Miracle-dz/UniFAR-FTUs huggingface dataset:
Short- and long-term effects of ibandronate treatment on bone turnover in Paget disease of bone.

BACKGROUND In Paget disease of bone (PD), serum total alkaline phosphatase (TAP) is a valid marker of disease activity. The aim of the present longitudinal study was to compare TAP with new and potentially more specific markers of bone turnover in bisphosphonate-treated patients with PD. METHODS Twenty patients with active PD were studied before and after treatment with 2 mg of intravenous ibandronate over a period of 12 months. TAP (by colorimetry), serum bone-specific alkaline phosphatase (BAP; by enzyme immunoassay), serum osteocalcin (OC; by ELISA), serum bone sialoprotein (BSP; by RIA), and urinary total pyridinoline (PYD; by HPLC) and deoxypyridinoline (DPD; by HPLC) were measured as markers of bone turnover. RESULTS Before treatment, TAP, BAP, and BSP were increased in all 20 patients, whereas OC was increased in 10, PYD in 13, and DPD in 15 patients. Three months post treatment, nine patients showed normalized TAP values, and a >/=25% re-increase (i.e. , relapse) was observed in all patients after 12 months. A normalization of BAP was achieved in six patients only. No significant changes were found for OC. BSP was decreased significantly at 24 h, and DPD at 48 h post treatment. A normalization of BSP was found in 8, of PYD in 18, and of DPD in 16 cases. Both PYD and DPD increased significantly from 9 months post treatment onward. CONCLUSIONS Most markers of bone turnover show similar long-term changes after treatment of active PD with ibandronate. With regard to cost-effectiveness and assay performance, TAP remains the marker of choice in therapeutic monitoring of PD. However, more specific markers may improve the biochemical assessment of PD in certain situations.
Propuesta didáctica para niños con déficit atencional: estimulando el razonamiento analógico verbal para desarrollar la oralidad tardía

El deficit atencional es un cuadro neuropsiquiatrico complejo que, cognitivamente, se caracteriza por unos niveles evolutivamente inapropiados en la atencion, sobreactividad e impulsividad (Barkley, 2003) y, linguisticamente, por presentar alteraciones a nivel fonologico, semantico, sintactico y en sus capacidades discursivas y pragmaticas, en especial en su capacidad para la comprension oral de significados figurados (Miranda-Casa, Ygual-Fernandez y Rosel-Remirez, 2004; Baixauli-Fortea, Rosello y Miranda-Casas, 2004; Garcia y Manghi, 2006). Este desarrollo linguistico descendido incide no solo en las habilidades comunicacionales sino que, ademas, en la comprension lectora, produccion escrita y en el aprendizaje de contenidos curriculares. Por esto, el presente trabajo da a conocer una propuesta didactica para desarrollar especificamente la capacidad de inferir significados figurados en la lengua oral. La propuesta fue aplicada a 25 escolares de entre 8 a 9 anos de edad con deficit atencional, los resultados en este grupo demuestran la efectividad de la propuesta
Generating blending surfaces with an iterative solution to fourth order PDE

In this paper, we develop an efficient method for surface blending. It is based on our previously proposed fourth order partial differential equation (PDE) with three vector-valued shape parameters. In order to solve this PDE efficiently, we have previously developed a closed form resolution method. However, a closed form solution only exists in a small number of situations, and therefore the application of a closed form solution based method is limited. By transforming the original PDE into an algebra equation, we can achieve an approximate closed form solution. The examples given in this paper indicate that the developed method can generate blending surfaces almost as accurately and quickly as the closed form solution. In addition, it can deal with any combinations of the shape parameters and greatly facilitate the computer programming of various surface blending tasks.
Research on Transmission Data System of Smart Grid based on IPv6 DiffServ Model

