Τετάρτη, 30 Μαρτίου 2016

Perception of speech in cartilage conduction.

Perception of speech in cartilage conduction.

Auris Nasus Larynx. 2016 Mar 25;

Authors: Miyamae R, Nishimura T, Hosoi H, Saito O, Shimokura R, Yamanaka T, Kitahara T

Abstract
OBJECTIVE: By attaching a transducer to the aural cartilage a relatively loud sound is audible even with a negligibly small fixation pressure applied to the transducer. This form of conduction is referred to as cartilage conduction (CC). Utilizing CC, novel audio devices can be developed, and one possible application is a CC hearing aid. However, there are no studies on speech perception in CC. In this study, CC speech recognition performance was measured and compared with that for air and bone conduction (AC and BC, respectively).
METHODS: Nine volunteers with normal hearing participated in the study. The performance-intensity functions were measured for AC, BC and CC. These measurements were performed in the conditions with and without an earplug.
RESULTS: Without the earplug, no differences in speech recognition scores were observed among AC, BC, and CC. With the earplug, the level at which the maximum speech recognition score was obtained did not increase in CC, which agreed with the result of BC but not AC. The maximum speech recognition CC score decreased with the earplug. The performance-intensity functions for AC and BC shifted in parallel with the earplug. These shifts approximated the average threshold shifts. In contrast, for CC, the performance-intensity function did not shift in parallel with the earplug. As for the CC threshold shifts with the earplug, although the threshold at 500Hz decreased by 15.4dB, those at 2000 and 4000Hz increased by 13.8 and 31.1dB, respectively. Compared with AC and BC, CC excessively emphasized low over high frequency sounds when the earplug was inserted. Confusion matrices analysis demonstrated that 4%, 22%, and 74% of the errors occurred at low, intermediate, and high frequency speech sounds, respectively. Thus, this excessive low frequency sound emphasis probably prevented the recognition of high frequency speech sounds.
CONCLUSION: The decrease in the maximum speech recognition score for CC with the earplug was derived from the biased frequency composition. It can be improved by frequency composition adjustment.

PMID: 27021264 [PubMed - as supplied by publisher]



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Adenylyl Cyclase-Associated Protein 1 in the Development of Head and Neck Squamous Cell Carcinomas.

Adenylyl Cyclase-Associated Protein 1 in the Development of Head and Neck Squamous Cell Carcinomas.

Bull Exp Biol Med. 2016 Mar 29;

Authors: Kakurina GV, Kondakova IV, Cheremisina OV, Shishkin DA, Choinzonov EL

Abstract
We compared the content of adenylyl cyclase-associated protein 1 (CAP1) in the blood and tissues of patients with head and neck squamous cell carcinomas (with and without regional metastases), patients with chronic inflammatory diseases aggravated by laryngeal and laryngopharyngeal dysplasia, and healthy individuals. The data suggest that serum CAP1 concentration correlated with the depth of primary tumor invasion and the presence of regional metastases. In cancer patients, the serum level of CAP1 was lower than in patients with laryngeal and laryngopharyngeal dysplasia, which can be of importance for differential and timely diagnostics of malignant tumors.

PMID: 27021082 [PubMed - as supplied by publisher]



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IJMS, Vol. 17, Pages 457: Meta-Analysis on Associations of RGS1 and IL12A Polymorphisms with Celiac Disease Risk

The pathogenesis of celiac disease (CD) has been related to polymorphisms in the regulator of G-protein signaling 1 (RGS1) and interleukin-12 A (IL12A) genes, but the existing findings are inconsistent. Our aim is to investigate the associations of two single-nucleotide polymorphisms (SNPs) (rs2816316 in RGS1 and rs17810546 in IL12A) with CD risk using meta-analysis. We searched PubMed and Web of Science on RGS1 rs2816316 and IL12A rs17810546 with CD risk. Odds ratio (OR) and 95% confidence interval (CI) of each SNP were estimated. All statistical analyses were performed on Stata 12.0. A total of seven studies were retrieved and analyzed. The available data indicated the minor allele C of rs2816316 was negatively associated with CD (C vs. A: OR = 0.77, 95% CI = 0.74–0.80), and a positive association was found for the minor allele G of rs17810546 (G vs. A: OR = 1.37, 95% CI = 1.31–1.43). The co-dominant model of genotype effect confirmed the significant associations between RGS1 rs2816316/IL12A rs17810546 and CD. No evidence of publication bias was observed. Our meta-analysis supports the associations of RGS1 and IL12A with CD and strongly calls for further studies to better understand the roles of RGS1 and IL12A in the pathogenesis of CD.

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IJMS, Vol. 17, Pages 463: Exploring Erythropoietin and G-CSF Combination Therapy in Chronic Stroke Patients

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Erythropoietin (EPO) and granulocyte-colony stimulating factor (G-CSF) are known to have neuroprotective actions. Based on previous reports showing the synergistic effects of EPO+G-CSF combination therapy in experimental models, we investigated the safety of EPO+G-CSF combination therapy in patients with chronic stroke. In a pilot study, 3 patients were treated with EPO and G-CSF for 5 consecutive days, with follow-up on day 30. In an exploratory double-blind study, 6 patients were allocated to treatment with either EPO+G-CSF or placebo. Treatment was applied once a day for 5 days per month over 3 months. Participants were followed up for 6 months. To substantiate safety, vital signs, adverse events, and hematological values were measured on days 0, 5, and 30 in each cycle and on day 180. Functional outcomes were determined on day 0 and 180. In the laboratory measurements, EPO+G-CSF combination therapy significantly elevated erythropoietin, CD34+ hematopoietic stem cells, white blood cells, and neutrophils on day 5 of each cycle. There were no observations of serious adverse events. In the functional outcomes, the grip power of the dominant hand was increased in the EPO+G-CSF treatment group. In conclusion, this exploratory study suggests a novel strategy of EPO+G-CSF combination therapy for stroke patients.

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IJMS, Vol. 17, Pages 473: Fluorescence-Lifetime Imaging Microscopy for Visualization of Quantum Dots’ Endocytic Pathway

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Accumulation of carboxylated polyethylene glycol (PEG) CdSe/ZnSquantum dots (QDs) has been monitored in living fibroblasts using confocal microscopy for fluorescence intensity and fluorescence-lifetime imaging (FLIM). The wide range of mean photoluminescence (PL) lifetime values was observed for the intracellular QDs in different intracellular microenvironment, which revealed structural heterogeneity of endosomes and enabled the distinguishing among endosomes of different maturity.

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Statement published on pairing smoking cessation with lung cancer screening

Researchers, including an associate professor from the Medical University of South Carolina Hollings Cancer Center, say smokers who go to a doctor to be screened for lung cancer should also be encouraged to quit smoking during their visit, according to a...

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Researchers found new clue to fighting acute myeloid leukaemia

A study led by researchers from the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore (NUS) has uncovered a new clue that may help fight acute myeloid leukaemia (AML), the most common form of cancer of the blood...

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Annular erythematous eruption with a high response to mosquito bite



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Orange pigmentation spots on the sole may be from a stink bug



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Levels of immunoglobulin E specific to the major food allergen and chemokine (C-C motif) ligand (CCL)17/thymus and activation regulated chemokine and CCL22/macrophage-derived chemokine in infantile atopic dermatitis on Ishigaki Island

Abstract

Atopic dermatitis (AD) is a multifactorial T-helper (Th)2-mediated skin disease frequently associated with elevated serum immunoglobulin (Ig)E and food allergy is also a Th2- and IgE-mediated adverse immunological reaction. Our previous study indicated the relation of egg allergy history and disease severity of AD. Thus, the purpose of the study was to investigate the levels of IgE specific to major food allergens (egg, milk, wheat) and Th2 chemokines (chemokine [C-C motif] ligand [CCL]17/thymus and activation regulated chemokine [TARC] and CCL22/macrophage-derived chemokine [MDC]) and the relationship between them. A total of 743 nursery school children were enrolled. Dermatologist-based physical examination and a questionnaire survey were also conducted. Significantly increased levels of disease severity markers (CCL17/TARC and CCL22/MDC) were confirmed in children with AD. The levels of CCL22/MDC in all of the children were markedly high compared with those reported in adults. IgE specific to egg white, ovomucoid, wheat and mite antigen were significantly higher in the AD group than in the non-AD group. Among them, IgE specific to egg allergens were well associated with disease severity markers, and IgE specific to ovomucoid seemed particularly well correlated with the presence of egg allergy history. In conclusion, the markedly high level of CCL22/MDC in children as compared with those reported in adults may partly explain the AD-prone nature of children and their spontaneous remission afterwards. Mild but significant correlation of IgE specific to egg allergens and Th2 chemokines may explain correlation of disease severity and comorbidity of egg allergy in our previous study.



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Relationship between androgenetic alopecia and cardiovascular risk factors according to BASP classification in Koreans

Abstract

There have been many studies on the relationship between androgenetic alopecia (AGA) and cardiovascular risk factors, but the study results were inconsistent and research on AGA in Asians remains insufficient. This study investigated the relationship between Korean AGA and various cardiovascular risk factors, considering life habits, type of hair loss and sex. We investigated subjects who visited a hospital for public or industrial health medical examinations between October 2012 and December 2014. A questionnaire as well as anthropometric measurements and a blood test were performed. Among the 1884 total subjects, 52.6% had AGA. AGA patients displayed a significantly higher prevalence rate of cardiovascular diseases, smoking rate, fasting glucose and triglyceride, and a significantly lower high-density lipoprotein cholesterol level than did the non-AGA group. The results of the subgroup analysis showed higher prevalence rates of hypertension, stroke, metabolic syndrome and smoking in male AGA patients. The more severe the AGA, the higher the incidences of hypertension, diabetes and smoking were observed. According to the analysis results by BASP classification, the F-type AGA patients displayed a higher body mass index, waist circumference and diastolic blood pressure, and had a significantly higher prevalence rate of hypertension. As a result of the large population-based study, modifications in lifestyle and early screening for cardiovascular disease, as well as hypertension and diabetes, are suggested.



