Ιατρικά Άρθρα Αλέξανδρος Γ. Σφακιανάκης: Μαΐου 2016

Δευτέρα 30 Μαΐου 2016

"Industrie 4.0" - Rechtsrahmen für eine Datenwirtschaft im digitalen Binnenmarkt

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Chemical synthesis of Burkholderia Lipid A modified with glycosyl phosphodiester-linked 4-amino-4-deoxy-β-L-arabinose and its immunomodulatory potential

Modification of the Lipid A phosphates by positively charged appendages is a part of the survival strategy of numerous opportunistic Gram-negative bacteria. The phosphate groups of the cystic fibrosis adapted Burkholderia Lipid A are abundantly esterified by 4-amino-4-deoxy-β-L-arabinose (β-L-Ara4N), which imposes resistance to antibiotic treatment and contributes to bacterial virulence. To establish structural features accounting for the unique pro-inflammatory activity of Burkholderia LPS we have synthesised Lipid A substituted by β-L-Ara4N at the anomeric phosphate and its Ara4N-free counterpart. The double glycosyl phosphodiester was assembled by triazolyl-tris-(pyrrolidinyl)phosphonium-assisted coupling of the β-L-Ara4N H-phosphonate to α-lactol of β(1→6) diglucosamine, pentaacylated with (R)-(3)-acyloxyacyl- and Alloc-protected (R)-(3)-hydroxyacyl residues. The intermediate 1,1'-glycosyl-H-phosphonate diester was oxidised in anhydrous conditions to provide, after total deprotection, β-L-Ara4N-substituted Burkholderia Lipid A. The β-L-Ara4N modification significantly enhanced the pro-inflammatory innate immune signaling of otherwise non-endotoxic Burkholderia Lipid A.

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Improved TV Algorithm Based on Adaptive Multiplier for Interference Hyperspectral Image Decomposition

Interference Hyperspectral Images (IHI) data acquired by Interference Hyperspectral Imaging Spectrometer exhibit many vertical interference stripes. The above characteristics will affect the application of dictionary learning and compressed sensing theory used on IHI data. According to the special characteristics of IHI data, many algorithms are proposed to separate the interference stripes layers and the background layers of IHI data in 2015, but the interference stripes layers are still not clean enough and the ideal background layers without interference stripes are also difficult to be obtained. In this paper, an improved total variation (TV) algorithm based on adaptive multiplier is proposed for IHI data decomposition. The value of the Lagrange multiplier is adaptive according to the unidirectional characteristics of IHI data. The proposed algorithm is used on Large Spatially Modulated Interference Spectral (LSMIS) images and is proved to provide better experimental results than the current algorithms both visually and quantitatively.

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A Novel Printable Watermarking Method in Dithering Halftone Images

Halftone images are commonly printed on books, newspapers, and magazines. How to protect the copyright of these printed halftone images becomes an important issue. Digital watermarking provides a solution for copyright protection. In this paper, we will propose a novel printable watermarking method for dithering halftone images. Based on downsampling and the property of a dispersed dithering screen, the method can resist cropping, tampering, and print-and-scan process attacks. In addition, comparing to Guo et al.’s method, the experimental results show that the proposed method provides higher robustness for the above-mentioned attacks and better visual quality in the high-frequency regions of halftone images.

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Integral Sliding Mode Control for Trajectory Tracking of Wheeled Mobile Robot in Presence of Uncertainties

Wheeled mobile robots present a typical case of complex systems with nonholonomic constraints. In the past few years, the dominance of these systems has been a very active research field. In this paper, a new method based on an integral sliding mode control for the trajectory tracking of wheeled mobile robots is proposed. The controller is designed to solve the reaching phase problem with the elimination of matched disturbances and minimize the unmatched one. We distinguish two parts in the suggested controller: a high-level controller to stabilize the nominal system and a discontinuous controller to assess the trajectory tracking in the presence of disturbances. This controller is robust during the entire motion. The effectiveness of the proposed controller is demonstrated through simulation studies for the unicycle with matched and unmatched disturbances.

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Innovative Correlation Coefficient Measurement with Fuzzy Data

Correlation coefficients are commonly found with crisp data. In this paper, we use Pearson’s correlation coefficient and propose a method for evaluating correlation coefficients for fuzzy interval data. Our empirical studies involve the relationship between mathematics achievement and other projects.

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Variants in genes belonging to the Fibroblast Growth Factor family are associated with lower extremity amputation in non-Hispanic whites: Findings from the Chronic Renal Insufficiency Cohort study

Abstract

Diabetes is the major risk factor for non-traumatic lower extremity amputation (LEA). The role of genetic polymorphisms in predisposing diabetics to impaired wound healing leading to LEA has not been sufficiently explored. We investigated the association between a set of genes belonging to the angiogenesis/wound repair pathway with LEA in the Chronic Renal Insufficiency Cohort (CRIC), a study of adults with chronic kidney disease (CKD) that includes a subgroup with diabetes. This study was performed on 3772 CRIC participants who were genotyped on the ITMAT-Broad-CARe array (IBC) chip. A total of 1017 single-nucleotide polymorphisms (SNPs) in 22 genes belonging to the angiogenesis/would repair pathway were investigated. LEA was determined from patient self-report. The association between genetic variants and LEA status was examined using logistic regression and additive genetic models after stratifying the cohort by race/ethnicity and diabetic status. Unadjusted analyses as well as analyses adjusted for age, sex, estimated glomerular filtration rate (eGFR), body mass index (BMI), peripheral vascular disease (PVD), hemoglobin A1c (HgbA1c) and population stratification were performed. In non-Hispanic white participants with diabetes, rs11938826 and rs1960669, both intronic SNPs in the gene basic fibroblast growth factor-2 (FGF2), were significantly associated with LEA in covariate-adjusted analysis (OR: 2.83 (95% CI: 1.73, 4.62); p-value: 0.000034; Bonferroni adjusted p-value: 0.0006) and (OR: 2.61 (95% CI: 1.48, 4.61); p-value: 0.00095; Bonferroni adjusted p-value: 0.02). In the same subgroup, rs10883688, an FGF8 SNP of unknown functional effect, was also associated with LEA (OR: 1.72 (95% Confidence Interval: 1.14, 2.6); p-value: 0.00999; Bonferroni adjusted p-value: 0.04). No statistically significant associations were identified in the other ethnic groups. In conclusion, variant/s in FGF2 and FGF8 may predispose diabetics with CKD to LEA. Dysregulation of the FGF2 gene represents an opportunity to understand further, and possibly intervene upon, mechanisms of wound healing in diabetics with CKD. This article is protected by copyright. All rights reserved.

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Examination of endothelial cell induced epidermal regeneration in a mice based chimney wound model

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ABSTRACT

As wound contraction in the cutaneous layer occurs rapidly in mice, mechanical means are typically used to deliberately expose the wound in order to properly investigate healing by secondary intention. Previously, silicon rings and splinting models were attempted to analyze histological recovery but prevention of surrounding epidermal cell migration and subsequent closure was minimal. Here, we developed an ideal chimney wound model to evaluate epidermal regeneration in murine under hESC-EC transplantation through histological analysis encompassing the three phases of regeneration; migration, proliferation, and remodeling. Human embryonic stem cell derived endothelial cells (hESC-EC) were transplanted due to possessing a well-known therapeutic effect in angiogenesis which also enhances epidermal repair in order to depict the process of regeneration. Following a standard 1mm biopsy punch, a chimney manufactured by modifying a 1.7ml micro tube was simply inserted into the excisional wound to complete the modeling process. Under this model, the excisional wound remained fully exposed for 14 days and even after 4 weeks, only a thin transparent layer of epidermal tissue covered the wound site. This approach is able to more accurately depict epidermal repair in relation to histology while also being a user-friendly and cost-effective way to mimic human recovery in rodents and evaluate epithelial repair induced by a form of therapy. This article is protected by copyright. All rights reserved.

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Ciprofloxacin-loaded keratin hydrogels reduce infection and support healing in a porcine partial-thickness thermal burn

Abstract

Infection is a leading cause of morbidity and mortality in burn patients. Current therapies include silver-based creams and dressings, which display limited antimicrobial effectiveness and impair healing. The need exists for a topical, point-of-injury antibiotic treatment that provides sustained antimicrobial activity without impeding wound repair. Fitting this description are keratin-based hydrogels, which are fully biocompatible and support the slow-release of antibiotics. Here we develop a porcine model of an infected partial-thickness burn to test the effects of ciprofloxacin-loaded keratin hydrogels on infection and wound healing. Partial-thickness burns were inoculated with either Pseudomonas aeruginosa or Methicillin-resistant Staphylococcus aureus, resulting in infections that persisted for greater than 2 weeks that exceeded 10⁵ and 10⁶ cfu per gram of tissue, respectively. Compared to silver sulfadiazine, ciprofloxacin-loaded keratin hydrogel treatment significantly reduced the amount of Pseudomonas aeruginosa and Staphylococcus aureus in the burn by greater than 99% on days 4, 7, 11 and 15 post-injury. Further, burns treated with ciprofloxacin-loaded keratin hydrogels exhibited similar healing patterns as uninfected burns with regards to reepithelialization, macrophage recruitment, and collagen deposition and remodeling. The ability of keratin hydrogels to deliver antibiotics to fight infection and support healing of partial-thickness burns make them a strong candidate as a first-line burn therapy. This article is protected by copyright. All rights reserved.

