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Δευτέρα, 30 Ιανουαρίου 2017

Otolaryngology (ENT) Sub-Specialties - News-Medical.net


News-Medical.net

Otolaryngology (ENT) Sub-Specialties
News-Medical.net
... and various sub-specialties. These include such disciplines as pediatrics, oncology, sinus disease, and surgery. Because of their range of capabilities, ENT surgeons might one day correct a child's tonsillitis and on the next day treat an adult's ...

and more »


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Pro Football Hall of Famer and Cancer Survivor Jim Kelly Teams Up with Merck and Leading Cancer Organizations to ... - Yahoo Finance


Pro Football Hall of Famer and Cancer Survivor Jim Kelly Teams Up with Merck and Leading Cancer Organizations to ...
Yahoo Finance
Head and neck cancer describes a number of different tumors that develop in or around the throat, larynx, nose, sinuses and mouth. Each year more than 60,000 new cases of head and neck cancer are diagnosed in the U.S. Many people with head and neck ...

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Long Non-coding RNAsinTriple Negative Breast Cancer

Abstract

Long non-coding RNAs (lncRNAs) are dysregulated in many cancer types, which are believed to play crucial roles in regulating several hallmarks of cancer biology. Triple Negative Breast Cancer (TNBC) is a very aggressive subtype of normal breast cancer, which has features of negativity for ER, PR and HER2. Great efforts have been made to identify an association between lncRNAs expression profiles and TNBC, and to understand the functional role and molecular mechanism on aberrant-expressed lncRNAs. In this review, we summarized the existed knowledge on the systematics, biology, and function of lncRNAs. The advances from the most recent studies of lncRNAs in the predicament of breast cancer, TNBC, are highlighted, especially the functions of specifically selected lncRNAs. We also discussed the potential value of these lncRNAs in TNBC, providing clues for the diagnosis and treatments of TNBC. This article is protected by copyright. All rights reserved



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High Glucose Alters the Secretome of Mechanically Stimulated Osteocyte-like Cells Affecting Osteoclast Precursor Recruitment and Differentiation

ABSTRACT

Diabetes mellitus (DM) induces bone deterioration, while mechanical stimulation promotes osteocyte-driven bone formation. We aimed to evaluate the interaction of acute exposure (24h) to high glucose (HG) with both the pro-survival effect conferred to osteocytic MLO-Y4 cells and osteoblastic MC3T3-E1 cells by mechanical stimulation and the interaction of these cells with osteoclast precursor RAW264.7 cells. We found that 24h of HG (25 mM) pre-exposure prevented both cell survival and ERK and β-catenin nuclear translocation upon mechanical stimulation by fluid flow (FF) (10 min) in both MLO-Y4 and MC3T3-E1 cells. However, migration of RAW 264.7 cells was inhibited by MLO-Y4 cell-conditioned medium (CM), but not by MC3T3-E1 cell-CM, with HG or FF. This inhibitory effect was associated with consistent changes in VEGF, RANTES, MIP-1α, MIP-1β MCP-1 and GM-CSF in MLO-Y4 cell-CM. RAW264.7 proliferation was inhibited by MLO-Y4 CM under static or HG conditions, but itincreased by FF-CM with or without HG. In addition, both FF and HG abrogated the capacity of RAW 264.7 cells to differentiate into osteoclasts, but in a different manner. Thus, HG-CM in static condition allowed formation of osteoclast-like cells, which were unable to resorb hydroxyapatite. In contrast, FF-CM prevented osteoclastogenesis even in HG condition. Moreover, HG did not affect basal RANKL or IL-6 secretion or their inhibition induced by FF in MLO-Y4 cells. In conclusion, this in vitro study demonstrates that HG exerts disparate effects on osteocyte mechanotransduction, and provides a novel mechanism by which DM disturbs skeletal metabolism through altered osteocyte-osteoclast communication. This article is protected by copyright. All rights reserved



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Gelation and thermal characteristics of microwave extracted fish gelatin–natural gum composite gels

Abstract

In this study, the gelation and thermal characteristics of microwave extracted fish scale gelatin blended with natural gums such as gum arabic (AG), xanthan gum (XG), guar gum (GG), and tragacanth gum (TG) was evaluated. The nature of interaction and behavior of gelatin in presence of various gums was confirmed by particle size analysis, viscosity profile, FT-IR analysis and turbidity measurements. DSC data revealed that addition of AG, TG and GG remarkably improved the thermal stability of fish gelatin gel. The composite gels of TG, AG, and XG exhibited higher hardness and bloom strength values as compared to pure fish gelatin implying its textural synergy. Based on qualitative descriptive analysis, TG was found to be superior in improving the stability of fish gelatin gel, closely followed by AG. The results suggest that addition of these gums can reduce syneresis and retard melting of gelatin gels at ambient temperature, which are otherwise soft and thermally unstable.



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One-step preparation of banana powder/silver nanoparticles composite films

Abstract

Silver nanoparticles (Ag-NPs) were synthesized using banana powder as a reducing and stabilizing agent, and banana/Ag-NPs composite films with different concentration of Ag-NPs were prepared simultaneously. The composite films were yellowish brown and exhibited characteristic plasmon resonance peak of Ag-NPs at 430 nm. The optical, mechanical, water vapor barrier, thermal stability, and antimicrobial properties of the composite films were greatly influenced by the concentration of Ag-NPs. The composite film with a silver concentration of 1.0 mM demonstrated the highest tensile strength, thermal stability, transparency, and water contact angle with the lowest water vapor permeability (1.36 ± 0.10 × 10−9 g m/m2 Pa s). Also, the composite films incorporated with 1.0 mM of Ag-NPs exhibited a strong antibacterial activity against both Gram-positive (Listeria monocytogenes) and Gram-negative (Escherichia coli) food-borne pathogenic bacteria.



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Optimization of process parameters for the production of collagen peptides from fish skin ( Epinephelus malabaricus) using response surface methodology and its characterization

Abstract

The study optimized the hydrolysis conditions for the production of fish collagen peptides from skin of Malabar grouper (Epinephelus malabaricus) using response surface methodology. The hydrolysis was done with enzymes pepsin, papain and protease from bovine pancreas. Effects of process parameters viz: pH, temperature, enzyme substrate ratio and hydrolysis time of the three different enzymes on degree of hydrolysis were investigated. The optimum response of degree of hydrolysis was estimated to be 10, 20 and 28% respectively for pepsin, papain and protease. The functional properties of the product developed were analysed which showed changes in the properties from proteins to peptides. SDS-PAGE combined with MALDI TOF method was successfully applied to determine the molecular weight distribution of the hydrolysate. The electrophoretic pattern indicated that the molecular weights of peptides formed due to hydrolysis were nearly 2 kDa. MALDI TOF spectral analysis showed the developed hydrolysate contains peptides having molecular weight in the range below 2 kDa.



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Monitoring volatile compounds production throughout fermentation by Saccharomyces and non- Saccharomyces strains using headspace sorptive extraction

Abstract

Currently, there is a growing interest in the use of non-Saccharomyces yeast to enhance the aromatic quality of wine, with pure or mixed cultures, as well as sequential inoculation. Volatile components of wines were closely related to their sensory quality. Hence, to study the evolution of volatile compounds during fermentation was of great interest. For this, sampling methods that did not alter the volume of fermentation media were the most suitable. This work reports the usefulness of headspace sorptive extraction as non-invasive method to monitor the changes in volatile compounds during fermentation. This method allowed monitoring of 141 compounds throughout the process of fermentation by Saccharomyces cerevisiae and Lachancea thermotolerans strains. Both strains showed a similar ability to ferment a must with high sugar content. The S. cerevisiae strain produced higher amount of volatile compounds especially esters that constitutes fruity aroma than L. thermotorelans.



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Postharvest chitosan, gallic acid and chitosan gallate treatments effects on shelf life quality, antioxidant compounds, free radical scavenging capacity and enzymes activities of ‘Sukkari’ bananas

Abstract

The effect of postharvest chitosan, gallic acid (GA) and chitosan gallate (CG) dipping treatments at different concentrations on quality parameters, antioxidant compounds, free radical scavenging capacity (FRSC) and enzymes activities of ‘Sukkari’ bananas were studied during storage (ripening) at 20 ± 2 °C and 60–70% RH for 13 days. Weight loss and peel color index (the change from green to yellow) increased while, membrane stability index of peel tissues, pulp firmness and acidity decreased during storage. CG and GA treatments slowed down the changes in these parameters compared to control. Total soluble solids (TSS) concentration increased during storage and was lower at CG than other treatments. TSS/acid ratio increased during storage and showed higher value after storage than initial. This ratio was lower at 1% chitosan, 0.075% GA and CG treatments than control. Both vitamin C and total flavonoids concentrations decreased during storage and were not affected by the applied treatments. Total phenols concentration decreased during storage and was higher at acetic acid and the high rate of chitosan, GA and CG treatments than control. FRSC (DPPH IC50 values) of fruit peel ranged from 2.54 to 4.19 µg phenolics concentration among the treatments. FRSC was not affected by the applied treatments but increased (lower IC50 value) during shelf life. The possible relations of these biochemical changes with the activities of the enzymes α-amylase, xylanase, polygalacturonase, peroxidase and polyphenoloxidase were discussed. It is concluded that postharvest CG and GA treatments delayed ripening and maintained better quality parameters of ‘Sukkari’ bananas during 13 days of shelf life than control.



