Structure theorems and the dynamics of nitrogen catabolite repression in yeast

By using current biological understanding, a conceptually simple, but mathematically complex, model is proposed for the dynamics of the gene circuit responsible for regulating nitrogen catabolite repression (NCR) in yeast. A variety of mathematical "structure" theorems are described that allow one to determine the asymptotic dynamics of complicated systems under very weak hypotheses. It is shown that these theorems apply to several subcircuits of the full NCR circuit, most importantly to the URE2-GLN3 subcircuit that is independent of the other constituents but governs the switching behavior of the full NCR circuit under changes in nitrogen source. Under hypotheses that are fully consistent with biological data, it is proven that the dynamics of this subcircuit is simple periodic behavior in synchrony with the cell cycle. Although the current mathematical structure theorems do not apply to the full NCR circuit, extensive simulations suggest that the dynamics is constrained in much the same way as that of the URE2-GLN3 subcircuit. This finding leads to the proposal that mathematicians study genetic circuits to find new geometries for which structure theorems may exist.     

Understanding Determinants of Patient Preferences Between Stool Tests and Colonoscopy for the Assessment of Disease Activity in Inflammatory Bowel Disease

Digestive Diseases and Sciences - Evidence is now available in support of using fecal biomarkers to monitor disease activity in inflammatory bowel disease (IBD). Patient adherence is often cited as...     

Increased Risk of Infections with Anti-TNF Agents in Patients with Crohn’s Disease After Elective Surgery: Meta-Analysis

Digestive Diseases and Sciences - Postoperative complication rates in patients with inflammatory bowel disease (IBD) receiving preoperative biologics have been analyzed without considering the...     

Bone tissue engineering in oral peri‐implant defects in preclinical in vivo research: A systematic review and meta‐analysis

The regeneration and establishment of osseointegration within oral peri‐implant bone defects remains a clinical challenge. Bone tissue engineering (BTE) is emerging as a promising alternative to autogenous and/or biomaterial‐based bone grafting. The objective of this systematic review was to answer the focused question: in animal models, do cell‐based BTE strategies enhance bone regeneration and/or implant osseointegration in experimental peri‐implant defects, compared with grafting with autogenous bone or only biomaterial scaffolds? Electronic databases were searched for controlled animal studies reporting on peri‐implant defects and implantation of mesenchymal stem cells (MSC) or other cells seeded on biomaterial scaffolds, following Preferred Reporting Items for Systematic reviews and Meta‐Analyses (PRISMA) guidelines. Random effects meta‐analyses were performed for the outcomes histomorphometric bone area fraction (BA) and bone‐to‐implant contact (BIC). Nineteen studies reporting on large animal models (dogs and sheep) were included. Experimental defects were created surgically (16 studies) or via ligature‐induced peri‐implantitis (LIPI, three studies). In general, studies presented with an unclear to high risk of bias. In most studies, MSC were used in combination with alloplastic mineral phase or polymer scaffolds; no study directly compared cell‐loaded scaffolds vs. autogenous bone. In three studies, cells were also modified by ex vivo gene transfer of osteoinductive factors. The meta‐analyses indicated statistically significant benefits in favour of: (a) cell‐loaded vs. cell‐free scaffolds [weighted mean differences (WMD) of 10.73–12.30% BA and 11.77–15.15% BIC] in canine surgical defect and LIPI models; and (b) gene‐modified vs. unmodified cells (WMD of 29.44% BA and 16.50% BIC) in canine LIPI models. Overall, heterogeneity in the meta‐analyses was high (I² 70–88%); considerable variation was observed among studies regarding the nature of cells and scaffolds used. In summary, bone regeneration and osseointegration in peri‐implant defects are enhanced by the addition of osteogenic cells to biomaterial scaffolds. Although the direction of treatment outcome is clearly in favour of BTE strategies, due to the limited magnitude of treatment effect observed, no conclusive statements regarding the clinical benefit of such procedures for oral indications can yet be made. Copyright © 2017 John Wiley & Sons, Ltd.     

Effect of Medicare Dialysis Payment Reform on Use of Erythropoiesis Stimulating Agents

ObjectiveIn 2011, the Centers for Medicare and Medicaid Services (CMS) replaced fee-for-service reimbursement for erythropoiesis stimulating agents (ESAs) with a fixed-sum bundled payment for all dialysis-related care and pay-for-performance incentives to discourage maintaining patients'' hematocrits above 36 percent. We examined the impact of the new payment policy on the use of ESAs.ConclusionsCMS''s payment reform for dialysis care reduced the use of ESAs in patients who may not benefit from these agents.