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Comparison of Frequency Domain and Time-Domain Methods for Aeromechanical Analysis

Unsteady flow around an oscillating plate cascade and that through a single compressor rotor subject to vibration have been computationally studied, aimed at examining the predictive ability of two low fidelity frequency methods compared with a high fidelity time-domain solution method for aeroelasticity. The computational solutions demonstrate the capabilities of the frequency domain methods compared with the nonlinear time-domain solution method in capturing small perturbations in the unsteady flow. They also show the great advantage of significant CPU time saving by the frequency methods over the nonlinear time method. Comparisons of two different frequency methods, nonlinear harmonic and phase solution method, show that these methods can produce different results due to the differences in numeric and physical conditioning. The results obtained using phase solutions method are in better agreement with the nonlinear time-domain solution. This is because the same numeric and physical conditioning are used in both the nonlinear time-domain method and phase solution frequency domain method.

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A Rare Complication of Herpes Zoster: Segmental Zoster Paresis

Herpes zoster is a common presentation in both the community and emergency department; however segmental zoster paresis is a rare complication that can lead to misdiagnosis. We present a case of a 74-year-old Indian gentleman with a background of well controlled diabetes mellitus, hypertension, and ischaemic heart disease who presented with sudden right lower limb weakness. This was preceded by a 5-day history of paraesthesia starting in the right foot and ascending up the right lower limb. On examination, there was a characteristic vesicular rash in the L2/3 region with MRC grading 3/5 in the right hip flexors. The rest of the neurological examination was unremarkable. MRI of the spine did not show any evidence of spinal disease. The patient was initiated on IV acyclovir with improvement of the lower limb weakness to MRC grading 5/5 as the vesicles improved. This is an interesting case as it highlights a rare presentation of zoster: segmental motor paresis that recovered fully with resolution of the rash. It shows the importance of recognizing motor neuropathy as a complication of shingles as it has a very good prognosis with most patients regaining full motor function of the affected limb with treatment.

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Uniform Attractors for Nonclassical Diffusion Equations with Memory

We introduce a new method (or technique), asymptotic contractive method, to verify uniform asymptotic compactness of a family of processes. After that, the existence and the structure of a compact uniform attractor for the nonautonomous nonclassical diffusion equation with fading memory are proved under the following conditions: the nonlinearity satisfies the polynomial growth of arbitrary order and the time-dependent forcing term is only translation-bounded in .

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Enhanced SDIoT Security Framework Models

Following the recent increase in the interest in IoT (Internet of Things) environment, devices that provide various services are being developed. As the diversity, research is required for efficient management of these devices and enhanced security. Previous network environments tend to be dependent on network devices and have difficulties in active processing of variable traffic. Moreover, it is expected that new or variant attacks will increase as packets of various patterns are generated from numerous devices, and hence immense research effort is required in solving this problem. In order to address such problems, this study aims to investigate strategies for establishing a security framework for the configuration of a software-defined IoT environment and efficient provision of security services. Moreover, the service to reduce the overhead involved in security service provision is configured, and a simple test is conducted to verify the feasibility of the proposed model.

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Pluripotency of Stem Cells from Human Exfoliated Deciduous Teeth for Tissue Engineering

Stem cells from human exfoliated deciduous teeth (SHED) are highly proliferative pluripotent cells that can be retrieved from primary teeth. Although SHED are isolated from the dental pulp, their differentiation potential is not limited to odontoblasts only. In fact, SHED can differentiate into several cell types including neurons, osteoblasts, adipocytes, and endothelial cells. The high plasticity makes SHED an interesting stem cell model for research in several biomedical areas. This review will discuss key findings about the characterization and differentiation of SHED into odontoblasts, neurons, and hormone secreting cells (e.g., hepatocytes and islet-like cell aggregates). The outcomes of the studies presented here support the multipotency of SHED and their potential to be used for tissue engineering-based therapies.

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Cereal chaff used as temper in loom-weights: new evidence from a Slovenian Eneolithic pile-dwelling site (ca. 3100 cal bc)

We present newevidence of the intentional use of cereal by-products at Stare gmajne, an Eneolithic piledwelling site in Slovenia, dated approximately 3160–3100 cal BC . The chaff material, which had been used for tempering, was discovered inside one of the largest discovered loomweights and analysed. Clay, which was used by the dwellers to make the weight, was tempered with cereal chaff to reinforce it. The practice of tempering, not necessarily for loom weights, has already been proven for earlier settlements, mostly in arid areas where firewood, grazing and building material were scarce. However, tempering has rarely been found in European prehistoric sites. More than 1,800 carbonised and half-carbonised, excellently preserved and well identifiable cereal plant macroremains in less than 1 l of waterlogged clayeymaterial were sorted and counted.Among the recognized plant macroremains, barley rachis fragments and glume wheat (emmer and einkorn) by-products such as spikelet forks and glume bases prevailed. A few grains were also found. Cultivation of the main crops of emmer, einkorn and barley at Slovenian Eneolithic pile-dwelling sites was confirmed again. Among the chaff, a new ‘‘strange type’’ of Triticum dicoccum (emmer) spikelet forks was discovered. The size of the weight and the intentional local use of cereal by-products as temper suggest that late Neolithic (Eneolithic) pile-dwelling societies all around the Alps were highly organized and developed due to expansion of crop production and processing.

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Unraveling the complexity of protein backbone dynamics with combined (13)C and (15)N solid-state NMR relaxation measurements

Typically, protein dynamics involve a complex hierarchy of motions occurring on different time scales between conformations separated by a range of different energy barriers. NMR relaxation can in principle provide a site-specific picture of both the time scales and amplitudes of these motions, but independent relaxation rates sensitive to fluctuations in different time scale ranges are required to obtain a faithful representation of the underlying dynamic complexity. This is especially pertinent for relaxation measurements in the solid state, which report on dynamics in a broader window of time scales by more than 3 orders of magnitudes compared to solution NMR relaxation. To aid in unraveling the intricacies of biomolecular dynamics we introduce (13)C spin-lattice relaxation in the rotating frame (R1ρ) as a probe of backbone nanosecond-microsecond motions in proteins in the solid state. We present measurements of (13)C'R1ρ rates in fully protonated crystalline protein GB1 at 600 and 850 MHz (1)H Larmor frequencies and compare them to (13)C'R1, (15)N R1 and R1ρ measured under the same conditions. The addition of carbon relaxation data to the model free analysis of nitrogen relaxation data leads to greatly improved characterization of time scales of protein backbone motions, minimizing the occurrence of fitting artifacts that may be present when (15)N data is used alone. We also discuss how internal motions characterized by different time scales contribute to (15)N and (13)C relaxation rates in the solid state and solution state, leading to fundamental differences between them, as well as phenomena such as underestimation of picosecond-range motions in the solid state and nanosecond-range motions in solution.

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An economic approach to efficient isotope labeling in insect cells using homemade 15N-, 13C- and 2H-labeled yeast extracts

Heterologous expression of proteins in insect cells is frequently used for crystallographic structural studies due to the high yields even for challenging proteins requiring the eukaryotic protein processing capabilities of the host. However for NMR studies, the need for isotope labeling poses extreme challenges in eukaryotic hosts. Here, we describe a robust method to achieve uniform protein (15)N and (13)C labeling of up to 90 % in baculovirus-infected insect cells. The approach is based on the production of labeled yeast extract, which is subsequently supplemented to insect cell growth media. The method also allows deuteration at levels of >60 % without decrease in expression yield. The economic implementation of the labeling procedures into a standard structural biology laboratory environment is described in a step-by-step protocol. Applications are demonstrated for a variety of NMR experiments using the Abelson kinase domain, GFP, and the beta-1 adrenergic receptor as examples. Deuterated expression of the latter provides spectra of very high quality of a eukaryotic G-protein coupled receptor.

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Energiewende braucht Wärmewende – Chancen und Limitierungen der intensiven thermischen Nutzung des oberflächennahen Untergrundes in urbanen Gebieten vor dem Hintergrund der aktuellen Energiedebatte in Deutschland

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Determining Which Phenotypes Underlie a Pleiotropic Signal

ABSTRACT

Discovering pleiotropic loci is important to understand the biological basis of seemingly distinct phenotypes. Most methods for assessing pleiotropy only test for the overall association between genetic variants and multiple phenotypes. To determine which specific traits are pleiotropic, we evaluate via simulation and application three different strategies. The first is model selection techniques based on the inverse regression of genotype on phenotypes. The second is a subset-based meta analysis ASSET [Bhattacharjee et al., ], which provides an optimal subset of nonnull traits. And the third is a modified Benjamini–Hochberg (B-H) procedure of controlling the expected false discovery rate [Benjamini and Hochberg, ] in the framework of phenome-wide association study. From our simulations we see that an inverse regression-based approach MultiPhen [O'Reilly et al., ] is more powerful than ASSET for detecting overall pleiotropic association, except for when all the phenotypes are associated and have genetic effects in the same direction. For determining which specific traits are pleiotropic, the modified B–H procedure performs consistently better than the other two methods. The inverse regression-based selection methods perform competitively with the modified B–H procedure only when the phenotypes are weakly correlated. The efficiency of ASSET is observed to lie below and in between the efficiency of the other two methods when the traits are weakly and strongly correlated, respectively. In our application to a large GWAS, we find that the modified B–H procedure also performs well, indicating that this may be an optimal approach for determining the traits underlying a pleiotropic signal.