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Generalized keratosis pilaris-like eruptions in a chronic myelogenous leukemia patient treated with nilotinib



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Persistent supravenous erythematous eruption-like changes from antibiotics



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Photolysis quantum yield measurements in the near-UV; a critical analysis of 1-(2-nitrophenyl)ethyl photochemistry

Photochem. Photobiol. Sci., 2016, Accepted Manuscript
DOI: 10.1039/C5PP00440C,
John E. T. Corrie, Jack Kaplan, Biff Forbush, David Ogden, David Trentham
None
The content of this RSS Feed (c) The Royal Society of Chemistry


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Viruses, Vol. 8, Pages 93: Enterovirus Control of Translation and RNA Granule Stress Responses

Enteroviruses such as poliovirus (PV) and coxsackievirus B3 (CVB3) have evolved several parallel strategies to regulate cellular gene expression and stress responses to ensure efficient expression of the viral genome. Enteroviruses utilize their encoded proteinases to take over the cellular translation apparatus and direct ribosomes to viral mRNAs. In addition, viral proteinases are used to control and repress the two main types of cytoplasmic RNA granules, stress granules (SGs) and processing bodies (P-bodies, PBs), which are stress-responsive dynamic structures involved in repression of gene expression. This review discusses these processes and the current understanding of the underlying mechanisms with respect to enterovirus infections. In addition, the review discusses accumulating data suggesting linkage exists between RNA granule formation and innate immune sensing and activation.

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NHS is unprepared for risks posed by climate change, warn leading UK health bodies

A newly formed coalition of leading UK health bodies has written to England’s health secretary, Jeremy Hunt, to urge that the NHS should be better prepared to deal with climate change risks.The UK...
recent?d=yIl2AUoC8zA recent?d=dnMXMwOfBR0 recent?i=5AjB6mhoNhM:TQN-T-jkho0:V_sGLiP recent?d=qj6IDK7rITs recent?i=5AjB6mhoNhM:TQN-T-jkho0:gIN9vFw recent?d=l6gmwiTKsz0 recent?d=7Q72WNTAKBA recent?i=5AjB6mhoNhM:TQN-T-jkho0:F7zBnMy recent?i=5AjB6mhoNhM:TQN-T-jkho0:-BTjWOF


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Five minutes with . . . Ian Green

“We’re shocked that NHS England has abandoned its own process for the approval of pre-exposure prophylaxis (PrEP) for HIV. PrEP is a real game changer: it could revolutionise the prevention of HIV....
recent?d=yIl2AUoC8zA recent?d=dnMXMwOfBR0 recent?i=YiOaQCvFl20:b_VtRjrQemI:V_sGLiP recent?d=qj6IDK7rITs recent?i=YiOaQCvFl20:b_VtRjrQemI:gIN9vFw recent?d=l6gmwiTKsz0 recent?d=7Q72WNTAKBA recent?i=YiOaQCvFl20:b_VtRjrQemI:F7zBnMy recent?i=YiOaQCvFl20:b_VtRjrQemI:-BTjWOF


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The Laplacian-Energy-Like Invariants of Three Types of Lattices

This paper mainly studies the Laplacian-energy-like invariants of the modified hexagonal lattice, modified Union Jack lattice, and honeycomb lattice. By utilizing the tensor product of matrices and the diagonalization of block circulant matrices, we derive closed-form formulas expressing the Laplacian-energy-like invariants of these lattices. In addition, we obtain explicit asymptotic values of these invariants with software-aided computations of some integrals.

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Generalized Fractional Integral Operators and -Series

Two fractional integral operators associated with Fox -function due to Saxena and Kumbhat are applied to -series, which is an extension of both Mittag-Leffler function and generalized hypergeometric function . The Mellin and Whittaker transforms are obtained for these compositional operators with -series. Further some interesting properties have been established including power function and Riemann-Liouville fractional integral operators. The results are expressed in terms of -function, which are in compact form suitable for numerical computation. Special cases of the results are also pointed out in the form of lemmas and corollaries.

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Physiological and Biochemical Changes in Moth Bean (Vigna aconitifolia L.) under Cadmium Stress

Moth bean (Vigna aconitifolia L.), a drought resistant legume, possesses high nutritional value. Cadmium (Cd) is a nonessential and the most toxic heavy metal in plants. The present study was to test the hypothesis of whether moth bean being a drought resistant legume can withstand the cadmium stress. Ten-day-old moth bean seedlings were subjected to cadmium stress and investigated for a period of 15 days every 3-day intervals. Cadmium quantification in moth bean tissues suggests root accumulation and translocation to aerial parts in a concentration dependent manner. Results of physiological and biochemical studies revealed that cadmium has affected the growth parameters like shoot and root lengths and tissue dry weights. Significant alternations in relative water content and cell membrane stability were observed in stressed seedlings. Similarly superoxide radical, lipoxygenase activity, membrane lipid peroxidation products, protein carbonyls, and reduced glutathione and nonprotein thiols were found increased in stressed seedlings compared to controls. However, hydrogen peroxide and ascorbic acid levels were not altered significantly in both stressed and control seedlings. Cadmium translocation ability from roots to aerial parts and elevated levels of nonenzymatic antioxidants in stressed seedlings suggest the cadmium stress withstanding ability of moth bean.

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Redox Signaling and Neural Control of Cardiovascular Function



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KvLEA, a New Isolated Late Embryogenesis Abundant Protein Gene from Kosteletzkya virginica Responding to Multiabiotic Stresses

The LEA proteins are a kind of hydrophilic proteins, playing main functions in desiccation tolerance. However, their importance as a kind of stress proteins in abiotic stress is being clarified little by little. In this study we isolated, cloned, and identified the first KvLEA gene in Kosteletzkya virginica. Bioinformatic analysis showed that the protein encoded by this gene had common properties of LEA proteins and the multiple sequences alignment and phylogenetic analysis further showed that this protein had high homology with two Arabidopsis LEA proteins. Gene expression analysis revealed that this gene had a higher expression in root and it was induced obviously by salt stress. Moreover, the transcripts of KvLEA were also induced by other abiotic stresses including drought, high temperature, chilling, and ABA treatment. Among these abiotic stresses, ABA treatment brought about the biggest changes to this gene. Collectively, our research discovered a novel LEA gene and uncovered its involvement in multiabiotic stresses in K. virginica. This research not only enriched studies on LEA gene in plant but also would accelerate more studies on K. virginica in the future.

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Immobilization of dehydrogenase onto epoxy-functionalized nanoparticles for synthesis of (R)-mandelic acid

Publication date: July 2016
Source:International Journal of Biological Macromolecules, Volume 88
Author(s): Xiao-Ping Jiang, Ting-Ting Lu, Cai-Hong Liu, Xiao-Ming Ling, Meng-Yao Zhuang, Jiu-Xun Zhang, Ye-Wang Zhang
Epoxy functionalized magnetic Fe3O4@SiO2 nanoparticles were successfully prepared and characterized by Fourier-transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM). The prepared nanoparticles were used for immobilization of alcohol dehydrogenase (ADH) from Saccharomyces cerevisiae by covalent attachment. The optimal immobilization conditions were obtained as follows: enzyme/support 4.49mg/g, pH 8.0, buffer concentration 0.05M, time 12h and temperature 30°C. Under these conditions, a high immobilization yield and efficiency of above 92% were obtained after the optimization. Broad pH tolerance and high thermostability were achieved by the immobilization. The immobilized ADH retained about 84% initial activity after five cycles. Kinetic parameters Vmax and Km of free and immobilized ADH were determined as 56.72μM/min, 44.27μM/min and 11.54mM, 31.32mM, respectively. (R)-mandelic acid synthesis with the immobilized ADH was carried out, and the yield of (R)-mandelic acid was as high as 64%. These results indicate that the ADH immobilized onto epoxy-functionalized nanoparticles is an efficient and simple way for preparation of stable ADH, and the immobilized ADH has potential applications in the production of (R)-mandelic acid.



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Biomolecule-loaded chitosan nanoparticles induce apoptosis and molecular changes in cancer cell line (SiHa)

Publication date: July 2016
Source:International Journal of Biological Macromolecules, Volume 88
Author(s): Anbu Sujima Anbu, Palanivel Velmurugan, ​Jeong-Ho Lee, Byung-Taek Oh, Perumal Venkatachalam
The present study reports on the synthesis of chitosan nanoparticles (CNPs) using methanol extracts of Gymnema sylvestre (GS) leaves and Cinnamomum zeylanicum (CZ) bark. Biomolecule-loaded nanoparticles induced apoptosis in a human cervical cancer (SiHa) cell line, and experiments were carried out to elucidate the underlying molecular mechanisms. FT-IR and XRD showed possible functional groups of the biomolecules and the crystalline nature of CNPs, respectively. Transmission electron microscopy images revealed that synthesized GSCNPs and CZCNPs had a smooth spherical shape with average sizes of about 58–80 and 60–120nm, respectively. Dynamic light scattering studies indicated that both GSCNPs and CZCNs were structurally stable with homogenous and heterogeneous natures, respectively. Furthermore, synthesized GSCNPs and CZCNPs exhibited dose-dependent cytotoxicity against the SiHa cancer cell line, with inhibitory concentration (IC50) values of 102.17μg/ml, 87.75μg/ml, 132.74μg/ml and 90.35μg/ml for GS leaf extract, GSCNPs, CZBE and CZCNPs, respectively.



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Control of microbiological corrosion on carbon steel with sodium hypochlorite and biopolymer

Publication date: July 2016
Source:International Journal of Biological Macromolecules, Volume 88
Author(s): Sara H. Oliveira, Maria Alice G.A. Lima, Francisca P. França, Magda R.S. Vieira, Pulkra Silva, Severino L. Urtiga Filho
In the present work, the interaction of a mixture of a biocide, sodium hypochlorite (NaClO), and a biopolymer, xanthan, with carbon steel coupons exposed to seawater in a turbulent flow regime was studied. The cell concentrations, corrosion rates, biomasses, and exopolysaccharides (EPSs) produced on the coupon surfaces with the various treatments were quantified. The corrosion products were evaluated using X-ray diffraction (XRD), and the surfaces of steels were analysed by scanning electron microscopy (SEM). The results indicated that xanthan and the hypochlorite-xanthan mixture reduced the corrosion rate of steel.



