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1.
Diabetes ; 71(6): 1170-1181, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35290440

RESUMO

Preclinical studies reveal maternal exercise as a promising intervention to reduce the transmission of multigenerational metabolic dysfunction caused by maternal obesity. The benefits of maternal exercise on offspring health may arise from multiple factors and have recently been shown to involve DNA demethylation of critical hepatic genes leading to enhanced glucose metabolism in offspring. Histone modification is another epigenetic regulator, yet the effects of maternal obesity and exercise on histone methylation in offspring are not known. Here, we find that maternal high-fat diet (HFD; 60% kcal from fat) induced dysregulation of offspring liver glucose metabolism in C57BL/6 mice through a mechanism involving increased reactive oxygen species, WD repeat-containing 82 (WDR82) carbonylation, and inactivation of histone H3 lysine 4 (H3K4) methyltransferase leading to decreased H3K4me3 at the promoters of glucose metabolic genes. Remarkably, the entire signal was restored if the HFD-fed dams had exercised during pregnancy. WDR82 overexpression in hepatoblasts mimicked the effects of maternal exercise on H3K4me3 levels. Placental superoxide dismutase 3 (SOD3), but not antioxidant treatment with N-acetylcysteine was necessary for the regulation of H3K4me3, gene expression, and glucose metabolism. Maternal exercise regulates a multicomponent epigenetic system in the fetal liver resulting in the transmission of the benefits of exercise to offspring.


Assuntos
Obesidade Materna , Efeitos Tardios da Exposição Pré-Natal , Animais , Proteínas Cromossômicas não Histona/metabolismo , Dieta Hiperlipídica , Feminino , Glucose/metabolismo , Histonas/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Placenta/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo
2.
Cell Metab ; 33(5): 939-956.e8, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33770509

RESUMO

Poor maternal diet increases the risk of obesity and type 2 diabetes in offspring, adding to the ever-increasing prevalence of these diseases. In contrast, we find that maternal exercise improves the metabolic health of offspring, and here, we demonstrate that this occurs through a vitamin D receptor-mediated increase in placental superoxide dismutase 3 (SOD3) expression and secretion. SOD3 activates an AMPK/TET signaling axis in fetal offspring liver, resulting in DNA demethylation at the promoters of glucose metabolic genes, enhancing liver function, and improving glucose tolerance. In humans, SOD3 is upregulated in serum and placenta from physically active pregnant women. The discovery of maternal exercise-induced cross talk between placenta-derived SOD3 and offspring liver provides a central mechanism for improved offspring metabolic health. These findings may lead to novel therapeutic approaches to limit the transmission of metabolic disease to the next generation.


Assuntos
Exercício Físico , Placenta/metabolismo , Superóxido Dismutase/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Células Cultivadas , Desmetilação do DNA , Dieta Hiperlipídica , Feminino , Hepatócitos/citologia , Hepatócitos/metabolismo , Humanos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oxigenases de Função Mista/genética , Oxigenases de Função Mista/metabolismo , Gravidez , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Receptores de Calcitriol/metabolismo , Transdução de Sinais , Superóxido Dismutase/genética
3.
Plast Reconstr Surg Glob Open ; 8(5): e2830, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-33154872

RESUMO

Autologous fat transfer-also referred to as fat grafting-has been reported to provide beneficial effects to overlying scar and skin. Despite procedural frequency, there is a paucity of high-level evidence guiding the surgeon in technique, patient selection, and efficacy. METHODS: A multicenter, double-blinded, randomized, internally placebo-controlled trial was performed with an aim to qualitatively and quantitatively evaluate the impact of autologous fat transfer on the quality of overlying scar tissue. Fat-grafted scars were evaluated and compared with paired, saline-injected "control" scars. Subjective and objective metrics were evaluated in treated sites for 12 months after treatment. RESULTS: Blinded qualitative results demonstrated a statistically significant improvement in scar quality over time in fat-grafted scars. However, these improvements were not found to be statistically different from changes noted in scars treated with saline. In addition, objective metrics did not statistically differ between saline-injected and autologous fat-grafted scars. CONCLUSIONS: Our results demonstrate that autologous fat grafting can improve the qualitative profile of a scar from both the patient and observer perspectives. However, there was no difference in improvement when compared with scars that were treated with saline in a randomized and blinded fashion. These results demonstrate that any improvements in scar quality related to fat grafting are also achieved using saline and suggest that mechanisms other than cell activity may be at play. Additional randomized, blinded, placebo-controlled trials are required to either corroborate or contest the putative beneficial effect(s) of adipose tissue on scar remodeling.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32111717

