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1.
J Craniofac Surg ; 35(4): 1129-1133, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38688025

RESUMO

Understanding rhinoplasty characteristics important to patients, physicians, and society is essential for evaluating outcomes and designing optimal treatment plans. The authors aimed to elucidate specific rhinoplasty-related outcomes that are most important to patients, surgeons, and the general population. A cross-sectional survey comprising 11 rhinoplasty-specific characteristics, was distributed to patients, facial plastic surgeons, and the general population. Adult patients presenting for rhinoplasty consideration or follow-up after undergoing rhinoplasty were recruited. Characteristics rankings were compared between the 3 respondent groups using Spearman's rank correlation coefficient (ρ). Responses from 150 surgeons, 111 patients, and 102 lay individuals from the general population were included for analysis. When ranking rhinoplasty-specific characteristics in order of importance, patients and the general population ranked "ability to breathe through nose while awake" first and "overall appearance of nose" as second. Surgeons ranked "overall appearance of nose" first and "ability to breathe through nose while awake" second. There were strong correlations between patients' and surgeons' rankings (Spearman's ρ=0.836, P =0.002), between patients' and the general population's rankings (Spearman's ρ=0.773, P =0.007), and between surgeons' and the general population's rankings (Spearman's ρ=0.782, P =0.006). Our results highlight a significant correlation between characteristics of the "ideal" nose as determined by patients, surgeons, and the general population.


Assuntos
Rinoplastia , Humanos , Feminino , Masculino , Estudos Transversais , Adulto , Pessoa de Meia-Idade , Cirurgiões/estatística & dados numéricos , Inquéritos e Questionários , Resultado do Tratamento , Satisfação do Paciente , Estética
2.
Nat Chem Biol ; 17(5): 558-566, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33649598

RESUMO

G-protein-coupled receptor-regulated cAMP production from endosomes can specify signaling to the nucleus by moving the source of cAMP without changing its overall amount. How this is possible remains unknown because cAMP gradients dissipate over the nanoscale, whereas endosomes typically localize micrometers from the nucleus. We show that the key location-dependent step for endosome-encoded transcriptional control is nuclear entry of cAMP-dependent protein kinase (PKA) catalytic subunits. These are sourced from punctate accumulations of PKA holoenzyme that are densely distributed in the cytoplasm and titrated by global cAMP into a discrete metastable state, in which catalytic subunits are bound but dynamically exchange. Mobile endosomes containing activated receptors collide with the metastable PKA puncta and pause in close contact. We propose that these properties enable cytoplasmic PKA to act collectively like a semiconductor, converting nanoscale cAMP gradients generated from endosomes into microscale elevations of free catalytic subunits to direct downstream signaling.


Assuntos
Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , AMP Cíclico/metabolismo , Citoplasma/metabolismo , Endossomos/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Transdução de Sinais/genética , Animais , Domínio Catalítico , Núcleo Celular/metabolismo , Núcleo Celular/ultraestrutura , Cadeias Pesadas de Clatrina/antagonistas & inibidores , Cadeias Pesadas de Clatrina/genética , Cadeias Pesadas de Clatrina/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/genética , Citoplasma/ultraestrutura , Dinamina I/genética , Dinamina I/metabolismo , Endossomos/ultraestrutura , Regulação da Expressão Gênica , Genes Reporter , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Holoenzimas/genética , Holoenzimas/metabolismo , Humanos , Luciferases/genética , Luciferases/metabolismo , Ligação Proteica , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Ratos , Receptores Adrenérgicos beta 2/genética
3.
J Craniofac Surg ; 34(8): 2453-2454, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37772877

RESUMO

Facial rejuvenation outcomes have not been well studied in patients with granulomatosis with polyangiitis (GP)-formerly Wegener granulomatosis. This report highlights a case of a 49-year-old female with a history of GP, presenting with facial aging and functional nasal concerns. The patient underwent facial rejuvenation and nasal reconstruction procedures, including primary open functional rhinoplasty, septal perforation repair with Alloderm, deep-plane rhytidectomy, platysmaplasty, nanofat grafting, and fractionated erbium laser to the face (sparing the nose and peri-incisional areas). Despite a routine operation, postoperative course was complicated by wound healing and vascular congestion issues related to her underlying autoimmune disease. This case highlights the risks associated with postsurgical healing in patients with GP undergoing esthetic surgery. To the best of our knowledge, this report is the first to discuss management considerations in a patient with GP undergoing facial rejuvenation surgery.


