Human intestinal macrophages contribute to tissue homeostasis in noninflamed mucosa through profound down-regulation of pro-inflammatory cytokine release. Here, we show that this down-regulation extends to Toll-like receptor (TLR)-induced cytokine release, as intestinal macrophages expressed TLR3–TLR9 but did not release cytokines in response to TLR-specific ligands. Likely contributing to this unique functional profile, intestinal macrophages expressed markedly down-regulated adapter proteins MyD88 and Toll interleukin receptor 1 domain-containing adapter-inducing interferon β, which together mediate all TLR MyD88-dependent and -independent NF-κB signaling, did not phosphorylate NF-κB p65 or Smad-induced IκBα, and did not translocate NF-κB into the nucleus. Importantly, transforming growth factor-β released from intestinal extracellular matrix (stroma) induced identical down-regulation in the NF-κB signaling and function of blood monocytes, the exclusive source of intestinal macrophages. Our findings implicate stromal transforming growth factor-β-induced dysregulation of NF-κB proteins and Smad signaling in the differentiation of pro-inflammatory blood monocytes into noninflammatory intestinal macrophages.

Male hypogonadism is characterized by abnormally low serum testosterone levels associated with typical symptoms, including mood disturbance, sexual dysfunction, decreased muscle mass and strength, and decreased bone mineral density. By restoring serum testosterone levels to the normal range using testosterone replacement therapy, many of these symptoms can be relieved. For many years, injectable testosterone esters or surgically implanted testosterone pellets have been the preferred treatment for male hypogonadism. Recently, newer treatment modalities have been introduced, including transdermal patches and gels. The development of a mucoadhesive sustained-release buccal tablet is the latest innovation, which will provide patients with an additional option. The availability of new treatment modalities has helped to renew interest in the management of male hypogonadism, highlighting the need to address a number of important but previously neglected questions in testosterone replacement therapy. These include the risks and benefits of treatment in different patient populations (e.g. the elderly) and the need for evidence-based diagnosis and treatment monitoring guidelines. While some recommendations have been developed in individual countries, up-to-date, internationally accepted evidence-based guidelines that take into account national differences in clinical practice and healthcare delivery would optimize patient care universally.

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Introduction Transanal total mesorectal excision (taTME) is a novel approach to surgery for rectal cancer. The technique has gained significant popularity in the surgical community due to the promising ability to overcome technical difficulties related to the access of the distal pelvis. Recently, Norwegian surgeons issued a local moratorium related to potential issues with the safety of the procedure. Early adopters of taTME in Canada have recognized the need to create guidelines for its adoption and supervision. The objective of the statement is to provide expert opinion based on the best available evidence and authors' experience. Methods The procedure has been performed in Canada since 2014 at different institutions. In 2016, the first Canadian taTME congress was held in the city of Toronto, organized by two of the authors. In early 2019, a multicentric collaborative was established [The Canadian taTME expert Collaboration] which aimed at ensuring safe performance and adoption of taTME in Canada. Recently surgeons from 8 major Canadian rectal cancer centers met in the city of Toronto on December 7 of 2019, to discuss and develop a position statement. There in person, meeting was followed by 4 rounds of Delphi methodology. Results The generated document focused on the need to ensure a unified approach among rectal cancer surgeons across the country considering its technical complexity and potential morbidity. The position statement addressed four domains: surgical setting, surgeons' requirements, patient selection, and quality assurance. Conclusions Authors agree transanal total mesorectal excision is technically demanding and has a significant risk for morbidity. As of now, there is uncertainty for some of the outcomes. We consider it is possible to safely adopt this operation and obtain adequate results, however for this purpose it is necessary to meet specific requirements in different domains.