Effects of chronic exercise on severity, quality of life and functionality in an elderly Parkinson’s disease patient: case report

Exercise produces potential influences on physical and mental capacity in patients with neuropsychiatric disor- ders, and can be made a viable form of therapy to treat Parkinson’s disease (PD). We report the chronic effects of a regu- lar physical exercise protocol on cognitive and motor functions, functional capacity, and symptoms in an elderly PD pa- tient without dementia. The patient participated of a program composed of proprioceptive, aerobic and flexibility exer- cises, during 1 hour, three days a week, for nine months. Patient used 600 mg of L-DOPA daily, and 1 hour prior to each exercise session. Assessment was conducted in three stages, 0-3, 3-6 and 6 to 9 months, using percentual variation to the scales Hoehn and Yahr, Mini-Mental State Examination (MMSE), Parkinson Activity Scale (PAS), Beck Depression In- ventory (BDI), and Unified Parkinson's Disease Rating Scale (UPDRS-III). Reassessment showed clear changes in clini- cal parameters for Hoehn and Yahr (4 to 2.5), MMSE (14 to 22), PAS (13 to 29), BDI (9 to 7) and UPDRS-III (39 to 27) at the end of 9 months. According to our data, exercise seems to be effective in promoting the functional capacity and the maintenance of cognitive and motor functions of PD patients. Regular exercise protocols can be implemented as an ad- junctive treatment for reducing the severity of PD

Determination of Pericardial Adipose Tissue Increases the Prognostic Accuracy of Coronary Artery Calcification for Future Cardiovascular Events

Objectives: Pericardial adipose tissue (PAT) is associated with coronary artery plaque accumulation and the incidence of coronary heart disease. We evaluated the possible incremental prognostic value of PAT for future cardiovascular events. Methods: 145 patients (94 males, age 60 10 years) with stable coronary artery disease underwent coronary artery calcification (CAC) scanning in a multislice CT scanner, and the volume of pericardial fat was measured. Mean observation time was 5.4 years. Results: 34 patients experienced a severe cardiac event. They had a significantly higher CAC score (1,708 +/- 2,269 vs. 538 +/- 1,150, p 400, 3.5 (1.9-5.4; p = 0.007) for scores > 800 and 5.9 (3.7-7.8; p = 0.005) for scores > 1,600. When additionally a PAT volume > 200 cm(3) was determined, there was a significant increase in the event rate and relative risk. We calculated a relative risk of 2.9 (1.9-4.2; p = 0.01) for scores > 400, 4.0 (2.1-5.0; p = 0.006) for scores > 800 and 7.1 (4.1-10.2; p = 0.005) for scores > 1,600. Conclusions:The additional determination of PAT increases the predictive power of CAC for future cardiovascular events. PAT might therefore be used as a further parameter for risk stratification. Copyright (C) 2012 S. Karger AG, Base

Revisiting clustering as matrix factorisation on the Stiefel manifold

International audienceThis paper studies clustering for possibly high dimensional data (e.g. images, time series, gene expression data, and many other settings), and rephrase it as low rank matrix estimation in the PAC-Bayesian framework. Our approach leverages the well known Burer-Monteiro factorisation strategy from large scale optimisation, in the context of low rank estimation. Moreover, our Burer-Monteiro factors are shown to lie on a Stiefel manifold. We propose a new generalized Bayesian estimator for this problem and prove novel prediction bounds for clustering. We also devise a componentwise Langevin sampler on the Stiefel manifold to compute this estimator

Autenticidad a partir de RV como método de documentación de patrimonio cultural. Aproximación teórica basada en prácticas de conservación y documetnación