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Crystal structure and dynamics of Spt16N-domain of FACT complex from Cicer arietinum

Publication date: July 2016
Source:International Journal of Biological Macromolecules, Volume 88
Author(s): Venkat N. Are, Biplab Ghosh, Ashwani Kumar, Rekha Gadre, Ravindra D. Makde
The facilitates chromatin transcription (FACT) complex, a heterodimer of SSRP1 and Spt16 proteins, is an essential histone chaperone that transiently reorganizes nucleosomes during transcription, replication and repair. N-terminal domain of Spt16 subunit (Spt16N) is strictly conserved in all the known Spt16 orthologs. Genetic studies in yeast have revealed a partially redundant role of Spt16N for the FACT functionality. Here, we report the crystal structure of Spt16N from a plant origin (Spt16Nca, Cicer arietinum) and its comparisons with the known Spt16N structures from yeasts and human. The inter-domain angle in Spt16Nca is significantly different from that of the yeast and human Spt16N structures. Normal mode analysis and classical molecular dynamics simulations reveal inter-domain movement in Spt16Nca and later also shows conformational flexibility of the critical loops. Spt16Nca binds to histone H3/H4 complex, similar to its orthologs from yeast and human origins. Further, conservation of electrostatic surface potentials in Spt16N structures from evolutionary distinct domains of eukaryotes (plant, human and fungi) have provided the potential sites on Spt16N for histone interactions. The structural comparisons with M24 peptidases show that the hydrophobic pocket shielded by a flexible loop of C-terminal domain of Spt16N that may be functionally important.



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Extraction of Angelica sinensis polysaccharides using ultrasound-assisted way and its bioactivity

Publication date: July 2016
Source:International Journal of Biological Macromolecules, Volume 88
Author(s): Ying Zhao, Yongyong Shi, Huixin Yang, Lijuan Mao
In the present article, ultrasound-assisted extraction (UAE) of polysaccharides from Angelica sinensis were investigated. The aim of the study is to examine the extraction parameters such as ultrasound power (140–180W), the ratio of liquid to solid (5–7), extraction time (40–50min) and extraction temperature (80–100°C) and to obtain the best possible combinations of these parameters through response surface methodology (RSM). Based on contour plots and variance analysis, optimum operational conditions for maximizing polysaccharides yield were found to be 180w, 7, 45min and 90°C. Under the optimum operating conditions determined, 6.96% polysaccharides were achieved. In addition, the results showed that A. sinensis polysaccharides (ASP) could increase antioxidant enzymes activities and decrease the MDA levels in the skeletal muscle of exhaustive exercise rats. This study provides strong evidence that A. sinensis polysaccharides supplementation possessed protective effects against exhaustive exercise-induced oxidative stress.



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Understanding the structure and digestibility of heat-moisture treated starch

Publication date: July 2016
Source:International Journal of Biological Macromolecules, Volume 88
Author(s): Hongwei Wang, Binjia Zhang, Ling Chen, Xiaoxi Li
To rationalize the effects of heat-moisture treatment (HMT) on starch digestibility, the HMT-induced alterations in the mesoscopic and molecular scale structures of regular and high-amylose maize starches, as well as in their digestibility, were evaluated. Accompanying the supramolecular structural disorganizations and certain molecular degradation induced by HMT, somewhat molecular rearrangements occurred to probably form densely packed starch fractions, which eventually weakened starch digestion and thus transformed RDS into SDS and RS for regular and high-amylose starches. Interestingly, due to its larger amount of inter-helical water molecules that could be induced by HMT, B-polymorphic high-amylose starch was more susceptible to HMT (relative A-polymorphic regular starch), causing more prominent structural evolutions including molecular re-assembly and thus increasingly slowed digestion. In particular, the treated high-amylose starch with 30% moisture content showed a high SDS+RS content (48.3%). The results indicate that HMT-treated starch may serve as a functional ingredient with adjustable enzymatic digestibility for various food products.



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Comprehensive study on the structure of the BSA from extended-to aged form in wide (2–12) pH range

Publication date: July 2016
Source:International Journal of Biological Macromolecules, Volume 88
Author(s): N. Varga, V. Hornok, D. Sebők, I. Dékány
In this work we studied the structure of the bovine serum albumin (BSA) and the protein-ligand interactions since researchers prefer to use them as carriers in drug delivery systems. Systematic study (between pH 2–12, in double distilled water and physiological salt solution) was carried out to determine the changes in the secondary and the tertiary structures of the BSA, the apparent molecular weight (Mw), the size (dLS) and the electrokinetic potential (ζ). At pH 7, the BSA has higher stability in the absence (ζ=−69mV, dLS=2.2nm, A2=1.4×10−3mlmol/g2) than in the presence of salt solution (ζ=−2.4mV, dLS=5.3nm, A2=−3.2×10−4mlmol/g2). The Mw strongly depends on the pH and the ionic strength (at pH 3 in the absence of salt, the Mw is 54.6kDa while in the presence of salt is 114kDa) which determines the geometry of the protein. The protein-ligand interactions were characterized by fluorescence (FL) and isothermal microcalorimetry (ITC) methods; these independent techniques provided similar thermodynamic parameters such as the binding constant (K) and the Gibbs free energy (ΔG).



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A study on the adsorption of methylene blue onto gum ghatti/TiO2 nanoparticles-based hydrogel nanocomposite

Publication date: July 2016
Source:International Journal of Biological Macromolecules, Volume 88
Author(s): Hemant Mittal, Suprakas Sinha Ray
The objective of this work was to study the isotherm and kinetic models for the adsorption of methylene blue (MB) onto a TiO2 nanoparticle (TiO2NP)-containing hydrogel nanocomposite (HNC) of polyacrylamide-grafted gum ghatti (PAAm-g-Gg). The grafting of PAAm onto Gg was conducted using N,N’-methylene-bis-acrylamide (MBA) as a crosslinker, and different weight percentages of TiO2NPs were incorporated into the hydrogel matrix during the grafting reaction. The graft co-polymerization and the formation of the HNC were confirmed using FTIR, XRD, BET, SEM, TEM and EDS analyses. The adsorption of MB was studied in batch mode and it was found to be highly dependent on solution pH, ionic strength temperature and adsorbent loading. The MB-adsorption process followed the pseudo-second-order rate model and Langmuir adsorption isotherm with a maximum adsorption capacity of 1305.5mgg−1. Thermodynamic studies revealed that the adsorption of MB onto the HNC surface was spontaneous, endothermic and through a process of physisorption. The results also showed that the HNC was much more effective for the adsorption of cationic dyes than anionic dyes, and it retained its original adsorption capacity for five successive cycles of adsorption-desorption. In conclusion, the hydrogel nanocomposite showed huge potential for remediating industrial wastewater polluted by toxic cationic dyes.



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C. butyricum lipoteichoic acid inhibits the inflammatory response and apoptosis in HT-29 cells induced by S. aureus lipoteichoic acid

Publication date: July 2016
Source:International Journal of Biological Macromolecules, Volume 88
Author(s): Jinbo Wang, Lili Qi, Lehe Mei, Zhige Wu, Hengzheng Wang
Lipoteichoic acid (LTA) is one of microbe-associated molecular pattern (MAMP) molecules of gram-positive bacteria. In this study, we demonstrated that Clostridium butyricum LTA (bLTA) significantly inhibited the inflammatory response and apoptosis induced by Staphylococcus aureus LTA (aLTA) in HT-29 cells. aLTA stimulated the inflammatory responses by activating a strong signal transduction cascade through NF-κB and ERK, but bLTA did not activate the signaling pathway. bLTA pretreatment inhibited the activation of the NF-κB and ERK signaling pathway induced by aLTA. The expression and release of cytokines such as IL-8 and TNF-α were also suppressed by bLTA pretreatment. aLTA treatment induced apoptosis in HT-29 cells, but bLTA did not affect the viability of the cells. Further study indicated that bLTA inhibited apoptosis in HT-29 cells induced by aLTA. These results suggest that bLTA may act as an aLTA antagonist and that an antagonistic bLTA may be a useful agent for suppressing the pro-inflammatory activities of gram-positive pathogenic bacteria.



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Biosynthesis, spectral properties and thermostability of cyanobacterial allophycocyanin holo-α subunits

Publication date: July 2016
Source:International Journal of Biological Macromolecules, Volume 88
Author(s): Huaxin Chen, Qiuzi Liu, Jin Zhao, Peng Jiang
Allophycocyanin (APC) is generally used as fluorescent labels. In this study, apcA genes from a mesophilic cyanobacterium Synechocystis sp. PCC 6803 and a thermophilic cyanobacterium Thermosynechococcus elongatus BP-1 were cloned into expression vectors to construct pathway for biosynthesis of allophycocyanin holo-α subunits (named as holo-ApcAS for Synechocystis sp. PCC 6803 and holo-ApcAT for T. elongatus BP-1) in Escherichia coli. The two holo-ApcAs were successfully reconstituted in E. coli and purified by metal affinity chromatography. Spectral analysis showed that the two proteins have similar spectroscopic properties, with absorbance maximum both at 614nm and emission maximum at 639nm for holo-ApcAS and 638nm for holo-ApcAT. At high temperature, the recombinant holo-ApcAT was much more stable than the recombinant holo-ApcAS. Holo-ApcAS was most fluorescent at pH 8.5 and stable in pH range of 6.0–9.0 while holo-ApcAT was most fluorescent at pH 6.0 and stable in pH range of 5.0–7.0, with residual fluorescence intensity no less than 90% of the maximum fluorescence. These findings will pave the way for further protein engineering to achieve high stable APC from extremophiles.



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Levels of anti-fructose-modified HSA antibodies correlate with disease status in diabetic subjects

Publication date: July 2016
Source:International Journal of Biological Macromolecules, Volume 88
Author(s): Shaziya Allarakha, Kiran Dixit, Mohammad Shoaib Zaheer, Sheelu Shafiq Siddiqi, Moinuddin, Asif Ali
ObjectiveThis study aimed to assess the changes induced in HSA upon fructose-modification and to use the modified protein as an antigen for studying the presence of antibodies in diabetic patients. Further, magnitude of oxidative stress was also assessed.MethodsHSA was modified with fructose, changes induced were studied by DSC measurements and near-UV CD. The binding characteristics of antibodies in the sera of diabetes patients to native and modified-HSA was assessed by ELISA and band shift assay. The oxidative stress in these patients was studied by carbonyl content estimation, FRAP assay and TBARS determinationResultsDSC revealed that fructose modified-HSA was more thermostable than its native form. Changes in tertiary structure of fructose-modified HSA were seen in near-UV CD. Patient studies showed that fructose-modified HSA acts as a potent immunogen compared to its native form and the levels of antibodies against fructose-modified HSA served as a parameter for tracking the glycemic control and oxidative stress parameters (carbonyl content, FRAP value and MDA level) in diabetic patients.ConclusionsFructose-modification of HSA causes perturbations in its structure and function, thereby, making the protein antigenic besides decreasing its antioxidant capacity. This study suggests that fructose-modified-HSA is an important contributor in diabetic pathophysiology.