Assuntos
Granulomatose com Poliangiite , Rinoplastia , Ritidoplastia , Envelhecimento da Pele , Humanos , Feminino , Pessoa de Meia-Idade , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/cirurgia , Rejuvenescimento , Ritidoplastia/métodos , Nariz/cirurgia , Rinoplastia/métodos
4.
Aesthetic Plast Surg ; 47(5): 2011-2022, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37369866

RESUMO

OBJECTIVE: The purpose of this systematic review is to critically examine the literature published on rhinoplasties in thick-skinned patients to determine how to maximize outcomes in these patients. METHODS: The PubMEd and Google Scholar databases were searched for clinical studies related to nasal skin thickness as it relates to rhinoplasty surgery and surgical outcomes. RESULTS: We performed a review of the current body of literature and identified twenty-eight articles that met our inclusion criteria for final analysis. Three articles were level of evidence 1 by CEBM guidelines, while the majority were level 4 (39%) and 5 (32%). Most papers were published in the USA (35%), followed by Saudi Arabia (14%). Here, we outline the current body of literature regarding thick-skinned noses in rhinoplasty surgery and identify optimization strategies. CONCLUSION: We highlight a management scheme subdivided into preoperative, intraoperative and postoperative timepoints for the comprehensive management of this patient population. Optimal results rely on an individualized medical and surgical treatment plan and regimen to achieve desired and realistic results. LEVEL OF EVIDENCE III: 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 .


Assuntos
Rinoplastia , Humanos , Rinoplastia/métodos , Nariz/cirurgia , Pele , Arábia Saudita , Resultado do Tratamento , Estética
5.
J Biol Chem ; 297(1): 100907, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34166681

RESUMO

Endosomal signaling downstream of G-protein-coupled receptors (GPCRs) has emerged as a novel paradigm with important pharmacological and physiological implications. However, our knowledge of the functional consequences of intracellular signaling is incomplete. To begin to address this gap, we combined an optogenetic approach for site-specific generation of the prototypical second messenger generated by active GPCRs, cyclic AMP (cAMP), with unbiased mass-spectrometry-based analysis of the phosphoproteome. We identified 218 unique, high-confidence sites whose phosphorylation is either increased or decreased in response to cAMP elevation. We next determined that the same amount of cAMP produced from the endosomal membrane led to more robust changes in phosphorylation than the plasma membrane. Remarkably, this was true for the entire repertoire of 218 identified targets and irrespective of their annotated subcellular localizations (endosome, cell surface, nucleus, cytosol). Furthermore, we identified a particularly strong endosome bias for a subset of proteins that are dephosphorylated in response to cAMP. Through bioinformatics analysis, we established these targets as putative substrates for protein phosphatase 2A (PP2A), and we propose compartmentalized activation of PP2A by cAMP-responsive kinases as the likely underlying mechanism. Altogether, our study extends the concept that endosomal signaling is a significant functional contributor to cellular responsiveness to cAMP by establishing a unique role for localized cAMP production in defining categorically distinct phosphoresponses.


Assuntos
AMP Cíclico/metabolismo , Endossomos/metabolismo , Fosfoproteínas/metabolismo , Proteoma/metabolismo , Animais , Células HEK293 , Humanos , Fosfoproteínas/química , Fosforilação , Domínios Proteicos , Proteína Fosfatase 2/metabolismo , Proteoma/química
6.
J Transl Med ; 18(1): 369, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32993675

