Metabolic topography of autoimmune non-paraneoplastic encephalitis

Abstract

Purpose

F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) is emerging to be a useful tool in supporting the diagnosis of AIE. In this study, we describe the metabolic patterns on F-18 FDG PET imaging in AIE.

Methods

Twenty-four antibody-positive patients (anti-NMDA-15, anti-VGKC/LGI1-6, and anti-GAD-3), 14 females and 10 males, with an age range of 2–83 years were included in this study. Each PET study was evaluated visually for the presence of hypometabolism or hypermetabolism and semiquantitatively using Cortex ID (GE) and Scenium (Siemens) by measuring regional Z-scores. These patterns were correlated with corresponding antibody positivity once available.

Results

Visually, a pattern of hypometabolism, hypermetabolism, or both in various spatial distributions was appreciated in all 24 patients. On quantitative analysis using scenium parietal and occipital lobes showed significant hypometabolism with median Z-score of −3.8 (R) and −3.7 (L) and −2.2 (R) and −2.5 (L) respectively. Two-thirds (16/24) showed significant hypermetabolism involving the basal ganglia with median Z-score of 2.4 (R) and 3.0 (L). Similarly on Cortex ID, the median Z-score for hypometabolism in parietal and occipital lobes was −2.2 (R) and −2.4 (L) and −2.6 (R) and −2.4 (L) respectively, while subcortical regions were not evaluated. MRI showed signal alterations in only 11 of these patients.

Conclusion

There is heterogeneity in metabolic topography of AIE which is characterized by hypometabolism most commonly involving the parietal and occipital cortices and hypermetabolism most commonly involving the basal ganglia. Scenium analysis using regional Z-scores can complement visual evaluation for demonstration of these metabolic patterns on FDG PET.

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vCJD : Integrated Approach

Presenting an integrated case discussion in DAMS Medicine Unplugged Series where we discuss different aspects of vCJD and Prion disease. Multi specialty  integration is theme of this series on damsdelhi channel on YouTube

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Systematic intrafraction shifts of mediastinal lymph node targets between setup imaging and radiation treatment delivery in lung cancer patients

Publication date: Available online 16 December 2017
Source:Radiotherapy and Oncology
Author(s): Mai Lykkegaard Schmidt, Lone Hoffmann, Ditte S. Møller, Marianne Marquard Knap, Torben Riis Rasmussen, Birgitte Holst Folkersen, Per Rugaard Poulsen
Background and purposeInternal target motion results in geometrical uncertainties in lung cancer radiotherapy. In this study, we determined the intrafraction motion and baseline shifts of mediastinal lymph node (LN) targets between setup imaging and treatment delivery.Material and methodsTen lung cancer patients with 2–4 fiducial markers implanted in LN targets received intensity-modulated radiotherapy with a daily setup cone-beam CT (CBCT) scan used for online soft-tissue match on the primary tumor. At a total of 122 fractions, 5 Hz fluoroscopic kV images were acquired orthogonal to the MV treatment beam during treatment delivery. Offline, the 3D trajectory of the markers was determined from their projected trajectory in the CBCT projections and in the intra-treatment kV images. Baseline shifts and changes in the respiratory motion amplitude between CBCT and treatment delivery were determined from the 3D trajectories.ResultsSystematic mean LN baseline shifts of 2.2 mm in the cranial direction (standard deviation (SD): 1.8 mm) and 1.0 mm in the posterior direction (SD: 1.2 mm) occurred between CBCT imaging and treatment delivery. The mean motion amplitudes during CBCT and treatment delivery agreed within 0.2 mm in all directions.ConclusionsSystematic cranial and posterior intrafraction baseline shifts between CBCT and treatment delivery were observed for mediastinal LN targets. Intrafraction motion amplitudes were stable.



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Modelling uncertainties in the diffusion-advection equation for radon transport in soil using interval arithmetic

Publication date: February 2018
Source:Journal of Environmental Radioactivity, Volume 182
Author(s): S. Chakraverty, B.K. Sahoo, T.D. Rao, P. Karunakar, B.K. Sapra
Modelling radon transport in the earth crust is a useful tool to investigate the changes in the geo-physical processes prior to earthquake event. Radon transport is modeled generally through the deterministic advection-diffusion equation. However, in order to determine the magnitudes of parameters governing these processes from experimental measurements, it is necessary to investigate the role of uncertainties in these parameters. Present paper investigates this aspect by combining the concept of interval uncertainties in transport parameters such as soil diffusivity, advection velocity etc, occurring in the radon transport equation as applied to soil matrix. The predictions made with interval arithmetic have been compared and discussed with the results of classical deterministic model. The practical applicability of the model is demonstrated through a case study involving radon flux measurements at the soil surface with an accumulator deployed in steady-state mode. It is possible to detect the presence of very low levels of advection processes by applying uncertainty bounds on the variations in the observed concentration data in the accumulator. The results are further discussed.

Graphical abstract

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Sacral Osteoneogenesis after Complete Sacrectomy in a Patient with Ewing Sarcoma

Ewing sarcomas are the second most common primary malignant bone tumors in childhood and adolescence which rapidly metastasize. Due to improvement of treatment options in recent years, the survival rate has significantly increased. Nevertheless, lethality is still high, and neurologic symptoms are frequent. To the best of our knowledge, this is the first reported case of a sacral osteoneogenesis after complete sacrectomy in a patient with Ewing sarcoma.

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The Interrelation between Reactive Oxygen Species and Autophagy in Neurological Disorders

Neurological function deficits due to cerebral ischemia or neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) have long been considered a thorny issue in clinical treatment. Recovery after neurologic impairment is fairly limited, which poses a major threat to health and quality of life. Accumulating evidences support that ROS and autophagy are both implicated in the onset and development of neurological disorders. Notably, oxidative stress triggered by excess of ROS not only puts the brain in a vulnerable state but also enhances the virulence of other pathogenic factors, just like mitochondrial dysfunction, which is described as the culprit of nerve cell damage. Nevertheless, autophagy is proposed as a subtle cellular defense mode against destructive stimulus by timely removal of damaged and cytotoxic substance. Emerging evidence suggests that the interplay of ROS and autophagy may establish a determinant role in the modulation of neuronal homeostasis. However, the underlying regulatory mechanisms are still largely unexplored. This review sets out to afford an overview of the crosstalk between ROS and autophagy and discusses relevant molecular mechanisms in cerebral ischemia, AD, and PD, so as to provide new insights into promising therapeutic targets for the abovementioned neurological conditions.

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A Robust Method for GPS/BDS Pseudorange Differential Positioning Based on the Helmert Variance Component Estimation

The use of global navigation satellite system (GNSS) is entering a new era of joint positioning based on the use of multifrequencies and multimodes. Ensuring the correct weighting of observations from each system and satellite has become a key problem during real-time positioning. This paper addresses the issue of weights of observations as well as the quality control of GPS/BDS pseudoranges in the context of real-time relative positioning. Thus, in the first place, the Helmert variance component estimation (VCE) is used to determine the relative weighting of observations from the two systems, and then, we introduce robustness estimation theory and construct a new method. The method is resistant to the influence of outliers in the observations by selecting weight iterations. To do this, we selected GPS/BDS observation data at baseline lengths of 40 km, 46 km, and 64 km for verification and analysis. Experimental results show that, in terms of the relative positioning of medium-to-long baseline based on GPS/BDS pseudorange observations, when observed values incorporate large gross errors, our method can reduce the weighting of suspicious or abnormal values and weaken their impact on positioning solutions, so that the positioning results will not appear to have large deviation.

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Spleen-Preserving Surgery in Splenic Artery Aneurysm

Endovascular interventions are increasingly used in the treatment of a splenic artery aneurysm (SAA), which is a rare and life-threatening clinical disorder. However, in cases of SAA rupture, minimally invasive interventions are unsuitable, and open surgery remains the gold standard method. In open surgery, care should be taken to preserve the spleen and its immune function in cases where an arterial segment of sufficient length allows for reconstruction. An SAA was detected in a 51-year-old woman who presented to our polyclinic with left upper quadrant pain. An endovascular intervention was unsuccessful, and open surgery was performed. Approximately 5 cm of aneurysm in the middle segment of the splenic artery was treated by arterial anastomosis, and the spleen was preserved. The patient experienced no postoperative complications and remained asymptomatic at the seventh month of follow-up. The aim of this case report is to emphasize the importance of splenic sparing surgery in cases of SAAs.

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Landslide Susceptibility in Relation to Correlation of Groundwater Development and Ground Condition

Rainfall is inevitably one of the main factors that trigger landslides. However, not much study has been conducted on the impact of groundwater rise on slope stability. Thus, this study is intended to focus on the rise of the groundwater level from the bottom of the slope which would lead to landslides due to pore pressure development by eliminating other landslide-triggering factors (i.e., infiltration and surface runoff). Saturated sand was used for slope modeling, and sand densities of 1523 kg/m3, 1562 kg/m3, and 1592 kg/m3 were tested with a constant slope angle of 45°. Another set of experiments was also performed on slopes having angles of 25°, 45°, and 60° and with a maintained density of sand at 1562 kg/m3. Through observation, failure was initiated first at the toe of the slope before minor and major slips or total collapse occurs. Dimensions of slip surfaces were measured and included in SLOPE/W for the computation of the safety factor. In conclusion, safety factors are found to be higher in denser soil and in the lowest slope angle. However, faster occurrence of collapse in denser soil was identified and could be contributed by the faster pore water pressure development.