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Optimized method for TAG protein homology modeling: In silico and experimental structural characterization

Publication date: July 2016
Source:International Journal of Biological Macromolecules, Volume 88
Author(s): Jyoti Singh Tomar, Rama Krishna Peddinti
The DNA glycosylases cleave CN glycosyl bond to release a free base and generate abasic sites concurrently. Function and structure of these enzymes in the pathogenic bacterium Acinetobacter baumannii and its closely related species are not well characterized. Inhibition of TAG enzyme is a promising drug design strategy against A. baumannii. Here optimized molecular modeling approaches were used to provide a structural scaffold of TAG. The recombinant TAG protein was expressed and purified to determine oligomeric state using size exclusion chromatography, which showed the existence of TAG protein as monomer (mwt ∼21kDa). Secondary structure and substrate binding were analyzed using CD are in good agreement with the in silico predictions. Near UV-CD spectrum shows the involvement of Tyr residues in substrate recognition. Molecular docking studies were performed to understand the molecular recognition interactions and this knowledge was used to identify the potent inhibitors using virtual screening. Residues crucial for DNA holding and enzyme catalysis are reconfirmed by the in silico mutational studies.



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Cell Cycle Arrest and Apoptosis Induction via Modulation of Mitochondrial Integrity by Bcl-2 Family Members and Caspase Dependence in Dracaena cinnabari-Treated H400 Human Oral Squamous Cell Carcinoma

Dracaena cinnabari Balf.f. is a red resin endemic to Socotra Island, Yemen. Although there have been several reports on its therapeutic properties, information on its cytotoxicity and anticancer effects is very limited. This study utilized a bioassay-guided fractionation approach to determine the cytotoxic and apoptosis-inducing effects of D. cinnabari on human oral squamous cell carcinoma (OSCC). The cytotoxic effects of D. cinnabari crude extract were observed in a panel of OSCC cell lines and were most pronounced in H400. Only fractions DCc and DCd were active on H400 cells; subfractions DCc15 and DCd16 exhibited the greatest cytotoxicity against H400 cells and D. cinnabari inhibited cells proliferation in a time-dependent manner. This was achieved primarily via apoptosis where externalization of phospholipid phosphatidylserine was observed using DAPI/Annexin V fluorescence double staining mechanism studied through mitochondrial membrane potential assay cytochrome enzyme-linked immunosorbent and caspases activities revealed depolarization of mitochondrial membrane potential (MMP) and significant activation of caspases 9 and 3/7, concomitant with S phase arrest. Apoptotic proteins array suggested that MMP was regulated by Bcl-2 proteins family as results demonstrated an upregulation of Bax, Bad, and Bid as well as downregulation of Bcl-2. Hence, D. cinnabari has the potential to be developed as an anticancer agent.

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Death of a 29-Year-Old Male from Undifferentiated Sepsis

Tumour necrosis factor alpha inhibitors, such as infliximab, and other biologic agents are associated with increased risk of opportunistic infection, including tuberculosis. Tuberculosis infections associated with infliximab tend to present atypically and can be difficult to diagnose, as they are more likely to manifest as extrapulmonary or disseminated disease. The authors report a case involving a 29-year-old male patient who died following 16 days of treatment for undifferentiated sepsis and who was found on autopsy to have widespread disseminated tuberculosis. Prior to the onset of illness, the patient had received infliximab for the treatment of Crohn’s disease. Following discussion of the case, the authors review the definition of adverse events, provide a root cause analysis of the cognitive errors and breakdowns in the health care system that contributed to the reported outcome, and identify opportunities to address these breakdowns and improve patient safety measures for future cases.

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Zinc Chelation Mediates the Lysosomal Disruption without Intracellular ROS Generation

We report the molecular mechanism for zinc depletion caused by TPEN (N,N,N′,N′-Tetrakis(2-pyridylmethyl)ethylenediamine) in neuroblastoma cells. The activation of p38 MAP kinase and subsequently caspase 3 is not due to or followed by redox imbalance or ROS generation, though these are commonly observed in literature. We found that TPEN is not responsible for ROS generation and the mechanism involves essentially lysosomal disruption caused by intracellular zinc depletion. We also observed a modest activation of Bax and no changes in the Bcl-2 proteins. As a result, we suggest that TPEN causes intracellular zinc depletion which can influence the breakdown of lysosomes and cell death without ROS generation.

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Determinants of Early Marriage from Married Girls’ Perspectives in Iranian Setting: A Qualitative Study

Early marriage is a worldwide problem associated with a range of health and social consequences for teenage girls. Designing effective health interventions for managing early marriage needs to apply the community-based approaches. However, it has received less attention from policymakers and health researchers in Iran. Therefore, the current study aimed to explore determinants of early marriage from married girls’ perspectives. The study was conducted from May 2013 to January 2015 in Ahvaz, Iran. A purposeful sampling method was used to select fifteen eligible participants. Data were collected through face-to-face, semistructured interviews and were analyzed using the conventional content analysis approach. Three categories emerged from the qualitative data including “family structure,” “Low autonomy in decision-making,” and “response to needs.” According to the results, although the participants were not ready to get married and intended to postpone their marriage, multiple factors such as individual and contextual factors propelled them to early marriage. Given that early marriage is a multifactorial problem, health care providers should consider a multidimensional approach to support and empower these vulnerable girls.

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Multivariate Statistics and Supervised Learning for Predictive Detection of Unintentional Islanding in Grid-Tied Solar PV Systems

Integration of solar photovoltaic (PV) generation with power distribution networks leads to many operational challenges and complexities. Unintentional islanding is one of them which is of rising concern given the steady increase in grid-connected PV power. This paper builds up on an exploratory study of unintentional islanding on a modeled radial feeder having large PV penetration. Dynamic simulations, also run in real time, resulted in exploration of unique potential causes of creation of accidental islands. The resulting voltage and current data underwent dimensionality reduction using principal component analysis (PCA) which formed the basis for the application of statistic control charts for detecting the anomalous currents that could island the system. For reducing the false alarm rate of anomaly detection, Kullback-Leibler (K-L) divergence was applied on the principal component projections which concluded that statistic based approach alone is not reliable for detection of the symptoms liable to cause unintentional islanding. The obtained data was labeled and a -nearest neighbor (-NN) binomial classifier was then trained for identification and classification of potential islanding precursors from other power system transients. The three-phase short-circuit fault case was successfully identified as statistically different from islanding symptoms.

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Urinary 3-(3-Hydroxyphenyl)-3-hydroxypropionic Acid, 3-Hydroxyphenylacetic Acid, and 3-Hydroxyhippuric Acid Are Elevated in Children with Autism Spectrum Disorders

Autism spectrum disorders (ASDs) are a group of mental illnesses highly correlated with gut microbiota. Recent studies have shown that some abnormal aromatic metabolites in autism patients are presumably derived from overgrown Clostridium species in gut, which may be used for diagnostic purposes. In this paper, a GC/MS based metabolomic approach was utilized to seek similar biomarkers by analyzing the urinary information in 62 ASDs patients compared with 62 non-ASDs controls in China, aged 1.5–7. Three compounds identified as 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA), 3-hydroxyphenylacetic acid (3HPA), and 3-hydroxyhippuric acid (3HHA) were found in higher concentrations in autistic children than in the controls (). After oral vancomycin treatment, urinary excretion of HPHPA (), 3HPA (), and 3HHA () decreased markedly, which indicated that these compounds may also be from gut Clostridium species. The sensitivity and specificity of HPHPA, 3HPA, and 3HHA were evaluated by receiver-operating characteristic (ROC) analysis. The specificity of each compound for ASDs was very high (>96%). After two-regression analysis, the optimal area under the curve (AUC, 0.962), sensitivity (90.3%), and specificity (98.4%) were obtained by ROC curve of Prediction probability based on the three metabolites. These findings demonstrate that the measurements of the three compounds are strong predictors of ASDs and support the potential clinical utility for identifying a subgroup of ASDs subjects.

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Diagnostic Laparoscopy with Ultrasound Still Has a Role in the Staging of Pancreatic Cancer: A Systematic Review of the Literature

Background. The reported incidence of noncurative laparotomies for pancreatic cancer using standard imaging (SI) techniques for staging remains high. The objectives of this study are to determine the diagnostic accuracy of diagnostic laparoscopy with ultrasound (DLUS) in assessing resectability of pancreatic tumors. Study Design. We systematically searched the literature for prospective studies investigating the accuracy of DLUS in determining resectability of pancreatic tumors. Results. 104 studies were initially identified and 19 prospective studies (1,573 patients) were included. DLUS correctly predicted resectability in 79% compared to 55% for SI. DLUS prevented noncurative laparotomies in 33%. Of those, the most frequent DLUS findings precluding resection were liver metastases, vascular involvement, and peritoneal metastases. DLUS had a morbidity rate of 0.8% with no mortalities. DLUS remained superior to SI when analyzing studies published only in the last five years (100% versus 81%), enrolling patients after the year 2000 (74% versus 58%), or comparing DLUS to modern multidimensional CT (100% versus 78%). Conclusion. DLUS seems to still have a role in the preoperative staging of pancreatic cancer. With its ability to detect liver metastases, vascular involvement, and peritoneal metastases, the use of DLUS leads to less noncurative laparotomies.

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Investigation on Microblasting Applied to CrN Coatings

A microblasting treatment carried out on CrN coated samples was studied to investigate the induced effect on corrosion and wear resistance. CrN coating was deposited through Cathodic Arc Evaporation technique on quenched and tempered steel. The properties of the coating were studied by hardness measurements, scratch, potentiodynamic, and pin-on-disk tests. The results show that microblasting reduces the corrosion resistance while improving the wear behavior.

