Previewing the 21st John H.P. Maley Lecture

Attend NEXT in Nashville, June 8-11, to experience the Maley Lecture, "Pain Management: Roadmap to Revolution," by Steven Z. George. www.apta.org/NEXT

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Previewing the 47th Mary McMillan Lecture

Attend NEXT in Nashville, June 8-11, to experience the McMillan Lecture, "Our Future Selves: Unprecedented Opportunities," by Carole B. Lewis, PT, DPT, PhD, GCS, GTC, MSC, FAPTA. www.apta.org/NEXT

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Catalysts, Vol. 6, Pages 47: Homo-Polymerization of 1-Hexene Catalysed by O^N^N (Salicylaldimine)Iron(III) Pre-Catalysts to Branched Poly(1-hexene)

Five new iron(III) 1-hexene polymerisation catalysts were prepared from the reactions of 2,4-di-tert-butyl-6-(2-(1H-imidazol-4-yl)ethylimino)methylphenol (L1), or 4-tert-butyl-6-(2-(1H-imidazol-4-yl)ethylimino)methylphenol (L2) or 2,4-di-tert-butyl-6-[(2-pyridin-2-yl-ethylimino)-methyl-phenol (L3) with anhydrous iron(II) halides to form [FeCl2(L1)] (1), [FeBr2(L1)] (2), [FeI2(L1)] (3), [FeBr2(L2)] (4) and [FeCl2(L3)] (5). All the iron(III) complexes 1–5 were activated with EtAlCl2 to produce active catalysts for the polymerisation of 1-hexene to low molecular weight poly(1-hexene) (Mn = 1021–1084 Da) and very narrow polydispersity indices (1.19–1.24). 1H and 13C{1H} NMR analysis showed the polymers are branched with methyl, butyl and longer chain branches. The longer chain branches are dominant indicating that 2,1-insertion of monomer is favoured over 1,2-insertion in the polymerisation reaction.

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Sinusitis, Vol. 1, Pages 49-54: Chronic Rhinosinusitis as a Crucial Symptom of Cystic Fibrosis—Case Report and Discussion on the Sinonasal Compartment as Site of Pseudomonas aeruginosa Acquisition into CF Airways

Cystic fibrosis (CF) is the most frequent congenital lethal disease in Caucasians. Impaired mucociliary clearance causes chronic bacterial rhinosinusitis in up to 62% of patients, and almost all patients exhibit sinonasal pathology in CT scans. Pathogens like Pseudomonas aeruginosa (P.a.) chronically colonize about 70% of the CF adults' lungs and are the major reason for pulmonary destruction and premature death. In our 34-year-old female CF patient, rhinosinusitis caused massive orbital hypertelorism despite three sinonasal operations. Her sputum samples had always been negative for P.a. Then, P.a. was primarily detected in her sputum and additionally in nasal lavage, which since then persisted in both, her upper and lower airways. The P.a. strains turned out to be genetically identical in both airway levels, indicating early colonization of the entire airway system with P.a. This first report on simultaneous primary P.a. detection in the sinonasal and pulmonary compartments highlights the need to include an assessment of upper airway colonization in the standards of CF care, particularly in patients without chronic P.a. colonization. Both airway levels need to be considered as one united system, and a strong cooperation between ENT and CF specialists should be established. Prospective longitudinal studies should assess the upper airways´ role in acquisition and persistence of pathogens and evaluate conservative and surgical therapeutic options.

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Inhibition of Asthma in OVA Sensitized Mice Model by a Traditional Uygur Herb Nepeta bracteata Benth.

Asthma is a chronic lung inflammation which affects many people. As current therapies for asthma mainly rely on administration of glucocorticoids and have many side effects, new therapy is needed. In this study, we investigated Nepeta bracteata Benth., a traditional Uygur Herb, for its therapeutics effect in OVA induced asthmatic mice model. Treatment of OVA sensitized asthma mice with extract from Nepeta bracteata Benth. demonstrated improved lung pathology, as well as reduced infiltration of eosinophil and neutrophil. Nepeta bracteata Benth. extract also contributed to the rebalance of Th17/Treg cell via decreasing the Th17 cell and increasing the Treg, which was corresponding with the inhibited Th17 cytokine response and increased IL-10 level. Moreover, the reduced TGF-β level and Smad2/3 protein level also suggested that Nepeta bracteata Benth. extract could inhibit TGF-β mediated airway remodelling as well. Taken together, these data suggested that Nepeta bracteata Benth. may be a novel candidate for future antiasthma drug development.

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The Effectiveness of Cupping Therapy on Relieving Chronic Neck and Shoulder Pain: A Randomized Controlled Trial

The research aimed to investigate the effectiveness of cupping therapy (CT) in changes on skin surface temperature (SST) for relieving chronic neck and shoulder pain (NSP) among community residents. A single-blind experimental design constituted of sixty subjects with self-perceived NSP. The subjects were randomly allocated to two groups. The cupping group received CT at SI 15, GB 21, and LI 15 acupuncture points, and the control group received no intervention. Pain was assessed using the SST, visual analog scale (VAS), and blood pressure (BP). The main results were SST of GB 21 acupuncture point raised from 30.6°C to 32.7°C and from 30.7°C to 30.6°C in the control group. Neck pain intensity (NPI) severity scores were reduced from 9.7 to 3.6 in the cupping group and from 9.7 to 9.5 in the control group. The SST and NPI differences between the groups were statistically significant (). One treatment of CT is shown to increase SST. In conjunction with the physiological effect the subjective experience of NSP is reduced in intensity. Further studies are required to improve the understanding and potential long-term effects of CT.

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Attentional guidance by relative features: Behavioral and electrophysiological evidence

Abstract

Our ability to select task-relevant information from cluttered visual environments is widely believed to be due to our ability to tune attention to the particular elementary feature values of a sought-after target (e.g., red, orange, yellow). By contrast, recent findings showed that attention is often tuned to feature relationships, that is, features that the target has relative to irrelevant features in the context (e.g., redder, yellower). However, the evidence for such a relational account is so far exclusively based on behavioral measures that do not allow a safe inference about early perceptual processes. The present study provides a critical test of the relational account, by measuring an electrophysiological marker in the EEG of participants (N2pc) in response to briefly presented distractors (cues) that could either match the physical features of the target or its relative features. In a first experiment, the target color and nontarget color were kept constant across trials. In line with a relational account, we found that only cues with the same relative color as the target were attended, regardless of whether the cues had the same physical color as the target. In a second experiment, we demonstrate that attention is biased to the exact target feature value when the target is embedded in a randomly varying context. Taken together, these results provide the first electrophysiological evidence that attention can modulate early perceptual processes differently; in a context-dependent manner versus a context-independent manner, resulting in marked differences in the range of colors that can attract attention.

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Emotional responses to irony and emoticons in written language: Evidence from EDA and facial EMG

Abstract

While the basic nature of irony is saying one thing and communicating the opposite, it may also serve additional social and emotional functions, such as projecting humor or anger. Emoticons often accompany irony in computer-mediated communication, and have been suggested to increase enjoyment of communication. In the current study, we aimed to examine online emotional responses to ironic versus literal comments, and the influence of emoticons on this process. Participants read stories with a final comment that was either ironic or literal, praising or critical, and with or without an emoticon. We used psychophysiological measures to capture immediate emotional responses: electrodermal activity to directly measure arousal and facial electromyography to detect muscle movements indicative of emotional expressions. Results showed higher arousal, reduced frowning, and enhanced smiling for messages with rather than without an emoticon, suggesting that emoticons increase positive emotions. A tendency toward less negative responses (i.e., reduced frowning and enhanced smiling) for ironic than literal criticism, and less positive responses (i.e., enhanced frowning and reduced smiling) for ironic than literal praise suggests that irony weakens the emotional impact of a message. The present findings indicate the utility of a psychophysiological approach in studying online emotional responses to written language.