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Regulating the Balance of Th17/Treg via Electroacupuncture and Moxibustion: An Ulcerative Colitis Mice Model Based Study

Aim. To investigate the relationship between the effects of electroacupuncture/moxibustion and the balance of Th17/Treg in treating ulcerative colitis (UC) and to preliminary compare the effects of the above two methods. Methods. DSS-induced UC mice were treated by electroacupuncture and moxibustion. Disease activity index (DAI) was scored; intestinal pathological structure and ultrastructure were observed. The levels of IL-2, IL-6, IL-10, IL-17A, IL-17F, and TGF-β in plasma were measured by ELISA. The percentages of Treg and Th17 in spleen lymphocytes were analyzed by flow cytometry. Also, the expressions of TLR2, TLR4, RORγt, and FOXP3 in the distal colon were detected by immunohistochemistry or western blot. Results. Both electroacupuncture and moxibustion can relieve UC. These effects are further supported by ELISA results. In addition, the ratio of Treg and Th17 in spleen lymphocytes and the expression of TLR2 and TLR4 are significantly improved. Also, the expression of RORγt and FOXP3 in distal colon were improved. Besides, the effect of moxibustion is better than that of electroacupuncture on TLR2, TLR4, and FOXP3 expression (). Conclusion. Both electroacupuncture and moxibustion may ameliorate UC by regulating the balance of Th17/Treg. Whether moxibustion has better efficacy than electroacupuncture needs further study.

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On Flows of Bingham-Type Fluids with Threshold Slippage

We investigate a mathematical model describing 3D steady-state flows of Bingham-type fluids in a bounded domain under threshold-slip boundary conditions, which state that flows can slip over solid surfaces when the shear stresses reach a certain critical value. Using a variational inequalities approach, we suggest the weak formulation to this problem. We establish sufficient conditions for the existence of weak solutions and provide their energy estimates. Moreover, it is shown that the set of weak solutions is sequentially weakly closed in a suitable functional space.

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Recognise CDK4 and 6 as key regulators of the G1- S transition of the cell cycle in our recent module:… https://t.co/uuFr0hC9xX

Recognise CDK4 and 6 as key regulators of the G1- S transition of the cell cycle in our recent module:… https://t.co/uuFr0hC9xX

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Curcuma longa Is Able to Induce Apoptotic Cell Death of Pterygium-Derived Human Keratinocytes

Pterygium is a relatively common eye disease that can display an aggressive clinical behaviour. To evaluate the in vitro effects of Curcuma longa on human pterygium-derived keratinocytes, specimens of pterygium from 20 patients undergoing pterygium surgical excision were collected. Pterygium explants were put into culture and derived keratinocytes were treated with an alcoholic extract of 1.3% Curcuma longa in 0.001% Benzalkonium Chloride for 3, 6, and 24 h. Cultured cells were examined for CAM5.2 (anti-cytokeratin antibody) and CD140 (anti-fibroblast transmembrane glycoprotein antibody) expression between 3th and 16th passage to assess cell homogeneity. TUNEL technique and Annexin-V/PI staining in flow cytometry were used to detect keratinocyte apoptosis. We showed that Curcuma longa exerts a proapoptotic effect on pterygium-derived keratinocytes already after 3 h treatment. Moreover, after 24 h treatment, Curcuma longa induces a significant increase in TUNEL as well as Annexin-V/PI positive cells in comparison to untreated samples. Our study confirms previous observations highlighting the expression, in pterygium keratinocytes, of nuclear VEGF and gives evidence for the first time to the expression of nuclear and cytoplasmic VEGF-R1. All in all, these findings suggest that Curcuma longa could have some therapeutic potential in the treatment and prevention of human pterygium.

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5G MIMO Conformal Microstrip Antenna Design

With the development of wireless communication technology, 5G will develop into a new generation of wireless mobile communication systems. MIMO (multiple-input multiple-output) technology is expected to be one of the key technologies in the field of 5G wireless communications. In this paper, 4 pairs of microstrip MIMO conformal antennas of 35 GHz have been designed. Eight-element microstrip Taylor antenna array with series-feeding not only achieves the deviation of the main lobe of the pattern but also increases the bandwidth of the antenna array and reduces sidelobe. MIMO antennas have been fabricated and measured. Measurement results match the simulation results well. The return loss of the antenna at 35 GHz is better than 20 dB, the first sidelobe level is −16 dB, and the angle between the main lobe and the plane of array is 60°.

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MeReg: Managing Energy-SLA Tradeoff for Green Mobile Cloud Computing

Mobile cloud computing (MCC) provides various cloud computing services to mobile users. The rapid growth of MCC users requires large-scale MCC data centers to provide them with data processing and storage services. The growth of these data centers directly impacts electrical energy consumption, which affects businesses as well as the environment through carbon dioxide (CO2) emissions. Moreover, large amount of energy is wasted to maintain the servers running during low workload. To reduce the energy consumption of mobile cloud data centers, energy-aware host overload detection algorithm and virtual machines (VMs) selection algorithms for VM consolidation are required during detected host underload and overload. After allocating resources to all VMs, underloaded hosts are required to assume energy-saving mode in order to minimize power consumption. To address this issue, we proposed an adaptive heuristics energy-aware algorithm, which creates an upper CPU utilization threshold using recent CPU utilization history to detect overloaded hosts and dynamic VM selection algorithms to consolidate the VMs from overloaded or underloaded host. The goal is to minimize total energy consumption and maximize Quality of Service, including the reduction of service level agreement (SLA) violations. CloudSim simulator is used to validate the algorithm and simulations are conducted on real workload traces in 10 different days, as provided by PlanetLab.

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Ticagrelor-Induced Angioedema: A Rare and Unexpected Phenomenon

Angioedema can cause potentially life-threatening airway obstruction. This case report describes an exceedingly rare episode of ticagrelor-induced hypersensitivity reaction, manifesting as angioedema with periorbital and likely respiratory involvement. The heart team should be vigilant for this precarious condition which may require emergent airway management. Desensitization protocols and alternative regimens (e.g., clopidogrel, prasugrel, and addition of an adjunctive anticoagulant) should be considered when there is an absolute indication for antiplatelet therapy.

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Existence Results for Fractional Hahn Difference and Fractional Hahn Integral Boundary Value Problems

The existence and uniqueness results of two fractional Hahn difference boundary value problems are studied. The first problem is a Riemann-Liouville fractional Hahn difference boundary value problem for fractional Hahn integrodifference equations. The second is a fractional Hahn integral boundary value problem for Caputo fractional Hahn difference equations. The Banach fixed-point theorem and the Schauder fixed-point theorem are used as tools to prove the existence and uniqueness of solution of the problems.

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Two-Dimensional DOA Estimation Using Arbitrary Arrays for Massive MIMO Systems

With the quick advancement of wireless communication networks, the need for massive multiple-input-multiple-output (MIMO) to offer adequate network capacity has turned out to be apparent. As a portion of array signal processing, direction-of-arrival (DOA) estimation is of indispensable significance to acquire directional data of sources and to empower the 3D beamforming. In this paper, the performance of DOA estimation for massive MIMO systems is analyzed and compared using a low-complexity algorithm. To be exact, the 2D Fourier domain line search (FDLS) MUSIC algorithm is studied to mutually estimate elevation and azimuth angle, and arbitrary array geometry is utilized to represent massive MIMO systems. To avoid the computational burden in estimating the data covariance matrix and its eigenvalue decomposition (EVD) due to the large-scale sensors involved in massive MIMO systems, the reduced-dimension data matrix is applied on the signals received by the array. The performance is examined and contrasted with the 2D MUSIC algorithm for different types of antenna configuration. Finally, the array resolution is selected to investigate the performance of elevation and azimuth estimation. The effectiveness and advantage of the proposed technique have been proven by detailed simulations for different types of MIMO array configuration.

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ANA-Negative Hydralazine-Induced Pericardial Effusion

This case describes a patient with pericardial effusion as a phenomenon of the drug-induced lupus erythematosus (DILE) syndrome due to hydralazine. The relevance of this case report lies in the fact that although hydralazine has been a known causative agent of DILE, its presentation may involve a negative anti-nuclear antibody (ANA) study. Pericardial effusion is a documented adverse effect as a result of hydralazine use. It is typically common to screen for DILE with the serum ANA test prior to proceeding to more costly and specific tests (i.e., anti-histone antibody). As per our literature review, this is the second case of hydralazine causing DILE with a negative ANA. As in our case, although the screening serum ANA is the initial next best step for suspicion of DILE by hydralazine, it is important to consider the diagnosis without ANA positivity.

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Latest Stored Information Based Adaptive Selection Strategy for Multiobjective Evolutionary Algorithm

The adaptive operator selection (AOS) and the adaptive parameter control are widely used to enhance the search power in many multiobjective evolutionary algorithms. This paper proposes a novel adaptive selection strategy with bandits for the multiobjective evolutionary algorithm based on decomposition (MOEA/D), named latest stored information based adaptive selection (LSIAS). An improved upper confidence bound (UCB) method is adopted in the strategy, in which the operator usage rate and abandonment of extreme fitness improvement are introduced to improve the performance of UCB. The strategy uses a sliding window to store recent valuable information about operators, such as factors, probabilities, and efficiency. Four common used DE operators are chosen with the AOS, and two kinds of assist information on operator are selected to improve the operators search power. The operator information is updated with the help of LSIAS and the resulting algorithmic combination is called MOEA/D-LSIAS. Compared to some well-known MOEA/D variants, the LSIAS demonstrates the superior robustness and fast convergence for various multiobjective optimization problems. The comparative experiments also demonstrate improved search power of operators with different assist information on different problems.

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A Novel Efficiency Measure Model for Industrial Land Use Based on Subvector Data Envelope Analysis and Spatial Analysis Method

With the rapid and unbalanced development of industry, a large amount of cultivated land is converted into industrial land with lower efficiency. The existing research is extensively concerned with industrial land use and industrial development in isolation, but little attention has been paid to the relationship between them. To help address this gap, the paper creates a new efficiency measure method for industrial land use combining Subvector Data Envelope Analysis (DEA) with spatial analysis approach. The proposed model has been verified by using the industrial land use data of 30 Chinese provinces from 2001 to 2013. The spatial autocorrelation relationship between industrial development and industrial land use efficiency is explored. Furthermore, this paper examines the effects of industrial development on industrial land use efficiency by spatial panel data model. The results indicate that the industrial land use efficiency and the industrial development level in the provinces of eastern region are higher than those of the western region. The spatial distribution of industrial land use efficiency shows remarkable positive spatial autocorrelation. However, the level of industrial development has obvious negative spatial autocorrelation since 2009. The improvement of industrial development has a significant positive impact on the industrial land use efficiency.