IEC 61850 provides the communication model and a set of unified interface for substation automation system (SAS) in Smart Grid. Using the DiffServ modern in IPv6 protocols to suit the IEC 61850 unity digital interface, the paper presents a novel method to implement the QoS guarantee system of metropolitan area electric power communication network. Different kinds of real-time data in SAS are aggregated and configured by abstract communication service interface (ASCI), and then the aggregated traffic are transmitted under the DiffServ system and TCP/UDP/IP protocols, which is a kind of guarantee QoS service.
Long QT 1 Mutation KCNQ1A344V Increases Local Anesthetic Sensitivity of the Slowly Activating Delayed Rectifier Potassium Current

Background:Anesthesia in patients with long QT syndrome (LQTS) is a matter of concern. Congenital LQTS is most frequently caused by mutations in KCNQ1 (Kv7.1), whereas drug-induced LQTS is a consequence of HERG (human ether-a-go-go–related gene) channel inhibition. The aim of this study was to investigate whether the LQT1 mutation A344V in the S6 region of KCNQ1, at a position corresponding to the local anesthetic binding site in HERG, may render drug insensitive KCNQ1 channels into a toxicologically relevant target of these pharmacologic agents. This may suggest that LQTS constitutes not only a nonspecific but also a specific pharmacogenetic risk factor for anesthesia. Methods:The authors examined electrophysiologic and pharmacologic properties of wild-type and mutant KCNQ1 channels. The effects of bupivacaine, ropivacaine, and mepivacaine were investigated using two-electrode voltage clamp and whole cell patch clamp recordings. Results:The mutation A344V induced voltage-dependent inactivation in homomeric KCNQ1 channels and shifted the voltage dependence of KCNQ1/KCNE1 channel activation by +30 mV. The mutation furthermore increased the sensitivity of KCNQ1/KCNE1 channels for bupivacaine 22-fold (KCNQ1wt/KCNE1: IC50 = 2,431 ± 582 &mgr;m, n = 20; KCNQ1A344V/KCNE1: IC50 = 110 ± 9 &mgr;m, n = 24). Pharmacologic effects of the mutant channels were dominant when mutant and wild-type channels were coexpressed. Simulation of cardiac action potentials with the Luo-Rudy model yielded a prolongation of the cardiac action potential duration and induction of early afterdepolarizations by the mutation A344V that were aggravated by local anesthetic intoxication. Conclusions:The results indicate that certain forms of the LQTS may constitute a specific pharmacogenetic risk factor for regional anesthesia.
Monocyte and microglial activation in patients with mood-stabilized bipolar disorder.

BACKGROUND Bipolar disorder is associated with medical comorbidities that have been linked to systemic inflammatory mechanisms. There is, however, limited evidence supporting a role of neuroinflammation in bipolar disorder. Here we tested whether microglial activation and associated tissue remodelling processes are related to bipolar disorder by analyzing markers in cerebrospinal fluid (CSF) and serum from patients and healthy controls. METHODS Serum was sampled from euthymic patients with bipolar disorder and healthy controls, and CSF was sampled from a large subset of these individuals. The levels of monocyte chemoattractant protein-1 (MCP-1), YKL-40, soluble cluster of differentiation 14 (sCD14), tissue inhibitor of metalloproteinases-1 (TIMP-1) and tissue inhibitor of metalloproteinases-2 (TIMP-2), were measured, and we adjusted comparisons between patients and controls for confounding factors. RESULTS We obtained serum samples from 221 patients and 112 controls and CSF samples from 125 patients and 87 controls. We found increased CSF levels of MCP-1 and YKL-40 and increased serum levels of sCD14 and YKL-40 in patients compared with controls; these differences remained after controlling for confounding factors, such as age, sex, smoking, blood-CSF barrier function, acute-phase proteins and body mass index. The CSF levels of MCP-1 and YKL-40 correlated with the serum levels, whereas the differences between patients and controls in CSF levels of MCP-1 and YKL-40 were independent of serum levels. LIMITATIONS The cross-sectional study design precludes conclusions about causality. CONCLUSION Our results suggest that both neuroinflammatory and systemic inflammatory processes are involved in the pathophysiology of bipolar disorder. Importantly, markers of immunological processes in the brain were independent of peripheral immunological activity.
Heterochromatin DNA replication and Rif 1 Buonomo

