Muscle activation of patients suffering from asymmetric ankle osteoarthritis during isometric contractions and level walking – A time–frequency analysis

Asymmetric osteoarthritis (OA) is a common type of OA in the ankle joint. OA also influences the muscles surrounding a joint, however, little is known about the muscle activation in asymmetric ankle OA. Therefore, the aim of this study was to characterize the patients’ muscle activation during isometric ankle torque measurements and level walking. Surface electromyography (EMG) was measured of gastrocnemius medialis (GM) and lateralis (GL), soleus (SO), tibialis anterior (TA), and peroneus longus (PL) in 12 healthy subjects and 12 ankle OA patients. To obtain time and frequency components of the EMG power a wavelet transformation was performed. Furthermore, entropy was introduced to characterize the homogeneity of the wavelet patterns.Patients produced lower plantar- and dorsiflexion torques and their TA wavelet spectrum was shifted towards lower frequencies. While walking, the patients’ muscles were active with a lower intensity and over a broader time–frequency region. In contrast to controls and varus OA patients, maximal GM activity of valgus OA patients lagged behind the activity of GL and SO. In both tasks, PL of the valgus patients contained more low frequency power. The results of this study will help to assess whether surgical interventions of ankle OA can reestablish the muscle activation patterns.     

Adipocytokines,Hepatic and Inflammatory Biomarkers and Incidence of Type 2 Diabetes. The CoLaus Study

Context

There is contradictory information regarding the prognostic importance of adipocytokines, hepatic and inflammatory biomarkers on the incidence of type 2 diabetes. The objective was to assess the prognostic relevance of adipocytokine and inflammatory markers (C-reactive protein – CRP; interleukin-1beta – IL-1β; interleukin-6– IL-6; tumour necrosis factor-α – TNF-α; leptin and adiponectin) and gamma-glutamyl transpeptidase (γGT) on the incidence of type 2 diabetes.

Methods

Prospective, population-based study including 3,842 non-diabetic participants (43.3% men, age range 35 to 75 years), followed for an average of 5.5 years (2003–2008). The endpoint was the occurrence of type 2 diabetes.

Results

208 participants (5.4%, 66 women) developed type 2 diabetes during follow-up. On univariate analysis, participants who developed type 2 diabetes had significantly higher baseline levels of IL-6, CRP, leptin and γGT, and lower levels of adiponectin than participants who remained free of type 2 diabetes. After adjusting for a validated type 2 diabetes risk score, only the associations with adiponectin: Odds Ratio and (95% confidence interval): 0.97 (0.64–1.47), 0.84 (0.55–1.30) and 0.64 (0.40–1.03) for the second, third and forth gender-specific quartiles respectively, remained significant (P-value for trend = 0.05). Adding each marker to a validated type 2 diabetes risk score (including age, family history of type 2 diabetes, height, waist circumference, resting heart rate, presence of hypertension, HDL cholesterol, triglycerides, fasting glucose and serum uric acid) did not improve the area under the ROC or the net reclassification index; similar findings were obtained when the markers were combined, when the markers were used as continuous (log-transformed) variables or when gender-specific quartiles were used.

Conclusion

Decreased adiponectin levels are associated with an increased risk for incident type 2 diabetes, but they seem to add little information regarding the risk of developing type 2 diabetes to a validated risk score.     

The Neuropeptide Y Y1 Receptor: A Diagnostic Marker? Expression in MCF-7 Breast Cancer Cells Is Down-Regulated by Antiestrogens In Vitro and in Xenografts

