Under conditions of starvation and disease, the gut barrier becomes impaired, and trophic feeding to prevent gut mucosal atrophy has become a standard treatment of critically ill patients. However, the mechanisms responsible for the beneficial effects of enteral nutrition have remained a mystery. Using in vitro and in vivo models, we demonstrate that the brush-border enzyme, intestinal alkaline phosphatase (IAP), has the ability to detoxify lipopolysaccharide and prevent bacterial invasion across the gut mucosal barrier. IAP expression and function are lost with starvation and maintained by enteral feeding. It is likely that the IAP silencing that occurs during starvation is a key component of the gut mucosal barrier dysfunction seen in critically ill patients.A mong the most critical functions of the mammalian gut mucosa is to provide a barrier to luminal microbes and toxins while simultaneously allowing for the necessary digestion and absorption of dietary nutrients. The molecular mechanisms that govern barrier function are incompletely understood, but it is clear that under conditions of starvation and disease, the gut barrier becomes impaired, leading to significant morbidity and mortality (1-8). Trophic enteral feeding to prevent gut mucosal atrophy and resultant barrier dysfunction has become part of the standard treatment of intensive care unit patients (9-14). The mechanism(s) responsible for the beneficial effects of trophic feeding are not understood.Intestinal alkaline phosphatase (IAP), a brush-border protein that hydrolyzes monophosphate esters, is expressed exclusively in villus-associated enterocytes and is considered an excellent marker for crypt-villus differentiation (15-18). Narisawa et al. (19) reported that compared with their wild-type (WT) littermates, mice lacking IAP gained more weight under conditions of a high-fat diet. In addition, several studies have shown that the IAP enzyme is capable of detoxifying LPS, likely through dephosphorylation of the lipid A moiety, the primary source of its endotoxic effects (20). Despite these few reports, the physiological role of IAP within the gut has not been elucidated. Results and DiscussionTo examine the functional role of IAP, we developed in vitro model systems using intestinal cell lines (T84, HT-29, and IEC-6) that express little or no IAP under basal conditions. Stable cell lines were created that overexpress IAP (Fig. 1A), and enzyme assays were used to determine the cellular localization of the ectopically expressed IAP protein. The results in Fig. 1B show that parent cells make little, if any, endogenous IAP. In contrast, large amounts of IAP enzyme are seen in the stably transfected cells. Importantly, the vast majority of the IAP activity is in the membrane fraction as opposed to the cytosol. Fig. 1C shows the results of the control experiment used to validate our separation of membranous and cytosolic fractions, confirming that the majority of the MAPK enzyme activity exists within the cytosol rather than the membrane. This membrane ...

Successful treatment of the painful neuroma is a particular challenge to the nerve surgeon. Historically, symptomatic neuromas have primarily been treated with excision and implantation techniques, which are inherently passive and do not address the terminal end of the nerve. Over the past decade, the surgical management of neuromas has undergone a paradigm shift synchronous with the development of contemporary techniques aiming to satisfy the nerve end. In this article, we describe the important features of surgical treatment, including the approach to diagnosis with consideration of neuroma type and the decision of partial versus complete neuroma excision. A comprehensive list of the available surgical techniques for management following neuroma excision is presented, the choice of which is often predicated upon the availability of the terminal nerve end for reconstruction. Techniques for neuroma reconstruction in the presence of an intact terminal nerve end include hollow tube reconstruction and auto- or allograft nerve reconstruction. Techniques for neuroma management in the absence of an intact or identifiable terminal nerve end include submuscular or interosseous implantation, centro-central neurorrhaphy, relocation nerve grafting, nerve cap placement, use of regenerative peripheral nerve interface, “end-to-side” neurorrhaphy, and targeted muscle reinnervation. These techniques can be further categorized into passive/ablative and active/reconstructive modalities. The nerve surgeon must be aware of available treatment options and should carefully choose the most appropriate intervention for each patient. Comparative studies are lacking and will be necessary in the future to determine the relative effectiveness of each technique.

Background Plastic surgeons have been early adopters of social media, and the efficacy and ethics of this practice have been studied. In addition, plastic and reconstructive surgery (PRS) training programs have begun using social media to connect with the public, including prospective PRS applicants. The ability of social media to attract prospective residency applicants is unknown. This study aims to examine the influence of social media on prospective residency applicants and their perception of a plastic surgery program. Methods In the academic years 2018 and 2019, we conducted an anonymous, voluntary survey among applicants applying to both the integrated and independent Harvard PRS residency programs. The survey collected data regarding demographics, social media usage, online information gathering, and PRS programs' social media influence on applicants' perception/rank position of programs. Results One hundred nine surveys were completed (23%). Ninety-seven percent of respondents reported searching online for information about residency programs. Twenty percent of respondents noted that a residency program's social media platform “influenced their perception of a program or intended rank position of a program” and 72% of those respondents indicated a positive effect on their perception of a program and its rank list position. At least 15% of respondents were concerned that engaging with a program's social media account would attract attention to their own social media accounts. Conclusions Applicants routinely rely on online resources to gather information regarding prospective residency programs. Fear of attracting attention to their own personal social media pages may limit applicants' engagement with PRS programs on social media. However, residency programs can still utilize social media to deliver important messages, especially as social media usage continues to grow.