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Symmetry, Vol. 8, Pages 15: Low Dimensional Vessiot-Guldberg-Lie Algebras of Second-Order Ordinary Differential Equations

A direct approach to non-linear second-order ordinary differential equations admitting a superposition principle is developed by means of Vessiot-Guldberg-Lie algebras of a dimension not exceeding three. This procedure allows us to describe generic types of second-order ordinary differential equations subjected to some constraints and admitting a given Lie algebra as Vessiot-Guldberg-Lie algebra. In particular, well-known types, such as the Milne-Pinney or Kummer-Schwarz equations, are recovered as special cases of this classification. The analogous problem for systems of second-order differential equations in the real plane is considered for a special case that enlarges the generalized Ermakov systems.

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Energies, Vol. 9, Pages 214: Application of Breathing Architectural Members to the Natural Ventilation of a Passive Solar House

The efficient operation of a passive solar house requires an efficient ventilation system to prevent the loss of energy and provide the required ventilation rates. This paper proposes the use of "breathing architectural members" (BAMs) as passive natural ventilation devices to achieve much improved ventilation and insulation performance compared to mechanical ventilation. Considering the importance of evaluating the ventilation and insulation performances of the members, we also propose numerical models for predicting the heat and air movements afforded by the members. The numerical model was validated by comparison with experimental results. The effectiveness of the BAMs was also verified by installation in houses located in an area with warm climate. For this purpose, chamber experiments were performed using samples of the BAMs, as well as numerical simulations to assess natural ventilation and heat load. The main findings of the study are as follows: (1) the one-dimensional chamber experiments confirmed the validity of the numerical models for predicting the heat and air movements afforded by the BAMs. Comparison of the experimental and calculated values for the temperature of air that flowed into the room from outside revealed a difference of less than 5%; (2) observations of the case studies in which BAMs were installed in the ceilings and exterior walls of Tokyo model houses revealed good annual ventilation and energy-saving effects. When BAMs with an opening area per unit area of A = 0.002 m2/m2 were applied to three surfaces, the required ventilation rate was 0.5 ACH (air changes per hour), and this was achieved consistently. Compared to a house with general insulation and conventional mechanical ventilation, heating load was reduced by 15.3%–40.2% depending on the BAM installation points and the differing areas of the house models.

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Symmetry, Vol. 8, Pages 14: Status of X(1835) and p\(\overline{p}\) Interaction from Chiral Symmetry

After the observation of the strong near-threshold enhancement of proton-antiproton mass spectrum in J / ψ → γp\(\overline{p}\) decay, lots of theoretical investigations have been available such as new resonance, the final-state p\(\overline{p}\) interaction (FSI), p\(\overline{p}\) bound state (or baryonium), glueball, or other exotic (tetra-quark) states. Here, we provide a short review on the current status, especially on the pertinent discussions concerning its relation to p\(\overline{p}\) interaction, for which the emphasis is put on the recently constructed chiral potential.

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Viruses, Vol. 8, Pages 82: Roles of the Picornaviral 3C Proteinase in the Viral Life Cycle and Host Cells

The Picornaviridae family comprises a large group of non-enveloped viruses that have a major impact on human and veterinary health. The viral genome contains one open reading frame encoding a single polyprotein that can be processed by viral proteinases. The crucial 3C proteinases (3Cpros) of picornaviruses share similar spatial structures and it is becoming apparent that 3Cpro plays a significant role in the viral life cycle and virus host interaction. Importantly, the proteinase and RNA-binding activity of 3Cpro are involved in viral polyprotein processing and the initiation of viral RNA synthesis. In addition, 3Cpro can induce the cleavage of certain cellular factors required for transcription, translation and nucleocytoplasmic trafficking to modulate cell physiology for viral replication. Due to interactions between 3Cpro and these essential factors, 3Cpro is also involved in viral pathogenesis to support efficient infection. Furthermore, based on the structural conservation, the development of irreversible inhibitors and discovery of non-covalent inhibitors for 3Cpro are ongoing and a better understanding of the roles played by 3Cpro may provide insights into the development of potential antiviral treatments. In this review, the current knowledge regarding the structural features, multiple functions in the viral life cycle, pathogen host interaction, and development of antiviral compounds for 3Cpro is summarized.

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Polymers, Vol. 8, Pages 90: Preparation of Uniform-Sized and Dual Stimuli-Responsive Microspheres of Poly(N-Isopropylacrylamide)/Poly(Acrylic acid) with Semi-IPN Structure by One-Step Method

A novel strategy was developed to synthesize uniform semi-interpenetrating polymer network (semi-IPN) microspheres by premix membrane emulsification combined with one-step polymerization. Synthesized poly(acrylic acid) (PAAc) polymer chains were added prior to the inner water phase, which contained N-isopropylacrylamide (NIPAM) monomer, N,N′-methylene bisacrylamide (MBA) cross-linker, and ammonium persulfate (APS) initiator. The mixtures were pressed through a microporous membrane to form a uniform water-in-oil emulsion. By crosslinking the NIPAM in a PAAc-containing solution, microspheres with temperature- and pH-responsive properties were fabricated. The semi-IPN structure and morphology of the microspheres were confirmed by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The average diameter of the obtained microspheres was approximately 6.5 μm, with Span values of less than 1. Stimuli-responsive behaviors of the microspheres were studied by the cloud-point method. The results demonstrated that semi-IPN microspheres could respond independently to both pH and temperature changes. After storing in a PBS solution (pH 7.0) at 4 °C for 6 months, the semi-IPN microspheres remained stable without a change in morphology or particle size. This study demonstrated a promising method for controlling the synthesis of semi-IPN structure microspheres with a uniform size and multiple functionalities.

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Energies, Vol. 9, Pages 215: Evaluation of a Mixed Method Approach for Studying User Interaction with Novel Building Control Technology

Energy-efficient building performance requires sophisticated control systems that are based on realistic occupant behaviour models. To provide robust data for the development of these models, research studies in real-world settings are needed. Yet, such studies are challenging and necessitate careful design in terms of data collection methods and procedures. This paper describes and critiques the design of a mixed methods approach for occupant behaviour research. It reviews the methodology developed for a longitudinal study in a real-world office environment where occupants' experience with a novel facade technology (electrochromic glazing) was investigated. The methodology integrates objective physical measurements, observational data and self-reported experience data. Using data from one day of the study, this paper illustrates how the different sources can be combined in order to derive an in-depth understanding of the interplay between external daylight conditions, characteristics of the facade technology, occupant interaction with the technology and the resulting occupant experience. It was found that whilst the individual methods may be affected by practical limitations, these can be partially offset by combining physical measurements and observations with self-reported data. The paper critically evaluates the individual techniques, as well as the benefits of their integration and makes recommendations for the design of future occupant behaviour studies in real-world settings.

