Structural basis for diversity in the SAM clan of riboswitches.

In bacteria, sulfur metabolism is regulated in part by seven known families of riboswitches that bind S-adenosyl-l-methionine (SAM). Direct binding of SAM to these mRNA regulatory elements governs a downstream secondary structural switch that communicates with the transcriptional and/or translational expression machinery. The most widely distributed SAM-binding riboswitches belong to the SAM clan, comprising three families that share a common SAM-binding core but differ radically in their peripheral architecture. Although the structure of the SAM-I member of this clan has been extensively studied, how the alternative peripheral architecture of the other families supports the common SAM-binding core remains unknown. We have therefore solved the X-ray structure of a member of the SAM-I/IV family containing the alternative "PK-2" subdomain shared with the SAM-IV family. This structure reveals that this subdomain forms extensive interactions with the helix housing the SAM-binding pocket, including a highly unusual mode of helix packing in which two helices pack in a perpendicular fashion. Biochemical and genetic analysis of this RNA reveals that SAM binding induces many of these interactions, including stabilization of a pseudoknot that is part of the regulatory switch. Despite strong structural similarity between the cores of SAM-I and SAM-I/IV members, a phylogenetic analysis of sequences does not indicate that they derive from a common ancestor.

Perioperative Management of Hepatitis C in Patients Undergoing Total Joint Arthroplasty.

¼: A small yet growing subset of total joint arthroplasty (TJA) candidates are diagnosed with the hepatitis C virus (HCV), which is a known risk factor for periprosthetic joint infections. Given the poor outcomes associated with TJA infection, we recommend that candidates with HCV receive treatment prior to elective TJA. ¼: Interferon and ribavirin have historically been the standard treatment regimen for the management of HCV; however, adverse events and an inconsistent viral response have limited the efficacy of these therapies. The advent of direct-acting antivirals has resolved many of the issues associated with interferon and ribavirin regimens. ¼: Despite the success of direct-acting antivirals, there are still barriers to seeking treatment for TJA candidates with HCV. Many patients are faced with financial burdens, as insurance coverage of direct-acting antiviral therapies is inconsistent and varies by the patient's state of residence and specific treatment regimen. ¼: TJA candidates with HCV present health-care providers with a unique set of challenges, often encompassing economic, psychosocial, and complex medical concerns. Multidisciplinary care teams can be beneficial when caring for and optimizing this patient cohort. ¼: Management of HCV prior to elective TJA is associated with higher up-front costs but ultimately reduces long-term patient morbidity as well as associated direct and indirect health-care expenditures.

Head Loss As an Explanation of the Steal Phenomenon in Microvascular Surgery.

Vascular steal has been cited to help explain end-organ ischemia after microvascular reconstruction. Attempts to clarify a mechanism of vascular steal have been made by modeling blood circulation after a simple electrical circuit, suggesting that the free flap provides a path of least resistance for blood flow and thereby compromises end-organ perfusion. We present a case of a posterior medial thigh perforator flap for the reconstruction of a diabetic foot ulcer in a patient with a single vessel providing inflow to the foot. In the context of this case, we provide a novel explanation for the steal phenomenon using the Hagen-Poiseuille law and the property of head loss in fluid dynamics and discuss how the vessel size of the free flap may contribute to a steal phenomenon.