Article Chronology: Received 5 January 2010 Revised version received 16 March 2010 Accepted 17 March 2010 Available online 25 March 2010 Constitutive heterochromatin is essential for chromosome maintenance in all eukaryotes. However, the repetitive nature of the underlying DNA, the presence of very stable protein–DNA complexes and the highly compacted nature of this type of chromatin represent a challenge for the DNA replication machinery. Data collected from different model organisms suggest that at least some of the components of the DNA replication checkpoint could be essential for ensuring the completion of DNA replication in the context of heterochromatin. I review and discuss the literature that directly or indirectly contributes to the formulation of this hypothesis. In particular, I focus my attention on Rif1, a newly discovered member of the DNA replication checkpoint. Recent data generated in mammalian cells highlight the spatial and temporal relation between Rif1, pericentromeric heterochromatin and S-phase. I review these recent and the previous data coming from studies performed in yeast in order to highlight the possible evolutionary conserved links and propose a molecular model for Rif1 role in heterochromatin replication. © 2010 Elsevier Inc. All rights reserved.
A Novel Four-leg Matrix Converter

There is an increased interest in four-leg converters that can effectively provide the neutral connection in three-phase four-wire systems. This paper introduces a two-stage four-leg matrix converter, which can synthesise any desirable three-phase output line to neutral voltage. Two independent stages performing rectification and inversion are identified. The rectification stage is controlled to exhibit the highest voltage on the DC-rails. A three-dimensional space vector modulation technique is adopted at the inversion stage. Methods to reduce the neutral current and common mode voltage for the new topology are proposed
Blind source separation using clustering-based multivariate density estimation algorithm

A learning algorithm is developed for blind separation of the independent source signals from their linear mixtures. The algorithm is based on minimizing a contrast function defined in terms of the Kullback-Leibler distance. We use a clustering-based multivariate density estimation approach to reduce the number of the parameters to be updated. Simulations illustrate the validity of the algorithm.
18.3 A multi-parameter signal-acquisition SoC for connected personal health applications

Connected personal healthcare, or Telehealth, requires smart, miniature wearable devices that can collect and analyze physiological and environmental parameters during a user's daily routine. To truly support emerging applications (Fig. 18.3.1), a generic platform is needed that can acquire a multitude of sensor modalities and has generic energy-efficient signal processing capabilities. SoC technology gives significant advantages for miniaturization. But meeting low-power, medical grade signal quality, multi-sensor support and generic signal processing is still a challenge. For instance, [1] demonstrated a multi-sensor interface but it lacks support for efficient on-chip signal processing and doesn't have a high performance AFE. [2] showed a very low power signal processor but without support for multi-sensor interfacing. [3] presented a highly integrated SoC but lacking power efficiency. This paper demonstrates a highly integrated low-power SoC with enough flexibility to support many emerging applications. A wide range of sensor modalities are supported including 3-lead ECG and bio-impedance via high-performance and low-power AFE. The ARM Cortex™ M0 processor and matrix-multiply-accumulate accelerator can execute numerous biomedical signal processing algorithms (e.g. Independent Component Analysis (ICA), Principal Component Analysis (PCA,) CWT, feature extraction/classification, etc.) in an energy efficient way without sacrificing flexibility. The diversity in supported modalities and the generic processing capabilities, all provided in a single-chip low-power solution, make the proposed SoC a key enabler for emerging personal health applications (Fig. 18.3.1).
Is Geriatric Depression Scale-15 a suitable instrument for measuring depression in Brazil? Results of a Rasch analysis