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Comparison of Parametric and Nonparametric Methods for Analyzing the Bias of a Numerical Model

Numerical models are presently applied in many fields for simulation and prediction, operation, or research. The output from these models normally has both systematic and random errors. The study compared January 2015 temperature data for Uganda as simulated using the Weather Research and Forecast model with actual observed station temperature data to analyze the bias using parametric (the root mean square error (RMSE), the mean absolute error (MAE), mean error (ME), skewness, and the bias easy estimate (BES)) and nonparametric (the sign test, STM) methods. The RMSE normally overestimates the error compared to MAE. The RMSE and MAE are not sensitive to direction of bias. The ME gives both direction and magnitude of bias but can be distorted by extreme values while the BES is insensitive to extreme values. The STM is robust for giving the direction of bias; it is not sensitive to extreme values but it does not give the magnitude of bias. The graphical tools (such as time series and cumulative curves) show the performance of the model with time. It is recommended to integrate parametric and nonparametric methods along with graphical methods for a comprehensive analysis of bias of a numerical model.

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Is Gastroparesis Found More Frequently in Patients with Cystic Fibrosis? A Systematic Review

Cystic fibrosis (CF) is associated with different gastrointestinal motility disturbances and syndromes. We aim to assess gastric emptying in patients with CF compared to healthy controls by a systematic review of existing literature. Medical databases and abstracts from major gastroenterology and CF meetings were reviewed. Emptying times in CF patients were compared with healthy controls using random effects models. Subgroup analysis stratified results by age and diagnostic modality. Nineteen studies from 7 countries included 574 subjects (359 CF patients and 215 controls). Using pooled analysis frequency of gastroparesis was high (38%, 95% CI 30–45%) but results were highly dependent on the diagnostic modality. Delayed gastric emptying is more common in CF compared to general population. Scintigraphy identified rapid gastric emptying in a subgroup of CF patients, but this finding disappeared with adequate pancreatic enzyme replacement and after other diagnostic modalities were included.

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Haploidentical Stem Cell Transplantation in Adult Haematological Malignancies

Haematopoietic stem cell transplantation is a well-established treatment option for both hematological malignancies and nonmalignant conditions such as aplastic anemia and haemoglobinopathies. For those patients lacking a suitable matched sibling or matched unrelated donor, haploidentical donors are an alternative expedient donor pool. Historically, haploidentical transplantation led to high rates of graft rejection and GVHD. Strategies to circumvent these issues include T cell depletion and management of complications thereof or T replete transplants with GVHD prophylaxis. This review is an overview of these strategies and contemporaneous outcomes for hematological malignancies in adult haploidentical stem cell transplant recipients.

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The Use of Glycomacropeptide in Dietary Management of Phenylketonuria

Dietary therapy is the most common therapy applied in treatment of Phenylketonuria (PKU) with restriction of intake of most natural proteins that are rich in Phenylalanine (Phe). Recently, it has been claimed that caseinoglycomacropeptide (GMP), derived of whey, may be used to replace the amino acid formulae (AAF). The Aim of Work. To study the feasibility of use of GMP for partial replacement of artificial formula in treatment of children with PKU. Methods. Ten patients with PKU were included in the study. They received the recommended daily allowances of protein in the form of AAF or a combination of AAF and GMP. The percent of intake of GMP in phases 1 and 2 was 50% and zero%, respectively. Results. The median and interquartiles of phenyl alanine Phe levels phase were not significantly different in phases I and II, 376 (167–551) μmol/L versus 490 (289–597) μmol/L, respectively. Phenylalanine/tyrosine ratio, amino acids, and other laboratory data showed no significant difference between the two phases. Conclusion. GMP may be used to replace 50% of the protein intake to improve the nutritive value and palatability of diet and to provide a more satisfactory diet. No toxicity or side effects were reported in patients on that regimen.

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Analysis and Numerical Simulation on the Reduction Effect of Stress Waves Caused by Water Jet Slotting Near Blasting Source

As one of the most serious “side effects” of blast excavation, blast-induced vibration must be controlled for existing buildings and human beings. This paper proposes a method for blast-induced vibration reduction with water jet assistance according to the cutting characters of low-noised, environment-friendly water jet. The mechanism of vibration-isolation with water jet assistance was analyzed, and the stress wave energy attenuation models were established based on blasting theory and stress wave theory. Influence law on shock wave attenuation by vibration-isolation slot was studied by numerical simulation. Simulation results agree with the theoretical analysis roughly. The results of this study put forward a method for blast-induced vibration near blasting source and provide a certain theoretical basis.

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Progressed Multivessel Spontaneous Coronary Artery Dissection That Naturally Healed in a Male Patient with Non-ST Segment Elevation Myocardial Infarction

Spontaneous coronary artery dissection (SCAD) is a rare condition that may have a serious outcome because of acute coronary syndrome. The condition especially affects young women. We evaluated a middle-aged male patient with a non-ST segment elevation myocardial infarction caused by multivessel SCAD. The SCAD had occurred in the distal right coronary artery (RCA), the mid left anterior descending artery (LAD), and the distal LAD at the same time. His culprit lesion was in the distal RCA, but the SCAD had progressed more proximally within the RCA 12 days later with no clinical symptoms. We treated the mid LAD with implantation of a drug-eluting stent on admission and the SCAD had not progressed 12 days later. Moreover, the SCAD in the distal RCA and distal LAD healed spontaneously 12 days later. He had no recurrent attack, and all SCAD lesions of the RCA and LAD had completely healed 6 months later. Given that SCAD appears in various forms over the clinical course, a strategy of intervention needs careful consideration.

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Hypertrophic lupus erythematosus successfully treated with hydroxychloroquine

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Increased blood flow and vasculature in solar lentigo

Abstract

Solar lentigo (SL) is a hallmark of ultraviolet (UV)-induced photoaged skin and growing evidence implicates blood vessels in UV-associated pigmentation. In this study, we investigated whether the vasculatures are modified in SL. Twenty-five women with facial SL were enrolled and colorimetric and blood flow studies were performed. There was a significant increase in erythema which was associated with increased blood flow in the lesional skin compared with perilesional normal skin. Immunohistochemical studies with 24 facial SL biopsies consistently revealed a significant increase in vessel density accompanied by increased levels of vascular endothelial growth factor expression. CD68 immunoreactivity was significantly higher in lesional skin suggesting increased macrophage infiltration in SL. In conclusion, SL is characterized by increased blood flow and vasculature. These findings suggest the possible influence of the characteristics of vasculature on development of SL.

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Eccrine poroma with calcification and metaplastic ossification

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Case of severe ulceration induced by pazopanib

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Hypocomplementemia is a diagnostic clue for parvovirus B19 infection in adults

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Up-dosing non-sedating antihistamines in patients with chronic spontaneous urticaria: A systematic review and meta-analysis

Abstract

Background

There is a lack of large, randomized, double-blind studies that address antihistamine up-dosing for chronic spontaneous urticaria (CSU).

Objectives

To explore and analyze available data to provide clinical evidence for antihistamine up-dosing.

Methods

We searched literature using the keywords “chronic, urticaria, antihistamines” in the Medline, Scopus, Google Scholar, Embase, Web of Science and Cochrane databases between January 1990 and November 2014. We assessed quality with the Jadad score that evaluates quality of randomization, double blinding, and losses to follow-up. We identified 1,042 articles, including 15 in the final evaluation. We performed two meta-analyses, one including studies that analyzed treatment response among groups receiving different antihistamine doses versus placebo, and another that analyzed antihistamine up-dosing in those patients who did not respond to standard doses.

Results

Only five articles reached a high quality level. We did not find significant differences in rate's response or number of wheals between those patients who received a standard dose vs. a high dose. We found a significant improvement only in the pruritus variable of the urticaria activity score (UAS) scale. The estimated relative risk for improvement by increasing the antihistamine dose was 2.27 (95% CI 1.68-3.06); however, there was significant heterogeneity. The proportion of non-respondent CSU patients who responded to antihistamine up-dosing was 63.2% (95% CI 57-69.6%).

Conclusions

We found that up-dosing antihistamines significantly improved control of pruritus but not of wheal number. However, the relative weakness of the studies and the significant heterogeneity among them made it difficult to reach a final conclusion.

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A bacterial type III secretion-based protein delivery tool for broad applications in cell biology

Methods enabling the delivery of proteins into eukaryotic cells are essential to address protein functions. Here we propose broad applications to cell biology for a protein delivery tool based on bacterial type III secretion (T3S). We show that bacterial, viral, and human proteins, fused to the N-terminal fragment of the Yersinia enterocolitica T3S substrate YopE, are effectively delivered into target cells in a fast and controllable manner via the injectisome of extracellular bacteria. This method enables functional interaction studies by the simultaneous injection of multiple proteins and allows the targeting of proteins to different subcellular locations by use of nanobody-fusion proteins. After delivery, proteins can be freed from the YopE fragment by a T3S-translocated viral protease or fusion to ubiquitin and cleavage by endogenous ubiquitin proteases. Finally, we show that this delivery tool is suitable to inject proteins in living animals and combine it with phosphoproteomics to characterize the systems-level impact of proapoptotic human truncated BID on the cellular network.