RESUMO

The complexities of modern biomedicine are rapidly increasing. Thus, modeling and simulation have become increasingly important as a strategy to understand and predict the trajectory of pathophysiology, disease genesis, and disease spread in support of clinical and policy decisions. In such cases, inappropriate or ill-placed trust in the model and simulation outcomes may result in negative outcomes, and hence illustrate the need to formalize the execution and communication of modeling and simulation practices. Although verification and validation have been generally accepted as significant components of a model's credibility, they cannot be assumed to equate to a holistic credible practice, which includes activities that can impact comprehension and in-depth examination inherent in the development and reuse of the models. For the past several years, the Committee on Credible Practice of Modeling and Simulation in Healthcare, an interdisciplinary group seeded from a U.S. interagency initiative, has worked to codify best practices. Here, we provide Ten Rules for credible practice of modeling and simulation in healthcare developed from a comparative analysis by the Committee's multidisciplinary membership, followed by a large stakeholder community survey. These rules establish a unified conceptual framework for modeling and simulation design, implementation, evaluation, dissemination and usage across the modeling and simulation life-cycle. While biomedical science and clinical care domains have somewhat different requirements and expectations for credible practice, our study converged on rules that would be useful across a broad swath of model types. In brief, the rules are: (1) Define context clearly. (2) Use contextually appropriate data. (3) Evaluate within context. (4) List limitations explicitly. (5) Use version control. (6) Document appropriately. (7) Disseminate broadly. (8) Get independent reviews. (9) Test competing implementations. (10) Conform to standards. Although some of these are common sense guidelines, we have found that many are often missed or misconstrued, even by seasoned practitioners. Computational models are already widely used in basic science to generate new biomedical knowledge. As they penetrate clinical care and healthcare policy, contributing to personalized and precision medicine, clinical safety will require established guidelines for the credible practice of modeling and simulation in healthcare.


Assuntos
Atenção à Saúde , Treinamento por Simulação , Comunicação , Simulação por Computador , Política de Saúde
7.
J Neurosci ; 38(29): 6427-6438, 2018 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-29921715

RESUMO

The BRAIN Initiative arose from a grand challenge to "accelerate the development and application of new technologies that will enable researchers to produce dynamic pictures of the brain that show how individual brain cells and complex neural circuits interact at the speed of thought." The BRAIN Initiative is a public-private effort focused on the development and use of powerful tools for acquiring fundamental insights about how information processing occurs in the central nervous system (CNS). As the Initiative enters its fifth year, NIH has supported >500 principal investigators, who have answered the Initiative's challenge via hundreds of publications describing novel tools, methods, and discoveries that address the Initiative's seven scientific priorities. We describe scientific advances produced by individual laboratories, multi-investigator teams, and entire consortia that, over the coming decades, will produce more comprehensive and dynamic maps of the brain, deepen our understanding of how circuit activity can produce a rich tapestry of behaviors, and lay the foundation for understanding how its circuitry is disrupted in brain disorders. Much more work remains to bring this vision to fruition, and the National Institutes of Health continues to look to the diverse scientific community, from mathematics, to physics, chemistry, engineering, neuroethics, and neuroscience, to ensure that the greatest scientific benefit arises from this unique research Initiative.


Assuntos
Mapeamento Encefálico/métodos , Neurociências/métodos , Animais , Humanos , National Institutes of Health (U.S.) , Estados Unidos
8.
Ann Surg ; 267(1): 26-34, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28562397

RESUMO

: A workshop on "Simulation Research in Gastrointestinal and Urologic Care: Challenges and Opportunities" was held at the National Institutes of Health in June 2016. The purpose of the workshop was to examine the extent to which simulation approaches have been used by skilled proceduralists (not trainees) caring for patients with gastrointestinal and urologic diseases. The current status of research findings in the use and effectiveness of simulation applications was reviewed, and numerous knowledge gaps and research needs were identified by the faculty and the attendees. The paradigm of "deliberate practice," rather than mere repetition, and the value of coaching by experts was stressed by those who have adopted simulation in music and sports. Models that are most useful for the adoption of simulation by expert clinicians have yet to be fully validated. Initial studies on the impact of simulation on safety and error reduction have demonstrated its value in the training domain, but the role of simulation as a strategy for increased procedural safety remains uncertain in the world of the expert practitioner. Although the basic requirements for experienced physicians to acquire new skills have been explored, the widespread availability of such resources is an unrealized goal, and there is a need for well-designed outcome studies to establish the role of simulation in improving the quality of health care.


