200 research outputs found
Appearance of the weight-bearing lateral radiograph in retrocalcaneal bursitis
Background and purpose A retrocalcaneal bursitis is caused by repetitive impingement of the bursa between the Achilles tendon and the posterosuperior calcaneus. The bursa is situated in the posteroinferior corner of Kager's triangle (retrocalcaneal recess), which is a radiolucency with sharp borders on the lateral radiograph of the ankle. If there is inflammation, the fluid-filled bursa is less radiolucent, making it difficult to delineate the retrocalcaneal recess. We assessed whether the radiographic appearance of the retrocalcaneal recess on plain digital (filmless) radiographs could be used in the diagnosis of a retrocalcaneal bursitis. Methods Whether or not there was obliteration of the retrocalcaneal recess (yes/no) on 74 digital weight-bearing lateral radiographs of the ankle was independently assessed by 2 observers. The radiographs were from 24 patients (25 heels) with retrocalcaneal bursitis (confirmed on endoscopic calcaneoplasty); the control group consisted of 50 patients (59 heels). Results The sensitivity of the test was 83% for observer 1 and 79% for observer 2. Specificity was 100% and 98%, respectively. The kappa value of the interobserver reliability test was 0.86. For observer 1, intraobserver reliability was 0.96 and for observer 2 it was 0.92. Interpretation On digital weight-bearing lateral radiographs of a retrocalcaneal bursitis, the retrocalcaneal recess has a typical appearanc
Active Singularities for Multivehicle Motion Planning in an N-Vortex System
Abstract. This paper presents a path-planning paradigm for distributed control of multiple sensor platforms in a geophysical flow well-approximated by a point-vortex model. We utilize Hamiltonian dynamics to generate control vector fields for vehicle motion in N-vortex flows using the con-cept of an active singularity whose strength is a tunable control input. We introduce active singularities that are virtual point vortices possibly collocated with virtual point sources or sinks. We provide a principled method to stabilize relative equilibria of these virtual vortices in the presence of the actual point vortices, which represent the underlying geo-physical flow. We illustrate how these relative equilibria may be useful for vehicle path planning and sampling in a geophysical flow. Preliminary results presented here are based on an adaptive control design
Pathologic and biologic response to preoperative endocrine therapy in patients with ER-positive ductal carcinoma in situ
Abstract Background Endocrine therapy is commonly recommended in the adjuvant setting for patients as treatment for ductal carcinoma in situ (DCIS). However, it is unknown whether a neoadjuvant (preoperative) anti-estrogen approach to DCIS results in any biological change. This study was undertaken to investigate the pathologic and biomarker changes in DCIS following neoadjuvant endocrine therapy compared to a group of patients who did not undergo preoperative anti-estrogenic treatment to determine whether such treatment results in detectable histologic alterations. Methods Patients (n = 23) diagnosed with ER-positive pure DCIS by stereotactic core biopsy were enrolled in a trial of neoadjuvant anti-estrogen therapy followed by definitive excision. Patients on hormone replacement therapy, with palpable masses, or with histologic or clinical suspicion of invasion were excluded. Premenopausal women were treated with tamoxifen and postmenopausal women were treated with letrozole. Pathologic markers of proliferation, inflammation, and apoptosis were evaluated at baseline and at three months. Biomarker changes were compared to a cohort of patients who had not received preoperative treatment. Results Median age of the cohort was 53 years (range 38β78); 14 were premenopausal. Following treatment, predominant morphologic changes included increased multinucleated histiocytes and degenerated cells, decreased duct extension, and prominent periductal fibrosis. Two postmenopausal patients had ADH only with no residual DCIS at excision. Postmenopausal women on letrozole had significant reduction of PR, and Ki67 as well as increase in CD68-positive cells. For premenopausal women on tamoxifen treatment, the only significant change was increase in CD68. No change in cleaved caspase 3 was found. Two patients had invasive cancer at surgery. Conclusion Preoperative therapy for DCIS is associated with significant pathologic alterations. These changes may be clinically significant. Further work is needed to identify which women may be the best candidates for such treatment for DCIS, and whether best responders may safely avoid surgical intervention. Trial Registration ClinicalTrials.gov NCT0029074
Plasma triglyceride concentrations are rapidly reduced following individual bouts of endurance exercise in women
