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BACKGROUND: While general population studies have demonstrated a relationship between cigarette smoking and weight loss, this association is not well established among the bariatric patient population. Given that bariatric patients are inherently weight-concerned, understanding the effects of smoking on postoperative weight loss is essential. We examined the association of preoperative smoking, postoperative smoking and changes in smoking status with weight loss after bariatric surgery. In addition, we examined the association of changes in smoking status with subjective indices of patient satisfaction while controlling for weight loss. METHODS: Retrospective chart review of patients who underwent Sleeve Gastrectomy or Roux-en-Y Gastric Bypass for weight loss at a single institution between August 2000 and November 2017. Additional follow up was obtained by telephone survey. Statistical analysis utilized multivariate logistical regressions. RESULTS: Our study included 512 patients. Majority were female (n = 390, 76.2%) and underwent laparoscopic Roux-en-Y gastric bypass (n = 362, 70.7%). Average age was 46.8 years and average follow up was 6.99 years. Preoperative, postoperative and changes in smoking status were not significantly associated with weight loss. Former smokers were significantly more likely to report postoperative satisfaction with self-overall OR 10.62 (p < 0.01), satisfaction with postoperative outcomes OR 4.18 (p = 0.02), and improvement in quality of life OR 4.05 (p = 0.04) compared to continued smokers independent of weight loss. No difference in rates of satisfaction were found between former smokers and never smokers. Smoking cessation and weight loss were independently predictive of positive responses to these satisfaction indices. CONCLUSIONS: We found no association between preoperative smoking, postoperative smoking or changes in smoking status with postoperative weight loss. Smoking cessation was associated with patient satisfaction and improvement in quality of life compared to continued smokers. Smoking cessation and postoperative weight loss were independently predictive of increased patient satisfaction.
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Cirurgia Bariátrica , Derivação Gástrica , Laparoscopia , Obesidade Mórbida , Feminino , Gastrectomia , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/cirurgia , Satisfação do Paciente , Qualidade de Vida , Estudos Retrospectivos , Fumar , Redução de PesoRESUMO
For decades, chemists have strived to mimic the intricate design and diverse functions of naturally occurring systems through the bioinspired synthesis of programmable inorganic nanomaterials. The development of thiol-capped gold nanoparticles (AuNPs) has driven advancement in this area; however, although versatile and readily accessible, hybrid AuNPs are rarely atomically precise, which limits control over their surface topology and therefore the study of complex structure-function relationships. Here, we present a bottom-up approach to the systematic assembly of atomically precise hybrid nanoclusters employing a strategy that mimics the synthetic ease with which thiol-capped AuNPs are normally constructed, while producing well-defined covalent nanoscale assemblies with diverse surface topologies. For the first time, using a structurally characterized cluster-based organometallic building block, we demonstrate the systematic synthesis of nanoclusters with multivalent binding capabilities to complex protein targets.
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Ouro/química , Nanopartículas Metálicas/química , Compostos Organometálicos/química , Espectroscopia de Ressonância Magnética/métodos , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
Multivalent protein-protein interactions serve central roles in many essential biological processes, ranging from cell signaling and adhesion to pathogen recognition. Uncovering the rules that govern these intricate interactions is important not only to basic biology and chemistry but also to the applied sciences where researchers are interested in developing molecules to promote or inhibit these interactions. Here we report the synthesis and application of atomically precise inorganic cluster nanomolecules consisting of an inorganic core and a covalently linked densely packed layer of saccharides. These hybrid agents are stable under biologically relevant conditions and exhibit multivalent binding capabilities, which enable us to study the complex interactions between glycosylated structures and a dendritic cell lectin receptor. Importantly, we find that subtle changes in the molecular structure lead to significant differences in the nanomolecule's protein-binding properties. Furthermore, we demonstrate an example of using these hybrid nanomolecules to effectively inhibit protein-protein interactions in a human cell line. Ultimately, this work reveals an intricate interplay between the structural design of multivalent agents and their biological activities toward protein surfaces.
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Nanoestruturas/química , Adesão Celular/efeitos dos fármacos , Moléculas de Adesão Celular/química , Moléculas de Adesão Celular/metabolismo , Engenharia , Proteína gp120 do Envelope de HIV/química , Proteína gp120 do Envelope de HIV/metabolismo , Lectinas Tipo C/química , Lectinas Tipo C/metabolismo , Simulação de Dinâmica Molecular , Ligação Proteica/efeitos dos fármacos , Conformação Proteica , Receptores de Superfície Celular/química , Receptores de Superfície Celular/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
This Viewpoint describes major advances pertaining to perfunctionalized boron clusters in synthesis and their respective applications. The first portion of this work highlights key synthetic methods, allowing one to access a wide range of polyhedral boranes (B4 and B6-B12 cluster cores) that contain exhaustively functionalized vertices. The second portion of this Viewpoint showcases the historical developments in using these molecules for applications ranging from materials science to medicine. Last, we suggest potential new directions for these clusters as they apply to both synthetic methods and applications.