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Three-Dimensional Hydromechanical Modeling during Shearing by Nonuniform Crust Movement

Hydromechanical modeling of a geological formation under shearing by the nonuniform crust movement during 10000 years was carried out to investigate the solid stress and pore pressure coupling processes of the formation from the intact to the fractured or faulted. Two three-dimensional numerical models were built and velocities in opposite directions were applied on the boundaries to produce the shearing due to the nonuniform crust movement. The results show that the stress and pore pressure became more and more concentrated in and around the middle of the formation as time progresses. In Model I with no fault, stress and pore pressure are concentrated in the middle of the model during shearing; however, in Model II with a fault zone of weakened mechanical properties, they are more complex and concentrated along the sides of the fault zone and the magnitudes decreased. The distribution of stress determines pore pressure which in turn controls fluid flow. Fluid flow occurs in the middle in Model I but along the sides of the fault zone in Model II. The results of this study improve our understanding of the rock-fluid interaction processes affected by crustal movement and may guide practical investigations in geological formations.

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Stopping rabies in its tracks

A co-ordinated approach to vaccination is stopping the disease spreading in Nepal

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Detailed Histologic Evaluation of Eosinophilic Esophagitis in Pediatric Patients Presenting with Dysphagia or Abdominal Pain and Comparison of the Histology between the Two Groups

EoE in children presents with four main symptoms. Most common symptoms exhibited by our clinic population are dysphagia (D) and abdominal pain (AP). Despite similar treatments, we found in an earlier study that the outcomes between these two groups were different. Therefore, we investigated if there exist any histological differences between these groups that could further our knowledge of EoE. Aim. To compare esophageal histology in detail, apart from the eosinophil count, between EoE-D and EoE-AP. Method. Biopsies of patients with EoE-D and EoE-AP were reevaluated for 10 additional histological criteria, in addition to the eosinophil count. Results. Both groups had 67 patients; peak mean eosinophil was 33.9 and 31.55 for EoE-D and EoE-AP (). Eosinophilic microabscesses, superficial layering of eosinophils, and epithelial desquamation were twice as common and significant in EoE-D group than EoE-AP. Eosinophil distribution around rete pegs was also significantly higher in EoE-D group. The remaining criteria were numerically higher in EoE-D, but not significant, with the exception of rete peg elongation. Conclusion. EoE-D patients have significantly higher eosinophils compared to EoE-AP, and the level of inflammation as seen from eosinophil microabscesses, superficial layering, desquamation, and the distribution around rete pegs is significantly higher.

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The Spatial Relationship between Apparent Diffusion Coefficient and Standardized Uptake Value of 18F-Fluorodeoxyglucose Has a Crucial Influence on the Numeric Correlation of Both Parameters in PET/MRI of Lung Tumors

The minimum apparent diffusion coefficient () derived from diffusion-weighted MRI (DW-MRI) and the maximum standardized uptake value () of FDG-PET are markers of aggressiveness in lung cancer. The numeric correlation of the two parameters has been extensively studied, but their spatial interplay is not well understood. After FDG-PET and DW-MRI coregistration, values and location of - and -voxels were analyzed. The upper limit of the 95% confidence interval for registration accuracy of sequential PET/MRI was 12 mm, and the mean distance () between - and -voxels was 14.0 mm (average of two readers). Spatial mismatch ( > 12 mm) between and was found in 9/25 patients. A considerable number of mismatch cases (65%) was also seen in a control group that underwent simultaneous PET/MRI. In the entire patient cohort, no statistically significant correlation between and was seen, while a moderate negative linear relationship () between and was observed in tumors with a spatial match ( ≤ 12 mm). In conclusion, spatial mismatch between and is found in a considerable percentage of patients. The spatial connection of the two parameters and has a crucial influence on their numeric correlation.

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Synthesis and Bactericidal Properties of Hyaluronic Acid Doped with Metal Nanoparticles

A study on the nanoparticles size and the antibacterial properties of hyaluronic acid (HA) doped with nanoparticles is reported. Nanoparticles from gold, silver, copper, and silver palladium with HA support were performed. The solvated metal atom dispersion (SMAD) method with 2-propanol and HA was used. High-resolution transmission electron microscopy (HRTEM), infrared spectroscopy (FT-IR), and thermogravimetric analysis (TGA) were conducted. The average sizes of nanoclusters were as follows: HA-Au = 17.88 nm; HA-Ag = 50.41 nm; HA-Cu = 13.33 nm; and HA-AgPd = 33.22 nm. The antibacterial activity of solutions and films containing nanoparticles against American Type Culture Collection (ATCC) bacterial strains Escherichia coli (EC), Staphylococcus aureus (SA), Staphylococcus epidermidis (SE), and Pseudomonas aeruginosa (PA) was determined. Inhibition was observed for HA-Ag, HA-Cu, and HA-AgPd. Toxicological tests were performed in rats that were injected intraperitoneally with two concentrations of gold, copper, silver, and silver-palladium nanoparticles. No alterations in hepatic parameters, including ALT (alanine aminotransferase), GGT (gamma-glutamyl transpeptidase) bilirubin, and albumin, were observed after 14 days. These films could be used as promoters of skin recovery and Grades I and II cutaneous burns and as scaffolds.

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On Flows of Bingham-Type Fluids with Threshold Slippage

We investigate a mathematical model describing 3D steady-state flows of Bingham-type fluids in a bounded domain under threshold-slip boundary conditions, which state that flows can slip over solid surfaces when the shear stresses reach a certain critical value. Using a variational inequalities approach, we suggest the weak formulation to this problem. We establish sufficient conditions for the existence of weak solutions and provide their energy estimates. Moreover, it is shown that the set of weak solutions is sequentially weakly closed in a suitable functional space.

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Epidemiology of Respiratory Pathogens among Elderly Nursing Home Residents with Acute Respiratory Infections in Corsica, France, 2013–2017

Background. The current study aims to describe the demographical and clinical characteristics of elderly nursing home (NH) residents with acute respiratory infections (ARIs) during four winter seasons (2013/2014–2016/2017), as well as the microbiological etiology of these infections. Methods. Seventeen NHs with at least one ARI resident in Corsica, France, were included. An ARI resident was defined as a resident developing a sudden onset of any constitutional symptoms in addition to any respiratory signs. Nasopharyngeal swabs from ARI residents were screened for the presence of 21 respiratory agents, including seasonal influenza viruses. Results. Of the 107 ARI residents enrolled from NHs, 61 (57%) were positive for at least one of the 21 respiratory pathogens. Forty-one (38.3%) of the 107 ARI residents had influenza: 38 (92%) were positive for influenza A (100% A(H3N2)) and three (8%) for influenza B/Victoria. Axillary fever (≥38°C) was significantly more common among patients infected with influenza A(H3N2). Conclusion. The circulation of seasonal respiratory viruses other than influenza A(H3N2) seems to be sporadic among elderly NH residents. Investigating the circulation of respiratory viruses in nonwinter seasons seems to be important in order to understand better the dynamic of their year-round circulation in NHs.

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Hydrological Cycle Algorithm for Continuous Optimization Problems

A new nature-inspired optimization algorithm called the Hydrological Cycle Algorithm (HCA) is proposed based on the continuous movement of water in nature. In the HCA, a collection of water drops passes through various hydrological water cycle stages, such as flow, evaporation, condensation, and precipitation. Each stage plays an important role in generating solutions and avoiding premature convergence. The HCA shares information by direct and indirect communication among the water drops, which improves solution quality. Similarities and differences between HCA and other water-based algorithms are identified, and the implications of these differences on overall performance are discussed. A new topological representation for problems with a continuous domain is proposed. In proof-of-concept experiments, the HCA is applied on a variety of benchmarked continuous numerical functions. The results were found to be competitive in comparison to a number of other algorithms and validate the effectiveness of HCA. Also demonstrated is the ability of HCA to escape from local optima solutions and converge to global solutions. Thus, HCA provides an alternative approach to tackling various types of multimodal continuous optimization problems as well as an overall framework for water-based particle algorithms in general.

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Effect of Water Saturation on the Diffusion/Adsorption of 22Na and Cesium onto the Callovo-Oxfordian Claystones

The diffusion and adsorption behaviors of sodium and cesium were investigated in the Callovo-Oxfordian claystones (France) under unsaturated conditions. Through-, out-, and in-diffusion laboratory experiments were performed on intact and compacted samples. These samples were partially saturated using an osmotic method for imposed suction up to 9 MPa. This specific technique enabled us to obtain water saturation degree ranging from 81% to 100% for intact samples and from 70% to 100% for compacted materials. The results showed a very low impact of water saturation on the extent of adsorption for 22Na and cesium, onto intact and compacted materials. Such observations suggest that the saturation degrees were not low enough to limit the access of cations to adsorption sites on clay surfaces. At full saturation, enhanced diffusion for 22Na and cesium was clearly evidenced onto intact and compacted samples. Under unsaturated conditions, the diffusion behavior for Cs and 22Na was not only slower but also distinct as compared to fully saturated samples. For the intact rock and under suction of 1.9 MPa, the Cs diffusivity was reduced by a factor of 17, whereas for sodium, it was reduced by a factor of 5. Explanation was then proposed to explain such a difference.

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Sequential Use of Second-Generation Tyrosine Kinase Inhibitor Treatment and Intensive Chemotherapy Induced Long-Term Complete Molecular Response in Imatinib-Resistant CML Patient Presenting as a Myeloid Blast Crisis

Myeloid blast crisis of chronic myeloid leukemia (CML-MBC) is rarely seen at presentation and has a poor prognosis. There is no standard therapy for CML-MBC. It is often difficult to distinguish CML-MBC from acute myeloid leukemia expressing the Philadelphia chromosome (Ph+ AML). We present a case in which CML-MBC was seen at the initial presentation in a 75-year-old male. He was treated with conventional AML-directed chemotherapy followed by imatinib mesylate monotherapy, which failed to induce response. However, he achieved long-term complete molecular response after combination therapy involving dasatinib, a second-generation tyrosine kinase inhibitor, and conventional chemotherapy.

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Fertility-sparing surgery in advanced stage malignant ovarian germ cell tumor: a case report

Malignant ovarian germ cell tumor is a rare type of disease, which generally has a good prognosis due to the high chemosensitivity of this type of tumor.

