Τετάρτη, 19 Απριλίου 2017

Lebensqualität nach endovaskulärer Intervention bei PAVK

Zusammenfassung

Die periphere arterielle Verschlusskrankheit (PAVK) ist grundsätzlich mit einer erheblichen Einschränkung der gesundheitsbezogenen Lebensqualität verbunden. Aufgrund der Häufigkeit der Erkrankung ist eine Optimierung der Therapiestrategien wichtig. Die Messung der gesundheitsbezogenen Lebensqualität ist dabei ein wichtiges Instrument in der Entscheidungsfindung und Differenzialindikation. Es konnte gezeigt werden, dass endovaskuläre Verfahren die Lebensqualität von PAVK-Patienten vor allem kurz- und mittelfristig verbessern. Für die Erzielung von positiven Langzeiteffekten ist eine Kombination von endovaskulären Techniken und strukturierten Trainingsprogrammen anzustreben.



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Chronische Schmerzen

Zusammenfassung

Chronischer Schmerz ist ein Phänomen mit komplexer und heterogener Ätiologie und klinischer Erscheinungsform. Er hat seine biologische Warnfunktion im Wesentlichen verloren, geht mit hohem Leidensdruck einher und wird als eigenständige Krankheit betrachtet. Im Rahmen der Chronifizierung treten neurologische strukturelle Veränderungen ein, die zu einer peripheren und zentralen Sensibilisierung führen und die Schmerzwahrnehmung verändern. Das perioperative Management chronischer Schmerzpatienten ist komplex und individuell, sollte sich aber stets an der vorbestehenden Medikation orientieren. Die Anwendung lokaler oder regionaler Anästhesieverfahren und der sachgerechte Einsatz von Koanalgetika können das Risiko für das Auftreten chronischer Schmerzen und Phantomschmerzen reduzieren. Über das perioperative Management hinaus ist die multimodale Schmerztherapie effektiv in der Behandlung chronischer Schmerzen und der Verbesserung der Lebensqualität.



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The use of smoothed particles approach in realistic mathematical model of intracardiac blood flow: Simulation of a self-organizing tornado-like flow

Abstract

We performed computer simulation and visualization of blood flow in the left ventricle by the method of smooth particle hydrodynamics (SPH). This visualization qualitatively describes the evolution of twisted stream and graphically demonstrates the direction of velocity field at each moment of time. The geometrical features of the left ventricle are approximated by three-dimensional segmentation of experimental clinical images obtained from multispiral computer tomography (MSCT). The model adequately describes the possible configuration of swirling flow in the left ventricle and is a part of a comprehensive study of swirling flows in different compartments of heart, which comply with a family of the exact solutions of hydrodynamic Navier–Stokes equations for the class of quasipotential1 swirling flows. Computer visualization shows how simulated by SPH method jet of a model liquid, which is placed in limited space, remains continuity and keeps its clockwise vorticity along the direction of the flow propagation during the whole cycle. Then it turns on approximately 120° by the time of ejection into the aorta. Such structure of the flow provides more effective pumping of blood as a model liquid through the ventricle as compared to a lamellar flow mode.



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Visual and oculomotor activity of first-grade school students during reading texts of varying complexity

Abstract

We present the results of investigation of visual perception (VP) and oculomotor activity during reading texts of various difficulties from the monitor screen in children 7–8 years of age. It has been shown that, at the initial stage of the development of the reading skill, morphological and psycholinguistic parameters of the text have no significant effect on the oculomotor activity. The degree of formation of VPand its structural components more clearly manifested in the first-graders in reading plain text and is not sufficient for a successful reading of the increased complexity of the text.



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Method for noninvasive diagnosis of functional state disorders in operators with the smooth pursuit test

Abstract

The article describes a videooculographic method to detect functional state disorders in operators in the target tracking test. The method is an improved version of the smooth pursuit test and can be used to detect and to estimate the effects of various adverse factors on operators in laboratory experiments. The method is noninvasive, allows a continuous data recording for a long period of time with the subject in comfortable conditions, and may employ various videooculographic devices (including portable and low-cost models). As an example, a series of experiments was performed to detect the negative effects of alcohol intoxication. A linear relationship was observed between changes in parameters of oculomotor reactions and changes in reaction time to the target stimulus.



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The factor structure of the functional state of boys aged 13–14 years

Abstract

We determined the independent factors that reflect the fundamental characteristics of the functional state (FS) in adolescents aged 13–14 years (n = 162): the sympathetic regulation and parasympathetic regulation of FS, physical working capability; the efficiency of cognitive performance; the hemodynamic basis of cognitive activity; nonspecific resistance to upper respiratory tract infections. Using the systematic approach, we investigated the physiological basis of these factors and determined the indices suitable for estimating the FS of adolescents at different stages of puberty. We observed progressive dynamics of FS parameters related to factors listed above in boys of the same chronological age at different puberty stages. Beginning from stage II to stage IV, we observed a heterochronic and nonlinear decrease in the tension of system of autonomic FS regulation, an increase in the efficiency of cognitive activity and its hemodynamic supply, as well as an improvement of anaerobic working capability.



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Voluntary regulation of the functional state and its influence on the effectiveness of cognitive activity during adolescence

Abstract

We have analyzed the impact of voluntary relaxation on the functional organization and the effectiveness of the voluntary prestimulus attention in performing cognitive tasks in adolescents at the ages of 12–13 and 13–14 years. The effectiveness of cognitive task performance (audio-verbal short-term memory) was estimated on the basis of the number of correctly remembered words. We have found that both age groups are characterized by reduced capacity for voluntary relaxation and its impact on the effectiveness of cognitive task performance. The analysis of the coherence function of EEG rhythmic components in a situation of voluntary attention focused on the performance of cognitive tasks showed no significant change in the interaction of the prefrontal cortex with other cortical areas during the switch from quiet wakefulness or post-relaxation state to the preparation to perform the task, which is typical of adults and young children. Our findings can be a result of sub-optimal functioning of voluntary regulation mechanisms and organization of activities during adolescence.



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Structural rearrangements of the cerebral cortex in children and adolescents

Abstract

The cortical formations of the brain involved in visual functions (the occipital and temporo-parieto- occipital areas, the oculomotor area of the prefrontal cortex), as well as the motor cortex in the representation zone of the arm and the medial region of the frontal cortex adjacent to the limbic lobe, were studied in post-mortem material. The thickness of the cortex and cortical layer III, the sizes of pyramidal neurons, the specific volumes of neurons and intracortical vessels were studied in subjects of both sexes, from birth to the age of 20 years, at yearly intervals (103 observations) using histological techniques, computer morphometric and stereological analysis. The thickness of the cortex of the cerebral hemispheres was observed to intensively increase from birth to the age of 3 years in the occipital, temporo-parieto-occipital and prefrontal cortical areas involved in visual recognition processes. The increase in thickness of the cerebral cortex continues until the age of 6 in the occipital cortex and in the oculomotor area, until the age of 7 years in the temporo-parietooccipital area and the medial prefrontal area, and until the age of 8–9 years in the motor cortex. The sizes of pyramidal neurons increase until the age of 6 years in the motor cortex, until the age of 8 years on the medial surface of the frontal lobe, and until the age of 9–10 years in the temporo-parieto-occipital area and in the dorsolateral area of the prefrontal cortex. The specific volume of neurons and blood vessels in the cortex of the cerebral hemispheres decreases and the volume of intracortical fibers increases throughout the ascending ontogeny, which is manifested most intensively in the prefrontal cortex.



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fMRI responses of the brain during active and passive movements in left-handed subjects

Abstract

The hemodynamic (magnetic resonance imaging, fMRI, 3T) brain responses were studied in 15 left-handed healthy subjects performing active and passive movements of the dominant and non-dominant hands. Group and individual fMRI responses to the motor load were analyzed. It was found that, during the active movements of dominant and non-dominant hands, the main activation cluster appeared in the preand postcentral gyrus of the contralateral hemisphere and which topographically similar during active and passive movements. The activation cluster of greater volume was identified in these areas; the response was more diffused during the non-dominant hand movements in comparison with the dominant hand. During passive movements, the cortical activation clusters of a smaller volume in comparison with the active movements were found, which was expressed most clearly during the performance of non-dominant hand movements and could reflect the weakening of the control from the cortical structures in these conditions.



