Annexin A1–containing extracellular vesicles and polymeric nanoparticles promote epithelial wound repair

Epithelial restitution is an essential process that is required to repair barrier function at mucosal surfaces following injury. Prolonged breaches in epithelial barrier function result in inflammation and further damage; therefore, a better understanding of the epithelial restitution process has potential for improving the development of therapeutics. In this work, we demonstrate that endogenous annexin A1 (ANXA1) is released as a component of extracellular vesicles (EVs) derived from intestinal epithelial cells, and these ANXA1-containing EVs activate wound repair circuits. Compared with healthy controls, patients with active inflammatory bowel disease had elevated levels of secreted ANXA1-containing EVs in sera, indicating that ANXA1-containing EVs are systemically distributed in response to the inflammatory process and could potentially serve as a biomarker of intestinal mucosal inflammation. Local intestinal delivery of an exogenous ANXA1 mimetic peptide (Ac2-26) encapsulated within targeted polymeric nanoparticles (Ac2-26 Col IV NPs) accelerated healing of murine colonic wounds after biopsy-induced injury. Moreover, one-time systemic administration of Ac2-26 Col IV NPs accelerated recovery following experimentally induced colitis. Together, our results suggest that local delivery of proresolving peptides encapsulated within nanoparticles may represent a potential therapeutic strategy for clinical situations characterized by chronic mucosal injury, such as is seen in patients with IBD.     

Links that speak: The global language network and its association with global fame

Languages vary enormously in global importance because of historical, demographic, political, and technological forces. However, beyond simple measures of population and economic power, there has been no rigorous quantitative way to define the global influence of languages. Here we use the structure of the networks connecting multilingual speakers and translated texts, as expressed in book translations, multiple language editions of Wikipedia, and Twitter, to provide a concept of language importance that goes beyond simple economic or demographic measures. We find that the structure of these three global language networks (GLNs) is centered on English as a global hub and around a handful of intermediate hub languages, which include Spanish, German, French, Russian, Portuguese, and Chinese. We validate the measure of a language’s centrality in the three GLNs by showing that it exhibits a strong correlation with two independent measures of the number of famous people born in the countries associated with that language. These results suggest that the position of a language in the GLN contributes to the visibility of its speakers and the global popularity of the cultural content they produce.Of the thousands of languages that have ever been spoken, only a handful have become influential enough to be considered global languages. However, how do we measure the global influence of a language? What are the implications of a world in which only a handful of languages are globally influential?In the past, researchers have used a variety of measures to determine the global influence of a language. Several studies have relied on measures that proxy the global influence of a language using the population and wealth of its speakers (1–4). While wealth and population approximate a language’s influence, as the dissemination of a language has historically required a strong power base (5), such measures fail to capture the global influence of a language: often the speakers of a language, and their wealth, are locally concentrated, making the language locally influential rather than globally influential.An alternative method to measure the global influence of a language is to focus on who speaks that language, and in particular, on how connected the speakers of that language are. In the words of linguist David Crystal, “Why a language becomes a global language has little to do with the number of people who speak it. It is much more to do with who those speakers are.” (5) In the past, Latin was the pan-European language, not because it was the mother tongue of most Europeans, but because it was the language of the Roman Empire and later the language of the Catholic Church, scholars, and educators (5). The use of Latin by well-connected elites set it apart from other languages and helped Latin endure as a universal language for more than 1,000 years.However, can we use these ideas to identify which modern languages are globally influential? If global languages are those connecting international elites, then we can identify the global languages associated with particular elites by mapping their networks of multilingual coexpressions. Examples of multilingual coexpressions include book translations, edits to multiple language editions of Wikipedia, and posting short messages on Twitter (“tweets”) in multiple languages. These coexpressions define networks (Fig. 1) that—even though not representative of the world’s general population—represent a coarse map of the links connecting the elites that participate of these three important global forums, as social connections often require a shared language.Open in a separate windowFig. 1.Visualizations of the three GLNs. The three GLNs contain all language connections that involve at least six users (Twitter and Wikipedia) or six translations and that are significant with P < 0.01.In this paper, we map the global language networks (GLNs) expressed in three large records of linguistic expression, and use the structure of these networks to determine the degree to which each language is global. First, we look at a collection of more than 2.2 million book translations compiled by UNESCO’s Index Translationum project. This dataset allows us to map the network of book translations, which are produced by individuals with a high literary capacity (authors and professional translators) and are shaped by market forces, such as the demand for books in different languages. Each translation from one language to another forms a connection. Next, we map the network of linguistic coexpressions expressed by the community of digitally engaged knowledge specialists that edit Wikipedia. Here, two languages are connected when users that edit an article in one Wikipedia language edition are significantly more likely to also edit an article in another language edition. Finally, we map the network of linguistic coexpressions expressed in Twitter. Here, two languages are connected when users that tweet in a language are also significantly more likely to tweet in another language.These three networks allow us to map the paths of direct and indirect communication between speakers from different languages. Our method formalizes the intuition that certain languages are disproportionately influential because they provide direct and indirect paths of translation among most of the world’s other languages. For example, it is easy for an idea conceived by a Spaniard to reach an Englishman through bilingual speakers of English and Spanish. An idea conceived by a Vietnamese speaker, however, might only reach a Mapudungun speaker in south-central Chile through a circuitous path that connects bilingual speakers of Vietnamese and English, English and Spanish, and Spanish and Mapudungun. In both cases, however, English and Spanish are still involved in the flow of information, indicating that they act as global languages. In the first example, Spanish and English have a direct involvement because communication is flowing among their speakers. In the latter case, the involvement is indirect and emerges from the lack of speakers that can communicate in both Vietnamese and Mapudungun. These indirect connections make multilingual speakers of global languages globally influential, as they mediate the flow of information not only among each other, but also, among people with whom they do not share a language (6).     