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Cancers, Vol. 8, Pages 42: Radioresistance of Brain Tumors

Radiation therapy (RT) is frequently used as part of the standard of care treatment of the majority of brain tumors. The efficacy of RT is limited by radioresistance and by normal tissue radiation tolerance. This is highlighted in pediatric brain tumors where the use of radiation is limited by the excessive toxicity to the developing brain. For these reasons, radiosensitization of tumor cells would be beneficial. In this review, we focus on radioresistance mechanisms intrinsic to tumor cells. We also evaluate existing approaches to induce radiosensitization and explore future avenues of investigation.

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Current Concepts Related to Hypertrophic Scarring in Burn Injuries

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Abstract

Scarring following burn injury and its accompanying aesthetic and functional sequelae still pose major challenges. Hypertrophic scarring (HTS) can greatly impact patients' quality of life related to appearance, pain, pruritus and even loss of function of the injured body region. The identification of molecular events occurring in the evolution of the burn scar has increased our knowledge; however, this information has not yet translated into effective treatment modalities. Although many of the pathophysiologic pathways that bring about exaggerated scarring have been identified, certain nuances in burn scar formation are starting to be recognized. These include the effects of neurogenic inflammation, mechanotransduction, and the unique interactions of burn wound fluid with fat tissue in the deeper dermal layers, all of which may influence scarring outcome. Tension on the healing scar, pruritus, and pain all induce signaling pathways that ultimately result in increased collagen formation and myofibroblast phenotypic changes. Exposure of the fat domes in the deep dermis is associated with increased HTS, possibly on the basis of altered interaction of adipose-derived stem cells and the deep burn exudate. These pathophysiologic patterns related to stem cell-cytokine interactions, mechanotransduction, and neurogenic inflammation can provide new avenues of exploration for possible therapeutic interventions. This article is protected by copyright. All rights reserved.



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Immunoglobulin G4-related disease presenting with prurigo: Circulating T-helper 2 cells may be involved in the pathogenesis

Abstract

We report a case of immunoglobulin G4-related disease (IgG4-RD) which presented with prurigo on the trunk and extremities. A 66-year-old man had a 2-month history of itchy erythematous papules on his trunk and extremities. Bilateral eyelid swelling and enlargement of the submandibular and parotid glands were also observed. Computed tomography revealed pleural thickening and diffuse pancreatic enlargement. Serum levels of IgG4 were markedly increased. A biopsy specimen obtained from an erythematous papule showed a perivascular inflammatory infiltrate of lymphocytes with eosinophils in the dermis, whereas a parotid gland biopsy revealed an infiltrate of abundant IgG4-positive plasma cells. Treatment with prednisolone resulted in improvement of the skin and other lesions along with a decrease in IgG4 serum levels. A flow cytometric assay revealed that percentages of interleukin (IL)-4- and IL-13-producing CD4+ T cells were markedly higher in the circulation of the IgG4-RD patient than in that of healthy subjects. Moreover, those populations dramatically decreased after treatment. Thus, prurigo may be a skin manifestation of IgG4-RD and T-helper 2 cells may contribute to the pathogenesis.



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Case of pigmented dermatofibrosarcoma protuberans with atrophic change



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First case of redness and erosion at bacillus Calmette–Guérin inoculation site after vaccination against influenza



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Viruses, Vol. 8, Pages 87: Natural History of Aerosol Exposure with Marburg Virus in Rhesus Macaques

Marburg virus causes severe and often lethal viral disease in humans, and there are currently no Food and Drug Administration (FDA) approved medical countermeasures. The sporadic occurrence of Marburg outbreaks does not allow for evaluation of countermeasures in humans, so therapeutic and vaccine candidates can only be approved through the FDA animal rule—a mechanism requiring well-characterized animal models in which efficacy would be evaluated. Here, we describe a natural history study where rhesus macaques were surgically implanted with telemetry devices and central venous catheters prior to aerosol exposure with Marburg-Angola virus, enabling continuous physiologic monitoring and blood sampling without anesthesia. After a three to four day incubation period, all animals developed fever, viremia, and lymphopenia before developing tachycardia, tachypnea, elevated liver enzymes, decreased liver function, azotemia, elevated D-dimer levels and elevated pro-inflammatory cytokines suggesting a systemic inflammatory response with organ failure. The final, terminal period began with the onset of sustained hypotension, dehydration progressed with signs of major organ hypoperfusion (hyperlactatemia, acute kidney injury, hypothermia), and ended with euthanasia or death. The most significant pathologic findings were marked infection of the respiratory lymphoid tissue with destruction of the tracheobronchial and mediastinal lymph nodes, and severe diffuse infection in the liver, and splenitis.

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Sleep duration estimates of Canadian children and adolescents

Summary

The objective of this study was to provide contemporary sleep duration estimates of Canadian school-aged children and adolescents and to determine the proportion adhering to the sleep duration recommendations. This study included 24 896 participants aged 10–17 years from the 2013/2014 Canadian Health Behaviour in School-aged Children study (HBSC), a nationally representative cross-sectional study. Bedtime and wake-up times were reported by participants and their sleep duration was calculated. Participants were then classified as having a sleep duration that met the recommended range (9–11 h per night for 10–13-year-olds or 8–10 h per night for 14–17-year-olds), a sleep duration that was shorter than the recommended range or a sleep duration that was longer than the recommended range. An estimated 68% of children aged 10–13 years and 72% of adolescents aged 14–17 years sleep for the recommended amount per night when averaged across all days of the week. Short sleepers represent 31% of school-aged children and 26% of adolescents. Long sleepers are rare (<2% overall). Children and adolescents sleep ~1 h more at weekends compared to weekdays. Approximately 5% of the participants typically went to bed after midnight on weekdays and 31% did so at weekends; these proportions reached 11 and 45%, respectively, within 16–17-year-olds. In general, differences in sleep times between boys and girls are small and not clinically significant. In conclusion, almost one-third of Canadian children and adolescents sleep less than the recommended amount. Public health efforts should continue to monitor the sleep of Canadian children and adolescents and identify subgroups of the population more likely to be affected by insufficient sleep.



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IJERPH, Vol. 13, Pages 383: Changes in Cosmetics Use during Pregnancy and Risk Perception by Women

Cosmetic products contain various chemical substances that may be potential carcinogen and endocrine disruptors. Women’s changes in cosmetics use during pregnancy and their risk perception of these products have not been extensively investigated. The main objective of this study was to describe the proportion of pregnant women changing cosmetics use and the proportion of non-pregnant women intending to do so if they became pregnant. The secondary objectives were to compare, among the pregnant women, the proportions of those using cosmetics before and during pregnancy, and to describe among pregnant and non-pregnant women, the risk perception of these products. A cross-sectional study was carried out in a gynaecology clinic and four community pharmacies. One hundred and twenty-eight women (60 non-pregnant and 68 pregnant women) replied to a self-administered questionnaire. Cosmetics use was identified for 28 products. The results showed that few women intended to change or had changed cosmetics use during pregnancy. Nail polish was used by fewer pregnant women compared to the period before pregnancy (p < 0.05). Fifty-five percent of the women considered cosmetics use as a risk during pregnancy and 65% would have appreciated advice about these products. Our findings indicate that all perinatal health professionals should be ready to advise women about the benefits and risks of using cosmetics during pregnancy.

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Τετάρτη, 23 Μαρτίου 2016

RT @AlvaroKohn : Very interesting personalized cancer care symposium @Oslounivsykehus https://t.co/SXV1jE7uXg

RT @AlvaroKohn : Very interesting personalized cancer care symposium @Oslounivsykehus https://t.co/SXV1jE7uXg

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‘Silencer molecules’ switch off cancer’s ability to spread around body https://t.co/SeGbuV1e4S https://t.co/PWQwNLDlPB

‘Silencer molecules’ switch off cancer’s ability to spread around body https://t.co/SeGbuV1e4S https://t.co/PWQwNLDlPB

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RAS mutation is a prognostic biomarker in colorectal cancer patients with metastasectomy

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Abstract

Studies have demonstrated a relationship between clinical outcomes after curative resection for colorectal cancer (CRC) and gene mutations of the EGFR pathway, however no studies have examined metastatic CRC (mCRC) patients with metastasectomy. The aim of this study was to evaluate the relationship between gene mutations of EGFR pathway and clinical outcomes after metastasectomy in mCRC patients. A total of 1053 patients histopathologically confirmed CRC received a genotyping test for the EGFR pathway from February 2012 to October 2013. Detailed information was obtained through review of medical records. Gene mutations of EGFR pathway were analyzed by Luminex assay. Overall survival (OS) and recurrence free survival (RFS) were estimated by the Kaplan-Meier method and the log-rank test was used to compare the survival outcomes by gene mutation status. A total of 132 patients received metastasectomy. The frequencies of KRAS exon 2, KRAS exon 3.4, NRAS, BRAF, and PIK3CA mutations were 38.6% (51/132), 3.6% (5/132), 5.1% (7/132), 5.1% (7/132), and 8.7% (12/132), respectively. With a median follow up of 84.1 months (57.2–NA) for a survivor, the 4-year OS rate was 65.6% for mCRC with RAS mutation, and 81.3% for mCRC with wild-type RAS (p < 0.05). We observed a statistically significant correlation for only the RAS mutation and OS. In multivariate analysis, RAS mutation and liver metastasis were independent factors for shorter OS. There were no significant differences between gene mutations of EGFR pathway and RFS.

RAS mutation in mCRC metastasectomy patients was associated with shorter overall survival. This article is protected by copyright. All rights reserved.



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Epidemiologic evidence of slow growing, non-progressive or regressive breast cancer: a systematic review

Abstract

The general aim of this systematic review is to mitigate breast cancer (BC) overdiagnosis and overtreatment. The specific aim is to summarize available data on the occurrence and features of indolent invasive or in situ (DCIS) BC, and precisely survival of untreated cases, prevalence of occult cancers found in autopsies, frequency of regressive BC.

PubMed, Embase and Cochrane Library were systematically searched up to 3/31/2014. Eligibility criteria were: cohort studies, case-control studies, uncontrolled case series assessing survival in women with a diagnosis of BC who did not receive treatment compared to treated women; case series of autopsies estimating the prevalence of undiagnosed BC; cohort studies, case-control studies, uncontrolled case series, case reports assessing the occurrence of spontaneous regression of BC in women with a confirmed histology diagnosis.