Assuntos
Bioengenharia/educação , Pesquisa Biomédica/educação , Simulação por Computador , Educação Médica/métodos , National Institute of Biomedical Imaging and Bioengineering (U.S.) , National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) , Docentes , Humanos , Estados Unidos
9.
J Biomech Eng ; 140(2)2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29247253

RESUMO

The role of computational modeling for biomechanics research and related clinical care will be increasingly prominent. The biomechanics community has been developing computational models routinely for exploration of the mechanics and mechanobiology of diverse biological structures. As a result, a large array of models, data, and discipline-specific simulation software has emerged to support endeavors in computational biomechanics. Sharing computational models and related data and simulation software has first become a utilitarian interest, and now, it is a necessity. Exchange of models, in support of knowledge exchange provided by scholarly publishing, has important implications. Specifically, model sharing can facilitate assessment of reproducibility in computational biomechanics and can provide an opportunity for repurposing and reuse, and a venue for medical training. The community's desire to investigate biological and biomechanical phenomena crossing multiple systems, scales, and physical domains, also motivates sharing of modeling resources as blending of models developed by domain experts will be a required step for comprehensive simulation studies as well as the enhancement of their rigor and reproducibility. The goal of this paper is to understand current perspectives in the biomechanics community for the sharing of computational models and related resources. Opinions on opportunities, challenges, and pathways to model sharing, particularly as part of the scholarly publishing workflow, were sought. A group of journal editors and a handful of investigators active in computational biomechanics were approached to collect short opinion pieces as a part of a larger effort of the IEEE EMBS Computational Biology and the Physiome Technical Committee to address model reproducibility through publications. A synthesis of these opinion pieces indicates that the community recognizes the necessity and usefulness of model sharing. There is a strong will to facilitate model sharing, and there are corresponding initiatives by the scientific journals. Outside the publishing enterprise, infrastructure to facilitate model sharing in biomechanics exists, and simulation software developers are interested in accommodating the community's needs for sharing of modeling resources. Encouragement for the use of standardized markups, concerns related to quality assurance, acknowledgement of increased burden, and importance of stewardship of resources are noted. In the short-term, it is advisable that the community builds upon recent strategies and experiments with new pathways for continued demonstration of model sharing, its promotion, and its utility. Nonetheless, the need for a long-term strategy to unify approaches in sharing computational models and related resources is acknowledged. Development of a sustainable platform supported by a culture of open model sharing will likely evolve through continued and inclusive discussions bringing all stakeholders at the table, e.g., by possibly establishing a consortium.


Assuntos
Simulação por Computador , Fenômenos Mecânicos , Fenômenos Biomecânicos
10.
Artigo em Inglês | MEDLINE | ID: mdl-27941471

RESUMO

PURPOSE: To evaluate the safety, subjectively assess outcome, and emphasize surgical pearls and critical clinical observations of upper blepharoplasty performed in conjunction with the brow fat pad suspension suture procedure, previously referred to as a "browpexy variant" or "brassiere suture procedure." METHODS: A retrospective 4-year analysis of patients who underwent the brow fat pad suspension suture with upper blepharoplasty was performed. Adjunctive procedures (brow lift and ptosis repair) were categorized. The surgical technique is detailed with emphasis placed on nuances to aid in optimal outcome. RESULTS: Two hundred and sixteen patients (149 women and 47 men) underwent upper blepharoplasty with the brow fat pad suspension suture. The average patient age is 54 years and follow up is 11 months. One hundred patients had adjudicative brow lift or ptosis repair, and in 20 patients the blepharoplasty was a revision procedure. Subjective assessment of outcome showed excellent aesthetic results with improved brow projection, and enhanced lateral tarsal platform show and eyebrow/eyelid contour. Surgical complications were infrequent and patient satisfaction was high. CONCLUSIONS: This initial large series description of the brow fat pad suspension suture demonstrates that it is a safe adjunct to upper blepharoplasty, which the authors believe subjectively improves overall outcome. Evidence-based quantitative assessments of objective measures of surgical results are currently underway.


