Listeria monocytogenes is a facultative intracellular bacterium that has predilection for causing central nervous systemic infections in humans and domesticated animals. This pathogen can be found worldwide in the food supply and most L. monocytogenes infections are acquired through ingestion of contaminated food. The main clinical syndromes caused by L. monocytogenes include febrile gastroenteritis, perinatal infection, and systemic infections marked by central nervous system infections with or without bacteremia. Experimental infection of mice has been used for over 50 years as a model system to study the pathogenesis of this organism including the mechanisms by which it invades the brain. Data from this model indicate that a specific subset of monocytes, distinguished in part by high expression of the Ly-6C antigen, become parasitized in the bone marrow and have a key role in transporting intracellular bacteria across the blood-brain barriers and into the central nervous system. This Minireview will summarize recent epidemiologic and clinical information regarding L. monocytogenes as a human pathogen and will discuss current in vitro and in vivo data relevant to the role of parasitized monocytes and the pathogenetic mechanisms that underlie its formidable ability to invade the central nervous system.

Osteoporosis commonly afflicts patients with inflammatory bowel disease, and many factors link the 2 states together. A literature review was conducted about the pathophysiology of osteoporosis in relation to inflammatory bowel disease. Screening guidelines for osteoporosis in general as well as those directed at patients with inflammatory bowel disease are reviewed, as are currently available treatment options. The purpose of this article is to increase physician awareness about osteopenia and osteoporosis occurring in patients with inflammatory bowel disease and to provide basic, clinically relevant information about the pathophysiology and guidelines to help them treat these patients in a cost-effective manner. KeywordsInflammatory bowel disease; Osteopenia; Osteoporosis Approximately 1.4 million people in the United States and 2.2 million people in Europe suffer from inflammatory bowel disease. 1 Patients with inflammatory bowel disease are at higher risk of developing osteoporosis and osteopenia than the general population, with relative risk of fracture 40% higher in patients with inflammatory bowel disease. 2 The prevalence of osteopenia and osteoporosis in patients with inflammatory bowel disease varies significantly depending on the study populations, location, and design, but ranges from 22%-77% and 17%-41%, respectively. 3,4 Because of the high prevalence, it is imperative that physicians recognize patients at risk for osteoporosis, screen appropriate patients, and prevent or treat accordingly. PATHOPHYSIOLOGY OF OSTEOPOROSIS IN INFLAMMATORY BOWEL DISEASEBone is a living tissue that undergoes constant remodeling by bone-forming cells (osteoblasts) and bone-resorbing cells (osteoclasts). Imbalances in bone formation and resorption lead to osteoporosis. Several gastrointestinal dis orders have been associated with osteoporosis and ROLE OF CORTICOSTEROIDSBecause glucocorticoids are a treatment mainstay for chronic inflammatory diseases, it is important to recognize the effects they have on bone remodeling. They have been shown to impair osteoblast function, induce osteoblast apoptosis, reduce intestinal calcium absorption, and increase renal excretion of calcium. 5,7 Patients on glucocorticoids are at increased risk for fracture, with the greatest bone loss occurring in the initial months of treatment. 8 Interestingly, studies show a decrease in fracture risk back toward baseline after stopping glucocorticoid therapy. 9 It is, however, difficult to distinguish how much impact glucocorticoid use has on bone compared with disease activity, as increased disease activity and higher degrees of inflammation are indications for steroid use. While prednisone, prednisolone, and methylprednisolone are systemically acting steroids and one of the major contributing factors in osteoporosis in inflammatory bowel disease, budesonide, a locally acting corticosteroid with low systemic bioavailability, has been increasingly used in the treatment of inflammatory bowel disease because of its lack of systemic effect...

Biologics such as antitumor necrosis factor (anti-TNF) drugs have emerged as important agents in the treatment of many chronic inflammatory diseases, especially in cases refractory to conventional treatment modalities. However, opportunistic infections have become a major safety concern in patients on anti-TNF therapy, and physicians who utilize these agents must understand the increased risks of infection. A literature review of the published data on the risk of bacterial, viral, fungal, and parasitic infections associated with anti-TNF therapy was performed and the clinical presentation, diagnostic tests, management, and prevention of opportunistic infections in patients receiving anti-TNF therapy were reviewed. Awareness of the therapeutic potential and associated adverse events is necessary for maximizing therapeutic benefits while minimizing adverse effects from anti-TNF treatments. Patients should be adequately vaccinated when possible and closely monitored for early signs of infection. When serious infections occur, withdrawal of anti-TNF therapy may be necessary until the infection has been identified and properly treated.

