Osteoprotegerin: A new biomarker for impaired bone metabolism in complex regional pain syndrome?

Osteoprotegerin (OPG) is important for bone remodeling and may contribute to complex regional pain syndrome (CRPS) pathophysiology. We aimed to assess the value of OPG as a biomarker for CRPS and a possible correlation with radiotracer uptake in 3-phase bone scintigraphy (TPBS). OPG levels were analyzed in 23 CRPS patients (17 women; mean age 50 ± 9.0 years; disease duration: 12 weeks [IQR 8–24]), 10 controls (6 women; mean age 58 ± 9.6 years) and 21 patients after uncomplicated fractures (12 women; mean age: 43 ± 15 years; time after fracture: 15 weeks [IQR: 6–22]). The CRPS and control patients also underwent TPBS. OPG in CRPS patients was significantly increased by comparison with both control groups (P = 0.001; Kruskal-Wallis test; CRPS patients: 74.1 pg/mL [IQR: 47.1–100.7]; controls: 46.7 pg/mL [IQR: 35.5–55.0]; P = 0.004; fracture patients: 45.9 pg/mL [IQR: 37.5–56.7]; P = 0.001). As a diagnostic test for CRPS, OPG had a sensitivity of 0.74, specificity of 0.80, positive predictive value of 68% and negative predictive value of 84%. Receiver operating characteristic curve analysis showed an area under the curve of 0.80 (CI: 0.68–0.91). For the CRPS-affected hand, a significant correlation between OPG and TPBS region of interest analysis in phase III was detected (carpal bones; r = 0.391; P = 0.03). The persistent OPG increase in CRPS indicates enhanced osteoblastic activity shown by increased radiotracer uptake in TPBS phase III. A contribution of bone turnover to CRPS pathophysiology is likely. OPG might be useful as a biomarker for CRPS.     

Separation of superficial and cerebral hemodynamics using a single distance time-domain NIRS measurement

In functional near-infrared spectroscopy (fNIRS) superficial hemodynamics can mask optical signals related to brain activity. We present a method to separate superficial and cerebral absorption changes based on the analysis of changes in moments of time-of-flight distributions and a two-layered model. The related sensitivity factors were calculated from individual optical properties. The method was validated on a two-layer liquid phantom. Absorption changes in the lower layer were retrieved with an accuracy better than 20%. The method was successfully applied to in vivo data and compared to the reconstruction of homogeneous absorption changes.OCIS codes: (170.5280) Photon migration, (170.6920) Time-resolved imaging, (170.3880) Medical and biological imaging, (170.6510) Spectroscopy, tissue diagnostics, (120.3890) Medical optics instrumentation, (170.1470) Blood or tissue constituent monitoring     

Seasonality in symptom severity influenced by temperature or grass pollen: results of a panel study in children with eczema

Although seasonal variations are well known in many patients with eczema, no systematic population-based panel study evaluating seasonality and quantifying the influence of factors like climate and pollen on symptom variations has been conducted so far. Thirty-nine children with eczema, who had been identified in 1996 in a cross-sectional study on 1673 6-y-olds in Augsburg (Germany), participated in the study. Between March and September 1999, they daily recorded itch, extent, and possibly triggering factors on quantitative scales. Daily temperature, humidity, radiation, and pollen concentration were measured. Mixed linear models, taking the time series structure and confounding into account, were used for analysis. Seasonal patterns were significantly different between children: twenty-one had symptoms mainly in winter. They were affected by changes in outdoor temperature: itch was reduced by 22% (95% confidence interval (CI): 16%-27%) and extent by 65% (CI: 54%-72%) per 15 degrees C temperature increase. Eighteen children exhibited more symptoms in summer and especially during days with high grass-pollen exposure when itch was 16% higher (CI: 8%-24%) and extent 19% (CI: 2%-39%). This effect was stronger for children sensitized against pollen. Consideration of the individual type of eczema may help to arrange appropriate preventive and therapeutic measures.     