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Remote Sensing, Vol. 8, Pages 255: Remote Sensing of Deformation of a High Concrete-Faced Rockfill Dam Using InSAR: A Study of the Shuibuya Dam, China

Settlement is one of the most important deformation characteristics of high concrete faced rockfill dams (CFRDs, >100 m). High CFRDs safety would pose a great threat to the security of people's lives and property downstream if this kind of deformation were not to be measured correctly, as traditional monitoring approaches have limitations in terms of durability, coverage, and efficiency. It has become urgent to develop new monitoring techniques to complement or replace traditional monitoring approaches for monitoring the safety and operation status of high CFRDs. This study examines the Shuibuya Dam (up to 233.5 m in height) in China, which is currently the highest CFRD in the world. We used space-borne Interferometric Synthetic Aperture Radar (InSAR) time series to monitor the surface deformation of the Shuibuya Dam. Twenty-one ALOS PALSAR images that span the period from 28 February 2007 to 11 March 2011 were used to map the spatial and temporal deformation of the dam. A high correlation of 0.93 between the InSAR and the in-situ monitoring results confirmed the reliability of the InSAR method; the deformation history derived from InSAR is also consistent with the in-situ settlement monitoring system. In addition, the InSAR results allow continuous investigation of dam deformation over a wide area that includes the entire dam surface as well as the surrounding area, offering a clear picture continuously of the dam deformation.

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Remote Sensing, Vol. 8, Pages 258: An Automatic Building Extraction and Regularisation Technique Using LiDAR Point Cloud Data and Orthoimage

The development of robust and accurate methods for automatic building detection and regularisation using multisource data continues to be a challenge due to point cloud sparsity, high spectral variability, urban objects differences, surrounding complexity, and data misalignment. To address these challenges, constraints on object's size, height, area, and orientation are generally benefited which adversely affect the detection performance. Often the buildings either small in size, under shadows or partly occluded are ousted during elimination of superfluous objects. To overcome the limitations, a methodology is developed to extract and regularise the buildings using features from point cloud and orthoimagery. The building delineation process is carried out by identifying the candidate building regions and segmenting them into grids. Vegetation elimination, building detection and extraction of their partially occluded parts are achieved by synthesising the point cloud and image data. Finally, the detected buildings are regularised by exploiting the image lines in the building regularisation process. Detection and regularisation processes have been evaluated using the ISPRS benchmark and four Australian data sets which differ in point density (1 to 29 points/m2), building sizes, shadows, terrain, and vegetation. Results indicate that there is 83% to 93% per-area completeness with the correctness of above 95%, demonstrating the robustness of the approach. The absence of over- and many-to-many segmentation errors in the ISPRS data set indicate that the technique has higher per-object accuracy. While compared with six existing similar methods, the proposed detection and regularisation approach performs significantly better on more complex data sets (Australian) in contrast to the ISPRS benchmark, where it does better or equal to the counterparts.

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Evaluation of the anti-inflammatory action of curcumin analog (DM1): effect on iNOS and COX-2 gene expression and autophagy pathways

Publication date: Available online 16 March 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Niraldo Paulino, Amarilis Scremin Paulino, Susana N. Diniz, Sergio de Mendonça, Ivair D. Gonçalves, Fernanda Faião Flores, Reginaldo Pereira Santos, Carina Rodrigues, Paulo Celso Pardi, José Agustin Quincoces Suarez
This work describes the anti-inflammatory effect of the curcumin-analog compound, sodium 4-[5-(4-hydroxy-3-methoxyphenyl)-3-oxo-penta-1,4-dienyl]-2-methoxy-phenolate (DM1), and shows that DM1 modulates iNOS and COX-2 gene expression in cultured RAW 264.7 cells and induces autophagy on human melanoma cell line A375.

Graphical abstract

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Exploration of the P3 region of PEXEL peptidomimetics leads to a potent inhibitor of the Plasmodium protease, plasmepsin V

Publication date: Available online 16 March 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Michelle Gazdik, Kate E. Jarman, Matthew T. O'Neill, Anthony N. Hodder, Kym N. Lowes, Helene Jousset Sabroux, Alan F. Cowman, Justin A. Boddey, Brad E. Sleebs
The use of arginine isosteres is a known strategy to overcome poor membrane permeability commonly associated with peptides or peptidomimetics that possess this highly polar amino acid. Here, we apply this strategy to peptidomimetics that are potent inhibitors of the malarial protease, plasmepsin V, with the aim of enhancing their activity against Plasmodium parasites, and exploring the structure-activity relationship of the P³ arginine within the S3 pocket of plasmepsin V. Of the arginine isosteres trialled in the P³ position, we discovered that canavanine was the ideal and that this peptidomimetic potently inhibits plasmepsin V, efficiently blocks protein export and inhibits parasite growth. Structure studies of the peptidomimetics bound to plasmepsin V provided insight into the structural basis for the enzyme activity observed in vitro and provides further evidence why plasmepsin V is highly sensitive to substrate modification.

Graphical abstract

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Identification of Small-Molecule Compounds Targeting the Dishevelled PDZ Domain by Virtual Screening and Binding Studies

Publication date: Available online 16 March 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Jiwon Choi, SongLing Ma, Hyun-Yi Kim, Ji-Hye Yun, Jung-Nyoung Heo, Weontae Lee, Kang-Yell Choi, Kyoung Tai No
The Dishevelled (Dvl) protein, which conveys signals from receptors to the downstream effectors, is a critical constituent of the Wnt/β-catenin signaling pathway. Because the PDZ domain of Dvl protein functions through associations with a wide range of protein partners, Dvl protein involved in the Wnt signaling pathway has been considered to be therapeutic targets in cancers. In this study, we performed structure-based pharmacophore model of the Dvl PDZ domain to discover novel small-molecule binders and identified eight compounds with micromolar affinity. The most potent compound identified, BMD4702, efficiently bound to the Dvl PDZ domain with 11.2 μM affinity and had a 0.186 μM KD value according to surface plasmon resonance and fluorescence spectroscopy, respectively. Combining both structural-kinetic relationship analyses and docking studies, we fourmulated that the ligand-binding site is composed of three H-bonds and three hydrophobic features. Thus, our approach led to the identification of potent binders of the Dvl PDZ domain and the findings provide novel insights into structure-based approaches to design high-affinity binders for the Dvl PDZ domain.

Graphical abstract

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Single-cell Mass Spectrometry with Multi-solvent Extraction Identifies Metabolic Differences between Left and Right Blastomeres in the 8-cell Frog (Xenopus) Embryo

Analyst, 2016, Accepted Manuscript
DOI: 10.1039/C6AN00200E, Paper

Rosemary M. Onjiko, Sydney E. Morris, Sally A. Moody, Peter Nemes
Single-cell metabolic mass spectrometry enables the discovery (untargeted) analysis of small molecules in individual cells. Using single-cell capillary electrophoresis high-resolution mass spectrometry (CE-HRMS), we recently uncovered small-molecule differences between embryonic...
The content of this RSS Feed (c) The Royal Society of Chemistry

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Quantification of Tunicamycin-Induced Protein Expression and N-Glycosylation Changes in Yeast

Analyst, 2016, Accepted Manuscript
DOI: 10.1039/C6AN00144K, Paper

Haopeng Xiao, Johanna M Smeekens, Ronghu Wu
Tunicamycin is a potent protein N-glycosylation inhibitor that has frequently been used to manipulate protein glycosylation in cells. However, protein expression and glycosylation changes as a result of tunicamycin treatment...
The content of this RSS Feed (c) The Royal Society of Chemistry

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Long-term changes in dysnatremia incidence in the ICU: a shift from hyponatremia to hypernatremia

Dysnatremia is associated with adverse outcome in critically ill patients. Changes in patients or treatment strategies may have affected the incidence of dysnatremia over time. We investigated long-term change...