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miRNAs in Prediction of Prognosis in Clear Cell Renal Cell Carcinoma

Renal cell carcinoma (RCC) is the most common type of urinary malignancy. Clear cell renal cell carcinoma (ccRCC) is the predominant RCC subtype, accounting for 70–80% of RCC. In recent years, miRNAs have been found to be closely associated with the outcome of the patients with ccRCC. In this review, we summarize recent advances in research exploring the role of miRNAs in predicting prognosis in patients with ccRCC.

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Minimally Invasive Repetitive UVA Irradiation along with Riboflavin Treatment Increased the Strength of Sclera Collagen Cross-Linking

Objective. This study aimed to investigate the efficacy of minimally invasive repetitive UVA irradiation along with riboflavin treatment on sclera collagen cross-linking in rabbits. Method. Forty-eight healthy adult New Zealand white rabbits were randomly divided into four groups: pseudosurgery group (group I), single-irradiation group (group II), duplicate-irradiation group (group III), and triplicate-irradiation group (group IV), with 12 rabbits in each group. For the single-irradiation group, a specially made LED light source was inserted through a minimally invasive conjunctival incision to gain close contact with the sclera for irradiation, and for the repetitive irradiation groups, the above experimental procedure was repeated once or twice every other week. Biomechanical parameters of the sclera including ultimate stress (σ) and 8% Young’s modulus (E) were compared among the groups. Results. In comparison with control group I, the ultimate stress of group II, group III, and group IV increased by 80.1%, 107.9%, and 182.1%, respectively, and their 8% Young’s modulus increased by 106.1%, 159.5%, and 208.5%, respectively, one day after surgery (). Conclusion. Repetitive minimally invasive UVA irradiation with riboflavin significantly increased biomechanical strength of the sclera in the irradiated area, and biomechanical strength increased with repeated times of irradiation.

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Extraosseous Multiple Myeloma: Case Report of Presentation in the Lower Extremity Soft Tissues with Literature Review

A rare presentation of extramedullary multiple myeloma in the soft tissues of the bilateral thighs prompted a literature review of published cases of extramedullary multiple myeloma (EM-MM) and solitary plasmacytomas to determine the relative anatomic distribution of these lesions. All available published cases in English were included in the analysis, dating back to 1966 and including 2,538 extramedullary myeloma or solitary plasmacytoma lesions. Analysis of the anatomic location of EM-MM lesions demonstrates the majority being in the upper airway (33.8%), soft tissues including retroperitoneum and abdomen (14.1%), gastrointestinal tract (10.3%), central nervous system, head and neck (16.0%), and GU (2.4%). We were able to find only 44 documented cases of extremity soft tissue lesions, comprising 1.7% of all lesions.

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A Fatty Acids Mixture Reduces Anxiety-Like Behaviors in Infant Rats Mediated by GABAA Receptors

Fatty acids (C6–C18) found in human amniotic fluid, colostrum, and maternal milk reduce behavioral indicators of experimental anxiety in adult Wistar rats. Unknown, however, is whether the anxiolytic-like effects of fatty acids provide a natural mechanism against anxiety in young offspring. The present study assessed the anxiolytic-like effect of a mixture of lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, elaidic acid, and linoleic acid in Wistar rats on postnatal day 28. Infant rats were subjected to the elevated plus maze, defensive burying test, and locomotor activity test. Diazepam was used as a reference anxiolytic drug. A group that was pretreated with picrotoxin was used to explore the participation of -aminobutyric acid-A (GABAA) receptors in the anxiolytic-like effects. Similar to diazepam, the fatty acid mixture significantly increased the frequency of entries into and time spent on the open arms of the elevated plus maze and decreased burying behavior in the defensive burying test, without producing significant changes in spontaneous locomotor activity. These anxiolytic-like effects were blocked by picrotoxin. Results suggest that these fatty acids that are contained in maternal fluid may reduce anxiety-like behavior by modulating GABAergic neurotransmission in infant 28-day-old rats.

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Seizure and Pulmonary Embolism: A Differential That Can Save a Life

Seizures is a relatively common presentation with a wide differential diagnosis. However, seizures presenting secondary to underlying pulmonary emboli are rare and, without prompt recognition and management, this easily treatable condition can be potentially fatal. The few available case reports discussing seizures and PE reveal a high mortality rate which underscores the importance of prompt diagnosis. A 38-year-old woman presented to the emergency room having experienced loss of consciousness and a generalized tonic-clonic seizure at home. In the emergency room, her presenting signs and symptoms included tachycardia, worsening dyspnea, mild hypoxemia, and elevated D-dimer. Pertinent history findings revealed she recently received depot hormonal contraceptive treatments. Her initial workup included an EKG which showed sinus tachycardia without evidence of right heart strain. Subsequently a chest CT with angiography revealed massive bilateral pulmonary emboli. DVT studies also revealed a unilateral acute DVT. The patient was promptly started on therapeutic anticoagulation and stabilized. Fortunately, the patient remained symptom-free and eventually was discharged with close follow-up. The goal of this report is to make clinicians more aware of the possibility that seizures, along with the appropriate clinical findings, can be caused by acute PE.

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Cellular Therapeutics for Heart Failure: Focus on Mesenchymal Stem Cells

Resulting from a various etiologies, the most notable remains ischemia; heart failure (HF) manifests as the common end pathway of many cardiovascular processes and remains among the top causes for hospitalization and a major cause of morbidity and mortality worldwide. Current pharmacologic treatment for HF utilizes pharmacologic agents to control symptoms and slow further deterioration; however, on a cellular level, in a patient with progressive disease, fibrosis and cardiac remodeling can continue leading to end-stage heart failure. Cellular therapeutics have risen as the new hope for an improvement in the treatment of HF. Mesenchymal stem cells (MSCs) have gained popularity given their propensity of promoting endogenous cellular repair of a myriad of disease processes via paracrine signaling through expression of various cytokines, chemokines, and adhesion molecules resulting in activation of signal transduction pathways. While the exact mechanism remains to be completely elucidated, this remains the primary mechanism identified to date. Recently, MSCs have been incorporated as the central focus in clinical trials investigating the role how MSCs can play in the treatment of HF. In this review, we focus on the characteristics of MSCs that give them a distinct edge as cellular therapeutics and present results of clinical trials investigating MSCs in the setting of ischemic HF.

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Investigation on Risk Factors of Ventilator-Associated Pneumonia in Acute Cerebral Hemorrhage Patients in Intensive Care Unit

Ventilator-associated pneumonia (VAP) is a predominant factor of pulmonary infection. We analyzed the risk factors of VAP with acute cerebral hemorrhage in intensive care unit (ICU) by univariate and multivariate logistic regression analyses. After comparison of 197 cases of the VAP and non-VAP patients, we found that age > 65 years (), smoke (), coronary heart disease (), diabetes (), chronic obstructive pulmonary disease (COPD) (), ICU and hospital stay (), and days on mechanical ventilation () were significantly different, indicating that they are risk factors of VAP. All the age > 65 years (OR = 3.350, 95% CI = 1.936–5.796, ), smoke (OR = 3.206, 95% CI = 1.909–5.385, ), coronary heart disease (OR = 3.179, 95% CI = 1.015–4.130, ), diabetes (OR = 5.042, 95% CI = 3.518–7.342, ), COPD (OR = 1.942, 95% CI = 1.258–2.843, ), ICU and hospital stay (OR = 2.34, 95% CI = 1.145–3.892, ), and days on mechanical ventilation (OR = 1.992, 95% CI = 1.107–3.287, ) are independent risk factors of VAP. After observation of patients with 6 months of follow-up, the BI score was significantly lower in VAP than that in non-VAP, and the rebleeding rate and mortality rate were significantly higher in VAP than those in non-VAP. Thus, the prognosis of the patients with acute cerebral hemorrhage and VAP in ICU is poor.

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C2 Solitary Bone Plasmacytoma Curettage and Vertebral Augmentation in an 83-Year-Old Female: Case Report and Review of Surgical Treatment Approaches in the Spine

Surgically, solitary bone plasmacytoma (SBP) of the craniocervical junction (CCJ) is typically treated with cement augmentation and occipital-cervical stabilization (OCS). In the orthopedic spine literature, various surgical treatment options have been described for SBP, but only a few studies exist describing SBP of the CCJ with treatment involving cement augmentation alone. We report the case of an 83-year-old female found to have C2 SBP that was successfully treated with curettage and cement augmentation alone.

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Emergence of Lassa Fever Disease in Northern Togo: Report of Two Cases in Oti District in 2016

Background. Lassa fever belongs to the group of potentially fatal hemorrhagic fevers, never reported in Togo. The aim of this paper is to report the first two cases of Lassa fever infection in Togo. Case Presentation. The two first Lassa fever cases occurred in two expatriate’s health professionals working in Togo for more than two years. The symptoms appeared among two health professionals of a clinic located in Oti district in the north of the country. The absence of clinical improvement after antimalarial treatment and the worsening of clinical symptoms led to the medical evacuation. The delayed diagnosis of the first case led to a fatal outcome. The second case recovered under ribavirin treatment. Conclusion. The emergence of this hemorrhagic fever confirms the existence of Lassa fever virus in Togo. After a period of intensive Ebola virus transmission from 2013 to 2015, this is an additional call for the establishment and enhancement of infection prevention and control measures in the health care setting in West Africa.

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Novel Evaporation Process for Deposition of Kesterite Thin Films Synthesized by Solvothermal Method

Kesterite, a quaternary compound of Cu2ZnSnS4, is a promising option as a material absorber to reduce the cost of photovoltaic solar cells. The solvothermal method is a way to synthesize nanoparticles of this material. In this work, once synthesized, particles were deposited on a substrate through evaporation, and their morphological, structural, and optical properties were studied. Results show that changes of precursor ratios during solvothermal synthesis result in a modification of particle morphology but not on its size. The deposition of already synthesized kesterite through evaporation preserves kesterite structure and permits the formation of a homogenous film on a substrate. Optical reflectance and transmittance measurements allowed estimating the band-gap energy between 1.41 and 1.46 eV for representative samples, which is near the optimum for the absorber material.