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Rheocardiography, an advanced noninvasive circulatory system test in children and adults: Progress and prospects

Abstract

This article provides an overview of theoretical studies and clinical practice of using thoracic electrical bioimpedance (TEB). TEB is a noninvasive method for the measurement of cardiac output, cardiac index, systolic time intervals, and other hemodynamic parameters. The opinions of modern authors regarding the usage of this method are still controversial. However, many studies have proved that TEB is an accurate, reliable and promising method for monitoring the relative changes in hemodynamics in many clinical situations and in physiological studies of cardiac activity.



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Evaluation of microcirculatory disturbances in patients with rheumatic diseases by the method of diffuse reflectance spectroscopy

Abstract

Immunoinflammatory reactions affecting the state of the microvasculature play the key role in the genesis of rheumatic diseases. Therefore, it is important to develop new methods for the early detection of microcirculatory disorders. The purpose of this study was to assess the possibilities of diffuse reflectance spectroscopy used to identify microcirculatory disturbances in patients with rheumatic diseases by measuring skin blood supply and oxygenation rate and their relationship with the varying degrees of inflammatory activity. A total of 36 patients with rheumatic diseases and 31 healthy volunteers took part in the study. We analyzed the skin diffuse reflectance spectra recorded on the palmar side of the distal phalange of the right middle finger using a FLAME spectrometer. The erythema index and saturation rate were calculated to quantify the content of hemoglobin and oxygen saturation of tissues in both groups. The differences in the parameters under study between the groups were found to be statistically significant. The average value of erythema index was twofold higher in patients with rheumatic diseases with the second degree of inflammatory activity and about 2.5-fold higher in patients with the third degree of inflammatory activity, compared to the control group. This fact indicates impaired blood circulation with increased blood flow caused by inflammatory processes. Thus, diffuse reflectance spectroscopy can be used as an additional non-invasive diagnostic test for assessing the severity of microcirculatory disturbances and the activity of inflammation in rheumatic diseases.



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Effect of computer work on the state of physiological functions in children aged 7 to 10 years

Abstract

We studied the age- and sex-related functional characteristics of the central nervous system (CNS), cardiovascular system (CVS), lability of the visual sensory system, and mental capacity before and after a continuous computer work for 15 min in children aged 7, 8, 9, and 10 years. The results of the research showed that the resistance of the physiological systems of the body to loads associated with computer work increases in primary school children with age. We also observed sex-related differences: many parameters of functional performance during computer work at the age of 8 years were better in girls than in boys, which was due to a higher rate of development; at the age of 10 years, girls had a larger number of adverse changes in the functional state of the body compared with boys, which is possibly due to the onset of puberty.



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Influence of cognitive load on the body functional state in children aged 9 to 12 years during early stages of puberty

Abstract

This article analyzes heart rate variability (HRV), the glucocorticoid function of adrenal glands, and brain electrical activity (EA) in children aged 9 to 12 years to study their functional state during early stages of puberty. The cognitive load (mental arithmetic) caused low-frequency waves in the heart rate spectrum in all subjects, regardless of the puberty stage and gender. With respect to the age range under study, the hormonal response to the arithmetic test, expressed in a decrease in the level of cortisol, was observed in boys only at the third stage of puberty. The visual analysis of the background electrical encephalogram showed frequent generalized bilateral and synchronous changes in the electrical activity (EA) in the form of diencephalic signs in children. The features of the relationship between the autonomic nervous system and the hypothalamic pituitary-adrenal system have been revealed in children aged 9 to 12 years during cognitive load. The closest correlations between HRV indices and cortisol levels have been found in girls at the first stage and boys at the third stage of puberty.



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Functional state of the cardiovascular system in 13-year-old adolescents with different types of autonomic nervous regulation

Abstract

The features of the functional state of cardiovascular system in 13-year-old children with different types of autonomic nervous regulation were studied. Children with normotonic and parasympathetic types of autonomic regulation were found to have the highest adaptation capacities. The autonomic nervous system influences the bioelectrical processes in myocardium, the duration of cardiac cycle phases, and cerebral blood flow. Schoolchildren aged 13 years with higher sympathetic activity have shorter duration of the cardiac cycle, the phase of isometric contraction, and diastole. They have a lower pulse blood flow rate and a higher tone of large and medium cerebral vessels. No relationship was revealed between the initial autonomic nervous regulation of heart rate and the type of adaptation of myocardium to physical dynamic loads, as well as the type of adaptation of cerebral circulation to mental stress.



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Relationships between the EEG θ- and β-parameters and heart rate variability during human cognitive performance

Abstract

We studied the dynamics of spectral coherence characteristics of the EEG θ-, β1-, and β2-activity and the heart rate variability (HRV) in subjects performing cognitive tests. We found an association between the HRV parameters in the process of cognitive activity and the coherence of potentials in the EEG θ-, β1-, and β2-bands. The heart rate parameters in the baseline state and during the test performance best correlated with the levels of the right-hemispheric coherence of potentials in the θ-, β1-, and β2-bands of the baseline EEG (eyes closed). The higher coherence levels corresponded to lower values of the mean time of RR intervals (RRNN), coefficient of variation (CV), total power (TP), the power of the high-frequency (HF) and low-frequency (LF) components in the HRV spectrum. During the performance of the test, higher coherence values in the EEG θ-bands with the focus in the right temporal lead corresponded to higher LF/HF values reflecting the predominance of sympathetic effects on heart rate.



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ASPP2 suppresses invasion and TGF-β1-induced epithelial–mesenchymal transition by inhibiting Smad7 degradation mediated by E3 ubiquitin ligase ITCH in gastric cancer

Publication date: 10 July 2017
Source:Cancer Letters, Volume 398
Author(s): Yasuyuki Gen, Kohichiroh Yasui, Tomoko Kitaichi, Naoto Iwai, Kei Terasaki, Osamu Dohi, Hikaru Hashimoto, Hayato Fukui, Yutaka Inada, Akifumi Fukui, Masayasu Jo, Michihisa Moriguchi, Taichiro Nishikawa, Atushi Umemura, Kanji Yamaguchi, Hiroyuki Konishi, Yuji Naito, Yoshito Itoh
ASPP2 regulates cell polarity and cell–cell adhesion by binding to, and co-localizing with PAR3 at tight junctions. Here we show a novel role of ASPP2 in suppressing gastric cancer (GC) invasiveness. Immunoprecipitation and immunofluorescence analyses showed that ASPP2 promoted the recruitment of PAR3 to cell–cell junctions in GC cells. Diminished expression of ASPP2 and loss of junctional PAR3 localization were significantly associated with diffuse-type histology, deeper invasion depth, positive peritoneal dissemination and worse prognosis in primary GC. ASPP2 suppressed migration and invasion of GC cells in vitro and peritoneal dissemination of GC cells in vivo in a mouse model. ASPP2 suppressed epithelial–mesenchymal transition (EMT) induced by TGF-β1-Smad2/3 signaling in GC cells through suppression of the degradation of Smad7, a negative regulator of TGF-β1-Smad2/3 signaling, by interacting with the E3 ubiquitin ligase ITCH. In conclusion, ASPP2 suppresses invasion, peritoneal dissemination and TGF-β1-induced EMT by inhibiting Smad7 degradation mediated by ITCH.