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Ann Agric Environ Med 2016; 23(1):79-83 "Relationships between personality traits, resting serum hormones and visuomotor ability in male judokas"

[b]Introduction.[/b] The purpose of this research was to study the relationships between selected personality features, the speed and accuracy of visumotor ability and hormonal status in the blood of male judokas. [b]Materials and method. [/b]Forty-five male judokas whose body mass ranged from 66–100 kg were included in the study. Each one was examined once during a single annual competitive season lasting from March – October. The protocol of the study comprised five procedures carried out in the following order: (a) capillary blood sampling in the morning (07:30), (b) second capillary blood sampling directly prior to the personality examination, (c) examination of the personality traits, (d) testing of visuo-motor ability with the use of an electronic cross-shape electronic device, (e) third capillary blood sampling after the entire study. The entire study started and ended in the morning. For each subject, the three serum samples were pooled and the levels of cortisol (C) and testosterone (T) were determined in the serum specimen. [b]Results.[/b] There were significant correlations among the scores in selected personality traits, anxiety (A), neuroticism (N), extraversion (E), perseveration (P), emotional reactivity (ER) and achievement motivation (AM). The C level did not correlate with any variables, however, it did positively correlate with E and visuo-motor ability. There were inverse relationships between E and A, N, P and ER. [b]Conclusions.[/b] The study confirmed relationships in the androgenic status in circulation, personality traits and psycho-motor abilities.

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Ann Agric Environ Med 2016; 23(1):106-110 "Cytotoxicity induced by cypermethrin in Human Neuroblastoma Cell Line SH-SY5Y"

The purpose of this study was to evaluate the cytotoxic potential of Cypermethrin (CM) on cultured human Neuroblastoma SH-SY5Y cells. SH-SY5Y cells were treated with CM at 0–200µM for 24, 48, and 72 h, [i]in vitro[/i]. It was found that CM induced the cell death of Neuroblastoma cells in a dose- and time-dependent manner, as shown by LDH assays. Next, some aspects of the process of cell death triggered by CM in the human SH-SY5Y cell line were investigated. It was revealed that the pan-caspase inhibitor Q-VD-OPh, sensitizes SH-SY5Y cells to necroptosis caused by CM. Furthermore, signal transduction inhibitors PD98059, SL-327, SB202190, SP600125 failed to attenuate the effect of the pesticide. Finally, it was shown that inhibition of TNF-a by Pomalidomide (PLD) caused statistically significant reduction in CM-induced cytotoxicity. Overall, the data obtained suggest that CM induces neurotoxicity in SH-SY5Y cells by necroptosis.

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Ann Agric Environ Med 2016; 23(1):30-36 "Microarrays – new possibilities for detecting biological factors hazardous for humans and animals, and for use in environmental protection"

Both the known biological agents that cause infectious diseases, as well as modified (ABF-Advanced Biological Factors) or new, emerging agents pose a significant diagnostic problem using previously applied methods, both classical, as well as based on molecular biology methods. The latter, such as PCR and real-time PCR, have significant limitations, both quantitative (low capacity), and qualitative (limited number of targets). The article discusses the results of studies on using the microarray method for the identification of viruses (e.g. Orthopoxvirus group, noroviruses, influenza A and B viruses, rhino- and enteroviruses responsible for the FRI (Febrile Respiratory Illness), European bunyaviruses, and SARS-causing viruses), and bacteria ([i]Mycobacterium spp., Yersinia spp., Campylobacter spp., Streptococcus pneumoniae, Salmonella typhi, Salmonella enterica, Staphylococcus aureus, Neisseria meningitidis, Clostridium difficile , Helicobacter pylori[/i]), including multiple antibiotic-resistant strains. The method allows for the serotyping and genotyping of bacteria, and is useful in the diagnosis of genetically modified agents. It allows the testing of thousands of genes in one experiment. In addition to diagnosis, it is applicable for gene expression studies, analysis of the function of genes, microorganisms virulence, and allows the detection of even single mutations. The possibility of its operational application in epidemiological surveillance, and in the detection of disease outbreak agents is demonstrated.

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Ann Agric Environ Med 2016; 23(1):157-162 "Opinions and attitudes of parturients, midwives , and obstetricians about Caesarean section in the provinces of Podkarpackie, Poland, and Ivano-Frankivsk, Ukraine"

[b][i][/i][/b][b]Introduction and objective. [/b]Present the opinions of parturients, midwives, and obstetricians concerning CS in the provinces of Podkarpackie (Poland) and Ivano-Frankivsk (Ukraine). [b]Material and methods[/b]. An anonymous questionnaire for parturients (n=1,295), midwives (n=47) and obstetricians (n=78), assessing demographics, knowledge and attitudes concerning CS, was distributed in 13 hospitals. In addition to measured anxiety among parturients, we also used the State-Trait Anxiety Inventory (STAI). [b]Results.[/b] Differences between the subgroups concerned respondents' ages and place of residence (p=0.0000). Parturients from Poland more often accepted the possibility of vaginal delivery after previous CS (p=0.0000), they more often believed that free access to epidural analgesia and the presence of a chosen partner in the delivery room would decrease the CS rate (p=0.0000). Polish midwives more rarely accept the idea of CS on maternal request (p=0.0012) and were convinced that free access to epidural analgesia could decrease the rate of CS (p=0.0479). In Poland parturients more often accepted CS on maternal request than obstetricians and midwives (p=0.0000). In Ukrainian population midwives and obstetricians more often accepted possibility of natural delivery after previous CS (p=0.0010). According connected with delivery in Poland parturients returned lower scores on the A-State scale (p=0.0000), but higher scores on the A-Trait scale (p=0.0067). [b]Conclusions.[/b] There are some differences in Polish and Ukrainian obstetricians, midwives and parturients in respect of: – vaginal delivery after CS, – epidural analgesia, – CS on request, – anxiety connected with labour. The above may to some extend explain the difference in Cs rate in two countries.

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Ann Agric Environ Med 2016; 23(1):37-43 "Obesity and renal cancer incidence and mortality – a systematic review of prospective cohort studies"

[b]Introduction and objective.[/b] There have been many studies published recently on obesity and the risk of renal cancer; however, the epidemiological evidence for such an association has not been consistent. Therefore, a systematic review was conducted of the prospective cohort studies to assess the association between obesity and the risk of renal cancer incidence and death. [b]Materials and methods.[/b] A search was conducted of the PubMed database and references to published studies from inception until May 2013. Guidelines for Assessing Quality in Prognostic Studies on the Basis of Framework for Potential Biases were followed for quality assessment of studies included in the systematic review. [b]Results. [/b]Twenty eligible studies were identified and included in the systematic review. Among the 20 selected studies, overall study quality was high. Although the evidence from the prospective cohort studies, linking obesity with renal cancer incidence, has not been entirely consistent, there is a convincing body of data for a positive relationship. Moreover, cumulative data is compelling for a strong positive association between obesity and fatal renal cancer. [b]Conclusions.[/b] There is a relatively consistent amount of evidence that obesity increases the risk of renal cancer and fatal renal cancer. Further research is needed as better understanding of mechanisms by which obesity may influence renal cancer development and progression will aid the fostering of strategies for prevention and treatment of one of the most lethal human malignancies.