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Olive fruits and vacuum impregnation, an interesting combination for dietetic iron enrichment

Abstract

In this study vacuum impregnation (VI) was employed for the iron enrichment of olive fruits, which are very interesting as food vehicle for VI mineral supplementation for the porosity of their pulp. NaFeEDTA was chosen for olives fortification since it prevents iron from binding with compounds that could hinder it from being efficiently absorbed and since it causes few organoleptic problems. In order to improve the efficiency of the VI process, several parameters of the whole process were studied by design of experiment techniques. First of all D-optimal design was employed for a preliminary screening of the most significant process variables and showed that the concentration of VI solution was by far the most significant process variable, though its time in contact with olives was also significant. A factorial design was then applied to the remaining variables and it showed that the speed of the addition of VI solution was also significant. Finally, the application of a face centered composite design to the three selected variables allowed to detect processing conditions leading to final iron contents of 1.5–3 mg/g, corresponding to an introduction of 10–15 mg Fe with four or five fortified olive fruits. No effect on olive taste was observed at these concentrations. The results showed that olive fruits were the most interesting vehicles for the supplementation of both iron and other minerals.



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Detection of pesticides in popular medicinal herbs: a modified QuEChERS and gas chromatography–mass spectrometry based approach

Abstract

Although a lot of work has been conducted in the pesticide residues analysis in food matrices but the quality determination (with respect to major contaminants such as pesticide residues) in medicinal plant matrices has a long way to go. Hence a study was conducted to determine pesticide residues in four medicinal herbs, which are highly traded commodities in international market. Samples were extracted and cleaned up by modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) approach and analyzed by gas chromatograph–mass spectrometer (GC–MS). The method was subjected to thorough validation procedure in-terms of accuracy, precision, limits of quantification (LOQ), matrix effect, linearity and uncertainty analysis. The mean recoveries for most of the pesticides were in the range of 70–120% with RSD <20% and measurement uncertainties were less than 20% for all the compounds at spiking level of 0.5 mg kg−1 in all the matrices. The limits of quantification (LOQ) ranged from 0.01 to 0.069 mg kg−1. The proposed method was successfully applied to determine pesticide residues in 52 commercial market samples obtained from different locations in India.



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HPV vaccine vital for cervical health - Pueblo Chieftain


Pueblo Chieftain

HPV vaccine vital for cervical health
Pueblo Chieftain
According to the Centers for Disease Control and Prevention, in 2008-2012 there were 38,793 HPV-associated cancers in the United States; 15,793 cases were in men (cancer at the back of the throat and tongue) and 23,000 cases in women (cervical cancer ...

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HPV vaccine now funded for boys - Scoop.co.nz


HPV vaccine now funded for boys
Scoop.co.nz
“Most countries who have to date introduced HPV vaccine have focused on the cervical cancer strategy as this is the biggest killer and when resources are constrained – i.e. particularly in low- and middle-income countries – the cost-benefit lines up ...

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Bone Tissue Engineering Under Xenogeneic-Free Conditions in a Large Animal Model as a Basis for Early Clinical Applicability

Tissue Engineering Part A , Vol. 0, No. 0.


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Controlled Retention of BMP-2-Derived Peptide on Nanofibers Based on Mussel-Inspired Adhesion for Bone Formation

Tissue Engineering Part A , Vol. 0, No. 0.


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Conditioned Medium from Periodontal Ligament Stem Cells Enhances Periodontal Regeneration

Tissue Engineering Part A , Vol. 0, No. 0.


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Production in Pichia pastoris, antifungal activity and crystal structure of a class I chitinase from cowpea (Vigna unguiculata): Insights into sugar binding mode and hydrolytic action

Publication date: Available online 31 January 2017
Source:Biochimie
Author(s): Patrícia G. Castro Landim, Tuana O. Correia, Fredy D.A. Silva, Denise R. Nepomuceno, Helen P.S. Costa, Humberto M. Pereira, Marina D.P. Lobo, Frederico B.M.B. Moreno, José Brandão-Neto, Suelen C. Medeiros, Ilka M. Vasconcelos, José T.A. Oliveira, Bruno L. Sousa, Ito L. Barroso-Neto, Valder N. Freire, Cristina P.S. Carvalho, Ana C.O. Monteiro-Moreira, Thalles B. Grangeiro
A cowpea class I chitinase (VuChiI) was expressed in the methylotrophic yeast P. pastoris. The recombinant protein was secreted into the culture medium and purified by affinity chromatography on a chitin matrix. The purified chitinase migrated on SDS-polyacrylamide gel electrophoresis as two closely-related bands with apparent molecular masses of 34 and 37 kDa. The identity of these bands as VuChiI was demonstrated by mass spectrometry analysis of tryptic peptides and N-terminal amino acid sequencing. The recombinant chitinase was able to hydrolyze colloidal chitin but did not exhibit enzymatic activity toward synthetic substrates. The highest hydrolytic activity of the cowpea chitinase toward colloidal chitin was observed at pH 5.0. Furthermore, most VuChiI activity (approximately 92%) was retained after heating to 50 °C for 30 min, whereas treatment with 5 mM Cu2+ caused a reduction of 67% in the enzyme's chitinolytic activity. The recombinant protein had antifungal activity as revealed by its ability to inhibit the spore germination and mycelial growth of Penicillium herquei. The three-dimensional structure of VuChiI was resolved at a resolution of 1.55 Å by molecular replacement. The refined model had 245 amino acid residues and 381 water molecules, and the final R-factor and Rfree values were 14.78 and 17.22%, respectively. The catalytic domain of VuChiI adopts an α-helix-rich fold, stabilized by 3 disulfide bridges and possessing a wide catalytic cleft. Analysis of the crystallographic model and molecular docking calculations using chito-oligosaccharides provided evidences about the VuChiI residues involved in sugar binding and catalysis, and a possible mechanism of antifungal action is suggested.

Graphical abstract

image


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Lipid-load in peripheral blood mononuclear cells: impact of food-consumption, dietary-macronutrients, extracellular lipid availability and demographic factors

Publication date: Available online 30 January 2017
Source:Biochimie
Author(s): Fatima Ameer, Rimsha Munir, Hina Usman, Rida Rashid, Muhammad Shahjahan, Shahida Hasnain, Nousheen Zaidi
Lipid-load in peripheral blood mononuclear cells (PBMCs) has recently gained attention of the researchers working on nutritional regulation of metabolic health. Previous works have indicated that the metabolic circuitries in the circulating PBMCs are influenced by dietary-intake and macronutrient composition of diet. In the present work, we analyzed the impact of diet and dietary macronutrients on PBMCs’ lipid-load. The overall analyses revealed that dietary carbohydrates and fats combinatorially induce triglyceride accumulation in PBMCs. On the other hand, dietary fats were shown to induce significant decrease in PBMCs’ cholesterol-load. The effects of various demographic factors –including age, gender and body-weight– on PBMCs’ lipid-load were also examined. Body-weight and age were both shown to affect PBMC’s lipid-load. Our study fails to provide any direct association between extracellular lipid availability and cholesterol-load in both, freshly isolated and cultured PBMCs. The presented work significantly contributes to the current understanding of the impact of food-consumption, dietary macronutrients, extracellular lipid availability and demographic factors on lipid-load in PBMCs.



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Otolaryngology (ENT) Sub-Specialties - News-Medical.net


News-Medical.net

Otolaryngology (ENT) Sub-Specialties
News-Medical.net
... and various sub-specialties. These include such disciplines as pediatrics, oncology, sinus disease, and surgery. Because of their range of capabilities, ENT surgeons might one day correct a child's tonsillitis and on the next day treat an adult's ...

and more »


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The need of standardization and of large clinical studies in an emerging indication of [ 18 F]FDG PET: the autoimmune encephalitis



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Intra-lesional spatial correlation of static and dynamic FET-PET parameters with MRI-based cerebral blood volume in patients with untreated glioma

Abstract

Purpose

18F-fluorethyltyrosine-(FET)-PET and MRI-based relative cerebral blood volume (rCBV) have both been used to characterize gliomas. Recently, inter-individual correlations between peak static FET-uptake and rCBV have been reported. Herein, we assess the local intra-lesional relation between FET-PET parameters and rCBV.

Methods

Thirty untreated glioma patients (27 high-grade) underwent simultaneous PET/MRI on a 3 T hybrid scanner obtaining structural and dynamic susceptibility contrast sequences. Static FET-uptake and dynamic FET-slope were correlated with rCBV within tumour hotspots across patients and intra-lesionally using a mixed-effects model to account for inter-individual variation. Furthermore, maximal congruency of tumour volumes defined by FET-uptake and rCBV was determined.

Results

While the inter-individual relationship between peak static FET-uptake and rCBV could be confirmed, our intra-lesional, voxel-wise analysis revealed significant positive correlations (median r = 0.374, p < 0.0001). Similarly, significant inter- and intra-individual correlations were observed between FET-slope and rCBV. However, rCBV explained only 12% of the static and 5% of the dynamic FET-PET variance and maximal overlap of respective tumour volumes was 37% on average.

Conclusions

Our results show that the relation between peak values of MR-based rCBV and static FET-uptake can also be observed intra-individually on a voxel basis and also applies to a dynamic FET parameter, possibly determining hotspots of higher biological malignancy. However, just a small part of the FET-PET signal variance is explained by rCBV and tumour volumes determined by the two modalities showed only moderate overlap. These findings indicate that FET-PET and MR-based rCBV provide both congruent and complimentary information on glioma biology.



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Intraindividual tumor heterogeneity in NET – Further insight by C-X-C motif chemokine receptor 4-directed imaging



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Erratum to: Role of PET/CT in malignant pediatric lymphoma



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Erratum to: The need of standardization and of large clinical studies in an emerging indication of [18 F]FDG PET: the autoimmune encephalitis



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Asymmetric relapse of an HIV-associated Kaposi sarcoma



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Predictive value of [ 18 F]-fluoride PET for monitoring bone remodeling in patients with orthopedic conditions treated with a Taylor spatial frame

Abstract

Purpose

The Taylor Spatial Frame (TSF) is used to correct orthopedic conditions such as correction osteotomies in delayed fracture healing and pseudarthrosis. Long-term TSF-treatments are common and may lead to complications. Current conventional radiological methods are often unsatisfactory for therapy monitoring. Hence, an imaging technique capable of quantifying bone healing progression would be advantageous.

