Involvement of the subthalamic nucleus in impulse control disorders associated with Parkinson’s disease

Behavioural abnormalities such as impulse control disorders may develop when patients with Parkinson’s disease receive dopaminergic therapy, although they can be controlled by deep brain stimulation of the subthalamic nucleus. We have recorded local field potentials in the subthalamic nucleus of 28 patients with surgically implanted subthalamic electrodes. According to the predominant clinical features of each patient, their Parkinson’s disease was associated with impulse control disorders (n = 10), dyskinesias (n = 9) or no dopaminergic mediated motor or behavioural complications (n = 9). Recordings were obtained during the OFF and ON dopaminergic states and the power spectrum of the subthalamic activity as well as the subthalamocortical coherence were analysed using Fourier transform-based techniques. The position of each electrode contact was determined in the postoperative magnetic resonance image to define the topography of the oscillatory activity recorded in each patient. In the OFF state, the three groups of patients had similar oscillatory activity. By contrast, in the ON state, the patients with impulse control disorders displayed theta-alpha (4–10 Hz) activity (mean peak: 6.71 Hz) that was generated 2–8mm below the intercommissural line. Similarly, the patients with dyskinesia showed theta-alpha activity that peaked at a higher frequency (mean: 8.38 Hz) and was generated 0–2mm below the intercommissural line. No such activity was detected in patients that displayed no dopaminergic side effects. Cortico-subthalamic coherence was more frequent in the impulsive patients in the 4–7.5 Hz range in scalp electrodes placed on the frontal regions anterior to the primary motor cortex, while in patients with dyskinesia it was in the 7.5–10 Hz range in the leads overlying the primary motor and supplementary motor area. Thus, dopaminergic side effects in Parkinson’s disease are associated with oscillatory activity in the theta-alpha band, but at different frequencies and with different topography for the motor (dyskinesias) and behavioural (abnormal impulsivity) manifestations. These findings suggest that the activity recorded in parkinsonian patients with impulse control disorders stems from the associative-limbic area (ventral subthalamic area), which is coherent with premotor frontal cortical activity. Conversely, in patients with L-dopa-induced dyskinesias such activity is recorded in the motor area (dorsal subthalamic area) and it is coherent with cortical motor activity. Consequently, the subthalamic nucleus appears to be implicated in the motor and behavioural complications associated with dopaminergic drugs in Parkinson’s disease, specifically engaging different anatomo-functional territories

Molecular and Cellular Mechanisms of Delayed Fracture Healing in Mmp10 (Stromelysin 2) Knockout Mice

The remodeling of the extracellular matrix is a central function in endochondral ossification and bone homeostasis. During secondary fracture healing, vascular invasion and bone growth requires the removal of the cartilage intermediate and the coordinate action of the collagenase matrix metalloproteinase (MMP)-13, produced by hypertrophic chondrocytes, and the gelatinase MMP-9, produced by cells of hematopoietic lineage. Interfering with these MMP activities results in impaired fracture healing characterized by cartilage accumulation and delayed vascularization. MMP-10, Stromelysin 2, a matrix metalloproteinase with high homology to MMP-3 (Stromelysin 1), presents a wide range of putative substrates identified in vitro, but its targets and functions in vivo and especially during fracture healing and bone homeostasis are not well defined. Here, we investigated the role of MMP-10 through bone regeneration in C57BL/6 mice. During secondary fracture healing, MMP-10 is expressed by hematopoietic cells and its maximum expression peak is associated with cartilage resorption at 14 days post fracture (dpf). In accordance with this expression pattern, when Mmp10 is globally silenced, we observed an impaired fracture-healing phenotype at 14 dpf, characterized by delayed cartilage resorption and TRAP-positive cell accumulation. This phenotype can be rescued by a non-competitive transplant of wild-type bone marrow, indicating that MMP-10 functions are required only in cells of hematopoietic linage. In addition, we found that this phenotype is a consequence of reduced gelatinase activity and the lack of proMMP-9 processing in macrophages. Our data provide evidence of the in vivo function of MMP-10 during endochondral ossification and defines the macrophages as the lead cell population in cartilage removal and vascular invasio

La galectina-3, una nueva diana terapéutica para las alteraciones cardiovasculares asociadas al desarrollo de la estenosis aórtica severa