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Identification of optimal parameter combinations for the emergence of bistability

Bistability underlies cellular memory and maintains alternative differentiation states. Bistability can emerge only if its parameter range is either physically realizable or can be enlarged to become realizable. We derived a general rule and showed that the bistable range of a reaction parameter is maximized by a pair of other parameters in any gene regulatory network provided they satisfy a general condition. The resulting analytical expressions revealed whether or not such reaction pairs are present in prototypical positive feedback loops. They are absent from the feedback loop enclosed by protein dimers but present in both the toggle-switch and the feedback circuit inhibited by sequestration. Sequestration can generate bistability even at narrow feedback expression range at which cooperative binding fails to do so, provided inhibition is set to an optimal value. These results help to design bistable circuits and cellular reprogramming and reveal whether bistability is possible in gene networks in the range of realistic parameter values.

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Development of a Lunar-Phase Observation System Based on Augmented Reality and Mobile Learning Technologies

Observing the lunar phase requires long-term involvement, and it is often obstructed by bad weather or tall buildings. In this study, a lunar-phase observation system is developed using the augmented reality (AR) technology and the sensor functions of GPS, electronic compass, and 3-axis accelerometer on mobile devices to help students observe and record lunar phases easily. By holding the mobile device towards the moon in the sky, the screen will show the virtual moon at the position of the real moon. The system allows the user to record the lunar phase, including its azimuth/elevation angles and the observation date and time. In addition, the system can shorten the learning process by setting different dates and times for observation, so it can solve the problem of being unable to observe and record lunar phases due to a bad weather or the moon appearing late in the night. Therefore, it is an effective tool for astronomy education in elementary and high schools. A teaching experiment has been conducted to analyze the learning effectiveness of the system and the results show that it is effective in learning the lunar concepts. The questionnaire results reveal that students considered the system easy to operate and it is useful in locating the moon and recording the lunar data.

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Compensatory Analysis and Optimization for MADM for Heterogeneous Wireless Network Selection

In the next-generation heterogeneous wireless networks, a mobile terminal with a multi-interface may have network access from different service providers using various technologies. In spite of this heterogeneity, seamless intersystem mobility is a mandatory requirement. One of the major challenges for seamless mobility is the creation of a network selection scheme, which is for users that select an optimal network with best comprehensive performance between different types of networks. However, the optimal network may be not the most reasonable one due to compensation of MADM (Multiple Attribute Decision Making), and the network is called pseudo-optimal network. This paper conducts a performance evaluation of a number of widely used MADM-based methods for network selection that aim to keep the mobile users always best connected anywhere and anytime, where subjective weight and objective weight are all considered. The performance analysis shows that the selection scheme based on MEW (weighted multiplicative method) and combination weight can better avoid accessing pseudo-optimal network for balancing network load and reducing ping-pong effect in comparison with three other MADM solutions.

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Antimicrobial Susceptibility of Escherichia coli Strains Isolated from Alouatta spp. Feces to Essential Oils

This study evaluated the in vitro antibacterial activity of essential oils from Lippia graveolens (Mexican oregano), Origanum vulgaris (oregano), Thymus vulgaris (thyme), Rosmarinus officinalis (rosemary), Cymbopogon nardus (citronella), Cymbopogon citratus (lemongrass), and Eucalyptus citriodora (eucalyptus) against Escherichia coli () strains isolated from Alouatta spp. feces. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined for each isolate using the broth microdilution technique. Essential oils of Mexican oregano (MIC mean = 1818 μg mL−1; MBC mean = 2618 μg mL−1), thyme (MIC mean = 2618 μg mL−1; MBC mean = 2909 μg mL−1), and oregano (MIC mean = 3418 μg mL−1; MBC mean = 4800 μg mL−1) showed the best antibacterial activity, while essential oils of eucalyptus, rosemary, citronella, and lemongrass displayed no antibacterial activity at concentrations greater than or equal to 6400 μg mL−1. Our results confirm the antimicrobial potential of some essential oils, which deserve further research.

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Long-Term Chronic Intermittent Hypobaric Hypoxia in Rats Causes an Imbalance in the Asymmetric Dimethylarginine/Nitric Oxide Pathway and ROS Activity: A Possible Synergistic Mechanism for Altitude Pulmonary Hypertension?

Chronic intermittent hypoxia (CIH) and chronic hypoxia (CH) are associated with high-altitude pulmonary hypertension (HAPH). Asymmetric dimethylarginine (ADMA), a NO synthase (NOS) inhibitor, may contribute to HAPH. This study assessed changes in the ADMA/NO pathway and the underlying mechanisms in rat lungs following exposure to CIH or CH simulated in a hypobaric chamber at 428 Torr. Twenty-four adult Wistar rats were randomly assigned to three groups: CIH2x2 (2 days of hypoxia/2 days of normoxia), CH, and NX (permanent normoxia), for 30 days. All analyses were performed in whole lung tissue. L-Arginine and ADMA were analyzed using LC-MS/MS. Under both hypoxic conditions right ventricular hypertrophy was observed () and endothelial NOS mRNA increased (), but the phosphorylated/nonphosphorylated vasodilator-stimulated phosphoprotein (VASP) ratio was unchanged. ADMA increased (), whereas dimethylarginine dimethylaminohydrolase (DDAH) activity decreased only under CH (). Although arginase activity increased () and L-arginine exhibited no changes, the L-arginine/ADMA ratio decreased significantly (). Moreover, NOX4 expression increased only under CH (), but malondialdehyde (MDA) increased (up to 2-fold) equally in CIH2x2 and CH (). Our results suggest that ADMA and oxidative stress likely reduce NO bioavailability under altitude hypoxia, which implies greater pulmonary vascular reactivity and tone, despite the more subdued effects observed under CIH.

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The Effect of Air Pollution on the Occurrence of Nonspecific Conjunctivitis

Purpose. To investigate the short-term effect of air pollution on occurrence of nonspecific conjunctivitis. Methods. Data were collected from outpatient visits from cases with conjunctivitis over a period of one year. Regression analysis was performed to evaluate the relationship between the number of outpatient visits and the air quality and the lag effect of air quality on conjunctivitis occurrence. Results. The air quality index on the day of presentation (), one day before presentation (), and two days before presentation day () had a positive relation with outpatient visits for conjunctivitis. The air quality index () and outpatient visits number per day () in autumn and winter (October to March) were significantly higher than those in spring (April) and summer (September). Conclusions. The air quality index within two days before presentation affected the probability of attending the outpatient clinic for nonspecific conjunctivitis. High number of cases can be expected in colder season.

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Drosophila Torsin Protein Regulates Motor Control and Stress Sensitivity and Forms a Complex with Fragile-X Mental Retardation Protein

We investigated unknown in vivo functions of Torsin by using Drosophila as a model. Downregulation of Drosophila Torsin (DTor) by DTor-specific inhibitory double-stranded RNA (RNAi) induced abnormal locomotor behavior and increased susceptibility to H2O2. In addition, altered expression of DTor significantly increased the numbers of synaptic boutons. One important biochemical consequence of DTor-RNAi expression in fly brains was upregulation of alcohol dehydrogenase (ADH). Altered expression of ADH has also been reported in Drosophila Fragile-X mental retardation protein (DFMRP) mutant flies. Interestingly, expression of DFMRP was altered in DTor mutant flies, and DTor and DFMRP were present in the same protein complexes. In addition, DTor and DFMRP immunoreactivities were partially colocalized in several cellular organelles in larval muscles. Furthermore, there were no significant differences between synaptic morphologies of dfmrp null mutants and dfmrp mutants expressing DTor-RNAi. Taken together, our evidences suggested that DTor and DFMRP might be present in the same signaling pathway regulating synaptic plasticity. In addition, we also found that human Torsin1A and human FMRP were present in the same protein complexes, suggesting that this phenomenon is evolutionarily conserved.

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Three Hong Kong nurses guilty of professional misconduct after patient dies due to blocked airway - South China Morning Post

South China Morning Post

Three Hong Kong nurses guilty of professional misconduct after patient dies due to blocked airway
South China Morning Post
Three nurses were found guilty of professional misconduct on Monday following a serious medical blunder in which a 73-year-old cancer patient died after a breathing hole on his throat was blocked by gauze. This was a landmark case for the Nursing ...

and more »

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Anti-cancer vaccine for boys being considered - Radio New Zealand

Radio New Zealand

Anti-cancer vaccine for boys being considered
Radio New Zealand
Doctors have urged that the vaccine be also given to boys, amid warnings that cancers caused by the virus, such as in the throat and tongue, will surpass cervical cancer rates in five years time. Other changes being proposed to the National ...

and more »

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Editorial Board

Publication date: June 2016
Source:Cryobiology, Volume 72, Issue 3

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Author Index

Publication date: June 2016
Source:Cryobiology, Volume 72, Issue 3

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Cumulative Subject Index

Publication date: June 2016
Source:Cryobiology, Volume 72, Issue 3

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Society for Cryobiology

Publication date: June 2016
Source:Cryobiology, Volume 72, Issue 3

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The Male Gaze in a Math Book

I kind of assumed I could get past page 2 of a math book before the author objectified women...