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Effect of platinum on sintering morphology of porous YSZ ceramics

Abstract

Platinum/yttria-stabilized zirconia (Pt/YSZ) porous ceramics were prepared by sintering of the Pt/PMMA/YSZ stripe-like membrane with a porogen of spherical polymethyl methacrylate (PMMA) and a precursor of platinum (Pt) of chloroplatinic acid. The microstructure of raw and processed material and Pt/ZrO2 calcination process at different sintering temperatures were investigated. The results showed that the spherically porous structure of Pt/YSZ was observed at a sintering temperature below 400 °C due to the thermal decomposition of PMMA. However, the pores were shrunk about 35% in diameter when YSZ compacts were sintered at the temperature of 1,450 °C. In addition, the spherical pores can be retained in the compacts when the content of Pt <5% and then gradually merged into changing when the content of Pt increased to 50%. The relative density was increased from 42% to 90% and the open porosity was decreased from 60% to 10% when Pt was added with content from 5% to 80%. The change of microstructure for Pt/YSZ is due to the migration of Pt and YSZ in the composites. The preferential migration and coalescence proceeded for Pt in Pt/YSZ is about 500 °C and YSZ clusters can keep stable until up to 900 °C. However, the growth of YSZ particle in the sintering process was hindered by the scattering of Pt phase.

Thumbnail image of graphical abstract

The pore relies on the amount of metal Pt.

Migration and coalescence proceeded for Pt species are proposed.

The particle growth relates to temperature.



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NINJ2– A novel regulator of endothelial inflammation and activation

Publication date: Available online 18 April 2017
Source:Cellular Signalling
Author(s): Jingjing Wang, Jingjing Fa, Pengyun Wang, Xinzhen Jia, Huixin Peng, Jing Chen, Yifan Wang, Chenhui Wang, Qiuyun Chen, Xin Tu, Qing K. Wang, Chengqi Xu
Previous genetic studies suggested that variants in NINJ2 (encode ninjurin2) confer risk to ischemic stroke or large artery atherosclerotic stroke. However, the underlying mechanisms of NINJ2 in ischemic stroke or atherosclerosis are still unknown. In this study, we hypothesized that NINJ2 may play a role in endothelial inflammation and activation, and regulate the process of atherosclerosis. Here, we demonstrated that NINJ2 can regulate the expression of a panel of genes that are associated with inflammation and atherosclerosis (e.g. IL-1β, TNF-α, IL-8, IL-6, ICAM-1 and E-selectin) in human vascular endothelial cells (HUVECs). Moreover, we found the expression of ninjurin2 is upregulated in LPS stimulated HUVECs and mouse aorta, and it can regulate LPS-induced endothelial activation and the adhesion of monocytes to endothelial cells. We also found that NINJ2 can regulate NF-κB and c-jun through interacting with TLR4. In conclusion, our study suggests that ninjurin2 is a novel regulator of endothelia inflammation and activation through TLR4 signaling pathways, and these data provided new insights into the mechanisms between NINJ2 and atherosclerosis.

Graphical abstract

image


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Once doesn't count: Phenotype-driven gene hunting in cohorts



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Cover Image, Volume 38, Issue 5

Thumbnail image of graphical abstract

On the cover: The cover image, by Jonathan Gallion et al., is based on the Research Article Predicting phenotype from genotype: Improving accuracy through more robust experimental and computational modeling, Pages 569–580. DOI 10.1002/humu.23193



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Issue Information



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Bad blood contaminating germline databases?



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Dynamic adaptation of online ensembles for drifting data streams

Abstract

The success of data stream mining techniques has allowed decision makers to analyze their data in multiple domains, ranging from monitoring network intrusion to financial markets analysis and online sales transactions exploration. Specifically, online ensembles that construct accurate models against drifting data streams have been developed. Recently, there has been a surge in interest in mobile (or so-called pocket) data stream mining, aiming to construct near real-time models for data stream mining applications that run on mobile devices. In such a setting, it follows that the computational resources are limited and that there is a need to adapt analytics to map the resource usage requirements. Consequently, the resultant models should not only be highly accurate, but they should also adapt swiftly to changes. In addition, the data mining techniques should be fast, scalable, and efficient in terms of resource allocation. It then becomes important to consider Return on Investment (ROI) issues such as storage requirements and memory utilization. This paper introduces the Adaptive Ensemble Size (AES) algorithm, an extension of the Online Bagging method, to address these issues. Our AES method dynamically adapts the sizes of ensembles, based on ROI usage patterns. We illustrate our approach by analyzing the performances against both synthetic and real-world data streams. The results, when comparing our AES algorithm with the state-of-the-art, indicate that we are able to obtain a high Return on Investment (ROI) and to swiftly adapt to change, without compromising on the predictive accuracy.



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About vortex equations of two dimensional flows

Abstract

A method to obtain a time-independent vortex solution of a nonlinear differential equation describing two-dimensional flow is investigated. In the usual way, starting from the Navier–Stokes equation the vortex equation is derived by taking a curl operation. After rearranging the equation of the vortex, we get a continuity equation or a divergence-free equation: \(\partial _1V_1+\partial _2V_2=0\) . Additional irrotationality of \(V_1\) and \(V_2\) leads us to the Cauchy–Riemann condition satisfied by a newly introduced stream function \(\Psi\) and velocity potential \(\Phi\) . As a result, if we know \(V_1\) and \(V_2\) or a combination of two, the differential equation is mapped to a lower-order partial differential equation. This differential equation is the one satisfied by the stream function \(\psi\) where the vorticity vector \(\omega\) is given by \(-(\partial _1^2+\partial _2^2) \psi\) . A simple solution is discussed for the two different limits of viscosity.



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Stochastic resonance in a fractal dimensional bistable system

Abstract

A fractal dimensional bistable system driven by multiplicative and additive noises and a periodic signal is investigated. We have derived analytically the fractal Fokker–Planck equation of the system, and obtained exact expression of its signal-to-noise ratio (SNR). Numerical results indicate that: (1) The curve of the SNR as a function of multiplicative noise intensity D or additive noise intensity Q exhibits a peak in the fractal dimensional system, i.e., a stochastic resonance phenomenon; (2) For the smaller values of D, the SNR first decreases then increases with increment of dimensionality \(\alpha \) . At the integer dimension of \(\alpha =1\) , response of the system to the weak periodic signal displays a minimum. Yet the SNR increases monotonically for the greater values of D. Our further investigation shows that the height of the potential barrier depends on the dimensionality, and influences on the SNR of the system.



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Association between active commuting and incident cardiovascular disease, cancer, and mortality: prospective cohort study

Objective To investigate the association between active commuting and incident cardiovascular disease (CVD), cancer, and all cause mortality.Design Prospective population based study. Setting UK...
recent?d=yIl2AUoC8zA recent?d=dnMXMwOfBR0 recent?i=BnqV37bxbp4:T0PUbfQ0BTM:V_sGLiP recent?d=qj6IDK7rITs recent?i=BnqV37bxbp4:T0PUbfQ0BTM:gIN9vFw recent?d=l6gmwiTKsz0 recent?d=7Q72WNTAKBA recent?i=BnqV37bxbp4:T0PUbfQ0BTM:F7zBnMy recent?i=BnqV37bxbp4:T0PUbfQ0BTM:-BTjWOF


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Childhood adversity and risk of suicide: cohort study of 548 721 adolescents and young adults in Sweden

Objective To examine the relation between childhood adversity, the role of school performance, and childhood psychopathology and the risk of suicide.Design Cohort study of register based indicators...
recent?d=yIl2AUoC8zA recent?d=dnMXMwOfBR0 recent?i=1cNZJtjFev4:FyQt84aXPwM:V_sGLiP recent?d=qj6IDK7rITs recent?i=1cNZJtjFev4:FyQt84aXPwM:gIN9vFw recent?d=l6gmwiTKsz0 recent?d=7Q72WNTAKBA recent?i=1cNZJtjFev4:FyQt84aXPwM:F7zBnMy recent?i=1cNZJtjFev4:FyQt84aXPwM:-BTjWOF


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Active commuting is beneficial for health

Physical inactivity increases the risk of many diseases such as type 2 diabetes, cardiovascular disease, and some cancers.1 Many adults are not attracted to sports and other leisure time physical...
recent?d=yIl2AUoC8zA recent?d=dnMXMwOfBR0 recent?i=yscCiqg29aY:dNb50YmAGJg:V_sGLiP recent?d=qj6IDK7rITs recent?i=yscCiqg29aY:dNb50YmAGJg:gIN9vFw recent?d=l6gmwiTKsz0 recent?d=7Q72WNTAKBA recent?i=yscCiqg29aY:dNb50YmAGJg:F7zBnMy recent?i=yscCiqg29aY:dNb50YmAGJg:-BTjWOF