Methods

A cohort of 24 patients with different orthopedic conditions, pseudarthrosis (n = 10), deformities subjected to correction osteotomy (n = 9), and fracture (n = 5) underwent dynamic [18F]-fluoride (Na18F) PET/CT at 8 weeks and 4 months, respectively, after application of a TSF. Parametric images, corresponding to the net transport rate of [18F]-fluoride from plasma to bone, K i were calculated. The ratio of the maximum K i at PET scan 2 and 1 ( \( {\overline{K}}_{i, \max } \) ) as well as the ratio of the maximum Standard Uptake Value at PET scan 2 and 1 ( \( {\overline{SUV}}_{\max } \) ) were calculated for each individual. Different treatment end-points were scored, and the overall treatment outcome score was compared with the osteoblastic activity progression as scored with \( {\overline{K}}_{i, \max } \) or \( {\overline{SUV}}_{\max } \) .

Results

\( {\overline{K}}_{i, \max } \) and \( {\overline{SUV}}_{\max } \) were not correlated within each orthopedic group (p > 0.1 for all groups), nor for the pooled population (p = 0.12). The distribution of \( {\overline{K}}_{i, \max } \) was found significantly different among the different orthopedic groups (p = 0.0046) -also for \( {\overline{SUV}}_{\max } \) (p = 0.022). The positive and negative treatment predictive values for \( {\overline{K}}_{i, \max } \) were 66.7 % and 77.8 %, respectively. Corresponding values for \( {\overline{SUV}}_{\max } \) were 25 % and 33.3 %

Conclusions

The \( {\overline{K}}_{i, \max } \) obtained from dynamic [18F]-fluoride-PET imaging is a promising predictive factor to evaluate changes in bone healing in response to TSF treatment.



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Radiosynoviorthesis in hemophilic arthropathy: pathologic blood pool imaging on pre-therapeutic bone scintigraphy is not a predictor of treatment success

Abstract

Purpose

Increased articular 99mTc MDP uptake on blood pool imaging (BPI) of patients with rheumatologic conditions is indicative of active inflammatory changes, and has been suggested as a strong predictor of response to radiosynoviorthesis (RSO). In this study, we aimed to assess the value of pretreatment BPI positivity (i.e. scintigraphic-apparent hyperemia) for successful RSO in hemophilic arthropathy.

Methods

Thirty-four male patients with painful hemophilic arthropathy underwent RSO after failure of conservative treatment. Treated joints comprised the knee in eight, elbow in five, and ankle in 21 patients. Pretreatment triple-phase bone scintigraphy showed hyperemic joints (pathologic BPI) in 17 patients, whereas 17 patients had no increased tracer uptake on BPI. Response to RSO was evaluated 6 months post-treatment by measuring changes in intensity of arthralgia according to the visual analog scale (VAS), bleeding frequency, and range of motion. The association between hyperemia (pathologic BPI) and treatment outcome was examined using nonparametric tests for independent samples.

Results

Clinically evident pain relief occurred in 26 patients (76.5 %), and the mean VAS decreased from 7.7 ± 1.1 to 4.6 ± 2.7 (p < 0.001). Joint bleeding frequency (hemarthrosis) decreased from 4.5 ± 0.6 to 2.1 ± 0.4 during the first 6 months after RSO (p < 0.001). For both parameters (pain relief and bleeding frequency), patients experienced a similar benefit from RSO regardless of pretreatment BPI: arthralgia (p = 0.312) and frequency of hemarthrosis (p = 0.396). No significant improvement was observed for range of motion, but it was significantly more restricted in hyperemic joints both before (p = 0.036) and after treatment (p = 0.022).

Conclusions

Hemophilic arthropathy can be effectively treated with RSO regardless of pre-therapeutic BPI. Patients in whom articular hyperemia is not detectable by scintigraphy may have similar (outstanding) outcomes, and thus should not be excluded from treatment.



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William C. Klingesmith III: The Mathematics and Biology of the Biodistribution of Radiopharmaceuticals: A Clinical Perspective



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A systematic review of lessons learned from PET molecular imaging research in atypical parkinsonism (Niccolini and Politis, 2016)



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The prognostic and predictive value of sstr 2 -immunohistochemistry and sstr 2 -targeted imaging in neuroendocrine tumors

Abstract

Purpose

Our aim was to assess the prognostic and predictive value of somatostatin receptor 2 (sstr2) in neuroendocrine tumors (NETs).

Methods

We established a tissue microarray and imaging database from NET patients that received sstr2-targeted radiopeptide therapy with yttrium-90-DOTATOC, lutetium-177-DOTATOC or alternative treatment. We used univariate and multivariate analyses to identify prognostic and predictive markers for overall survival, including sstr2-imaging and sstr2-immunohistochemistry.

Results

We included a total of 279 patients. In these patients, sstr2-immunohistochemistry was an independent prognostic marker for overall survival (HR: 0.82, 95 % CI: 0.67 – 0.99, n = 279, p = 0.037). In DOTATOC patients, sstr2-expression on immunohistochemistry correlated with tumor uptake on sstr2-imaging (n = 170, p < 0.001); however, sstr2-imaging showed a higher prognostic accuracy (positive predictive value: +27 %, 95 % CI: 3 – 56 %, p = 0.025). Sstr2-expression did not predict a benefit of DOTATOC over alternative treatment (p = 0.93).

Conclusions

Our results suggest sstr2 as an independent prognostic marker in NETs. Sstr2-immunohistochemistry correlates with sstr2-imaging; however, sstr2-imaging is more accurate for determining the individual prognosis.



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A systematic review of lessons learned from PET molecular imaging research in atypical parkinsonism



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Computed-tomography-guided anatomic standardization for quantitative assessment of dopamine transporter SPECT

Abstract

Purpose

For the quantitative assessment of dopamine transporter (DAT) using [123I]FP-CIT single-photon emission computed tomography (SPECT) (DaTscan), anatomic standardization is preferable for achieving objective and user-independent quantification of striatal binding using a volume-of-interest (VOI) template. However, low accumulation of DAT in Parkinson’s disease (PD) would lead to a deformation error when using a DaTscan-specific template without any structural information. To avoid this deformation error, we applied computed tomography (CT) data obtained using SPECT/CT equipment to anatomic standardization.

Methods

We retrospectively analyzed DaTscan images of 130 patients with parkinsonian syndromes (PS), including 80 PD and 50 non-PD patients. First we segmented gray matter from CT images using statistical parametric mapping 12 (SPM12). These gray-matter images were then anatomically standardized using the diffeomorphic anatomical registration using exponentiated Lie algebra (DARTEL) algorithm. Next, DaTscan images were warped with the same parameters used in the CT anatomic standardization. The target striatal VOIs for decreased DAT in PD were generated from the SPM12 group comparison of 20 DaTscan images from each group. We applied these VOIs to DaTscan images of the remaining patients in both groups and calculated the specific binding ratios (SBRs) using nonspecific counts in a reference area. In terms of the differential diagnosis of PD and non-PD groups using SBR, we compared the present method with two other methods, DaTQUANT and DaTView, which have already been released as software programs for the quantitative assessment of DaTscan images.

Results

The SPM12 group comparison showed a significant DAT decrease in PD patients in the bilateral whole striatum. Of the three methods assessed, the present CT-guided method showed the greatest power for discriminating PD and non-PD groups, as it completely separated the two groups.

Conclusion

CT-guided anatomic standardization using the DARTEL algorithm is promising for the quantitative assessment of DaTscan images.



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**-Postprandial pancreatic [ 11 C]methionine uptake after pancreaticoduodenectomy mirrors basal beta cell function and insulin release

Abstract

Purpose

[S-methyl-11C]-L-methionine ([11C]MET) uptake in the pancreas might be a central indicator of beta cell function. Since gastric emptying was recently shown to influence glycemic control in subjects after pancreaticoduodenectomy (PD, the surgical treatment of neoplasms of the pancreas head), we looked for imaginable relationships between gastric emptying, pre- and postprandial insulin concentrations, and [11C]MET uptake.

Methods

Nineteen tumor-free survivors after PD (age mean ± SD: 61 ± 8.7 yrs.; 10 male, 9 female) and 10 healthy controls (age: 27 ± 8.7 yrs.; 7 male, 3 female) were given a mixed test meal. One gram of paracetamol was ingested with the meal to evaluate the speed of gastric emptying. Insulin, glucose, and paracetamol plasma concentrations were measured before and over 180 minutes after ingestion. Beta cell function was calculated from fasting glucose and insulin plasma concentrations. Simultaneously, 800 MBq of [11C]MET were administered and the activity (maximum tissue standardized uptake values [SUVmax]) over the pancreas was measured at 15, 30, and 60 minutes after injection. Total integrated SUVmax (area under the curve [AUC]) and incremental SUVmax were calculated.

Results

The uptake of [11C]MET in the pancreas was significantly higher (p < 0.0001) in controls compared to the PD group. Gastric emptying was significantly slower in controls compared to pancreatectomy subjects (p < 0.0001). Paracetamol AUC30 correlated with the SUVmax increment between 15 and 30 minutes (R2 = 0.27, p = 0.0263), suggesting a relationship between gastric emptying and the uptake of [11C]MET. Total integrated SUVmax correlated with insulin AUC60 (R2 = 0.66,p < 0.0001) in patients after PD. Multivariate regression analysis revealed insulin AUC60 and beta cell function, calculated from the fasting insulin to glucose ratio, as independent predictors of 11C-methionine uptake, i.e. total integrated SUVmax, in patients after PD (R2 = 0.78, p < 0.0001).

Conclusion

Postprandial [11C]MET uptake may represent basal and postprandial beta cell function. The findings suggest a possible usefulness of this imaging procedure for further studying beta cell function.