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BackgroundMore than 80% of intestinal neoplasia is associated with the adenomatous polyposis coli (APC) mutation. Doublecortin-like kinase 1 (Dclk1), a kinase protein, is overexpressed in colorectal cancer and specifically marks tumor stem cells (TSCs) that self-renew and increased the tumor progeny in Apc Min/+ mice. However, the role of Dclk1 expression and its contribution to regulating pro-survival signaling for tumor progression in Apc mutant cancer is poorly understood.MethodsWe analyzed DCLK1 and pro-survival signaling gene expression datasets of 329 specimens from TCGA Colon Adenocarcinoma Cancer Data. The network of DCLK1 and pro-survival signaling was analyzed utilizing the GeneMANIA database. We examined the expression levels of Dclk1 and other stem cell-associated markers, pro-survival signaling pathways, cell self-renewal in the isolated intestinal epithelial cells of Apc Min/+mice with high-grade dysplasia and adenocarcinoma. To determine the functional role of Dclk1 for tumor progression, we knocked down Dclk1 and determined the pro-survival signaling pathways and stemness. We used siRNA technology to gene silence pro-survival signaling in colon cancer cells in vitro. We utilized FACS, IHC, western blot, RT-PCR, and clonogenic (self-renewal) assays.ResultsWe found a correlation between DCLK1 and pro-survival signaling expression. The expression of Dclk1 and stem cell-associated markers Lgr5, Bmi1, and Musashi1 were significantly higher in the intestinal epithelial cells of Apc Min/+mice than in wild-type controls. Intestinal epithelial cells of Apc Min/+mice showed increased expression of pro-survival signaling, pluripotency and self-renewal ability. Furthermore, the enteroids formed from the intestinal Dclk1+ cells of Apc Min/+mice display higher pluripotency and pro-survival signaling. Dclk1 knockdown in Apc Min/+ mice attenuates intestinal adenomas and adenocarcinoma, and decreases pro-survival signaling and self-renewal. Knocking down RELA and NOTCH1 pro-survival signaling and DCLK1 in HT29 and DLD1 colon cancer cells in vitro reduced the tumor cells’ ability to self-renew and survive.ConclusionOur results indicate that Dclk1 is essential in advancing intestinal tumorigenesis. Knocking down Dclk1 decreases tumor stemness and progression and is thus predicted to regulate pro-survival signaling and tumor cell pluripotency. This study provides a strong rationale to target Dclk1 as a treatment strategy for colorectal cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-017-0594-y) contains supplementary material, which is available to authorized users.

To study the role of the group A streptococcal capsule in pharyngeal colonization, we used two acapsular mutants derived from a type 24 strain of group A Streptococcus by transposon mutagenesis. One mutant had a stable acapsular phenotype due to a transposon-associated chromosomal deletion of essential capsule synthetic genes, while the second mutant could revert to the encapsulated phenotype at a low frequency (<10-4) upon spontaneous excision of the transposon from the capsule-synthesis region of the chromosome. Both acapsular mutants were sensitive to phagocytic killing in vitro and had reduced virulence in mice after intraperitoneal challenge. Mice inoculated intranasally with the stable acapsular mutant rapidly cleared the organisms from the pharynx, and no mice died. In contrast, throat cultures of animals challenged with the revertible mutant yielded many encapsulated revertants, and mortality was similar to that of animals challenged with the parent strain. The rapid emergence of a population of encapsulated revertants in the pharynx implies that the capsule conferred a powerful selective advantage in this environmental niche. Together with the complete avirulence of the stable acapsular mutant, these observations indicate that the hyaluronic acid capsule plays a critical role in colonization and infection of the pharynx by group A streptococci.A critical first step in the pathogenesis of streptococcal pharyngitis is colonization of the mucosal epithelium of the pharynx by group A streptococci (GAS). Successful colonization leads to bacterial proliferation in the pharynx, local tissue invasion, and host inflammatory responses that result in the clinical manifestations of pharyngitis. Pharyngeal infection occasionally progresses to invasion of deeper tissues to produce local suppurative complications or systemic infection. In addition, colonization of the pharynx is not only important as a prelude to pharyngitis and related infectious syndromes but also appears to be an absolute prerequisite for development of the postinfectious autoimmune syndrome of acute rheumatic fever.Studies of adherence of GAS to epithelial cells have implicated several bacterial surface molecules in the attachment process including lipoteichoic acid, M protein, and fibronectin-binding proteins (reviewed in ref.

Hepatitis C virus (HCV) infection is a prominent risk factor for the development of hepatocellular carcinoma (HCC).

Robert Koch's discovery of the anthrax bacillus in 1876 launched the field of medical bacteriology. A 'golden age' of scientific discovery ensued. A century after Koch's death, we remember his life and work.