Inhibition of Methyltransferase Setd7 Allows the In Vitro Expansion of Myogenic Stem Cells with Improved Therapeutic Potential.

The development of cell therapy for repairing damaged or diseased skeletal muscle has been hindered by the inability to significantly expand immature, transplantable myogenic stem cells (MuSCs) in culture. To overcome this limitation, a deeper understanding of the mechanisms regulating the transition between activated, proliferating MuSCs and differentiation-primed, poorly engrafting progenitors is needed. Here, we show that methyltransferase Setd7 facilitates such transition by regulating the nuclear accumulation of ß-catenin in proliferating MuSCs. Genetic or pharmacological inhibition of Setd7 promotes in vitro expansion of MuSCs and increases the yield of primary myogenic cell cultures. Upon transplantation, both mouse and human MuSCs expanded with a Setd7 small-molecule inhibitor are better able to repopulate the satellite cell niche, and treated mouse MuSCs show enhanced therapeutic potential in preclinical models of muscular dystrophy. Thus, Setd7 inhibition may help bypass a key obstacle in the translation of cell therapy for muscle disease.

Prospective Randomized Trial Comparing the Efficacy of Surgical Preparation Solutions in Hand Surgery.

BACKGROUND: Decontamination of the skin prior to incision is part of the standard of care for any surgical procedure. Previous studies have demonstrated variable efficacy of different surgical preparation solutions based on anatomic location. The purpose of this study is to determine the effectiveness of 3 commonly used surgical preparation solutions in eliminating bacteria from the skin prior to incision for common elective soft tissue hand procedures. METHODS: A total of 240 patients undergoing clean, elective, soft tissue hand surgery were prospectively randomized to 1 of 3 groups (ChloraPrep, DuraPrep, or Betadine). Prepreparation and postpreparation cultures were obtained adjacent to the surgical incision and neutralization was performed on the obtained specimen. Cultures were held for 14 days and patients followed for 6 weeks postoperatively. RESULTS: Postpreparation cultures were positive in 21 of 80 (26.3%) ChloraPrep patients, 3 of 79 (3.8%) DuraPrep patients, and 1 of 81 (1.2%) Betadine patients ( P < .001). There was no difference in the postpreparation culture rate between DuraPrep and Betadine ( P = 1.000). CONCLUSIONS: Duraprep and Betadine were found to be superior to Chloraprep for skin decontamination prior to clean elective soft tissue hand surgery. The bacterial flora of the hand was found to be different from those of the shoulder and spine. The clinical significance of this finding requires clinical consideration because the majority of prepreparation and postpreparation positive cultures were of Bacillus species, which are rarely a cause of postoperative infections.

CCM-3/STRIPAK promotes seamless tube extension through endocytic recycling.

The mechanisms governing apical membrane assembly during biological tube development are poorly understood. Here, we show that extension of the C. elegans excretory canal requires cerebral cavernous malformation 3 (CCM-3), independent of the CCM1 orthologue KRI-1. Loss of ccm-3 causes canal truncations and aggregations of canaliculular vesicles, which form ectopic lumen (cysts). We show that CCM-3 localizes to the apical membrane, and in cooperation with GCK-1 and STRIPAK, promotes CDC-42 signalling, Golgi stability and endocytic recycling. We propose that endocytic recycling is mediated through the CDC-42-binding kinase MRCK-1, which interacts physically with CCM-3-STRIPAK. We further show canal membrane integrity to be dependent on the exocyst complex and the actin cytoskeleton. This work reveals novel in vivo roles of CCM-3·STRIPAK in regulating tube extension and membrane integrity through small GTPase signalling and vesicle dynamics, which may help explain the severity of CCM3 mutations in patients.

Preoperative decolonization effective at reducing staphylococcal colonization in total joint arthroplasty patients.

Staphylococcus decolonization prior to surgery is used to prevent surgical site infections (SSIs) after total joint arthroplasty (TJA). To determine if current treatment protocols result in successful decolonization of methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA), 106 consecutive patients were screened for nasal MSSA/MRSA colonization pre-operatively and on the day of surgery. Colonized patients used intranasal mupirocin twice a day and chlorhexidine showers daily 5 days prior to surgery. Pre-operatively, 24 joints (22.0%) were positive for MSSA colonization and 5 joints (4.6%) were positive for MRSA colonization. On the day of surgery, 3 joints (2.8%) who underwent decolonization were positive for MSSA colonization and 0 joints were positive for MRSA colonization. The reduction in MSSA colonization was significant (P<0.001), while the eradication of MRSA colonization approached statistical significance (P=0.063). Current decolonization protocols using intranasal mupirocin and chlorhexidine washes are effective for reducing MRSA/MSSA colonization.