A distal effect of microsomal triglyceride transfer protein deficiency on the lysosomal recycling of CD1d

Microsomal triglyceride transfer protein (MTP) is an endoplasmic reticulum (ER)–resident lipid transfer protein involved in the biosynthesis and lipid loading of apolipoprotein B. MTP was recently suggested to directly regulate the biosynthesis of the MHC I–like, lipid antigen presenting molecule CD1d, based on coprecipitation experiments and lipid loading assays. However, we found that the major impact of MTP deficiency occurred distal to the ER and Golgi compartments. Thus, although the rates of CD1d biosynthesis, glycosylation maturation, and internalization from the cell surface were preserved, the late but essential stage of recycling from lysosome to plasma membrane was profoundly impaired. Likewise, functional experiments indicated defects of CD1d-mediated lipid presentation in the lysosome but not in the secretory pathway. These intriguing findings suggest a novel, unexpected role of MTP at a late stage of CD1d trafficking in the lysosomal compartment

Interleukin 6 increases production of cytokines by colonic innate lymphoid cells in mice and patients with chronic intestinal inflammation

Background & Aims: Innate lymphoid cells (ILCs) are a heterogeneous group of mucosal inflammatory cells that participate in chronic intestinal inflammation. We investigated the role of interleukin 6 (IL6) in inducing activation of ILCs in mice and in human beings with chronic intestinal inflammation. Methods: ILCs were isolated from colons of Tbx21-/- × Rag2-/- mice (TRUC), which develop colitis; patients with inflammatory bowel disease (IBD); and patients without colon inflammation (controls). ILCs were characterized by flow cytometry; cytokine production was measured by enzyme-linked immunosorbent assay and cytokine bead arrays. Mice were given intraperitoneal injections of depleting (CD4, CD90), neutralizing (IL6), or control antibodies. Isolated colon tissues were analyzed by histology, explant organ culture, and cell culture. Bacterial DNA was extracted from mouse fecal samples to assess the intestinal microbiota. Results: IL17A- and IL22-producing, natural cytotoxicity receptor-negative, ILC3 were the major subset of ILCs detected in colons of TRUC mice. Combinations of IL23 and IL1α induced production of cytokines by these cells, which increased further after administration of IL6. Antibodies against IL6 reduced colitis in TRUC mice without significantly affecting the structure of their intestinal microbiota. Addition of IL6 increased production of IL17A, IL22, and interferon-γ by human intestinal CD3-negative, IL7-receptor-positive cells, in a dose-dependent manner. Conclusions: IL6 contributes to activation of colonic natural cytotoxicity receptor-negative, CD4-negative, ILC3s in mice with chronic intestinal inflammation (TRUC mice) by increasing IL23- and IL1α-induced production of IL17A and IL22. This pathway might be targeted to treat patients with IBD because IL6, which is highly produced in colonic tissue by some IBD patients, also increased the production of IL17A, IL22, and interferon-γ by cultured human colon CD3-negative, IL7-receptor-positive cells

Environmental influences on reproductive health: the importance of chemical exposures

Chemical exposures during pregnancy can have a profound and life-long impact on human health. Due to the omnipresence of chemicals in our daily life, there is continuous contact with chemicals in food, water, air and consumer products. Consequently, human biomonitoring studies show that pregnant women around the globe are exposed to a variety of chemicals. In this review, we provide a summary of current data on maternal and fetal exposure as well as health consequences from these exposures. We review several chemical classes including polychlorinated biphenyls (PCBs), perfluoroalkyl substances (PFAS), polybrominated diphenyl ethers (PBDEs), phenols, phthalates, pesticides, and metals. Additionally, we discuss environmental disparities and vulnerable populations, and future research directions. We conclude by providing some recommendations for prevention of chemical exposure and its adverse reproductive health consequences

A Radical Innovative Change in the Practice of Hand Surgery Using Wide Awake Local Anesthesia

Wide-awake local anesthesia no tourniquet (WALANT) technique is characterized by using local anesthetic plus adrenaline administered into the opera­tive field, enabling us to perform longer and complex hand procedures without the need of an anesthetist. We assessed the impact of integrating WALANT on the practice of hand surgery in our center. We retrospectively reviewed charts of all hand surgeries performed in the years 2011 and 2016. The number of trauma cases performed in the ambulatory OR increased from 56 cases in 2011 to 131 in 2016, and elective complex cases increased from 9 to 65. Number of elective procedures conducted in the main OR increased from 67 to 105, and trauma cases performed “off hours” decreased from 53 to 21. We conclude that WALANT enables us to better utilize our OR resources, to treat hand trauma patients on an outpatient basis, and to shorten the wait time for elective hand surgery.