RESUMO

OBJECTIVE: Poor maternal and paternal environments increase the risk for obesity and diabetes in offspring, whereas maternal and paternal exercise in mice can improve offspring metabolic health. We determined the effects of combined maternal and paternal exercise on offspring health and the effects of parental exercise on offspring pancreas phenotype, a major tissue regulating glucose homeostasis. RESEARCH DESIGN AND METHODS: Breeders were high fat fed and housed±running wheels before breeding (males) and before and during gestation (females). Offspring groups were: both parents sedentary (Sed); maternal exercise only (Mat Ex); paternal exercise only (Pat Ex); and maternal+paternal exercise (Mat+Pat Ex). Offspring were sedentary, chow fed, and studied at weaning, 12, 20 and 52 weeks. RESULTS: While there was no effect of parental exercise on glucose tolerance at younger ages, at 52 weeks, offspring of Mat Ex, Pat Ex and Mat+Pat Ex displayed lower glycemia and improved glucose tolerance. The greatest effects were in offspring from parents that both exercised (Mat+Pat Ex). Offspring from Mat Ex, Pat Ex, and Mat+Pat Ex had decreased beta cell size, whereas islet size and beta cell mass only decreased in Mat+Pat Ex offspring. CONCLUSIONS: Maternal and paternal exercise have additive effects to improve glucose tolerance in offspring as they age, accompanied by changes in the offspring endocrine pancreas. These findings have important implications for the prevention and treatment of type 2 diabetes.


Assuntos
Glicemia/análise , Pai , Homeostase/fisiologia , Células Secretoras de Insulina/metabolismo , Mães , Fenótipo , Condicionamento Físico Animal/métodos , Animais , Diabetes Mellitus Tipo 2/prevenção & controle , Dieta Hiperlipídica , Feminino , Teste de Tolerância a Glucose , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/prevenção & controle , Gravidez , Comportamento Sedentário , Desmame
5.
Aesthet Surg J ; 40(11): 1208-1215, 2020 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-31680144

RESUMO

BACKGROUND: A variety of regional nerve blocks have been utilized in abdominoplasty procedures, including transversus abdominis plane (TAP), intercostal, rectus sheath (RS), pararectus + ilioinguinal/iliohypogastric, quadratus lumborum, and paravertebral blocks. No consensus exists regarding the most effective nerve block modality in optimizing postprocedural comfort levels. OBJECTIVES: The purpose of this systematic review was to explore the efficacy of the various abdominal nerve blocks employed in abdominoplasty surgery and to draw attention to any modality that may be superior in regards to effectiveness and/or administration. METHODS: Utilizing Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review was performed to identify studies that have employed regional nerve blocks in abdominoplasty procedures. Opioid consumption, pain scores, time to ambulation, time in the recovery room, and time to first analgesia request were extracted when available. RESULTS: A total of 191 articles were reviewed, of which 8 met inclusion criteria. The nerve blocks represented included TAP, RS, pararectus + ilioinguinal/iliohypogastric, intercostal, and quadratus lumborum. All modalities were effective in reducing opioid consumption except quadratus lumborum. CONCLUSIONS: TAP, RS, pararectus + ilioinguinal/iliohypogastric, and intercostal regional nerve blocks have been shown to optimize postoperative pain management in abdominoplasty procedures. The existing literature suggests that when studied against one another, TAP is more efficacious than RS and pararectus + ilioinguinal/iliohypogastric. When ultrasound guidance is unavailable, consideration should be given to TAP employing the direct visualization approach.