Untreated BC: 8 cohort studies and 12 case series (3593 BC) were included. In 3 controlled cohort studies (diagnoses 1978-2006), the 5-years overall survival was 19%-43%.

Occult BC: 8 case series (2279 autopsies) were included. The prevalence of invasive BC undiagnosed during lifetime range was 0-1.5%, while for DCIS the range was 0.2%-14.7%.

Spontaneous regression: 2 cohort studies, 3 case reports, 1 case series included. In the cohort studies the relative risk of regression for screen detected compared to non-screened BC was estimated as 1.2 and 1.1.

It seems plausible that around 10% of invasive BC are not symptomatic during life, and that one fith of BC patients if untreated would be alive after 5 years. Around 1 of 10 screen-detected BC may regress according two studies. This article is protected by copyright. All rights reserved.



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Human papillomavirus mRNA and DNA testing in women with atypical squamous cells of undetermined significance: A prospective cohort study

Abstract

In this prospective cohort study, we compared the performance of human papillomavirus (HPV) mRNA and DNA testing of women with atypical squamous cells of undetermined significance (ASC-US) during cervical cancer screening. Using a nationwide Danish pathology register, we identified women aged 30–65 years with ASC-US during 2005–2011 who were tested for HPV16/18/31/33/45 mRNA using PreTect HPV-Proofer (n=3,226) or for high-risk HPV (hrHPV) DNA using Hybrid Capture 2 (HC2) (n=9,405) or Linear Array HPV-Genotyping test (LA) (n=1,533). Women with ≥1 subsequent examination in the register (n=13,729) were followed for up to 9.5 years for high-grade cervical intraepithelial neoplasia (CIN) or cancer. After 3 years' follow-up, mRNA testing had higher specificity for CIN3 or worse (CIN3+) than HC2 testing (88.1% [95% confidence interval (CI): 86.8%–89.6%] versus 59.3% [95% CI: 58.1%–60.4%]) and higher positive predictive value (PPV) (38.2% [95% confidence interval [CI]: 33.8%–43.1%] versus 19.5% [95% CI: 17.8%–20.9%]). However, the sensitivity of mRNA testing was lower than that of HC2 testing (66.7% [95% CI: 59.3%–74.5%] versus 97.0% [95% CI: 95.5%–98.4%]), and women testing mRNA negative had higher 3-year risk for CIN3+ than those testing HC2 negative (3.2% [95% CI: 2.2%–4.2%] versus 0.5% [95% CI: 0.3%–0.7%]). Patterns were similar after 18 months and 5 years' follow-up; for CIN2+ and cancer as outcomes; across all age groups; and when comparing mRNA testing to hrHPV DNA testing using LA. In conclusion, the HPV16/18/31/33/45 mRNA test is not optimal for ASC-US triage due to its low sensitivity and the substantial risk for precancer following a negative test. This article is protected by copyright. All rights reserved.



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Use of thermo-coagulation as an alternative treatment modality in a ‘screen and treat' programme of cervical screening in rural Malawi

Abstract

The incidence of cervical cancer in Malawi is the highest in the world and projected to increase in the absence of interventions. Although Government policy supports screening using visual inspection with acetic acid (VIA), screening provision is limited due to lack of infrastructure, trained personnel, cost and availability of gas for cryotherapy. Recently, thermo-coagulation has been acknowledged as a safe and acceptable procedure suitable for low–resource settings. We introduced thermo-coagulation for treatment of VIA positive lesions as an alternative to cryotherapy within a cervical screening service based on VIA, coupled with appropriate, sustainable pathways of care for women with high grade lesions and cancers. Detailed planning was undertaken for VIA clinics, approvals were obtained from the Ministry of Health, and Regional and Village Chiefs. Educational resources were developed. Thermo-coagulators were introduced into hospital and health centre settings, with theoretical and practical training in safe use and maintenance of equipment. 7088 previously unscreened women attended VIA clinics between October 2013 and March 2015. Screening clinics were held daily in the hospital and weekly in the health centres. Overall VIA positivity was 6.1%. Almost 90% received same day treatment in the hospital setting, and 3-6 month cure rates of over 90% are observed. Thermo-coagulation proved feasible and acceptable in this setting. Effective implementation requires comprehensive training and provider support, ongoing competency assessment, quality assurance and improvement audit. Thermo-coagulation offers an effective alternative to cryotherapy and encouraged VIA screening of many more women. This article is protected by copyright. All rights reserved.



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Preferential Tumor Cellular Uptake and Retention of Indocyanine Green for In Vivo Tumor Imaging

Abstract

Indocyanine green (ICG) is a fluorescent agent approved for clinical applications by the Food and Drug Administration and European Medicines Agency. This study examined the mechanism of tumor imaging using intravenously administered ICG. The in vivo kinetics of intravenously administered ICG were determined in tumor xenografts using microscopic approaches that enabled both spatio-temporal and high-magnification analyses. The mechanism of ICG-based tumor imaging was examined at the cellular level in six phenotypically different human colon cancer cell lines exhibiting different grades of epithelioid organization. ICG fluorescence imaging detected xenograft tumors, even those < 1 mm in size, based on their preferential cellular uptake and retention of the dye following its rapid tissue-non-specific delivery, in contrast to its rapid clearance by normal tissue. Live-cell imaging revealed that cellular ICG uptake is temperature-dependent and occurs after ICG binding to the cellular membrane, a pattern suggesting endocytic uptake as the mechanism. Cellular ICG uptake correlated inversely with the formation of tight junctions. Intracellular ICG was entrapped in the membrane traffic system, resulting in its slow turnover and prolonged retention by tumor cells. Our results suggest that tumor-specific imaging by ICG involves non-specific delivery of the dye to tissues followed by preferential tumor cellular uptake and retention. The tumor cell-preference of ICG is driven by passive tumor-cell-targeting, the inherent ability of ICG to bind to cell membranes, and the high endocytic activity of tumor cells in association with the disruption of their tight junctions. This article is protected by copyright. All rights reserved.



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Prognostic factors and disease-specific survival among immigrants diagnosed with cutaneous malignant melanoma in Sweden

Abstract

Little is known about cutaneous malignant melanoma (CMM) among immigrants in Europe. We aimed to investigate clinical characteristics and disease-specific survival among first- and second-generation immigrants in Sweden This nationwide population-based study included 27,235 patients from the Swedish Melanoma Register diagnosed with primary invasive CMM 1990-2007. Data were linked to nationwide, population-based registers followed up through 2013. Logistic regression and Cox regression models were used to determine the association between immigrant status and stage and CMM prognosis, respectively. stage. After adjustments for confounders, first generation immigrant from Southern Europe were associated with significantly more advanced stages of disease compared to Swedish-born patients (Stage II vs I: Odds ratio (OR)=2.37, 95% CI=1.61 to 3.50. Stage III-IV vs I: OR=2.40, 95% CI = 1.08-5.37). stageThe ORsof stage II-IV vs stage I disease were increased among men (OR=1.9; 95% CI=1.1 - 3.3; P=0.020), and inwomen (OR=4.8; 95% CI=2.6 - 9.1; P < 0.001) in a subgroup of immigrants from former Yugoslavia compared to Swedish-born patients. In conclusion, the CMM-specific survival was significantly decreased among women from former Yugoslavia compared to Swedish-born women (hazard ratio (HR) = 2.2; 95% CI=1.1 - 4.2; P=0.043). After additional adjustment including stage, the survival difference was no longer significant. No survival difference between the second generation immigrant group and Swedish-born patients were observed. A worse CMM-specific survival in women from former Yugoslavia was associated with more advanced stages of CMM at diagnosis. Secondary prevention efforts focusing on specific groups may be needed to further improve CMM prognosis. This article is protected by copyright. All rights reserved.



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Development of ZMYM2-FGFR1 driven AML in human CD34+ cells in immunocompromised mice

Abstract

Acute myelogenous leukemia (AML) has an overall poor survival rate and shows considerable molecular heterogeneity in its etiology. In the WHO classification there are >50 cytogenetic subgroups of AML, many showing highly specific chromosome translocations that lead to constitutive activation of individual kinases. In a rare stem cell leukemia/lymphoma syndrome, translocations involving 8p11 lead to constitutive activation of the fibroblast growth factor receptor 1 (FGFR1) kinase. This disorder shows myeloproliferative disease with almost invariable progresses to AML and conventional therapeutic strategies are largely unsuccessful. Because of the rare nature of this syndrome, models that faithfully recapitulate the human disease are need to evaluate therapeutic strategies. The t(8;13)(p11;q12) chromosome translocation is most common rearrangement seen in this syndrome and creates a ZMYM2-FGFR1 chimeric kinase. To understand more about the molecular etiology of AML induced by this particular rearrangement, we have created a model human CD34+ cells transplanted into immunocompromized mice which develop myeloproliferative disease that progresses to AML with a long (> 12 months) latency period. As in humans, these mice show hepatospenomegaly, hypercellular bone marrow and a CD45+CD34+CD13+ immunophenotype. Molecular studies demonstrate upregulation of genes such as KLF4 and FLT3 that promote stemness, and overexpression of MYC, which is associated with suppression of myeloid cell differentiation. This murine model, therefore, provides a opportunity to develop therapeutic strategies against the most common subtype within these FGFR1 driven neoplasms and study the molecular etiology in more depth. This article is protected by copyright. All rights reserved.



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Hva er likheten mellom et oblat og en tablett?

Oppsiktsvekkende nok kan man sammenligne oblaten man får utdelt under nattverden med legemiddelbruk.

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Cross-modal symbolic processing can elicit either an N2 or a protracted N2/N400 response

Abstract

A cross-modal symbolic paradigm was used to elicit EEG activity related to semantic incongruence. Twenty-five undergraduate students viewed pairings of visual lexical cues (e.g., DOG) with congruent (50% of trials) or incongruent (50%) auditory nonlexical stimuli (animal vocalizations; e.g., sound of a dog woofing or a cat meowing). In one condition, many different pairs of congruent/incongruent stimuli were shown, whereas in a second condition only two pairs of stimuli were repeatedly shown. A typical N400-like pattern of incongruence-related activity (including activity in the N2 time window) was evident in the condition using many stimuli, whereas the incongruence-related activity in the two-stimuli condition was confined to differential N2-like activity. A supplementary analysis excluded stimulus characteristics as the source of this differential activity between conditions. We found that a single individual performing a fixed task can demonstrate either a protracted N400-like pattern of activity or a more temporally focused N2-like pattern of activity in response to the same stimulus, which suggests that the N2 may be a precursor to the protracted N400 response.