Efficacy of imidacloprid 10%/moxidectin 1% (Advocate®/Advantage Multi™) against fleas (Ctenocephalides felis felis) on ferrets (Mustela putorius furo)

Ferrets (Mustela putorius furo) are becoming increasingly popular as pets and are kept in households with other pet animals such as dogs and cats, from which they may catch flea infestations with the predominant flea species Ctenocephalides felis. In this study, the efficacy of imidacloprid/moxidectin spot-on (Advocate/Advantage Multi) was investigated in the therapy and prevention of flea infestation in ferrets. Sixteen adult ferrets of varying weights and ages and of both sexes were included. Ferrets were infested with 50 fleas each on days -7, -1, 7, 14, 21, and 28. On study day -6, the animals were randomized into two groups based on body weight and flea count. Each ferret allocated to group 1 was treated with 0.4 ml of imidacloprid 10%/moxidectin 1% (Advocate/Advantage Multi). The ferrets in group 2 remained untreated. Flea counts were performed by combing 24 to 48 h after infestation. The primary efficacy criterion was the reduction in the number of fleas at each time point post treatment compared to the ferrets in the untreated control group. On day 1, the therapeutic efficacy was 100%. The preventative efficacy was 100% at 1 and 2 weeks post treatment, and it was >97% and >90% at 3 and 4 weeks post treatment. No local or systemic side effects were observed in any of the ferrets treated.     

mGlu1 and mGlu5 receptor antagonists lack anticonvulsant efficacy in rodent models of difficult-to-treat partial epilepsy

Modulation of metabotropic glutamate (mGlu) receptors represents an interesting new approach for the treatment of a range of neurological and psychiatric disorders. Several lines of evidence suggest that functional blockade of group I (mGlu1 and mGlu5) receptors may be beneficial for treatment of epileptic seizures. This study was conducted to investigate whether mGlu1 or mGlu5 receptor antagonists have the potential to block partial or secondarily generalized seizures as occurring in partial epilepsy, the most common and difficult-to-treat type of epilepsy in patients. For this purpose, we systemically administered novel highly selective and brain penetrable group I mGlu receptor antagonists, i.e., the mGlu1 receptor antagonist EMQMCM [3-ethyl-2-methyl-quinolin-6-yl-(4-methoxy-cyclohexyl)-methanone methanesulfonate] and the mGlu5 receptor antagonist MTEP ([(2-methyl-1,3-thiazol-4-yl) ethynyl] pyridine), at doses appropriate for mGlu1 or mGlu5 receptor-mediated effects in rodent models of partial seizures. Two models were used: the 6-Hz electroshock model of partial seizures in mice and the amygdala-kindling model in rats. Clinically established antiepileptic drugs were included in the experiments for comparison. Antiepileptic drugs exerted significant anticonvulsant effects in both models, while EMQMCM and MTEP were ineffective in this regard, although both compounds were administered up to doses associated with essentially full receptor occupancy and with typical mGlu receptor-mediated effects in rodent models of anxiety or pain. Brain microdialysis for determining extracellular levels of MTEP following i.p. administration in rats substantiated that effective brain concentrations were reached at times of our experiments in seizure models. The present results do not support a significant anticonvulsant potential of group I mGlu receptor antagonists in rodent models of difficult-to-treat partial epilepsy.     

Impact of estrogens on resting energy expenditure: A systematic review

The fear of weight gain is one of the main reasons for women not to initiate or to early discontinue hormonal contraception or menopausal hormone therapy. Resting energy expenditure is by far the largest component and the most important determinant of total energy expenditure. Given that low resting energy expenditure is a confirmed predictive factor for weight gain and consecutively for the development of obesity, research into the influence of sex steroids on resting energy expenditure is a particularly exciting area. The objective of this systematic review was to evaluate the effects of medication with natural and synthetic estrogens on resting energy expenditure in healthy normal weight and overweight women. Through complex systematic literature searches, a total of 10 studies were identified that investigated the effects of medication with estrogens on resting energy expenditure. Our results demonstrate that estrogen administration increases resting energy expenditure by up to +208 kcal per day in the context of contraception and by up to +222 kcal per day in the context of menopausal hormone therapy, suggesting a preventive effect of circulating estrogen levels and estrogen administration on weight gain and obesity development.     

Revisiting the concept of drug-resistant epilepsy: A TASK1 report of the ILAE/AES Joint Translational Task Force

Despite progress in the development of anti-seizure medications (ASMs), one third of people with epilepsy have drug-resistant epilepsy (DRE). The working definition of DRE, proposed by the International League Against Epilepsy (ILAE) in 2010, helped identify individuals who might benefit from presurgical evaluation early on. As the incidence of DRE remains high, the TASK1 workgroup on DRE of the ILAE/American Epilepsy Society (AES) Joint Translational Task Force discussed the heterogeneity and complexity of its presentation and mechanisms, the confounders in drawing mechanistic insights when testing treatment responses, and barriers in modeling DRE across the lifespan and translating across species. We propose that it is necessary to revisit the current definition of DRE, in order to transform the preclinical and clinical research of mechanisms and biomarkers, to identify novel, effective, precise, pharmacologic treatments, allowing for earlier recognition of drug resistance and individualized therapies.