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Dominguez-Bello M.G.,University of Puerto Rico at San Juan | Blaser M.J.,NY | Blaser M.J.,New York Harbor Veterans Affairs Medical Center | Blaser M.J.,New York University | And 3 more authors.
Gastroenterology | Year: 2011

Little was known about the development of the gastrointestinal (GI) tract microbiota, until recently, because of difficulties in obtaining sufficient sequence information from enough people or time points. Now, with decreased costs of DNA sequencing and improved bioinformatic tools, we can compare GI tract bacterial communities among individuals, of all ages from infancy to adulthood. Some key recent findings are that the initial bacterial community, even in the GI tract, depends strongly on delivery mode; that the process of early development of the microbiota is highly unstable and idiosyncratic; that the microbiota differs considerably among children from different countries; and that older adults have substantially different GI tract communities than younger adults, indicating that the GI tract microbiota can change throughout life. We relate these observations to different models of evolution including the evolution of senescence and suggest that probiotics be selected based on patient age. Studies of the microbiota in older people might tell us which probiotics could increase longevity. Drug metabolism varies among individuals with different microbial communities, so age- and region-specific clinical trials are required to ensure safety and efficacy. © 2011 AGA Institute.

Pantoja J.L.,University of California at San Francisco | Ge L.,University of California at San Francisco | Ge L.,Veterans Affairs Medical Center | Zhang Z.,Veterans Affairs Medical Center | And 7 more authors.
Annals of Thoracic Surgery | Year: 2014

Background. The role of posterior papillary muscle nchoring (PPMA) in the management of chronic schemic mitral regurgitation (CIMR) is controversial. e studied the effect of anchoring point direction and elocation displacement on left ventricular (LV) egional myofiber stress and pump function.Methods. Previously described finite element models f sheep 16 weeks after posterolateral myocardial nfarction (MI) were used. True-sized mitral annuloplasty MA) ring insertion plus different PPM nchoring techniques were simulated. Anchoring points ested included both commissures and the central nterior mitral annulus; relocation displacement varied rom 10% to 40% of baseline diastolic distance from the PM to the anchor points on the annulus. For each econstruction scenario, myofiber stress in the MI, order zone, and remote myocardium as well as pump unction were calculated.Results. PPMA caused reductions in myofiber stress at nd-diastole and end-systole in all regions of the left entricle that were proportional to the relocation displacement. lthough stress reduction was greatest in the MI region, t also occurred in the remote region. The maximum 0% displacement caused a slight reduction in LV pump unction. However, with the correction of regurgitation by A plus PPMA, there was an overall increase in forward troke volume. Finally, anchoring point direction had no ffect on myofiber stress or pump functionConclusions. PPMA reduces remote myofiber stress, hich is proportional to the absolute distance of relocation nd independent of anchoring point. Aggressive use f PPMA techniques to reduce remote myofiber stress ay accelerate reverse LV remodeling without impairing V function. © 2014 by The Society of Thoracic Surgeons.

Mahana D.,NYU Langone Medical Center | Trent C.M.,NYU Langone Medical Center | Kurtz Z.D.,NYU Langone Medical Center | Bokulich N.A.,NYU Langone Medical Center | And 10 more authors.
Genome Medicine | Year: 2016

Background: Obesity, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD) are serious health concerns, especially in Western populations. Antibiotic exposure and high-fat diet (HFD) are important and modifiable factors that may contribute to these diseases. Methods: To investigate the relationship of antibiotic exposure with microbiome perturbations in a murine model of growth promotion, C57BL/6 mice received lifelong sub-therapeutic antibiotic treatment (STAT), or not (control), and were fed HFD starting at 13weeks. To characterize microbiota changes caused by STAT, the V4 region of the 16S rRNA gene was examined from collected fecal samples and analyzed. Results: In this model, which included HFD, STAT mice developed increased weight and fat mass compared to controls. Although results in males and females were not identical, insulin resistance and NAFLD were more severe in the STAT mice. Fecal microbiota from STAT mice were distinct from controls. Compared with controls, STAT exposure led to early conserved diet-independent microbiota changes indicative of an immature microbial community. Key taxa were identified as STAT-specific and several were found to be predictive of disease. Inferred network models showed topological shifts concurrent with growth promotion and suggest the presence of keystone species. Conclusions: These studies form the basis for new models of type 2 diabetes and NAFLD that involve microbiome perturbation. © 2016 Mahana et al.

Dalal R.P.,NYU Langone Medical Center | Goldfarb D.S.,New York Harbor Veterans Affairs Medical Center
Nature Reviews Nephrology | Year: 2011

Several well-documented outbreaks of melamine poisoning have occurred in both animals and humans during the past 7 years, which led to the identification of melamine and cyanuric acid as nephrotoxins. This Review provides an overview of the known experimental and observational data (including toxicology, epidemiology, and pathology) concerning melamine contamination of foodstuffs, both alone and in combination with cyanuric acid. The various renal effects of ingestion of these compounds in both animals and humans are described, and a hypothesis on the mechanism of formation of melamine-based kidney stones is presented. Finally, the public health measures taken in the wake of the melamine contamination events are discussed. © 2011 Macmillan Publishers Limited. All rights reserved.

Carrick R.,University of Vermont | Ge L.,University of California at San Francisco | Ge L.,The Surgical Center | Lee L.C.,University of California at San Francisco | And 11 more authors.
Annals of Thoracic Surgery | Year: 2012

Background: We sought to determine regional myofiber stress after Coapsys device (Myocor, Inc, Maple Grove, MN) implantation using a finite element model of the left ventricle (LV). Chronic ischemic mitral regurgitation is caused by LV remodeling after posterolateral myocardial infarction. The Coapsys device consists of a single trans-LV chord placed below the mitral valve such that when tensioned it alters LV shape and decreases chronic ischemic mitral regurgitation. Methods: Finite element models of the LV were based on magnetic resonance images obtained before (preoperatively) and after (postoperatively) coronary artery bypass grafting with Coapsys implantation in a single patient. To determine the effect of Coapsys and LV before stress, virtual Coapsys was performed on the preoperative model. Diastolic and systolic material variables in the preoperative, postoperative, and virtual Coapsys models were adjusted so that model LV volume agreed with magnetic resonance imaging data. Chronic ischemic mitral regurgitation was abolished in the postoperative models. In each case, myofiber stress and pump function were calculated. Results: Both postoperative and virtual Coapsys models shifted end-systolic and end-diastolic pressure-volume relationships to the left. As a consequence and because chronic ischemic mitral regurgitation was reduced after Coapsys, pump function was unchanged. Coapsys decreased myofiber stress at end-diastole and end-systole in both the remote and infarct regions of the myocardium. However, knowledge of Coapsys and LV prestress was necessary for accurate calculation of LV myofiber stress, especially in the remote zone. Conclusions: Coapsys decreases myofiber stress at end-diastole and end-systole. The improvement in myofiber stress may contribute to the long-term effect of Coapsys on LV remodeling. © 2012 The Society of Thoracic Surgeons.

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