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Diminished heart rate reactivity to acute psychological stress is associated with enhanced carotid intima-media thickness through adverse health behaviors

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Abstract

Recent evidence demonstrates that individuals with low heart rate (HR) reactions to acute psychological stress are more likely to be obese or smokers. Smoking and obesity are established risk factors for increased carotid intima-media thickness (IMT). The aim of this study was to examine the potential pathways linking intima-media thickness, smoking, body mass index (BMI), and HR stress reactivity. A total of 552 participants, 47.6% male, M (SD) age = 58.3 (0.94) years, were exposed to three psychological stress tasks (Stroop, mirror drawing, and speech) preceded by a resting baseline period; HR was recorded throughout. HR reactivity was calculated as the average response across the three tasks minus average baseline HR. Smoking status, BMI, and IMT were determined by trained personnel. Controlling for important covariates (e.g., socioeconomic status), structural equation modeling revealed that BMI and smoking mediated the negative relationship between HR reactivity and IMT. The hypothesized model demonstrated a good overall fit to the data, χ2(8) = 0.692, p = .403; CFI = 1.00; TLI = 1.00 SRMR = .01; RMSEA < .001 (90% CI < 0.01–0.11). HR reactivity was negatively related to BMI (β = −.16) and smoking (β = −.18), and these in turn were positively associated with IMT (BMI: β = .10; smoking: β = .17). Diminished HR stress reactivity appears to be a marker for enlarged IMT and appears to be exerting its impact through already established risks. Future research should examine this relationship longitudinally and aim to intervene early.



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Preventing (impulsive) errors: Electrophysiological evidence for online inhibitory control over incorrect responses

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Abstract

In a rich environment, with multiple action affordances, selective action inhibition is critical in preventing the execution of inappropriate responses. Here, we studied the origin and the dynamics of incorrect response inhibition and how it can be modulated by task demands. We used EEG in a conflict task where the probability of compatible and incompatible trials was varied. This allowed us to modulate the strength of the prepotent response, and hence to increase the risk of errors, while keeping the probability of the two responses equal. The correct response activation and execution was not affected by compatibility or by probability. In contrast, incorrect response inhibition in the primary motor cortex ipsilateral to the correct response was more pronounced on incompatible trials, especially in the condition where most of the trials were compatible, indicating a modulation of inhibitory strength within the course of the action. Two prefrontal activities, one medial and one lateral, were also observed before the response, and their potential links with the observed inhibitory pattern observed are discussed.



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JCM, Vol. 5, Pages 40: Is there A Role for Alpha-Linolenic Acid in the Fetal Programming of Health?

The role of ω3 alpha linolenic acid (ALA) in the maternal diet during pregnancy and lactation, and its effect on the prevention of disease and programming of health in offspring, is largely unknown. Compared to ALA, ω3 docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids have been more widely researched due to their direct implication in fetal neural development. In this literature search we found that ALA, the essential ω3 fatty acid and metabolic precursor of DHA and EPA has been, paradoxically, almost unexplored. In light of new and evolving findings, this review proposes that ALA may have an intrinsic role, beyond the role as metabolic parent of DHA and EPA, during fetal development as a regulator of gene programming for the prevention of metabolic disease and promotion of health in offspring.

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Are Doctors Destroyed by their Frankensteins? - Daijiworld.com


Are Doctors Destroyed by their Frankensteins?
Daijiworld.com
He also looked at the outstretched tongue, probed the nose and the ears with a torch and pressed the stomach and other parts below the rib cage. And he asked questions about the lifestyle of the patient and the health and longevity of the ... For ...



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IJERPH, Vol. 13, Pages 355: Using a Hybrid Model to Forecast the Prevalence of Schistosomiasis in Humans

Background: We previously proposed a hybrid model combining both the autoregressive integrated moving average (ARIMA) and the nonlinear autoregressive neural network (NARNN) models in forecasting schistosomiasis. Our purpose in the current study was to forecast the annual prevalence of human schistosomiasis in Yangxin County, using our ARIMA-NARNN model, thereby further certifying the reliability of our hybrid model. Methods: We used the ARIMA, NARNN and ARIMA-NARNN models to fit and forecast the annual prevalence of schistosomiasis. The modeling time range included was the annual prevalence from 1956 to 2008 while the testing time range included was from 2009 to 2012. The mean square error (MSE), mean absolute error (MAE) and mean absolute percentage error (MAPE) were used to measure the model performance. We reconstructed the hybrid model to forecast the annual prevalence from 2013 to 2016. Results: The modeling and testing errors generated by the ARIMA-NARNN model were lower than those obtained from either the single ARIMA or NARNN models. The predicted annual prevalence from 2013 to 2016 demonstrated an initial decreasing trend, followed by an increase. Conclusions: The ARIMA-NARNN model can be well applied to analyze surveillance data for early warning systems for the control and elimination of schistosomiasis.

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IJERPH, Vol. 13, Pages 353: Salivary Alpha-Amylase Reactivity in Breast Cancer Survivors

The two main components of the stress system are the hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal-medullary (SAM) axes. While cortisol has been commonly used as a biomarker of HPA functioning, much less attention has been paid to the role of the SAM in this context. Studies have shown that long-term breast cancer survivors display abnormal reactive cortisol patterns, suggesting a dysregulation of their HPA axis. To fully understand the integrity of the stress response in this population, this paper explored the diurnal and acute alpha-amylase profiles of 22 breast cancer survivors and 26 women with no history of cancer. Results revealed that breast cancer survivors displayed identical but elevated patterns of alpha-amylase concentrations in both diurnal and acute profiles relative to that of healthy women, F (1, 39) = 17.95, p < 0.001 and F (1, 37) = 7.29, p = 0.010, respectively. The average area under the curve for the diurnal and reactive profiles was 631.54 ± 66.94 SEM and 1238.78 ± 111.84 SEM, respectively. This is in sharp contrast to their cortisol results, which showed normal diurnal and blunted acute patterns. The complexity of the stress system necessitates further investigation to understand the synergistic relationship of the HPA and SAM axes.

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IJERPH, Vol. 13, Pages 356: Heavy Physical Work: Cardiovascular Load in Male Construction Workers

This study aimed to elucidate cardiovascular loads (CVL) in construction workers during work and leisure by relative heart rate (RHR) over several days. Furthermore, we sought to evaluate the level of CVL in relation to individual factors, work ability, musculoskeletal pain and subjective general health. From a group of 255 construction workers responding to the baseline questionnaire, the CVL during work and leisure time was determined by recording RHR in 42 workers over 3–4 days. Almost 60% of the workday was spent below 20% RHR. The mean RHR during work for all participants was 16% RHR, with large differences between professions. On average, the 42 workers spent 14% of the workday at a RHR above 33%, and four subjects (10%) had a mean RHR above 33% during work. Eight (19%) of the participants had a mean length of their workday exceeding calculated maximal acceptable work time. Seven persons (17%) experienced on average one or more episode(s) of 5 min or more continuously above 33% RHR. The cardiovascular load at work was significantly associated with age and  V ˙O2max, but not with work ability, musculoskeletal pain or subjective general health.

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The Diagnostic Accuracy of Optical Coherence Tomography Angiography for Neovascular Age-Related Macular Degeneration: A Comparison with Fundus Fluorescein Angiography

Purpose. To describe the morphological characteristics and efficacy of OCTA in detecting CNV in nAMD. We retrospectively reviewed 53 patients (86 eyes) with suspected CNV secondary to wet AMD. All the patients underwent a multimodal assessment for CNV. Two independent readers calculated the sensitivity and specificity of OCTA in detecting CNV compared with FA. A qualitative analysis of OCTA was also performed to describe the morphological appearance of CNV. Among 86 eyes of 53 patients, 52 eyes were diagnosed as having CNV based on the FA imaging analysis. According to FA, CNV was classified as classic in 28 eyes, predominantly classic in 6 eyes, minimally classic in 9 eyes, and occult in 9 eyes. In 56 eyes, CNV was visualized on OCTA and corresponding OCT B-scans. In total, 46.4% (26/56) had well-circumscribed vessels, and 53.6% (30/56) showed poorly circumscribed vessels. There were 11 false positives and 7 false negatives using OCTA. The specificity of OCTA for the detection of CNV was 67.6%, with sensitivity of 86.5%. OCTA may help in the noninvasive diagnosis of CNV and may provide a method for monitoring the evolution of CNV.

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The Role of Initial Credit Distribution Scheme in Managing Network Mobility and Maximizing Reserve Capacity: Considering Traveler’s Cognitive Illusion

The role of initial credit distribution scheme (ICDS) in managing network mobility has long been overlooked in previous studies of tradable credit scheme (TCS), which may make their results disputable in the reality, as the travelers possessing leftover credits can get some subsidy from the credit market and offset part of travel cost. In this paper, the disequilibrium phenomenon of previous user equilibrium (UE) solution is shown when traveler’s cognitive illusion (CI) is considered. Then, a new UE condition with TCS is defined with the ICDS and CI explicitly considered. To comprehensively reveal the impacts of ICDS on UE solution, four different types of ICDS are introduced and analyzed in a unified variational inequality (VI) modeling framework. The uniqueness of the UE link flow and market equilibrium (ME) credit price is also investigated. Furthermore, the mathematical program with equilibrium constraint (MPEC) for the optimal ICDS design problem is established, with the optimization objective being maximizing network reserve capacity. A modified relaxation algorithm is adopted to solve the MPEC. The numerical example shows that a properly designed ICDS can not only improve the network reserve capacity, but also decrease the travel cost of all the travelers in the network simultaneously.