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Chiari 1 Malformation in a Child with Febrile Seizures, Parasomnias, and Sleep Apnea Syndrome

Introduction. The type I is the most common Chiari malformation in children. In this condition, the lower part of the cerebellum, but not the brain stem, extends into the foramen magnum at the base of the skull leading to disturbances in cerebrospinal fluid circulation and to direct compression of nervous tissue. Case report. We describe a 4-year-old Caucasian female child with febrile seizures, headache, parasomnias, and a delay of speech. The child underwent a magnetic resonance imaging to investigate these neurological signs, disclosing a Chiari malformation type 1. The polysomnography showed a mild-moderate sleep-disordered breathing, increased number of central sleep apneas, and generalized spike waves at sleep onset. Conclusions. Seizures have been seldom described in CM1 patients. The main reasons for performing MRI in this case were frequent seizures, a delay of speech, and headache, leading to an unexpected diagnosis of CM1. Polysomnography detected a discrete SDB.

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In Vitro Activity of Iclaprim against Methicillin-Resistant Staphylococcus aureus Nonsusceptible to Daptomycin, Linezolid, or Vancomycin: A Pilot Study

Iclaprim is a bacterial dihydrofolate reductase inhibitor in Phase 3 clinical development for the treatment of acute bacterial skin and skin structure infections and hospital-acquired bacterial pneumonia caused by Gram-positive bacteria. Daptomycin, linezolid, and vancomycin are commonly used antibiotics for these indications. With increased selective pressure to these antibiotics, outbreaks of bacterial resistance to these antibiotics have been reported. This in vitro pilot study evaluated the activity of iclaprim against methicillin-resistant Staphylococcus aureus (MRSA) isolates, which were also not susceptible to daptomycin, linezolid, or vancomycin. Iclaprim had an MIC ≤ 1 µg/ml to the majority of MRSA isolates that were nonsusceptible to daptomycin (5 of 7 (71.4%)), linezolid (26 of 26 (100%)), or vancomycin (19 of 28 (66.7%)). In the analysis of time-kill curves, iclaprim demonstrated ≥ 3 log10 reduction in CFU/mL at 4–8 hours for tested strains and isolates nonsusceptible to daptomycin, linezolid, or vancomycin. Together, these data support the use of iclaprim in serious infections caused by MRSA nonsusceptible to daptomycin, linezolid, or vancomycin.

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Shorter Path Design and Control for an Underactuated Satellite

In the event of a control failure on an axis of a spacecraft, a target attitude can be achieved by several sequential rotations around the remaining control axes. For a spacecraft actuating with wheels, the form of each submaneuver should be a pure single axis rotation since the failed axis should not be perturbed. The rotation path length in sequential submaneuvers, however, increases extremely but is short under normal conditions. In this work, it is shown that the path length is reduced dramatically by finding a proper number of sequential submaneuvers, especially for the target attitude rotation around the failed axis. A numerical optimization is suggested to obtain the shortest path length and the relevant number of maneuvers. Optimal solutions using the sequential rotation approach are confirmed by numerical simulations.

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Pigmented Cells in the Pineal Gland of Female Viscacha (Lagostomus maximus maximus): A Histochemical and Ultrastructural Study

The presence of pigment has been demonstrated in different nervous structures such as those of retina, substantia nigra, and locus coeruleus. These pigments have also been described in the pineal gland of different mammal species. Histochemical and ultrastructural studies of the pineal gland of female viscacha (Lagostomus maximus maximus) were performed to analyze the presence of pigmented cells under natural conditions and to evaluate a probable relation between pigment content and glandular activity during pregnancy. The following techniques were applied: hematoxylin-eosin, phosphotungstic acid-hematoxylin, Masson-Fontana silver, DOPA histochemistry, Schmorl’s reaction and toluidine blue. Estradiol and progesterone serum levels were determined by RIA. The ultrastructural features of the pineal pigment granules were also analyzed. Pigment granules were observed in a random distribution, but the pigmented cells were frequently found near blood vessels. The pineal pigment was histochemically identified as melanin. Differences in the amount of pigmented cells were found between pregnant and nonpregnant viscachas. The ultrastructural analysis revealed the presence of premelanosomes and melanosomes. Estradiol and progesterone levels vary during pregnancy. In conclusion, the changes in the amount of pigment content and hormone levels may indicate that the pineal gland of female viscacha is susceptible to endocrine variations during pregnancy.

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Modulation of Oxidative Stress: Pharmaceutical and Pharmacological Aspects 2017

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Multicomponent Lifestyle Interventions for Treating Overweight and Obesity in Children and Adolescents: A Systematic Review and Meta-Analyses

Background. Treatment of childhood obesity is important in preventing development of obesity-related diseases later in life. This systematic review evaluates the effect of multicomponent lifestyle interventions for children and adolescents from 2 to 18 years. Methods and Results. We performed systematic searches in nine databases. Thirty-nine studies met the criteria for meta-analyses. We found a significant difference in body mass index (BMI) after 6 months (MD −0.99 (95% CI −1.36 to −0.61)), 12 months (MD −0.67 (95% CI −1.01 to −0.32)), and 24 months (MD −0.96 (95% CI −1.63 to −0.29)) in favour of multicomponent lifestyle interventions compared to standard, minimal, and no treatment. We also found a significant difference in BMI Z scores after 6 months (MD −0.12 (95% CI −0.17 to −0.06)), 12 months (MD −0.16 (95% CI −0.21 to −0.11)), and 24 months (MD −0.16 (95% CI −0.21 to −0.10)) in favour of multicomponent lifestyle interventions. Subgroup analyses suggested an increased effect in specialist health care with a group treatment component included in the intervention. Conclusion. Multicomponent lifestyle interventions have a moderate effect on change in BMI and BMI Z score after 6, 12, and 24 months compared with standard, minimal, and no treatment.

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Tuberculous Spondylitis: A Report of Different Clinical Scenarios and Literature Update

Tuberculosis is still one of the most important health problems in the world. In developed countries, the proportion of extrapulmonary tuberculosis cases is increasing. Nowadays tuberculous spondylitis, also known as Pott disease, is a rare clinical condition but can cause severe vertebral and neurological sequelae that can be prevented with an early correct diagnosis. The aim of this paper is to increase awareness of tuberculous spondylitis in modern times, describing three different cases and discussing its best diagnostic and therapeutic approach based on the current literature.

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Treatment of Extensively Comminuted Mandibular Fracture with the Aid of a Condylar Positioning Device

We describe a case of extensively comminuted mandibular fracture that extends bilaterally to the angle of mandible successfully treated with the use of condylar positioning device (CPD). This simple, yet effective, technique that almost exclusively described in orthognathic surgery is useful when advance surgical techniques such as pre- or intraoperative landmark identification may not be readily available. CPD technique optimizes the manual manipulations of the comminuted distal segments during fracture reduction and internal fixation. At the same time, it allows greater control of the proximal segments to avoid further surgical complication.

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Influence of Chemical Admixtures on Fresh and Hardened Properties of Prolonged Mixed Concrete

Effects of different chemical admixtures on fresh and hardened properties of prolonged mixed concrete and their cost-effectiveness were investigated. Influence of sand to aggregate volume ratio, cement content, and use of chilled mixing water on the properties of prolonged mixed concrete was studied as well. Different concrete mixtures were prepared using five different types of chemical admixture (one water reducer based on lignosulfonate and four superplasticizers based on sulfonated naphthalene polymer, polycarboxylic ether, second-generation polycarboxylic ether polymer, and organic polymer), varying s/a ratio (0.40 and 0.45) and cement content (340 kg/m3 and 380 kg/m3) and using chilled mixing water. Slump tests were performed at 15-minute intervals to assess the fresh performance of each prolonged mixed concrete mixture. 100 mm by 200 mm cylindrical concrete specimens were prepared and tested for compressive strength, Young’s modulus, splitting tensile strength, and ultrasonic pulse velocity. Results indicate that concretes with sulfonated naphthalene polymer-based superplasticizer and second-generation polycarboxylic ether-based superplasticizer show best performances in both fresh and hardened states. Concrete with lignosulfonate-based water reducer exhibits poor performance in comparison with the concretes with superplasticizers. The cost per unit compressive strength of concrete with sulfonated naphthalene polymer-based superplasticizer is lower compared with the concretes with other types of chemical admixture.

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Metabolomics in COPD Acute Respiratory Failure Requiring Noninvasive Positive Pressure Ventilation

We aimed to investigate whether metabolomic analysis can discriminate acute respiratory failure due to COPD exacerbation from respiratory failure due to heart failure and pneumonia. Since COPD exacerbation is often overdiagnosed, we focused on those COPD exacerbations that were severe enough to require noninvasive mechanical ventilation. We enrolled stable COPD subjects and patients with acute respiratory failure requiring noninvasive mechanical ventilation due to COPD, heart failure, and pneumonia. We excluded subjects with history of both COPD and heart failure and patients with obstructive sleep apnea and obstructive lung disease other than COPD. We performed metabolomics analysis using NMR. We constructed partial least squares discriminant analysis (PLS-DA) models to distinguish metabolic profiles. Serum (,R2 = 0.397, Q2 = 0.058) and urine metabolic profiles (,R2 = 0.419, Q2 = 0.142) were significantly different between the four diagnosis groups by PLS-DA. After excluding stable COPD patients, the metabolomes of the various respiratory failure groups did not cluster separately in serum (,R2 = 0.631, Q2 = 0.246) or urine (,R2 = 0.602, Q2 = −0.134). However, several metabolites in the serum were reduced in patients with COPD exacerbation and pneumonia. We did not find a metabolic profile unique to COPD exacerbation, but we were able to clearly and reliably distinguish stable COPD patients from patients with respiratory failure in both serum and urine.

