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Lamont R.J.,University of Louisville | Hajishengallis G.,Penn Medicine
Trends in Molecular Medicine | Year: 2015

Uncontrolled inflammation of the periodontal area may arise when complex microbial communities transition from a commensal to a pathogenic entity. Communication among constituent species leads to polymicrobial synergy between metabolically compatible organisms that acquire functional specialization within the developing community. Keystone pathogens, even at low abundance, elevate community virulence, and the resulting dysbiotic community targets specific aspects of host immunity to further disable immune surveillance while promoting an overall inflammatory response. Inflammophilic organisms benefit from proteinaceous substrates derived from inflammatory tissue breakdown. Inflammation and dysbiosis reinforce each other, and the escalating environmental changes further select for a pathobiotic community. We have synthesized the polymicrobial synergy and dysbiotic components of the process into a new model for inflammatory diseases. © 2014 Elsevier Ltd. Source


Rogers A.M.,Penn Medicine
Surgery for Obesity and Related Diseases | Year: 2010

Background: Patients undergoing adjustable gastric banding can develop clinically apparent alterations in esophageal motility. There is little data on how such patients do after band removal and revision to other bariatric operations. One article in the literature describes long term manometric evidence of dysmotility in a band patient converted to gastric bypass. Methods: 132 patients undergoing placement of an adjustable gastric band by a single surgeon in a university hospital setting were followed over a two year period. 15 (11%) developed unrelenting dysphagia, reflux and regurgitation despite conservative management including complete deflation, and were revised to gastric bypass. Pre-revision contrast studies demonstrated esophageal dysmotility in all patients. The first seven were converted in a staged fashion, with a period of six to eight weeks between band removal and gastric bypass. During this time, motility was again studied to confirm a return to normal. The last eight were converted at the time of band removal and motility was restudied after gastric bypass. Results: Esophageal motility normalized radiologically after band removal and remained normal after conversion to bypass in all patients. Symptoms of dysphagia similarly resolved. The revisional complication rate was acceptable. Conclusion: The presence of a gastric band may be sufficient in some patients to bring about esophageal dysmotility. However, many will bring this about through forced eating against the band. When the band is poorly tolerated and further weight loss is required, such patients can safely convert to gastric bypass and can expect a return to normal motility. © 2010 American Society for Metabolic and Bariatric Surgery. Source


Noninvasive imaging tools have been the standard in mummy studies for several decades focusing primarily on CT scan technology. Although magnetic resonance imaging (MRI) has been attempted on mummified tissues on numerous occasions these have met with varying degrees of success. The basic physics of MRI are reviewed here with an emphasis on how the physics limit the success of MRI in mummified tissues. Adjusting MRI parameters can enhance the images produced with a summary table that considers the effect of adjustments within these parameters. Several mummies with varying methods of preservation have been included in this study and MRI images presented and the results are critically assessed. MRI can generate basic images in most tissues even when significantly desiccated. Using an understanding of the essentials of MRI physics, with the adjustment of MRI parameters, the data acquisition process can be enhanced to create the best possible images. When successfully applied, MRI generated images can allow for the resolution of soft tissue differences, especially of collapsed internal organ masses, even in dehydrated mummies that are much less effectively rendered in CT scans. © 2015 Wiley Periodicals, Inc. Source


Chen G.,Penn Medicine
Pharmacogenetics and genomics | Year: 2012

Trans-3'-Hydroxycotinine (3HC) and its glucuronide are major nicotine metabolites excreted in the urine of smokers and other tobacco users. Although several members of the UDP-glucuronosyltransferase (UGT) family of enzymes were previously shown to be active in catalyzing the formation of 3HC and its glucuronide, a comprehensive screening of all known human UGT1A and 2B enzymes for glucuronidation activity against 3HC was not previously performed. In the present study, human liver microsomes (HLM), eight UGT1A and six UGT2B enzymes were screened for activity against 3HC. UGT2B17 exhibited the highest O-glucuronidation activity, exhibiting a four-fold lower (P<0.005) KM (8.3 mmol/l) compared with that observed for UGTs 1A9 (35 mmol/l) or 2B7 (31 mmol/l) and a KM smaller compared with that observed for human liver microsomes (HLM; 26 mmol/l). The KM for 3HC-O-Gluc formation was 3.1-fold lower (P<0.0005) in HLM from male participants exhibiting the wild-type genotype UGT2B17 (*1/*1) compared with that in HLM from participants homozygous for the UGT2B17 deletion genotype [UGT2B17 (*2/*2)]. Both UGTs 2B10 and 1A4 exhibited 3HC-N-Gluc formation activity, with UGT2B10 exhibiting a four-fold lower (P<0.05) KM (13 mmol/l) compared with that observed for UGT1A4 (57 mmol/l) and, which was similar to the KM observed in HLM (14 mmol/l). There was 91 (P<0.0001) and 39% (P<0.001) decreases in the 3HC-N-Gluc formation activities in HLM from participants with the UGT2B10 (*2/*2) and UGT2B10 (*1/*2) genotypes, respectively, compared with that of HLM from participants with the wild-type UGT2B10 (*1/*1) genotype. These results suggest that UGT2B17 and UGT2B10 play key roles in the glucuronidation of 3HC in the human liver and that functional polymorphisms in UGT2B17 and UGT2B10 are associated with significantly reduced glucuronidation activities against 3HC. Source


George D.R.,Penn Medicine | Whitehouse P.J.,Case Western Reserve University
Gerontologist | Year: 2011

In the therapeutic void created by over 20 failed Alzheimer's disease drugs during the past decade, a new marketplace of "brain fitness" technology products has emerged. Ranging from video games and computer software to mobile phone apps and hand-held devices, these commercial products promise to maintain and enhance the memory, concentration, visual and spatial skills, verbal recall, and executive functions of individual users. It is instructive to view these products as sociocultural objects deeply imbued with the values and ideologies of our age; consequently, this article offers a critique of the brain fitness technology marketplace while identifying limitations in the capacity of commercial products to realistically improve cognitive health. A broader conception of brain health is presented, going beyond the reductionism of the commercial brain fitness marketplace and asking how our most proximate relationships and local communities can play a role in supporting cognitive and psychosocial well-being. This vision is grounded in recent experiences at The Intergenerational School in Cleveland, OH, a multigenerational community-oriented learning environment that is implementing brain fitness technology in novel ways. © 2011 The Author. Source

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