Assuntos
Tecido Adiposo/cirurgia , Blefaroplastia/métodos , Exoftalmia/cirurgia , Pálpebras/cirurgia , Ritidoplastia/métodos , Técnicas de Sutura/instrumentação , Suturas , Adulto , Idoso , Idoso de 80 Anos ou mais , Sobrancelhas , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Retrospectivos , Fatores de Tempo
11.
Ophthalmic Plast Reconstr Surg ; 34(1): 37-42, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28151825

RESUMO

PURPOSE: To assess current practice patterns for management of upper and lower eyelid blepharoplasty by active American Society of Ophthalmic Plastic and Reconstructive Surgery members. METHODS: An invitation to participate in a web-based anonymous survey was sent to the active American Society of Ophthalmic Plastic and Reconstructive Surgery membership via email. The survey consists of 34 questions, both multiple choice and free response, regarding upper and lower eyelid blepharoplasty surgery. Practice patterns for both aesthetic and functional blepharoplasty are assessed. RESULTS: Thirty-four percent (161/472) of American Society of Ophthalmic Plastic and Reconstructive Surgery members polled responded to the survey. Members perform an average of 196 upper eyelid, 46 lower eyelid, and 53 four-eyelid blepharoplasty procedures per year, with 70% of cases being functional and 30% purely aesthetic. Most members prefer monitored care (71%) to local (21%) or general (8%) anesthesia. Eighty-nine percent of surgeons use topical antibiotics after surgery, erythromycin being the most common (51%). Fourteen percent of members use postoperative oral antibiotics, with cephalexin (81%) being most common. In upper eyelid blepharoplasty, orbicularis muscle is excised by 86% of respondents. Orbital fat is excised, when deemed appropriate, in 97% of cases, with nasal fat excised most commonly (88%). Less commonly, fat repositioning (36%) and adjunctive fat grafting (33%) are performed. In lower eyelid blepharoplasty, surgeons report using one or more of the following approaches: transconjunctival (96%), transcutaneous (82%), and both transconjunctival and transcutaneous (51%). Common adjunctive procedures include orbital fat excision (99%), fat repositioning (80%), and lateral canthal suspension (96%). Less common adjunctive procedures include laser skin resurfacing (36%) and chemical peels (29%). CONCLUSIONS: This report outlines contemporary practice patterns among active American Society of Ophthalmic Plastic and Reconstructive Surgery members in the management of upper and lower eyelid blepharoplasty. It is important to quantify such data periodically to update the membership as to how this common surgical procedure is approached. This also allows eyelid surgeons to compare their practice patterns with a national group specializing in such surgery.


Assuntos
Blefaroplastia/tendências , Pálpebras/cirurgia , Oftalmologia , Ritidoplastia/métodos , Sociedades Médicas , Tecido Adiposo/cirurgia , Blefaroplastia/métodos , Humanos , Estudos Retrospectivos , Inquéritos e Questionários , Estados Unidos
13.
J Clin Gastroenterol ; 2017 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-28562441

RESUMO

A workshop on ''Simulation Research in Gastrointestinal and Urologic Care: Challenges and Opportunities'' was held at the National Institutes of Health in June 2016. The purpose of the workshop was to examine the extent to which simulation approaches have been used by skilled proceduralists (not trainees) caring for patients with gastrointestinal and urologic diseases. The current status of research findings in the use and effectiveness of simulation applications was reviewed, and numerous knowledge gaps and research needs were identified by the faculty and the attendees. The paradigm of ''deliberate practice,'' rather than mere repetition, and the value of coaching by experts was stressed by those who have adopted simulation in music and sports. Models that are most useful for the adoption of simulation by expert clinicians have yet to be fully validated. Initial studies on the impact of simulation on safety and error reduction have demonstrated its value in the training domain, but the role of simulation as a strategy for increased procedural safety remains uncertain in the world of the expert practitioner. Although the basic requirements for experienced physicians to acquire new skills have been explored, the widespread availability of such resources is an unrealized goal, and there is a need for well-designed outcome studies to establish the role of simulation in improving the quality of health care.

