Timing of ibuprofen use and musculoskeletal adaptations to exercise training in older adults

AbstractProstaglandins (PGs) increase in bone in response to mechanical loading and stimulate bone formation. Inhibition of cyclooxygenase (COX), the enzyme responsible for PG synthesis, by non-steroidal anti-inflammatory drugs (NSAIDs) impairs the bone formation response to loading in animals when administered before, but not after, loading. The aim was to determine whether the timing of ibuprofen use (400mg before versus after exercise sessions) is a significant determinant of the adaptive response of BMD to exercise training in older adults. We hypothesized that taking ibuprofen before exercise would attenuate the improvements in total hip and lumbar spine BMD in response to 36weeks of training when compared with placebo or with ibuprofen use after exercise. Untrained women and men (N=189) aged 60 to 75years were randomly assigned to 1 of 3 treatment arms: placebo before and after exercise (PP); ibuprofen before and placebo after exercise (IP); and placebo before and ibuprofen after exercise (PI).The difference between groups in the change in BMD was not significant when IP was compared with either PP (hip, −0.5% (−1.4, 0.4); spine, 0.1% (−0.9, 1.2)) or PI (hip, 0.3% (−0.6, 1.2); spine, 0.5% (−0.5, 1.5)). Ibuprofen use appeared to have more adverse effects on BMD in women than men. The study demonstrated that ibuprofen use did not significantly alter the BMD adaptations to exercise in older adults, but this finding should be interpreted cautiously. It had been expected that the inhibition of bone formation by ibuprofen would be more robust in men than in women, but this did not appear to be the case and may have limited the power to detect the effects of ibuprofen. Further research is needed to understand whether NSAID use counteracts, in part, the beneficial effects of exercise on bone

The influence of acute exercise on bone biomarkers: protocol for a systematic review with meta-analysis. [Protocol]

Background: Bone is a plastic tissue that is responsive to its physical environment. As a result, exercise interventions represent a potential means to influence bone. However, little is currently known about how various exercise and participant characteristics interact to influence bone metabolism. Acute, controlled, interventions provide an in-vivo model through which the acute bone response to exercise can be investigated, typically by monitoring circulating bone biomarkers. Currently, substantial heterogeneity in factors such as study design, quality, exercise and participant characteristics render it difficult to synthesize and evaluate the available evidence. Using a systematic review and meta-analytic approach, the aim of this investigation is to quantify the effect of an acute exercise bout on circulating bone biomarkers as well as examine potential factors that may moderate this response e.g., variation in participant, exercise and sampling characteristics. Methods: This protocol was designed in accordance with PRISMA-P guidelines. Seven databases (Medline, Embase, Sport Discus, Cochrane CENTRAL, PEDro, LILACS and Ibec) will be systematically searched and supplemented by secondary screening of the reference lists of all included articles. The PICOS (Population, Intervention, Comparator, Outcomes and Study Design) approach was used to guide the determination of eligibility criteria. Participants of any age, sex, training or health status will be considered for inclusion. We will select studies that have measured the bone biomarker response before and after an acute exercise session. All biomarkers considered to represent bone metabolism will be considered for inclusion and sensitivity analyses will be conducted using reference biomarkers for the measurement of bone resorption and formation (namely β-CTX-1 and P1NP). Multi-level, meta-regression models within a Bayesian framework will be used to explore the main effect of acute exercise on bone biomarkers as well as potential moderating factors. Risk of bias for each individual study will be evaluated using a modified version of the Downs and Black checklist while certainty in resultant outcomes will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Discussion: A better understanding of the bone metabolic response to an acute bout of exercise has the potential to advance our understanding of the mechanisms through which this stimulus impacts bone metabolism, including factors that may moderate this response. Additionally, we will identify current gaps in the evidence base and provide recommendations to inform future research. Registration: This protocol was prospectively registered in the Open Science Framework Registry (https://osf.io/6f8dz

Validation of the English and Swahili Adaptation of the Patient Health Questionnaire–9 for Use Among Adolescents in Kenya

Purpose: Our study aimed to validate culturally adapted English and Swahili versions of the Patient Health Questionnairee9 (PHQ-9) for use with adolescents in Kenya. Criterion validity was determined with clinician-administered diagnostic interviews using the Kiddie Schedule of Affective Disorders and Schizophrenia. Methods: A total of 250 adolescents comprising 148 (59.2%) females and 102 (40.8%) males aged 10e19 years (mean ¼ 14.76; standard deviation ¼ 2.78) were recruited. The PHQ-9 was administered to all respondents concurrently in English and Swahili. Adolescents were later interviewed by clinicians using Kiddie Schedule of Affective Disorders and Schizophrenia to determine the presence or absence of current symptoms of major depressive disorder. Sensitivity specificity, positive predictive value (PPV) and negative predictive value (NPV), and likelihood ratios for various cut-off scores for PHQ-9 were analyzed using receiver operating characteristic curves. Results: The internal consistency (Cronbach’s a) for PHQ-9 was 0.862 for the English version and 0.834 for Swahili version. The area under the curve was 0.89 (95% confidence interval, 0.84e0.92) and 0.87 (95% confidence interval, 0.82e0.90) for English and Swahili version, respectively, on receiver operating characteristic analysis. A cut-off of 9 on the English-language version had a sensitivity of 95.0%, specificity of 73.0%, PPV of 0.23, and NPV of 0.99; a cut-off of 9 on the Swahili version yielded a sensitivity of 89.0%, specificity of 70.0%, PPV of 0.20, and NPV of 0.9

