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Progressive Proximal-to-Distal Reduction in Expression of the Tight Junction Complex in Colonic Epithelium of Virally-Suppressed HIV+ Individuals
Effective antiretroviral therapy (ART) dramatically reduces AIDS-related complications, yet the life expectancy of long-term ART-treated HIV-infected patients remains shortened compared to that of uninfected controls, due to increased risk of non-AIDS related morbidities. Many propose that these complications result from translocated microbial products from the gut that stimulate systemic inflammation--a consequence of increased intestinal paracellular permeability that persists in this population. Concurrent intestinal immunodeficiency and structural barrier deterioration are postulated to drive microbial translocation, and direct evidence of intestinal epithelial breakdown has been reported in untreated pathogenic SIV infection of rhesus macaques. To assess and characterize the extent of epithelial cell damage in virally-suppressed HIV-infected patients, we analyzed intestinal biopsy tissues for changes in the epithelium at the cellular and molecular level. The intestinal epithelium in the HIV gut is grossly intact, exhibiting no decreases in the relative abundance and packing of intestinal epithelial cells. We found no evidence for structural and subcellular localization changes in intestinal epithelial tight junctions (TJ), but observed significant decreases in the colonic, but not terminal ileal, transcript levels of TJ components in the HIV+ cohort. This result is confirmed by a reduction in TJ proteins in the descending colon of HIV+ patients. In the HIV+ cohort, colonic TJ transcript levels progressively decreased along the proximal-to-distal axis. In contrast, expression levels of the same TJ transcripts stayed unchanged, or progressively increased, from the proximal-to-distal gut in the healthy controls. Non-TJ intestinal epithelial cell-specific mRNAs reveal differing patterns of HIV-associated transcriptional alteration, arguing for an overall change in intestinal epithelial transcriptional regulation in the HIV colon. These findings suggest that persistent intestinal epithelial dysregulation involving a reduction in TJ expression is a mechanism driving increases in colonic permeability and microbial translocation in the ART-treated HIV-infected patient, and a possible immunopathogenic factor for non-AIDS related complications.
Journal Article
The unwinding of the miracle : a memoir of life, death, and everything that comes after
\"Born blind in Vietnam, Julie Yip-Williams narrowly escaped euthanasia by her grandmother, only to then flee the political upheaval of the late 1970s with her family. Loaded into a rickety boat with three hundred other refugees, Julie made it to Hong Kong and, ultimately, America, where a surgeon at UCLA gave her partial sight. Against all odds, she became a Harvard-educated lawyer, with a husband, a family, a life. Then, at age thirty-seven, with two little girls at home, Julie was diagnosed with terminal metastatic colon cancer, and a different journey began. The Unwinding of the Miracle is the story of a vigorous life refracted through the prism of imminent death. Motherhood, marriage, ambition, love, wanderlust, tennis, grief, jealousy, anger, comfort, pain, disease--there is simply nothing this book is not about. Growing out of a blog Julie has kept through the past four years of her life (undertaken because she couldn't find the guidance she needed through her disease), this is the story of a life lived so well, and cut too short. It is inspiring and instructive, delightful and shattering. It is a book of indelible moments, seared deep. With glorious humor, beautiful and bracing honesty, and the cleansing power of well-deployed anger, Julie Yip-Williams has set the stage for her lasting legacy and one final miracle: the story of her life\"-- Provided by publisher.
Book
Denali : a man, a dog, and the friendship of a lifetime
\"Denali is the story of the friendship between the author, Ben Moon, and his dog Denali as they traveled the American West, and of how Denali supported the author as he battled cancer, and how the author dealt with the cancer illness and death of his dog\"-- Provided by publisher.
Book
Intestinal ultrasound for monitoring therapeutic response in patients with ulcerative colitis: results from the TRUST&UC study
ObjectiveProspective evaluation of intestinal ultrasound (IUS) for disease monitoring of patients with ulcerative colitis (UC) in routine medical practice.DesignTRansabdominal Ultrasonography of the bowel in Subjects with IBD To monitor disease activity with UC (TRUST&UC) was a prospective, observational study at 42 German inflammatory bowel disease-specialised centres representing different care levels. Patients with a diagnosis of a proctosigmoiditis, left-sided colitis or pancolitis currently in clinical relapse (defined as Short Clinical Colitis Activity Index ≥5) were enrolled consecutively. Disease activity and vascularisation within the affected bowel wall areas were assessed by duplex/Colour Doppler ultrasonography.ResultsAt baseline, 88.5% (n=224) of the patients had an increased bowel wall thickness (BWT) in the descending or sigmoid colon. Even within the first 2 weeks of the study, the percentage of patients with an increased BWT in the sigmoid or descending colon decreased significantly (sigmoid colon 89.3%–38.6%; descending colon 83.0%–42.9%; p<0.001 each) and remained low at week 6 and 12 (sigmoid colon 35.4% and 32.0%; descending colon 43.4% and 37.6%; p<0.001 each). Normalisation of BWT and clinical response after 12 weeks of treatment showed a high correlation (90.5% of patients with normalised BWT had symptomatic response vs 9.5% without symptomatic response; p<0.001).ConclusionsIUS may be preferred in general practice in a point-of-care setting for monitoring the disease course and for assessing short-term treatment response. Our findings give rise to the assumption that monitoring BWT alone has the potential to predict the therapeutic response, which has to be verified in future studies.
Journal Article
Happy gut cookbook : good food for sensitive stomachs
\"Digestive disorders such as IBS and Crohn's disease are rapidly increasing, and many sufferers are struggling with their symptoms ... The low-FODMAP diet eliminates common carbohydrates that may trigger a reaction, but getting rid of such everyday staples as onions, garlic, milk, and bread can make cooking challenging. [This book] features more than 80 ... recipes that are extremely low in FODMAP but tempting enough for the entire family to enjoy\"--Amazon.com.
Book
Demystifying Colons and Semicolons
Most people were taught the uses of the colon inadequately, if at all. Very few were ever taught how to use the semicolon; as a result, they tend to shy away from using it at all. But the proper use of these two punctuation marks can help writers better control a reader's reading experience. For both the colon and the semicolon, the grammatical rule states that what precedes those punctuation marks must be able to stand by itself as a complete sentence. By giving syntactic closure to the preceding main clause, the colon and semicolon are able to create a stress position in the middle of a sentence.
Journal Article