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On the accuracy and reproducibility of a novel probabilistic atlas-based generation for calculation of head attenuation maps on integrated PET/MR scanners

Abstract

Purpose

To propose an MR-based method for generating continuous-valued head attenuation maps and to assess its accuracy and reproducibility. Demonstrating that novel MR-based photon attenuation correction methods are both accurate and reproducible is essential prior to using them routinely in research and clinical studies on integrated PET/MR scanners.

Methods

Continuous-valued linear attenuation coefficient maps (“μ-maps”) were generated by combining atlases that provided the prior probability of voxel positions belonging to a certain tissue class (air, soft tissue, or bone) and an MR intensity-based likelihood classifier to produce posterior probability maps of tissue classes. These probabilities were used as weights to generate the μ-maps. The accuracy of this probabilistic atlas-based continuous-valued μ-map (“PAC-map”) generation method was assessed by calculating the voxel-wise absolute relative change (RC) between the MR-based and scaled CT-based attenuation-corrected PET images. To assess reproducibility, we performed pair-wise comparisons of the RC values obtained from the PET images reconstructed using the μ-maps generated from the data acquired at three time points.

Results

The proposed method produced continuous-valued μ-maps that qualitatively reflected the variable anatomy in patients with brain tumor and agreed well with the scaled CT-based μ-maps. The absolute RC comparing the resulting PET volumes was 1.76 ± 2.33 %, quantitatively demonstrating that the method is accurate. Additionally, we also showed that the method is highly reproducible, the mean RC value for the PET images reconstructed using the μ-maps obtained at the three visits being 0.65 ± 0.95 %.

Conclusion

Accurate and highly reproducible continuous-valued head μ-maps can be generated from MR data using a probabilistic atlas-based approach.



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“la synoviorthèse” can more than synovitis!



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FDG-PET imaging to detect and characterize infectious disorders; an unavoidable path for the foreseeable future



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[ 18 F]FDG PET accurately differentiates infected and non-infected non-unions after fracture fixation

Abstract

Purpose

Complete fracture healing is crucial for good patient outcomes. A major complication in the treatment of fractures is non-union. The pathogenesis of non-unions is not always clear, although implant-associated infections play a significant role, especially after surgical treatment of open fractures. We aimed to evaluate the value of [18F]FDG PET in suspected infections of non-union fractures.

Methods

We retrospectively evaluated 35 consecutive patients seen between 2000 and 2015 with suspected infection of non-union fractures, treated at a level I trauma center. The patients underwent either [18F]FDG PET/CT (N = 24), [18F]FDG PET (N = 11) plus additional CT (N = 8), or conventional X-ray (N = 3). Imaging findings were correlated with final diagnosis based on intraoperative culture or follow-up.

Results

In 13 of 35 patients (37 %), infection was proven by either positive intraoperative tissue culture (N = 12) or positive follow-up (N = 1). [18F]FDG PET revealed 11 true-positive, 19 true-negative, three false-positive, and two false-negative results, indicating sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 85 %, 86 %, 79 %, 90 %, and 86 %, respectively. The SUVmax was 6.4 ± 2.7 in the clinically infected group and 3.0 ± 1.7 in the clinically non-infected group (p <0.01). The SUVratio was 5.3 ± 3.3 in the clinically infected group and 2.6 ± 1.5 in the clinically non-infected group (p <0.01).

Conclusion

[18F]FDG PET differentiates infected from non-infected non-unions with high accuracy in patients with suspected infections of non-union fractures, for whom other clinical findings were inconclusive for a local infection. [18F]FDG PET should be considered for therapeutic management of non-unions.



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Long-term follow-up and role of FDG PET in advanced pancreatic neuroendocrine patients treated with 177 Lu-D OTATATE

Abstract

Purpose

Lu-DOTATATE (Lu-PRRT) is a valid therapeutic option in differentiated pancreatic neuroendocrine tumors (P-NETs). FDG PET seems to be an important prognostic factor in P-NETs. We evaluated the efficacy of Lu-PRRT and the role of FDG PET in 60 patients with advanced P-NETs.

Methods

From March 2008 to June 2011, 60 consecutive patients with P-NETs were enrolled in the study. Follow-up lasted until March 2016. Eligible patients were treated with two different total cumulative activities (18.5 or 27.8 GBq in 5 cycles every 6–8 weeks), according to kidney and bone marrow parameters.

Results

Twenty-eight patients received a mean full activity (FA) of 25.9 GBq and 32 a mean reduced activity (RA) of 18.5 GBq. The disease control rate (DCR), defined as the sum of CR+PR+SD was 85.7 % in the FA group and 78.1 % in the RA group. Median progression-free survival (mPFS) was 53.4 months in the FA group and 21.7 months in the RA group (P = 0.353). Median overall survival (mOS) was not reached (nr) in FA patients and was 63.8 months in the RA group (P = 0.007). Fifty-five patients underwent an FDG PET scan before Lu-PRRT, 32 (58 %) showing an increased FDG uptake in tumor sites. mPFS was 21.1 months in FDG PET-positive patients and 68.7 months in the FDG PET-negative group (P < 0.0002), regardless of the total activity administered.

Conclusion

Both FA and RA are active in patients undergoing Lu-PRRT. However, an FA of 27.8 GBq of Lu-PRRT prolongs PFS and OS compared to an RA of 18.5 GBq. Our results indicate that FDG PET is an independent prognostic factor in this patient setting.



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Otolaryngology (ENT) Sub-Specialties - News-Medical.net


News-Medical.net

Otolaryngology (ENT) Sub-Specialties
News-Medical.net
... and various sub-specialties. These include such disciplines as pediatrics, oncology, sinus disease, and surgery. Because of their range of capabilities, ENT surgeons might one day correct a child's tonsillitis and on the next day treat an adult's ...

and more »


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Menopause

Menopause: The time in a woman's life when menstrual periods permanently stop; it is also called the "change of life."

Menopause is defined as the time when there has been no menstrual periods for 12 consecutive months and no other biological or physiological cause can be identified. It is the end of fertility, the end of the childbearing years. (A woman may still, however, be able to become pregnant unless 12 consecutive months have passed without a period.)

A woman can usually tell if she is approaching menopause because her menstrual periods starts changing. The medical terms used to describe this time are "perimenopause" and the "menopause transition."

Natural menopause occurs when the ovaries naturally begin decreasing their production of the sex hormones estrogen and progesterone.

Induced menopause occurs if the ovaries are surgically removed (by bilateral oophorectomy) or damaged by radiation or drugs. Due to the abrupt cutoff of ovarian hormones, induced menopause causes the sudden onset of hot flashes and other menopause-related symptoms such as a dry vagina and a decline in sex drive. Early menopause (before age 40), whether natural or induced, carries a greater risk for heart disease and osteoporosis since there are more years spent beyond the protective cover of estrogen.

A "simple" hysterectomy (when the uterus but not the ovaries are removed) before natural menopause should not affect the production of sex hormones and so not cause menopause (unless the nerves or blood supply to the ovaries is damaged during the hysterectomy).

The timing of natural menopause is variable. In the western world, the average age at which menopause starts is now 51. Natural menopause can, however, be in a woman's 30s or 60s. Factors influencing the time of menopause include heredity (genetics) and cigarette smoking. Smokers (and former smokers) reach menopause an average of 2 years before women who have never smoked.

There is no relation between the time of a woman's first period and her age at menopause. The age at menopause is not influenced by a woman's race, height, number of children or use of oral contraceptives.

The changes of the menopause transition (perimenopause) begin about 6 years before the natural menopause. This is a time when the levels of hormones produced by the aging ovaries fluctuate, leading to irregular menstrual patterns (irregularity in the length of the period, the time between periods, and the level of flow) and hot flashes (a sudden warm feeling with blushing). Other changes associated with the perimenopause and menopause include night sweats, mood swings, vaginal dryness, fluctuations in sexual desire (libido), forgetfulness, trouble sleeping and fatigue (probably from the loss of sleep).



MedTerms (TM) is the Medical Dictionary of MedicineNet.com.
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Combined PET imaging of the inflammatory tumor microenvironment identifies margins of unique radiotracer uptake

The tumor microenvironment is highly heterogeneous. For gliomas, the tumor-associated inflammatory response is pivotal to support growth and invasion. Factors of glioma growth, inflammation, and invasion, such as the translocator protein (TSPO) and matrix metalloproteinases (MMP), may serve as specific imaging biomarkers of the glioma microenvironment. In this study, non-invasive imaging by positron emission tomography (PET) with [18F]DPA-714 (TSPO) and [18F]BR-351 (MMP) was used for assessment of localization and quantification of the expression of TSPO and MMP. Imaging was performed in addition to established clinical imaging biomarker of active tumor volume ([18F]FET) in conjunction with magnetic resonance imaging (MRI). We hypothesized that each imaging biomarker revealed distinct areas of the heterogeneous glioma tissue in a mouse model of human glioma. Tracers were found to be increased 1.4-1.7 fold with [18F]FET showing the biggest volume as depicted by a thresholding-based, volumes of interest (VOI) analysis. Tumor areas, which could not be detected by a single tracer and/or MRI parameter alone, were measured. Specific compartments of [18F]DPA-714 (14%) and [18F]BR-351 (11%) volumes along the tumor rim could be identified. [18F]DPA-714 (TSPO) and [18F]BR-351 (MMPs) matched with histology. Glioma-associated microglia/macrophages (GAM) were identified as TSPO and MMP sources. Multi-tracer and multi-modal molecular imaging approaches may allow us to gain important insights into glioma-associated inflammation (GAM, MMP). Moreover, this non-invasive technique enables characterization of the glioma microenvironment with respect to the disease-driving cellular compartments at the various disease stages.

