Parathyroid Hormone Treatment Increases Fixation of Orthopedic Implants with Gap Healing: A Biomechanical and Histomorphometric Canine Study of Porous Coated Titanium Alloy Implants in Cancellous Bone

Parathyroid hormone (PTH) administered intermittently is a bone-building peptide. In joint replacements, implants are unavoidably surrounded by gaps despite meticulous surgical technique and osseointegration is challenging. We examined the effect of human PTH(1–34) on implant fixation in an experimental gap model. We inserted cylindrical (10 × 6 mm) porous coated titanium alloy implants in a concentric 1-mm gap in normal cancellous bone of proximal tibia in 20 canines. Animals were randomized to treatment with PTH(1–34) 5 μg/kg daily. After 4 weeks, fixation was evaluated by histomorphometry and push-out test. Bone volume was increased significantly in the gap. In the outer gap (500 μm), the bone volume fraction median (interquartile range) was 27% (20–37%) for PTH and 10% (6–14%) for control. In the inner gap, the bone volume fraction was 33% (26–36%) for PTH and 13% (11–18%) for control. At the implant interface, the bone fraction improved with 16% (11–20%) for PTH and 10% (7–12%) (P = 0.07) for control. Mechanical implant fixation was improved for implants exposed to PTH. For PTH, median (interquartile range) shear stiffness was significantly higher (PTH 17.4 [12.7–39.7] MPa/mm and control 8.8 [3.3–12.4] MPa/mm) (P < 0.05). Energy absorption was significantly enhanced for PTH (PTH 781 [595–1,198.5] J/m2 and control 470 [189–596] J/m2). Increased shear strength was observed but was not significant (PTH 3.0 [2.6–4.9] and control 2.0 [0.9–3.0] MPa) (P = 0.08). Results show that PTH has a positive effect on implant fixation in regions where gaps exist in the surrounding bone. With further studies, PTH may potentially be used clinically to enhance tissue integration in these challenging environments

I Going Away. I Going Home. : Austin Clarke\u27s Leaving this Island Place

Austin Clarke’s “Leaving This Island Place” is one of scores of Caribbean autobiographical works that focus on a bright, young, lower-class islander leaving his/her small island place and setting out on “Eldorado voyages.” The narrative of that journey away from home to Europe or Canada or the United States and the later efforts to return may be said to be the Caribbean story, as suggested in the subtitle of Wilfred Cartey’s study of Caribbean literature, Whispers from the Caribbean: I Going Away, I Going Home, which argues that while in Caribbean literature there is much movement away, there is also a body of literature in which “the notion of ‘away’ and images of movement out are replaced by images of return” (xvi). Traditionally, however, the first autobiographical works, such as George Lamming’s In the Castle of My Skin, V. S. Naipaul’s A House for Mr. Biswas, Merle Hodge’s Crick Crack, Monkey, Jamaica Kincaid’s Annie John, Michelle Cliff’s No Telephone to Heaven, Edwidge Danticat’s Breath, Eyes, Memory, and Elizabeth Nunez’s Beyond the Limbo Silence, have focused on the childhood in the Caribbean and the journey away—or at least the preparation for that journey. Such is the case with Clarke’s “Leaving This Island Place.

Assessment of acute myocardial infarction: current status and recommendations from the North American society for cardiovascular imaging and the European society of cardiac radiology

There are a number of imaging tests that are used in the setting of acute myocardial infarction and acute coronary syndrome. Each has their strengths and limitations. Experts from the European Society of Cardiac Radiology and the North American Society for Cardiovascular Imaging together with other prominent imagers reviewed the literature. It is clear that there is a definite role for imaging in these patients. While comparative accuracy, convenience and cost have largely guided test decisions in the past, the introduction of newer tests is being held to a higher standard which compares patient outcomes. Multicenter randomized comparative effectiveness trials with outcome measures are required

Injection of Pseudomonas aeruginosa Exo Toxins into Host Cells Can Be Modulated by Host Factors at the Level of Translocon Assembly and/or Activity

Pseudomonas aeruginosa type III secretion apparatus exports and translocates four exotoxins into the cytoplasm of the host cell. The translocation requires two hydrophobic bacterial proteins, PopB and PopD, that are found associated with host cell membranes following infection. In this work we examined the influence of host cell elements on exotoxin translocation efficiency. We developed a quantitative flow cytometry based assay of translocation that used protein fusions between either ExoS or ExoY and the ß-lactamase reporter enzyme. In parallel, association of translocon proteins with host plasma membranes was evaluated by immunodetection of PopB/D following sucrose gradient fractionation of membranes. A pro-myelocytic cell line (HL-60) and a pro-monocytic cell line (U937) were found resistant to toxin injection even though PopB/D associated with host cell plasma membranes. Differentiation of these cells to either macrophage- or neutrophil-like cell lines resulted in injection-sensitive phenotype without significantly changing the level of membrane-inserted translocon proteins. As previous in vitro studies have indicated that the lysis of liposomes by PopB and PopD requires both cholesterol and phosphatidyl-serine, we first examined the role of cholesterol in translocation efficiency. Treatment of sensitive HL-60 cells with methyl-ß-cyclodextrine, a cholesterol-depleting agent, resulted in a diminished injection of ExoS-Bla. Moreover, the PopB translocator was found in the membrane fraction, obtained from sucrose-gradient purifications, containing the lipid-raft marker flotillin. Examination of components of signalling pathways influencing the toxin injection was further assayed through a pharmacological approach. A systematic detection of translocon proteins within host membranes showed that, in addition to membrane composition, some general signalling pathways involved in actin polymerization may be critical for the formation of a functional pore. In conclusion, we provide new insights in regulation of translocation process and suggest possible cross-talks between eukaryotic cell and the pathogen at the level of exotoxin translocation