Assuntos
Abdominoplastia , Bloqueio Nervoso , Músculos Abdominais/cirurgia , Abdominoplastia/efeitos adversos , Analgésicos , Humanos , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle
6.
Diabetes ; 66(8): 2124-2136, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28572303

RESUMO

Poor maternal diet can lead to metabolic disease in offspring, whereas maternal exercise may have beneficial effects on offspring health. In this study, we determined ifmaternal exercise could reverse the detrimental effects of maternal high-fat feeding on offspring metabolism of female mice. C57BL/6 female mice were fed a chow (21%) or high-fat (60%) diet and further divided by housing in static cages or cages with running wheels for 2 weeks prior to breeding and throughout gestation. Females were bred with chow-fed sedentary C57BL/6 males. High fat-fed sedentary dams produced female offspring with impaired glucose tolerance compared with offspring of chow-fed dams throughout their first year of life, an effect not present in the offspring from high fat-fed dams that had trained. Offspring from high fat-fed trained dams had normalized glucose tolerance, decreased fasting insulin, and decreased adiposity. Liver metabolic function, measured by hepatic glucose production in isolated hepatocytes, hyperinsulinemic-euglycemic clamps, liver triglyceride content, and liver enzyme expression, was enhanced in offspring from trained dams. In conclusion, maternal exercise negates the detrimental effects of a maternal high-fat diet on glucose tolerance and hepatocyte glucose metabolism in female offspring. The ability of maternal exercise to improve the metabolic health of female offspring is important, as this intervention could combat the transmission of obesity and diabetes to subsequent generations.


Assuntos
Intolerância à Glucose/fisiopatologia , Glucose/metabolismo , Fenômenos Fisiológicos da Nutrição Materna , Condicionamento Físico Animal/fisiologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Adiposidade/fisiologia , Animais , Dieta Hiperlipídica/efeitos adversos , Jejum/sangue , Feminino , Técnica Clamp de Glucose , Intolerância à Glucose/etiologia , Intolerância à Glucose/prevenção & controle , Insulina/sangue , Fígado/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Efeitos Tardios da Exposição Pré-Natal/etiologia , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Fatores Sexuais , Triglicerídeos/metabolismo
7.
Ann Plast Surg ; 74 Suppl 4: S218-21, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25978553

RESUMO

BACKGROUND: When composite scalp and calvarial defects with dural or cortical brain exposure are encountered, active infection or indeterminate oncologic margins complicate the timing of scalp reconstruction. The purpose of this study was to evaluate the safety and efficacy of vacuum-assisted closure (VAC) therapy as a temporizing measure in these complex scalp defects with dural or cortical brain exposure and a hostile local wound environment. METHODS: From December 2012 to December 2013, all composite scalp and calvarial defects reconstructed by the senior author (D.S.) were reviewed and 10 cases were identified. Five of these cases were temporized with VAC therapy. The medical records of these patients were reviewed. RESULTS: Five patients (mean age, 66.2 years) with composite scalp and calvarial defects were temporized with VAC therapy. The indications for delay included gross wound infection in 4 patients and an indeterminate intraoperative oncologic margin. The average size of the scalp and calvarial defects measured 123 and 49 cm, respectively. One patient underwent VAC therapy over exposed cortical brain with a dural defect measuring 25 cm. The average time between the initial operation and definitive reconstruction was 4.8 days. The average daily VAC output was 74 mL. Reconstructive methods included 1 free flap, 2 scalp rotational advancement flaps, and readvancement of 2 prior free flaps. At an average follow-up of 32 weeks, 1 patient developed a subcentimeter postoperative wound breakdown that was treated successfully with an incisional VAC. CONCLUSIONS: We found the use of VAC therapy applied directly to the dura or cortical brain as a safe and effective technique for short-term wound temporization in the setting of indeterminate oncologic margins or active infection.