Aortic stenosis is one of the most common heart valve diseases, as well as one of the most common causes of heart failure in the elderly. Currently, there are no medical therapies to prevent or slow the progression of the disease. When symptoms develop alongside severe aortic stenosis, there is a poor prognosis unless aortic valve replacement is performed. Aortic stenosis is a heterogeneous disease with a complex pathophysiology involving structural and biological changes of the valve, as well as adaptive and maladaptive compensatory changes in the myocardium and vasculature in response to chronic pressure overload. Galectin-3 serves important functions in numerous biological activities including cell growth, apoptosis, differentiation, inflammation and fibrosis. With evidence emerging to support the function of Galectin-3, the current review aims to summarize the latest literature regarding the potential of Galectin-3 as therapeutic target in aortic valve and cardiovascular alterations associated with aortic stenosis.La estenosis aórtica severa degenerativa (EA) es una enfermedad muy prevalente, cuya incidencia se incrementará en los próximos años debido al envejecimiento de la población. Actualmente no existe ningún tratamiento farmacológico que retarde su progresión y, cuando aparecen los síntomas, la cirugía de recambio valvular es la única opción. La EA se caracteriza por la calcificación de la válvula aórtica y por la aparición de fibrosis miocárdica. Sin embargo, no se conocen los mecanismos fisiopatológicos de la EA necesarios para identificar y desarrollar nuevas estrategias terapéuticas adecuadas. La Galectina-3 (Gal-3) regula funciones biológicas como el crecimiento, la diferenciación, la apoptosis, la inflamación o la fibrosis. Esta revisión resume los principales trabajos que describen el potencial de la Gal-3 como diana terapéutica para las alteraciones cardíacas y valvulares asociadas con el desarrollo de EA

Nuevos horizontes en cirugía mamaria. Cirugía radioguiada y biopsia selectiva de ganglio centinela

Although needle-wire localization is the most commonly used localization technique for nonpalpable breast lesion biopsy, the technique of radioguided occult lesion localization (ROLL), is becoming increasingly used for open-surgery diagnosis in such cases. Sentinel lymph node biopsy(SLNB) is based on the hypothesis that lymphatic drainage from a tumor reaches the sentinel node(SLN) first and that it can be identified accurately and removed. If SLN exactly reflects the lymph-node status, a negative SLN for metastasis might allow complete axillary lymph node dissection (ALDN) to be avoided

A randomized phase II trial of platinum salts in basal-like breast cancer patients in the neoadjuvant setting. Results from the GEICAM/2006-03, multicenter study

Este artículo ha sido publicado en Breast Cancer Research and Treatment Siguiendo las instruciones y dado que la revista dice que el artículo fue publicado tal cual se envió, hacemos un postprint copiando dicho texto enviado por la revista en un documento Word y luego convertido a PDF para así respetar el contenido, y sin dar acceso a los "extras" de la versión publicada. Esta versión tiene Licencia Creative Commons CC-BY-NC-NDAbstract Chemotherapy remains as the only systemic treatment option available for basal-like breast cancer (BC) patients. Preclinical models and several phase II studies suggested that platinum salts are active drugs in this BC subtype though there is no randomized study supporting this hypothesis. This study investigates if the addition of carboplatin to a combination of an alkylating agent together with anthracyclines and taxanes is able to increase the efficacy in the neoadjuvant treatment context. Patients with operable breast cancer and immunophenotypically defined basal-like disease (ER-/PR-/HER2- and cytokeratin 5/6? or EGFR?) were recruited. Patients were randomized to receive EC (epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 for 4 cycles) followed either by D (docetaxel 100 mg/m2 9 4 cycles; EC–D) or DCb (docetaxel 75 mg/ m2 plus carboplatin AUC 6 9 4 cycles; EC–DCb). The primary end point was pathological complete response (pCR) in the breast following the Miller and Payne criteria. Ninety-four patients were randomized (46 EC–D, 48 EC– DCb). pCR rate in the breast was seen in 16 patients (35 %) with EC–D and 14 patients (30 %) with EC–DCb (P value = 0.61). pCR in the breast and axilla was seen in 30 % of patients in both arms. The overall clinical response rate was 70 % (95 % CI 56–83) in the EC–D arm and 77 % (95 % CI 65–87) in the EC–DCb arm. Grade 3/4 toxicity was similar in both arms. The addition of carboplatin to conventional chemotherapy with EC–D in basal-like breast cancer patients did not improve the efficacy probably because they had already received an alkylating agent. These findings should be taken into consideration when developing new agents for this disease.This trial was partially supported by Pfizer S.L.U

Comparative study of CuO supported on CeO2, Ce0.8Zr0.2O2 and Ce0.8Al0.2O2 based catalysts in the CO-PROX reaction

CuO supported on CeO2, Ce0.8Zr0.2O2 and Ce0.8Al0.2O2 based catalysts (6%wt Cu) were synthesized and tested in the preferential oxidation of CO in a H2-rich stream (CO-PROX). Nanocrystalline supports, CeO2 and solid solutions of modified CeO2 with zirconium and aluminum were prepared by a freeze-drying method. CuO was supported by incipient wetness impregnation and calcination at 400 C. All catalysts exhibit high activity in the CO-PROX reaction and selectivity to CO2 at low reaction temperature, being the catalyst supported on CeO2 the more active and stable. The influence of the presence of CO2 and H2O was also studied