It is known that chronic endurance training leads to improvements in the lipoprotein profile, but less is known about changes that occur during postexercise recovery acutely. We analyzed triglyceride (TG), cholesterol classes and apolipoproteins in samples collected before, during and after individual moderate- and hard-intensity exercise sessions in men and women that were isoenergetic between intensities. Young healthy men (nΒ =Β 9) and young healthy women (nΒ =Β 9) were studied under three different conditions with diet unchanged between trials: (1) before, during and 3Β h after 90Β min of exercise at 45% VO2peak (E45); (2) before, during and 3Β h after 60Β min of exercise at 65% VO2peak (E65), and (3) in a time-matched sedentary control trial (C). At baseline, high-density lipoprotein cholesterol (HDL-C) was higher in women than men (PΒ <Β 0.05). In men and in women, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), HDL-C, apolipoprotein A-I (apoA-I), apolipoprotein B (apoB), and LDL peak particle size were unaltered by exercise either during exertion or after 3Β h of recovery. In women, but not in men, average plasma TG was significantly reduced below C at 3Β h postexercise by approximately 15% in E45 and 25% in E65 (PΒ <Β 0.05) with no significant difference between exercise intensities. In summary, plasma TG concentration rapidly declines following exercise in women, but not in men. These results demonstrate an important mechanism by which each individual exercise session may incrementally reduce the risk for cardiovascular disease (CVD) in women
Sex differences in experiences of multiple traumas and mental health problems in the UK Biobank cohort
PurposeExperiences of reported trauma are common and are associated with a range of mental health problems. Sex differences in how reported traumas are experienced over the life course in relation to mental health require further exploration. Methods157,358 participants contributed data for the UK Biobank Mental Health Questionnaire (MHQ). Stratified Latent Class Analysis (LCA) was used to analyse combinations of reported traumatic experiences in males and females separately, and associations with mental health. ResultsIn females, five trauma classes were identified: a low-risk class (58.6%), a childhood trauma class (13.5%), an intimate partner violence class (12.9%), a sexual violence class (9.1%), and a high-risk class (5.9%). In males, a three-class solution was preferred: a low-risk class (72.6%), a physical and emotional trauma class (21.9%), and a sexual violence class (5.5%). In comparison to the low-risk class in each sex, all trauma classes were associated with increased odds of current depression, anxiety, and hazardous/harmful alcohol use after adjustment for covariates. The high-risk class in females and the sexual violence class in males produced significantly increased odds for recent psychotic experiences. ConclusionThere are sex differences in how reported traumatic experiences co-occur across a lifespan, with females at the greatest risk. However, reporting either sexual violence or multiple types of trauma was associated with increased odds of mental health problems for both males and females. Findings emphasise the public mental health importance of identifying and responding to both men and womenβs experiences of trauma, including sexual violence
Mycobacterium indicus pranii Supernatant Induces Apoptotic Cell Death in Mouse Peritoneal Macrophages In Vitro
Mycobacterium indicus pranii (MIP), also known as Mw, is a saprophytic, non-pathogenic strain of Mycobacterium and is commercially available as a heat-killed vaccine for leprosy and recently tuberculosis (TB) as part of MDT. In this study we provide evidence that cell-free supernatant collected from original MIP suspension induces rapid and enhanced apoptosis in mouse peritoneal macrophages in vitro. It is demonstrated that the MIP cell-free supernatant induced apoptosis is mitochondria-mediated and caspase independent and involves mitochondrial translocation of Bax and subsequent release of AIF and cytochrome c from the mitochondria. Experiments with pharmacological inhibitors suggest a possible role of PKC in mitochondria-mediated apoptosis of macrophages
The effects of traditional, superset, and tri-set resistance training structures on perceived intensity and physiological responses.
PURPOSE: Investigate the acute and short-term (i.e., 24Β h) effects of traditional (TRAD), superset (SS), and tri-set (TRI) resistance training protocols on perceptions of intensity and physiological responses. METHODS: Fourteen male participants completed a familiarisation session and three resistance training protocols (i.e., TRAD, SS, and TRI) in a randomised-crossover design. Rating of perceived exertion, lactate concentration ([Lac]), creatine kinase concentration ([CK]), countermovement jump (CMJ), testosterone, and cortisol concentrations was measured pre, immediately, and 24-h post the resistance training sessions with magnitude-based inferences assessing changes/differences within/between protocols. RESULTS: TRI reported possible to almost certainly greater efficiency and rate of perceived exertion, although session perceived load was very likely lower. SS and TRI had very likely to almost certainly greater lactate responses during the protocols, with changes in [CK] being very likely and likely increased at 24Β h, respectively. At 24-h post-training, CMJ variables in the TRAD protocol had returned to baseline; however, SS and TRI were still possibly to likely reduced. Possible increases in testosterone immediately post SS and TRI protocols were reported, with SS showing possible increases at 24-h post-training. TRAD and SS showed almost certain and likely decreases in cortisol immediately post, respectively, with TRAD reporting likely decreases at 24-h post-training. CONCLUSIONS: SS and TRI can enhance training efficiency and reduce training time. However, acute and short-term physiological responses differ between protocols. Athletes can utilise SS and TRI resistance training, but may require additional recovery post-training to minimise effects of fatigue
