A Novel Algorithm for Movement Artifact Removal in ECG Signals Acquired from Wearable Systems Applied to Horses

This study reports on a novel method to detect and reduce the contribution of movement artifact (MA) in electrocardiogram (ECG) recordings gathered from horses in free movement conditions. We propose a model that integrates cardiovascular and movement information to estimate the MA contribution. Specifically, ECG and physical activity are continuously acquired from seven horses through a wearable system. Such a system employs completely integrated textile electrodes to monitor ECG and is also equipped with a triaxial accelerometer for movement monitoring. In the literature, the most used technique to remove movement artifacts, when noise bandwidth overlaps the primary source bandwidth, is the adaptive filter. In this study we propose a new algorithm, hereinafter called Stationary Wavelet Movement Artifact Reduction (SWMAR), where the Stationary Wavelet Transform (SWT) decomposition algorithm is employed to identify and remove movement artifacts from ECG signals in horses. A comparative analysis with the Normalized Least Mean Square Adaptive Filter technique (NLMSAF) is performed as well. Results achieved on seven hours of recordings showed a reduction greater than 40% of MA percentage (between before- and after- the application of the proposed algorithm). Moreover, the comparative analysis with the NLMSAF, applied to the same ECG recordings, showed a greater reduction of MA percentage in favour of SWMAR with a statistical significant difference (p–value < 0.0.5).     

Activities of Daily Living,Depression, and Quality of Life in Parkinson's Disease

This study examined whether activities of daily living (ADL) mediate the relationship between depression and health-related quality of life (HR-QOL) in people with Parkinson''s disease (PD). A cross-sectional, correlational research design examined data from 174 participants who completed the Geriatric Depression Scale (GDS-15), Parkinson''s Disease Questionnaire-39 (PDQ-39), and Unified Parkinson''s Disease Rating Scale-section 2 (UPDRS-section 2 [ADL]). Multiple Regression Analysis (MRA) was used to examine the mediator model. Depression and ADL significantly (p<.001) predicted HR-QOL, and depression significantly (p<.001) predicted ADL. Whilst ADL did not impact on the relationship between depression and HR-QOL, there was a significant (p<.001) indirect effect of depression on HR-QOL via ADL, suggesting both direct and indirect (via ADL) effects of depression on HR-QOL. The magnitude of this effect was moderate (R ² = .13). People with PD who report depression also experience greater difficulty completing ADL, which impacts upon their HR-QOL. It is recommended that clinicians adopt a multidisciplinary approach to care by combining pharmacological treatments with psycho/occupational therapy, thereby alleviating the heterogeneous impact of motor and non-motor symptoms on HR-QOL in people with PD.     

Carbonic anhydrase inhibitors: Inhibition of the tumor-associated isozymes IX and XII with polyfluorinated aromatic/heterocyclic sulfonamides

The tumor-associated transmembrane carbonic anhydrase (CA, EC 4.2.1.1) isozymes IX (CA IX) and XII (CA XII) are involved in acidification of hypoxic tumors, a process correlated with poor prognosis and clinical outcome of patients harboring such tumors. This process may be reversed by inhibiting these enzymes with potent sulfonamide/sulfamate inhibitors. A series of such aromatic/heterocyclic sulfonamides incorporating 2,3,5,6-tetrafluorobenzoyl-, 2,3,5,6-tetrafluoro- phenylsulfonyl- and pentafluorophenylureido moieties has been investigated for its interaction with the catalytic domain of the human isozymes hCA IX and hCA XII. Some of these compounds showed excellent inhibitory properties against both isozymes IX and XII, with several subnanomolar inhibitors detected for the first time. These sulfonamides may constitute valuable candidates for the development of novel antitumor therapies based on the inhibition of such tumor-associated CA isozymes.     

Mathematical Modeling of Renal Tubular Glucose Absorption after Glucose Load

A partial differential Progressive Tubular Reabsorption (PTR) model, describing renal tubular glucose reabsorption and urinary glucose excretion following a glucose load perturbation, is proposed and fitted to experimental data from five subjects. For each subject the Glomerular Filtration Rate was estimated and both blood and urine glucose were sampled following an Intra-Venous glucose bolus. The PTR model was compared with a model representing the conventional Renal Threshold Hypothesis (RTH). A delay bladder compartment was introduced in both formulations. For the RTH model, the average threshold for glycosuria varied between 9.90±4.50 mmol/L and 10.63±3.64 mmol/L (mean ± Standard Deviation) under different hypotheses; the corresponding average maximal transport rates varied between 0.48±0.45 mmol/min (86.29±81.22 mg/min) and 0.50±0.42 mmol/min (90.62±76.15 mg/min). For the PTR Model, the average maximal transports rates varied between 0.61±0.52 mmol/min (109.57±93.77 mg/min) and 0.83±0.95 mmol/min (150.13±171.85 mg/min). The time spent by glucose inside the tubules before entering the bladder compartment varied between 1.66±0.73 min and 2.45±1.01 min.The PTR model proved much better than RTH at fitting observations, by correctly reproducing the delay of variations of glycosuria with respect to the driving glycemia, and by predicting non-zero urinary glucose elimination at low glycemias. This model is useful when studying both transients and steady-state glucose elimination as well as in assessing drug-related changes in renal glucose excretion.     