Admission Norton scale scores (ANSS) and postoperative complications following hip fracture surgery in the elderly

We sought to determine if low ANSS, usually associated with high pressure ulcer risk, are also associated with postoperative complications and in-hospital mortality following hip fracture surgery in the elderly. This was a retrospective cross-sectional study conducted in a tertiary medical center. The medical charts of consecutive elderly (≥ 65 years) patients admitted for hip fracture surgery were studied for the following measurements: ANSS, demographic data, co-morbidities, postoperative complications, the need for revision procedures, and in-hospital mortality. Except for pressure ulcers, postoperative complications included: acute coronary syndrome, acute renal failure, confusion, pneumonia, urinary tract infection, venous thromboembolism, and wound infection. The final cohort included 269 patients: 198 (73.6%) females and 71 (26.4%) males. Mean age for the entire cohort was 82.8 ± 0.4 years. Most patients underwent an internal fixation (n=146; 54.3%) or hemiarthroplasty (n=92; 34.2%). Overall, 110 (40.9%) patients had low (<15) ANSS. Patients with low ANSS had significantly more postoperative complications relative to patients with high ANSS (0.77 ± 0.09 vs. 0.23 ± 0.04; p<0.0001). Among all postoperative complications, urinary tract infection was independently associated with low ANSS (p<0.0001). ANSS were independently associated with postoperative complications (p<0.0001), the need for revision procedures (p=0.019), and in-hospital mortality (p=0.016). We conclude that the Norton scoring system may be used for predicting postoperative complications and in-hospital mortality following hip fracture surgery in the elderly.     

Graves' disease presenting with severe cholestasis

BACKGROUND: Hyperthyroidism has been associated with liver function abnormalities; however, cholestasis as the presenting feature of adolescent Graves' disease has not been previously reported. PATIENT SUMMARY: The patient was a 17-year-old girl who presented with severe cholestasis and was found to have Graves' disease. She also had a positive hepatitis A immunoglobulin M antibody but her clinical course, the liver histopathology, and her mildly elevated transaminases indicated that the acute hepatitis A infection was not dominant at the time of presentation with severe cholestasis. Other causes of cholestasis, including congestive heart failure, autoimmune hepatitis, and viral infection, were excluded. Treatment with methimazole resolved the hyperthyroidism, and the cholestasis improved, as well. CONCLUSION: Severe cholestasis is a rare presenting feature of Graves' disease. With careful monitoring, methimazole can be used to treat the hyperthyroidism in the setting of cholestasis.