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miR-191 suppresses angiogenesis by activation of NF-{kappa}B signaling [Research]

MicroRNAs (miRNAs) are powerful regulators of diverse biologic processes. However, the function of most miRNAs in angiogenesis remains elusive. In this study, we identified miR-191-5p (miR-191) as a potent inhibitor of blood vessel development. Transfection of human dermal microvascular endothelial cells with miR-191 mimic (miR-191m) inhibited their proliferation, migration, and tube formation. Moreover, vascular sprouting of miR-191m–transfected mouse aortic rings was significantly reduced when compared with controls. Transfection with miR-191 inhibitor (miR-191i) induced proangiogenic effects. The anti- and proangiogenic activities of miR-191m and -191i were further demonstrated in vivo. Additional molecular biologic analyses revealed that miR-191m activates NF-B signaling by up-regulating the mRNA expression of p65. miR-191 also increased the mRNA levels of the antiangiogenic factors p21 and tissue inhibitor of metalloproteinase-1 and reduced the expression of the proangiogenic factors eNOS and matrix metalloproteinase-1 and -9. Blockade of NF-B activation with Bay 11-7082 reversed the antiangiogenic effects of miR-191m. These findings indicate that miR-191 effectively suppresses angiogenesis by activation of the NF-B signaling pathway.—Gu, Y., Ampofo, E., Menger, M. D., Laschke, M. W. miR-191 suppresses angiogenesis by activation of NF-B signaling.



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Tau haploinsufficiency causes prenatal loss of dopaminergic neurons in the ventral tegmental area and reduction of transcription factor orthodenticle homeobox 2 expression [Research]

Homozygous tau knockout (Mapt–/–) mice develop age-dependent dopaminergic (DA) neuronal loss in the substantia nigra (SN) and ventral tegmental area (VTA), supporting an important function of tau in maintaining the survival of midbrain dopaminergic neurons (mDANs) during aging. However, it remains to be determined whether the microtubule-associated protein tau regulates the differentiation and survival of mDANs during embryonic developmental stages. Here, we show that tau haploinsufficiency in postnatal day 0 (P0) heterozygous (Mapt+/–) pups, but not a complete loss of tau in the Mapt–/– littermates, led to a significant reduction of DA neurons in the VTA. This selective loss of DA neurons correlated with a similar reduction in orthodenticle homeobox 2 (Otx2), which is restricted to VTA neurons at the postmitotic stage and selectively controls the neurogenesis and survival of specific neuronal subtypes of VTA. Moreover, the prenatal developmental cell death in the Mapt+/– VTA specifically increased, and the expression of microtubule-associated protein (MAP)-1A was significantly up-regulated in the P0 Mapt–/–, but not the Mapt+/–, pups. These results suggest that tau haploinsufficiency, without the compensation effect of MAP1A, induces reduction of Otx2 expression, increases prenatal cell death, and accordingly leads to selective loss of VTA DA neurons in the early postnatal stage. Our findings highlight the impact of tau haploinsufficiency on the survival of mDANs and indicate that tau may participate in midbrain development in a dose-dependent way.—Zheng, M., Jiao, L., Tang, X., Xiang, X., Wan, X., Yan, Y., Li, X., Zhang, G., Li, Y., Jiang, B., Cai, H., Lin X. Tau haploinsufficiency causes prenatal loss of dopaminergic neurons in the ventral tegmental area and reduction of transcription factor orthodenticle homeobox 2 expression.



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Sporadic Insulinoma as a Rare Cause of Recurrent Hypoglycemia in Children

Insulinoma is a rare pancreatic tumor in children and adolescents. As a result of insulin hypersecretion, signs and symptoms are more commonly consequences of the pathophysiologic responses to hypoglycemia. According to rarity of this tumor in children and nonspecificity of clinical presentations, diagnosis of insulinoma in this group of patients is usually delayed. Early diagnosis is very important for preventing neurologic damage. In this case report, we present the case of a 10-year-old boy with signs and symptoms of hypoglycemia and final diagnosis of insulinoma.

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Two-Dimensional River Flow Patterns Observed with a Pair of UHF Radar System

A pair of ultrahigh-frequency (UHF) radars system for measuring the two-dimensional river flow patterns is presented. The system consists of two all-digital UHF radars with exactly the same hardware structure, operating separately at 329–339 MHz and 341–351 MHz. The adoption of direct radio frequency (RF) sampling technique and digital pulse compression simplifies the structure of radar system and eliminates the distortion introduced by the analog mixer, which improves the SNR and dynamic range of the radar. The field experiment was conducted at Hanjiang River, Hubei province, China. Over a period of several weeks, the radar-derived surface velocity has been very highly correlated with the measurements of EKZ-I, with a correlation coefficient of 0.958 and a mean square error of 0.084 m/s.

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Redefinition of -Distance in Metric Spaces

The concept of -distance was introduced in 2001; on the other hand, that of -function was introduced by Lin and Du. Strongly inspired by -function, we introduce a new concept, which is a very slight generalization of -distance and is more natural than -distance. So we could say that we redefine -distance in some sense.

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Oncolytic Virus-Based Immunotherapies for Hepatocellular Carcinoma

Hepatocellular carcinoma is highly refractory cancer which is resistant to conventional chemotherapy and radiotherapy, carrying a dismal prognosis. Although many anticancer drugs have been developed for treating HCC, sorafenib is the only effective treatment, but it only prolongs survival duration for about 3 months. Recently, oncolytic virotherapy has shown promising results in treating HCCs and the effects can be more enhanced by adopting immune modulatory molecules. This review discusses the current status of treating HCC and the effective strategy of oncolytic virus-based immunotherapy for the treatment of HCCs.

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Study on the Permeability Characteristics of Polyurethane Soil Stabilizer Reinforced Sand

A polymer material of polyurethane soil stabilizer (PSS) is used to reinforce the sand. To understand the permeability characteristics of PSS reinforced sand, a series of reinforcement layer form test, single-hole permeability test, and porous permeability test of sand reinforced with PSS have been performed. Reinforcement mechanism is discussed with scanning electron microscope images. The results indicated that the permeability resistance of sand reinforced with polyurethane soil stabilizer is improved through the formation of reinforcement layer on the sand surface. The thickness and complete degree of the reinforcement layer increase with the increasing of curing time and PSS concentration. The water flow rate decreases with the increasing of curing time or PSS concentration. The permeability coefficient decreases with the increasing of curing time and PSS concentration and increases with the increasing of depth in specimen. PSS fills up the voids of sand and adsorbs on the surface of sand particle to reduce or block the flowing channels of water to improve the permeability resistance of sand. The results can be applied as the reference for chemical reinforcement sandy soil engineering, especially for surface protection of embankment, slope, and landfill.

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Neuroprotective Effect of Fagopyrum dibotrys Extract against Alzheimer’s Disease

Accumulated evidence suggests that polyphenolic antioxidants present in herbs play important roles in prevention of AD; the molecular mechanisms behind neuroprotective actions rely on the phenols through different effects on the amyloid-aggregation pathway. Fagopyrum dibotrys is a traditional herbal medicine which contains high quantity phenols. In present study, we investigate the beneficial pharmacological actions of Fagopyrum dibotrys extract in the APP/PS1 transgenic mouse mode; meanwhile, effects of the FDE on the fibrillation and cytotoxicity of Aβ peptide were evaluated in vitro. After 9-month treatment, FDE exhibited multifunctional properties on Aβ-related pathologies, which cleaned Aβ deposits in the brain and decreased Aβ burden in the plasma, inhibited microhaemorrhage, and reduced reactive microglia in APP/PS1 transgenic mice and also promoted Aβ fibrils disaggregation and inhibited neurotoxicity induced by Aβ in SH-SY5Y cells. These results highlighted that FDE is an AD type pathology modulator with therapeutic potential against AD.