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Ann Agric Environ Med 2016; 23(1):125-128 "Clinical and health care aspects of respiratory tract disorders in Poland"

[b]Introduction.[/b] Respiratory diseases constitute a public health priority worldwide. This is related to the increasing exposure to microorganisms, toxic factors, allergens, drugs and smoking, as the most important factors. Increasing costs of health promotion, prevention, diagnosis and treatment of respiratory tract diseases forces the search for effective strategies in the reduction of costs without making a significant impact of these activities on health results. Chronic obstructive pulmonary disease (COPD) is an example of these diseases with increasing incidence, which has few known modifiable factors and absorbs large medical and social costs. [b]Objectives.[/b] The aim of this study is to present the conception of cost driver analysis that could be useful in constructing a good combination of the EBM-based treatment with cost reduction decisions. [b]Material and Methods[/b]. Analysis of cost drivers was based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines and Polish recommendations of COPD diagnosis and treatment. The proposition of cost reduction strategy in COPD treatment was based on identification of cost drivers in value chain conception. [b]Results and Conclusions[/b]. An increasing incidence and treatment costs of COPD force the search for methods of costs reduction in health care. Identifying, evaluating and modifying the cost drivers with use of the value chain conception could be an effective method in achieving these objectives.

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Ann Agric Environ Med 2016; 23(1):44-53 "Sublingual immunotherapy (SLIT) – indications, mechanism, and efficacy Position paper prepared by the Section of Immunotherapy, Polish Society of Allergy"

SLIT ([i]sublingual immunotherapy[/i],) induces allergen-specific immune tolerance by sublingual administration of a gradually increasing dose of an allergen. The mechanism of SLIT is comparable to those during SCIT (subcutaneous immunotherapy), with the exception of local oral dendritic cells, pre-programmed to elicit tolerance. In the SLIT dose, to achieve the same efficacy as in SCIT, it should be 50–100 times higher with better safety profile. The highest quality evidence supporting the efficacy of SLIT lasting 1 – 3 years has been provided by the large scale double-blind, placebo-controlled (DBPC) trials for grass pollen extracts, both in children and adults with allergic rhinitis. Current indications for SLIT are allergic rhinitis (and conjunctivitis) in both children and adults sensitized to pollen allergens (trees, grass, [i]Parietaria[/i]), house dust mites ([i]Dermatophagoides pteronyssinus, Dermatophagoides farinae[/i]), cat fur, as well as mild to moderate controlled atopic asthma in children sensitized to house dust mites. There are positive findings for both asthma and new sensitization prevention. Severe adverse events, including anaphylaxis, are very rare, and no fatalities have been reported. Local adverse reactions develop in up to 70 – 80% of patients. Risk factors for SLIT adverse events have not been clearly identified. Risk factors of non-adherence to treatment might be dependent on the patient, disease treatment, physician-patient relationship, and variables in the health care system organization.

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Ann Agric Environ Med 2016; 23(1):182-192 "Augmentative and Alternative Communication (AAC) for a patient with a nonfluent/ agrammatic variant of PPA in the mutism stage"

[b]Introduction. [/b]The paper presents an example of the successful administration of the Augmentative and Alternative Communication (AAC) system. Such an approach is of particular significance in cases of patients with speech and language deterioration, which is observed in a nonfluent/agrammatic variant of primary progressive aphasia (PPA-G). Regaining the ability to communicate with others proves to be very important for the patients' self-esteem and enables them to restore previously broken social bonds. [b]Case history.[/b] The patient A.G., aged 73, a right-handed woman, had been a teacher of Polish before suffering from speech disorders of the PPA-G type. As the disease progressed, her communication deteriorated and finally she developed mutism. The patient was given a clinical and imaging-supported diagnosis of an isolated nonfluent/ agrammatic variant of primary progressive aphasia (PPA-G). The Augmentative and Alternative Communication (AAC) system specially designed for her needs was introduced to help the patient to regain the possibility to communicate. After 20 sessions of training with the use of simple equipment she was again able to communicate non-verbally with her son and with the staff of the nursing home. At the same time, a considerable improvements in her social functioning, including daily activities, was observed. [b]Conclusions. [/b]Loss of the ability to communicate with others has a serious impact upon a patient's quality of life, and often results in withdrawal and an inability to lead an independent life. The introduction of the Augmentative and Alternative Communication (AAC) system proves to be a great help, not only for regaining the ability to communicate, but also for the restoration of social bonds. In consequence, the previously mute patient begins to show signs of social cooperation.

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Metals, Vol. 6, Pages 68: NURBS-Based Collocation Methods for the Structural Analysis of Shells of Revolution

In this work we present a collocation method for the structural analysis of shells of revolution based on Non-Uniform Rational B-Spline (NURBS) interpolation. The method is based on the strong formulation of the equilibrium equations according to Reissner-Mindlin theory, with Fourier series expansion of dependent variables, which makes the problem 1D. Several numerical tests validate convergence, accuracy, and robustness of the proposed methodology, and its feasibility as a tool for the analysis and design of complex shell structures.

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Materials, Vol. 9, Pages 207: Fatigue Life Prediction of Fiber-Reinforced Ceramic-Matrix Composites with Different Fiber Preforms at Room and Elevated Temperatures

In this paper, the fatigue life of fiber-reinforced ceramic-matrix composites (CMCs) with different fiber preforms, i.e., unidirectional, cross-ply, 2D (two dimensional), 2.5D and 3D CMCs at room and elevated temperatures in air and oxidative environments, has been predicted using the micromechanics approach. An effective coefficient of the fiber volume fraction along the loading direction (ECFL) was introduced to describe the fiber architecture of preforms. The statistical matrix multicracking model and fracture mechanics interface debonding criterion were used to determine the matrix crack spacing and interface debonded length. Under cyclic fatigue loading, the fiber broken fraction was determined by combining the interface wear model and fiber statistical failure model at room temperature, and interface/fiber oxidation model, interface wear model and fiber statistical failure model at elevated temperatures, based on the assumption that the fiber strength is subjected to two-parameter Weibull distribution and the load carried by broken and intact fibers satisfies the Global Load Sharing (GLS) criterion. When the broken fiber fraction approaches the critical value, the composites fatigue fracture.

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IJMS, Vol. 17, Pages 395: Intronic Polymorphisms in the CDKN2B-AS1 Gene Are Strongly Associated with the Risk of Myocardial Infarction and Coronary Artery Disease in the Saudi Population

Recent genome-wide association studies identified single nucleotide polymorphisms (SNPs) on the chromosome 9p21.3 conferring the risk for CAD (coronary artery disease) in individuals of Caucasian ancestry. We performed a genetic association study to investigate the effect of 12 candidate SNPs within 9p21.3 locus on the risk of CAD in the Saudi population of the Eastern Province of Saudi Arabia. A total of 250 Saudi CAD patients who had experienced an myocardial infarction (MI) and 252 Saudi age-matched healthy controls were genotyped using TaqMan assay. Controls with evidenced lack of CAD provided 90% of statistical power at the type I error rate of 0.05. Five percent of the results were rechecked for quality control using Sanger sequencing, the results of which concurred with the TaqMan genotyping results. Association analysis of 12 SNPs indicated a significant difference in the genotype distribution for four SNPs between cases and controls (rs564398 p = 0.0315, χ2 = 4.6, odds ratio (OD) = 1.5; rs4977574 p = 0.0336, χ2 = 4.5, OD = 1.4; rs2891168 p = 1.85 × 10 − 10, χ2 = 40.6, OD = 2.1 and rs1333042 p = 5.14 × 10 − 9, χ2 = 34.1, OD = 2.2). The study identified three protective haplotypes (TAAG p = 1.00 × 10 − 4; AGTA p = 0.022 and GGGCC p = 0.0175) and a risk haplotype (TGGA p = 2.86 × 10 − 10) for the development of CAD. This study is in line with others that indicated that the SNPs located in the intronic region of the CDKN2B-AS1 gene are associated with CAD.