14.
Biochim Biophys Acta ; 1854(10 Pt A): 1425-37, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26093111

RESUMO

The genome of the α-proteobacterium Pseudaminobacter salicylatoxidans codes for a ferrous iron containing ring-fission dioxygenase which catalyzes the 1,2-cleavage of (substituted) salicylate(s), gentisate (2,5-dihydroxybenzoate), and 1-hydroxy-2-naphthoate. Sequence alignments suggested that the "salicylate 1,2-dioxygenase" (SDO) from this strain is homologous to gentisate 1,2-dioxygenases found in bacteria, archaea and fungi. In the present study the catalytic mechanism of the SDO and gentisate 1,2-dioxygenases in general was analyzed based on sequence alignments, mutational and previously performed crystallographic studies and mechanistic comparisons with "extradiol- dioxygenases" which cleave aromatic nuclei in the 2,3-position. Different highly conserved amino acid residues that were supposed to take part in binding and activation of the organic substrates were modified in the SDO by site-specific mutagenesis and the enzyme variants subsequently analyzed for the conversion of salicylate, gentisate and 1-hydroxy-2-naphthoate. The analysis of enzyme variants which carried exchanges in the positions Arg83, Trp104, Gly106, Gln108, Arg127, His162 and Asp174 demonstrated that Arg83 and Arg127 were indispensable for enzymatic activity. In contrast, residual activities were found for variants carrying mutations in the residues Trp104, Gly106, Gln108, His162, and Asp174 and some of these mutants still could oxidize gentisate, but lost the ability to convert salicylate. The results were used to suggest a general reaction mechanism for gentisate-1,2-dioxygenases and to assign to certain amino acid residues in the active site specific functions in the cleavage of (substituted) salicylate(s).


Assuntos
Alphaproteobacteria/química , Aminoácidos/química , Proteínas de Bactérias/química , Dioxigenases/química , Alphaproteobacteria/enzimologia , Sequência de Aminoácidos , Aminoácidos/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Dioxigenases/genética , Dioxigenases/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Gentisatos/química , Gentisatos/metabolismo , Cinética , Dados de Sequência Molecular , Mutação , Naftóis/química , Naftóis/metabolismo , Oxirredução , Conformação Proteica , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Salicilatos/química , Salicilatos/metabolismo , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Relação Estrutura-Atividade , Especificidade por Substrato
15.
J Surg Oncol ; 114(1): 27-31, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27144672

RESUMO

OBJECTIVES: The purpose of this study was to analyze TGF-ß1 and MyoD expression in cervical muscles during radiation therapy (RT) and their role in inducing muscle fibrosis in head and neck cancer (HNC) patients. We also studied the effect of combined traditional swallow therapy (TST) and neuromuscular electrical stimulation (NMES) therapy on TGF-ß1/MyoD homeostasis in patients undergoing post-operative RT for HNC. STUDY DESIGN: Case-control study. METHODS: Thirty patients, 10 with benign thyroid lesions and non-radiated muscle (control), and 20 with advanced-stage HNC receiving primary resection and post-operative radiation (study group) were enrolled. Patients in the study group were randomly assigned to receive post-operative RT alone (Group I) or post-operative RT with TST/NMES therapy (Group II). Intraoperative biopsies were obtained in all 30 patients. In the study groups, biopsies were repeated 4 weeks after completion of RT. TGF-ß1 and MyoD expression were evaluated by immunohistochemistry and Western Blot. RESULTS: The control group demonstrated low expression of TGF-ß1 and high expression of MyoD. Following RT, patients in study Group I had high expression of TGF-ß1 and low levels of MyoD. Group II patients demonstrated TGF-ß1 levels more consistent with that of non-irradiated tissue. CONCLUSION: The molecular pathogenesis of RT-induced muscle fibrosis involves the TGF-ß1 pathway and its repression of MyoD expression. Our results suggest a correlation between TST/NMES combined therapy and the restoration of TGF-ß1/MyoD homeostasis in cervical muscles. TST/NMES is a plausible prophylaxis and/or treatment for RT-induced muscle fibrosis and dysphagia. J. Surg. Oncol. 2016;114:27-31. © 2016 Wiley Periodicals, Inc.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Terapia por Estimulação Elétrica , Neoplasias de Cabeça e Pescoço/radioterapia , Músculo Esquelético/patologia , Músculo Esquelético/efeitos da radiação , Proteína MyoD/metabolismo , Lesões por Radiação/terapia , Fator de Crescimento Transformador beta1/metabolismo , Biomarcadores/metabolismo , Biópsia , Western Blotting , Carcinoma de Células Escamosas/cirurgia , Estudos de Casos e Controles , Fibrose , Neoplasias de Cabeça e Pescoço/cirurgia , Homeostase , Humanos , Imuno-Histoquímica , Músculo Esquelético/metabolismo , Lesões por Radiação/metabolismo , Lesões por Radiação/patologia , Radioterapia Adjuvante/efeitos adversos , Carcinoma de Células Escamosas de Cabeça e Pescoço
16.
Nature ; 460(7259): 1127-31, 2009 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-19657334