-- Read more on ScientificAmerican.com

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Gene regulation: Expression feels two pulses

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Πέμπτη 26 Μαΐου 2016

Pregnancy Desire, Partner Serodiscordance, and Partner HIV Disclosure among Reproductive Age HIV-Infected Women in an Urban Clinic

Women comprise 25% of the US HIV epidemic, with many women of reproductive age. There is a need for providers to address the reproductive needs and desires of women with HIV given that effective antiretroviral therapy has transformed HIV into a chronic disease. This cross-sectional study shows high rates of partner serodiscordance (61%) and moderate HIV disclosure to partners (61%). Patients surveyed reported practitioners discuss condoms (94%) and contraception (71%) more often than pregnancy desire (38%). In our sample, 44% of the surveyed women intended future pregnancy, whereas women who did not intend future pregnancy cited HIV/health and serodiscordance as the most common reasons (56% and 35%, resp.). There was no difference in the knowledge of mother-to-child transmission risk between women who intended or did not intend future pregnancy (). These results underline the need for provider training in reproductive counseling to promote risk reduction and education.

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Integrated whole-heart computational workflow for inverse potential mapping and personalized simulations

Integration of whole-heart activation simulations and inverse potential mapping (IPM) could benefit the guidance and planning of electrophysiological procedures. Routine clinical application requires a fast an...

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Miltefosine for mucosal and complicated cutaneous old world leishmaniasis : a case series and review of the literature

Complicated Old World cutaneous leishmaniasis (OWCL) and Old World mucosal leishmaniasis (OWML) constitute an indication for systemic treatment. To date, there no controlled clinical studies that compare treatment options for these diseases. We compiled a case series of 24 cases successfully treated with miltefosine. We conclude that oral miltefosine is an effective treatment option for both OWCL and OWML.

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DNA methylation in newborns and maternal smoking in pregnancy : genome-wide consortium meta-analysis

Epigenetic modifications, including DNA methylation, represent a potential mechanism for environmental impacts on human disease. Maternal smoking in pregnancy remains an important public health problem that impacts child health in a myriad of ways and has potential lifelong consequences. The mechanisms are largely unknown, but epigenetics most likely plays a role. We formed the Pregnancy And Childhood Epigenetics (PACE) consortium and meta-analyzed, across 13 cohorts (n = 6,685), the association between maternal smoking in pregnancy and newborn blood DNA methylation at over 450,000 CpG sites (CpGs) by using the Illumina 450K BeadChip. Over 6,000 CpGs were differentially methylated in relation to maternal smoking at genome-wide statistical significance (false discovery rate, 5%), including 2,965 CpGs corresponding to 2,017 genes not previously related to smoking and methylation in either newborns or adults. Several genes are relevant to diseases that can be caused by maternal smoking (e.g., orofacial clefts and asthma) or adult smoking (e.g., certain cancers). A number of differentially methylated CpGs were associated with gene expression. We observed enrichment in pathways and processes critical to development. In older children (5 cohorts, n = 3,187), 100% of CpGs gave at least nominal levels of significance, far more than expected by chance (p value < 2.2 × 10(-16)). Results were robust to different normalization methods used across studies and cell type adjustment. In this large scale meta-analysis of methylation data, we identified numerous loci involved in response to maternal smoking in pregnancy with persistence into later childhood and provide insights into mechanisms underlying effects of this important exposure.

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Inclusion of children with airway disease for the development of spirometry reference data

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Strengthening post-graduate educational capacity for health policy and systems research and analysis : the strategy of the Consortium for Health Policy and Systems Analysis in Africa

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Global Allergy Forum and 3rd Davos Declaration 2015 : Atopic dermatitis/Eczema : challenges and opportunities toward precision medicine

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Associations between domains of physical activity, sitting time, and different measures of overweight and obesity

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Synthesis of novel amide and urea derivatives of thiazol-2-ethylamines and their activity against Trypanosoma brucei rhodesiense

2-(2-Benzamido)ethyl-4-phenylthiazole (1) was one of 1035 molecules (grouped into 115 distinct scaffolds) found to be inhibitory to Trypanosoma brucei, the pathogen causing human African trypanosomiasis, at concentrations below 3.6μM and non-toxic to mammalian (Huh7) cells in a phenotypic high-throughput screen of a 700,000 compound library performed by the Genomics Institute of the Novartis Research Foundation (GNF). Compound 1 and 72 analogues were synthesized in this lab by one of two general pathways. These plus 10 commercially available analogues were tested against T. brucei rhodesiense STIB900 and L6 rat myoblast cells (for cytotoxicity) in vitro. Forty-four derivatives were more potent than 1, including eight with IC50 values below 100nM. The most potent and most selective for the parasite was the urea analogue 2-(2-piperidin-1-ylamido)ethyl-4-(3-fluorophenyl)thiazole (70, IC50=9nM, SI>18,000). None of 33 compounds tested were able to cure mice infected with the parasite; however, seven compounds caused temporary reductions of parasitemia (⩾97%) but with subsequent relapses. The lack of in vivo efficacy was at least partially due to their poor metabolic stability, as demonstrated by the short half-lives of 15 analogues against mouse and human liver microsomes.

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Giant host red blood cell membrane mimicking polymersomes bind parasite proteins and malaria parasites

Malaria is an infectious disease that needs to be addressed using innovative approaches to counteract spread of drug resistance and to establish or optimize vaccination strategies. With our approach, we aim for a dual action with drug- and 'vaccine-like' activity against malaria. By inhibiting entry of malaria parasites into host red blood cells (RBCs) - using polymer vesicle-based (polymersome) nanomimics of RBC membranes - the life cycle of the parasite is interrupted and the exposed parasites are accessible to the host immune system. Here, we describe how host cell-sized RBC membrane mimics, formed with the same block copolymers as nanomimics, also bind the corresponding malaria parasite ligand and whole malaria parasites, similar to nanomimics. This was demonstrated using fluorescence imaging techniques and confirms the suitability of giant polymersomes (GUVs) as simple mimics for RBC membranes.

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Burden and historical trend of Buruli Ulcer prevalence in selected communities along the Offin River of Ghana

Buruli ulcer (BU) is a neglected tropical skin disease caused by Mycobacterium ulcerans with more than two thirds of the global cases reported in West Africa. A nationwide active BU case search conducted in 1999 identified two health districts along the Offin River as two of the three most endemic districts in Ghana. Based on recent anecdotal accounts that transmission is unstable along the Offin River, we conducted from March to June 2013 an exhaustive household survey and active case search in 13 selected communities within a five-kilometer radius along the Offin River. The overall prevalence of BU was 2.3% among the surveyed population of 20,390 inhabitants and 477 of the total 480 cases detected (99.4%) were historical (healed) cases. By estimating the year of occurrence for each case per community and taking into account available passive surveillance records of health facilities and the District Health Directorate, we observed a general trend of continuous emergence of cases in communities located midstream the Offin River whereas downstream communities showed more sporadic patterns. We monitored the incidence of cases after the survey and recorded a cumulative incidence rate of 0.04% for the 13 communities over a 17-month active surveillance period from August 2013 to December 2014. Our data reveal an overall decline in BU incidence along the Offin River similar to the general decline in BU incidence in recent years reported by the World Health Organization for West Africa.

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Genes, Vol. 7, Pages 22: Telomere and Telomerase Therapeutics in Cancer

Telomerase is a reverse transcriptase capable of utilizing an integrated RNA component as a template to add protective tandem telomeric single strand DNA repeats, TTAGGG, to the ends of chromosomes. Telomere dysfunction and telomerase reactivation are observed in approximately 90% of human cancers; hence, telomerase activation plays a unique role as a nearly universal step on the path to malignancy. In the past two decades, multiple telomerase targeting therapeutic strategies have been pursued, including direct telomerase inhibition, telomerase interference, hTERT or hTERC promoter driven therapy, telomere-based approaches, and telomerase vaccines. Many of these strategies have entered clinical development, and some have now advanced to phase III clinical trials. In the coming years, one or more of these new telomerase-targeting drugs may be expected to enter the pharmacopeia of standard care. Here, we briefly review the molecular functions of telomerase in cancer and provide an update about the preclinical and clinical development of telomerase targeting therapeutics.

