The global prevalence of severe Clostridium difficile infection highlights the profound clinical significance of clostridial glucosylating toxins1–4. Virulence is dependent on the autoactivation of a toxin cysteine protease5–9, which is promoted by the allosteric cofactor inositol hexakisphosphate (InsP6)10–17. Host mechanisms that protect against such exotoxins are poorly understood. It is increasingly appreciated that the pleiotropic functions attributed to nitric oxide (NO), including host immunity, are in large part mediated by S-nitrosylation of proteins18,19. Here we show that C. difficile toxins are S-nitrosylated by the infected host and that S-nitrosylation attenuates virulence by inhibiting toxin self-cleavage and cell entry. Notably, InsP6- and inositol pyrophosphate (InsP7)-induced conformational changes in the toxin enabled host S-nitrosothiols to transnitrosylate the toxin catalytic cysteine, which forms part of a structurally conserved nitrosylation motif. Moreover, treatment with exogenous InsP6 enhanced the therapeutic actions of oral S-nitrosothiols in mouse models of C. difficile infection. Allostery in bacterial proteins has thus been successfully exploited in the evolutionary development of nitrosothiol-based innate immunity and may provide an avenue to new therapeutic approaches.

Total ear reconstruction has been approached by several techniques involving autologous graft, prosthetic implant, and alloplastic implant options. Recent studies have shown the superiority of porous polyethylene (Medpor, Porex Surgical) reconstruction over autologous reconstruction based on improved aesthetic results, earlier age of intervention, shorter surgery times, fewer number of required procedures, and a simpler postoperative recovery process. A durable and permanent option for total ear reconstruction, like Medpor, can help alleviate the cosmetic concerns that patients with auricular deformities may be burdened with on a daily basis. In this article, the authors discuss the advantages of Medpor-based ear reconstruction and discuss recent advances in the surgical techniques involved, such as harvesting a temporoparietal fascia flap and full-thickness skin graft to adequately cover the Medpor framework and decrease extrusion rates.

The hands are one of the most visible parts of the body, and prominent dorsal veins and extensor tendons are the most readily recognized signs of the aging process. Fat grafting has been demonstrated to be a safe and effective method of hand rejuvenation by restoration of subcutaneous fat. Despite some variability in the technical approach, fat grafting techniques are consistent in their use of low-pressure injection with standard cannula sizes, small aliquots of graft, and a total volume of graft greater than or equal to 15 mL per hand. While distribution of the fat is an area of debate and a topic of active research, published studies have shown high patient satisfaction rates, suggesting that perhaps the restoration of volume alone is paramount. In this article, we will review the applications of fat grafting to the hand, focusing primarily on its role in hand rejuvenation.

Ear prominence is a relatively common cosmetic deformity with no associated functional deficits, but with profound psychosocial impact, especially in young patients. Protruding ears in children have propagated surgical advances that incorporate reconstructive techniques. Here we outline a systematic framework to evaluate the protruding ear and present various reconstructive surgical options for correction. Both cosmetic and reconstructive perspectives should be entertained when addressing this anatomical deformity.

Traumatic panfacial fracture repair is one of the most complex and challenging reconstructive procedures to perform. Several principles permeate throughout literature regarding the repair of panfacial injuries in a stepwise fashion. The primary goal of management in most of these approaches is to restore the occlusal relationship at the beginning of sequential repair so that other structures can fall into alignment. Through proper positioning of the occlusion and the mandibular-maxillary unit with the skull base, the spatial relationships and stability of midface buttresses and pillars can then be re-established. Here, the authors outline the sequencing of panfacial fracture repair for the restoration of anatomical relationships and the optimization of functional and structural outcomes.

Background and Objectives:With advances in laparoscopic surgery, the goal of surgeons and patients is to minimize pain to allow for faster recovery and return to normal daily activities. One of these advances is single-site surgery. In this study, we compared postoperative pain in laparoendoscopic single-site surgery (LESS) to that in traditional multiple-incision hysterectomy.Methods:Seventy patients were selected for this prospective cohort study, with 35 undergoing multiple-incision and 35 undergoing LESS hysterectomy. All patients were included who were undergoing hysterectomy with the primary surgeon. All multiport hysterectomies were performed laparoscopically. Six patients underwent LESS hysterectomy and 29 underwent robotic single-site surgery (rLESS). Patients recorded pain levels for 3 weeks after surgery on a variety of measures, including overall and incisional pain. Linear mixed effects models for repeated measures were used for all multivariate analyses, with an unstructured covariance matrix accounting for correlation between time points.Results:Overall, across all time points, there was an average reduction in pain by 1.26 (SD 0.69) points in the single-site group (P = .06). Days 3 and 14 had a marginally significant reduction in pain (P = .06 and 0.058, respectively). On days 4 and 7 there was a significant reduction in overall pain (P = .04 and .04, respectively).Conclusion:Based on the results, it is likely that single-site hysterectomy leads to less postoperative pain and achieves a lower pain score faster than multiport surgery. A randomized control trial is necessary to confirm these results before accepting them in clinical practice.

Microtia is a congenital auricular deformity that commonly presents with associated congenital aural atresia. The most acute concern in these patients is concomitant hearing loss at birth. A team-based approach by plastic surgeons and otologists is necessary to address both the otologic and audiologic concerns of microtia and atresia. Hearing rehabilitation is imperative; yet it should not compromise the aesthetic components of reconstruction and vice versa. Here, the authors propose a framework to evaluate and manage patients with microtia and atresia with the goal of optimizing functional and cosmetic outcomes.

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