Non-invasive imaging in the diagnosis of acute viral myocarditis

Autopsy series of consecutive cases have demonstrated an incidence of myocarditis at approximately 1–10%; on the contrary, myocarditis is seriously underdiagnosed clinically. In a traditional view, the gold standard has been myocardial biopsy. However, it is generally specific but invasive and less sensitive, mostly because of the focal nature of the disease. Thus, non-invasive approaches to detect myocarditis are necessary. The traditional diagnostic tools are electrocardiography, laboratory values, especially troponin T or I, creatine kinase and echocardiography. For a long period, nuclear technique with indium-111 antimyosin antibody has been used as a diagnostic approach. In the last years, the use of this technique has declined because of radiation exposure and 48-h delay in obtaining imaging after injection to prevent blood pool effect. Thus, a non-invasive diagnostic approach without radiation and online image availability has been awaited. Cardiac magnetic resonance imaging has these promising characteristics. With this technique, it is possible to analyse inflammation, oedema and necrosis in addition to functional parameters such as left ventricular function, regional wall motion and dimensions. Thus, cardiovascular magnetic resonance imaging has emerged as the most important imaging tool in the diagnostic procedure and the review focus on this field. But there are also advances in echocardiography and computer tomography, which are described in detail

Teaching the science of learning

The science of learning has made a considerable contribution to our understanding of effective teaching and learning strategies. However, few instructors outside of the field are privy to this research. In this Tutorial Review, we focus on six specific cognitive strategies that have received robust support from decades of research: spaced practice, interleaving, retrieval practice, elaboration, concrete examples, and dual coding. We describe the basic research behind each strategy and relevant applied research, present examples of existing and suggested implementation, and make recommendations for further research that would broaden the reach of these strategies

In vivo MRI and ex vivo histological assessment of the cardioprotection induced by ischemic preconditioning, postconditioning and remote conditioning in a closed-chest porcine model of reperfused acute myocardial infarction: importance of microvasculature

BACKGROUND: Cardioprotective value of ischemic post- (IPostC), remote (RIC) conditioning in acute myocardial infarction (AMI) is unclear in clinical trials. To evaluate cardioprotection, most translational animal studies and clinical trials utilize necrotic tissue referred to the area at risk (AAR) by magnetic resonance imaging (MRI). However, determination of AAR by MRI' may not be accurate, since MRI-indices of microvascular damage, i.e., myocardial edema and microvascular obstruction (MVO), may be affected by cardioprotection independently from myocardial necrosis. Therefore, we assessed the effect of IPostC, RIC conditioning and ischemic preconditioning (IPreC; positive control) on myocardial necrosis, edema and MVO in a clinically relevant, closed-chest pig model of AMI. METHODS AND RESULTS: Acute myocardial infarction was induced by a 90-min balloon occlusion of the left anterior descending coronary artery (LAD) in domestic juvenile female pigs. IPostC (6 x 30 s ischemia/reperfusion after 90-min occlusion) and RIC (4 x 5 min hind limb ischemia/reperfusion during 90-min LAD occlusion) did not reduce myocardial necrosis as assessed by late gadolinium enhancement 3 days after reperfusion and by ex vivo triphenyltetrazolium chloride staining 3 h after reperfusion, however, the positive control, IPreC (3 x 5 min ischemia/reperfusion before 90-min LAD occlusion) did. IPostC and RIC attenuated myocardial edema as measured by cardiac T2-weighted MRI 3 days after reperfusion, however, AAR measured by Evans blue staining was not different among groups, which confirms that myocardial edema is not a measure of AAR, IPostC and IPreC but not RIC decreased MVO. CONCLUSION: We conclude that IPostC and RIC interventions may protect the coronary microvasculature even without reducing myocardial necrosis

The cytoskeleton in cell-autonomous immunity: structural determinants of host defence

Host cells use antimicrobial proteins, pathogen-restrictive compartmentalization and cell death in their defence against intracellular pathogens. Recent work has revealed that four components of the cytoskeleton — actin, microtubules, intermediate filaments and septins, which are well known for their roles in cell division, shape and movement — have important functions in innate immunity and cellular self-defence. Investigations using cellular and animal models have shown that these cytoskeletal proteins are crucial for sensing bacteria and for mobilizing effector mechanisms to eliminate them. In this Review, we highlight the emerging roles of the cytoskeleton as a structural determinant of cell-autonomous host defence