RESUMO

Long interspersed element 1 (LINE-1 or L1) retrotransposons have markedly affected the human genome. L1s must retrotranspose in the germ line or during early development to ensure their evolutionary success, yet the extent to which this process affects somatic cells is poorly understood. We previously demonstrated that engineered human L1s can retrotranspose in adult rat hippocampus progenitor cells in vitro and in the mouse brain in vivo. Here we demonstrate that neural progenitor cells isolated from human fetal brain and derived from human embryonic stem cells support the retrotransposition of engineered human L1s in vitro. Furthermore, we developed a quantitative multiplex polymerase chain reaction that detected an increase in the copy number of endogenous L1s in the hippocampus, and in several regions of adult human brains, when compared to the copy number of endogenous L1s in heart or liver genomic DNAs from the same donor. These data suggest that de novo L1 retrotransposition events may occur in the human brain and, in principle, have the potential to contribute to individual somatic mosaicism.


Assuntos
Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Retroelementos/genética , Regiões 5' não Traduzidas/genética , Encéfalo/citologia , Linhagem Celular , Imunoprecipitação da Cromatina , Metilação de DNA , Feto/citologia , Dosagem de Genes , Humanos , Reação em Cadeia da Polimerase
17.
Facial Plast Surg ; 31(2): 128-33, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25958898

RESUMO

Dynamic facial reanimation is the gold standard treatment for a paralyzed face. Over the last century, multiple nerves have been utilized for grafting to the facial nerve in an attempt to produce improved movement. However, in recent years, the use of cross facial nerve grafting with a second stage gracilis free flap has gained popularity due to the ability to generate a spontaneous smile and facial movement. Preoperative history taking and careful examination, as well as pre-surgical planning, are imperative to whether cross facial nerve grafting with a second stage gracilis free flap is appropriate for the patient. A sural nerve graft is ideal given the accessibility of the nerve, the length, as well as the reliability and ease of the nerve harvest. The nerve can be harvested using a small incision, which leaves the patient with minimal post operative morbidity. In this chapter, we highlight the pearls and pitfalls of cross facial nerve grafting.


Assuntos
Nervo Facial/cirurgia , Paralisia Facial/cirurgia , Músculo Esquelético/transplante , Transferência de Nervo , Procedimentos de Cirurgia Plástica/métodos , Nervo Sural/cirurgia , Retalhos de Tecido Biológico , Humanos , Anamnese , Músculo Esquelético/inervação , Planejamento de Assistência ao Paciente , Exame Físico , Procedimentos de Cirurgia Plástica/efeitos adversos , Coleta de Tecidos e Órgãos/métodos
18.
Proc Natl Acad Sci U S A ; 108(51): 20382-7, 2011 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-22159035