The neuropeptide Y (NPY) Y₁ receptor (Y₁R) has been suggested as a tumor marker for in vivo imaging and as a therapeutic target. In view of the assumed link between estrogen receptor (ER) and Y₁R in mammary carcinoma and with respect to the development of new diagnostic tools, we investigated the Y₁R protein expression in human MCF-7 cell variants differing in ER content and sensitivity against antiestrogens. ER and Y₁R expression were quantified by radioligand binding using [³H]-17β-estradiol and the Y₁R selective antagonist [³H]-UR-MK114, respectively. The latter was used for cellular binding studies and for autoradiography of MCF-7 xenografts. The fluorescent ligands Cy5-pNPY (universal Y₁R, Y₂R and Y₅R agonist) and UR-MK22 (selective Y₁R antagonist), as well as the selective antagonists BIBP3226 (Y₁R), BIIE0246 (Y₂R) and {"type":"entrez-protein","attrs":{"text":"CGP71683","term_id":"876483490","term_text":"CGP71683"}}CGP71683 (Y₅R) were used to identify the NPY receptor subtype(s) by confocal microscopy. Y₁R functionality was determined by mobilization of intracellular Ca²⁺. Sensitivity of MCF-7 cells against antiestrogen 4-hydroxytamoxifen correlated directly with the ER content. The exclusive expression of Y₁Rs was confirmed by confocal microscopy. The Y₁R protein was up-regulated (100%) by 17β-estradiol (EC₅₀ 20 pM) and the predominant role of ERα was demonstrated by using the ERα-selective agonist “propylpyrazole triol”. 17β-Estradiol-induced over-expression of functional Y₁R protein was reverted by the antiestrogen fulvestrant (IC₅₀ 5 nM) in vitro. Furthermore, tamoxifen treatment of nude mice resulted in an almost total loss of Y₁Rs in MCF-7 xenografts. In conclusion, the value of the Y₁R as a target for therapy and imaging in breast cancer patients may be compromised due to Y₁R down-regulation induced by hormonal (antiestrogen) treatment.     

Phylogeographic analysis elucidates the influence of the ice ages on the disjunct distribution of relict dragonflies in Asia

Unusual biogeographic patterns of closely related groups reflect events in the past, and molecular analyses can help to elucidate these events. While ample research on the origin of disjunct distributions of different organism groups in the Western Paleartic has been conducted, such studies are rare for Eastern Palearctic organisms. In this paper we present a phylogeographic analysis of the disjunct distribution pattern of the extant species of the strongly cool-adapted Epiophlebia dragonflies from Asia. We investigated sequences of the usually more conserved 18 S rDNA and 28 S rDNA genes and the more variable sequences of ITS1, ITS2 and CO2 of all three currently recognised Epiophlebia species and of a sample of other odonatan species. In all genes investigated the degrees of similarity between species of Epiophlebia are very high and resemble those otherwise found between different populations of the same species in Odonata. This indicates that substantial gene transfer between these populations occurred in the comparatively recent past. Our analyses imply a wide distribution of the ancestor of extant Epiophlebia in Southeast Asia during the last ice age, when suitable habitats were more common. During the following warming phase, its range contracted, resulting in the current disjunct distribution. Given the strong sensitivity of these species to climatic parameters, the current trend to increasing global temperatures will further reduce acceptable habitats and seriously threaten the existences of these last representatives of an ancient group of Odonata.     

Neutrophil Gelatinase-Associated Lipocalin (NGAL) Predicts Response to Neoadjuvant Chemotherapy and Clinical Outcome in Primary Human Breast Cancer

In our previous work we showed that NGAL, a protein involved in the regulation of proliferation and differentiation, is overexpressed in human breast cancer (BC) and predicts poor prognosis. In neoadjuvant chemotherapy (NACT) pathological complete response (pCR) is a predictor for outcome. The aim of this study was to evaluate NGAL as a predictor of response to NACT and to validate NGAL as a prognostic factor for clinical outcome in patients with primary BC. Immunohistochemistry was performed on tissue microarrays from 652 core biopsies from BC patients, who underwent NACT in the GeparTrio trial. NGAL expression and intensity was evaluated separately. NGAL was detected in 42.2% of the breast carcinomas in the cytoplasm. NGAL expression correlated with negative hormone receptor (HR) status, but not with other baseline parameters. NGAL expression did not correlate with pCR in the full population, however, NGAL expression and staining intensity were significantly associated with higher pCR rates in patients with positive HR status. In addition, strong NGAL expression correlated with higher pCR rates in node negative patients, patients with histological grade 1 or 2 tumors and a tumor size <40 mm. In univariate survival analysis, positive NGAL expression and strong staining intensity correlated with decreased disease-free survival (DFS) in the entire cohort and different subgroups, including HR positive patients. Similar correlations were found for intense staining and decreased overall survival (OS). In multivariate analysis, NGAL expression remained an independent prognostic factor for DFS. The results show that in low-risk subgroups, NGAL was found to be a predictive marker for pCR after NACT. Furthermore, NGAL could be validated as an independent prognostic factor for decreased DFS in primary human BC.