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Regulation of ASK1 signaling by scaffold and adaptor proteins

Publication date: December 2017
Source:Advances in Biological Regulation, Volume 66
Author(s): Lauren Rusnak, Haian Fu
The mitogen-activated protein kinase (MAPK) signaling pathway is a three-tiered kinase cascade where mitogen-activated protein kinase kinase kinases (MAP3Ks) lead to the activation of mitogen-activated protein kinase kinases (MAP2K), and ultimately MAPK proteins. MAPK signaling can promote a diverse set of biological outcomes, ranging from cell death to proliferation. There are multiple mechanisms which govern MAPK output, such as the duration and strength of the signal, cellular localization to upstream and downstream binding partners, pathway crosstalk and the binding to scaffold and adaptor molecules. This review will focus on scaffold and adaptor proteins that bind to and regulate apoptosis signal-regulating kinase 1 (ASK1), a MAP3K protein with a critical role in mediating stress response pathways.



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Structural aspects of protein kinase ASK1 regulation

Publication date: December 2017
Source:Advances in Biological Regulation, Volume 66
Author(s): Tomas Obsil, Veronika Obsilova
Apoptosis signal-regulating kinase 1 (ASK1, also known as MAP3K5), a member of the mitogen-activated protein kinase kinase kinase (MAP3K) family, activates the p38 mitogen-activated protein kinase and the c-Jun N-terminal kinase (JNK) signaling cascades in response to various stressors. ASK1 activity is tightly regulated through phosphorylation and interaction with various binding partners. However, the mechanistic details underlying the ASK1 regulation are still not fully understood. This review focuses on recent advances in structural studies of protein kinase ASK1 and on the insights they provide into its mechanism of regulation. In addition, we also discuss protein–protein interactions between ASK1 and its binding partners thioredoxin (TRX) and 14-3-3 protein.



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ASK family in infection and inflammatory disease

Publication date: December 2017
Source:Advances in Biological Regulation, Volume 66
Author(s): Tomohiko Okazaki
Living organisms are continuously exposed to pathogens such as viruses and bacteria. Soon after a limited number of germline-encoded receptors, called pathogen recognition receptors, sense pathogen-associated molecular patterns, hosts trigger innate immune responses, including production of type Ⅰ interferons, proinflammatory cytokines, and cellular apoptosis, to limit propagation of invading pathogens. Importantly, these host responses are also activated during inflammatory diseases, irrespective of pathogen infection, and often play a causal role in pathogenesis and progression of these diseases, thereby implying an intimate link between immune responses and inflammatory disease. The apoptosis signal-regulating kinase (ASK) family belongs to the larger MAP3K family that controls various stress responses. Here, I summarize the critical roles of members of the ASK family during infection and inflammatory disease, and discuss the relationship between these two noxious conditions.



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Physiological roles of ASK family members in innate immunity and their involvement in pathogenesis of immune diseases

Publication date: December 2017
Source:Advances in Biological Regulation, Volume 66
Author(s): Atsushi Matsuzawa
Cells are always exposed to various types of stress, including physical, chemical, and biological stresses, and are required to sense immediately and respond appropriately to these stresses. The apoptosis signal-regulating kinase (ASK) family members are stress-responsive kinases, which are activated by not only physicochemical stresses, such as oxidative stress, osmotic pressure, calcium overload, and anti-cancer drugs, but also biological stresses, such as inflammatory cytokines and pathogen infection. Recently, we found that ASK1, a member of ASK family, is activated by bacterial components, such as lipopolysaccharide, in a reactive oxygen species (ROS)-dependent manner, demonstrating that ASK1 is required for the innate immune response and plays a critical role in the regulation of innate immune signaling. Moreover, our findings indicate that ROS are common mediators in physicochemical stress signaling, including redox signaling, and biological stress signaling, including innate immune signaling. This review especially focuses on the roles of ASK family in innate immunity and provides recent progress in our knowledge on activation mechanisms and physiological functions of ASK family kinases in innate immune responses.



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Foreword

Publication date: December 2017
Source:Advances in Biological Regulation, Volume 66
Author(s): Hidenori Ichijo




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ASK family in cardiovascular biology and medicine

Publication date: December 2017
Source:Advances in Biological Regulation, Volume 66
Author(s): Tingting Liu, Huanjiao Jenny Zhou, Wang Min
Cardiovascular disease is a major cause of death worldwide. Mitogen-activated protein kinase (MAPK) signal cascades signaling pathways play crucial roles in cardiovascular pathophysiology. Apoptosis signal-regulating kinase (ASK) family members ASK1, ASK2 and ASK3 are the key molecules in MAPK signal cascades and are activated by various stresses. ASK1 is the most extensively studied MAPKKK and is involved in regulation of the cellular functions such as cell survival, proliferation, inflammation and apoptosis. The current review focuses on the relationship between ASK1 and cardiovascular disease, while exploring the novel therapeutic strategies for cardiovascular disease involved in the ASK1 signal pathway.



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Therapeutic application of apoptosis signal-regulating kinase 1 inhibitors

Publication date: December 2017
Source:Advances in Biological Regulation, Volume 66
Author(s): Takao Fujisawa
Apoptosis signal-regulating kinase 1 (ASK1) is a member of the stress-activated mitogen-activated protein kinase kinase kinase (MAP3K) family. ASK1 is an attractive drug target, owing to its essential role in a wide variety of human diseases including neurodegenerative disorders, inflammatory diseases and cancer. Recent studies have suggested that pharmacological manipulations using small molecule ASK1 inhibitors may be beneficial in experimental human disease models. In this review, we highlight the current understanding of ASK1 inhibitors as a potential therapy for human diseases.



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Forms and functions of store-operated calcium entry mediators, STIM and Orai

Publication date: Available online 22 November 2017
Source:Advances in Biological Regulation
Author(s): James W. Putney
Calcium signals arise by multiple mechanisms, including mechanisms of release of intracellular stored Ca²⁺, and the influx of Ca²⁺ through channels in the plasma membrane. One mechanism that links these two sources of Ca²⁺ is store-operated Ca²⁺ entry, the most commonly encountered version of which involves the extensively studied calcium-release-activated Ca²⁺ (CRAC) channel. The minimal and essential molecular components of the CRAC channel are the STIM proteins that function as Ca²⁺ sensors in the endoplasmic reticulum, and the Orai proteins that comprise the pore forming subunits of the CRAC channel. CRAC channels are known to play significant roles in a wide variety of physiological functions. This review discusses the multiple forms of STIM and Orai proteins encountered in mammalian cells, and discusses some specific examples of how these proteins modulate or mediate important physiological processes.



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Molecular and cellular mechanisms of chemoresistance in pancreatic cancer

Publication date: Available online 22 November 2017
Source:Advances in Biological Regulation
Author(s): Aleksandra Adamska, Omar Elaskalani, Aikaterini Emmanouilidi, Minkyoung Kim, Norbaini Binti Abdol Razak, Pat Metharom, Marco Falasca
Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most chemoresistant cancers, and current therapies targeting cancer-associated molecular pathways have not given satisfactory results, owing in part to rapid upregulation of alternative compensatory pathways. Most of the available treatments are palliative, focussing on improving the quality of life. At present, available options are surgery, embolization, radiation, chemotherapy, immunotherapy and use of other more targeted drugs. In this review, we describe the cellular and molecular effects of current chemotherapy drugs such as gemcitabine, FOLFIRINOX (5-fluorouracil [5-FU], oxaliplatin, irinotecan, and leucovorin) and ABRAXANE (nab-Paclitaxel), which have shown a survival benefit, although modest, for pancreatic cancer patients. Nevertheless, gemcitabine remains the standard first-line option for advanced-stage pancreatic cancer patients and, as resistance to the drug has attracted an increasing scientific interest, we deliberate on the main intracellular processes and proteins vital in acquired chemoresistance to gemcitabine. Lastly, our review examines various microenvironmental factors capable of instigating PDAC to develop resistance to chemotherapeutic drugs.



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Normalization of mass spectrometry data (NOMAD)

Publication date: Available online 20 November 2017
Source:Advances in Biological Regulation
Author(s): Carl Murie, Brian Sandri, Ann-Sofi Sandberg, Timothy J. Griffin, Janne Lehtiö, Christine Wendt, Ola Larsson
iTRAQ and TMT reagent-based mass spectrometry (MS) are commonly used technologies for quantitative proteomics in biological samples. Such studies are often performed over multiple MS runs, potentially resulting in introduction of MS run bias that could affect downstream analysis. Such MS data have therefore commonly been normalized using a reference sample which is included in each MS run. We show, however, that reference normalization does not effectively remove systematic MS run bias. A linear model approach was previously proposed to improve on the reference normalization approach but does not computationally scale to larger data sets. Here we describe the NOMAD (normalization of mass spectrometry data) R package which implements a computationally efficient ANOVA normalization approach with protein assembly functionality. NOMAD provides the same advantages as the linear regression solution but is more computationally efficient which allows superior scaling to larger sample sizes. Moreover, NOMAD effectively removes bias which improves valid across MS run comparisons.



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Proliferative and metastatic roles for Phospholipase D in mouse models of cancer

Publication date: Available online 14 November 2017
Source:Advances in Biological Regulation
Author(s): Eric Roth, Michael A. Frohman
Phospholipase D (PLD) activity has been proposed to facilitate multiple steps in cancer progression including growth, metabolism, angiogenesis, and mobility. The canonical enzymes PLD1 and PLD2 enact their diverse effects through hydrolyzing the membrane lipid phosphatidylcholine to generate the second messenger and signaling lipid phosphatidic acid (PA). However, the widespread expression of PLD1 and PLD2 in normal tissues and the additional distinct enzymatic mechanisms through which PA can be generated have produced uncertainty regarding the optimal settings in which PLD inhibition might ameliorate cancer. Recent studies in mouse model systems have demonstrated that inhibition or elimination of PLD activity reduces tumor growth and metastasis. One mechanism proposed for this outcome involves proliferative signaling mediated by receptor tyrosine kinases (RTK) and G protein-coupled receptors (GPCR), which is attenuated when downstream PLD signal propagation is suppressed. The reduced proliferative signaling has been reported to be compounded by dysfunctional energetic metabolism in the tumor cells under conditions of nutrient deprivation. Moreover, cancer cells lacking PLD activity display inefficiencies across multiple steps of the metastatic cascade, limiting the tumor's lethal spread. Using PLD isoform knockout mice, recent studies have reported on the net effects of inhibition and ablation in multiple cancer models through examining the role of PLD in the non-tumor cells comprising the stroma and microenvironment. The promising results of such in vivo studies, combined with the apparent low toxicity of highly-specific and potent inhibitors, highlights PLD as an attractive target for therapeutic inhibition in cancer. We discuss here the array of anti-tumor effects produced by PLD inhibition and ablation in cancer models with a focus on animal studies.