Eccentric Exercise Activates Novel Transcriptional Regulation of Hypertrophic Signaling Pathways Not Affected by Hormone Changes
Unaccustomed eccentric exercise damages skeletal muscle tissue, activating mechanisms of recovery and remodeling that may be influenced by the female sex hormone 17Ξ²-estradiol (E2). Using high density oligonucleotide based microarrays, we screened for differences in mRNA expression caused by E2 and eccentric exercise. After random assignment to 8 days of either placebo (CON) or E2 (EXP), eighteen men performed 150 single-leg eccentric contractions. Muscle biopsies were collected at baseline (BL), following supplementation (PS), +3 hours (3H) and +48 hours (48H) after exercise. Serum E2 concentrations increased significantly with supplementation (P<0.001) but did not affect microarray results. Exercise led to early transcriptional changes in striated muscle activator of Rho signaling (STARS), Rho family GTPase 3 (RND3), mitogen activated protein kinase (MAPK) regulation and the downstream transcription factor FOS. Targeted RT-PCR analysis identified concurrent induction of negative regulators of calcineurin signaling RCAN (P<0.001) and HMOX1 (Pβ=β0.009). Protein contents were elevated for RND3 at 3H (Pβ=β0.02) and FOS at 48H (P<0.05). These findings indicate that early RhoA and NFAT signaling and regulation are altered following exercise for muscle remodeling and repair, but are not affected by E2
The Chemokine CXCL12 Is Essential for the Clearance of the Filaria Litomosoides sigmodontis in Resistant Mice
Litomosoides sigmodontis is a cause of filarial infection in rodents. Once infective larvae overcome the skin barrier, they enter the lymphatic system and then settle in the pleural cavity, causing soft tissue infection. The outcome of infection depends on the parasite's modulatory ability and also on the immune response of the infected host, which is influenced by its genetic background. The goal of this study was to determine whether host factors such as the chemokine axis CXCL12/CXCR4, which notably participates in the control of immune surveillance, can influence the outcome of the infection. We therefore set up comparative analyses of subcutaneous infection by L. sigmodontis in two inbred mouse strains with different outcomes: one susceptible strain (BALB/c) and one resistant strain (C57BL/6). We showed that rapid parasite clearance was associated with a L. sigmodontis-specific CXCL12-dependent cell response in C57BL/6 mice. CXCL12 was produced mainly by pleural mesothelial cells during infection. Conversely, the delayed parasite clearance in BALB/c mice was neither associated with an increase in CXCL12 levels nor with cell influx into the pleural cavity. Remarkably, interfering with the CXCL12/CXCR4 axis in both strains of mice delayed filarial development, as evidenced by the postponement of the fourth molting process. Furthermore, the in vitro growth of stage 4 filariae was favored by the addition of low amounts of CXCL12. The CXCL12/CXCR4 axis thus appears to have a dual effect on the L. sigmodontis life cycle: by acting as a host-cell restriction factor for infection, and as a growth factor for worms
CXCR4 Mediated Chemotaxis Is Regulated by 5T4 Oncofetal Glycoprotein in Mouse Embryonic Cells
5T4 oncofetal molecules are highly expressed during development and upregulated in cancer while showing only low levels in some adult tissues. Upregulation of 5T4 expression is a marker of loss of pluripotency in the early differentiation of embryonic stem (ES) cells and forms an integrated component of an epithelial-mesenchymal transition, a process important during embryonic development and metastatic spread of epithelial tumors. Investigation of the transcriptional changes in early ES differentiation showed upregulation of CXCL12 and down-regulation of a cell surface protease, CD26, which cleaves this chemokine. CXCL12 binds to the widely expressed CXCR4 and regulates key aspects of development, stem cell motility and tumour metastasis to tissues with high levels of CXCL12. We show that the 5T4 glycoprotein is required for optimal functional cell surface expression of the chemokine receptor CXCR4 and CXCL12 mediated chemotaxis in differentiating murine embryonic stem cells and embryo fibroblasts (MEF). Cell surface expression of 5T4 and CXCR4 molecules is co-localized in differentiating ES cells and MEF. By contrast, differentiating ES and MEF derived from 5T4 knockout (KO) mice show only intracellular CXCR4 expression but infection with adenovirus encoding mouse 5T4 restores CXCL12 chemotaxis and surface co-localization with 5T4 molecules. A series of chimeric constructs with interchanged domains of 5T4 and the glycoprotein CD44 were used to map the 5T4 sequences relevant for CXCR4 membrane expression and function in 5T4KO MEF. These data identified the 5T4 transmembrane domain as sufficient and necessary to enable CXCR4 cell surface expression and chemotaxis. Furthermore, some monoclonal antibodies against m5T4 can inhibit CXCL12 chemotaxis of differentiating ES cells and MEF which is not mediated by simple antigenic modulation. Collectively, these data support a molecular interaction of 5T4 and CXCR4 occurring at the cell surface which directly facilitates the biological response to CXCL12. The regulation of CXCR4 surface expression by 5T4 molecules is a novel means to control responses to the chemokine CXCL12 for example during embryogenesis but can also be selected to advantage the spread of a 5T4 positive tumor from its primary site
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