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Enaminonitrile as Building Block in Heterocyclic Synthesis: Synthesis of Novel 4H-Furo[2,3-d][1,3]oxazin-4-one and Furo[2,3-d]pyrimidin-4(3H)-one Derivatives

2-Amino-4,5-diphenylfuran-3-carbonitrile 1 was utilized as building block for the construction of new furo[2,3-d]pyrimidin-4(3H)-one derivative 2 and 4H-furo2,3-d1,3oxazin-4-one derivative 3 via treatment with acetic anhydride and benzoyl chloride, respectively. The 4H-furo2,3-d1,3oxazin-4-one derivative 3 was transformed into novel furo[2,3-d]pyrimidin-4(3H)-ones 4–8, tetrazolylfuran derivative 10, and furo[3,2-d]imadazolone derivative 11 via reaction with various nitrogen nucleophiles. The structure features of the synthesized compounds were established from their spectral and elemental analyses.

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Synthesizing Sum and Difference Patterns with Low Complexity Feeding Network by Sharing Element Excitations

In monopulse radar antennas, the synthesizing process of the sum and difference patterns must be fast enough to achieve good tracking of the targets. At the same time, the feed networks of such antennas must be as simple as possible for efficient implementation. To achieve these two goals, an iterative fast Fourier transform (FFT) algorithm is used to synthesize sum and difference patterns with the main focus on obtaining a maximum allowable sharing percentage in the element excitations. The synthesizing process involves iterative calculations of FFT and its inverse transformations; that is, starting from an initial excitation, the successive improved radiation pattern and its corresponding modified element excitations can be found repeatedly until the required radiation pattern is reached. Here, the constraints are incorporated in both the array factor domain and the element excitation domain. By enforcing some constraints on the element excitations during the synthesizing process, the described method provides a significant reduction in the complexity of the feeding network while achieving the required sum and difference patterns. Unlike the standard optimization approaches such as genetic algorithm (GA), the described algorithm performs repeatedly deterministic transformations on the initial field until the prescribed requirements are satisfied. This property makes the proposed synthesizing method converge much faster than GA.

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Rapid Determination of Six Low Molecular Carbonyl Compounds in Tobacco Smoke by the APCI-MS/MS Coupled to Data Mining

A simple method was established for the rapid determination of low molecular carbonyl compounds by the combination of atmospheric pressure chemical ionization tandem mass spectrometry (APCI-MS/MS) and data mining. The ionization was carried out in positive mode, and six low molecular carbonyl compounds of acrolein, acetone, propionaldehyde, crotonaldehyde, butanone, and butyraldehyde were analyzed by both full scan mode and daughter scan mode. To overcome the quantitative difficulties from isomer of acetone/propionaldehyde and butanone/butyraldehyde, the quantitation procedure was performed with the characteristic ion of [CH3O]+ under CID energy of 5 and 15 eV. Subsequently, the established method was successfully applied to analysis of six low molecular carbonyl compounds in tobacco smoke with analytical period less than four minutes. The contents of acrolein, acetone, propionaldehyde, crotonaldehyde, butanone, and butyraldehyde for a cigarette were about , , , , , and  μg/cig, respectively. The experimental results indicated that the established method had the potential application in rapid determination of low molecular carbonyl compounds.

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Rescue EUS-guided intrahepatic biliary drainage for malignant hilar biliary stricture after failed transpapillary re-intervention

Abstract

Background

Treatment of unresectable malignant hilar biliary stricture (UMHBS) is challenging, especially after failure of repeated transpapillary endoscopic stenting. Endoscopic ultrasonography-guided intrahepatic biliary drainage (EUS-IBD) is a recent technique for intrahepatic biliary decompression, but indications for its use for complex hilar strictures have not been well studied. The aim of this study was to assess the feasibility and safety of EUS-IBD for UMHBS after failed transpapillary re-intervention.

Methods

Retrospective analysis of all consecutive patients with UMHBS of Bismuth II grade or higher who, between December 2008 and May 2016, underwent EUS-IBD after failed repeated transpapillary interventions. The technical success, clinical success, and complication rates were evaluated. Factors associated with clinical ineffectiveness of EUS-IBD were explored.

Results

A total of 30 patients (19 women, median age 66 years [range 52–87]) underwent EUS-IBD for UMHBS during the study period. Hilar biliary stricture morphology was classified as Bismuth II, III, or IV in 5, 13, and 12 patients, respectively. The median number of preceding endoscopic interventions was 4 (range 2–14). EUS-IBD was required because the following procedures failed: duodenal scope insertion (n = 4), accessing the papilla after duodenal stent insertion (n = 5), or achieving desired intrahepatic biliary drainage (n = 21). Technical success with EUS-IBD was achieved in 29 of 30 patients (96.7%) and clinical success was attained in 22 of these 29 (75.9%). Mild peritonitis occurred in three of 30 (10%) and was managed conservatively. Stent dysfunction occurred in 23.3% (7/30). There was no procedure-related mortality. On multivariable analysis, Bismuth IV stricture predicted clinical ineffectiveness (odds ratio = 12.7, 95% CI 1.18–135.4, P = 0.035).

Conclusions

EUS-IBD may be a feasible and effective rescue alternative with few major complications after failed transpapillary endoscopic re-intervention in patients with UMHBS, particularly for Bismuth II or III strictures.



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Long-term outcomes of endoscopic resection of gastric GISTs

Abstract

Objective

Although the endoscopic treatment of gastric stromal tumors is a recently accepted therapy, the long-term outcomes of this approach remain unknown. The aims of this study were to assess the long-term effectiveness and safety of endoscopic resection for gastric GISTs.

Methods

A total of 60 consecutive patients undergoing endoscopic resection of gastric GISTs were enrolled in a retrospective single-center study. Clinical data, perioperative complications, histopathologic characteristics of the tumors, and long-term outcomes were recorded.

Results

Sixty patients successfully underwent complete resection of lesions, including 25 cases of endoscopic submucosal dissection (ESD) and 35 cases of endoscopic full-thickness resection (EFTR), with an average tumor size of 1.76 ± 1.55 cm (range 0.5–7.6 cm). The average operation time was 43.97 ± 26.95 min (range 11.7–138.9 min). Two cases were observed with an intraoperative hemorrhage of 200 mL, which were successfully managed by hemostatic forceps. Perforations of 2–11 mm of ESD occurred in four cases (4/25) and were well closed with endoclips, with no conversions to surgical operation. Mucosal laceration of esophagus occurred in 1 case, when a large tumor was removed. The average length of hospitalization was 6.50 ± 3.06 days (range 3–21 days). Out of a total of 60 patients, 44 (73.3%) were at very low risk, 10 (16.7%) were at low risk, 5 (8.3%) were at intermediate risk, and 1 (1.7%) was at high risk. All patients were followed-up for 36.15 ± 12.92 months (range 14–73 months). Primary tumor recurrence occurred in 1 patient who underwent a second operation after 32 months, and no other cases were observed to have either tumor recurrence or metastasis.

Conclusions

For long-term outcomes, endoscopic resection of ESD or EFTR is a safe and effective approach for removing gastric stromal tumors (<5 cm), and it can be a resection technique for them with no metastasis.



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Can further gastrectomy be avoided in patients with incomplete endoscopic resection?

Abstract

Background

Endoscopic resection (ER) is a widely accepted treatment for patients with early gastric cancer (EGC) with no lymph node metastasis. Occasionally, however, additional surgery is needed due to an incomplete resection. The purpose of this study was to detect clinical factors which might identify patients at greater risk of additional surgery after ER and to suggest an alternative treatment strategy for these patients.

Methods

This study retrospectively analyzed 350 patients with gastric cancer who underwent radical gastrectomy and lymphadenectomy after ER in a single institution between July 2004 and July 2014. Risk factors for incomplete resection were identified using binary logistic multiple regression tests and a classification and regression tree analysis.

