Postoperative complications after procedure for prolapsed hemorrhoids (PPH) and stapled transanal rectal resection (STARR) procedures

Procedure for prolapsing hemorrhoids (PPH) and stapled transanal rectal resection for obstructed defecation (STARR) carry low postoperative pain, but may be followed by unusual and severe postoperative complications. This review deals with the pathogenesis, prevention and treatment of adverse events that may occasionally be life threatening. PPH and STARR carry the expected morbidity following anorectal surgery, such as bleeding, strictures and fecal incontinence. Complications that are particular to these stapled procedures are rectovaginal fistula, chronic proctalgia, total rectal obliteration, rectal wall hematoma and perforation with pelvic sepsis often requiring a diverting stoma. A higher complication rate and worse results are expected after PPH for fourth-degree piles. Enterocele and anismus are contraindications to PPH and STARR and both operations should be used with caution in patients with weak sphincters. In conclusion, complications after PPH and STARR are not infrequent and may be difficult to manage. However, if performed in selected cases by skilled specialists aware of the risks and associated diseases, some complications may be prevented

Inflammatory biomarkers in Alzheimer's disease plasma

Introduction: Plasma biomarkers for Alzheimer's disease (AD) diagnosis/stratification are a \u201cHoly Grail\u201d of AD research and intensively sought; however, there are no well-established plasma markers. Methods: A hypothesis-led plasma biomarker search was conducted in the context of international multicenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL; 259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed. Results: Ten analytes showed significant intergroup differences. Logistic regression identified five (FB, FH, sCR1, MCP-1, eotaxin-1) that, age/APO\u3b54 adjusted, optimally differentiated AD and CTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1) that optimally differentiated AD and MCI (AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Two analytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71). Discussion: Plasma markers of inflammation and complement dysregulation support diagnosis and outcome prediction in AD and MCI. Further replication is needed before clinical translation

Transient electrostatic interactions dominate the conformational equilibrium sampled by multidomain splicing factor U2AF65: A combined NMR and SAXS study.

Multidomain proteins containing intrinsically disordered linkers exhibit large-scale dynamic modes that play key roles in a multitude of molecular recognition and signaling processes. Here, we determine the conformational space sampled by the multidomain splicing factor U2AF65 using complementary nuclear magnetic resonance spectroscopy and small-angle scattering data. Available degrees of conformational freedom are initially stochastically sampled and experimental data then used to delineate the potential energy landscape in terms of statistical probability. The spatial distribution of U2AF65 conformations is found to be highly anisotropic, comprising significantly populated interdomain contacts that appear to be electrostatic in origin. This hypothesis is supported by the reduction of signature PREs reporting on expected interfaces with increasing salt concentration. The described spatial distribution reveals the complete spectrum of the unbound forms of U2AF65 that coexist with the small percentage of a preformed RNA-bound domain arrangement required for polypyrimidine-tract recognition by conformational selection. More generally, the proposed approach to describing conformational equilibria of multidomain proteins can be further combined with other experimental data that are sensitive to domain dynamics