Depressive symptoms are the most prevalent mental health condition in older adults. Since it cannot be measured directly, the use of instruments is mandatory. The 15-item Geriatric Depression Scale (GDS) is one of the most widely used scales to measure depression in the elderly. It is recognized that the cultural context is a major determinant of the instrument's psychometric performance. Up to the present, this scale has mainly been investigated through classical psychometric approaches. The present study aims to explore whether the 15-item GDS is a suitable instrument in a Brazilian sample. In addition, it explores the potential improvement in the psychometric performance by item refinement. Four hundred twenty-four elderly adults selected through convenience sampling completed the 15-item GDS. Data were analyzed by the Rasch Measurement Model. The Rasch analysis is a powerful modern approach to explore psychometric performance of instruments in health sciences. It examines both the scale and the individual item performance in depth. The 15-item GDS proved not to be suitable in a Brazilian sample. Item misfit and differential item functioning were responsible for considerable misperformance. Scale reduction led to a 10-item structure. This refined format presented adequate psychometric performance and no differential item functioning. The present study offers an alternative and more adequate version of the GDS to be applied in Brazilian subjects. It is also in line with the need for shorter, valid scales in clinical settings. Further investigations are needed to develop a set of cultural-invariant items, which could then be applied in transcultural investigations free of bias.
PSIHIČKI POREMEĆAJI I SOCIJALNA ZRELOST DJECE I MLADIH S POREMEĆAJIMA IZ AUTISTIČNOG SPEKTRA I DJECE I MLADIH S VEĆIM INTELEKTUALNIM TEŠKOĆAMA

Prema definiciji Svjetske zdravstvene organizacije (SZO) (1) moguce je razmisljati o mentalnom (psihickom) zdravlju kao stanju u kojem pojedinac postiže stanje ravnoteže u sebi i s okolinom. Psihicko zdravlje determinirano je zadovoljenjem osnovnih ljudskih potreba, kao sto su ona za drustvenim prihvacanjem, odnosima i pozitivnim osjecajima (2). Psihicko zdravlje uvjetovano je cimbenicima stabilne licnosti, cvrstom pozicijom i ulogom u drustvu te iskoristavanjem vlastitih sposobnosti. Stabilnu osobu obilježava i harmonican razvoj kognitivnog, socijalnog i Soc. psihijat. , 42 (2014) 21 – 32 Izvorni znanstveni rad
Electron microscopic localization of photoaffinity‐labelled delta opioid receptors in the neostriatum of the rat

The distribution of delta opioid receptors, selectively labelled in vitro with the photoaffinity probe monoiodo azido‐DTLET ([D‐Thr2, pN3Phe4, Leu5] enkephalyl‐Thr6), was analyzed by light and electron micrsocopic radioautography in sections from rat neostriatum. Preliminary experiments indicated that up to 65% of specific 125I‐azido‐DTLET binding to rat striatal sections was still detectable following prefixation of the brain with 0.5% glutaraldehyde. These experiments also showed that up to 20–30% of the specifically bound radioactivity was covalently linked following ultraviolet irradiation and was thereby retained in tissue during subsequent postfixation and dehydration steps. Accordingly, the topographic distribution of the covalently attached azido‐DTLET molecules was similar to that seen in fresh frozen sections and characteristic of that previously described for delta sites. Light and electron microscopic examination of the label in prefixed, striatal sections irradiated with ultraviolet light revealed that a significant proportion of specifically bound 125I‐azido‐DTLET molecules was intraneuronal. Specifically, 16% of the labelled binding sites were found in dendrites, 12% in perikarya and 4% in axon terminals. These results suggest that an important proportion of delta opioid binding sites labelled in the neostriatum correspond to receptors that are undergoing synthesis, transport and/or recycling. They also imply that a major fraction of delta sites are associated with intrastriatal neurons, as opposed to afferent axons. Approximately 44% of the labelled binding sites were associated with neuronal plasma membranes. Although most of these were found at the level of axodendritic (20%) and dendrodendritic (7%) appositions, comparison of the labelling incidence of these two compartments with their frequency of occurrence in tissue suggested that delta sites are fairly widely dispersed along neuronal plasma membranes. Only a small proportion (smaller than that of mu or kappa sites labelled in the same region) was associated with synaptic specializations. These results support the concept that delta receptors correspond to molecular entities that are distinct from mu and kappa sites and suggest that delta ligands act primarily nonjunctionally on the plasma membrane of striatal neurons. © 1992 Wiley‐Liss, Inc.
The suitability of human adipose‐derived stem cells for the engineering of ligament tissue

