Osteoclasts: What Do They Do and How Do They Do It?

As Americans live longer, degenerative skeletal diseases, such as osteoporosis, become increasingly prevalent. Regardless of cause, osteoporosis reflects a relative enhancement of osteoclast activity. Thus, this unique bone resorptive cell is a prominent therapeutic target. A number of key observations provide insights into the mechanisms by which precursors commit to the osteoclast phenotype and how the mature cell degrades bone. The osteoclast is a member of the monocyte/macrophage family that differentiates under the aegis of two critical cytokines, namely RANK ligand and M-CSF. Tumor necrosis factor (TNF)-alpha also promotes osteoclastogenesis, particularly in states of inflammatory osteolysis such as that attending rheumatoid arthritis. Once differentiated, the osteoclast forms an intimate relationship with the bone surface via the alphavbeta3 integrin, which transmits matrix-derived, cytoskeleton-organizing, signals. These integrin-transmitted signals include activation of the associated proteins, c-src, syk, Vav3, and Rho GTPases. The organized cytoskeleton generates an isolated microenvironment between the cell's plasma membrane and the bone surface in which matrix mineral is mobilized by the acidic milieu and organic matrix is degraded by the lysosomal protease, cathepsin K. This review focuses on these and other molecules that mediate osteoclast differentiation or function and thus serve as candidate anti-osteoporosis therapeutic targets.     

Optimism and Adaptation to Multiple Sclerosis: What Does Optimism Mean?

The aim of the present study was to determine the meaning of optimism by explicating the dimensions underlying the notion and their links to adjusting to MS. Seventy-three patients responded to optimism questionnaires (i.e., the LOT, Generalized Self-Efficacy Scale) and outcome questionnaires. In confirmatory factor analyses, the underlying dimensions of optimism were specified. Explanatory structural equation modeling was used to examine the relation of the dimensions of optimism to coping (CISS), depression (BDI), and impaired mobility range (SIP). Optimism was found to consist of three dimensions, namely, outcome expectancies, efficacy expectancies, and unrealistic thinking. Outcome and efficacy expectancies explained depression via emotion-oriented coping but did not explain impaired mobility range either directly or indirectly. Unrealistic thinking directly explained impaired mobility range. The present study can be seen as a first step in explicating the role of optimism in the management of chronic disease.     

Toll-like Receptor 9, What O'Clock Is It?

In this issue of Immunity, Silver et al. (2012) provide evidence that murine Toll-like receptor 9 (TLR9) expression and function in innate and adaptive immunity is controlled by the circadian cycle.     

Stress,Religious Involvement,and Cholesterol: Is It Better to Give than to Receive?

The purpose of this study is to see if social support that is exchanged in religious institutions moderates the relationship between stressful life events and cholesterol. The data come from a nationwide survey of adults of all ages (N  = 816). Based on data from blood samples, cholesterol was measured by subtracting high‐density lipoprotein from total cholesterol. Questions were administered to assess how often study participants provide and receive spiritual support from fellow church members. Spiritual support is assistance that is exchanged with the explicit purpose of increasing the religious beliefs and behaviors of the recipient. Controls were established in the analyses for a number of health behaviors (e.g., exercise), other types of religious involvement (e.g., church attendance), and demographic characteristics (e.g., age, sex, education). The study variables were assessed with ordinary least squares regression procedures. The data suggest that providing spiritual support tends to reduce the magnitude of the relationship between stress and cholesterol. In contrast, similar stress‐buffering effects were not observed with the measure of receiving spiritual support at church. The findings contribute to mounting evidence on the relationship between religion and health because they are based on biological measures.     

Serum Calprotectin in Rheumatoid Arthritis: A Promising Diagnostic Marker,How Far Is It Related to Activity and Sonographic Findings?

Background

In the past 2 decades, there has been increasing interest in calprotectin. It is released and detected in serum and body fluids as a potentially useful clinical inflammatory marker. The protein has been described in synovial tissue in rheumatoid arthritis (RA) patients, specifically in the lining layer adjacent to the cartilage–pannus junction, which is the primary site of cartilage destruction and bone erosion. Assessment of inflammatory activity in RA is of pivotal importance for the optimal treatment. Our aim in this study is to measure the serum calprotectin levels in RA patients and to assess its association—if there is any—with disease activity score and radiological findings using the musculoskeletal ultrasound.

Integrating TMS with EEG: How and What For?