Conspecific plant–soil feedback scales with population size in Lobelia siphilitica (Lobeliaceae)

Plant–soil interactions directly affect plant success in terms of establishment, survival, growth and reproduction. Negative plant–soil feedback on such traits may therefore reduce the density and abundance of plants of a given species at a given site. Furthermore, if conspecific feedback varies among population sites, it could help explain geographic variation in plant population size. We tested for among-site variation in conspecific plant–soil feedback in a greenhouse experiment using seeds and soils from 8 natural populations of Lobelia siphilitica hosting 30–330 plants. The first cohort of seeds was grown on soil collected from each native site, while the second cohort was grown on the soil conditioned by the first. Our goal was to distinguish site-specific effects mediated by biotic and/or abiotic soil properties from those inherent in seed sources. Cohort 1 plants grown from seeds produced in small populations performed better in terms of germination, growth, and survival compared to plants produced in large populations. Plant performance decreased substantially between cohorts, indicating strong negative feedback. Most importantly, the strength of negative feedback scaled linearly (i.e., was less negative) with increasing size of the native plant population, particularly for germination and survival, and was better explained by soil- rather than seed-source effects. Even with a small number of sites, our results suggest that the potential for negative plant–soil feedback varies among populations of L. siphilitica, and that small populations were more susceptible to negative feedback. Conspecific plant–soil feedback may contribute to plant population size variation within a species’ native range.     

Altered Intracellular Localization of SOD1 in Leukocytes from Patients with Sporadic Amyotrophic Lateral Sclerosis

Several lines of evidence support the hypothesis of a toxic role played by wild type SOD1 (WT-SOD1) in the pathogenesis of sporadic amyotrophic lateral sclerosis (SALS). In this study we investigated both distribution and expression profile of WT-SOD1 in leukocytes from 19 SALS patients and 17 healthy individuals. Immunofluorescence experiments by confocal microscopy showed that SOD1 accumulates in the nuclear compartment in a group of SALS subjects. These results were also confirmed by western blot carried out on soluble nuclear and cytoplasmic fractions, with increased nuclear SOD1 level (p<0.05). In addition, we observed the presence of cytoplasmic SOD1 aggregates in agreement with an increased amount of the protein recovered by the insoluble fraction. A further confirmation of the overall increased level of SOD1 has been obtained from single cells analysis using flow cytometry as cells from SALS patients showed an higher SOD1 protein content (p<0.05). These findings add further evidence to the hypothesis of an altered WT-SOD1 expression profile in peripheral blood mononuclear cells (PBMCs) from patients with ALS suggesting that WT-SOD1 species with different degrees of solubility could be involved in the pathogenesis of the disease.     

The Role of Angiopoietins as Potential Therapeutic Targets in Renal Cell Carcinoma

Angiopoietin 2 (Ang2) is a secreted glycoprotein upregulated at sites of angiogenesis and has been implicated in cancer neovascularization. Recent studies have suggested efficacy of combined Ang and vascular endothelial growth factor receptor (VEGFR) inhibition for patients with metastatic renal cell carcinoma (mRCC). We measured Ang2 expression in human tissue and plasma, and tested the effect of dual Ang1/2 (trebananib; AMG386) or Ang2 alone (L1-7) inhibition with VEGFR inhibition on murine RCC growth and blood flow. Ang2 levels were higher in human tumors than normal tissues with RCC ranking highest for Ang2 expression across all tumor types tested. Plasma Ang2 was significantly higher in patients with mRCC compared to controls or patients with stage I disease. Plasma Ang2 decreased with sunitinib treatment and increased at time of disease progression. In the RCC mouse, dual Ang1/2 and Ang2 inhibition improved the activity of sunitinib. Combined Ang1/2 and VEGFR inhibition prevented the resumption of blood flow associated with sunitinib resistance. Thus, Ang2 inhibition, independent of Ang1 inhibition, improves the activity of sunitinib and plasma Ang2 increases in the setting of progression on sunitinib possibly contributing to resistance. Further, arterial spin-labeled perfusion magnetic resonance imaging might be a non-invasive marker of the antiangiogenic activity of Ang inhibitors.     

CoupTFI Interacts with Retinoic Acid Signaling during Cortical Development

We examined the role of the orphan nuclear hormone receptor CoupTFI in mediating cortical development downstream of meningeal retinoic acid signaling. CoupTFI is a regulator of cortical development known to collaborate with retinoic acid (RA) signaling in other systems. To examine the interaction of CoupTFI and cortical RA signaling we utilized Foxc1-mutant mice in which defects in meningeal development lead to alterations in cortical development due to a reduction of RA signaling. By analyzing CoupTFI^−/−;Foxc1^H/L double mutant mice we provide evidence that CoupTFI is required for RA rescue of the ventricular zone and the neurogenic phenotypes in Foxc1-mutants. We also found that overexpression of CoupTFI in Foxc1-mutants is sufficient to rescue the Foxc1-mutant cortical phenotype in part. These results suggest that CoupTFI collaborates with RA signaling to regulate both cortical ventricular zone progenitor cell behavior and cortical neurogenesis.