Results

Residual cancer cells were found in the remnant stomach or lymph node in 96 patients (27.4%). In multivariate analysis, lymphovascular invasion (p < 0.001, odds ratio [OR] 5.619) and depth of invasion greater than the second submucosal layer (SM2) (p < 0.01, OR 3.224) were independent risk factors for lymph node metastasis. Positive resection margin (p < 0.001, OR 7.565), depth of invasion to mucosa (M) and the first submucosal layer (SM1) (p < 0.001, OR 4.219), and size over 3 cm (p < 0.029, OR 2.306) were significant risk factors for residual tumor in the remnant stomach. Of 106 patients who had invasion of the M or SM1 without lymphatic invasion at the time of ER, residual cancer was found in 53 patients. Of these 53 patients, 50 (94.3%) had residual cancer in the mucosal layer and only one had lymph node metastasis.

Conclusion

In patients with EGC with M or SM1 invasion without lymphovascular invasion at the time of ER, who had an incomplete resection, additional endoscopic treatment or close monitoring can be performed instead of additional surgery, especially in patients who are unable to tolerate gastrectomy, for example elderly patients or those with comorbidities.



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Colonel (Rtd) Peter Roberts CBE SM MS FRCS L/RAMC 20 December 1940-11 March 2017



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Crossbow bolt injury: an unusual case of penetrating trauma



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Disease-Associated Extracellular Loop Mutations in the Adhesion G Protein-Coupled Receptor G1 (ADGRG1; GPR56) Differentially Regulate Downstream Signaling [Molecular Bases of Disease]

Mutations to the adhesion G protein-coupled receptor ADGRG1 (G1; also known as GPR56) underlie the neurological disorder bilateral frontoparietal polymicrogyria (BFPP). Disease-associated mutations in G1 studied to date are believed to induce complete loss of receptor function, either through disruption of receptor trafficking or signaling activity. Given that N-terminal truncation of G1 and other adhesion G protein-coupled receptors has been shown to significantly increase the receptors' constitutive signaling, we examined two different BFPP-inducing extracellular loop mutations (R565W and L640R) in the context of both full-length and N-terminally truncated (deltaNT) G1. Interestingly, we found that these mutations reduced surface expression of full-length G1 but not G1-deltaNT in HEK-293 cells. Moreover, the mutations ablated receptor-mediated activation of serum response factor luciferase, a classic measure of Galpha12/13-mediated signaling, but had no effect on G1-mediated signaling to nuclear factor of activated T cells (NFAT) luciferase. Given these differential signaling results, we sought to further elucidate the pathway by which G1 can activate NFAT luciferase. We found no evidence that deltaNT activation of NFAT is dependent on Galphaq/11-mediated or beta-arrestin-mediated signaling, but rather involves liberation of G beta gamma subunits and activation of calcium channels. These findings reveal that disease-associated mutations to the extracellular loops of G1 differentially alter receptor trafficking, depending on the presence of the N-terminus, and also differentially alter signaling to distinct downstream pathways.

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Effects of altered sialic acid biosynthesis on N-linked glycan branching and cell surface interactions [Glycobiology and Extracellular Matrices]

GNE myopathy is a rare muscle disorder associated with aging and is related to sporadic inclusion body myositis (sIBM), the most common acquired muscle disease of aging. While the cause of sIBM is unknown, GNE myopathy is associated with mutations in UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE). GNE harbors two enzymatic activities required for biosynthesis of sialic acid in mammalian cells. Mutations to both GNE domains are linked to GNE myopathy. However, correlation between mutation-associated reductions in sialic acid production and disease severity is imperfect. To investigate other potential effects of GNE mutations, we compared sialic acid production in cell lines expressing wild-type or mutant forms of GNE. Although we did not detect any differences attributable to disease-associated mutations, lectin binding and mass spectrometry analysis revealed that GNE deficiency is associated with unanticipated effects on the structure of cell-surface glycans. In addition to exhibiting low levels of sialylation, GNE-deficient cells produced distinct N-linked glycan structures with increased branching and extended poly-N-acetyllactosamine (polyLacNAc). GNE deficiency may affect levels of UDP-GlcNAc, a key metabolite in the nutrient-sensing hexosamine biosynthetic pathway, but this modest effect did not fully account for the change in N-linked glycan structure. Further, GNE deficiency and glucose supplementation acted independently and additively to increase N-linked glycan branching. Notably, N-linked glycans produced by GNE-deficient cells displayed enhanced binding to galectin-1, indicating that changes in GNE activity can alter affinity of cell-surface glycoproteins for the galectin lattice. These findings suggest an unanticipated mechanism by which GNE activity might affect signaling through cell-surface receptors.

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Identification of a Multienzyme Complex for Glucose Metabolism in Living Cells [Cell Biology]

Sequential metabolic enzymes in glucose metabolism have long been hypothesized to form multienzyme complexes that regulate glucose flux in living cells. However, it has been challenging to directly observe these complexes and their functional roles in living systems. In this work, we have used wide-field and confocal fluorescence microscopy to investigate the spatial organization of metabolic enzymes participating in glucose metabolism in human cells. We provide compelling evidence that human liver-type phosphofructokinase 1 (PFKL), which catalyzes a bottleneck step of glycolysis, forms various sizes of cytoplasmic clusters in human cancer cells, independent of protein expression levels and of the choice of fluorescent tags. We also report that these PFKL clusters colocalize with other rate-limiting enzymes in both glycolysis and gluconeogenesis, supporting the formation of multienzyme complexes. Subsequent biophysical characterizations with fluorescence recovery after photobleaching (FRAP) and fluorescence resonance energy transfer (FRET) corroborate the formation of multienzyme metabolic complexes in living cells, which appears to be controlled by post-translational acetylation on PFKL. Importantly, quantitative high-content imaging assays indicated that the direction of glucose flux between glycolysis, the pentose phosphate pathway and serine biosynthesis seem to be spatially regulated by the multienzyme complexes in a cluster size-dependent manner. Collectively, our results reveal a functionally relevant, multienzyme metabolic complex for glucose metabolism in living human cells.

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The Kielin/chordin-like Protein (KCP) Attenuates High Fat Diet Induced Obesity and Metabolic Syndrome in Mice [Molecular Bases of Disease]

Obesity and its associated complications, such as insulin resistance and non-alcoholic fatty liver disease, are reaching epidemic proportions. In mice, the TGF-beta superfamily is implicated in the regulation of white and brown adipose tissue differentiation. The Kielin/chordin-like Protein (KCP) is a secreted regulator of the TGF-beta superfamily pathways that can inhibit both TGF-beta and activin signals while enhancing bone morphogenetic protein (BMP) signaling. However, KCP's effects on metabolism and obesity have not been studied in animal models. Therefore, we examined the effects of KCP loss or gain of function in mice that were maintained on either a regular or a high fat diet. KCP loss sensitized the mice to obesity and associated complications such as glucose intolerance and adipose tissue inflammation and fibrosis. In contrast, transgenic mice that expressed KCP in the kidney, liver and adipose tissues were resistant to developing high fat diet induced obesity and had significantly reduced white adipose tissue. Moreover, KCP over-expression shifted the pattern of Smad signaling in vivo, increasing the levels of P-Smad1 and decreasing P-Smad3. Adipocytes in culture showed a cell autonomous effect in response to added TGF-beta1 or BMP7. Metabolic profiling indicated increased energy expenditure in KCP overexpressing mice and reduced expenditure in the KCP mutants, with no effect on food intake or activity. These findings demonstrate that shifting the TGF-beta superfamily signaling with a secreted protein can alter the physiology and thermogenic properties of adipose tissue to reduce obesity even when mice are fed a high fat diet.

