Parallels between Pathogens and Gluten Peptides in Celiac Sprue

Pathogens are exogenous agents capable of causing disease in susceptible organisms. In celiac sprue, a disease triggered by partially hydrolyzed gluten peptides in the small intestine, the offending immunotoxins cannot replicate, but otherwise have many hallmarks of classical pathogens. First, dietary gluten and its peptide metabolites are ubiquitous components of the modern diet, yet only a small, genetically susceptible fraction of the human population contracts celiac sprue. Second, immunotoxic gluten peptides have certain unusual structural features that allow them to survive the harsh proteolytic conditions of the gastrointestinal tract and thereby interact extensively with the mucosal lining of the small intestine. Third, they invade across epithelial barriers intact to access the underlying gut-associated lymphoid tissue. Fourth, they possess recognition sequences for selective modification by an endogenous enzyme, transglutaminase 2, allowing for in situ activation to a more immunotoxic form via host subversion. Fifth, they precipitate a T cell–mediated immune reaction comprising both innate and adaptive responses that causes chronic inflammation of the small intestine. Sixth, complete elimination of immunotoxic gluten peptides from the celiac diet results in remission, whereas reintroduction of gluten in the diet causes relapse. Therefore, in analogy with antibiotics, orally administered proteases that reduce the host's exposure to the immunotoxin by accelerating gluten peptide destruction have considerable therapeutic potential. Last but not least, notwithstanding the power of in vitro methods to reconstitute the essence of the immune response to gluten in a celiac patient, animal models for the disease, while elusive, are likely to yield fundamentally new systems-level insights

Body Composition, Dietary Intake, and Energy Expenditure After Laparoscopic Roux-en-Y Gastric Bypass and Laparoscopic Vertical Banded Gastroplasty: A Randomized Clinical Trial

OBJECTIVE: To assess body composition, eating pattern, and basal metabolic rate in patients undergoing obesity surgery in a randomized trial. INTRODUCTION: There is limited knowledge regarding how different bariatric surgical techniques function in terms of altering body composition, dietary intake, and basic metabolic rate. METHODS: Non-superobese patients were randomized to laparoscopic Roux-en-Y gastric bypass (LGBP, n = 37) or laparoscopic vertical banded gastroplasty (LVBG, n = 46). Anthropometry, dual-energy x-ray absorptiometry (DEXA), computed tomography (CT), indirect calorimetry, and reported dietary intake were registered prior to and 1 year after surgery. RESULTS: Follow-up rate was 97.6%. LGBP patients had significantly greater reduction of waist circumference and sagittal diameter compared with LVBG. DEXA demonstrated a larger reduction of body fat in all compartments after LGBP, especially at the trunk (P<0.001). CT demonstrated more reduction of the visceral fat (P=0.016). Patients were able to eat all types of food after LGBP, although about 30% claimed they avoided fats. LGBP patients decreased their proportion of dietary fat significantly more than those operated on with LVBG (P = 0.005), who consumed more sweet foods and avoided whole meat and vegetables. Lean tissue mass (LTM) was proportionally less reduced, especially in men, after LGBP. The decreases in BMR postoperatively reflected the lower body mass in a pattern that did not differ among the groups. CONCLUSION: LGBP patients demonstrated better outcomes compared with LVBG patients in terms of body composition. Energy expenditure developed as expected postoperatively. A “steering” away from fatty foods after LGBP may be an important mechanism of action in gastric bypass

Democratizing Startups

President Obama signed the Jumpstart Our Business Startups (“JOBS Act”) of 2012 into law to “help entrepreneurs raise the capital they need to put Americans back to work and create an economy that’s built to last.” The goal is to “democratize startups” by making capital available to diverse entrepreneurs in new geographies. Yet the net effect of securities regulations and market conditions is the opposite. Startup companies are encouraged to stay private so capital is consolidating in large, mature firms instead of recycling into new startups. Evidence of consolidation is that once-rare “Unicorns” (billion-dollar startups) now number at least 170. More money is going into huge private companies, yet total venture capital investment is flat, so less is going to new startups. This could stall out the innovation economy. Democratizing startups requires safe-harbor exemptions from securities regulations for both original issuance and resale of stock, but securities regulations do not permit resale on exchanges. This Article proposes “Rule 144B,” a regulatory provision that could be enacted without an act of Congress, to permit transparent web-based venture exchanges with fraud-prevention intermediaries termed “independent analysts.” This Article answers the SEC’s call for rulemaking comments and informs Congress’s new work on JOBS Act 2.0