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Fixed Point Theorems for Multivalued Nonself -Almost Contractions in Banach Spaces Endowed with Graphs

In this paper, we prove some fixed point theorems for multivalued nonself -almost contractions in Banach spaces with a directed graph and give some examples to illustrate our main results. The main results in this paper extend and generalize many known results in the literature therein.

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Disseminated Histoplasmosis with Oral Manifestation in an Immunocompetent Patient

A case of disseminated histoplasmosis (DH) in a 60-year-old female patient is reported from Jaipur, Rajasthan, India. The patient presented with multiple papules on the skin surrounding the lips, face, torso, trunk, and back. She also complained of growth in the palate. Histoplasmosis was confirmed by biopsy and histopathology of skin and palatal lesions. This case report highlights the presenting features and occurrence of histoplasmosis in nonendemic region in India.

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Osteopathic Manipulative Treatment Limits Chronic Constipation in a Child with Pitt-Hopkins Syndrome

Pitt-Hopkins Syndrome (PTHS) is a rare genetic disorder caused by insufficient expression of the TCF4 gene. Children with PTHS typically present with gastrointestinal disorders and early severe chronic constipation is frequently found (75%). Here we describe the case of a PTHS male 10-year-old patient with chronic constipation in whom Osteopathic Manipulative Treatment (OMT) resulted in improved bowel functions, as assessed by the diary, the QPGS-Form A Section C questionnaire, and the Paediatric Bristol Stool Form Scale. The authors suggested that OMT may be a valid tool to improve the defecation frequency and reduce enema administration in PTHS patients.

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Accurate and Autonomous Star Acquisition Method for Star Sensor under Complex Conditions

Star sensor is a preferred attitude measurement device for its extremely high accuracy. Star acquisition is the essential and critical procedure, which is aiming at acquiring accurate star areas. However, degenerated acquisition results under complex conditions become one of the major restrictions for modern star sensor. In this paper, an accurate and autonomous star acquisition method is proposed. Mathematical morphology and variable thresholding are combined for accurate star extraction; motion PSF is estimated in frequency domain and nonlinear filter is adopted for star restoration. Accurate star acquisition can be achieved based on only one star image. Simulations and laboratory experiments are conducted for verification. Several existing methods are also reproduced for comparison. Acquisition results demonstrate that the proposed method is effective and an excellent performance can be achieved autonomously under complex conditions, along with more detected stars and improved acquisition accuracy.

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Sinonasal Melanoma: A Case Report and Literature Review

Purpose. Sinonasal malignant mucosal melanoma is a rare, aggressive tumour. Nasal obstruction and epistaxis are the most commonly reported symptoms, although symptomatology may develop late and be nonspecific, which tends to delay diagnosis, resulting in a poorer prognosis. Case Report. This report describes a 64-year-old male patient with nasal obstruction and epistaxis. Computed tomography of the facial sinuses revealed a large lesion in the right nasal cavity, with infiltration into the left cavity, ethmoidal cells, and erosion of the cribriform plate. Initial incisional biopsy revealed an undifferentiated carcinoma of the right maxillary sinus, staged as T4aN0M0. Induction chemotherapy was initiated with cisplatin and etoposide. Response to treatment was complete. The patient was then submitted to radiotherapy with concomitant cisplatin. Immunochemical analysis revealed positivity for vimentin, S100, and HMB-45 (human melanoma black 45), a result compatible with a diagnosis of malignant melanoma. Discussion. Due to the rarity of the tumour and the patient’s complete response to chemotherapy and since no blackened lesion had been found at the previous exam, treatment was continued as planned. The patient remains healthy, with no metastasis or recurrence. He is currently being monitored by the clinical oncology team.

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Electroacupuncture for Functional Constipation: A Multicenter, Randomized, Control Trial

Background and Aim. To investigate the efficacy and safety of electroacupuncture (EA) with different current intensities for functional constipation (FC) and to assess whether the effects of EA with different current intensities are superior to the mosapride. Methods. Patients with FC were randomly divided into low current intensity group (LCI), high current intensity group (HCI), and mosapride group (MC). The primary outcome was three or more spontaneous bowel movements (SBMs) per week and an increase of one or more SBMs from baseline during at least 3 of the 4 weeks. Results. The primary outcome was reached by 53.45%, 66.15%, and 52.24% of the patients who received LCI, HCI, and mosapride, respectively. EA can significantly improve the weekly SBMs and stool consistency and reduce straining severity (, all). HCI improved the quality of life better than mosapride () and reduced the proportion of severe constipation more than LCI and mosapride (, both). Conclusions. EA is effective and safe at both current intensities for FC; therapeutic effects of LCI and HCI are not superior to mosapride. EA is superior to mosapride in improving patients’ life quality and satisfaction level of treatment; EA has fewer adverse events than mosapride.

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Equilibrium Decision Method for Earthquake First-Aid Medicine Allocation Based on Demand Information Updating

The allocation of rescue resources after an earthquake has become a popular research topic in the field of emergency management. The allocation of first-aid medicine for earthquake rescue has stronger time sensitivity than that of general rescue materials. This study focuses on the problem of first-aid medicine allocation in earthquake response. First, we consider the incompleteness and renewal of decision information in an emergency environment, as well as the balance between the risk of decision error and delay. Second, we propose an equilibrium decision method for the allocation of first-aid medicine in earthquake rescue based on information update. This method attempts to realize a fair allocation to all disaster places and minimize total transport time loss. Third, a simulation analysis is performed in which the proposed method is applied to the first-aid medicine allocation problem in the Wenchuan earthquake response. Results show that the method can be used to create a good allocation plan in an earthquake rescue situation.

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A Computer-Aided Analysis Method of SPECT Brain Images for Quantitative Treatment Monitoring: Performance Evaluations and Clinical Applications

The objective and quantitative analysis of longitudinal single photon emission computed tomography (SPECT) images are significant for the treatment monitoring of brain disorders. Therefore, a computer aided analysis (CAA) method is introduced to extract a change-rate map (CRM) as a parametric image for quantifying the changes of regional cerebral blood flow (rCBF) in longitudinal SPECT brain images. The performances of the CAA-CRM approach in treatment monitoring are evaluated by the computer simulations and clinical applications. The results of computer simulations show that the derived CRMs have high similarities with their ground truths when the lesion size is larger than system spatial resolution and the change rate is higher than 20%. In clinical applications, the CAA-CRM approach is used to assess the treatment of 50 patients with brain ischemia. The results demonstrate that CAA-CRM approach has a 93.4% accuracy of recovered region’s localization. Moreover, the quantitative indexes of recovered regions derived from CRM are all significantly different among the groups and highly correlated with the experienced clinical diagnosis. In conclusion, the proposed CAA-CRM approach provides a convenient solution to generate a parametric image and derive the quantitative indexes from the longitudinal SPECT brain images for treatment monitoring.

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Urban Aerodynamic Roughness Length Mapping Using Multitemporal SAR Data

Aerodynamic roughness is very important to urban meteorological and climate studies. Radar remote sensing is considered to be an effective means for aerodynamic roughness retrieval because radar backscattering is sensitive to the surface roughness and geometric structure of a given target. In this paper, a methodology for aerodynamic roughness length estimation using SAR data in urban areas is introduced. The scale and orientation characteristics of backscattering of various targets in urban areas were firstly extracted and analyzed, which showed great potential of SAR data for urban roughness elements characterization. Then the ground truth aerodynamic roughness was calculated from wind gradient data acquired by the meteorological tower using fitting and iterative method. And then the optimal dimension of the upwind sector for the aerodynamic roughness calculation was determined through a correlation analysis between backscattering extracted from SAR data at various upwind sector areas and the aerodynamic roughness calculated from the meteorological tower data. Finally a quantitative relationship was set up to retrieve the aerodynamic roughness length from SAR data. Experiments based on ALOS PALSAR and COSMO-SkyMed data from 2006 to 2011 prove that the proposed methodology can provide accurate roughness length estimations for the spatial and temporal analysis of urban surface.

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Stenosing Tenosynovitis of the Flexor Hallucis Longus Tendon Associated with the Plantar Capsular Accessory Ossicle at the Interphalangeal Joint of the Great Toe

This report presents a case of stenosing tenosynovitis of the flexor hallucis longus tendon associated with the plantar capsular accessory ossicle at the interphalangeal joint of the great toe, which was confirmed by intraoperative observation and was successfully treated with surgical resection of the ossicle. As the plantar capsular accessory ossicle was not visible radiographically due to the lack of ossification, ultrasonography was helpful for diagnosing this disorder.

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Optimal Container Routing in Liner Shipping Networks Considering Repacking 20 ft Containers into 40 ft Containers

The volume of a 40 ft container is twice as large as that of a 20 ft container. However, the handling cost (loading, unloading, and transshipment) of a 40 ft container is much lower than twice the corresponding handling cost of two 20 ft containers. Enlightened by this observation, we propose a novel container routing with repacking problem in liner shipping, where two 20 ft containers can be repacked to a 40 ft container in order to reduce the handling cost. We develop a mixed-integer linear programming model that formulates the routing decisions and the repacking decisions in a holistic manner. An illustrative example is reported to demonstrate the applicability of the model. Results show that the benefit of repacking is the most significant when containers are transshipped several times.

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Pencil Graphite Electrodes: A Versatile Tool in Electroanalysis

Due to their electrochemical and economical characteristics, pencil graphite electrodes (PGEs) gained in recent years a large applicability to the analysis of various types of inorganic and organic compounds from very different matrices. The electrode material of this type of working electrodes is constituted by the well-known and easy commercially available graphite pencil leads. Thus, PGEs are cheap and user-friendly and can be employed as disposable electrodes avoiding the time-consuming step of solid electrodes surface cleaning between measurements. When compared to other working electrodes PGEs present lower background currents, higher sensitivity, good reproducibility, and an adjustable electroactive surface area, permitting the analysis of low concentrations and small sample volumes without any deposition/preconcentration step. Therefore, this paper presents a detailed overview of the PGEs characteristics, designs and applications of bare, and electrochemically pretreated and chemically modified PGEs along with the corresponding performance characteristics like linear range and detection limit. Techniques used for bare or modified PGEs surface characterization are also reviewed.