Rupture of the anterior cruciate ligament (ACL) is the one of the most common sports‐related injuries. With its poor healing capacity, surgical reconstruction using either autografts or allografts is currently required to restore function. However, serious complications are associated with graft reconstructions and the number of such reconstructions has steadily risen over the years, necessitating the search for an alternative approach to ACL repair. Such an approach may likely be tissue engineering. Recent engineering approaches using ligament‐derived fibroblasts have been promising, but the slow growth rate of such fibroblasts in vitro may limit their practical application. More promising results are being achieved using bone marrow mesenchymal stem cells (MSCs). The adipose‐derived stem cell (ASC) is often proposed as an alternative choice to the MSC and, as such, may be a suitable stem cell for ligament engineering. However, the use of ASCs in ligament engineering still remains relatively unexplored. Therefore, in this study, the potential use of human ASCs in ligament tissue engineering was initially explored by examining their ability to express several ligament markers under growth factor treatment. ASC populations treated for up to 4 weeks with TGFβ1 or IGF1 did not show any significant and consistent upregulation in the expression of collagen types 1 and 3, tenascin C and scleraxis. While treatment with EGF or bFGF resulted in increased tenascin C expression, increased expression of collagens 1 and 3 were never observed. Therefore, simple in vitro treatment of human ASC populations with growth factors may not stimulate their ligament differentiative potential. Copyright © 2011 John Wiley & Sons, Ltd.
Effects of anti-myosin drugs on anaphase chromosome movement and cytokinesis in crane-fly primary spermatocytes.

To investigate whether myosin is involved in crane-fly primary spermatocyte division, we studied the effects of myosin inhibitors on chromosome movement and on cytokinesis. With respect to chromosome movement, the myosin ATPase inhibitor 2,3-butanedione 2-monoxime (BDM) added during autosomal anaphase reversibly perturbed the movements of all autosomes: autosomes stopped, slowed, or moved backwards during treatment. BDM added before anaphase onset altered chromosome movement less than when BDM was added during anaphase: chromosome movements only rarely were stopped. They often were normal initially and then, if altered at all, were slowed. To confirm that the effects of BDM were due to myosin inhibition, we treated cells with ML-7, a drug that inhibits myosin light chain kinase (MLCK), an enzyme necessary to activate myosin. ML-7 affected anaphase movement only when added in early prometaphase: this treatment prevented chromosome attachment to the spindle. We treated cells with H-7 as a control for possible non-myosin effects of ML-7. H-7, which has a lower affinity than ML-7 for MLCK but a higher affinity than ML-7 for other potential targets, had no effect. These data confirm that the BDM effect is on myosin and indicate that the myosin used for chromosome movement is activated near the start of prometaphase. With respect to cytokinesis, BDM did not block furrow initiation but did block subsequent contraction of the contractile ring. When BDM was added after initiation of the furrow, the contractile ring either stalled or relaxed. ML-7 blocked contractile ring contraction when added at all stages after autosomal anaphase onset, including when added during cytokinesis. H-7 had no effect. These results confirm that the effects of BDM are on myosin and indicate that the myosin used for cytokinesis is activated starting from autosomal anaphase and continuing throughout cytokinesis.
Confidence-Interval Construction for Rate Ratio in Matched-Pair Studies with Incomplete Data

Matched-pair design is often used in clinical trials to increase the efficiency of establishing equivalence between two treatments with binary outcomes. In this article, we consider such a design based on rate ratio in the presence of incomplete data. The rate ratio is one of the most frequently used indices in comparing efficiency of two treatments in clinical trials. In this article, we propose 10 confidence-interval estimators for the rate ratio in incomplete matched-pair designs. A hybrid method that recovers variance estimates required for the rate ratio from the confidence limits for single proportions is proposed. It is noteworthy that confidence intervals based on this hybrid method have closed-form solution. The performance of the proposed confidence intervals is evaluated with respect to their exact coverage probability, expected confidence interval width, and distal and mesial noncoverage probability. The results show that the hybrid Agresti–Coull confidence interval based on Fieller’s theorem performs satisfactorily for small to moderate sample sizes. Two real examples from clinical trials are used to illustrate the proposed confidence intervals.