to beef, pork and poultry and do not capture niche products. In this study, imported reptile and amphibian products were screened for antimicrobial-resistant bacteria. METHODS AND RESULTS: In all, 53 items including soft shell turtles, frog legs, geckos, snakes and a turtle carapace were purchased from specialty markets in Vancouver and Saskatoon, Canada. Samples were selectively cultured for Salmonella sp., Escherichia coli, extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae and meropenem-resistant organisms. Salmonella, all pan-susceptible, were grown from six dried geckos. Escherichia coli were isolated from 19 samples, including ESBL producers from six items. One multidrug-resistant E. coli possessed both the blaCTX-M-55 and mcr-1 genes. An NDM-1-producing Acinetobacter sp. was also isolated from a dried turtle carapace. CONCLUSIONS: Our results suggest that imported reptile and amphibian meats are an underappreciated source of resistant bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: The international trade of food may play a role in the dissemination of resistant bacteria. The presence of these bacteria in niche market foods represents a risk of unknown magnitude to public health and a gap in current national resistance surveillance programmes.
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Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Bactérias Gram-Negativas/isolamento & purificação , Internacionalidade , Carne/microbiologia , Anfíbios , Animais , Canadá , Farmacorresistência Bacteriana/genética , Farmacorresistência Bacteriana Múltipla/genética , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/genética , RépteisRESUMO
BACKGROUND: Autologous fat transfer in the form of lipoaspirates for the reconstruction of the breast after breast cancer surgery is a commonly used procedure in plastic surgery. However, concerns regarding the oncologic risk of nutrient-rich fat tissue are widely debated. Previous studies have primarily focused on studying the interaction between adipose-derived stem cells (ASCs) and breast cancer cells. METHODS: In this study, we performed a comprehensive analysis of the paracrine- and contact-based interactions between lipoaspirates, ASCs and breast cancer cell lines. An inverted flask culture method was used to study the contact-based interaction between lipoaspirates and breast cancer cells, while GFP-expressing breast cancer cell lines were generated to study the cell-cell contact interaction with ASCs. Three different human breast cancer cell lines, MCF-7, MDA-MB-231 and BT-474, were studied. We analyzed the impact of these interactions on the proliferation, cell cycle and epithelial-to-mesenchymal (EMT) transition of the breast cancer cells. RESULTS: Our results revealed that both lipoaspirates and ASCs do not increase the proliferation rate of the breast cancer cells either through paracrine- or contact-dependent interactions. We observed that lipoaspirates selectively inhibit the proliferation of MCF-7 cells in contact co-culture, driven by the retinoblastoma (Rb) protein activity mediating cell cycle arrest. Additionally, ASCs inhibited MDA-MB-231 breast cancer cell proliferation in cell-cell contact-dependent interactions. Quantitative real-time PCR revealed no significant increase in the EMT-related genes in breast cancer cells upon co-culture with ASCs. CONCLUSION: In conclusion, this study provides evidence of the non-oncogenic character of lipoaspirates and supports the safety of clinical fat grafting in breast reconstruction after oncological surgical procedures. In vivo studies in appropriate animal models and long-term post-operative clinical data from patients are essential to reach the final safety recommendations.
Assuntos
Tecido Adiposo/citologia , Neoplasias da Mama/metabolismo , Comunicação Celular , Células-Tronco/metabolismo , Biomarcadores , Neoplasias da Mama/patologia , Diferenciação Celular , Proliferação de Células , Técnicas de Cocultura , Meios de Cultivo Condicionados , Feminino , Humanos , Imunofenotipagem , Lipectomia , Mamoplastia , Cultura Primária de CélulasRESUMO
The ability of chemotherapeutic agents to affect the growth of common bacterial pathogens and the relationship between the effects of chemotherapeutics and antimicrobials is largely unknown. The purpose of this study was to describe the susceptibility of canine bacterial isolates to chemotherapeutic agents and to compare these results to their antimicrobial susceptibility. The effects of bleomycin, doxorubicin, cytarabine, cyclophosphamide, methotrexate, 5-fluorouracil and gemcitabine on the growth of 33 Staphylococcus pseudintermedius isolates and 32 Escherichia coli isolates from dogs was determined by agar dilution. In addition to MICs, the lowest drug concentration associated with a decreased colony size was recorded. Results were compared to the MICs of a panel of antimicrobial agents. Bleomycin consistently inhibited bacterial growth of S. pseudintermedius and E. coli. Doxorubicin inhibited S. pseudintermedius but not E. coli while the opposite was seen for gemcitabine. Reduction in colony size on exposure to 5-fluorouracil for both organisms, and methotrexate for S. pseudintermedius was seen. No observable effect of cyclophosphamide or cytarabine was observed. Associations between elevated MICs to chemotherapeutic drugs and antimicrobial resistance were not found. These results indicate that chemotherapeutic agents affect the growth of bacteria, but do not support a role in the selection of antimicrobial resistance. SIGNIFICANCE AND IMPACT OF THE STUDY: This study shows that chemotherapy drugs commonly used in veterinary oncology have an effect of the growth of canine isolates of Escherichia coli and Staphylococcus pseudintermedius. No associations between susceptibility to chemotherapeutic drugs and antibiotics were found, which does not support selection of antimicrobial resistance by chemotherapy drugs.
Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Bleomicina/farmacologia , Doenças do Cão/microbiologia , Escherichia coli/efeitos dos fármacos , Fluoruracila/farmacologia , Staphylococcus/efeitos dos fármacos , Animais , Cães , Escherichia coli/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Staphylococcus/crescimento & desenvolvimento , Staphylococcus/isolamento & purificaçãoRESUMO
In 1991, Dr Paul Schnur and his colleagues published an article correlating the weight of breast tissue to be removed in a breast reduction operation with the total body surface area (BSA) of the patient. They presented a very cogent argument for selecting three groups of patients: those with medical indications for operation, those who merit review, and those whose operation could be considered cosmetic. The Schnur Sliding Scale is widely used by insurance companies in the western United States in the process of preauthorizing breast reduction operations, and its use may be spreading eastward. The Schnur group presented a nomogram for calculating BSA and a scale in the form of a table for guiding a determination of whether the patient is a reconstructive patient as opposed to an aesthetic patient. We have combined the scale and the BSA nomogram for a simplified nomogram calculator that facilitates rapid determination of anticipated tissue weight of resection for a patient of a given size. This calculator yields the required weight of tissue to remove with just knowledge of the patient's height and weight and the use of a straight edge. We demonstrate and compare performance of this calculation by hand and by nomogram. There is ample evidence that the practice of applying the Schnur Sliding Scale may be prohibitive to symptomatic patients seeking reduction mammaplasty and should be abandoned. While this practice continues, our simplified Schnur Sliding Scale nomogram is meant to help easily determine the insurer-required minimum breast resection weight and thereby both improve patient counseling prior to planning surgery and assist the surgeon with achieving insurer reimbursement for the procedure while avoiding rejected claims.
Assuntos
Superfície Corporal , Mama/anormalidades , Mama/anatomia & histologia , Hipertrofia/cirurgia , Cobertura do Seguro/economia , Adulto , Índice de Massa Corporal , Mama/cirurgia , Estudos de Coortes , Feminino , Humanos , Hipertrofia/diagnóstico , Nomogramas , Tamanho do Órgão , Mecanismo de Reembolso , Estudos Retrospectivos , Sensibilidade e Especificidade , Inquéritos e Questionários , Estados UnidosRESUMO
Fat grafting was first described in the early 20th century but for many years remained a relatively underused technique due to the unreliability of long-term volume expansion. Significant improvements in reliability have been made in the last 2 decades and there is a large body of literature pertaining to extraction, processing and injection methods to obtain more lasting effects. However, volume loss and graft resorption remain a major challenge in the long term and lead to unpredictability in results. Enriching adipose graft with stromal vascular fraction, ex vivo cultured adipose stem cells and platelet-derived growth factor among others is one method under active investigation which may assist graft survival through a range of mechanisms including increased angiogenesis. Breaking adipose graft into smaller fragments such that engrafted cells have greater access to donor-site oxygenation and nutrition is another method which in theory may promote survival. Presently, adipose grafting in the face is usually for the addition of volume to fill defects. However, the stem-cell containing fraction of adipose grafting (stromal vascular fraction) appears to exert a rejuvenating effect on overlying skin and soft tissue when administered alone. The application of these low-volume injections represents a significant shift in thinking away from mere volume expansion. These techniques have been tested in a range of animal models and some human studies. In this review, the authors provide a broad overview of present research and highlight both limitations in previous research and current areas of investigation.
Assuntos
Tecido Adiposo , Face , Rejuvenescimento , Tecido Adiposo/citologia , Tecido Adiposo/transplante , Animais , Face/fisiologia , Face/cirurgia , Humanos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologiaRESUMO
BACKGROUND: The obese population has a higher incidence of mood disorders compared to individuals with normal body mass index (BMI). A better understanding of the unique psychosocial challenges faced by this patient population will allow physicians to better optimize patient psychosocial support systems perioperatively, as well as help the patient to maintain appropriate expectations. METHODS: A large, retrospective database of 1135 patients with greater than 50 pounds of weight loss was reviewed. Data were analyzed using a multinomial regression model to determine the influence of psychosocial factors on the incidence of depression and anxiety. RESULTS: Prior to massive weight loss, patients reported an overall incidence of depression and anxiety of 42.5% and 26.3%, respectively. Following massive weight loss, the incidence of depression decreased to 32.3% and the incidence of anxiety decreased to 22.0%. Patients with spousal support and with positive self-image were more likely to experience resolution of depression. Patients with positive self-image were likely to experience resolution of anxiety. Resolution of medical comorbidities correlated with a decrease in the rate of depression. CONCLUSION: Depression and anxiety are prevalent in the massive weight loss patient population undergoing body contouring surgery. Support systems are a vital resource for patients with psychological comorbidities undergoing massive weight loss. Patients who have a positive self-image of themselves are more likely to experience resolution of psychological comorbidities. Physicians should consider recommending support groups and/or counseling in patients who have poor support and negative self-image. 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.