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Influence of Different Patellofemoral Design Variations Based on Genesis II Total Knee Endoprosthesis on Patellofemoral Pressure and Kinematics

In total knee arthroplasty (TKA), patellofemoral groove design varies greatly and likely has a distinct influence on patellofemoral biomechanics. To analyse the selective influence, five patellofemoral design variations were developed based on Genesis II total knee endoprosthesis (original design, being completely flat, being laterally elevated, being medially elevated, and both sides elevated) and made from polyamide using rapid prototyping. Muscle-loaded knee flexion was simulated on 10 human knee specimens using a custom-made knee simulator, measuring the patellofemoral pressure distribution and tibiofemoral and patellofemoral kinematics. The measurements were carried out in the native knee as well as after TKA with the 5 design prototypes. The overall influence of the different designs on the patellofemoral kinematics was small, but we found detectable effects for mediolateral tilt ( for 35°–80° flexion) and translation of the patella ( for 20°–65° and 75°–90°), especially for the completely flat design. Considering patellofemoral pressures, major interindividual differences were seen between the designs, which, on average, largely cancelled each other out. These results suggest that the elevation of the lateral margin of the patellofemoral groove is essential for providing mediolateral guidance, but smooth contouring as with original Genesis II design seems to be sufficient. The pronounced interindividual differences identify a need for more patellofemoral design options in TKA.

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Dirac Field as a Source of the Inflation in Dimensional Teleparallel Gravity

In this paper, we study early-time inflation and late-time acceleration of the universe by nonminimally coupling the Dirac field with torsion in the spatially flat Friedman-Robertson-Walker (FRW) cosmological model background. The results obtained by the Noether symmetry approach with and without a gauge term are compared. Additionally, we compare these results with that of the dimensional teleparallel gravity under Noether symmetry approach. And we see that the study explains early-time inflation and late-time acceleration of the universe.

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Hard Physical Work Intensifies the Occupational Consequence of Physician-Diagnosed Back Disorder: Prospective Cohort Study with Register Follow-Up among 10,000 Workers

While musculoskeletal pain is common in the population, less is known about its labor market consequences in relation to physical activity at work. This study investigates whether hard physical work aggravates the consequences of back disorder. Using Cox regression analyses, we estimated the joint association of physical activity at work and physician-diagnosed back disorder in 2010 with the risk of register-based long-term sickness absence (LTSA) of at least 6 consecutive weeks during 2011-2012 among 9,544 employees from the general working population (Danish Work Environment Cohort Study). Control variables were age, gender, psychosocial work environment, smoking, leisure physical activity, BMI, depression, and mental health. At baseline, 19.4% experienced high low-back pain intensity (≥5, 0–9 scale) and 15.2% had diagnosed back disorder. While high pain intensity was a general predictor for LTSA, physician-diagnosed back disorder was a stronger predictor among those with hard physical work (HR 2.23; 95% CI 1.68–2.96) compared with light work (HR 1.40; 95% CI 1.09–1.80). Similarly, physician-diagnosed back disorder with simultaneous high pain intensity predicted LTSA to a greater extent among those with hard physical work. In conclusion, the occupational consequence of physician-diagnosed back disorder on LTSA is greater among employees with hard physical work.

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Application of Spontaneous Photon Emission in the Growth Ages and Varieties Screening of Fresh Chinese Herbal Medicines

Ultraweak photon emission emitted by all living organisms has been confirmed to be a noninvasive indicator for their physiological and pathological characteristics. In this study, we investigated the characteristics of spontaneous photon emission (SPE) and the contents of specific active compounds of roots and flowers buds of several fresh Chinese herbal medicines (natural medicines) with different growth ages and varieties. The results revealed that the contents of specific active compounds from same species herbs with different growth ages and varieties were significantly different, and this difference could be reflected by their SPE. Because the contents of specific bioactive constituents in Chinese herbs are closely related to their quality and curative effect, the SPE measurement technique may contribute to the quality control of Chinese herbal medicine in the future.

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African Ancestry Gradient Is Associated with Lower Systemic F2-Isoprostane Levels

Context. Low levels of systemic F2-isoprostanes (F2-IsoP) increase the risk of diabetes and weight gain and were found in African Americans. Low F2-IsoPs could reflect an unfavorable metabolic characteristic, namely, slow mitochondrial metabolism in individuals with African ancestry. Objective. To examine differences in plasma F2-IsoPs in three groups with a priori different proportion of African ancestry: non-Hispanic Whites (NHWs), US-born African Americans (AAs), and West African immigrants (WAI). Design. Cross-sectional study. Setting. Georgia residents recruited from church communities. Participants. 218 males and females 25–74 years of age, who are self-identified as NHW (), AA (), or WAI (). Main Outcome Measure(s). Plasma F2-IsoPs quantified by gas chromatography-mass spectrometry. Results. After adjustment for age, gender, obesity, and other comorbidities, WAI had lower levels of plasma F2-IsoP than AA (beta-coefficient = −9.8, ) and AA had lower levels than NHW (beta-coefficient = −30.3, ). Similarly, among healthy nonobese participants, F2-IsoP levels were lowest among WAI, followed by AA, and the highest levels were among NHW. Conclusion. Plasma F2-IsoPs are inversely associated with African ancestry gradient. Additional studies are required to test whether optimization of systemic F2-IsoP levels can serve as means to improve race-specific lifestyle and pharmacological intervention targeted to obesity prevention and treatment.

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A Nation Divided by Social Media

How are you dealing with dissenting opinions in your news feed? And within your circle of friends and family? 

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Functional evaluation of the restored mucosa after nasal reconstruction with a forehead-galea flap

Abstract

Background

Recovery of the internal mucosal lining is the most problematic step in nasal reconstruction. Restoration of both aesthetic and functional components should be the goal to be pursued. For this purpose, we performed a study for functional evaluation of the restored mucosa after nasal reconstruction.

Methods

From April 2009 to May 2016, 10 patients in whom the galea was used to reconstruct the nasal lining were selected from our casuistic of nasal reconstruction. In order to visualize the nasal and nasopharyngeal cavity, an antero-posterior rhinoendoscopy was performed in all patients. Additionally, patients were asked to complete a visual analogue scale (VAS) evaluation regarding nasal obstruction. Active anterior rhinomanometry analysis, olfactometry analysis and a cytologic examination were also conducted.

Results

Near-normal results in nasal obstruction evaluation were reported subjectively by patients. Near-normal inspiratory values were obtained using rhinomanometry. Average values of TDI (threshold, discrimination and identification), a comprehensive olfactometric parameter, were essentially normal. Cytological sampling examination did not reveal any substantial abnormal variation.

Conclusions

Based on our morphological and functional results, we can assert that the forehead flap in association with galea for lining is a safe and practical surgical technique in total nasal reconstruction.

Level of Evidence: Level V, prognostic study



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Common Ear, Nose & Throat (ENT) Procedures - News-Medical.net


News-Medical.net

Common Ear, Nose & Throat (ENT) Procedures
News-Medical.net
Tympanoplasty is reconstructive surgery involving the eardrum. In stapedectomy, a surgeon removes at least part of the bone in the middle ear. Malignancies in the head and neck – such as larynx, oral, and temporal bone cancers - may require ENT surgery.

and more »


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A KRAS GTPase K104Q Mutant Retains Downstream Signaling by Offsetting Defects in Regulation [Protein Structure and Folding]

The KRAS GTPase plays a critical role in control of cellular growth. The activity of KRAS is regulated by guanine nucleotide exchange factors (GEFs), GTPase-activating proteins (GAPs), and also by posttranslational modification. Lysine 104 in KRAS can be modified by ubiquitylation and acetylation, but the role this residue in intrinsic KRAS function has not been well characterized. We find that lysine 104 is important for GEF recognition, as mutations at this position impair GEF-mediated nucleotide exchange. Because the KRAS K104Q mutant has recently been employed as an acetylation mimetic, we conducted a series of studies to evaluate in its vitro and cell-based properties. Herein, we find that KRAS K104Q exhibits defects in both GEF-mediated exchange and GAP-mediated GTP hydrolysis, consistent with NMR-detected structural perturbations in localized regions of KRAS important for recognition of these regulatory proteins. Despite the partial defect in both GEF and GAP regulation, KRAS K104Q did not alter steady-state GTP-bound levels or the ability of the oncogenic KRAS G12V mutant to cause morphologic transformation of NIH 3T3 mouse fibroblasts and of WT KRAS to rescue the growth defect of mouse embryonic fibroblasts deficient in all Ras genes. We conclude that the KRAS K104Q mutant retains both WT and mutant KRAS function, likely due to offsetting defects in recognition of factors that upregulate (GEF) and downregulate (GAP) RAS activity.