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Anti-apoptosis engineering is an established technique to prolong the viability of mammalian cell cultures used for industrial production of recombinant proteins. However, the effect of overexpressing anti-apoptotic proteins on central carbon metabolism has not been systematically studied. We transfected CHO-S cells to express Bcl-2∆, an engineered anti-apoptotic gene, and selected clones that differed in their Bcl-2∆ expression and caspase activity. (13)C metabolic flux analysis (MFA) was then applied to elucidate the metabolic alterations induced by Bcl-2∆. Expression of Bcl-2Δ reduced lactate accumulation by redirecting the fate of intracellular pyruvate toward mitochondrial oxidation during the lactate-producing phase, and it significantly increased lactate re-uptake during the lactate-consuming phase. This flux redistribution was associated with significant increases in biomass yield, peak viable cell density (VCD), and integrated VCD. Additionally, Bcl-2∆ expression was associated with significant increases in isocitrate dehydrogenase and NADH oxidase activities, both rate-controlling mitochondrial enzymes. This is the first comprehensive (13)C MFA study to demonstrate that expression of anti-apoptotic genes has a significant impact on intracellular metabolic fluxes, especially in controlling the fate of pyruvate carbon, which has important biotechnology applications for reducing lactate accumulation and enhancing productivity in mammalian cell cultures.
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Proteínas Reguladoras de Apoptose/metabolismo , Ácido Láctico/metabolismo , Análise do Fluxo Metabólico/métodos , Proteínas Mitocondriais/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ácido Pirúvico/metabolismo , Transdução de Sinais/fisiologia , Animais , Proteínas Reguladoras de Apoptose/genética , Células CHO , Cricetinae , Cricetulus , Proteínas Mitocondriais/genética , Proteínas Proto-Oncogênicas c-bcl-2/genéticaRESUMO
BACKGROUND: A growing body of evidence has demonstrated racial disparities in bariatric surgery (BS) outcomes. We aimed to investigate the impact of race on postoperative percent excess weight loss (%EWL) and patient satisfaction. METHODS: Single center retrospective study of patients who underwent BS January 2012 to November 2017. Statistical analysis utilized Chi-squared, ANOVA and multivariable regression. RESULTS: A total of 378 patients were included. African American patients lost significantly less weight compared to Caucasian and Hispanic patients (39.0 %EWL, 53.4 %EWL and 52.3 %EWL, respectively). A significant difference remained after adjustment for possible confounders. No difference in postoperative satisfaction was found. CONCLUSIONS: Our study adds to the existing literature demonstrating racial disparities in BS postoperative EWL, despite adjusting for possible confounders, while contributing to the limited literature examining Hispanic patients. Furthermore, we examined an understudied outcome in postoperative patient satisfaction and found no racial disparity despite disparity in EWL.
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Cirurgia Bariátrica , Obesidade Mórbida , Índice de Massa Corporal , Humanos , Obesidade Mórbida/cirurgia , Satisfação do Paciente , Estudos Retrospectivos , Resultado do Tratamento , Redução de PesoRESUMO
BACKGROUND: The association between preoperative weight loss and bariatric surgery outcomes remains unclear. We explored the utility of preoperative weight loss as a predictor of postoperative weight loss success. Additionally, we examined the association of preoperative weight loss with perioperative complication rates. METHODS: Retrospective chart review of patients who underwent primary sleeve gastrectomy or primary Roux-en-Y gastric bypass for weight loss at a single institution between January 2003 and November 2017. Additional follow-up was obtained by a postoperative standardized patient questionnaire. Statistical analysis consisted of bivariate and multivariate logistic regression analysis. RESULTS: Our study included 427 patients. Majority were female (n = 313, 73.3%) and underwent sleeve gastrectomy (n = 261, 61.1%). Average age was 45.6 years, and average follow-up was 6.3 years. Greater preoperative weight loss was associated with decreased length of stay (1.8 vs 1.3 days) in patients who underwent sleeve gastrectomy. Multivariable regression analysis revealed that preoperative weight loss was not associated with postoperative weight loss. CONCLUSIONS: Preoperative weight loss is not predictive of postoperative weight loss success after bariatric surgery. Greater preoperative weight loss was associated with a mild decreased in length of stay but was not associated with a reduction in operative time, overall complication rates, ICU admissions, or intraoperative complications. The inconclusive literature and our findings do not support the medical necessity of weight loss prior to bariatric surgery for the purpose of reducing surgical complications or predicting successful postoperative weight loss success.