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Acoustic Analysis of Indian Teachers’ Voice: Pre and Post Teaching Circumstances

Abstract

Compared to people employed in other occupations, teachers are more likely to report having voice problems. They are more likely to perceive that their voice problems limit their current job performance and also adversely affect their future career options. The current study examines the acoustic parameters that are sensitive to vocal loading in pre and post teaching circumstances and adds to the existing literature. Voice samples were recorded from 30 primary school teachers, 15 females and 15 males in the age range of 28–35 years (mean age 29.3 years), with teaching experience of 10–12 years. Mean pitch, minimum pitch, maximum pitch, number of voice breaks, jitter local, shimmer local and mean harmonic to noise ratio were estimated using PRAAT software before and after a typical teaching day. Significant difference was seen when number of voice breaks was compared in pre and post teaching conditions in both males (p = 0.02) and females (p = 0.02) in the conversation task. Moreover, significant differences in mean pitch was observed in the task of slogan repetition (p = 0.03), but only in males. These parameter can be used as indicators of vocal fatigue among teachers and can be used in objective determination of at risk population.



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News in Thyroid Research and Care: A Q&A with the American Thyroid Association

thyroid.jpg

A leading worldwide organization dedicated to the advancement, understanding, prevention, diagnosis, and treatment of thyroid disorders, the American Thyroid Association president-elect, Dr. Charles Emerson, spoke with WomensHealth.com. Read the Interview

The post News in Thyroid Research and Care: A Q&A with the American Thyroid Association appeared first on American Thyroid Association.



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MiR-590-5p, a density-sensitive microRNA, inhibits tumorigenesis by targeting YAP1 in colorectal cancer

YAP1, a transcription co-activator, mediates the biological functions of the Hippo pathway. YAP1 inactivation is involved in cell–cell contact inhibition. In various tumors, YAP1 is upregulated through multiple mechanisms, and it functions as an oncogene. Here, we provided evidence that YAP1 influenced multiple signaling pathways in colorectal cancer (CRC) cells. We reported that miR-590-5p directly targets YAP1 and inhibits tumorigenesis in CRC cells both in vitro and in vivo xenograft model. We analyzed different cell densities and found that increased density caused increased expression of miR-590-5p, and decreased expression of its precursors (pri- and pre-miR-590).

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The effect of high-dose vitamin D supplementation on muscular function and quality of life in postmenopausal women – a randomized controlled trial

Abstract

Objective

Observational studies have suggested positive associations between serum 25-hydroxyvitamin D (25(OH)D) levels and muscular strength, balance and quality of life. Our aim was to examine whether high-dose vitamin D supplementation would improve these measures as compared to standard-dose vitamin D, as well as the possible muscular effects of Single Nucleotide Polymorphisms (SNPs) in genes encoding vitamin D-related enzymes.

Design

A 12-month randomized, double-blind, controlled trial where the participants received daily elemental calcium (1,000 mg) plus vitamin D3 (800 IU). In addition, the participants were randomized to receive either capsules with vitamin D3 (20,000 IU) or matching placebos to be taken twice a week.

Patients

297 postmenopausal women with osteopenia or osteoporosis.

Measurements

Muscle strength (handgrip and knee extensor strength), balance (tandem test) and quality of life (EQ-5D) were measured at baseline and after 12 months. The subjects were genotyped for SNPs related to vitamin D metabolism.

Results

Of the 297 included women, 275 completed the study. Mean serum 25(OH)D levels dramatically increased in the high-dose group (from 64.7 to 164.1 nmol/l; p<0.01), while a more moderate increased was observed in the standard-dose group (from 64.1 to 81.8 nmol/l; p<0.01). There was no significant difference between the groups in change in muscular strength, balance or quality of life over the intervention period. Polymorphisms in rs3829251 (located in the 7-dehydrocholesterol reductase gene) was associated with muscle strength and treatment effects.

Conclusion

One-year treatment with high-dose vitamin D had no effect on muscular strength, balance or quality of life in postmenopausal women with osteopenia or osteoporosis as compared to standard-dose. The association between rs3829251 and muscle strength needs confirmation in other populations

This article is protected by copyright. All rights reserved.



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Primary lymphocytic hypophysitis: clinical characteristics and treatment of 50 cases in a single centre in China over 18 years

Summary

Objective

Primary lymphocytic hypophysitis (LYH) is rare and it is often evaluated in a small case series. This study aimed to describe the diagnosis and treatment of primary LYH in a larger cohort.

Design

A retrospective study of the diagnosis and treatment of primary LYH was conducted at Peking Union Medical College Hospital from 1999 to 2016.

Patients

Fifty patients (28 histologically-diagnosed and 22 clinically-diagnosed) were eligible for inclusion.

Measurements

Clinical, endocrine, pathological, and imaging findings; therapies and outcomes were assessed. Ordinal logistic regression analysis was used to evaluate the association between the clinical parameters and outcomes (e.g., improvements in pituitary function, regression of lesion size on MRI, and disease recurrence).

Results

Central diabetes insipidus (CDI) (72.0%) was the most common endocrine dysfunction. Hypogonadotropic hypogonadism (HH) was the most frequently observed (60.0%) manifestation of anterior pituitary dysfunction; adrenal insufficiency was the third most common (26.0%) manifestation; and IGF-1 axis defects were the least frequent (22.0%). Thickening of the pituitary stalk was the most frequent (96.0%) imaging finding, and 78.0% of the patients exhibited both intrasellar and suprasellar expansion. Pharmacological dose of glucocorticoids was identified to be significantly associated with increased odds of anterior pituitary function improvement. No observed covariates were significantly associated with improvement of CDI and recurrence.

Conclusion

The sequence of anterior pituitary deficiencies in Chinese primary LYH patients was atypical (LH/FSH > TSH > ACTH > IGF-1 axis deficiency). A pharmacological dose of glucocorticoids was significantly associated with the improved anterior pituitary insufficiency.

This article is protected by copyright. All rights reserved.



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Well Spotted: A New Look at the Cave Hyena

Fossils from Spain offer a rare look at Europe's extinct, bonecrushing carnivore.

-- Read more on ScientificAmerican.com
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Isolated crayfish are more resistant to the effects of alcohol

Crayfish forced to be solitary are less affected by alcohol, because being alone appears to alter the way their nerves function

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Non-Canonical Activation of NRF2: New Insights and Its Relevance to Disease

Abstract

Purpose of Review

The goal of this review is to summarize the current knowledge in the field regarding the non-canonical activation of the NRF2 pathway. Specifically, we address what role p62 plays in mediating this pathway, which pathologies have been linked to the p62-dependent activation of NRF2, as well as what therapeutic strategies could be used to treat diseases associated with the non-canonical pathway.

Recent Findings

It has recently been shown that autophagic dysfunction leads to the aggregation or autophagosomal accumulation of p62, which sequesters KEAP1, resulting in prolonged activation of NRF2. The ability of p62 to outcompete NRF2 for KEAP1 binding depends on its abundance, or post-translational modifications to its key domains. Furthermore, the relevance of the p62-dependent activation of NRF2 in disease has been demonstrated in human hepatocellular carcinomas, as well as neurodegenerative diseases.

Summary

These findings indicate that targeting p62, or the enzymes that modify it, could prove to be an advantageous strategy for treating diseases associated with autophagy dysregulation and prolonged activation of NRF2. Other therapeutic possibilities include restoring proper autophagic function, or directly inhibiting NRF2 or its targets, to restore redox and metabolic homeostasis. Future studies will help further clarify the mechanisms, regulation, and relevance of the non-canonical pathway in driving disease pathogenesis.



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Erratum to: Laparoscopic image-based navigation for microwave ablation of liver tumors: A multi-center study



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Delayed closure of open abdomen in septic patients treated with negative pressure wound therapy and dynamic fascial suture: the long-term follow-up study

Abstract

Introduction

Negative pressure wound therapy (NPWT) is widely used in the treatment of open abdomen (OA). The use of dynamic fascial sutures (DFS) increases the rate of successful delayed closure by reducing fascial lateralization. We recently published a prospective controlled trial including 87 patients undergoing abdominal surgery for secondary peritonitis between 2007 and 2012. Patients were treated with NPWT and DFS for approximation of fascial edges. The present study represents a follow-up assessment of these patients 5–9 years after OA treatment with NPWT and DFS.