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Reply: Dynamics of Gluteal Cleft Morphology in Lower Body Lift: Predictors of Unfavorable Outcomes

No abstract available

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Discussion: Bacterial Biofilm Infection Detected in Breast Implant–Associated Anaplastic Large-Cell Lymphoma

No abstract available

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Unnecessary Emergency Transfers for Evaluation by a Plastic Surgeon: A Burden to Patients and the Health Care System

Background: Plastic surgeons are frequently consulted for hand and facial injuries, and patients are often transferred to trauma centers for evaluation of these problems. The authors sought to identify the frequency and impact of “unnecessary” transfers for emergency evaluation by a plastic surgeon at a Level I trauma center. Methods: The authors reviewed more than 32,000 consecutive emergency department encounters at their institution between April of 2009 and April of 2013 and found 1181 patients transferred for evaluation by plastic surgery. Using a retrospective chart review, necessity of transfer was determined based on the intervention performed at the authors’ institution and the availability of resources at the transferring site. Results: Of all the patients referred for “emergency” evaluation, 860 (74.1 percent) were unnecessary. Transfers for hand-related issues were more likely to be coded as unnecessary compared with referrals for facial trauma and infection (76 percent versus 66 percent; p

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Breast Cancer–Related Lymphedema: Quality of Life after Lymph Node Transfer

Background: Breast cancer–related lymphedema affects multiple aspects of patients’ daily lives. The main aim of this study was to assess the impact of vascularized lymph node transfer on the quality of life in patients with lymphedema. Methods: Between 2007 and 2012, 25 female patients with breast cancer–related lymphedema underwent vascularized lymph node transfer. In 22 cases, the patients underwent a simultaneous deep inferior epigastric artery perforator flap breast reconstruction based on the superficial circumflex iliac artery. The influence on quality of life was evaluated using the Upper Limb Lymphedema-27 questionnaire, which includes physical, psychological, and social dimensions. The authors also investigated risk factors for lymphedema, such as body mass index, smoking, age, and time between start of lymphedema and vascularized lymph node transfer, and their impact on quality of life. Results: Twenty-one patients (84 percent) had an improvement of quality of life after vascularized lymph node transfer. The mean physical, psychological, and social scores were significantly improved postoperatively (p

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Effect of Cooling on Free Flap Ischemia

No abstract available

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Clinical Significance of Internal Mammary Lymph Node Biopsy during Microsurgical Breast Reconstruction: Review of 264 Cases

Background: Despite the knowledge of alternate lymphatic draining patterns of the breast, routine evaluation of the internal mammary lymph node basin is still not considered standard of care. The advent of microsurgical breast reconstruction using the internal mammary vessels as recipients, however, has allowed sampling of internal mammary lymph nodes with technical ease, thus revisiting their role in breast cancer management. In the present study, the authors reviewed their experience with this practice. Methods: A retrospective analysis of patients who underwent internal mammary lymph node biopsy at the time of autologous breast reconstruction using the internal mammary vessels between 2004 and 2012 was performed. Parameters of interest included patient age, timing of reconstruction (immediate versus delayed), disease stage, and pathologic findings of internal mammary lymph nodes. Results: A total of 264 autologous breast reconstructions using the internal mammary vessels were performed in 204 patients with a median age of 44.5 years. The majority of reconstructions were immediate [n = 211 (79.9 percent)]. Seventy-two percent of patients had either stage I [72 patients (35.3 percent)] or stage II disease [75 patients (36.8 percent)]. Six patients were found to have internal mammary lymph node metastasis. Stage migration and alteration in adjuvant therapy occurred in all patients. Conclusion: Internal mammary lymph node sampling at the time of autologous breast reconstruction using the internal mammary system should become routine practice, as the morbidity associated with internal mammary lymph node harvest is low and the impact in cases of nodal involvement is quite substantial. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

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Explore a map of London’s extraordinary archaeological finds

From the grisly aftermath of a distant volcanic eruption, to the huge amphitheatre where criminals met their deaths, dig into one of the world's greatest cities

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Social perception of morbidity in facial nerve paralysis

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ABSTRACT

Background

There are many patient-based and clinician-based scales measuring the severity of facial nerve paralysis and the impact on quality of life, however, the social perception of facial palsy has received little attention. The purpose of this pilot study was to measure the consequences of facial paralysis on selected domains of social perception and compare the social impact of paralysis of the different components.

Method

Four patients with typical facial palsies (global, marginal mandibular, zygomatic/buccal, and frontal) and 1 control were photographed. These images were each shown to 100 participants who subsequently rated variables of normality, perceived distress, trustworthiness, intelligence, interaction, symmetry, and disability. Statistical analysis was performed to compare the results among each palsy.

Results

Paralyzed faces were considered less normal compared to the control on a scale of 0 to 10 (mean, 8.6; 95% confidence interval [CI] = 8.30–8.86) with global paralysis (mean, 3.4; 95% CI = 3.08–3.80) rated as the most disfiguring, followed by the zygomatic/buccal (mean, 6.0; 95% CI = 5.68–6.37), marginal (mean, 6.5; 95% CI = 6.08–6.86), and then temporal palsies (mean, 6.9; 95% CI = 6.57–7.21). Similar trends were seen when analyzing these palsies for perceived distress, intelligence, and trustworthiness, using a random effects regression model.

Conclusion

Our sample suggests that society views paralyzed faces as less normal, less trustworthy, and more distressed. Different components of facial paralysis are worse than others and surgical correction may need to be prioritized in an evidence-based manner with social morbidity in mind. © 2016 Wiley Periodicals, Inc. Head Neck, 2016

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Utility of up-front transoral robotic surgery in tailoring adjuvant therapy

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Abstract

Background

The purpose of this study was to describe how the up-front transoral robotic surgery (TORS) approach could be used to individually tailor adjuvant therapy based on surgical pathology.

Methods

Between January 2009 and December 2013, 76 patients received TORS for oropharyngeal squamous cell carcinoma (OPSCC). Clinical predictors of adjuvant therapy were analyzed and comparisons were made between recommended treatment guidelines for up-front surgery versus definitive nonsurgical approaches.

Results

Advanced N classification, human papillomavirus (HPV)-positive tumor, extracapsular spread (ECS; 26 of 76), perineural invasion (PNI; 14 of 76), and positive margins (7 of 76) were significant predictors of adjuvant chemoradiotherapy (CRT) (p < .05). Up-front TORS deintensified adjuvant therapy; 76% of stage I/II and 46% of stage III/IV patients avoided CRT. Conversely, pathologic staging resulted in 33% of patients who would have received radiotherapy (RT) alone based on clinical staging, to be intensified to receive adjuvant CRT.

Conclusion

The TORS approach deintensifies adjuvant therapy and provides valuable pathologic information to intensify treatment in select patients. TORS may be less effective in deintensification of adjuvant therapy in patients with clinically advanced N classification disease. © 2016 Wiley Periodicals, Inc. Head Neck, 2016

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IJMS, Vol. 17, Pages 378: A Theoretical Study of the Hydration of Methane, from the Aqueous Solution to the sI Hydrate-Liquid Water-Gas Coexistence

Monte Carlo and molecular dynamics simulations were done with three recent water models TIP4P/2005 (Transferable Intermolecular Potential with 4 Points/2005), TIP4P/Ice (Transferable Intermolecular Potential with 4 Points/ Ice) and TIP4Q (Transferable Intermolecular Potential with 4 charges) combined with two models for methane: an all-atom one OPLS-AA (Optimal Parametrization for the Liquid State) and a united-atom one (UA); a correction for the C–O interaction was applied to the latter and used in a third set of simulations. The models were validated by comparison to experimental values of the free energy of hydration at 280, 300, 330 and 370 K, all under a pressure of 1 bar, and to the experimental radial distribution functions at 277, 283 and 291 K, under a pressure of 145 bar. Regardless of the combination rules used for σC,O, good agreement was found, except when the correction to the UA model was applied. Thus, further simulations of the sI hydrate were performed with the united-atom model to compare the thermal expansivity to the experiment. A final set of simulations was done with the UA methane model and the three water models, to study the sI hydrate-liquid water-gas coexistence at 80, 230 and 400 bar. The melting temperatures were compared to the experimental values. The results show the need to perform simulations with various different models to attain a reliable and robust molecular image of the systems of interest.

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Genotype and allele frequencies of isoniazid-metabolizing enzymes NAT2 and GSTM1 in Latvian tuberculosis patients

Publication date: Available online 25 May 2016
Source:Journal of Infection and Chemotherapy
Author(s): Viktorija Igumnova, Valentina Capligina, Alvils Krams, Andra Cirule, Didzis Elferts, Ilva Pole, Inta Jansone, Dace Bandere, Renate Ranka
Pharmacogenomic testing of tuberculosis drug-metabolizing enzyme genes was proposed as a strategy to identify patients at risk for suboptimal responses to medications. However, variations of the genotype frequencies among ethnic groups exist and new alleles are been identified. The aim of this study was to identify polymorphisms of genes encoding metabolic enzymes NAT2 and GSTM1 in tuberculosis patients in Latvia and to estimate the frequency of NAT2 slow acetylator and GSTM1 null genotypes. In total, 85 DNA samples were genotyped, all individuals were Caucasian. An ethnic heterogeneity reflecting the multiethnic population of the country was observed. 49 patients were Latvians, 30 were Russians and 6 of other ethnicity. In total, 7 NAT2 alleles were identified: *4, *5, *6, *7, *11, *12, * and *13. The most frequent was the slow acetylation allele NAT2*6 (frequency 0.388) followed by the slow acetylation allele NAT2*5 and the rapid acetylation allele NAT2*4 (frequencies 0.306 and 0.194, respectively). The predominance of slow (51.8%) and intermediate (43.5%) acetylators compared with rapid acetylators (4.7%) was observed. The GSTM1 null genotype was detected in 48.2% of tuberculosis patients. When subgroup analysis was performed according to ethnicity, the results showed that neither NAT2 allele frequencies nor GSTM1 null genotype frequency did not differ significantly in TB patients of Latvian or Russian ethnicity. Overall, genotyping results were similar with previous reports of a NAT2 gene variation and GSTM1 null genotype frequency in Caucasians. Our findings have a contribution for the pharmacogenetics-based tuberculosis therapy in Latvia in future.