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Cirurgia Bariátrica , Derivação Gástrica , Laparoscopia , Obesidade Mórbida , Feminino , Gastrectomia/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Redução de PesoRESUMO
Although postoperative diet modification, exercise, and regular dietitian and surgeon follow-up are often recommended after bariatric surgery (BS), their impact on weight loss is unclear. A Retrospective chart review was conducted for patients who received sleeve gastrectomy or Roux-en-Y gastric bypass (RYGB) between August 2000 and November 2017 with telephone follow-up. Multivariable logistic regression models were used for analyses. There were 514 patients included in our study. Most were female (76.3%), mean age was 46.9 years (Standard Deviation [SD] = 11.8), and mean weight loss was 11.6 (SD = 6.5) BMI points at a mean follow-up of 7 years (SD = 4.3). Current surgeon follow-up OR = 2.08 (P < .01) was positively associated with postoperative weight loss, while current dietitian follow-up=OR .41 (P < .01) was negatively associated. Current weight loss supplement use OR = .45 (P = .03) was associated with reduced willingness to undergo surgery again. Increasing preoperative BMI OR = 1.06 (P = .04) and increasing age OR = 1.04 (P = .02) were associated with improved quality of life (QoL) due to BS. Lack of surgeon follow-up and regular dietician consultation was associated with suboptimal weight loss after BS. Older age was positively associated with improved QoL, while current weight loss supplement use was associated with lower likelihood of undergoing surgery again, both independent of weight loss.
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Cirurgia Bariátrica , Derivação Gástrica , Nutricionistas , Obesidade Mórbida , Cirurgiões , Feminino , Seguimentos , Gastrectomia , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento , Redução de PesoRESUMO
We report a class of perfunctionalized dodecaborate clusters that exhibit high stability towards high concentration electrochemical cycling. These boron clusters afford several degrees of freedom in material design to tailor properties including solubility and redox potential. The exceptional stability of these clusters was demonstrated using a symmetric flow cell setup for electrochemical cycling between two oxidation states for 45 days, with post-run analysis showing negligible decomposition of the active species (<0.1%). To further probe the limits of this system, a prototype redox flow battery with two different cluster materials was used to determine mutual compatibility. This work effectively illustrates the potential of bespoke boron clusters as robust material platform for electrochemical energy conversion and storage.
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We report the discovery that a perhydroxylated dodecaborate cluster ([B12(OH)12]2-) can act as an inorganic polyol, serving as a molecular cross-linker in the synthesis of polyurethane-based materials. We further demonstrate how the inherent robustness of the utilized boron cluster can effectively enhance the thermal stability of the produced polyurethane materials incorporating [B12(OH)12]2- building blocks compared to analogous polymers made from carbon-based polyols. Ultimately, this approach provides a potential route to tune the chemical and physical properties of soft materials through incorporation of polyhedral boron-rich clusters into the polymer network.
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We report a new class of redox-active vertex-differentiated dodecaborate clusters featuring pentafluoroaryl groups. These [B12(OR)11NO2] clusters share several unique photophysical properties with their [B12(OR)12] analogues, while exhibiting significantly higher (+0.5 V) redox potentials. This work describes the synthesis, characterization, and isolation of [B12(O-CH2C6F5)11NO2] clusters in all 3 oxidation states (dianion, radical, and neutral). Reactivity to post-functionalization with thiol species via SNAr on the pentafluoroaryl groups is also demonstrated.
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The majority of biomolecules are intrinsically atomically precise, an important characteristic that enables rational engineering of their recognition and binding properties. However, imparting a similar precision to hybrid nanoparticles has been challenging because of the inherent limitations of existing chemical methods and building blocks. Here we report a new approach to form atomically precise and highly tunable hybrid nanomolecules with well-defined three-dimensionality. Perfunctionalization of atomically precise clusters with pentafluoroaryl-terminated linkers produces size-tunable rigid cluster nanomolecules. These species are amenable to facile modification with a variety of thiol-containing molecules and macromolecules. Assembly proceeds at room temperature within hours under mild conditions, and the resulting nanomolecules exhibit high stabilities because of their full covalency. We further demonstrate how these nanomolecules grafted with saccharides can exhibit dramatically improved binding affinity towards a protein. Ultimately, the developed strategy allows the rapid generation of precise molecular assemblies to investigate multivalent interactions.
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We have developed a fast and efficient route to obtain perfunctionalized ether-linked alkyl and benzyl derivatives of the closo-[B12(OH)12]2- icosahedral dodecaborate cluster via microwave-assisted synthesis. These icosahedral boron clusters exhibit three-dimensional delocalization of the cage-bonding electrons, tunable photophysical properties, and a high degree of stability in air in both solid and solution states. A series of closo-[B12(OR)12]2-, hypocloso-[B12(OR)12]1- and hypercloso-[B12(OR)12]0 clusters have been prepared with reaction times ranging from hours to several minutes. This method is superior to previously reported protocols since it dramatically decreases the reaction times required and eliminates the need for inert atmosphere conditions. The generality of the new microwave-based method has been further demonstrated through the synthesis of several new derivatives, which feature redox potentials up to 0.6 V more positive than previously known B12(OR)12 cluster compounds. We further show how this method can be applied to a one-pot synthesis of hybrid, vertex-differentiated species B12(OR)11(OR) that was formerly accessible only via multi-step reaction sequence.