Chronic Porphyromonas gingivalis lipopolysaccharide induces adverse myocardial infarction wound healing through activation of CD8+ T cells.

Oral and gum health have long been associated with incidence and outcomes of cardiovascular disease. Periodontal disease increases myocardial infarction (MI) mortality by sevenfold through mechanisms that are not fully understood. The goal of this study was to evaluate whether lipopolysaccharide (LPS) from a periodontal pathogen accelerates inflammation after MI through memory T-cell activation. We compared four groups [no MI, chronic LPS, day 1 after MI, and day 1 after MI with chronic LPS (LPS + MI); n = 68 mice] using the mouse heart attack research tool 1.0 database and tissue bank coupled with new analyses and experiments. LPS + MI increased total CD8+ T cells in the left ventricle versus the other groups (P < 0.05 vs. all). Memory CD8+ T cells (CD44 + CD27+) were 10-fold greater in LPS + MI than in MI alone (P = 0.02). Interleukin (IL)-4 stimulated splenic CD8+ T cells away from an effector phenotype and toward a memory phenotype, inducing secretion of factors associated with the Wnt/ß-catenin signaling that promoted monocyte migration and decreased viability. To dissect the effect of CD8+ T cells after MI, we administered a major histocompatibility complex-I-blocking antibody starting 7 days before MI, which prevented effector CD8+ T-cell activation without affecting the memory response. The reduction in effector cells diminished infarct wall thinning but had no effect on macrophage numbers or MertK expression. LPS + MI + IgG attenuated macrophages within the infarct without effecting CD8+ T cells, suggesting these two processes were independent. Overall, our data indicate that effector and memory CD8+ T cells at post-MI day 1 are amplified by chronic LPS to potentially promote infarct wall thinning.NEW & NOTEWORTHY Although there is a well-documented link between periodontal disease and heart health, the mechanisms are unclear. Our study indicates that in response to circulating periodontal endotoxins, memory CD8+ T cells are activated, resulting in an acceleration of macrophage-mediated inflammation after MI. Blocking activation of effector CD8+ T cells had no effect on the macrophage numbers or wall thinning at post-MI day 1, indicating that this response was likely due in part to memory CD8+ T cells.

Gross trunnion failure after a metal-on-polyethylene total hip arthroplasty leading to dissociation at the femoral head-trunnion interface.

Gross trunnion failure (GTF) leading to dissociation at the femoral head-trunnion interface is an uncommon complication after total hip arthroplasty (THA). The incidence of this complication is currently unknown due to the limited number of reported cases but it is significantly more common in the context of a recalled femoral head. This report details the case of a gross trunnion failure and secondary polyethylene failure of a non-recalled metal-on-polyethylene primary THA from a taper type previously reported to be associated with an increased prevalence of mechanically assisted crevice corrosion (MACC). This case describes a 77-year-old man who was 10 years status post right THA presenting with acute-onset right hip pain after trying to rise from a seated position. Radiographs showed that the right femoral head was dissociated from the femoral component. At the time of surgical revision, there was extensive dark metallic debris in the hip joint. A revision THA was performed using a modular revision system. Clinicians must be aware that MACC can eventually lead to GTF, which can result in dissociation at the femoral head-trunnion interface in metal-on-polyethylene primary THA. Further research is needed to determine patient and implant factors that make patients susceptible to MACC/GTF so that adequate screening and patient counseling can be performed.

Day of Week and Surgery Location Effects on Stay Length and Cost for Total Joint Arthroplasty: Academic versus Orthopaedic-Specific Hospital.

Demand for total hip (THA) and knee arthroplasties (TKA) is expected to rise sharply by 2030. Increasing demand in conjunction with financial pressure requires the use of cost-effective total joint arthroplasty (TJA) strategies. This study examined the effects that day of week and surgery location [academic (AH) versus orthopaedic-specific (OsH) hospital] have on length of stay (LOS) and cost for primary TJA patients in one multihospital university-based medical center. An Institutional Review Board-approved database of adult patients undergoing primary THA or TKA from June 2013 to December 2014 was constructed. Surgery location, day of procedure, age, American Society of Anesthesiologists (ASA) classification, LOS, and cost were recorded for each patient. Data were compared for significant differences using analysis of variance, t-Test or rank sum and for strength of correlations using Pearson's or Spearman's tests. A total of 1,291 patients met inclusion criteria. OsH showed significantly lower cost and shorter LOS than AH. Wednesday surgeries had significantly higher cost and longer LOS than all other days. Friday surgeries had significantly lower cost and shorter LOS than other days. ASA 3 and 4 were associated with the highest cost and longest LOS. LOS had a moderately strong direct correlation to cost. ASA did not have a strong correlation with LOS or cost. Data separated for THA and TKA showed similar results. At our institution, OsH provides more consistent and lower LOS and cost across all ASA classes. Wednesday and Thursday surgeries have increased LOS and cost than other days, which may be due to weekend discharge difficulties (average LOS is 3.0 days).

The Role of Carrageenan and Carboxymethylcellulose in the Development of Intestinal Inflammation.

Although the exact pathophysiology remains unknown, the development of inflammatory bowel disease (IBD) is influenced by the interplay between genetics, the immune system, and environmental factors such as diet. The commonly used food additives, carrageenan and carboxymethylcellulose (CMC), are used to develop intestinal inflammation in animal models. These food additives are excluded from current dietary approaches to induce disease remission in Crohn's disease such as exclusive enteral nutrition (EEN) using a polymeric formula. By reviewing the existing scientific literature, this review aims to discuss the role that carrageenan and CMC may play in the development of IBD. Animal studies consistently report that carrageenan and CMC induce histopathological features that are typical of IBD while altering the microbiome, disrupting the intestinal epithelial barrier, inhibiting proteins that provide protection against microorganisms, and stimulating the elaboration of pro-inflammatory cytokines. Similar trials directly assessing the influence of carrageenan and CMC in humans are of course unethical to conduct, but recent studies of human epithelial cells and the human microbiome support the findings from animal studies. Carrageenan and CMC may trigger or magnify an inflammatory response in the human intestine but are unlikely to be identified as the sole environmental factor involved in the development of IBD or in disease recurrence after treatment. However, the widespread use of carrageenan and CMC in foods consumed by the pediatric population in a "Western" diet is on the rise alongside a corresponding increase in IBD incidence, and questions are being raised about the safety of frequent usage of these food additives. Therefore, further research is warranted to elucidate the role of carrageenan and CMC in intestinal inflammation, which may help identify novel nutritional strategies that hinder the development of the disease or prevent disease relapse post-EEN treatment.

Potent and orally efficacious benzothiazole amides as TRPV1 antagonists.

Benzothiazole amides were identified as TRPV1 antagonists from high throughput screening using recombinant human TRPV1 receptor and structure-activity relationships were explored to pinpoint key pharmacophore interactions. By increasing aqueous solubility, through the attachment of polar groups to the benzothiazole core, and enhancing metabolic stability, by blocking metabolic sites, the drug-like properties and pharmokinetic profiles of benzothiazole compounds were sufficiently optimized such that their therapeutic potential could be verified in rat pharmacological models of pain.