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Contamination of healthcare workers' hands with bacterial spores

Publication date: Available online 25 May 2016
Source:Journal of Infection and Chemotherapy
Author(s): Teppei Sasahara, Ryusuke Ae, Michiyo Watanabe, Yumiko Kimura, Chikara Yonekawa, Shunji Hayashi, Yuji Morisawa
Clostridium species and Bacillus spp. are spore-forming bacteria that cause hospital infections. The spores from these bacteria are transmitted from patient to patient via healthcare workers' hands. Although alcohol-based hand rubbing is an important hand hygiene practice, it is ineffective against bacterial spores. Therefore, healthcare workers should wash their hands with soap when they are contaminated with spores. However, the extent of health care worker hand contamination remains unclear. The aim of this study is to determine the level of bacterial spore contamination on healthcare workers' hands. The hands of 71 healthcare workers were evaluated for bacterial spore contamination. Spores attached to subject's hands were quantitatively examined after 9 working hours. The relationship between bacterial spore contamination and hand hygiene behaviors was also analyzed. Bacterial spores were detected on the hands of 54 subjects (76.1%). The mean number of spores detected was 468.3 CFU/hand (maximum: 3300 CFU/hand). Thirty-seven (52.1%) and 36 (50.7%) subjects were contaminated with Bacillus subtilis and Bacillus cereus, respectively. Nineteen subjects (26.8%) were contaminated with both Bacillus species. Clostridium difficile was detected on only one subject's hands. There was a significant negative correlation between the hand contamination level and the frequency of handwashing (r = −0.44, P < 0.01) and a significant positive correlation between the hand contamination level and the elapsed time since last handwashing (r = 0.34, P < 0.01). Healthcare workers' hands may be frequently contaminated with bacterial spores due to insufficient handwashing during daily patient care.

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Old-and With Severe Heart Failure: Telemonitoring by Using Digital Pen Technology in Specialized Homecare: System Description, Implementation, and Early Results.

Telehealth programs for heart failure have been studied using a variety of techniques. Because currently a majority of the elderly are nonusers of computers and Internet, we developed a home telehealth system based on digital pen technology. Fourteen patients (mean age, 84 years [median, 83 years]) with severe heart failure participated in a 13-month pilot study in specialized homecare. Participants communicated patient-reported outcome measures daily using the digital pen and health diary forms, submitting a total of 3 520 reports. The reports generated a total of 632 notifications when reports indicated worsening health. Healthcare professionals reviewed reports frequently, more than 4700 times throughout the study, and acted on the information provided. Patients answered questionnaires and were observed in their home environment when using the system. Results showed that the technology was accepted by participants: patients experienced an improved contact with clinicians; they felt more compliant with healthcare professionals' advice, and they felt more secure and more involved in their own care. Via the system, the healthcare professionals detected heart failure-related deteriorations at an earlier stage, and as a consequence, none of the patients were admitted into hospital care during the study. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Metformin, other antidiabetic drugs, and endometrial cancer risk: a nested case-control study within Italian healthcare utilization databases.

Metformin may reduce the risk of endometrial cancer whereas other drugs for the treatment of type 2 diabetes mellitus appear to increase it, although the evidence is still limited. We investigated this issue using data from a nested case-control study within the healthcare utilization databases of the Lombardy Region, Italy. This study included 376 diabetic women with endometrial cancer and 7485 diabetic controls matched for cases on age, date at cohort entry, and duration of follow-up. We used conditional logistic regression models to estimate the odds ratio (OR) of endometrial cancer in relation to use of antidiabetic drugs, adjusted for the Charlson's comorbidity index, selected medical conditions, prescription of selected drugs, and concomitant use of other antidiabetic drugs. At cohort entry, no significant associations were observed for metformin [OR=0.99, 95% confidence interval (CI) 0.80-1.23], sulfonylureas (OR=1.14, 95% CI 0.91-1.42), insulin (OR=0.72, 95% CI 0.34-1.56), and other antidiabetic drugs (OR=1.21, 95% CI 0.75-1.95). When we considered use during follow-up, a borderline significant excess risk was found for metformin (OR=1.30, 95% CI 1.00-1.70). However, this estimate decreased to 1.07 (95% CI 0.82-1.41) when taking into account BMI using a Monte Carlo sensitivity analysis. No significant associations were found for sulfonylureas (OR=1.16, 95% CI 0.91-1.47), thiazolidinediones (OR=0.77, 95% CI 0.48-1.24), repaglinide (OR=1.32, 95% CI 0.94-1.87), incretins (OR=1.21, 95% CI 0.63-2.32), and insulin (OR=1.19, 95% CI 0.82-1.71). Our data indicate that metformin, insulin, and other antidiabetic drugs did not meaningfully affect the risk of endometrial cancer. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Lung cancer screening with low-dose spiral computed tomography: evidence from a pooled analysis of two Italian randomized trials.

The benefits and harms of lung cancer (LC) screening with low-dose computed tomography (LDCT) are debatable. Positive results from the US National Lung Screening Trial were not evident in the European trials, possibly due to their smaller sample sizes. To address this issue, we conducted a patient-level pooled analysis of two Italian randomized controlled trials. Data from DANTE and MILD trials were combined for a total of 3640 individuals in the LDCT arm and 2909 in the control arm. LC and overall mortality were analyzed using multivariate hazard ratios (HRs) and log-rank tests stratified by study. The median follow-up was 8.2 years, with a total of 30 480 person-years in the LDCT arm and 22 157 in the control arm. A total of 192 patients developed LC in the LDCT arm and 105 in the control arm. Half of the LC cases in the LDCT arm had stage IA or IB cancer, as compared with 21% in the control arm. Overall mortality rates/100 000 person-years were 925 in the LDCT arm and 1074 in the control arm, and LC mortality rates were 299 and 357, respectively. The multivariate pooled overall mortality HR was 0.89 (95% confidence interval: 0.74-1.06) and the LC mortality HR was 0.83 (95% confidence interval: 0.61-1.12) for the LDCT arm as compared with the control arm. The present pooled analysis shows a nonsignificant 11% reduction in overall mortality in individuals undergoing LDCT screening as compared with the control arm. A pooled analysis of all European trials would be a useful contribution to assess the real benefit of LDCT screening. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Determination of amino acids in urine of patients with prostate cancer and benign prostate growth.

Prostate cancer is the leading type of cancer diagnosed in men. Serum prostate-specific antigen levels and digital rectal exam are far from perfect when it comes to differentiation of patients with prostate cancer and benign prostatic hyperplasia. In this study, we attempt to determine whether amino acids can be used as prostate cancer biomarkers. Concentrations of derivatized amino acids and amines were quantified by liquid chromatography tandem mass spectrometry. A total of 100 urine samples from the two groups including samples provided before and after prostate massage were examined quantitatively for amino acid and amine concentrations with 50 urine samples collected from cancer patients and 50 samples from patients diagnosed with benign prostatic hyperplasia. Arginine, homoserine, and proline were more abundant in urine samples of cancer patients compared with arginine, homoserine, and proline levels determined in urine collected from patients with benign growth. We also show that sarcosine is not a definitive indicator of prostate cancer when analyzed in urine samples collected either before or after prostate massage. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Analysis of Different Series-Parallel Connection Modules for Dye-Sensitized Solar Cell by Electrochemical Impedance Spectroscopy

The internal impedances of different dye-sensitized solar cell (DSSC) models were analyzed by electrochemical impedance spectrometer (EIS) with an equivalent circuit model. The Nyquist plot was built to simulate the redox reaction of internal device at the heterojunction. It was useful to analyze the component structure and promote photovoltaic conversion efficiency of DSSC. The impedance of DSSC was investigated and the externally connected module assembly was constructed utilizing single cells on the scaled-up module. According to the experiment results, the impedance was increased with increasing cells connected in series. On the contrary, the impedance was decreased with increasing cells connected in parallel.

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Simplified Finite Set Model Predictive Control Strategy of Grid-Connected Cascade H-Bridge Converter

Finite set model predictive control (FS-MPC) has become a promising control technology in power converter, because of the advantages of good dynamic response and accurate current tracking capability. In real-time control process, the conventional FS-MPC strategy requires more time for prediction and optimization. As a result, there will be a certain delay between sampling and output. In order to reduce the amount of calculation and overcome the adverse effect of the delay on the system performance, this paper presents a simplified FS-MPC method. Firstly, adjacent levels method is used to reduce the amount of the calculation, and then two-step FS-MPC is adopted to compensate the calculation delay. The control strategy is validated by the simulation and experimental results of a grid-connected cascaded H-bridge converter.

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Gender and Age Related Effects While Watching TV Advertisements: An EEG Study

The aim of the present paper is to show how the variation of the EEG frontal cortical asymmetry is related to the general appreciation perceived during the observation of TV advertisements, in particular considering the influence of the gender and age on it. In particular, we investigated the influence of the gender on the perception of a car advertisement (Experiment ) and the influence of the factor age on a chewing gum commercial (Experiment ). Experiment results showed statistically significant higher approach values for the men group throughout the commercial. Results from Experiment showed significant lower values by older adults for the spot, containing scenes not very enjoyed by them. In both studies, there was no statistical significant difference in the scene relative to the product offering between the experimental populations, suggesting the absence in our study of a bias towards the specific product in the evaluated populations. These evidences state the importance of the creativity in advertising, in order to attract the target population.