[EN] The visualization of 3D reconstructed artifacts often requires significant computing resources. The implementation of an object in a virtual reality (VR) application even necessitates the reduction of the polygonal mesh. Consequently, the communication and dissemination of “authentic” 3D reconstructions via immersive VR technologies has been a nearly impossible feat for many researchers. However, is the issue really computing resources, or is it rather the notion of authenticity in an “auratic” sense, i.e., an excessive focus on physical evidence and survey data? In the present paper, we will discuss the authenticity requirements for virtual archaeology as set by the Seville Principles(2011), and we will analyse some limitations related to the current approaches. Furthermore, we will propose a pluralistic notion based on the contextualization of 3D objects in VR environments with synesthetic (i.e. multisensory) information. This new notion of authenticity relies on conservation meanings rather than physical features. In line with this approach, two case studies will be commented: the multimodal 3D-documentation of the Jupiter Column(2AD) in Ladenburg, and the VR-based re-enactment of a modern work of art, the audio-kinetic sculpture Kaleidophonic Dog(1967) by Stephan von Huene. These two projects provide valuable data for a revision of the notion of authenticity in both virtual archaeology and art conservation.[ES] La visualización deartefactos reconstruidos en 3D requiere a menudo demasiados recursos computacionales. La implementación en una aplicación de realidad virtual (RV) requiere incluso la reducción de la red poligonal delobjeto.Consecuentemente,la comunicación y la divulgaciónde reconstrucciones 3D “auténticas”representa todavía una tarea casi imposiblepara muchos investigadores. ¿Pero se trata realmente solo de una cuestión de computación, o tiene algo que ver con una noción de autenticidad en un sentido“aurático”, es decir, con un enfoqueexcesivo sobre pruebas materiales y datosmensurables?En esteartículo discutimos los requisitos de autenticidad para la arqueología virtual tal y como se formulan en los “Principios de Sevilla” (2011) y analizamos algunaslimitaciones de los enfoques actuales. Proponemos,además,una noción pluralista basada en la contextualización de objetos 3D en entornos de RV con información sinestésica (es decir, multisensorial). Esta nueva noción de autenticidad se basa más enla conservación de significados que en la conservación de características físicas. En línea con esta propuesta teórica, se comentarán dos casos de estudio: la documentación multimodal 3D de la Columna de Júpiterde Ladenburg (II d.C.) y la recreación en RV de una obra de arte moderno, la escultura audio-cinética Kaleidophonic Dog(1967) de Stephan von Huene. Estos dos proyectos ofrecen experiencias valiosas para una revisión de la noción de autenticidad tanto en la arqueología virtual como en la conservación de arte.This work was supported by the Stadt Karlsruhe (“Interdisziplinärer Fördertopf”) and the HEiKAResearch fonds (HEiKA, Heidelberg Karlsruhe Research Partnership)Muñoz Morcillo, J.; Schaaf, F.; Schneider, RH.; Robertson-Von Trotha, CY. (2017). Authenticity through VR-based documentation of cultural heritage. A theoretical approach based on conservation and documentation practices. Virtual Archaeology Review. 8(16):35-43. doi:10.4995/var.2017.5932.SWORD354381

Cryo-EM structure of a helicase loading intermediate containing ORC-Cdc6-Cdt1-MCM2-7 bound to DNA

In eukaryotes, the Cdt1-bound replicative helicase core MCM2-7 is loaded onto DNA by the ORC-Cdc6 ATPase to form a prereplicative complex (pre-RC) with an MCM2-7 double hexamer encircling DNA. Using purified components in the presence of ATP-γS, we have captured in vitro an intermediate in pre-RC assembly that contains a complex between the ORC-Cdc6 and Cdt1-MCM2-7 heteroheptamers called the OCCM. Cryo-EM studies of this 14-subunit complex reveal that the two separate heptameric complexes are engaged extensively, with the ORC-Cdc6 N-terminal AAA+ domains latching onto the C-terminal AAA+ motor domains of the MCM2-7 hexamer. The conformation of ORC-Cdc6 undergoes a concerted change into a right-handed spiral with helical symmetry that is identical to that of the DNA double helix. The resulting ORC-Cdc6 helicase loader shows a notable structural similarity to the replication factor C clamp loader, suggesting a conserved mechanism of action

Influence of Polymorphisms Involved in Platelet Activation and Inflammatory Response on Aspirin-Related Upper Gastrointestinal Bleeding: A Case-Control Study