RESUMO

Long interspersed element-1 (L1) retrotransposons compose ∼20% of the mammalian genome, and ongoing L1 retrotransposition events can impact genetic diversity by various mechanisms. Previous studies have demonstrated that endogenous L1 retrotransposition can occur in the germ line and during early embryonic development. In addition, recent data indicate that engineered human L1s can undergo somatic retrotransposition in human neural progenitor cells and that an increase in human-specific L1 DNA content can be detected in the brains of normal controls, as well as in Rett syndrome patients. Here, we demonstrate an increase in the retrotransposition efficiency of engineered human L1s in cells that lack or contain severely reduced levels of ataxia telangiectasia mutated, a serine/threonine kinase involved in DNA damage signaling and neurodegenerative disease. We demonstrate that the increase in L1 retrotransposition in ataxia telangiectasia mutated-deficient cells most likely occurs by conventional target-site primed reverse transcription and generate either longer, or perhaps more, L1 retrotransposition events per cell. Finally, we provide evidence suggesting an increase in human-specific L1 DNA copy number in postmortem brain tissue derived from ataxia telangiectasia patients compared with healthy controls. Together, these data suggest that cellular proteins involved in the DNA damage response may modulate L1 retrotransposition.


Assuntos
Proteínas de Ciclo Celular/genética , Proteínas de Ligação a DNA/genética , Elementos Nucleotídeos Longos e Dispersos/genética , Células-Tronco Neurais/citologia , Proteínas Serina-Treonina Quinases/genética , Retroelementos/genética , Proteínas Supressoras de Tumor/genética , Animais , Proteínas Mutadas de Ataxia Telangiectasia , Linhagem Celular , Reparo do DNA , Endonucleases/metabolismo , Fibroblastos/citologia , Proteínas de Fluorescência Verde/metabolismo , Humanos , Camundongos , Camundongos Transgênicos , Transdução de Sinais
19.
Facial Plast Surg Clin North Am ; 32(4): 565-583, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39341674

RESUMO

Autologous cartilage can be easily and safely harvested as a reliable source of cartilage in rhinoplasty through a small, well-hidden incision. Rib cartilage can be utilized during a primary rhinoplasty when there is insufficient cartilage from the septum or often in revisional nasal surgeries where the initial septal cartilage has previously been used or removed. Rib cartilage carving can be done on a cutting board prior to the beginning of the rhinoplasty in order to allow time for the cartilage to present any warping while it is soaked in saline. Overall autologous rib cartilage is a good source of copious and often good quality cartilage.


Assuntos
Cartilagem Costal , Rinoplastia , Transplante Autólogo , Rinoplastia/métodos , Humanos , Cartilagem Costal/transplante , Septo Nasal/cirurgia , Coleta de Tecidos e Órgãos/métodos
20.
Ophthalmic Plast Reconstr Surg ; 29(3): 220-4, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23503060

RESUMO

PURPOSE: An age-related depression can develop over the superonasal orbital rim, which the authors have called the "orbitoglabellar groove (OGG)." It is, in part, related to volume loss over the rim as is seen at the lower eyelid/cheek interface (nasojugal groove). An upper eyelid fat pedicle can be transposed over the OGG during standard upper blepharoplasty surgery to reduce this depression. METHODS: The charts of patients who underwent fat transposition to the OGG during upper blepharoplasty over a 20-month period (2010-2012) are retrospectively reviewed. Only primary eyelid surgery patients are included in the study. The procedure, its results, and complications are presented. RESULTS: Seventeen patients are included in this study. Eleven patients (65%) are women and 6 (35%) patients are men. The average patient age is 56 years (range 47-80 years), and the average follow up is 10 months (6-14 months). Two patients (12%) developed a transient induration over the transposed fat pedicle in the postoperative period which resolved with a combination 5-fluorouracil/kenalog injection. There were no cases of postoperative infection, prolonged swelling, motility disturbance, diplopia, or eyelid malposition. Clinical effacement of the OGG was noted in all cases, and physician and patient assessment of surgical results are equally good. CONCLUSIONS: The OGG is an involutional periorbital hollow present over the superonasal orbital rim. The depression can be reduced with native eyelid fat transposition during upper blepharoplasty in a similar way that lower blepharoplasty with fat repositioning effaces the nasojugal groove. The learning curve for the procedure is quick, especially for those who have experience with its lower eyelid counterpart.


Assuntos
Tecido Adiposo/transplante , Blefaroplastia , Pálpebras/cirurgia , Órbita/cirurgia , Envelhecimento da Pele/fisiologia , Idoso , Idoso de 80 Anos ou mais , Estética , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ritidoplastia , Retalhos Cirúrgicos , Técnicas de Sutura
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