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Materials, Vol. 9, Pages 205: Computational Study of the Effect of Cortical Porosity on Ultrasound Wave Propagation in Healthy and Osteoporotic Long Bones

Computational studies on the evaluation of bone status in cases of pathologies have gained significant interest in recent years. This work presents a parametric and systematic numerical study on ultrasound propagation in cortical bone models to investigate the effect of changes in cortical porosity and the occurrence of large basic multicellular units, simply called non-refilled resorption lacunae (RL), on the velocity of the first arriving signal (FAS). Two-dimensional geometries of cortical bone are established for various microstructural models mimicking normal and pathological tissue states. Emphasis is given on the detection of RL formation which may provoke the thinning of the cortical cortex and the increase of porosity at a later stage of the disease. The central excitation frequencies 0.5 and 1 MHz are examined. The proposed configuration consists of one point source and multiple successive receivers in order to calculate the FAS velocity in small propagation paths (local velocity) and derive a variation profile along the cortical surface. It was shown that: (a) the local FAS velocity can capture porosity changes including the occurrence of RL with different number, size and depth of formation; and (b) the excitation frequency 0.5 MHz is more sensitive for the assessment of cortical microstructure.

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Molecules, Vol. 21, Pages 363: Comparison of the Profile and Composition of Volatiles in Coniferous Needles According to Extraction Methods

The enantiomeric distribution and profile of volatiles in plants, which affect the biological and organoleptic properties, can be varied depending on extraction methods as well as their cultivars. The secondary volatile components of the needles of three conifer cultivars (Chamaecyparispisifera, Chamaecyparisobtusa, and Thujaorientalis) were compared. Furthermore, the effects of three different extraction methods—solid-phase microextraction (SPME), steam distillation (SD), and solvent extraction (SE)—on the composition and enantiomeric distribution of those volatiles were elucidated. Monoterpene hydrocarbons predominated in all samples, and the compositions of sesquiterpenes and diterpenes differed according to the cultivar. In particular, the yields of oxygenated monoterpenes and sesquiterpenes were greatest for SD, whereas those of sesquiterpenes and diterpenes were highest for SE. On the other hand, more monoterpenes with higher volatility could be obtained with SPME and SD than when using SE. In addition, the enantiomeric composition of nine chiral compounds found in three cultivars differed according to their chemotype. There were also some differences in the yielded oxygenated monoterpenes and sesquiterpene hydrocarbons, but not monoterpene hydrocarbons, according to the extraction method. These results demonstrate that the extraction methods used as well as the cultivars influence the measured volatile profiles and enantiomeric distribution of coniferous needle extracts.

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Lubricants, Vol. 4, Pages 8: Tribological Behaviour of PVD Coatings Lubricated with a FAP− Anion-Based Ionic Liquid Used as an Additive

This paper studies 1-butyl-1-methylpyrrolidinium tris(pentafluoroethyl) trifluorophosphate ionic liquid ([BMP][FAP]) as a 1 wt% additive to a polyalphaolefin (PAO 6) in the lubrication of CrN and TiN PVD coatings. Friction and wear behaviour were determined by using a ball-on-plate reciprocating tribometer at two loads (20 and 40 N) and a reciprocating frequency of 10 Hz. The tribological behaviour of this mixture has also been compared to a traditional oil additive, like zinc dialkyldithiophosphate (ZDDP). As an additive, ionic liquid exhibited an important friction and wear reduction compared to the base oil. However, tests conducted with ZDDP show slightly better results. XPS was used to analyse wear surfaces. The interactions of each additive with the surface contributed to improving the tribological behaviour of the lubricants.

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Sensors, Vol. 16, Pages 384: A Differential Monolithically Integrated Inductive Linear Displacement Measurement Microsystem

An inductive linear displacement measurement microsystem realized as a monolithic Application-Specific Integrated Circuit (ASIC) is presented. The system comprises integrated microtransformers as sensing elements, and analog front-end electronics for signal processing and demodulation, both jointly fabricated in a conventional commercially available four-metal 350-nm CMOS process. The key novelty of the presented system is its full integration, straightforward fabrication, and ease of application, requiring no external light or magnetic field source. Such systems therefore have the possibility of substituting certain conventional position encoder types. The microtransformers are excited by an AC signal in MHz range. The displacement information is modulated into the AC signal by a metal grating scale placed over the microsystem, employing a differential measurement principle. Homodyne mixing is used for the demodulation of the scale displacement information, returned by the ASIC as a DC signal in two quadrature channels allowing the determination of linear position of the target scale. The microsystem design, simulations, and characterization are presented. Various system operating conditions such as frequency, phase, target scale material and distance have been experimentally evaluated. The best results have been achieved at 4 MHz, demonstrating a linear resolution of 20 µm with steel and copper scale, having respective sensitivities of 0.71 V/mm and 0.99 V/mm.

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Cloning and Expression of the γ-Polyglutamic Acid Synthetase Gene pgsBCA in Bacillus subtilis WB600

To clone and express the γ-polyglutamic acid (γ-PGA) synthetase gene pgsBCA in Bacillus subtilis, a pWB980 plasmid was used to construct and transfect the recombinant expression vector pWB980-pgsBCA into Bacillus subtilis WB600. PgsBCA was expressed under the action of a P43 promoter in the pWB980 plasmid. Our results showed that the recombinant bacteria had the capacity to synthesize γ-PGA. The expression product was secreted extracellularly into the fermentation broth, with a product yield of 1.74 g/L or higher. γ-PGA samples from the fermentation broth were purified and characterized. Hydrolysates of γ-PGA presented in single form, constituting simple glutamic acid only, which matched the characteristics of the infrared spectra of the γ-PGA standard, and presented as multimolecular aggregates with a molecular weight within the range of 500–600 kDa. Expressing the γ-PGA synthetase gene pgsBCA in B. subtilis system has potential industrial applications.