Background: Despite the wide benefits of aspirin and its cost-effectiveness, aspirin prescriptions have been reduced due to idiosyncratic responses in susceptible individuals. Low-dose aspirin and single-nucleotide polymorphisms (SNPs) are independently associated with increased risk of gastrointestinal hemorrhage; however, to-date, no studies investigated the SNP-aspirin interaction effect on upper gastrointestinal hemorrhage (UGIH). Therefore, we aimed to evaluate the role of 25 SNPs in multiple genes involved in platelet activation, angiogenesis and inflammatory response in aspirin-related UGIH. Methods: A multicenter, full case-control study was conducted in patients exposed and unexposed to aspirin. Three hundred twenty-six cases diagnosed with UGIH were matched with 748 controls (1:3) by age, gender, health center, and recruitment date. Only adults of European origin were included. Participants were stratified by aspirin exposure and genotype [(Aspirin(-), wild-type), (Aspirin(+), wild-type), (Aspirin(+), genetic variation), (Aspirin(-), genetic variation)]. For each SNP, the Odds Ratio of UGIH and their 95% confidence intervals were estimated in each subgroup by using the generalized linear mixed models for dependent binomial variables. SNP-aspirin interaction effect was estimated through Relative Excess Risk due to Interaction (RERI) measures. Results: We observed two categories of SNPs that might modify the risk magnitude of UGIH in aspirin consumers. Seven SNPs (rs1387180 A > G, rs2238631 T > C, rs1799964 T > C, rs5050 T > C/T > G, rs689466 T > C, rs1799983 T > A/T > G, and rs7756935 C > A) were "positive modifiers" associated with an excess of risk from aspirin exposure and carrying that genetic variation (1.75 T, rs1131882 G > A, rs4311994 C > T, rs10120688 G > A, rs4251961 T > C, rs3778355 G > C, rs1330344 C > T, rs5275 A > G/A > T, and rs3779647 C > T) were "negative modifiers" and associated with a reduced risk in aspirin users (-2.74 </= RERI </= -0.95). Conclusion: This preliminary study suggests that polymorphisms in genes involved in platelets activity, angiogenesis and inflammatory response might modify the risk of aspirin-related UGIH. Further studies with larger sample size and in different populations are needed to confirm our findings. If confirmed, this might have great impact on public health, thanks to aspirin's prophylactic properties in diseases of high incidence and severity

I–II Loop Structural Determinants in the Gating and Surface Expression of Low Voltage-Activated Calcium Channels

The intracellular loops that interlink the four transmembrane domains of Ca2+- and Na+-channels (Cav, Nav) have critical roles in numerous forms of channel regulation. In particular, the intracellular loop that joins repeats I and II (I–II loop) in high voltage-activated (HVA) Ca2+ channels possesses the binding site for Cavβ subunits and plays significant roles in channel function, including trafficking the α1 subunits of HVA channels to the plasma membrane and channel gating. Although there is considerable divergence in the primary sequence of the I–II loop of Cav1/Cav2 HVA channels and Cav3 LVA/T-type channels, evidence for a regulatory role of the I–II loop in T-channel function has recently emerged for Cav3.2 channels. In order to provide a comprehensive view of the role this intracellular region may play in the gating and surface expression in Cav3 channels, we have performed a structure-function analysis of the I–II loop in Cav3.1 and Cav3.3 channels using selective deletion mutants. Here we show the first 60 amino acids of the loop (post IS6) are involved in Cav3.1 and Cav3.3 channel gating and kinetics, which establishes a conserved property of this locus for all Cav3 channels. In contrast to findings in Cav3.2, deletion of the central region of the I–II loop in Cav3.1 and Cav3.3 yielded a modest increase (+30%) and a reduction (−30%) in current density and surface expression, respectively. These experiments enrich our understanding of the structural determinants involved in Cav3 function by highlighting the unique role played by the intracellular I–II loop in Cav3.2 channel trafficking, and illustrating the prominent role of the gating brake in setting the slow and distinctive slow activation kinetics of Cav3.3