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PLCγ1: Potential arbitrator of cancer progression

Publication date: Available online 8 November 2017
Source:Advances in Biological Regulation
Author(s): Hyun-Jun Jang, Pann-Ghill Suh, Yu Jin Lee, Kyeong Jin Shin, Lucio Cocco, Young Chan Chae
Phospholipase C (PLC) is an essential mediator of cellular signaling. PLC regulates multiple cellular processes by generating bioactive molecules such as inositol-1,4,5-triphosphate (IP3) and diacylglycerol (DAG). These products propagate and regulate cellular signaling via calcium (Ca²⁺) mobilization and activation of protein kinase C (PKC), other kinases, and ion channels. PLCγ1, one of the primary subtypes of PLC, is directly activated by membrane receptors, including receptor tyrosine kinases (RTKs), and adhesion receptors such as integrin. PLCγ1 mediates signaling through direct interactions with other signaling molecules via SH domains, as well as its lipase activity. PLCγ1 is frequently enriched and mutated in various cancers, and is involved in the processes of tumorigenesis, including proliferation, migration, and invasion. Although many studies have suggested that PLCγ functions in cell mobility rather than proliferation in cancer, questions remain as to whether PLCγ regulates mitogenesis and whether PLCγ promotes or inhibits proliferation. Moreover, how PLCγ regulates cancer-associated cellular processes and the interplay among other proteins involved in cancer progression have yet to be fully elucidated. In this review, we discuss the current understanding of the role of PLCγ1 in cancer mobility and proliferation.



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Dysregulation of mRNA translation and energy metabolism in cancer

Publication date: Available online 2 November 2017
Source:Advances in Biological Regulation
Author(s): Matthew Leibovitch, Ivan Topisirovic
Dysregulated mRNA translation and aberrant energy metabolism are frequent in cancer. Considering that mRNA translation is an energy demanding process, cancer cells must produce sufficient ATP to meet energy demand of hyperactive translational machinery. In recent years, the mammalian/mechanistic target of rapamycin (mTOR) emerged as a central regulatory node which coordinates energy consumption by the translation apparatus and ATP production in mitochondria. Aberrant mTOR signaling underpins the vast majority of cancers whereby increased mTOR activity is thought to be a major determinant of both malignant translatomes and metabolomes. Nonetheless, the role of mTOR and other related signaling nodes (e.g. AMPK) in orchestrating protein synthesis and cancer energetics is only recently being unraveled. In this review, we discuss recent findings that provide insights into the molecular underpinnings of coordination of translational and metabolic programs of cancer cells, and potential strategies to translate these findings into clinical treatments.



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Phospholipase C zeta and calcium oscillations at fertilisation: The evidence, applications, and further questions

Publication date: Available online 27 October 2017
Source:Advances in Biological Regulation
Author(s): Junaid Kashir, Michail Nomikos, F. Anthony Lai
Oocyte activation is a fundamental event at mammalian fertilisation, initiated by a series of characteristic calcium (Ca²⁺) oscillations in mammals. This characteristic pattern of Ca²⁺ release is induced in a species-specific manner by a sperm-specific enzyme termed phospholipase C zeta (PLCζ). Reduction or absence of functional PLCζ within sperm underlies male factor infertility in humans, due to mutational inactivation or abrogation of PLCζ protein expression. Underlying such clinical implications, a significant body of evidence has now been accumulated that has characterised the unique biochemical and biophysical properties of this enzyme, further aiding the unique clinical opportunities presented. Herein, we present and discuss evidence accrued over the past decade and a half that serves to support the identity of PLCζ as the mammalian sperm factor. Furthermore, we also discuss the potential novel avenues that have yet to be examined regarding PLCζ mechanism of action in both the oocyte, and the sperm. Finally, we discuss the advances that have been made regarding the clinical therapeutic and diagnostic applications of PLCζ in potentially treating male infertility as a result of oocyte activation deficiency (OAD), and also possibly more general cases of male subfertility.



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Nuclear inositide signaling and cell cycle

Publication date: Available online 23 October 2017
Source:Advances in Biological Regulation
Author(s): Stefano Ratti, Giulia Ramazzotti, Irene Faenza, Roberta Fiume, Sara Mongiorgi, Anna Maria Billi, James A. McCubrey, Pann-Ghill Suh, Lucia Manzoli, Lucio Cocco, Matilde Y. Follo
Phosphatidylinositols (PIs) are responsible for several signaling pathways related to many cellular functions, such as cell cycle regulation at different check-points, cell proliferation, cell differentiation, membrane trafficking and gene expression. PI metabolism is not only present at the cytoplasmic level, but also at the nuclear one, where different signaling pathways affect essential nuclear mechanisms in eukaryotic cells. In this review we focus on nuclear inositide signaling in relation to cell cycle regulation. Many evidences underline the pivotal role of nuclear inositide signaling in cell cycle regulation and cell proliferation associated to different strategic physiopathological mechanisms in several cell systems and diseases.



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Review of four major distinct types of human phospholipase A2

Publication date: Available online 23 October 2017
Source:Advances in Biological Regulation
Author(s): Alexis M. Vasquez, Varnavas D. Mouchlis, Edward A. Dennis
The phospholipase A2 superfamily of enzymes plays a significant role in the development and progression of numerous inflammatory diseases. Through their catalytic action on membrane phospholipids, phospholipases are the upstream regulators of the eicosanoid pathway releasing free fatty acids for cyclooxygenases, lipoxygenases, and cytochrome P450 enzymes which produce various well-known inflammatory mediators including leukotrienes, thromboxanes and prostaglandins. Elucidating the association of phospholipases A2 with the membrane, the extraction and binding of phospholipid substrates, and their interactions with small-molecule inhibitors is crucial for the development of new anti-inflammatory therapeutics. Studying phospholipases has been challenging because they act on the surface of cellular membranes and micelles. Multidisciplinary approaches including hydrogen/deuterium exchange mass spectrometry, molecular dynamics simulations, and other computer-aided drug design techniques have been successfully employed by our laboratory to study interactions of phospholipases with membranes, phospholipid substrates and inhibitors. This review summarizes the application of these techniques to study four human recombinant phospholipases A2.



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PIM activity in tumours: A key node of therapy resistance

Publication date: Available online 22 October 2017
Source:Advances in Biological Regulation
Author(s): Richard J. Rebello, Alisée V. Huglo, Luc Furic
The PIM kinases are proto-oncogenes which have been shown to facilitate cell survival and proliferation to drive malignancy and resistance post-therapy. They are able to suppress cell death signals, sustain PI3K/AKT/mTORC1 pathway activity and regulate the MYC oncogenic program. Recent work has revealed PIM kinase essentiality for advanced tumour maintenance and described tumour sensitivity to small molecule inhibitors targeting PIM kinase in multiple malignancies.



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Signaling by cell surface death receptors: Alterations in head and neck cancer

Publication date: Available online 18 October 2017
Source:Advances in Biological Regulation
Author(s): Brandon C. Leonard, Daniel E. Johnson
Cell surface death receptors are members of the tumor necrosis factor receptor (TNFR) superfamily and mediate signals leading to the induction of apoptosis or necroptosis, as well as NF-κB-mediated cell survival. These biochemical processes play key roles in cell growth, development, tissue homeostasis, and immune responses. The downstream signaling complexes activated by different death receptors can differ significantly and are subject to multiple, distinct regulatory mechanisms. Dysregulation of signaling by the TNFR superfamily contributes to a variety of pathologic conditions, including defective immune responses and cancer. Caspase-8 signaling is important for mediating death receptor signals leading to either apoptosis or NF-κB activation. By contrast, inactivation of caspase-8 or loss of caspase-8 expression shifts death receptor signaling to the necroptosis pathway. Notably, the gene encoding caspase-8 is mutated in roughly ten percent of head and neck cancers. These findings support the hypothesis that alterations in the biochemical pathways mediated by death receptors have important consequences for the development of head and neck, and possibly other, cancers.



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Sphingosine kinase 1 in breast cancer

Publication date: Available online 16 October 2017
Source:Advances in Biological Regulation
Author(s): Kurt Geffken, Sarah Spiegel
Breast cancer affects 1 out of 8 women in the US and is the second highest cause of death from cancer for women, leading to considerable research examining the causes, progression, and treatment of breast cancer. Over the last two decades, sphingosine-1-phosphate (S1P), a potent sphingolipid metabolite, has been implicated in many processes important for breast cancer including growth, progression, transformation and metastasis, and is the focus of this review. In particular, one of the kinases that produces S1P, sphingosine kinase 1 (SphK1), has come under increasing scrutiny as it is commonly upregulated in breast cancer cells and has been linked with poorer prognosis and progression, possibly leading to resistance to certain anti-cancer therapies. In this review, we will also discuss preclinical studies of both estrogen receptor (ER) positive as well as triple-negative breast cancer mouse models with inhibitors of SphK1 and other compounds that target the S1P axis and have shown good promise in reducing tumor growth and metastasis. It is hoped that in the future this will lead to development of novel combination approaches for effective treatment of both conventional hormonal therapy-resistant breast cancer and triple-negative breast cancer.



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The Effect of On-Pump and Off-Pump Bypass Operations on Oxidative Damage and Antioxidant Parameters

Objective. The aim of the study is to determine the oxidative status in on-pump and off-pump coronary artery surgery and contribute to possible surgical choices in clinical practices in accordance with the information obtained as a result of this study. Methods. 52 patients undergoing open heart surgery (26 patients in on-pump group and 26 patients in off-pump group) were included in the study. MDA, GPx, GSH, CAT, and SOD were investigated in blood samples. Results. In the on-pump group, it was determined that there were a significant increase in MDA level in the peroperative period compared to the preoperative and postoperative periods and a significant increase in GSH level in the postoperative period than in the preoperative period. Additionally, while there was a significant decrease in CAT activity in the postoperative period than in the peroperative period, there was a statistically significant increase in SOD enzyme activity in the postoperative period compared to the preoperative and peroperative periods. A statistically significant increase was observed in SOD enzyme activity in the postoperative period in on-pump compared to off-pump group. Conclusion. It is thought that this oxidative damage can be suppressed by administering a suitable antioxidant supplement in the preoperative and peroperative periods among patients undergoing the on-pump operation.