Methods

The 39 patients still alive were included in the recent study according to the protocol of our last study in 2013. All patients received a questionnaire regarding long-term complications after OA treatment between 2007 and 2012. Mean follow-up was 5–9 years. Analyzed parameters included pain, the presence of incisional hernia, and subsequent surgical interventions. Results were analyzed quantitatively.

Results

One patient had deceased since the last publication in 2013, and hence 38 patients were included in the current study. The median age was 60.9 (25.2–86.1) years, and 17 (44.7%) were females. Overall 56.3% of the original 87 patients had died during the long-term follow-up period. 21 patients (55.3%) answered the questionnaire. Six (28.6%) declared that they suffered from pain in the previous operating field, five (23.8%) at rest, and three (14.3%) during exercise. In five patients (23.8%), pain lasted for more than 3 months. One patient (4.8%) still requires analgesic treatment. Among the 21 patients, seven (33.3%) were found to have incisional hernias. Three hernias (42.9%) were treated by surgery.

Conclusion

Incisional hernia rates after OA treatment remain high, but are accompanied by little pain. The ideal technique of fascial closure after NPWT should be investigated in further research.



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Comparison of clinical outcomes and quality of life between laparoscopic and open central pancreatectomy with pancreaticojejunostomy

Abstract

Background

The studies comparing laparoscopic and open central pancreatectomy with pancreaticojejunostomy are limited. This study aimed to compare clinical outcomes and quality of life of patients undergoing laparoscopic and open central pancreatectomy with pancreaticojejunostomy.

Methods

Between December 1997 and December 2015, patients who underwent central pancreatectomy with pancreaticojejunostomy were reviewed. Patients were divided into 2 groups as laparoscopic central pancreatectomy (LCP) and open central pancreatectomy (OCP). Data considered for comparison analysis were patient demographics, intraoperative variables, morbidity, postoperative hospital stay, mortality, pathologic findings, and quality of life (SF-36 questionnaire).

Results

Thirty-six patients (17 LCP and 19 OCP) were included in the final analysis. Baseline characteristics were similar in the 2 groups. The operating time (280.4 ± 33.6 vs. 290.5 ± 62.5 min, p = 0.455) were similar between two groups. LCP group showed significantly lower estimated blood loss (76.4 ± 70.3 vs. 390.3 ± 279.0 ml, p = 0.001), shorter first flatus time (2.4 ± 0.9 vs. 3.9 ± 1.3 days, p = 0.001), and shorter diet start time (4.1 ± 2.2 vs. 6.1 ± 2.4 days, p = 0.030). However, the postoperative hospital stay was not significantly different between two groups (15.6 ± 12.1 vs. 24.0 ± 27.5 days, p = 0.347). Postoperative outcomes, including morbidity (58.8 vs. 52.6%, p = 0.749), pancreatic fistula rates (≥grade B: 17.6 vs. 36.8%, p = 0.106), and mortality, were similar in the 2 groups. The median follow-up period was 45 months (range 4–216 months). No local recurrence or distant metastasis was detected in either group. On the follow-up survey, the total quality of life score (702.9 ± 47.9 vs. 671.8 ± 94.1), physical health score (353.9 ± 24.8 vs. 326.6 ± 67.6) and mental health score (349.0 ± 26.5 vs. 345.2 ± 34.6) were higher in the LCP group compared with the OCP group. However, these differences were not statistically significant (p > 0.05). The score in role physical (100 vs. 73.1 ± 4.8, p = 0.042) was significantly higher in LCP group, and not statistically significant in other areas (p > 0.05).

Conclusions

LCP with pancreaticojejunostomy is safe and feasible for benign or borderline malignant lesions in the pancreatic neck and proximal body. Compared to OCP, LCP is associated with lower estimated blood loss, faster recovery, and better quality of life.



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A Pathway to Personalizing Therapy for Metastases Using Liver-on-a-Chip Platforms

Abstract

Metastasis accounts for most cancer-related deaths. The majority of solid cancers, including those of the breast, colorectum, prostate and skin, metastasize at significant levels to the liver due to its hemodynamic as well as tumor permissive microenvironmental properties. As this occurs prior to detection and treatment of the primary tumor, we need to target liver metastases to improve patients' outcomes. Animal models, while proven to be useful in mechanistic studies, do not represent the heterogeneity of human population especially in drug metabolism lack proper human cell-cell interactions, and this gap between animals and humans results in costly and inefficient drug discovery. This underscores the need to accurately model the human liver for disease studies and drug development. Further, the occurrence of liver metastases is influenced by the primary tumor type, sex and race; thus, modeling these specific settings will facilitate the development of personalized/targeted medicine for each specific group. We have adapted such all-human 3D ex vivo hepatic microphysiological system (MPS) (a.k.a. liver-on-a-chip) to investigate human micrometastases. This review focuses on the sources of liver resident cells, especially the iPS cell-derived hepatocytes, and examines some of the advantages and disadvantages of these sources. In addition, this review also examines other potential challenges and limitations in modeling human liver.



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Blastocyst-Derived Stem Cell Populations under Stress: Impact of Nutrition and Metabolism on Stem Cell Potency Loss and Miscarriage

Abstract

Data from in vitro and in vivo models suggest that malnutrition and stress trigger adaptive responses, leading to small for gestational age (SGA) blastocysts with fewer cell numbers. These stress responses are initially adaptive, but become maladaptive with increasing stress exposures. The common stress responses of the blastocyst-derived stem cells, pluripotent embryonic and multipotent placental trophoblast stem cells (ESCs and TSCs), are decreased growth and potency, and increased, imbalanced and irreversible differentiation. SGA embryos may fail to produce sufficient antiluteolytic placental hormone to maintain corpus luteum progesterone secretion that provides nutrition at the implantation site. Myriad stress inputs for the stem cells in the embryo can occur in vitro during in vitro fertilization/assisted reproductive technology (IVF/ART) or in vivo. Paradoxically, stresses that diminish stem cell growth lead to a higher level of differentiation simultaneously which further decreases ESC or TSC numbers in an attempt to functionally compensate for fewer cells. In addition, prolonged or strong stress can cause irreversible differentiation. Resultant stem cell depletion is proposed as a cause of miscarriage via a "quiet" death of an ostensibly adaptive response of stem cells instead of a reactive, violent loss of stem cells or their differentiated progenies.



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The importance of optic nerve sheath hemorrhage as a postmortem finding in cases of fatal abusive head trauma: a 13-year study in a tertiary hospital

Physical child abuse is a major cause of death in infants and toddlers. Up to 80% of fatal child abuse cases are due to abusive head trauma.[1–3] The mechanism of injury in cases of abusive head trauma may result from severe rotational and translational acceleration due to vigorous shaking (non-contact force), direct impact (contact force), or a combination of both.[2,4] Generally, an initial given history in correlation with the mechanism of injury is usually inadequate and not reliable in most cases of child abuse.

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Isolated crayfish are more resistant to the effects of alcohol

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Crayfish forced to be solitary are less affected by alcohol, because being alone appears to alter the way their nerves function

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Shape-Controlled Metal-Free Catalysts: Facet-Sensitive Catalytic Activity Induced by the Arrangement Pattern of Noncovalent Supramolecular Chains

TOC Graphic

ACS Nano
DOI: 10.1021/acsnano.7b01427
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In lasting tribute: Dr James J. Lee (1958-2017)

It is with deep sorrow that we report the untimely death of our friend and colleague Dr James (Jamie) Lee, who passed away on Saturday, March 25, 2017, at his home in Scottsdale, Arizona.

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Biomechanical Flow Amplification Arising From the Variable Deformation of the Subglottic Mucosa

This study mapped the variation in tissue elasticity of the subglottic mucosa, applied these data to provide initial models of the likely deformation of the mucosa during the myoelastic cycle, and hypothesized as to the impact on the process of phonation.

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Association between active commuting and incident cardiovascular disease, cancer, and mortality: prospective cohort study

Objective To investigate the association between active commuting and incident cardiovascular disease (CVD), cancer, and all cause mortality.Design Prospective population based study. Setting UK...
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