Assuntos
Tratamento de Ferimentos com Pressão Negativa/métodos , Procedimentos de Cirurgia Plástica/métodos , Couro Cabeludo/cirurgia , Crânio/cirurgia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Estudos Retrospectivos , Retalhos Cirúrgicos
8.
Plast Reconstr Surg Glob Open ; 3(3): e327, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25878938

RESUMO

BACKGROUND: The purpose of this study is to assess which personal characteristics and external factors are important contributors to eventual success. METHODS: The authors distributed a survey to all members of the American Association of Plastic Surgeons and asked responders to rate the importance of 10 preselected qualities in contributing to their personal success. Survey outcomes were analyzed across different demographic groups. RESULTS: Of the 580 American Association of Plastic Surgeons members who were surveyed, 295 returned completed surveys. Overall analysis indicates that hard work, compassion, and manual dexterity are the 3 most important attributes. Many significant differences are observed across demographic groups, indicating potential biases among the survey responders. Notably, we find that male surgeons attribute mentorship to success much more so than female surgeons (Column Trend Exact [CTE], P = 0.021), whereas female surgeons are more likely to attribute their success to hard work (CTE, P = 0.023). Similarly, those who have been program directors credit their success to mentoring more so than nonprogram directors (CTE, P < 0.00001). The authors also found that senior surgeons, as measured by years in practice, place greater emphasis on mentoring and career opportunities than younger surgeons (Mantel-Haenszel Trend, P = 0.003 and 0.0009, respectively). It is also interesting to note that individual talent qualities tend to be favored by more senior surgeons and those with more distant ties to academia. CONCLUSION: The authors believe that recognizing the relative importance of such factors, and their associated biases, is essential for the process of selecting and developing future successful plastic surgeons.

9.
J Surg Educ ; 72(1): 8-15, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25218369

RESUMO

OBJECTIVE: Our purpose was to provide a metric by which evaluation criteria are prioritized during resident selection. In this study, we assessed which residency applicant qualities are deemed important by members of the American Association of Plastic Surgeons (AAPS). METHODS: A survey was distributed to all 580 AAPS members, and 295 responded to rate the importance of resident metrics, including measures of competency and personal characteristics. Demographic information, background training, and interaction with residents were also noted. Using SAS v9.2 (SAS Institute, Cary, NC), outcomes were analyzed across demographic groups with column trend exact (CTE) test for ordinal variables, Mantel-Haenszel trend test for interval variables, and Fisher exact test for discrete variables. RESULTS: Regarding competency metrics, letters of recommendation from known sources is the most important factor, whereas letters from unknown sources ranks the lowest. Character evaluations identified honesty as the most desirable trait; dishonesty was the most despised. Across demographic groups, academic surgeons and program directors value letters from known sources more than nonacademicians or nonprogram directors (CTE p = 0.005 and 0.002, respectively). Academicians and current program directors regard research more highly than their counterparts do (CTE p = 0.022 and 0.022, respectively). Currently, practicing surgeons, academicians, and program directors value hard work more than others (CTE p = 0.008, 0.033, and 0.029, respectively). Program directors emphasize maturity and patient commitment and are less tolerant of narcissism (CTE p = 0.002, 0.005, and 0.003, respectively). Lastly, academic surgeons and program directors look more favorably upon strong team players (CTE p < 0.00001 and p = 0.008, respectively), but less so over time (Mantel-Haenszel trend p = 0.006). CONCLUSIONS: We have examined applicant metrics that were deemed important by AAPS members and assessed their demographic interpretation. We hope this article provides a framework for plastic surgery resident selection and a guide for applicants to ascertain which qualities are highly regarded by programs. Although these attributes are highly desirable, future studies could identify if they are predictive of successful and productive plastic surgery residencies and careers.


Assuntos
Internato e Residência , Seleção de Pessoal , Cirurgia Plástica/educação , Adulto , Atitude do Pessoal de Saúde , Competência Clínica , Comunicação , Avaliação Educacional , Humanos , Personalidade , Estudantes de Medicina/psicologia
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