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HSP27 Alleviates Cardiac Aging in Mice via a Mechanism Involving Antioxidation and Mitophagy Activation

Aging-induced cardiac dysfunction is a prominent feature of cardiac aging. Heat shock protein 27 (HSP27) protects cardiac function against ischemia or chemical challenge. We hypothesized that HSP27 attenuates cardiac aging. Transgenic (Tg) mice with cardiac-specific expression of the HSP27 gene and wild-type (WT) littermates were employed in the experiments. Echocardiography revealed a significant decline in the cardiac function of old WT mice compared with young WT mice. In striking contrast, the aging-induced impairment of cardiac function was attenuated in old Tg mice compared with old WT mice. Levels of cardiac aging markers were lower in old Tg mouse hearts than in old WT mouse hearts. Less interstitial fibrosis and lower contents of reactive oxygen species and ubiquitin-conjugated proteins were detected in old Tg hearts than in old WT hearts. Furthermore, old Tg hearts demonstrated lower accumulation of LC3-II and p62 than old WT hearts. Levels of Atg13, Vps34, and Rab7 were also higher in old Tg hearts than in old WT hearts. Additionally, old Tg hearts had higher levels of PINK1 and Parkin than old WT hearts, suggesting that mitophagy was activated in old Tg hearts. Taken together, HSP27 alleviated cardiac aging and this action involved antioxidation and mitophagy activation.

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Integrated Power and Attitude Control Design of Satellites Based on a Fuzzy Adaptive Disturbance Observer Using Variable-Speed Control Moment Gyros

To satisfy the requirements for small satellites that seek agile slewing with peak power, this paper investigates integrated power and attitude control using variable-speed control moment gyros (VSCMGs) that consider the mass and inertia of gimbals and wheels. The paper also details the process for developing the controller by considering various environments in which the controller may be implemented. A fuzzy adaptive disturbance observer (FADO) is proposed to estimate and compensate for the effects of equivalent disturbances. The algorithms can simultaneously track attitude and power. The simulation results illustrate the effectiveness of the control approach, which exhibits an improvement of 80 percent compared with alternate approaches that do not employ a FADO.

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Development of a Robotic Assembly for Analyzing the Instantaneous Axis of Rotation of the Foot Ankle Complex

Ankle instantaneous axis of rotation (IAR) measurements represent a more complete parameter for characterizing joint motion. However, few studies have implemented this measurement to study normal, injured, or pathological foot ankle biomechanics. A novel testing protocol was developed to simulate aspects of in vivo foot ankle mechanics during mid-stance gait in a human cadaveric specimen. A lower leg was mounted in a robotic testing platform with the tibia upright and foot flat on the baseplate. Axial tibia loads (ATLs) were controlled as a function of a vertical ground reaction force (vGRF) set at half body weight (356 N) and a 50% vGRF (178 N) Achilles tendon load. Two specimens were repetitively loaded over 10 degrees of dorsiflexion and 20 degrees of plantar flexion. Platform axes were controlled within 2 microns and 0.008 degrees resulting in ATL measurements within ±2 N of target conditions. Mean ATLs and IAR values were not significantly different between cycles of motion, but IAR values were significantly different between dorsiflexion and plantar flexion. A linear regression analysis showed no significant differences between slopes of plantar flexion paths. The customized robotic platform and advanced testing protocol produced repeatable and accurate measurements of the IAR, useful for assessing foot ankle biomechanics under different loading scenarios and foot conditions.

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Dynamic Friction Parameter Identification Method with LuGre Model for Direct-Drive Rotary Torque Motor

Attainment of high-performance motion/velocity control objectives for the Direct-Drive Rotary (DDR) torque motor should fully consider practical nonlinearities in controller design, such as dynamic friction. The LuGre model has been widely utilized to describe nonlinear friction behavior; however, parameter identification for the LuGre model remains a challenge. A new dynamic friction parameter identification method for LuGre model is proposed in this study. Static parameters are identified through a series of constant velocity experiments, while dynamic parameters are obtained through a presliding process. Novel evolutionary algorithm (NEA) is utilized to increase identification accuracy. Experimental results gathered from the identification experiments conducted in the study for a practical DDR torque motor control system validate the effectiveness of the proposed method.

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In memoriam: Dr. Irene Claudia Floriani (1964–2016)



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Screening of endocrine organ-specific humoral autoimmunity in 47,XXY Klinefelter’s syndrome reveals a significant increase in diabetes-specific immunoreactivity in comparison with healthy control men

Abstract

The aim of this study was to evaluate the frequency of humoral endocrine organ-specific autoimmunity in 47,XXY Klinefelter’s syndrome (KS) by investigating the autoantibody profile specific to type 1 diabetes (T1DM), Addison’s disease (AD), Hashimoto thyroiditis (HT), and autoimmune chronic atrophic gastritis (AG). Sixty-one adult Caucasian 47,XXY KS patients were tested for autoantibodies specific to T1DM (Insulin Abs, GAD Abs, IA-2 Abs, Znt8 Abs), HT (TPO Abs), AD (21-OH Abs), and AG (APC Abs). Thirty-five of these patients were not undergoing testosterone replacement therapy TRT (Group 1) and the remaining 26 patients started TRT before the beginning of the study (Group 2). KS autoantibody frequencies were compared to those found in 122 control men. Six of 61 KS patients (9.8 %) were positive for at least one endocrine autoantibody, compared to 6.5 % of controls. Interestingly, KS endocrine immunoreactivity was directed primarily against diabetes-specific autoantigens (8.2 %), with a significantly higher frequency than in controls (p = 0.016). Two KS patients (3.3 %) were TPO Ab positive, whereas no patients were positive for AD- and AG-related autoantigens. The autoantibody endocrine profile of untreated and treated KS patients was not significantly different. Our findings demonstrate for the first time that endocrine humoral immunoreactivity is not rare in KS patients and that it is more frequently directed against type 1 diabetes-related autoantigens, thus suggesting the importance of screening for organ-specific autoimmunity in clinical practice. Follow-up studies are needed to establish if autoantibody-positive KS patients will develop clinical T1DM.



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Type of fish consumed and thyroid autoimmunity in pregnancy and postpartum

Abstract

Fish consumption or supplementation with omega-3 fatty acids was reported to cure and/or prevent autoimmune and nonautoimmune disorders. Serum positivity for thyroid autoantibodies is a predictive marker of postpartum thyroiditis and postpartum depression. We hypothesized that stable consumption of the omega-3-rich oily fish was associated with a more favorable profile of serum thyroid antibodies throughout pregnancy and early postpartum compared with stable consumption of swordfish, a predator that concentrates pollutants. We prospectively measured serum thyroglobulin antibodies and thyroperoxidase antibodies in pregnancy (first, second trimesters) and postpartum (day 4), in 236 thyroid disease-free, nonsmoker Caucasian women with stable dietary habits. We did not measure thyroid autoantibodies prior to pregnancy. Women were divided into groups A (n = 48; swordfish), B (n = 52; oily fish), C (n = 68; swordfish + other fish, not necessarily oily fish), and D (n = 68; fish other than swordfish and oily fish). Major endpoints were positivity rates and serum concentrations of the two autoantibodies. We resorted to previous studies for the estimated content of fatty acids and microelements in the consumed fish. Positivity rates and serum concentrations of both antibodies were the greatest in group A and the lowest in group B (P < 0.001 and P < 0.05 to < 0.001, respectively). Relationship between monthly fish consumption and serum concentrations of either antibody was direct in group A but inverse in group B. The estimated content of omega-3 fatty acids in fish consumed by group B was the greatest (P < 0.001 vs. any other group). These data reinforce recommendations that pregnant women should avoid consuming swordfish and indicate consumption of oily fish as a favorable alternative. Because thyroid autoantibodies are markers of autoimmune-related postpartum problems, our data suggest a dietary prophylaxis of such problems.



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New guideline addresses long-term needs of head and neck cancer survivors - EurekAlert (press release)


New guideline addresses long-term needs of head and neck cancer survivors
EurekAlert (press release)
ATLANTA - March 22, 2016-A new American Cancer Society guideline provides clinicians with recommendations on key areas of clinical follow-up care for survivors of head and neck cancer, a growing population numbering approximately 436,060 and ...

and more »


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Statistical shape analysis of the human spleen geometry for probabilistic occupant models

Publication date: Available online 23 March 2016
Source:Journal of Biomechanics
Author(s): Keegan M. Yates, Yuan-Chiao Lu, Costin D. Untaroiu
Statistical shape models are an effective way to create computational models of human organs that can incorporate inter-subject geometrical variation. The main objective of this study was to create statistical mean and boundary models of the human spleen in an occupant posture. Principal component analysis was applied to fifteen human spleens in order to find the statistical modes of variation, mean shape, and boundary models. A landmark sliding approach was utilized to refine the landmarks to obtain a better shape correspondence and create a better representation of the underlying shape contour. The first mode of variation was found to be the overall volume, and it accounted for 69% of the total variation. The mean model and boundary models could be used to develop probabilistic finite element (FE) models which may identify the risk of spleen injury during vehicle collisions and consequently help to improve automobile safety systems.



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Ring apophysis fractures induced by low-load low-angle repetitive flexion in an ex-vivo cervine model

Publication date: Available online 22 March 2016
Source:Journal of Biomechanics
Author(s): Nicole C. Corbiere, Stacey L. Zeigler, Kathleen A. Issen, Arthur J. Michalek, Laurel Kuxhaus
Ring apophysis fratures of the spine occur in physically-active adolescents causing low back pain and the potential for chronic pain. Many of these fractures occur without memorable trauma, suggesting that the fractures occur during everyday movements and activities. The benign nature of this poorly understood potential mechanism of injury hampers appropriate diagnosis and early treatment. The purpose of this study was to establish an ex-vivo model of ring apophysis fracture and demonstrate that these fractures can be initiated by repetitive non-traumatic loading. Six 5-vertebra cervine lumbar (L1-L5) motion segments were cyclically loaded in low-angle low-load flexion (to 15° flexion, with peak load of 230 ± 50N), a representative movement component of daily activities for both human and deer lumbar spines. Pinned end conditions replicated physiologically realistic loading. Ring apophysis fractures were created under low-load low-angle conditions in healthy vertebrae of similar bone mineral density and a similar degree of skeletal maturity to adolescent humans. All specimens developed ring apophysis fractures; some as early as 1,400 cycles. The load-displacement data, and hysteresis loops during the cyclic loading, suggest that the fractures occurred gradually, i.e., without trauma. The ease at which these fractures were created suggests that ring apophysis fractures may be more prevalent than current diagnosis rates. Therefore, clinically, healthcare providers should include the potential for ring apophysis fracture in the differential diagnosis of all physically-active adolescents who present with back pain.



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