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Message Passing Based Time Synchronization in Wireless Sensor Networks: A Survey

Various protocols have been proposed in the area of wireless sensor networks in order to achieve network-wide time synchronization. A large number of proposed protocols in the literature employ a message passing mechanism to make sensor node clocks tick in unison. In this paper, we first classify Message Passing based Time Synchronization (MPTS) protocols and then analyze them based on different metrics. The classification is based on the following three criteria: structure formation of the network affected by the synchronization protocol, frequency of synchronization process (synchronization interval), and synchronization message overhead. Proposed protocols are analyzed and evaluated from different perspectives based on available data. A comparison table of the reviewed protocols is presented according to the evaluation metrics. Finally, some potential methods will be proposed to improve the synchronization process.

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A New Approach to Fuzzy Metric Spaces and Their Similarity-Based Construction

We introduce a space of functions which can be interpreted as a similarity-based approach to fuzzy metric spaces. The triangle inequality we propose is defined by means of a fuzzy ordering. We compare the introduced space with fuzzy metric spaces in the sense of Seikkala and Kaleva. Finally we complete the work discovering the corresponding classical as well as fuzzy topologies.

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Recombinant bone morphogenetic protein in patients under 18 years of age

Publication date: Available online 25 May 2016
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): K. Kumar, M. Nagarjuna, R. Raut, H. Pipalia

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Home Opinions Tobacco isn't the most dangerous drug on campus, so why only target... - Concordiensis

Home Opinions Tobacco isn't the most dangerous drug on campus, so why only target...
Concordiensis
Long term habitual alcohol use cause severe liver problems, brain damage, and, like long term tobacco use, increases the risk of developing mouth, esophagus, pharynx, larynx, liver and breast cancers as well as cardiovascular diseases. Unlike smoking ...

and more »

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Monocyte exosomes induce adhesion molecules and cytokines via activation of NF-{kappa}B in endothelial cells [Research]

HIV-infected individuals have activated monocytes with an IFNα phenotype and elevated levels of circulating LPS. These individuals also have a risk of premature cardiovascular disease. The effect of activated monocyte exosomes (Exos) on endothelial cells is unknown. To determine whether Exos from immune-activated monocytes could alter endothelial cell expression and contribute to monocyte/macrophage transmigration and adhesion, we isolated Exos from monocytes stimulated with IFNα, LPS, or a combination of the two (I/L). We show that monocyte Exos contain different inflammatory microRNA cargo depending on stimulation. When LPS Exo or I/L Exo was added to HUVECs, we found a significant increase in adhesion molecule ICAM-1, chemokine ligand (CCL)-2, and cytokine IL-6 mRNAs and proteins compared with cells treated with IFNα Exo or Exos derived from unstimulated monocytes. Inhibition of transcription factor NF-B, a common inflammatory cytokine pathway, prevented induction of CCL2, IL6, and ICAM1. Inhibition of TLR4 resulted in differential blockage of the targets. Our results demonstrate for the first time that primary human monocyte Exos enter endothelial cells and cause dysfunction via the TLR4 and NF-B pathways, which may contribute to heart disease in HIV infection and other diseases involving chronic immune activation.—Tang, N., Sun, B., Gupta, A., Rempel, H., Pulliam, L. Monocyte exosomes induce adhesion molecules and cytokines via activation of NF-B in endothelial cells.

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Τετάρτη 25 Μαΐου 2016

Asia Pacific Media Educator

Asia Pacific Media Educator, published by SAGE Publications, last updated on 2016-05-25, available at http://ame.sagepub.com

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Perceptual and Motor Skills

Perceptual and Motor Skills, published by SAGE Publications, last updated on 2016-05-25, available at http://pms.sagepub.com

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County Freeholder on the Road to Recovery - Shorebeat

Shorebeat

County Freeholder on the Road to Recovery
Shorebeat
Ocean County Freeholder John C. Bartlett has successfully completed radiation and chemotherapy treatment for cancer and returned to the board at a work session meeting Wednesday. “I had very little side effects from either of them,” said Bartlett ...

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Hepatic Aryl Hydrocarbon Receptor Attenuates Fibroblast Growth Factor 21 Expression [Gene Regulation]

The Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor involved in many physiological processes. Several studies indicate that AHR is also involved in energy homeostasis. Fibroblast growth factor 21 (FGF21) is an important regulator of the fasting and feeding responses. When administered to various genetic and diet-induced mouse models of obesity, FGF21 can attenuate obesity-associated morbidities. Here, we explore the role of AHR in hepatic Fgf21 expression through the use of a conditional, hepatocyte-targeted AHR knockout mouse model (CreAlbAhrFx/Fx). Compared to the congenic parental strain (AhrFx/Fx), non-fasted CreAlbAhrFx/Fx mice exhibit a 4-fold increase in hepatic Fgf21 expression, as well as elevated expression of FGF21-target gene Igfbp1. Furthermore, in vivo agonist activation of AHR reduces hepatic Fgf21 expression during a fast. The Fgf21 promoter contains several putative dioxin response elements (DREs). Using EMSA, we demonstrate that the AHR/ARNT heterodimer binds to a specific DRE that overlaps binding sequences for peroxisome proliferator-activated receptor alpha (PPARα), carbohydrate response element-binding protein (ChREBP), and cAMP response element binding protein, hepatocyte specific (CREBH). In addition, we reveal that agonist-activated AHR impairs PPARα-, ChREBP-, and CREBH-mediated promoter activity in Hepa-1 cells. Accordingly, agonist treatment in Hepa-1 cells ablates potent ER stress-driven Fgf21 expression, and pre-treatment with AHR antagonist blocks this effect. Finally, we show that pre-treatment of primary human hepatocytes with AHR agonist diminishes PPARα-, glucose-, and ER stress-driven induction of FGF21 expression, indicating the effect is not mouse-specific. Together, our data show that AHR contributes to hepatic energy homeostasis, partly through the regulation of FGF21 expression and signaling.

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Activation of EGFR/p38/HIF-1{alpha} is pivotal for angiogenesis and tumorigenesis of malignantly transformed cells induced by hexavalent chromium [Gene Regulation]

Cr(VI)-containing compounds are well-established environmental carcinogens. Most mechanistic investigations of Cr(VI)-induced carcinogenesis focus on oxidative stress and various cellular responses, leading to malignant cell transformation, or the first stage of metal-induced carcinogenesis. The development of malignantly transformed cells into tumors which require angiogenesis is the second stage. This study focuses on the second stage, in particular, the role of epidermal growth factor receptor (EGFR) signaling in angiogenesis and tumorigenesis of Cr(VI)-transformed cells. Our preliminary studies have shown that EGFR is constitutively activated in Cr(VI)-transformed cells, in lung tissue from Cr(VI)-exposed animals, and in lung tumor tissue from a non-smoking worker occupationally exposed to Cr(VI) for 19 years. Using in vitro and in vivo models, the present study has investigated the role of EGFR in angiogenesis of Cr(VI)-transformed cells. The results show that Cr(VI)-transformed cells are angiogenic. Hypoxia inducible factor (HIF) 1α, proangiogenic protein matrix metalloproteinase-1 (MMP-1), and vascular endothelial growth factor (VEGF) are all highly expressed in Cr(VI)-transformed cells, in lung tissue from animals exposed to Cr(VI), and in lung tumor tissue from a non-smoking worker occupationally exposed to Cr(VI) for 19 years. p38 MAPK was also activated in Cr(VI)-transformed cells and in the human lung tumor tissue. Inhibition of EGFR reduces p38 MAPK, resulting in decreased expressions of HIF-1α, MMP-1, and VEGF, leading to suppressions of angiogenesis and tumorigenesis. Overall, the present study has demonstrated that EGFR plays an important role in angiogenesis and tumorigenesis of Cr(VI)-transformed cells.

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Examining the pathways for young people with drug and alcohol dependence: a mixed-method design to examine the role of a treatment programme

Introduction

Young people with drug and alcohol problems are likely to have poorer health and other psychosocial outcomes than other young people. Residential treatment programmes have been shown to lead to improved health and related outcomes for young people in the short term. There is very little robust research showing longer term outcomes or benefits of such programmes. This paper describes an innovative protocol to examine the longer term outcomes and experiences of young people referred to a residential life management and treatment programme in Australia designed to address alcohol and drug issues in a holistic manner.

Methods and analysis

This is a mixed-methods study that will retrospectively and prospectively examine young people's pathways into and out of a residential life management programme. The study involves 3 components: (1) retrospective data linkage of programme data to health and criminal justice administrative data sets, (2) prospective cohort (using existing programme baseline data and a follow-up survey) and (3) qualitative in-depth interviews with a subsample of the prospective cohort. The study will compare findings among young people who are referred and (a) stay 30 days or more in the programme (including those who go on to continuing care and those who do not); (b) start, but stay fewer than 30 days in the programme; (c) are assessed, but do not start the programme.

Ethics and dissemination

Ethics approval has been sought from several ethics committees including a university ethics committee, state health departments and an Aboriginal-specific ethics committee. The results of the study will be published in peer-reviewed journals, presented at research conferences, disseminated via a report for the general public and through Facebook communications. The study will inform the field more broadly about the value of different methods in evaluating programmes and examining the pathways and trajectories of vulnerable young people.

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Πληροφορίες

Δευτέρα 30 Μαΐου 2016

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Πέμπτη 26 Μαΐου 2016

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Τετάρτη 25 Μαΐου 2016

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