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Autophosphorylation-based calcium (Ca2+) sensitivity priming and Ca2+/Calmodulin inhibition of Arabidopsis thaliana Ca2+-dependent protein kinase 28 (CPK28) [Signal Transduction]

Plant calcium (Ca2+) dependent protein kinases (CPKs) are composed of a dual specificity (Ser/Thr and Tyr) kinase domain tethered to a Calmodulin-like domain (CLD) via an autoinhibitory junction (J) and represent the primary Ca2+-dependent protein kinase activities in plant systems. While regulation of CPKs by Ca2+ has been extensively studied, the contribution of autophosphorylation in the control of CPK activity is less well understood. Furthermore, whether Calmodulin (CaM) contributes to CPK regulation, as is the case for Ca2+/CaM-dependent protein kinases (CaMKs) outside the plant lineage, remains an open question. We screened a subset of plant CPKs for CaM-binding and found that CPK28 is a high-affinity Ca2+/CaM-binding protein. Using synthetic peptides and native gel electrophoresis, we coarsely mapped the CaM-binding domain to a site within the CPK28 J domain that overlaps with the known site of intramolecular interaction between the J domain and CLD. Peptide kinase activity of fully dephosphorylated CPK28 was Ca2+-responsive and inhibited by Ca2+/CaM. Using in situ autophosphorylated protein, we expand on the known set of CPK28 autophosphorylation sites, and demonstrate that, unexpectedly, autophosphorylated CPK28 had enhanced activity at physiological concentrations of Ca2+ compared to dephosphorylated protein, suggesting that autophosphorylation functions to prime CPK28 for Ca2+-activation. Furthermore, CPK28 autophosphorylation substantially reduced sensitivity of the kinase to Ca2+/CaM inhibition. Overall, our analyses uncover new complexities in the control of CPK28 and provide mechanistic support for Ca2+ signaling specificity through Ca2+ sensor priming.

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Amplified pathogenic actions of angiotensin II in cysteine-rich LIM-only protein 4-negative mouse hearts [Research]

LIM domain proteins have been identified as essential modulators of cardiac biology and pathology; however, it is unclear which role the cysteine-rich LIM-only protein (CRP)4 plays in these processes. In studying CRP4 mutant mice, we found that their hearts developed normally but lack of CRP4 exaggerated multiple parameters of the cardiac stress response to the neurohormone angiotensin II (Ang II). Aiming to dissect the molecular details we find a link between CRP4 and the cardioprotective cGMP pathway, as well as a multiprotein complex comprising well-known hypertrophy-associated factors. Significant enrichment of the cysteine-rich intestinal protein (CRIP)1 in murine hearts lacking CRP4, as well as severe cardiac defects and premature death of CRIP1 and CRP4 morphant zebrafish embryos further support the notion that depleting CRP4 is incompatible with a proper cardiac development and function. Together, amplified Ang II signaling identified CRP4 as a novel antiremodeling factor regulated, at least to some extent, by cardiac cGMP.—Straubinger, J., Boldt, K., Kuret, A., Deng, L., Krattenmacher, D., Bork, N., Desch, M., Feil, R., Feil, S., Nemer, M., Ueffing, M., Ruth, P., Just, S., Lukowski, R. Amplified pathogenic actions of angiotensin II in cysteine-rich LIM-only protein 4 negative mouse hearts.



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Early suppression of adipocyte lipid turnover induces immunometabolic modulation in cancer cachexia syndrome [Research]

Cancer cachexia is a multifactorial syndrome characterized by body weight loss, atrophy of adipose tissue (AT) and systemic inflammation. However, there is restrict information regarding the mechanisms of immunometabolic response in AT from cancer cachexia. Male Wistar rats were inoculated with 2 x 107 of Walker 256 tumor cells [tumor bearing (TB)]. The mesenteric AT (MeAT) was collected on d 0, 4, 7 (early stage), and 14 (cachexia stage) after tumor cell injection. Surgical biopsies for MeAT were obtained from patients who had gastrointestinal cancer with cachexia. Lipolysis showed an early decrease in glycerol release in TB d 4 (TB4) rats in relation to the control, followed by a 6-fold increase in TB d 14 (TB14), whereas de novo lipogenesis was markedly lower in the incorporation of glucose into fatty acids in TB14 during the development of cachexia. CD11b and CD68 were positive in TB rats (d 7 and 14, respectively). In addition, we found cachexia stage results similar to those of animals in MeAT from patients: an increased presence of CD68+, iNOS2+, TNFα+, and HSL+ cells. In summary, translational analysis of MeAT from patients and animal model of cancer cachexia enabled us to identify early disruption in Adl turnover and subsequent inflammatory response during the development of cancer cachexia.—Henriques, F. S., Sertié, R. A. L., Franco, F. O., Knobl, P., Neves, R. X., Andreotti, S., Lima, F. B., Guilherme, A., Seelaender, M., Batista, M. L., Jr. Early suppression of adipocyte lipid turnover induces immunometabolic modulation in cancer cachexia syndrome.



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The Norwegian dietary guidelines and colorectal cancer survival (CRC-NORDIET) study: a food-based multicentre randomized controlled trial

Colorectal cancer survivors are not only at risk for recurrent disease but also at increased risk of comorbidities such as other cancers, cardiovascular disease, diabetes, hypertension and functional decline. ...

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Healthy Canadian adolescents perspectives of cancer using metaphors: a qualitative study

Objectives

Cancer has been described using metaphors for over 4 decades. However, little is known about healthy adolescents’ perspectives of cancer using metaphors. This paper reports on findings specific to adolescents’ perspectives of cancer using metaphors. The findings emerged from a qualitative ethnographic study that sought to understand Canadian adolescents’ conceptualisation of cancer and cancer prevention.

Design

To arrive at a detailed description, data were obtained using individual interviews, focus groups and photovoice.

Setting

6 high schools from a western Canada province.

Participants

75 Canadian adolescents.

Results

Use of 4 metaphors emerged from the data: loss (cancer as the sick patient and cancer as death itself); military (cancer as a battle); living thing (haywire cells and other living things) and faith (cancer as God's will) metaphors, with the loss and military metaphors being the ones most frequently used by adolescents. Adolescents’ descriptions of cancer were partly informed by their experiences with family members with cancer but also what occurs in their social worlds including mass media. Adolescents related cancer to emotions such as sadness and fear. Accordingly, more holistic and factual cancer descriptions, education and psychosocial support are needed to direct cancer messaging and clinical practice.

Conclusions

Findings from this study suggest that the public and healthcare providers be more aware of how they communicate cancer messages.



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General practitioner management related to skin cancer prevention and screening during standard medical encounters: a French cross-sectional study based on the International Classification of Primary Care

Objective

The aim of this study was to assess general practitioner (GP) management practices related to skin cancer prevention and screening during standard medical encounters.

Setting

Data on medical encounters addressing skin cancer issues were obtained from a French database containing information from 17 019 standard primary care consultations.

Participants

Data were collected between December 2011 and April 2012 by 54 trainees who reported the regular practice of 128 GPs using the International Classification of Primary Care.

Outcome measures

Reasons for encounters and the following care processes were recorded: counselling, clinical examinations and referral to a specialist. Medical encounters addressing skin cancer issues were compared with medical encounters that addressed other health problems using a multivariate analysis.

Results

Only 0.7% of medical encounters addressed skin cancer issues. When patients did require management of a skin cancer-related issue, this was more likely initiated by the doctor than the patient (70.7% vs 29.3%; p<0.001). Compared with medical encounters addressing other health problems, encounters that addressed skin cancer problems required more tasks (3.7 vs 2.5; p<0.001) and lasted 1 min and 20 s longer (p=0.003). GPs were less involved in clinical examinations (67.5% vs 97.1%; p<0.001), both complete (7.3% vs 22.3%, p<0.001) and partial examinations (60.2% vs 74.9%), and were less involved in counselling (5.7% vs 16.9%; p<0.001). Patients presenting skin cancer issues were referred to a specialist more often than patients consulting for other health problems (39.0% vs 12.1%; p<0.001). GPs performed a biopsy in 6.7% of all skin cancer-related encounters.

Conclusions

This study demonstrates discrepancies between the high prevalence of skin cancer and the low rate of medical encounters addressing these issues in general practice. Our findings should be followed by qualitative interviews to better understand the observed practices in this field.



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Prognostic value of plasma lactate levels in a retrospective cohort presenting at a university hospital emergency department

Objectives

The prognostic value of lactate in the setting of an emergency department (ED) has not been studied extensively. The goal of this study was to assess 28-day mortality in ED patients in whom lactate was elevated (≥4.0 mmol/L), <4.0 mmol/L or not determined and to study the impact of the underlying cause of hyperlactatemia, that is, type A (tissue hypoxia) or type B (non-hypoxia), on mortality.

Design

Retrospective study.

Setting

A secondary and tertiary referral centre in the Netherlands.

Materials and methods

All internal medicine patients with hyperlactatemia (≥4.0 mmol/L) at the ED between January 2011 and October 2014 were included in this study. Samples of patients with lactate levels <4.0 mmol/L and of patients in whom no lactate was measured were included as a reference.

Results

In 1144 of 19 822 patients (5.8%), lactate was measured. Hyperlactatemia (n=197) was associated with a higher 28-day mortality than in those with lactate <4.0 mmol/L (40.6% vs 18.5%; p<0.001) and in those without lactate measurements (9.5%). Type A hyperlactatemia, present in 84% of those with hyperlactatemia, was associated with higher mortality than type B hyperlactatemia (45.8% vs 12.5%, p=0.001).

Conclusions

This study demonstrates that the prognostic value of lactate depends largely on the underlying cause and the population in whom lactate has been measured. Prospective studies are required to address the true added value of lactate at the ED.



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Efficiency of physical therapy on postural imbalance after stroke: study protocol for a systematic review and meta-analysis

Introduction

Stroke frequently results in balance disorders, leading to lower levels of activity and a diminution in autonomy. Current physical therapies (PT) aiming to reduce postural imbalance have shown a large variety of effects with low levels of evidence. The objectives are to determine the efficiency of PT in recovering from postural imbalance in patients after a stroke and to assess which PT is more effective.

Methods and analysis

We will search several databases from inception to October 2015. Only randomised controlled trials assessing PT to recover from poststroke postural imbalance in adults will be considered.

Outcome measures will be the Berg Balance Scale (BBS), the Postural Assessment Scale for Stroke (PASS), the ‘weight-bearing asymmetry’ (WBA), the ‘centre of pressure’ (COP) and the ‘limit of stability’ (LOS). WBA, COP and LOS are measured by a (sitting or standing) static evaluation on force plate or another device.