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Changes in pigment, spectral transmission and element content of pink chicken eggshells with different pigment intensity during incubation

Objective. The objective of this study was to investigate changes in pigment, spectral transmission and element content of chicken eggshells with different intensities of pink pigment during the incubation period. We also investigated the effects of the region (small pole, equator and large pole) and pink pigment intensity of the chicken eggshell on the percent transmission of light passing through the chicken eggshells. Method. Eggs of comparable weight from a meat-type breeder (Meihuang) were used, and divided based on three levels of pink pigment (light, medium and dark) in the eggshells. During the incubation (0–21 d), the values of the eggshell pigment (ΔE, L∗, a∗, b∗) were measured. The percent transmission of light for different regions and intensities of eggshell pigmentation was measured by using the visible wavelength range of 380–780 nm. Result. Three measured indicators of eggshell color, ΔE, L∗ and a∗, did not change significantly during incubation. Compared with other regions and pigment intensities, eggshell at the small pole and with light pigmentation intensity showed the highest percent transmission of light. The transmission value varied significantly (P

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Sponge distribution and the presence of photosymbionts in Moorea, French Polynesia

Photosymbionts play an important role in the ecology and evolution of diverse host species within the marine environment. Although sponge-photosymbiont interactions have been well described from geographically disparate sites worldwide, our understanding of these interactions from shallow water systems within French Polynesia is limited. We surveyed diverse habitats around the north coast of Moorea, French Polynesia and screened sponges for the presence of photosymbionts. Overall sponge abundance and diversity were low, with

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Omega-3 fatty acids shown to exert a positive effect on the aging brain

Changes in cognitive function and memory decline form a normal part of aging. However, in neurodegenerative diseases such as Alzheimer's disease or mild cognitive impairment (the pre-dementia phase of Alzheimer's disease), these changes occur more quickly. There are currently no effective treatments for these diseases. Physicians and researchers are constantly looking for new treatment methods that will maintain their patients' cognitive performance and independence for as long as possible. Targeted prevention is another essential component when trying to preserve cognitive function for as long as possible.

"Ideally, any measures used should be aimed at long-term prevention. This means that measures must be suitable for use in healthy older adults, and should be easy to integrate into day-to-day life," says Dr. Nadine Külzow, a researcher at Charité's Department of Neurology. Nutritional supplements represent one such option. "A number of different dietary components, including omega-3 fatty acids, are currently thought to have a direct effect on nerve cell function. This is why we decided to study the effects on memory function of a daily dose of 2,200 milligrams taken for a duration of six months," says Dr. Külzow.

Study participants who received omega-3 fatty acids showed greater improvements on an object location memory task than participants who received a placebo containing sunflower oil. However, there was no evidence of improved performance on a verbal learning test. "Results from this study suggest that a long-term approach to prevention is particularly effective in preserving cognitive function in older individuals. A targeted approach involving dietary supplements can play a central role in this regard," concluded the researchers. Whether or not the improvements recorded can make a noticeable difference in day-to-day life will need to be investigated as part of a larger clinical study. As a next step, however, the researchers are planning to test the effect of supplementation with a combination of omega-3 fatty acids and vitamin B. According to research conducted at Oxford, this combination may be associated with synergistic effects.

Külzow N, Witte AV, Kerti L, Grittner U, Schuchardt JP, Hahn A, Flöeel A (2016). Impact of Omega-3 Fatty Acid Supplementation on Memory Functions in Healthy Older Adults. J Alzheimers Dis 2016 Feb 10. DOI: 10.3233/JAD-150886

The article will be published in the The Journal of Alzheimer's Disease 51(3), which is scheduled for publication on March 29, 2016.

Boilerplate:

ABOUT THE JOURNAL OF ALZHEIMER'S DISEASE (JAD)

The Journal of Alzheimer's Disease is an international multidisciplinary journal to facilitate progress in understanding the etiology, pathogenesis, epidemiology, genetics, behavior, treatment and psychology of Alzheimer's disease. The journal publishes research reports, reviews, short communications, book reviews, and letters-to-the-editor. Groundbreaking research that has appeared in the journal includes novel therapeutic targets, mechanisms of disease and clinical trial outcomes. The Journal of Alzheimer's Disease has an Impact Factor of 4.151 according to Thomson Reuters' 2014 Journal Citation Reports. The Journal is published by IOS Press.

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IJMS, Vol. 17, Pages 392: Spatial Temporal Dynamics and Molecular Evolution of Re-Emerging Rabies Virus in Taiwan

Taiwan has been recognized by the World Organization for Animal Health as rabies-free since 1961. Surprisingly, rabies virus (RABV) was identified in a dead Formosan ferret badger in July 2013. Later, more infected ferret badgers were reported from different geographic regions of Taiwan. In order to know its evolutionary history and spatial temporal dynamics of this virus, phylogeny was reconstructed by maximum likelihood and Bayesian methods based on the full-length of glycoprotein (G), matrix protein (M), and nucleoprotein (N) genes. The evolutionary rates and phylogeographic were determined using Beast and SPREAD software. Phylogenetic trees showed a monophyletic group containing all of RABV isolates from Taiwan and it further separated into three sub-groups. The estimated nucleotide substitution rates of G, M, and N genes were between 2.49 × 10−4–4.75 × 10−4 substitutions/site/year, and the mean ratio of dN/dS was significantly low. The time of the most recent common ancestor was estimated around 75, 89, and 170 years, respectively. Phylogeographic analysis suggested the origin of the epidemic could be in Eastern Taiwan, then the Formosan ferret badger moved across the Central Range of Taiwan to western regions and separated into two branches. In this study, we illustrated the evolution history and phylogeographic of RABV in Formosan ferret badgers.

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Sensors, Vol. 16, Pages 388: Node Deployment Algorithm for Underwater Sensor Networks Based on Connected Dominating Set

Existing node deployment algorithms for underwater sensor networks are nearly unable to improve the network coverage rate under the premise of ensuring the full network connectivity and do not optimize the communication and move energy consumption during the deployment. Hence, a node deployment algorithm based on connected dominating set (CDS) is proposed. After randomly sowing the nodes in 3D monitoring underwater space, disconnected nodes move to the sink node until the network achieves full connectivity. The sink node then performs centralized optimization to determine the CDS and adjusts the locations of dominated nodes. Simulation results show that the proposed algorithm can achieve a high coverage rate while ensuring full connectivity and decreases the communication and movement energy consumption during deployment.

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Molecules, Vol. 21, Pages 367: Pharmacokinetics of Maleic Acid as a Food Adulterant Determined by Microdialysis in Rat Blood and Kidney Cortex

Maleic acid has been shown to be used as a food adulterant in the production of modified starch by the Taiwan Food and Drug Administration. Due to the potential toxicity of maleic acid to the kidneys, this study aimed to develop an analytical method to investigate the pharmacokinetics of maleic acid in rat blood and kidney cortex. Multiple microdialysis probes were simultaneously inserted into the jugular vein and the kidney cortex for sampling after maleic acid administration (10 or 30 mg/kg, i.v., respectively). The pharmacokinetic results demonstrated that maleic acid produced a linear pharmacokinetic phenomenon within the doses of 10 and 30 mg/kg. The area under concentration versus time curve (AUC) of the maleic acid in kidney cortex was 5-fold higher than that in the blood after maleic acid administration (10 and 30 mg/kg, i.v., respectively), indicating that greater accumulation of maleic acid occurred in the rat kidney.

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Pathogens, Vol. 5, Pages 32: Evasion of Neutrophil Killing by Staphylococcus aureus

Staphylococcus aureus causes many types of infections, ranging from self-resolving skin infections to severe or fatal pneumonia. Human innate immune cells, called polymorphonuclear leukocytes (PMNs or neutrophils), are essential for defense against S. aureus infections. Neutrophils are the most prominent cell type of the innate immune system and are capable of producing non-specific antimicrobial molecules that are effective at eliminating bacteria. Although significant progress has been made over the past few decades, our knowledge of S. aureus-host innate immune system interactions is incomplete. Most notably, S. aureus has the capacity to produce numerous molecules that are directed to protect the bacterium from neutrophils. Here we review in brief the role played by neutrophils in defense against S. aureus infection, and correspondingly, highlight selected S. aureus molecules that target key neutrophil functions.