Estimation of the interfacial shears strength, orientation factor and mean equivalent intrinsic tensile strength in old newspaper fiber/polypropylene composites

The present paper investigates the suitability of old newspapers (ONPs) as a source of reinforcing fibers for composite materials. Different percentages of ONP fibers were compounded with polypropylene (PP). A coupling agent was added to the compound to improve the interface between matrix and reinforcing fibers. Tensile test were performed to obtain the mechanical properties of the composite materials. Micromechanics of the fibers were obtained using Hirsch model, Bowyer Bader methodology and Kelly-Tyson equations. Due to the presence of a percentage of calcium carbonate in the obtained fibers (10%), the computed intrinsic characteristics were addressed as equivalent. The most important results were the mean equivalent intrinsic tensile strength of the ONP fibers, the mean orientation angle and the mean interfacial shear strength. The contributions of the matrix, the subcritical and the supercritical fibers to the tensile strength of the composite material were also computed. (C) 2013 Elsevier Ltd. All rights reserved.Serrano, A.; Espinach, FX.; Julian, F.; Rey Tormos, RMD.; Mendez, JA.; Mutje, P. (2013). Estimation of the interfacial shears strength, orientation factor and mean equivalent intrinsic tensile strength in old newspaper fiber/polypropylene composites. Composites Part B: Engineering. 50:232-238. doi:10.1016/j.compositesb.2013.02.018S2322385

Knowledge, attitudes and preventive practices of primary health care professionals towards alcohol use: A national, cross-sectional study

Introduction Primary care (PC) professionals' knowledge about alcohol use has been identified as one of the barriers PC providers face in their clinic. Both PC professionals' level of training and attitude are crucial in the clinical practice regarding alcohol use. Objective To evaluate the knowledge, attitude, and preventive practices of Spanish PC physicians and nurses towards alcohol use. Design An observational, descriptive, cross-sectional, multi-center study. Methodology Location: PC centers of the Spanish National Health System (NHS). Participants: PC physicians and nurses selected randomly from health care centers, and by sending an e-mail to semFYC and SEMERGEN members. Healthcare providers completed an online survey on knowledge, attitude, and follow-up recommendations for reducing alcohol intake. A descriptive, bivariate, and multivariate statistical analysis was conducted (p<0.05). Results Participants: 1, 760 healthcare providers completed the survey (75.6% [95% CI 73.5-77.6] family physicians; 11.4% [95% CI 9.9-12.9] medical residents; and 12.5% [95% CI 10.9-14.1] nurses), with a mean age of 44.7 (SD 11.24, range: 26-64, 95% CI: 47.2-48.2). Knowledge was higher in family physicians (p<0.001), older professionals (Spearman's r = 0.11, p<0.001), and resident trainers (p<0.001). The PC professional most likely to provide advice for reducing alcohol use was: a nurse (p<0.001), female (p = 0.010), between 46 and 55 years old (p <0.001). Conclusions PC providers' knowledge and preventive practices regarding alcohol use are scarce, hence specific training strategies to increase their knowledge and improve their attitude and skills with regard to this health problem should be considered a healthcare policy priority

FCNC Top Quark Decays in Extra Dimensions

The flavor changing neutral top quark decay t -> c X is computed, where X is a neutral standard model particle, in a extended model with a single extra dimension. The cases for the photon, X= \gamma$, and a Standard Model Higgs boson, X = H, are analyzed in detail in a non-linear$R_\xi gauge. We find that the branching ratios can be enhanced by the dynamics originated in the extra dimension. In the limit where 1/R >> ->, we have found Br(t -> c \gamma) \simeq 10^{-10} for 1/R = 0.5 TeV. For the decay t -> c H, we have found Br(t -> cH) \simeq 10^{-10} for a low Higgs mass value. The branching ratios go to zero when 1/R -> \infty.Comment: Accepted to be published in the Europ. Phys. Jour. C; 16 pages, 2 figure

A precise measurement of the magnetic field in the corona of the black hole binary V404 Cygni

Observations of binary stars containing an accreting black hole or neutron star often show x-ray emission extending to high energies (>10 kilo­–electron volts), which is ascribed to an accretion disk corona of energetic particles akin to those seen in the solar corona. Despite their ubiquity, the physical conditions in accretion disk coronae remain poorly constrained. Using simultaneous infrared, optical, x-ray, and radio observations of the Galactic black hole system V404 Cygni, showing a rapid synchrotron cooling event in its 2015 outburst, we present a precise 461 ± 12 gauss magnetic field measurement in the corona. This measurement is substantially lower than previous estimates for such systems, providing constraints on physical models of accretion physics in black hole and neutron star binary systems. This article has a correction. Please see: http://science.sciencemag.org/content/360/6386/eaat927