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Comparison of Adult Hippocampal Neurogenesis and Susceptibility to Treadmill Exercise in Nine Mouse Strains

The genetic background of mice has various influences on the efficacy of physical exercise, as well as adult neurogenesis in the hippocampus. In this study, we investigated the basal level of hippocampal neurogenesis, as well as the effects of treadmill exercise on adult hippocampal neurogenesis in 9 mouse strains: 8 very commonly used laboratory inbred mouse strains (C57BL/6, BALB/c, A/J, C3H/HeJ, DBA/1, DBA/2, 129/SvJ, and FVB) and 1 outbred mouse strain (ICR). All 9 strains showed diverse basal levels of cell proliferation, neuroblast differentiation, and integration into granule cells in the sedentary group. C57BL/6 mice showed the highest levels of cell proliferation, neuroblast differentiation, and integration into granule cells at basal levels, and the DBA/2 mice showed the lowest levels. The efficacy of integration into granule cells was maximal in ICR mice. Treadmill exercise increased adult hippocampal neurogenesis in all 9 mouse strains. These results suggest that the genetic background of mice affects hippocampal neurogenesis and C57BL/6 mice are the most useful strain to assess basal levels of cell proliferation and neuroblast differentiation, but not maturation into granule cells. In addition, the DBA/2 strain is not suitable for studying hippocampal neurogenesis.

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Development and Validation of a Chromatography Method Using Tandem UV/Charged Aerosol Detector for Simultaneous Determination of Amlodipine Besylate and Olmesartan Medoxomil: Application to Drug-Excipient Compatibility Study

A study was carried out to investigate compatibility of amlodipine besylate and olmesartan medoxomil with a variety of pharmaceutical excipients. Both drugs are antihypertensive agents that can be administered alone, in monotherapy, or in pharmaceutical association. The studies were performed using binary and ternary mixtures, and samples were stored for 3 and 6 months at 40°C under 75% relative humidity and dry conditions. For this study, a method based on high-performance liquid chromatography (HPLC) was developed and validated for the simultaneous determination of amlodipine besylate and olmesartan medoxomil in samples from pharmaceutical preformulation studies using diode array detector (DAD) and charged aerosol detector (CAD). The runtime per sample was 10 min with retention time of 7.926 min and 4.408 min for amlodipine and olmesartan, respectively. The validation was performed according to ICH guidelines. The calibration curve presents linear dynamic range from 12 to 250 μg mL−1 for amlodipine and from 25 to 500 μg mL−1 for olmesartan with coefficient of determination (R2 ≥ 0.9908) while repeatability and reproducibility (expressed as relative standard deviation) were lower than 1.0%. The excipients such as corn starch, croscarmellose sodium, magnesium stearate, polyvinyl alcohol, talc, polyvinylpyrrolidone, lactose monohydrate, and polyethylene glycol showed potential incompatibilities after accelerated stability testing.

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Roles of Endoplasmic Reticulum Stress in NECA-Induced Cardioprotection against Ischemia/Reperfusion Injury

Objective. This study aimed to investigate whether the nonselective A2 adenosine receptor agonist NECA induces cardioprotection against myocardial ischemia/reperfusion (I/R) injury via glycogen synthase kinase 3β (GSK-3β) and the mitochondrial permeability transition pore (mPTP) through inhibition of endoplasmic reticulum stress (ERS). Methods and Results. H9c2 cells were exposed to H2O2 for 20 minutes. NECA significantly prevented H2O2-induced TMRE fluorescence reduction, indicating that NECA inhibited the mPTP opening. NECA blocked H2O2-induced GSK-3β phosphorylation and GRP94 expression. NECA increased GSK-3β phosphorylation and decreased GRP94 expression, which were prevented by both ERS inductor 2-DG and PKG inhibitor KT5823, suggesting that NECA may induce cardioprotection through GSK-3β and cGMP/PKG via ERS. In isolated rat hearts, both NECA and the ERS inhibitor TUDCA decreased myocardial infarction, increased GSK-3β phosphorylation, and reversed GRP94 expression at reperfusion, suggesting that NECA protected the heart by inhibiting GSK-3β and ERS. Transmission electron microscopy showed that NECA and TUDCA reduced mitochondrial swelling and endoplasmic reticulum expansion, further supporting that NECA protected the heart by preventing the mPTP opening and ERS. Conclusion. These data suggest that NECA prevents the mPTP opening through inactivation of GSK-3β via ERS inhibition. The cGMP/PKG signaling pathway is responsible for GSK-3β inactivation by NECA.

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Enhancing Plasticity of the Central Nervous System: Drugs, Stem Cell Therapy, and Neuro-Implants

Stroke represents the first cause of adult acquired disability. Spontaneous recovery, dependent on endogenous neurogenesis, allows for limited recovery in 50% of patients who remain functionally dependent despite physiotherapy. Here, we propose a review of novel drug therapies with strong potential in the clinic. We will also discuss new avenues of stem cell therapy in patients with a cerebral lesion. A promising future for the development of efficient drugs to enhance functional recovery after stroke seems evident. These drugs will have to prove their efficacy also in severely affected patients. The efficacy of stem cell engraftment has been demonstrated but will have to prove its potential in restoring tissue function for the massive brain lesions that are most debilitating. New answers may lay in biomaterials, a steadily growing field. Biomaterials should ideally resemble lesioned brain structures in architecture and must be proven to increase functional reconnections within host tissue before clinical testing.

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Hydroxychloroquine Use in Lupus Patients during Pregnancy Is Associated with Longer Pregnancy Duration in Preterm Births

Objective. To investigate the effect of hydroxychloroquine (HCQ) in pregnant women with systemic lupus erythematosus (SLE). Methods. In SLE pregnancies of a single Dutch center (2000–2015), lupus activity and flares before and during pregnancy and postpartum were assessed using the SLE Disease Activity Index (SLEDAI)/SLEPDAI (SLEDAI adjusted for pregnancy). The association between HCQ use and pregnancy outcomes (early spontaneous abortion, fetal death, and preterm and term live birth) was analyzed using generalized estimating equations (GEE) accounting for the occurrence of multiple pregnancies per patient. Analyses were adjusted for antiphospholipid antibody (aPL) status. Results. 110 pregnancies (63 mostly Caucasian patients) were included, of which, in 30, HCQ was used; overall occurrence of flares was low (non-HCQ group: 5 mild (6.4%) and 2 severe (2.6%); HCQ group: 2 mild (6.7%) and no severe flares). The HCQ group showed a trend towards lower dosage of prednisone (OR 0.2 (95% CI 0.0–1.4); ). Pregnancy outcomes were comparable between groups. Among preterm live births, pregnancy duration was significantly longer in HCQ users (2.4 weeks (95% CI 1.0–3.8; )). Conclusion. HCQ use was associated with longer pregnancy duration in the vulnerable preterm birth population, underscoring the beneficial effect of HCQ use during pregnancy.

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Design of Internal Wire-Based Impedance Matching of Helical Antennas Using an Equivalent Thin-Wire Model

We propose a novel design of internal impedance matching networks for axial-mode helical antennas. This network comprises a single wire attached to the helix. One of the main challenges when designing an internal matching network is its strong electromagnetic coupling with the antenna. The matching network must hence be designed in the presence of the antenna, which slows down the design process. To overcome this problem, we formulate an equivalent thin-wire model of the complete helix, including the matching wire (matching network) and the dielectric support. This computationally low-demanding model can be analyzed extremely rapidly, yielding accurate results, which are in excellent agreement with alternative numerical solutions and measurements.

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Wearable Antennas for Remote Health Care Monitoring Systems

Remote monitoring of the elderly in telehealth applications requires that the monitoring must not affect the elderly’s regular habits. To ensure this requirement, the components (i.e., sensor and antenna) necessary to carry out such monitoring should blend in with the elderly’s daily routine. To this end, an effective strategy relies on employing wearable antennas that can be fully integrated with clothes and that can be used for remotely transmitting/receiving the sensor data. Starting from these considerations, in this work, two different methods for wearable antenna fabrication are described in detail: the first resorts to the combined use of nonwoven conductive fabrics and of a cutting plotter for shaping the fabric, whereas the second considered fabrication method resorts to the embroidery of conductive threads. To demonstrate the suitability of the considered fabrication techniques and to highlight their pros and cons, numerical and experimental results related to different wearable antennas are also reported and commented on. Results demonstrate that the presented fabrication techniques and strategies are very flexible and can be used to obtain low-cost wearable antennas with performance tailored for the specific application at hand.

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Drosophila: An Emergent Model for Delineating Interactions between the Circadian Clock and Drugs of Abuse

Endogenous circadian oscillators orchestrate rhythms at the cellular, physiological, and behavioral levels across species to coordinate activity, for example, sleep/wake cycles, metabolism, and learning and memory, with predictable environmental cycles. The 21st century has seen a dramatic rise in the incidence of circadian and sleep disorders with globalization, technological advances, and the use of personal electronics. The circadian clock modulates alcohol- and drug-induced behaviors with circadian misalignment contributing to increased substance use and abuse. Invertebrate models, such as Drosophila melanogaster, have proven invaluable for the identification of genetic and molecular mechanisms underlying highly conserved processes including the circadian clock, drug tolerance, and reward systems. In this review, we highlight the contributions of Drosophila as a model system for understanding the bidirectional interactions between the circadian system and the drugs of abuse, alcohol and cocaine, and illustrate the highly conserved nature of these interactions between Drosophila and mammalian systems. Research in Drosophila provides mechanistic insights into the corresponding behaviors in higher organisms and can be used as a guide for targeted inquiries in mammals.

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