Transcranial magnetic stimulation (TMS) has developed into a powerful tool for studying human brain physiology and brain–behavior relations. When applied in sessions of repeated stimulation, TMS can lead to changes in neuronal activity/excitability that outlast the stimulation itself. Such aftereffects are at the heart of the offline TMS protocols in cognitive neuroscience and neurotherapeutics. However, whether these aftereffects are of applied interest critically depends on their magnitude and duration, which should fall within an experimentally or clinically useful range without increasing risks and adverse effects. In this short review, we survey combined TMS-EEG studies to characterize the TMS-aftereffects as revealed by EEG to contribute to the characterization of the most effective and promising repetitive TMS-parameters. With one session of conventional repetitive TMS (of fixed pulse frequency), aftereffects were consistently comparable in magnitude to EEG-changes reported after learning or with fatigue, and were short-lived (<70 min). The few studies using recently developed protocols (such as theta burst stimulation) suggest comparable effect-size but longer effect-durations. Based on the reviewed data, it is expected that TMS-efficacy can be further promoted by repeating TMS-sessions, by using EEG-gated TMS to tailor TMS to current neuronal state, or by other, non-conventional TMS-protocols. Newly emerging developments in offline TMS research for cognitive neuroscience and neurotherapeutics are outlined.     

Seven Steps to the Diagnosis of NSAIDs Hypersensitivity: How to Apply a New Classification in Real Practice?

Frequent use of non-steroidal anti-inflammatory drugs (NSAIDs) has been paralleled by increasing occurrence of adverse reactions, which vary from mild local skin rashes or gastric irritation to severe, generalized symptoms and even life-threatening anaphylaxis. NSAID-induced hypersensitivity reactions may involve both immunological and non-immunological mechanisms and should be differentiated from type A adverse reactions. Clinical diagnosis and effective management of a hypersensitive patient cannot be achieved without identifying the underlying mechanism. In this review, we discuss the current classification of NSAID-induced adverse reactions and propose a practical diagnostic algorithm that involves 7 steps leading to the determination of the type of NSAID-induced hypersensitivity and allows for proper patient management.     

What Is Behavioural Medicine? Commentary on Definition Proposed by Dekker,Stauder and Penedo

Purpose

Dekker et al. (2016) propose an updated definition of behavioural medicine.

Method

In this commentary, we discuss how the field and the disciplines involved have changed over time before suggesting small amendments to the proposed definition.

Results

We suggest that the range of medicine which might be considered ‘behavioural’ is increasing to encompass virtually all medical practice. In addition, the role of behaviour and the potential for behaviour change as a means of improving health have become increasingly important. A defining characteristic of behavioural medicine is the involvement of multiple disciplines, working together or in parallel and, as the extent of the field expands, more disciplines are likely to be involved.

Conclusion

We therefore propose that the definition should represent the full width of the research, practice and disciplines involved in behavioural medicine.

     

Finding the 'Ideal' Regimen for Fentanyl-Based Intravenous Patient-Controlled Analgesia: How to Give and What to Mix?

Purpose

This analysis was done to investigate the optimal regimen for fentanyl-based intravenous patient-controlled analgesia (IV-PCA) by finding a safe and effective background infusion rate and assessing the effect of adding adjuvant drugs to the PCA regimen.

Materials and Methods

Background infusion rate of fentanyl, type of adjuvant analgesic and/or antiemetic that was added to the IV-PCA, and patients that required rescue analgesics and/or antiemetics were retrospectively reviewed in 1827 patients who underwent laparoscopic abdominal surgery at a single tertiary hospital.

Results

Upon multivariate analysis, lower background infusion rates, younger age, and IV-PCA without adjuvant analgesics were identified as independent risk factors of rescue analgesic administration. Higher background infusion rates, female gender, and IV-PCA without additional 5HT₃ receptor blockers were identified as risk factors of rescue antiemetics administration. A background infusion rate of 0.38 µg/kg/hr [area under the curve (AUC) 0.638] or lower required rescue analgesics in general, whereas, addition of adjuvant analgesics decreased the rate to 0.37 µg/kg/hr (AUC 0.712) or lower. A background infusion rate of 0.36 µg/kg/hr (AUC 0.638) or higher was found to require rescue antiemetics in general, whereas, mixing antiemetics with IV-PCA increased the rate to 0.37 µg/kg/hr (AUC 0.651) or higher.

Conclusion

Background infusion rates of fentanyl between 0.12 and 0.67 µg/kg/hr may safely be used without any serious side effects for IV-PCA. In order to approach the most reasonable background infusion rate for effective analgesia without increasing postoperative nausea and vomiting, adding an adjuvant analgesic and an antiemetic should always be considered.