5-HT3A serotonin receptor in the gastrointestinal tract: the link between immune system and enteric nervous system in the digestive form of Chagas disease

Chagas disease is caused by Trypanosoma cruzi and remains one of the most neglected diseases in Latin America. One of its clinical forms is Chagas megacolon. Despite being known for more than half a century, detailed causes are still obscure. Recent evidence indicates a close relationship between the immune system and the enteric nervous system in the etiology of chagasic megacolon pathology. It is believed that low expression of the 5-HT_3A serotonin receptor on lymphocytes could be linked to megacolon development. To test this hypothesis, this work investigated the distribution of CD4, CD8, and CD20 lymphocytes and their 5-HT_3A receptor expression. The results demonstrated that Chagas patients without megacolon present a higher expression of the 5-HT_3A receptor in all analyzed lymphocytes compared with Chagas patients with megacolon. These data suggest that the high expression of this receptor may lead to immunomodulation and prevent the development of Chagas megacolon.

     

Tissue-Specific shRNA Delivery: A Novel Approach for Gene Therapy in Cancer

A novel tissue-specific shRNA delivery system has been developed using cre-lox technology. Conditionally silenced pSico vector containing oligonucleotides of CD44shRNA and tissue-specific promoter-driven Cre-recombinase expression vector are packaged into transferrin-coated nanoparticles that can deliver shRNA into specific tumors. This system has strong potential in cancer therapy.     

Prophylactic oral antibiotics reduce reinfection rates following two-stage revision total knee arthroplasty

The purpose of this study was to compare the incidence of reinfection in patients who received oral antibiotic prophylaxis with those who did not following two-stage revision knee arthroplasty. Additional purposes included: (1) comparison of these findings to the infection rate in patients who underwent revision for aseptic reasons, and (2) characterisation of the organisms responsible for reinfection following revision procedures. Twenty-eight two-stage revision knee arthroplasty procedures were followed up by a mean of 33 days of oral antibiotics (range, 28–43 days), while the remaining 38 procedures received only 24–72 hours of in-patient antibiotics. The incidence of reinfection in each group within 12 months was compared. The reinfection rates were additionally compared to those of 237 patients who underwent revision for aseptic loosening over the same time period. Patients who were treated with postoperative antibiotic prophylaxis had a considerably lower reinfection rate, with one reinfection in the prophylaxis group (4%), compared to six reinfections in the no-prophylaxis group (16%). The reinfection rates remained higher compared to those found in patients who underwent revision knee arthroplasty for aseptic loosening (1 of 237 patients; 0.4%). Both high and low virulence organisms were identified in the patients who were subsequently reinfected. A minimum of 28 days of postoperative oral antibiotics appeared to decrease reinfection rates following two-stage revision knee arthroplasty. These results suggest that the use of oral antibiotic prophylaxis following re-implantation may be appropriate in all patients undergoing two-stage revision, even in the absence of any signs of active infection.     

Update on Inclusion Body Myositis

Purpose of Review

While sporadic inclusion body myositis (sIBM) is the most common acquired muscle disease after age 50, the pathogenesis of this disease is still poorly understood. In this review, we discuss our current state of knowledge in sIBM and provide an update on our current understanding of its pathophysiology and management.

Recent Findings

Lines of evidence in support of an inflammatory pathogenesis include inflammatory infiltrates in the target organ, NFκB activation, cytokine response, MHC I upregulation, and cN1A antibody. Refractoriness to immunotherapies has led to suggestion of a degenerative pathophysiology. Evidence for impaired protein homeostasis with misfolding burden is coupled with findings of endoplasmic reticulum stress, proteasome dysfunction, and mitochondrial lesion. Recent treatment trials have focused more on correcting the degenerative process or muscle growth rather than controlling the inflammation.

Summary

There has been growing evidence toward degeneration as the primary process in sIBM. This is consistent with the refractory nature of this disease. Improving our understanding of this disease pathogenesis will propel efforts to find an effective therapy.

     

Piloting a Nationally Disseminated,Interactive Human Subjects Protection Program for Community Partners: Unexpected Lessons Learned from the Field

Funders, institutions, and research organizations are increasingly recognizing the need for human subjects protections training programs for those engaged in academic research. Current programs tend to be online and directed toward an audience of academic researchers. Research teams now include many nonacademic members, such as community partners, who are less likely to respond to either the method or the content of current online trainings. A team at the CTSA‐supported Michigan Institute for Clinical and Health Research at the University of Michigan developed a pilot human subjects protection training program for community partners that is both locally implemented and adaptable to local contexts, yet nationally consistent and deliverable from a central administrative source. Here, the developers of the program and the collaborators who participated in the pilot across the United States describe 10 important lessons learned that align with four major themes: The distribution of the program, the implementation of the program, the involvement of community engagement in the program, and finally lessons regarding the content of the program. These lessons are relevant to anyone who anticipates developing or improving a training program that is developed in a central location and intended for local implementation.