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Molecules, Vol. 21, Pages 368: Binding Mode and Selectivity of Steroids towards Glucose-6-phosphate Dehydrogenase from the Pathogen Trypanosoma cruzi

Glucose-6-phosphate dehydrogenase (G6PDH) plays a housekeeping role in cell metabolism by generating reducing power (NADPH) and fueling the production of nucleotide precursors (ribose-5-phosphate). Based on its indispensability for pathogenic parasites from the genus Trypanosoma, G6PDH is considered a drug target candidate. Several steroid-like scaffolds were previously reported to target the activity of G6PDH. Epiandrosterone (EA) is an uncompetitive inhibitor of trypanosomal G6PDH for which its binding site to the enzyme remains unknown. Molecular simulation studies with the structure of Trypanosoma cruzi G6PDH revealed that EA binds in a pocket close to the G6P binding-site and protrudes into the active site blocking the interaction between substrates and hence catalysis. Site directed mutagenesis revealed the important steroid-stabilizing effect of residues (L80, K83 and K84) located on helix α-1 of T. cruzi G6PDH. The higher affinity and potency of 16α-Br EA by T. cruzi G6PDH is explained by the formation of a halogen bond with the hydrogen from the terminal amide of the NADP+-nicotinamide. At variance with the human enzyme, the inclusion of a 21-hydroxypregnane-20-one moiety to a 3β-substituted steroid is detrimental for T. cruzi G6PDH inhibition. The species-specificity of certain steroid derivatives towards the parasite G6PDH and the corresponding biochemically validated binding models disclosed in this work may prove valuable for the development of selective inhibitors against the pathogen's enzyme.

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Molecules, Vol. 21, Pages 365: Silver Nanoparticles Exhibit the Dose-Dependent Anti-Proliferative Effect against Human Squamous Carcinoma Cells Attenuated in the Presence of Berberine

The biological activity of nanosize silver particles towards oral epithelium-derived carcinoma seems to be still underinvestigated. We evaluated the influence of low doses of nanosize scale silver particles on the proliferation and viability of malignant oral epithelial keratinocytes in vitro, alone and in conjunction with the plant alkaloid berberine. Cells of human tongue squamous carcinoma SCC-25 (ATCC CRL-1628), cultivated with the mixture of Dulbecco's modified Eagle's medium, were exposed to silver nanoparticles alone (AgNPs, concentrations from 0.31 to 10 μg/mL) and to a combination of AgNPs with berberine chloride (BER, 1/2 IC50 concentration) during 24 h and 48 h. The cytotoxic activity of AgNPs with diameters of 10 nm ± 4 nm was measured by 3-(4,5-dimethyl-2-thiazyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Cell cycle analysis was performed by treating cells with propidium iodide followed by flow-activated cell sorting. RT-QPCR reaction was used to assess expression of anti-apoptotic proteins Bcl-2 and pro-apoptotic protein Bcl-2-associated X protein Bax genes expression. Monodisperse silver nanoparticles at a concentration of 10 μg/mL arrested SCC-25 cells cycle after 48 h at the G0/G1 phase in a dose- and time-dependent manner through disruption G0/G1 checkpoint, with increase of Bax/Bcl-2 ratio gene expression. AgNPs exhibit cytotoxic effects on SCC-25 malignant oral epithelial keratinocytes, which is diminished when combined with BER. The AgNPs concentration required to inhibit the growth of carcinoma cells by 50% (IC50) after 48 h was estimated at 5.19 μg/mL. AgNPs combined with BER increased the expression of Bcl-2 while decreasing the ratio of Bax/Bcl-2 in SCC-25 cells. Silver particles at low doses therefore reduce the proliferation and viability of oral squamous cell carcinoma cells. SCC-25 cells are susceptible to damage from AgNPs-induced stress, which can be regulated by the natural alkaloid berberine, suggesting that nanoparticles may be potentially used in a chemoprevention/chemotherapy by augmentation of action of standard anti-cancer drugs.

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Energies, Vol. 9, Pages 212: Exergy Flows inside a One Phase Ejector for Refrigeration Systems

The evaluation of the thermodynamic performance of the mutual transformation of different kinds of exergy linked to the intensive thermodynamic parameters of the flow inside the ejector of a refrigeration system is undertaken. Two thermodynamic metrics, exergy produced and exergy consumed, are introduced to assess these transformations. Their calculation is based on the evaluation of the transiting exergy within different ejector sections taking into account the temperature, pressure and velocity variations. The analysis based on these metrics has allowed pinpointing the most important factors affecting the ejector's performance. A new result, namely the temperature rise in the sub-environmental region of the mixing section is detected as an important factor responsible for the ejector's thermodynamic irreversibility. The overall exergy efficiency of the ejector as well as the efficiencies of its sections are evaluated based on the proposed thermodynamic metrics.

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Molecules, Vol. 21, Pages 362: Searching for Multi-Targeting Neurotherapeutics against Alzheimer’s: Discovery of Potent AChE-MAO B Inhibitors through the Decoration of the 2H-Chromen-2-one Structural Motif

The need for developing real disease-modifying drugs against neurodegenerative syndromes, particularly Alzheimer's disease (AD), shifted research towards reliable drug discovery strategies to unveil clinical candidates with higher therapeutic efficacy than single-targeting drugs. By following the multi-target approach, we designed and synthesized a novel class of dual acetylcholinesterase (AChE)-monoamine oxidase B (MAO-B) inhibitors through the decoration of the 2H-chromen-2-one skeleton. Compounds bearing a propargylamine moiety at position 3 displayed the highest in vitro inhibitory activities against MAO-B. Within this series, derivative 3h emerged as the most interesting hit compound, being a moderate AChE inhibitor (IC50 = 8.99 µM) and a potent and selective MAO-B inhibitor (IC50 = 2.8 nM). Preliminary studies in human neuroblastoma SH-SY5Y cell lines demonstrated its low cytotoxicity and disclosed a promising neuroprotective effect at low doses (0.1 µM) under oxidative stress conditions promoted by two mitochondrial toxins (oligomycin-A and rotenone). In a Madin-Darby canine kidney (MDCK)II-MDR1 cell-based transport study, Compound 3h was able to permeate the BBB-mimicking monolayer and did not result in a glycoprotein-p (P-gp) substrate, showing an efflux ratio = 0.96, close to that of diazepam.

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Entropy, Vol. 18, Pages 102: Development of a Refractory High Entropy Superalloy

Microstructure, phase composition and mechanical properties of a refractory high entropy superalloy, AlMo0.5NbTa0.5TiZr, are reported in this work. The alloy consists of a nano-scale mixture of two phases produced by the decomposition from a high temperature body-centered cubic (BCC) phase. The first phase is present in the form of cuboidal-shaped nano-precipitates aligned in rows along <100>-type directions, has a disordered BCC crystal structure with the lattice parameter a1 = 326.9 ± 0.5 pm and is rich in Mo, Nb and Ta. The second phase is present in the form of channels between the cuboidal nano-precipitates, has an ordered B2 crystal structure with the lattice parameter a2 = 330.4 ± 0.5 pm and is rich in Al, Ti and Zr. Both phases are coherent and have the same crystallographic orientation within the former grains. The formation of this modulated nano-phase structure is discussed in the framework of nucleation-and-growth and spinodal decomposition mechanisms. The yield strength of this refractory high entropy superalloy is superior to the yield strength of Ni-based superalloys in the temperature range of 20 °C to 1200 °C.

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