CD137 Is Expressed in Follicular Dendritic Cell Tumors and in Classical Hodgkin and T-Cell Lymphomas Diagnostic and Therapeutic Implications

CD137 (also known as 4-1BB and TNFRSF9) is a member of the tumor necrosis factor receptor superfamily. Originally identified as a costimulatory molecule expressed by activated T cells and NK cells, CD137 is also expressed by follicular dendritic cells, monocytes, mast cells, granulocytes, and endothelial cells. Anti-CD137 immunotherapy has recently shown promise as a treatment for solid tumors and lymphoid malignancies in preclinical models. We defined the expression of CD137 protein in both normal and neoplastic hematolymphoid tissue. CD137 protein is expressed by follicular dendritic cells in the germinal center and scattered paracortical T cells, but not by normal germinal-center B cells, bone marrow progenitor cells, or maturing thymocytes. CD137 protein is expressed by a select group of hematolymphoid tumors, including classical Hodgkin lymphoma, T-cell and NK/T-cell lymphomas, and follicular dendritic cells neoplasms. CD137 is a novel diagnostic marker of these tumors and suggests a possible target for tumor-directed antibody therapy

Acute Modulation of Adipose Tissue Lipolysis by Intravenous Estrogens

Objective: The aim of this study was to determine whether intravenous (IV) conjugated estrogens (EST) acutely enhance the suppression of whole-body or regional subcutaneous adipose tissue (SAT) lipolysis by insulin in postmenopausal women. Research Methods and Procedures: We assessed whole-body lipolysis by [2H5]glycerol rate of appearance (GlycRA) and abdominal and femoral SAT lipolysis (interstitial glycerol; GlycIS) by subcutaneous microdialysis. Postmenopausal women (n = 12) were studied on two occasions, with IV EST or saline control (CON), under basal conditions and during a 3-stage (4, 8, and 40 mU/m2/ min) hyperinsulinemic, euglycemic clamp. Ethanol outflow/inflow ratio and recovery of [13C] glycerol during microdialysis were used to assess blood flow changes and interstitial glycerol concentrations, respectively. Results: Compared with CON, EST did not affect systemic basal or insulin-mediated suppression of lipolysis (GlycRA) or SAT nutritive blood flow. Basal GlycIS in SAT was reduced on the EST day. However, insulin-mediated suppression of lipolysis in SAT was not significantly influenced by EST. Discussion: These findings suggest that estrogens acutely reduce basal lipolysis in SAT through an unknown mechanism but do not alter whole-body or SAT suppression of lipolysis by insulin. Originally published Obesity (Silver Spring), Vol. 14, No. 12, Dec 200

HER2-family signalling mechanisms, clinical implications and targeting in breast cancer.

Approximately 20 % of human breast cancers (BC) overexpress HER2 protein, and HER2-positivity is associated with a worse prognosis. Although HER2-targeted therapies have significantly improved outcomes for HER2-positive BC patients, resistance to trastuzumab-based therapy remains a clinical problem. In order to better understand resistance to HER2-targeted therapies in HER2-positive BC, it is necessary to examine HER family signalling as a whole. An extensive literature search was carried out to critically assess the current knowledge of HER family signalling in HER2-positive BC and response to HER2-targeted therapy. Known mechanisms of trastuzumab resistance include reduced receptor-antibody binding (MUC4, p95HER2), increased signalling through alternative HER family receptor tyrosine kinases (RTK), altered intracellular signalling involving loss of PTEN, reduced p27kip1, or increased PI3K/AKT activity and altered signalling via non-HER family RTKs such as IGF1R. Emerging strategies to circumvent resistance to HER2-targeted therapies in HER2-positive BC include co-targeting HER2/PI3K, pan-HER family inhibition, and novel therapies such as T-DM1. There is evidence that immunity plays a key role in the efficacy of HER-targeted therapy, and efforts are being made to exploit the immune system in order to improve the efficacy of current anti-HER therapies. With our rapidly expanding understanding of HER2 signalling mechanisms along with the repertoire of HER family and other targeted therapies, it is likely that the near future holds further dramatic improvements to the prognosis of women with HER2-positive BC

Low appendicular muscle mass is correlated with femoral neck bone mineral density loss in postmenopausal women

<p>Abstract</p> <p>Background</p> <p>After menopause, rapid bone mass loss occurs in response to hypoestrogenism. Several studies suggest that muscle mass and bone mineral density (BMD) are positively associated in postmenopausal women. Therefore, it may be assumed that postmenopausal low appendicular muscle mass (aMM) can increase BMD loss in a short period of time.</p> <p>Objective</p> <p>The purpose of this study was to assess relationship of aMM with femoral neck BMD in postmenopausal women.</p> <p>Methods</p> <p>Prospective, controlled clinical Trial including 64 women aged 45-70 years, who had not had their last menstruation for at least one year. Subjects were divided into two groups: low aMM (n = 32), and normal aMM (n-32). Femoral neck BMD and muscle mass were measured by DXA at baseline and after twelve months. Pairwise and independent t tests were used for data analysis.</p> <p>Results</p> <p>Baseline weight, BMI and muscle mass (total and appendicular) significantly differ between groups (p < 0.05). After twelve months, femoral neck BMD was significantly lower in the group with low aMM, whereas no significant difference was observed in the group with normal aMM (p < 0.05).</p> <p>Conclusion</p> <p>In postmenopausal women, low appendicular muscle mass is associated negatively with femoral neck BMD in a short period of time.</p