Two independent reviewers will screen titles, abstracts and full-text articles, evaluate the risk of bias and will perform data extraction. In addition to the outcomes, measures of independence will be analysed. This study will aim at determining the effects of PT on the function (WBA, COP, LOS), the activity (BBS, PASS) and the independence of patients. Subgroup analyses will be planned according to the location of brain lesion (hemispheric, brainstem or cerebellum), the time since stroke (early, late, chronic), the PT (type, main aim (direct effect or generalisation), overall duration), the type of approaches (top-down or bottom-up) and the methodological quality of studies.

Ethics and dissemination

No ethical statement will be required. The results will be published in a peer-reviewed journal. This meta-analysis aims at managing the rehabilitation after postural imbalance by PT after a stroke.

Trial registration number

Prospero CRD42016037966;Pre-results.



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Calibrated prevalence of disabling chronic pain according to different approaches: a face-to-face cross-sectional population-based study in Southern Spain

Objectives

To calculate the prevalence of disabling chronic pain (DCP) and to offer a more representative and accurate estimation by applying different calibration techniques.

Settings

2011 Andalusian Health Survey, a cross-sectional population survey based on face-to-face home interviews.

Participants

6507 people aged 16 years or older and living in Andalusia, Spain.

Outcomes

Design weights, linear calibration based on marginals and on crossings, and model-assisted calibration were used to estimate the prevalence and variance of DCP, for the whole sample and for the domains of sex and age groups (16–44; 45–64; +65).

Results

Calibration variables were sex, age groups and educational level. In the whole sample, DCP prevalence calibration reduced by more than 5.2% and 8.2% the estimated prevalences and variances, respectively, obtained with the design weights. Regarding the domains, prevalence reductions are from 33% to 1%, and variance reductions are from 0.2% to 1%. Model-assisted calibration is the best technique to estimate DCP prevalence for the whole population and crossing calibration for their domains, although with almost no differences compared to marginal calibration.

Conclusions

The validity and accuracy of estimations of DCP prevalence are improved by calibration adjustments. Model-assisted calibrated prevalence of DCP is 10.78% for the whole population, being at least 2-fold higher in women in all age groups. The results and methodology developed could be useful in clinical and population-based studies on chronic pain and disability.



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Correlates of non-technical skills in surgery: a prospective study

Background

Communication and teamwork failures have frequently been identified as the root cause of adverse events and complications in surgery. Few studies have examined contextual factors that influence teams’ non-technical skills (NTS) in surgery. The purpose of this prospective study was to identify and describe correlates of NTS.

Methods

We assessed NTS of teams and professional role at 2 hospitals using the revised 23-item Non-TECHnical Skills (NOTECHS) and its subscales (communication, situational awareness, team skills, leadership and decision-making). Over 6 months, 2 trained observers evaluated teams’ NTS using a structured form. Interobserver agreement across hospitals ranged from 86% to 95%. Multiple regression models were developed to describe associations between operative time, team membership, miscommunications, interruptions, and total NOTECHS and subscale scores.

Results

We observed 161 surgical procedures across 8 teams. The total amount of explained variance in NOTECHS and its 5 subscales ranged from 14% (adjusted R2 0.12, p<0.001) to 24% (adjusted R2 0.22, p<0.001). In all models, inverse relationships between the total number of miscommunications and total number of interruptions and teams’ NTS were observed.

Conclusions

Miscommunications and interruptions impact on team NTS performance.



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Ixekizumab: A Review in Moderate to Severe Plaque Psoriasis

Abstract

Ixekizumab (Taltz®) is a subcutaneously administered, humanized anti-interleukin-17A monoclonal antibody indicated for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy (USA and EU) or phototherapy (USA). In the phase 3 UNCOVER trials in this patient population, ixekizumab was superior to placebo or etanercept in terms of the proportion of patients achieving a ≥75% reduction from baseline in the Psoriasis Area and Severity Index and in those achieving a static Physician Global Assessment score of 0 or 1, after 12 weeks of induction treatment. Clinical responses to ixekizumab were seen as early as week 1. Patients receiving ixekizumab also reported improvements in health-related quality of life, itching, and work productivity. Clinical responses to ixekizumab were sustained during additional 48 weeks of maintenance treatment. Ixekizumab was generally well tolerated and exhibited low immunogenicity in the UNCOVER trials during up to 60 weeks of therapy. Currently available data indicate that ixekizumab is an effective and generally well tolerated treatment option for patients with moderate to severe plaque psoriasis. It has the potential advantage of one maintenance dose for every 4 weeks.



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Preparation and evaluation of biopolymeric nanoparticles as drug delivery system in effective treatment of rheumatoid arthritis

Abstract

Purpose

The study purposes to evaluate nanocrystalline biopolymeric nanoparticles encapsulating methotrexate and dexamethasone with high biocompatibility, enhanced therapeutic efficacy and reduced toxicity.

Methods

Chitosan nanoparticles were prepared by ionic gelation, and Methotrexate (MTX) and Dexamethasone (DEX) were loaded during the preparation and screened for their in vitro efficacy in HEK and RAW264.7 cells, ex vivo and in vivo efficacy.

Results

FTIR confirmed the involvement of phosphoric group of sTPP with amine groups of chitosan and also role of hydrogen bonding involved in the preparation of MTXCHNP and DEXCHNP. Controlled release patterns coupled with diffusion of drug were observed in two different buffers (PBS) at pH 7.4 and pH 5.8. The IC50 for MTXCHNP for HEK was 26.1 μg/ml and 7.7 μg/ml for RAW 264.7 cells. In DEXCHNP, the IC50 was 20.12 μg/ml for HEK and 7.37 μg/ml for RAW264.7 cells. Enhanced uptake of FITC-CHNP by RAW cells indicated internalization of nanoparticles by phagocytosis. The enhanced release of drug at lower pH justified increased cytotoxicity. Negligible ex-vivo hemolysis indicated the higher biocompatibility of the nanoparticles. 99mTc-CHNP exhibited maximum absorption in blood circulation in 3 h, followed by hepatic metabolism and renal clearance. Higher in-vivo anti-arthritic activity and antioxidant activity was observed post-intraperitoneal (i.p.) injections by both MTXCHNP and DEXCHNP when compared to MTX (0.75 mg/Kg by i.p. route) and DEX (0.2 mg/Kg/i.p./daily) per se.

Conclusion

The nanocrystalline biopolymeric nanoparticles were stable, biocompatible and have potential to be administered through i.p. route with minimal toxicity and high efficacy.



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Dodecyl Amino Glucoside Enhances Transdermal and Topical Drug Delivery via Reversible Interaction with Skin Barrier Lipids

Abstract

Purpose

Skin permeation/penetration enhancers are substances that enable drug delivery through or into the skin.

Methods

To search for new enhancers with high but reversible activity and acceptable toxicity, we synthesized a series of d-glucose derivatives, both hydrophilic and amphiphilic.

Results

Initial evaluation of the ability of these sugar derivatives to increase permeation and penetration of theophylline through/into human skin compared with a control (no enhancer) or sorbitan monolaurate (Span 20; positive control) revealed dodecyl 6-amino-6-deoxy-α-d-glucopyranoside 5 as a promising enhancer. Furthermore, this amino sugar 5 increased epidermal concentration of a highly hydrophilic antiviral cidofovir by a factor of 7. The effect of compound 5 on skin electrical impedance suggested its direct interaction with the skin barrier. Infrared spectroscopy of isolated stratum corneum revealed no effect of enhancer 5 on the stratum corneum proteins but an overall decrease in the lipid chain order. The enhancer showed acceptable toxicity on HaCaT keratinocyte and 3T3 fibroblast cell lines. Finally, transepidermal water loss returned to baseline values after enhancer 5 had been removed from the skin.

Conclusions

Compound 5, a dodecyl amino glucoside, is a promising enhancer that acts through a reversible interaction with the stratum corneum lipids.



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Supramolecular Cocrystals of Gliclazide: Synthesis, Characterization and Evaluation

Abstract

Purpose

To prepare the supramolecular cocrystals of gliclazide (GL, a BCS class II drug molecule) via mechanochemical route, with the goal of improving physicochemical and biopharmaceutical properties.

Methods

Two cocrystals of GL with GRAS status coformers, sebacic acid (GL-SB; 1:1) and α-hydroxyacetic acid (GL-HA; 1:1) were screened out using liquid assisted grinding. The prepared cocrystals were characterized using thermal and analytical techniques followed by evaluation of antidiabetic activity and pharmacokinetic parameters.

Results

The generation of new, single and pure crystal forms was characterized by DSC and PXRD. The crystal structure determination from PXRD revealed the existence of both cocrystals in triclinic (P-1) crystal system. The hydrogen bonded network, determined by material studio was well supported by shifts in FTIR and SSNMR. Both the new solid forms displayed improved solubility, IDR, antidiabetic activity and pharmacokinetic parameters as compared to GL.

Conclusions

The improvement in these physicochemical and biopharmaceutical properties corroborated the fact that the supramolecular cocrystallization may be useful in the development of pharmaceutical crystalline materials with interesting network and properties.



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The Impact of Inspiratory Flow Rate on Drug Delivery to the Lungs with Dry Powder Inhalers

Abstract

Current marketed dry powder inhalers utilize the energy from patient inspiration to fluidize and disperse bulk powder agglomerates into respirable particles. Variations in patient inspiratory flow profiles can lead to marked differences in total lung dose (TLD), and ultimately patient outcomes for an inhaled therapeutic. The present review aims to quantitate the flow rate dependence in TLD observed for a number of drug/device combinations using a new metric termed the Q index. With this data in hand, the review explores key attributes in the design of the formulation and device that impact flow rate dependence. The review also proposes alternative in vitro methods to assess flow rate dependence that more closely align with in vivo observations. Finally, the impact of variations in flow rate on lung function for inhaled bronchodilators is summarized.



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